5.22 Rearrangements of Vinylcyclopropanes, Divinylcyclopropanes, and Related Systems

5.22 Rearrangements of Vinylcyclopropanes, Divinylcyclopropanes, and Related Systems S Vshyvenko, JW Reed, T Hudlicky, and E Piers†, Brock University, St. Catharines, ON, Canada r 2014 Elsevier Ltd. All rights reserved.

5.22.1 5.22.1.1 5.22.1.2 5.22.1.2.1 5.22.1.2.2 5.22.1.2.3 5.22.1.3 5.22.1.3.1 5.22.1.3.2 5.22.1.3.2.1 5.22.1.3.2.1.1 5.22.1.3.2.1.2 5.22.1.3.2.2 5.22.1.3.2.3 5.22.1.3.2.4 5.22.1.3.2.5 5.22.1.3.2.6 5.22.1.4 5.22.1.4.1 5.22.1.4.1.1 5.22.1.4.1.2 5.22.1.4.2 5.22.1.4.2.1 5.22.1.5 5.22.1.5.1 5.22.1.5.1.1 5.22.1.5.1.2 5.22.1.5.1.3 5.22.1.5.2 5.22.1.6 5.22.1.6.1 5.22.1.6.2 5.22.1.6.3 5.22.1.6.4 5.22.1.7 5.22.2 5.22.2.1 5.22.2.2 5.22.2.2.1 5.22.2.2.2 5.22.2.2.3 5.22.2.3 5.22.2.3.1 5.22.2.3.2 5.22.2.3.3 5.22.2.4 5.22.2.4.1 5.22.2.5 5.22.2.6

Vinylcyclopropanes Introduction Theoretical and Mechanistic Considerations of the Vinylcyclopropane System Bonding and energetics of cyclopropane systems Reactive tendencies Guide to preparation Rearrangements of Vinylcyclopropanes [1,5] Shift pathways Vinylcyclopropane−cyclopentene rearrangements Metal-catalyzed rearrangements Vinylcyclopropane–cyclopentene rearrangements Metal-catalyzed opening and [3+2] cycloadditions Formal [4+1] cycloadditions catalyzed by metals [5+1] Cycloadditions [5+2] Cycloadditions Intermolecular [5+2] cycloadditions Asymmetric [5+2] cycloadditions Rearrangements of Vinyloxiranes and Cyclopropyl Carbonyls Vinyloxiranes Thermal isomerization Nucleophilic opening Cyclopropyl carbonyls Transient cyclopropyl carbonyls Rearrangements of Vinylaziridines and Cyclopropyl Imines Rearrangement of vinylaziridines Thermal rearrangements of vinylaziridines Nucleophilic opening of vinylaziridines Cycloadditions of vinylaziridines Cyclopropyl imines Miscellaneous Systems Isomerizations of oxyvinylcyclopropanes to cyclobutanones Radical reactions and cycloadditions of vinylcyclopropanes [2,3] Rearrangements of vinylaziridines and vinyl epoxides Rearrangements of silavinylcyclopropanes Total Syntheses Divinylcyclopropanes Introduction Mechanistic Considerations Rearrangement pathways Substituent effects Guide to preparation Monocyclic Divinylcyclopropanes Stereospecificity Enantiospecificity Synthesis of functionalized cycloheptanes β-(2-Vinylcyclopropyl)-α,β-Unsaturated Ketones Synthesis of functionalized bicyclo[5.n.0]alkanes and related substances Heterocyclic Divinylcyclopropanes Total Syntheses

1000 1000 1000 1000 1001 1003 1004 1005 1007 1011 1011 1016 1019 1020 1021 1023 1023 1024 1024 1025 1027 1029 1032 1033 1033 1033 1035 1037 1039 1043 1043 1046 1047 1048 1049 1054 1054 1054 1054 1055 1056 1059 1059 1060 1061 1063 1063 1066 1067

† Deceased, 2010; portions of the divinylcyclopropane section are excerpted from: Piers, E. In Comprehensive Organic Synthesis; Trost, B., Ed.; Vol. 5, Chapter 8.2, Pergamon, Oxford, 1991.

Comprehensive Organic Synthesis II, Volume 5

doi:10.1016/B978-0-08-097742-3.00523-1

999

1000

Rearrangements of Vinylcyclopropanes, Divinylcyclopropanes, and Related Systems

5.22.3 References

5.22.1

Outlook

1068 1069

Vinylcyclopropanes

5.22.1.1

Introduction

It has been more than 125 years since von Baeyer1 and Perkin2 reported the first syntheses of cyclopropane derivatives and von Baeyer1 formulated of the “theory of ring strain.” The chemistry of small-ring compounds has risen to prominence in the past 50 years. The popularity especially of three-membered rings as intermediates in synthetic transformations has been due primarily to their latent energy content and to the seemingly endless chemical transformations in which these compounds and their derivatives can participate. New applications and novel permutations of the basic systems continue to appear at a fast pace. The fascinating chemistry associated with the strain of these intermediates continues to find wide applicability in the field of synthetic methodology and in the total synthesis of complex molecules. The following discussion highlights those transformations of vinylcyclopropanes and their derivatives that are selective with regard to the regio- and stereochemistry of products. The discussion of such transformations is done from the position of a synthetic practitioner interested in their actual use. At the end of both major sections, a survey of useful and general methodologies based on these transformations is provided along with a tabular compilation of total syntheses featuring these rearrangements as key steps.

5.22.1.2 5.22.1.2.1

Theoretical and Mechanistic Considerations of the Vinylcyclopropane System Bonding and energetics of cyclopropane systems

The bonding in cyclopropane requires that the sp3 hybrids be misaligned by approximately 22° from the imaginary line connecting the carbon atoms, as shown in Figure 1. The result is the so-called bent or banana bond, which has approximately 20% less orbital overlap than the corresponding bond in ethane. The Coulson–Moffitt3 model 1 and the Walsh4 model 2 use three sp3-hybridized CH2 groups and three sp2-hybridized CH2 groups, respectively. The overall hybridization of cyclopropane carbon–carbon bonds is thus sp2.3; this greater p-character can be invoked in rationalizing the similarity of cyclopropane chemistry to that of alkenes. Because the bond angles are considerably less than the ideal 109.5°, cyclopropane suffers from significant angular (Baeyer) strain and hydrogen repulsions, as well as from torsional (Pitzer) strain from eclipsed carbon–hydrogen bonds.

ψ3

ψ2 E 22%

ψ1

1

2

Figure 1 Bonding in cyclopropane.

A unique treatment of cyclopropane was advanced by Dewar,5 who introduced the concept of σ-aromaticity, which explains some of its anomalous chemical and physical properties. The notion of σ-conjugation implies that three σ-bonds form a cyclic system of six electrons; thus cyclopropane is aromatic by the (4n+2) rule. This explanation accounts well for its strain energy. The actual value (27.5 kcal mol−1)6 is much lower than the predicted value of 104 kcal mol−1 (1 cal¼ 4.2 J), calculated from the C–C– C bending force constants obtained spectroscopically.5,7 A similar comparison for cyclobutane (antiaromatic by the above notion and the 4n rule) underestimated the strain energy.8 σ-Aromaticity also accounts for such observations as 1H NMR chemical shifts and the reactivity of cyclopropane toward electrophiles. The cyclopropane ring is subject to a number of chemical transformations that are only possible because of its unique bonding and high energy content. It is the energy content (27.5 kcal mol−1) that drives the diradical opening of cyclopropane, especially so if one (or both) of the resulting radicals becomes a part of a delocalized allylic system, as in the case of vinyl- or divinylcyclopropanes. The resonance stabilization energy of an allylic radical system (12.6 kcal mol−1)8 can be used to explain the lower activation energy for reactions involving vinylcyclopropane (34–55 kcal mol−1) compared with the activation energy for reaction resulting from diradical processes that involve only the cyclopropane ring (59–66 kcal mol−1).9–13

Rearrangements of Vinylcyclopropanes, Divinylcyclopropanes, and Related Systems

1001

The vinylcyclopropane unit contains the strain energy of the cyclopropane ring (27.5 kcal mol−1), and it is this energy content that is primarily responsible for its reactive options. Thermal ring fission can occur by any one of three mechanisms: [1,5] sigmatropic hydrogen shift, [2σs+2πs] concerted reorganization to cyclopentene, or a diradical fission followed by further reactions of the diradicals (recombination or hydrogen abstraction). This discussion has received considerable attention in both the mechanistic and the synthetic sense and has been the subject of several reviews.9,14–25 The bonding in vinylcyclopropane 3 is such that an s-trans-gauche conformational equilibrium exists to allow for maximum orbital overlap of the asymmetric component of cyclopropane orbitals with the π- or π⁎-orbitals of the ethylene unit, as shown in 3a. From thermochemical studies it appears that conjugation of an alkene with cyclopropane stabilizes the system by 1.2 kcal mol−1.26,27 The conformational equilibrium for vinylcyclopropane was shown to consist of an s-trans minimum 3b and two gauche conformers that are equal in energy and destabilized by 1.43 kcal mol−1 with respect to the s-trans conformation. The barrier to interconversion has been determined to be 3.92 kcal mol−1.28 H

H H 3a

3

H

H

H H

H 3b

The details of bonding and spectroscopic properties of cyclopropane derivatives have been reviewed.13,27,29 In addition, the properties and energetics of cyclopropyl cations, anions, radicals, anion radicals, and cation radicals have been amply reviewed, and comparisons have been made with their corresponding alkenic counterparts.13,27,30,31 Recently, theoretical calculations in a study of properties have been performed on vinylcyclopropyl cation radicals,32 anion radicals,33–35 and neutral radicals.34

5.22.1.2.2

Reactive tendencies

For a synthetic chemist the analogy between cyclopropanes and alkenes is an appropriate one. Virtually every reaction that an alkene undergoes has a counterpart in the repertoire of transformations possible with cyclopropanes. Thus, conjugation of a cyclopropane to an alkene makes it possible to invoke a number of reaction modes and reactive intermediates that can be compared directly to their alkenic counterparts. How a particular vinylcyclopropane will be electronically perturbed toward a specific mode of reactivity depends on the substitution of either the cyclopropane or the vinyl portion. All of the principal reactions of vinylcyclopropanes proceed via transition states that require stabilization by activating groups and/or release of the ring strain. To understand and to alter the reactive tendencies of substituted vinylcyclopropanes, we must understand the components of the possible transition state and the probable reactive intermediates involved. Table 1 shows the principal reaction pathways of the vinylcyclopropane system in the context of their intermediates, products, and alkenic equivalents. The cyclopropylcarbinyl radical 4, the cyclopropylcarbinyl cation 5, and the cyclopropylcarbinyl anion 6 all dominate the expected reactivity of vinylcyclopropanes as one of these forms will be expected to be a major contributor to either a radical or a polar transition state. It is important to consider the various reactive subunits in some detail in order to understand the “big picture” reactivity of a vinylcyclopropane system, especially as perturbed by additional substituents. The dominant contributor to the reactivity of vinylcyclopropanes in any radical reaction is the form 4a, the cyclopropylcarbinyl radical system. The opening of a cyclopropylcarbinyl radical to a butenyl radical is among the fastest radical processes known, with a rate constant of 1.3×108 s−1.36,37 The various stereoelectronic effects of this rearrangement have been reviewed.38,39 The structure of 4a, deduced from its electronic spin resonance spectrum40,41 and in agreement with calculations (STO-36 basis set),42 is in the bisected conformation shown, predicted to be 1.4 kcal mol−1 more stable than its perpendicularly oriented counterpart. Above −100 °C, only the butenyl radical 4b can be detected. Substituent effects do not seem to operate when the substituents are on the cyclopropane (i.e., product stabilization).43 The cyclopropylcarbinyl cation and anion have structures similar to 4a, bisected conformations 5 and 6, respectively. A concise summary of solvolytic and mechanistic data for system 5 has appeared.27 Reviews of the chemistry of cyclopropylcarbinyl anions and carbenes are also available.12,13

4a

5

4b

6

To understand how substituents, especially heteroatoms, change the reactivity of these systems, the basic transformations shown in Table 1 should be kept in mind. The number of possibilities is limitless, especially on the recognition that, depending on the substituents, any one of the above contributing structures 4, 5, or 6 can become operational on the mode of subsequent rearrangement of the vinylcyclopropane when such rearrangements occur from the homolytic or heterolytic manifolds. The question of concerted rearrangements, or [2πs+2σs] processes, is more difficult to address. Evidence exists on both sides of the argument with no clear-cut rules for or against a universally accepted mechanism. The next section presents the debate concerning this topic in more detail.

1002

Table 1

Rearrangements of Vinylcyclopropanes, Divinylcyclopropanes, and Related Systems

Principal reaction modes of vinylcyclopropanes

Reaction type

Reactive intermediate

Alkenic counterpart

[1,X] Sigmatropic migration

Product(s)

H

H H [1,5 shift] R

Radical addition

X

R R

4 (Cyclopropylcarbiny l radical)

E

Nu

E

Electrophilic addition

R

X

R

+

E E

E

Nu

5 (Cyclopropylcarbinyl cation) Nucleophilic addition −

−

Nu

E

Nu

−

Nu Nu

Nu

6 (Cyclopropylcarbinyl anion)

E

Radical cleavage

One-electron oxidation

+

+

+ +

+

7 radical-cation

In terms of retrosynthetic or disconnective reasoning, cyclopropane is an ideal molecular building block. Because it can be expected to act as an alkene, all of the standard reactions can be performed with it. As it has an extra carbon, however, it serves as a marvelous “synthetic wedge tool”12 that can be used to either disrupt existing symmetry or consonance or to introduce it to the target. The concepts of synthetic consonance and dissonance formulated by Evans44,45 or the “cyclopropane trick” analogy of Seebach46 are ideal in understanding the synthetic utility of cyclopropanes. Thus, for example, equilibrium addition of HBr to 1,3butadiene yields 1-bromo-2-butene 8 (equation 1), in which the halide enjoys an allylic relationship with the alkene. Similar addition to a vinylcyclopropane (equation 2) will, however, produce 1-bromo-3-pentene 9 where the same relationship is homoallylic. One can immediately see that the charge parity in the product alkenes has been inverted by the introduction of the odd carbon, and thus inverted reactivity of such alkenes can be expected in subsequent synthetic steps. This criterion is extremely important in synthetic schemes involving long-range planning and placement of functional groups. This property of cyclopropane has been exploited in the pioneering efforts of Wenkert, who developed 1,4-dicarbonyl compound synthesis based on the ability of oxycyclopropylcarbinyl systems such as 10 to act as pseudo enols (equation 3).20,47,48 +

HBr

+

−

−

Br

−

ð1Þ

8 HBr

− +

−

− +

9

Br +

ð2Þ

Rearrangements of Vinylcyclopropanes, Divinylcyclopropanes, and Related Systems O

1003

O R

R

H

ð3Þ

O

OH 10

Finally, the introduction of cyclopropane or vinylcyclopropane into organic compounds provides an opportunity to cross the odd/even manifolds in further synthetic steps aimed at the preparation of compounds of increased molecular complexity. Traditionally, any synthesis that involves cyclic intermediates with an odd number of atoms (or acyclic intermediates with an even number) is more difficult because proper charge parity or consonance cannot be observed. A cyclopropane unit then functions as a topological operator in those cases where such crossover is desired.49–51 The most fascinating features of vinylcyclopropane reveal themselves upon the introduction of not only substituents, but also heteroatoms. The number of possible permutations of molecular connectivity in a system such as Z (Figure 2) is virtually limitless. (Consider the series of connectivity operations for a chemical system composed of an odd number of atoms with an external operator X. Although there is only one way to connect A and X, there are now six ways to connect X through the ring opening of the three-membered ring system (i) and 120 such different connections in the ring opening of the heterovinylcyclopropane (ii) and its interactions with X.52) The complexity of connectivities of Z with an external operator X is related through the factorial (!) function and becomes even greater when the presence or the position of substituents in Z or the complexity of X is added for consideration. The success in predicting the reactivity of a system such as Z depends on the nature of component atoms, substituents, electronic perturbations, and the preference of some mechanistic pathways over others. To consider selective transformations of a system that has in excess of 120 possibilities may seem frivolous; fortunately there exists a number of simplifying parameters that provide for surprising selectivity as well as predictability of the rearrangements of any hetero-substituted system of type Z.

C B

D

B A C E D

A E

(and/or isomers)

Z A−X

A+X

A B C

+

XABC or XACB or XBAC or XBCA or XCAB or XCBA (6 possibilities = 3!)

X

(i) A B C

D

E

+

X

(120 possibilities = 5!)

(ii) Figure 2 Permutations in connectivity.

In the context of specific transformations, for example the vinylcyclopropane–cyclopentene rearrangement, substituent effects have been quantitatively addressed and are discussed in the appropriate sections. Donor/acceptor principles have been applied to thermal, heterolytic, and transition metal-catalyzed rearrangements and have been reviewed.16,21,53–56 These take into account the possible intermediate structures listed in Table 1 and are used to explain the reactivity of a particular cyclopropane system. In the discussion that follows, emphasis is given to the processes that are uniformly selective with regard to regio-, stereo-, and enantiochemical integrity of the products.

5.22.1.2.3

Guide to preparation

The inherent energy content of the cyclopropane ring demands that the method of introduction of a cyclopropyl subunit itself relies either on highly reactive intermediates or on irreversible or energetically, if not entropically, favored processes. Thus the synthesis of cyclopropane derivatives can be classified into four major categories: 1,3 bond forming sequences (equation 4);57–59 carbene or carbenoid routes (equation 5);60–65 insertion of η2 complexes of alkenes to electron-deficient unsaturated compounds (equation 7);66–74 and rearrangement pathways (equations 8 and 9).75–78 X

Y

H2C CH2

+

CR2

+ XY

ð4Þ

R1 R2

ð5Þ

1004

Rearrangements of Vinylcyclopropanes, Divinylcyclopropanes, and Related Systems R1

R1 Ti(OR)2

E

+

R2

E

ð6Þ

R2

Y−

ð7Þ

Y X SO2

+

ð8Þ

SO2

The procedures for the synthesis of cyclopropane derivatives, especially by the carbenoid route57,59–63,79–84 or the ylide route (1,3-displacement),19,20,59,85–88 have been amply reviewed. Equally well reviewed are the reactions of cyclopropanes and their use in synthetic methodology.53,54–56,70,89 For the preparation of the more common cyclopropane derivatives, the use of suitably functionalized cyclopropyl building blocks that are commercially available is recommended. Vinylcyclopropanes are most easily prepared by one of the following methods: 1. 2. 3. 4.

Cyclopropanation of conjugated dienes (inter- and intramolecular) by carbenes or carbenoids (equation 9)51,83 Permutations of the reactions of allylic ylides with Michael acceptors (equation 10)19,20,59 Ring opening of oxaspirocyclopentanes (equation 11)19,20,90,91 and Kulinkovich reaction of titanium diene intermediates with esters/amides/nitriles/thioacetals (equation 12)69,70,73,74

Carbene equivalent R

X

R

O X+

−

−

X+

ð9Þ

+

O

ð10Þ

+

+

Ti(OR)2

OR

O

ð11Þ

O

+

N

NH2

ð12Þ

Indirect methods of formation can be used, for example, Wittig reaction of acylcyclopropanes and rearrangement pathways;58,59 and in certain specific cases where the vinylcyclopropanes are immediately reacted further, by thermolysis of 1,4-dienes via [1,5] shift sigmatropic reactions.51,92 The preparations of vinyloxiranes, vinylaziridines, cyclopropylcarbonyls, and cyclopropylimines have been reviewed in different contexts (addition of ylides to carbonyl compounds, interaction of azides or diazo compounds with alkenes, etc.), but their preparations have not been summarized under a common heading; however, any reference dealing with the use of these compounds will provide a guide to one or more methods of their synthesis.

5.22.1.3

Rearrangements of Vinylcyclopropanes

The vinylcyclopropane system is subject to a wide variety of transformations ranging from thermolysis and photolysis to nucleophilic, electrophilic, and radical ring-opening reactions as well as transition metal-catalyzed rearrangements and cycloadditions. A common trait in all such transformations is the release of the ring strain and further reaction of the intermediates thus generated. Until 1990s the most commonly recognized transformations of vinylcyclopropanes were those resulting from thermally induced bond reorganizations. There are two major pathways available to vinylcyclopropanes on thermolysis: rearrangement to cyclopentene and ring opening to alkenes or dienes. The ability to predict which of these transformations is the most likely depends to a great extent on

Rearrangements of Vinylcyclopropanes, Divinylcyclopropanes, and Related Systems

1005

the substituents and on the precise conformational definitions and the orientation of the π-system of the vinyl group to the cyclopropane. The thermal cleavage of vinylcyclopropane can in principle provide any of the products depicted in Scheme 1. The analysis of the mechanistic pathways has been reviewed and widely accepted mechanism of such rearrangements includes a diradical intermediate/transition state.22

Ea = 57.3 kcal mol−1 log A = 14.4

3

Ea = 49.6 kcal mol−1 log A = 13.5

Ea = 56.2 kcal mol−1 log A = 13.9

Ea = 53.6 kcal mol−1 log A = 13.0 Scheme 1

5.22.1.3.1

[1,5] Shift pathways

Under some circumstances, the [1,5] sigmatropic shift of a hydrogen from an alkyl group oriented cis to the vinyl group is the lowest energy pathway available to a vinylcyclopropane.10,11,92 The classic experiments that led to the understanding of this process were performed by Winstein93 and Frey.92,94,95 The rearrangement of vinylcyclopropane 11 proceeded at 260 °C to furnish only the cis-alkene 12 (equation 13).94 The rearrangement usually proceeds with an activation energy of 30–35 kcal mol−1 9–11 and is thought to involve a chair-like (13) rather than a boat-like (14) transition state. Most of these rearrangements are stereospecific, yielding only the cis-alkene. 260 °C

11

12

H

Chair: 4.5 kcal mol−1 more stable 13

H

ð13Þ

Boat 14

The transformation has been shown to be reversible by careful study of the temperature profiles of flash vacuum pyrolysis (FVP) of either cis-methylvinylcyclopropane 15 or diene 16 (equation 14).96 Only above 400 °C did the vinylcyclopropane show the expected tendency toward diradical cleavage, a process that requires a substantially higher activation energy (15–20 kcal mol−1 higher) than the concerted [1,5] shift. This rearrangement also occurs stereospecifically in endocyclic vinylcyclopropanes such as 17 (equation 15).97 The migration of the hydrogen atom is governed by the principles of sigmatropic rearrangements, that is, the pathway of the hydrogen atom is suprafacial.98 The effect of substituents and their stereochemistry in this rearrangement was investigated.99 The fact that suitably sterically biased cis-alkylvinylcyclopropanes participate in these types of reactions attests to the ability of the cyclopropane ring to transfer conjugative properties and to act as a pseudo-ene unit. Competing pathways of higher order may become dominant in those cases where the transition state is stabilized by extended conjugation, as in the case of 18 and its predominant [1,7] hydrogen shift (Scheme 2).100

1006

Rearrangements of Vinylcyclopropanes, Divinylcyclopropanes, and Related Systems O

O Below 400 °C H

ð14Þ

Above 450 °C H 16

H 15

H

H

ð15Þ 17

O

HO

HO

H

CHO

[1,7]

[1,5] H 9%

91%

(18)

Scheme 2

Oxygen, nitrogen, and carbon atoms can equally well participate in the “vinyl” system. Table 2 provides a survey of some synthetically useful rearrangements of this type. In all cases shown in Table 2 the formation of the alkene is regioselective and in most cases it is stereospecific as well, according to the principles outlined below. The distinction between boat and chair transition states depends on the precise conformation of the reacting system, and this factor can be somewhat manipulated experimentally. Table 2

Thermal rearrangements of cis-alkylvinylcyclopropanes

Cyclopropane

Temperature (°C)

Alkene

Yield

300

95,101

150

O

References

89.4

102

82.5 (trans) 17.5 (cis)

102

O CO2Me

280

CO2Me CHO

CHO

120

100,103,104

H 200

OH

80

105

80

96

O

O

360

O

The synthetic utility of this process can be seen by evaluating the examples in Table 2. For example, because the cyclopropane serves as a pseudo alkene and because the [1,5] shift requires a six-membered transition state, it relates conceptually to the Cope and Claisen rearrangements. The γ,δ-unsaturated carbonyl compounds in Table 2 are those that would otherwise be obtained via

Rearrangements of Vinylcyclopropanes, Divinylcyclopropanes, and Related Systems

1007

Claisen or orthoester Claisen rearrangements, which are normally effected under strongly acidic or strongly basic conditions (Scheme 3).

O O +

O R

HC

O

R

R

R

H Scheme 3

For compounds of small molecular weight, the [1,5] shift pathway may therefore be superior in the ease of preparation, simplicity, and cost. In those instances where 1,4-dienes are easily constructed with the alkene predisposed cis, the resulting conversion to vinylcyclopropanes may in fact be superior to the use of carbenoid-based reagents in those instances where the resulting vinylcyclopropanes need not be isolated (Scheme 4). The retro-ene reaction of 1,4-dienes requires temperatures that induce immediate further reactive options in the vinylcyclopropane as soon as it is generated.96

R

R

Δ

CHCH2R

Not isolated Scheme 4

Two examples that show selectivity in synthetic applications are the synthesis of cycloheptanone 19,105 which involves ring expansion via a [1,5] hydrogen shift, and the synthesis of sarkomycin 20 (Scheme 5).96,106 In both of these protocols, the intermediate cyclopropyl ketone or vinylcyclopropane system could be rearranged to dihydrofurans or cyclopentenes, respectively, by the appropriate adjustments in the experimental conditions.9,51

O

O i

ii 80%

O

19 O

N2

O

O iii

O

iv

v

85% 15

16

20

CO2H

i. LiAIH4; Simmons−Smith cyclopropanation, Collins oxidation; ii. 200 °C, 2 h; iii. Cu(acac)2, PhH, Δ; iv. 450 °C, Pyrex; v. O3, CH2Cl2, Me2S; Jones oxidation Scheme 5

5.22.1.3.2

Vinylcyclopropane–cyclopentene rearrangements

The thermal rearrangement of vinylcyclopropanes to cyclopentenes is probably the most recognized mode of reactivity of the vinylcyclopropyl system and the one that has received the most attention. Discovered independently by Neureiter in 1959,107 Vogel,108 and Overberger and Borchert in 1960109 it was scrutinized in detail during the 1960s. Mechanistic details of the thermal vinylcyclopropane–cyclopentene rearrangement have been reviewed.22,23 The fundamental issue at the time revolved around the concerted [2πs+2σs] versus diradical nature of the rearrangement. No resolution of this question materialized as both mechanisms were invoked to explain specific cases.9–13 The experimental evidence in the majority of cases studied, however, supports a diradical-type cleavage of the vinylcyclopropane system and a reclosure of the allylic diradical with an average activation energy of approximately 45 kcal mol−1, or approximately 15 kcal mol−1 higher than the competing [1,5] shift pathway discussed in the Sections 5.22.1.3 and 5.22.1.3.1. What is puzzling is the apparent stereospecificity

1008

Rearrangements of Vinylcyclopropanes, Divinylcyclopropanes, and Related Systems

of the rearrangement of optically pure vinylcyclopropanes such as 21 (equation 16).110 The presence of “forbidden” products, (–)-23 and (+)-23, would suggest a biradical mechanism, but the high degree of retention of optical purity (80.1±0.4% at 60 °C, 68.8±0.5% at 120 °C) rules out any freely rotating diradical species.110,111 This observation implies that if the regiochemistry of the rearrangement is controlled, the stereo- and enantiochemical consequences will follow. Ph

R1

Ph

21 Ph

23

R1

+

Ph

Ph

Ph R1

R1

+

24

25

R1

+

ð16Þ

26

R1 22

Further studies conducted since 1990,112–117 thus support, to a varying extent, a diradical-type cleavage of the vinylcyclopropane system and a reclosure of the allylic diradical with an average activation energy for unsubstituted vinylcyclopropane– cyclopentene rearrangement system of approximately 51.7±0.5 kcal mol−1, as recently determined.118 This value is approximately 6 kcal mol−1 higher than the one previously measured. Introduction of activating groups lowers the Ea for diradical opening by 5–20 kcal mol−1.114 One of the major drawbacks is the apparent scrambling of enantiospecificity and sometimes stereospecificity. Opening and reclosure of vinylcyclopropane occurs more readily than the rearrangement to cyclopentene. Usage of cis- and trans-alkene can lead to the same manifold of products with different ratios. The use of optically pure vinylcyclopropanes indicated that both “allowed” (antarafacial retention, ar, and suprafacial inversion, si) and symmetry “forbidden” (antarafacial inversion, ai, and suprafacial retention, sr) products are formed although with different ratios. For example, for two cases of 21 and 22, the distribution of products of (sr+ai) and (si+ar) pathways are shown in the Table 3.119,120 In vicinally disubstituted donor–acceptor vinylcyclopropanes (i.e., functionalities on adjacent carbons), the transition state is believed to involve to some extent 1,3-zwitterionic intermediates.54 The actual level of radical–zwitterionic character is likely influenced by the choice of solvent.121 Table 3

Distribution of products of the thermal rearrangement of enantiomerically pure vinylcyclopropanes 21 or 22 1

Substrate, R 21, 21, 22, 22,

R1 ¼Me R1 ¼Ph R1 ¼Me R1 ¼Ph

23

24

25

26

References

44 67 90 (mix) 91 (mix)

20 12

25 17 10 (mix) 9 (mix)

11 4

119 120 119 120

The molecular topology of this rearrangement is fascinating in its potentially limitless permutations. As indicated in Section 5.22.1.2.2, any one of the five atoms in the vinylcyclopropyl system may be replaced with almost any other atom (C, Si, P, N, O, S, etc.), and the overall reorganization to an unsaturated five-membered ring system remains operational. Thus cyclopropyl aldehydes, imines, ketones, and esters yield the corresponding heteroatom analogs of cyclopentene, as do vinyloxiranes, vinylaziridines, and vinylthiiranes. When electronegative elements are contained within the vinylcyclopropane framework, the mechanism may change from a diradical to a dipolar one. In the parent system 3, only one bond is activated toward a cleavage that produces an allylic radical. In more substituted cases, however, different degrees of activation may exist, and these will control the rate as well as the regiochemistry of the rearrangement. Some examples of recent synthetic utilization of the thermal vinylcyclopropane–cyclopentene rearrangement are presented in Table 4. Nonthermal rearrangements can proceed under significantly milder conditions. For example, a radical-cation of vinylcyclopropane has a barrier of rearrangement of only 21.7 kcal mol−1.134 The photolytic vinylcyclopropane–cyclopentene rearrangement usually proceeds with the same stereoselectivity as the thermal rearrangement. It can be performed under direct irradiation or with photosensitizers and has been subject of several reviews.135,136 It is interesting to note that, in some cases, the outcome of the photochemical rearrangement can be different: the vinylcyclopropane–cyclopentene rearrangement takes place in the presence of the photosensitizer and the cyclopropylcarbonyl–lactone rearrangement under direct irradiation conditions (see Scheme 6).137 Photosensitized reactions are believed to proceed through single-electron transfer (SET).138 Studies on cyclopropanes substituted with electron-withdrawing groups (EWGs) and electron-donating groups (EDGs) at position 1 (point of the connectivity of the vinyl group) of the cyclopropane ring showed that the former substrates tend to form an open-chain radical, which attacks

Rearrangements of Vinylcyclopropanes, Divinylcyclopropanes, and Related Systems

Table 4

1009

Thermal rearrangements of vinylcyclopropanes

Starting material (SM)

Conditions

Product

500 °C

n

n

Yield (%)

References

68–88

122

87, 80

123

74–100

53

Vinylcyclopropane–cyclopentene rearrangement: 63–96 Cope: 0–37

124

33–40 + SM

125

95–97

126

27–95

127

60–77

128

n-mono/bycliclic

MeO

OMe

300 °C

R

n-C6H13

n-C6H13

R = H, CH2CO2Me CO2Me

Decalin, benzonitrile, 190 ° C; or: DMF, 150 °C

MeO Ph R2

CO2Me

MeO Ph R1

R2

R1 R1,R2 = alkyl, aryl, H

O

O

130–180 °C, benzene

R

O

X

O

H

X

R VCP

X = H, Me, Cl, Ph

O

R = H, Me

O X R Cope NC CN O

150 °C, toluene, 4 days

O

OMe

CN CN

Ph

R OMe

Ph R

R = H, CO2Me

N

O

230 °C, benzene, 6 h

N

O

R

S

R

S

R

R

R = H, Me 400–600 °C, 10−5 mbar

R2

R1 NBn2

NBn2

R2

R1 R1=H, alkyl, Ph R2=H, alkyl, Ph

550 °C, 10−2 mbar

R1 R2

CN N

R1 R2

CN N

R1 = Alkyl, aryl R2 = Alkyl

(Continued )

1010

Rearrangements of Vinylcyclopropanes, Divinylcyclopropanes, and Related Systems

Table 4

Continued

Starting material (SM) Cl Cl

Br

Conditions

Product

480 °C, 5×10−5 mbar

Br Cl Cl

F

References

Mass recovery 90

129

Not reported

130

n ¼1, 89 n ¼2, 90 n ¼3, 84

131

n ¼1, syn:anti¼4:96, 65 n ¼3, syn:anti¼99:1, 45

132,133

Br

Br

F

Yield (%)

F

F F

80–140 °C

F F

R F F

R

F

R = H, Me Me2N

H NMe2

n¼ 1, 500 °C, 10−5 mbar n¼ 2, decalin 220 °C n¼ 3, decalin 240 °C

n

n n = 1,2,3 CO2Me

H

110 °C, toluene; 132 °C, chlorobenzene

n O MeO CO Me 2

H OMe

syn

O n n = 1,3

H

n O MeO CO Me 2

syn n = 1, 3

SM

+ O Ph

65% 75%

O

Direct irradiation

O

Ph

Ph

19% 15%

OR Ph

+

Sensitizer

O

Ph

R=H R = Et

SM

OR Ph

19% 17%

74% 80%

Scheme 6

the aromatic ring and undergoes divinylcyclopropane–cycloheptadiene rearrangement to form compounds 28. With electrondonating substituents on the cyclopropane, the products of the classical vinylcyclopropane–cyclopentene rearrangement, namely 27, were formed (equation 17). R1 R2

Ph R1

R1 = EDG Ph Ph

R2 h

27

Sensitizer Ph

ð17Þ

R2

R1

R2=H, Me, Ph

R1 = EWG Ph 28

Rearrangements of Vinylcyclopropanes, Divinylcyclopropanes, and Related Systems

1011

Cation–radical rearrangement mechanism and periselectivity have been studied.139 Upon reaction with an amidyl radical source (i) in equation 18, the product of the rearrangement was formed. The same product was formed under conditions of oneelectron oxidation in (ii) equation 18 and photochemical rearrangement (iii) in equation 18. Almost identical stereoselectivity and product distribution led to the conclusion that all three reactions operate under the same mechanism. These methods present a complementary approach to the thermal rearrangement. Formal periselectivity of the latter one is different and a main product of it would be the retro-ene product. MeO i or ii or iii

MeO

ð18Þ •+

i. (p-ClC6H4)3NSbF6−; ii. Fe(1,10-phenantroline)33+(PF6−)3; iii. h, 350 nm

The Skattebøl rearrangement, shown in equations 19 and 20, constitutes a rare case of the vinylcyclopropane–cyclopentene rearrangement. It is used especially for the generation of cyclopentadienyl anions140,141 and is believed to proceed through the formation of carbene intermediates.

Br

Br

Br

Br

4 equivalents MeLi

ð19Þ

THF −78 °C 48%

Br

Br

Br

Br

-

4 equivalents MeLi THF −78 to >0 °C

-

TiCl3*THF 18%

X

Ti Y

ð20Þ

2 Li+ X, Y = Cl, Br

Lewis acids are known to facilitate the vinylcyclopropane–cyclopentene rearrangement under mild conditions. For this protocol to be effective the cyclopropane ring must contain a functionality that can interact with the Lewis acid in order to stabilize charged zwitterionic intermediates. Some recent examples of these rearrangements are shown in Table 5. 5.22.1.3.2.1 Metal-catalyzed rearrangements 5.22.1.3.2.1.1 Vinylcyclopropane–cyclopentene rearrangements The metal-catalyzed vinylcyclopropane–cyclopentene rearrangement has a much shorter history of development than the thermal version. The major difference from thermal rearrangement lies in the fact that the thermal rearrangement requires high temperatures to ensure cleavage of the C–C bond to diradicals with very similar energy, which in turn produce mixtures of products. Because metal insertion takes place at significantly lower temperatures through a concerted pathway, the stereoselectivity of the outcome can be controlled much more efficiently than in the case of thermal rearrangements. In addition, the use of chiral ligands provides an opportunity to control enantioselectivity, which cannot be achieved using other conditions unless at least one chiral center retains its original configuration. This aspect was sufficiently demonstrated through the early work of Hudlicky.152 A general discussion on the topic of the transition-metal-catalyzed rearrangement of vinylcyclopropanes and related systems is provided in several reviews.89,153,154 Initially rhodium, low valent nickel, and copper catalysts were used.155 Ryu and Sonoda156 discovered that the catalytic system Ni(0)/PPh3 can catalyze vinylcyclopropane–cyclopentene rearrangements of activated 1-silyloxyvinylcyclopropanes in good yields (equation 21).

R1

OTBS

OTBS i or ii

R2 R3 R1,2,3=H,Me,Bu,Ph

R3 R2 R1 78−90%

i. Ni(COD)2 10 mol%, PPh3 20 mol%, PhMe, reflux, 17 h; ii. NiCl2(PPh3)2 5 mol%, Zn 10 mol%, PhMe, reflux, 20−40 h

ð21Þ

1012

Rearrangements of Vinylcyclopropanes, Divinylcyclopropanes, and Related Systems

Table 5

Lewis acid-mediated rearrangements of vinylcyclopropane systems

Starting material

Conditions

Product

Et2AlCl, CH2Cl2, 0 °C

93

142

H

TBSO

O

O

O

MeO

(a) Et2AlCl, CH2Cl2, r.t. (b) AlMe3, Et2O, reflux

MeO2C

MeO2C

Prn

(a) 75 for cis, 90 for trans 143 (b) 48 for cis, 56 for trans

Prn

MeS

SMe

SnCl4, CH3NO2

SMe R1

References

H TBSO

O

Yield (%)

O

144

61–87

145,146

45–87

147

39–80

148

SMe

R1

R2

61–85

R2

O R1 = aryl R2 = H, alkyl CO2Me

Me2AlCl, CH2Cl2, −78 °Ca

R1

R1

CO2Me R2O

R2O

R3

R3 R1 = H, alkyl, aryl R2 = Et R3 = Ph, Me Cl Cl

O

AgBF4, CH2Cl2 or TFE, r.t.

R2

TIPSO R2

Cl

R3

R1 R1

R3 O

R1,2,3 = H, alkyl, aryl

R2

Cl

R1 Cl Cl

AgBF4, MeCN, reflux

R3

X O

TIPSO

X X = OH, OMe, Br, Me

O

Me2AlCl, CH2Cl2, −78 °C to 0 ° MOM C

O methoxymethyl (MOM) N O

N MOM

n

O

H O

N N MOM

O

n=1,2

O MOM O

H

51 for n¼1 88 for n¼2 n 20 for n¼1

149

HO

N N MOM (Continued )

Rearrangements of Vinylcyclopropanes, Divinylcyclopropanes, and Related Systems

Table 5

Continued

Starting material

O

1013

Conditions

Product

O

MgI2, MeCN, 40 °C

CO2Me

CO2Me

Yield (%)

References

74–86

150

89–98

151

R

R

H

H

CO2Et

MgBr2, THF reflux

MeO2C

X MeO C 2

CO2Et

X N

O N O

N

OO

N

X = H, Br a

Significant erosion of enantiomeric excess (ee) for monocyclic substrates, retention of ee for bicyclic substrates. Abbreviations: TFE, trifluoroethanol; TIPS, triisopropyl silyl.

An enantioselective version of the vinylcyclopropane–cyclopentene rearrangement was developed by Hiroi,157 who studied a wide range of metal catalysts, ligands, and solvent systems. Best results were obtained with Ni(1,5-cyclooctadiene; COD)2/ (+)-MOD-DIOP/DMSO, which produced the desired compound with 90% ee. It is interesting to note that the use of Pd(PPh3)4 under the same conditions158 gave complete inversion of the enantioselectivity for the same substrates, albeit with lower ee. This suggests different modes operating in Ni- versus Pd-catalyzed rearrangements. Other metals, such as Cr, Mo, Pt, and W either failed to promote the rearrangement or their use did not lead to significant enantioselectivity (Scheme 7).

Ni(COD)2 15 mol% Phosphine 20 mol%, solvent, r.t.,

H MeO2C MeO2C

(+)-MOD-DIOP/DMSO 77% 90 ee (−)-BINAP 97% 84 ee (−) - (R)

MeO2C Pd(PPh3)4 15 mol%

MeO2C

Phosphine 20 mol%, solvent, r.t.,

(+) - (S)

(−)-BINAP/DMSO 68% 40% ee (+)-MOD-DIOP/MeCN 100% 31% ee

OMe

O

P

O

P

2 (+)-MOD-DIOP

PPh2 PPh2

(−)-BINAP

OMe 2 Scheme 7

A chiral sulfoxide auxiliary was used by Hiroi in the rearrangement shown in Scheme 8.159 High levels of diastereomeric excess (de) (90–94%) were observed and the unexpected retention of configuration of the diene double bond was noted. Most of the early discoveries of rearrangements catalyzed by Ni and Pd were made on “activated” vinylcyclopropane systems, either those containing EWGs on the cyclopropane ring, whose presence is thought to facilitate oxidative addition of the metal, or those containing an extended diene system, which would help precoordination of the transition metal. Rhodium catalysis did not require such additional functionalities in order to undergo C–C bond insertion, but in the case of simple unsubstituted vinylcyclopropanes a stable complex is formed that does not undergo a further transformation to cyclopentene, as shown in Scheme 9.160 Cyclopropylallenes and cyclopropylalkynes can be considered to be activated systems. Examples of rearrangement of cyclopropylallenes with rhodium are known, as shown in equations 22, 23 and Table 6.161,162

1014

Rearrangements of Vinylcyclopropanes, Divinylcyclopropanes, and Related Systems

O−

O − Ar S+

E E

Ar S+

E

i

E

5−74%, de 70−94% E E

E S+

O

E

i

−

S+

O− Ar

Ar 8−26%, de 55−90% E = CO2Et Ar = p-tolyl, 1-(2-methoxynaphthalene) Diphospine ligand = dppe, 1,1-bis(diphenylphosphino)propane (dppp), 1,1′-bis(diphenylphosphino)ferrocene, dppb, 1,2-bis(diphenylphosphino)hexane i. Pd2(dba)3*CHCl310 mol%, diphosphine ligand 20 mol%, PhMe, r.t., 18 h Scheme 8

R

R

R

[Rh(C2H4)2Cl]2

Phosphines Rh

−C2H4 r.t.

Cl

R = H, Me

R Scheme 9

R2

2 (a) R

R1

R2

Rh-cat

+ R1

• (b)

Path a

R1

B(OR)2 B(OR)2

R2

ð22Þ

R1

Catalyst 10 mol%, benzene, 80 °C

•

R1

Path b

B(OR)2

R2

B(OR)2

+ R2

B(OR)2

R1

B(OR)2

O B(OR)2 =

B O

Catalyst = A [Rh(MeCN)2(cod)]BF4, B [Rh(cod)2]BF4, C [RhCl(cod)]2

R1, R2

ð23Þ Catalyst Yield

Ratio of isomers

Vinyl, H

A

46%

80:20

Ph,H

B

79%

55:45

−(CH2)4−

B

58%

−

−CH2(CH2)2O− C

46%

57:43

The regioselectivity of the rearrangement can be somewhat controlled161 by using either a cationic or a neutral rhodium catalyst, as indicated in Table 6. Transient cyclopropylallenes generated in situ from propargyl acetates can also be rearranged under

Rearrangements of Vinylcyclopropanes, Divinylcyclopropanes, and Related Systems

Table 6

Rhodium-catalyzed rearrangement of vinylcyclopropylallenes as shown in equation 22

Substituent

Catalyst +

R ¼H, R ¼CO2Bn R1 ¼n-Pr, R2 ¼CO2Bn R1 ¼n-Pr, R2 ¼CO2Bn R1 ¼Ph, R2 ¼H R1 ¼Ph, R2 ¼H R1 ¼Ph, R2 ¼CO2Me R1 ¼Ph, R2 ¼CO2Me 1

1015

2

RhCl(PPh)3; [Rh(COD)2] RhCl(PPh)3 [Rh(PPh3)3]+ BF− 4 [Rh(PPh3)3]+ BF− 4 [Rh(COD)2]+BF− 4 RhCl(PPh)3 [Rh(COD)2]+BF− 4

BF− 4

Ratio a:b

Yield (%)

– 12:88 1:99 8:92 95:5 44:56 97:3

88 89 98 98 95 73 78

copper163 and gold catalysis.164,165 Both reactions are believed to proceed through similar allenic–metal complexes, as shown in Scheme 10.

R1 OAc E

Cat A 50 mol% Toluene, r.t. E

E TMS

•

E

R1

E E

R1=Pri 71%

Cat B = PPh3AuSbF6 Cat C = (IPr)Au(NTf2)

R4

Cat B 1 mol%

• [M]

MeNO2, r.t.

OR2

R3

Cat A = Stryker’s reagent [(PPh3)CuH]6

X R5 OR6

Cat C 5 mol% CH2Cl2, r.t.

Ph

OPiv Ph

R2=Piv, R3,4=Ph 75% R5

OR6

R5=Pri, R6=Ac 75% Scheme 10

The unactivated vinylcyclopropane 29 was shown by Suginome and Ito to isomerize in the presence of Ni(pentane-2,4-dione; acac)2/PCy3/diisobutylaluminium hydride (DIBAL).166 It is interesting to note that in an earlier chapter by Nishida155f the same substrate was shown to be inactive under Ni(COD)2/PBu3 conditions. Ph

29 167

Ni(acac)2, 5 mol% DIBAL, 5 mol%

Ph

ð24Þ

P(c-C6H12)3 5 mol%, toluene, 90 °C >95%

In 2004 Louie discovered that the rearrangement of unactivated vinylcyclopropanes can be performed with a catalytic system consisting of Ni(COD)2/N-heterocyclic carbene (NHC). (NOTE: Although the term “NHC” is widespread in the literature, the authors suggest refraining from the usage of this terminology. As there is no experimental proof that such species are true carbenes (they are in fact zwitter-ions!) the term NHC is misleading, inaccurate, and incorrect. It is only a resonance form of the zwitterion, not a true reactive entity. The metal complexes of such species should be referred to as carbenoids.) Utilization of sterically hindered “NHC” ligands allowed this reaction to proceed at significantly lower temperatures (room temperature to 60 °C) than with phosphine ligands, equation 25. Later this reaction was also utilized by Murakami168 for bicyclic systems. Louie and Tantillo studied the mechanism of the rearrangement under the Ni catalytic system.169 They showed that the rearrangement is likely to proceed via sequential formation of an alkene complex followed by the opening of the cyclopropane and formation of complexes with different hapticity, as shown in Scheme 11.

1016

Rearrangements of Vinylcyclopropanes, Divinylcyclopropanes, and Related Systems

R2

R2

R1

Ni(COD)2 1 mol%

R1

R3

IPr 2 mol% solvent, r.t. to 60 °C

R3 R1,3 =

H, Ph, alkyl R2 = H, TMS Solvent = PhMe, benzene, hexanes

ð25Þ 91−96%

[M] [M] [M]-metal catalyst [M] [M]

−[M]

[M]

*[M]

* Scheme 11 Reproduced from Wang, S. C.; Troast, D. M.; Conda-Sheridan, M.; et al. J. Org. Chem. 2009, 74, 7822–7833, with permission from ACS.

5.22.1.3.2.1.2 Metal-catalyzed opening and [3+2] cycloadditions When a vinylcyclopropane is substituted with an electron withdrawing group (EWG), donor/acceptor symmetry causes the electrons to flow in one particular direction. Such a system, for example 30, is susceptible to insertion of a transition metal followed by nucleophilic addition or cycloaddition of unsaturated compounds. Control of the outcome of the three possible modes of reaction is available by changing the metal and/or the ligand environment. As well, the use of chiral complexes can provide access to chiral compounds. Similar reactivity can be observed via Lewis acid mediated cycloaddition. This particular subject has been thoroughly covered in recent reviews.54–56 Most developed metal-catalyzed insertions involve palladium catalysis, proceeding via the formation of η3-metal complexes. The regioselectivity of cycloaddition is dictated by the electronic effects of the second coupling partner as shown in Scheme 12. E E

−A=B+

E

M M

E=CO2R, CN, SO2R, PO(OR)2

E E

E NuH vinylogous mode

30

A B

NuH

Nu

E

E E

E

Nu Scheme 12

The first example of such a [3+2] cycloaddition of an activated vinylcyclopropane as 1,3-dipolar equivalent with an activated alkene was described by Tsuji in 1985.170 Different unsaturated fragments have been used as partners for coupling with activated cyclopropanes. Johnson171 showed that aldehydes also undergo such cycloadditions. The main products are 2,5-disubstituted tetrahydrofurans (THFs) 31. It was shown that electron-poor aldehydes perform better under the chosen reaction conditions (equation 26).

CO2Me CO2Me O +

Pd2(MeO-dba)3 2.5 mol% R

32 5 mol%, PhMe, r.t. to 40 °C

R = aryl

R

31

ð26Þ

Ph

OMe MeO-dba

O

CO2Me

53−99%

O

MeO

MeO2C

Ph

N

N 32

Rearrangements of Vinylcyclopropanes, Divinylcyclopropanes, and Related Systems

1017

Rhodium-catalyzed [3+2] intramolecular cycloadditions of unactivated vinycyclopropanes were shown to proceed selectively172 under the same conditions employed for the [5+2] cycloadditions (see Section 5.22.1.3.2.4). The configuration of the vinylcyclopropane plays a crucial role in the outcome of such process as shown in Scheme 13.

H R1 X

[Rh(CO)2Cl]2 5 mol% R1

X = NTs, O

PhMe 80−110 °C

H

1

R = H, Me R2 = H, Me, Et, Ph,

49−89% R

R

[Rh(1,1-bis(diphenylphosphino) methane)]SbF6 5 mol%

X

H

X

4 Å mol. sieves, DCE 95 °C

n

R

X

X = NTs, NBoc

n

H

69−91%

n = 1,2 R = H, Ph, Bn

H [Rh(dppp)]SbF6 5 mol%

X

X = NTs, NBoc

X

DCE, 80−90 °C

66% for X = NBoc, 93% X = NTs Scheme 13

Complexes of iron173,174 were shown to be efficient and inexpensive catalysts in formal [3+2] cycloadditions as well as in nucleophilic opening. Fürstner173 has shown that activated vinylcyclopropanes undergo nucleophilic opening by Grignard reagents in the presence of Fe(acac)3 to produce allylic products. A more recent study by Plietker174 showed that the mode of reactivity catalyzed by the Bu4N[Fe(CO)3NO]/NHC system can be altered by modifying the NHC ligand as shown in Scheme 14.

E

RMgCl, Fe-cat A 10 mol%

E

PhMe, −30 °C E = CO2Et R = Me, Pri, Prn, But, Bui, c-C5H9

E1

E R

E

N Ph Mes N

Ph N

Yield = 48−83%

R E2 E3

Fe-cat A = Fe(acac)3 Fe-cat B = Bu4NFe[(CO)3NO]/NHC

R

E3

E1

E1

NuH

Fe-cat B/NHC 2 THF, 80 °C R, E2, E3

Fe-cat B/NHC 1 THF, 80 °C E1

H E1

E1 Nu

NuH O 96%

SO2Ph CN

Scheme 14

NHC 2

NHC 1

E2 E1

N Mes

95%

H, SO2Ph, SO2Ph

CO2Me

79%

H, SO2Ph, SO2Ph

CO2CH2CF3

82%

Ph, CN, CN

CN

CH2(CN)2

70%

1018

Rearrangements of Vinylcyclopropanes, Divinylcyclopropanes, and Related Systems

Asymmetric versions of a formal [3+2] cycloadditions have a much shorter history. One of the first examples was performed by Hiroi who used chiral auxiliaries.175 Despite the modest diastereoselectivity, the starting material can be easily accessed in an enantiodivergent way.

E

CO2But

CO2But

E −O

S

+

CN

E E

Pd(PPh3)4 10 mol% PPh3 20 mol% THF, 66 °C

R

E = CO2Me R = 4-Me-C6H4

−O

S+

R

ð27Þ

CN 51% de 66%

Trost176 developed an asymmetric version of the [3+2] cycloaddition with alkylidene azalactones as the ene fragment. Additional activation of the cyclopropyl ring was required by introduction of electron-poor trifluoroethyl esters in order for the reaction to proceed in good yield. The reaction provided products with high enantioselectivity and high diastereomeric ratios (419:1 for R¼ aryl) (equation 28).

O

Ph

O E E

Ph

N

O

R

N

R E E

Pd2(dba)3*CHCl3 2 mol% 33 6 mol%, PhMe, r.t.

51−87% ee 85−98% for R = aryl

E = CO2CH2CF3 R = aryl, n-C6H13, OEt, CH2OSiMe2But O

ð28Þ

O N H

N H

PPh2 Ph2P 33

A similar approach was also described by Shi.177 Palladium catalysis was shown to be quite efficient with the new type of chiral ligands 35. Starting from standard activated cyclopropanes and activated alkenes 34, chiral cyclopentanes were produced with good yields and high enantioselectivity (equation 29).

MeO2C

O

MeO2C

CO2R2

+ R1

1

R = aryl, cyclopropyl R2 = Et, Pri, But, Bn Ts Ph N N

34

Pd2(dba)3*CHCl3 5 mol%

MeO2C

CO2R2

MeO2C 35 10 mol%, PhMe, r.t.

R1

O

61−96% ee 82−96%

ð29Þ

Ph

PPh2 35

Unusual regioselectivity was observed with the iridium catalyst 36 during the coupling of aldehydes with activated vinylcyclopropanes. In contrast to the analogs coupling under palladium catalysis,171 the introduction of iridium led to the opposite regioselectivity of aldehyde insertion. Homoallylic alcohols were produced with good yields and high enantioselectivity (equation 30).

Rearrangements of Vinylcyclopropanes, Divinylcyclopropanes, and Related Systems E E

1019

OH O +

36 5 mol% R K3PO4 5 mol%, H2O, PriOH, 60 °C

R E E

E=CO2Me, CO2Et, PO(OEt)2 R=Ph, n-C8H17, (E)-CH=CH2Ph,

63−89% >17:1 dr, 92−97% ee

O

ð30Þ

O

O

Ir

(S)-BINAP

O CN NO2 36

Different functional groups can be introduced via metal-catalyzed insertion. One of the most useful examples is the borylation of vinylcyclopropanes. The use of the palladium pincer complex 37 was shown178 to lead selectively to E-allyl boronates. Similar transformations were also performed with the Ni(COD)2/phosphine system under milder conditions and were shown to be less demanding with regard to the activation of the cyclopropane ring by EWGs (Scheme 15).179

E

E E

i, ii

B(OR)2

E

PhSe

Pd Cl

SePh

37

E=CO2Me, SO2Ph, CO2Et, CO2But i. B2(OH)4, 37 5 mol%, DMSO, 40 °C, 92−98%;

ii.

O O

B B

O , Ni(COD)2 10 mol%, P(c-C5H9)3 30 mol%, K3PO4 2.25 equivalents, PhMe/MeOH = 30:1, r.t., 44−84% O

Scheme 15

5.22.1.3.2.2 Formal [4+1] cycloadditions catalyzed by metals In some cases no cyclopropanes are isolated during attempted cyclopropanations of electron-rich enolates by vinyl carbenoids. Such a difference in the product outcome has been observed by Davies.145 Depending on the nature of the rhodium catalyst, it was possible to isolate either a cyclopropane or a cyclopentene. The latter outcome was believed to proceed via charged intermediates, which lead directly to the cyclopentene, the product of a “formal” [4+1] annulation, (equation 31).

Ph MeO

N2 +

CO2Me

Rh2(S-DOSP)4 1 mol% CH2Cl2, r.t.

Ph

ð31Þ

MeO CO2Me 79%, 98% ee

1020

Rearrangements of Vinylcyclopropanes, Divinylcyclopropanes, and Related Systems

Hegedus180 discovered that the addition of an electron-rich chromium carbene to methyl sorbate provided the product of the formal [4+1] cycloaddition in one step. It is believed to form through sequential addition and rearrangement of a chromium complex, followed by reductive elimination, as shown in Scheme 16.

H

NMe2

(CO)5 Cr

i

+

Cr(CO)5

(OC)5Cr

NMe2

CO2Me

NMe2 CO2Me

ii

CO2Me

NMe2 CO2Me

i. MeCN, reflux, 27 h; ii. air, sunlight

Yield 34% for two steps Scheme 16

5.22.1.3.2.3 [5+1] Cycloadditions The formal [5+1] rearrangement has a significantly shorter history than other cycloadditions of the vinylcyclopropane system. Before 1990, only a limited number of examples of vinylcyclopropane–cyclopentene rearrangements with stoichiometric iron carbonyls were explored. The first version of the [5+1] cycloaddition with metals other than Fe was discovered for “activated” vinylcyclopropane system containing allene and/or oxygen substituents on the cyclopropane ring. Cobalt 181 and iridium182 catalysts were among the first to be investigated. Mechanistic studies of such cycloadditions were carried out with Fe(CO)5.183 Taber184 showed that this transformation can be used for the synthesis of enantiopure cyclohexenones. A catalytic version of the [5+1] cycloaddition catalyzed by Co2(CO)8 was developed by de Meijere,185 and similar activity was observed for [Rh(CO)2Cl]2 (equation 34). Only vinyl cyclopropanes with substituents on both the double bond and the cyclopropane ring undergo rearrangement under such conditions. Cationic rhodium catalysts, which were developed for [5+2] cycloadditions (vide infra), proved applicable in some cases to [5+1] cycloaddition with unactivated vinylcyclopropane systems186 (equation 35 and Table 7). Yu and coworkers described187 formal [5+1]/[2+2+1] cycloadditions (equation 36). The scope of this transformation is limited to 5-5-6 system. The product of such transformation possesses elements of homo-angular triquinane skeletons. OH

R1 HO

•

R2

R1

1.1 equivalents Co2(CO)8

R2

THF, 0 °C−r.t.

OH 60−87%

R1,2 = H, Ph, n-C6H14

R1

R3

•

R1

R2

IrCl(CO)(PPh3)2 5 mol%

R1 R1

CO 5 atm, xylene, 130 °C

R3 O

R1 = H, Ph R2,3 = Me, Ph, H

R1

R1 R3

R2

Co2(CO)8 5 mol% or [Rh(CO)2Cl]2 2.5 mol% CO, THF, 60 °C

R4

ð32Þ

R4

R1, R4=(CH2)2, H R2=Me, Ph, c-C3H7 R3=Me, vinyl, O(CH2)2OMe

R2

ð33Þ

63−83%

R1

O

R1 R2 R3

R4 R4

Co2(CO)8 16−89% [Rh(CO)2Cl]2 0−95%

ð34Þ

Rearrangements of Vinylcyclopropanes, Divinylcyclopropanes, and Related Systems

R1

O R4

R4 +

CO (0.2 atm) DCE, reflux 4 Å mol. sieves

R3

Table 7

O

[Rh(dppp)]OTf 10 mol%

R2

R1

1021

R3

R1

ð35Þ

R3

R2

R2

38

39

Rhodium-catalyzed [5+1] cycloaddition of unactivated vinylcyclopropanes (equation 35)

Substituents R ¼aryl, CH2NTs R ,R ,R ¼H R1,R3,R4 ¼H, R2 ¼ Ph, CH2OBn R1,R2,R4 ¼H, R3 ¼ CH2OBn CH2OBn, CH2OH, CH2OTBS R1,R4 ¼H,R2,R3 ¼(CH2)4 1

2

3

R1 X

R2

4

Yield of 38 (%)

Yield of 39 (%)

41–74 80, 42 41–68 56

7–43 – 11 –

R1 [Rh(CO)2Cl]2 5 mol%

R1 O

X O + R2

CO (0.2−1 atm) DCE, 80 °C

X

ð36Þ

R2 O 40

X = C(CO2Me)2, NTs, O R1 = alkyl, TMS R2 = H, Me

Table 8

41

Representative examples of distribution of products in formal [5+1]/[2+2+1] reaction (equation 36)

Substituents

Yield of 40 (%)

Yield of 41 (%)

X ¼NTs R1 ¼Pri, R2 ¼H XQC(CO2Me)2 R1 ¼But, R2 ¼H XQO R1 ¼Pri, R2 ¼H X ¼NTs R1 ¼Pri, R2 ¼Me XQC(CO2Me)2 R1 ¼But, R2 ¼Me

72

9

74

–

87

–

31

46

55

18

5.22.1.3.2.4 [5+2] Cycloadditions A [5+2] cycloaddition or rearrangement between vinylcyclopropane and an unsaturated two-carbon partner has been an attractive goal for synthetic chemists over the years, as it offers the possibility to generate multifunctionalized polycyclic structures containing seven-membered rings. This topic has been reviewed extensively over the past 10 years.188 Seminal work was presented by Wender,189 who described intramolecular cycloadditions of vinylcyclopropanes and alkynes with Wilkinson`s catalyst. The addition of AgO trifluoromethanesulfonate (Tf) has shown to lower the catalyst loading significantly and shorten the reaction time. More efficient catalysts were discovered,190 such as [Rh(CO)2Cl]2 with higher functional group compatibility and improved selectivity. It has been shown that cationic Rh(I) complexes are most likely to be the active intermediates in such reactions. For example, other Rh catalysts that induced the [5+2] transformation at room temperature included those developed by Gilbertson191 ((Rh(1,2-bis(diphenylphosphino)ethane; dppe)(CH2Cl2)2]SbF6) and Zhang ([Rh(1,4-bis(diphenylphosphino) butane; dppb)Cl]2/AgSbF6).192 The recent development in this field is the discovery of the tendency of the arene complexes 42193 and 43194 to catalyze [5+2] cycloadditions with exceptional effectiveness and wide substrate scope at room temperature. Arene complex 42 allowed the migration of the double bond in the final product to be suppressed, which was a common problem with [Rh(CO)2Cl]2. [Rh(nbd)Cl]2/AgSbF6 (nbd ¼ norbornadiene) was shown to accomplish successfully the transformation in water in the presence of the water soluble phosphine 46.195 The use of a water–methanol mixture as the solvent facilitated the isolation of nonpolar products. High formal dilution helps to suppress unwanted side reactions.

1022

Rearrangements of Vinylcyclopropanes, Divinylcyclopropanes, and Related Systems Me

Me −

N N Rh SbF6−

+

−

Rh+ SbF6−

p-C6H4SO3− P p-C6H4SO3− p-C6H4SO3− P p-C6H4SO3− 46

44

43

N

Li+

Li+

Fe

42

Fe

45

N

47

Because of the prohibitive cost of rhodium, other metal complexes have been investigated as alternatives in the catalysis of the [5+2] cycloaddition. Trost196 found the commercially available [CpRu(MeCN)3]PF6 complex to be an effective catalyst at room temperature but with somewhat lower yields that the rhodium system 42. Low-valent iron complexes of type 44 and 45 were utilized by Fürstner197 for similar reactions. The Ni(COD)2/SIPr system developed by Louie198 was active in a limited number of cases (Table 8). The scope of this reaction was later expanded to include alkenes and allenes as the cycloaddition partners.199–201 The general reaction is depicted in Scheme 17, and representative examples of rhodium-catalyzed reactions are presented in Table 9. Only geminally disubstituted alkenes are suitable substrates for cycloaddition. Chiral allenes underwent the rearrangement enantioselectively. Vicinally disubstituted alkenes produced inseparable mixtures of products.201

Catalyst

Scheme 17 Table 9

Rhodium-catalyzed [5+2] cycloadditions

Starting material (SM)

R1

Conditions 10 mol% Rh(PPh3)3Cl, PhMe, reflux or 0.5 mol% Rh(PPh3)3Cl, AgOTf, PhMe, reflux

X R2

Product R1

Yield(s) (%)

References

74–88

189

77–94

200, 201

96

199

X R2

R1 = Me, TMS, Ph, CO2Me R2 = H, Me X = O, C(CO2Me)2 R

10 mol% Rh(PPh3)3Cl, PhMe 100–110 °C or 0.1 mol% Rh(PPh3)3Cl, AgOTf, PhMe, reflux

n MeO2C MeO2C

R MeO2C MeO2C

n H

R = H, Me n = 1, 2 • MeO2C MeO2C

R R

R H

10 mol% Rh(PPh3)3Cl, benzene, 100 °C

MeO2C MeO2C H

91% ee 92% ee

Rearrangements of Vinylcyclopropanes, Divinylcyclopropanes, and Related Systems

1023

5.22.1.3.2.5 Intermolecular [5+2] cycloadditions The intermolecular version of the [5+2] cycloaddition, first described by Wender202 for alkynes and vinylcyclopropanes, poses a greater challenge than the intramolecular case. It was shown that additional coordinating siloxy or carboxy groups203 on the vinylcyclopropane ring helped to facilitate such reactions. The scope of alkyne substrates has been shown to be quite extensive, including electron-rich, electron-poor, and terminal alkynes, as depicted in equation 37. The reaction has also shown to be chemoselective toward the alkyne moiety in enynes. The use of alkynes containing coordinating groups has led to higher yields of the cycloaddition products.

+ CH2OH 1

O

i. [Rh(CO)2Cl]2 0.5 mol% DCE, 80 °C

OR1

ii. H+

ð37Þ CH2OH

t

R = SiMe2Bu , CH2CH2OMe

74% for R1 = tert-butyl dimethylsilyl (TBS) 86% R1 = CH2CH2OMe

Reactions with “unactivated” vinylcyclopropanes are possible at higher temperatures; however, these vinylcyclopropanes must contain bulky substituents on position 1 of the cyclopropyl ring and/or oxygen coordinating substituents on the alkene portion of the vinylcyclopropane as shown in equation 38.204 OSiMe2But [Rh(CO)2Cl]2 5 mol%

+ R1 R1 = CO2Me, Ph, CH2OH, CH2OMe, TMS,

DCE or DCE/TFE = 95:5 80 °C

CH2OSiMe2But

ð38Þ

1

R

Yield 81−95%

Wender205 later discovered that intermolecular vinylcyclopropane–alkyne cycloadditions can be performed at room temperature and low loading (0.2–0.5%) with the cationic complex [Rh(C10H8)cod]+ SbF6−. Simple allenes do not undergo cycloaddition, but it has been shown that extra coordinating groups such as alkynes, alkenes, and nitriles facilitate the cycloaddition.206 Alkenes are not suitable substrates for intermolecular cycloadditions of this type. 5.22.1.3.2.6 Asymmetric [5+2] cycloadditions There are very few examples of enantioselective [5+2] cycloadditions. Wender201 observed the first example for the vinylcyclopropane–alkene system by using [Rh(C2H4)2Cl]2/AgOTf with (–)-CHIRAPHOS; however, only 63% ee was obtained. Later207 he showed that the best ligand for such transformations is R-BINAP. The highest ee was achieved for gem-disubstituted alkene fragments. In case of an alkyne or an unsubstituted alkene moiety, low ee's were obtained. Hayashi208 discovered a new catalytic system which was useful in achieving high ee's for vinylcyclopropane–alkyne coupling, as shown in Scheme 18. R1

R1

[Rh(C2H4)2Cl]2 5 mol% X R2

AgOTf 10 mol%, R-BINAP 11 mol%, DCE, 40−70 °C

X H

R2 1

2

X = C(CO2Me)2, R = Me, R = H X = C(CO2Me)2, R1 = H, R2 = Me X = NTs, R1,2 = H Ph X

Ph

[Rh(C2H4)2Cl]2 5 mol% NaBArF4 6 mol%, 48 7.5 mol%, DCM, 30 °C

X H Yield

X=NTs X=C(CO2Me)

Ph O P O

88% 82%

N N Ph

ee 99% 83%

Scheme 18 NaBArF4, sodium tetrakis[3,5-bis (trifluoromethyl)phenyl]borate.

48

Yield 72% 92% 90%

ee 95% 95% 96%

1024

Rearrangements of Vinylcyclopropanes, Divinylcyclopropanes, and Related Systems

Recently, Hudlicky 209 studied the [5+2] cycloaddition with vinylcyclopropanes in which the olefin was constrained into a ring, as shown in equations 39 and 40; however, the yields were extremely low in both inter- and intramolecular applications. Calculations have shown a 16° misalignment of the olefin with the cyclopropane (see Figure 3). (Illustration provided by Dr. Travis Dudding (the structure was optimized with density functional theory (DFT) using B3LYP/6–31G(d)).) The yield of the cycloaddition was later improved to 22% for the intramolecular version.210

O

O

O

[Rh(CO)2Cl]2 5 mol%

O

DCE, 105 °C

O O O

NHAc

NHAc 49

22%

CO2Me + CO2Me

ð39Þ

O

O

[Rh(CO)2Cl]2 5 mol%

O

DCE, 105 °C

MeO2C O MeO2C O

ð40Þ

NHAc 50

Traces

Figure 3 Predicted geometry of compound 49.

5.22.1.4 5.22.1.4.1

Rearrangements of Vinyloxiranes and Cyclopropyl Carbonyls Vinyloxiranes

Rearrangements of vinyloxiranes proceed in an analogous fashion to those of the corresponding vinylcyclopropane, with two notable exceptions. First, they generally require a lower activation energy and therefore take place under milder conditions. Second, most of the thermal rearrangements proceed through zwitterionic or ylide-like intermediates, which are uncommon in carbocyclic cases. The nucleophilic opening of systems such as 51 is more complex because of the coordinative abilities of oxygen and the increased number of possible nucleophilic interactions (Scheme 19). Nevertheless, there is some parallel behavior and predictability in vinyloxirane rearrangements.

Rearrangements of Vinylcyclopropanes, Divinylcyclopropanes, and Related Systems

a

Thermal, a

O

Thermal, b

O

1025

O

b

OH

51

Nu Nu−, a

Nu−, b

Nu O

OH

Nu−, a

Nu−, b O Nu

Nu Scheme 19

5.22.1.4.1.1 Thermal isomerization The study of benzene oxide–oxepin tautomerism, reviewed in the late 1960s, revealed a competing pathway in the rearrangements of trans-divinyloxiranes of type 52 (Scheme 20).211,212 The corresponding cis isomer gave only oxepin 54, whereas the trans isomer gave a 7:3 mixture of dihydrofuran 55 and oxepin 54. The activation parameters implied that the intermediate was biradical 53 (cis-oxide: ΔH‡ ¼ 24.6 kcal mol−1, ΔS‡ ¼ −11.3 cal deg−1 mol−1; trans-oxide: ΔH‡ ¼ 36 kcal mol−1, ΔS‡ ¼  0.4 cal deg−1 mol−1).211 These values indicate processes far lower in energy than those operating in the vinylcyclopropane rearrangement, whereas their difference (11 kcal mol−1) led to the conclusion that the rearrangement was concerted for the syn isomer and biradical for the trans compound.

O

O

53

52

54

170−200 °C

O

O 55

Scheme 20

The mechanism has since been studied on a number of occasions, and it is generally agreed that concerted, electrocyclic closures of ylides are operating in the formation of either oxepins or vinylfurans.213–217 The rate of racemization of optically pure vinyloxiranes has been shown to be 6 times faster than the isomerization to the dihydrofuran.213 Alternatively, cleavage of a vinyloxirane to a carbon–oxygen diradical pair or to a carbene–carbonyl pair has been considered for processes that do not usually lead to the formation of dihydrofuran213,215,218 (though there is a notable exception, see ref.218). Corresponding [1,5] shift pathways are also known for those oxiranes that contain a cis-oriented alkyl group having at least one hydrogen.215 The regio- and stereoselectivity of this rearrangement was found to be excellent.214 Thus the rearrangement of either isomer of vinyloxirane 56 yielded dihydrofuran 57 stereoselectively, whereas that of vinyloxiranes 58 led to a mixture of cis and trans isomers (Scheme 21); cis/trans isomerization was also accomplished photochemically.219 The results were rationalized by involving ylides

O

O Ph

Ph

CO2Me 56a

Scheme 21

MeO2C 70% 57

450 °C MeO C 2 FVP 64%

O

FVP

+

CO2Me 58

CO2Me 56b

O MeO2C

Ph

315 °C

O

R

O −

MeO2C

R 59

60

1026

Rearrangements of Vinylcyclopropanes, Divinylcyclopropanes, and Related Systems

of type 60 and this allowed [2πs+2σa] or [2πa+2σs] closures for the former case and biradicals for the latter, although the epimerization may have taken place after the rearrangement because of the presence of an acidic proton.214 A number of substituents can be placed on the periphery of the vinyloxirane system. For example, alkynyl- and dienyl-oxiranes of the general structures represented by 61a to 61d were extensively studied. Their isomerization to various oxidation states of oxepins competed in some cases with the formation of the corresponding vinylfurans.167,214,215,217,220 O

O

O

61a

61b

61c

O

61d

The control of furan versus oxepin manifolds has been addressed. Vinyloxiranes of type 62 yielded oxepins 63 at lower temperatures, whereas higher temperatures gave dihydrofurans (64; Scheme 22),221 indicating that the Cope-type rearrangement of cis-divinyloxirane may be controlled by precisely defining the temperature profile of the FVP.221,222 A [2+3] dihydrofuran annulation methodology was developed based on this rearrangement. Vinyloxiranes 65 were generated by the stereospecific addition of the lithium dienolate of ethyl α-bromocrotonate to aldehydes, and the subsequent pyrolysis to dihydrofurans 66 (Scheme 23) proceeded in excellent isolated yields (except for R ¼ Bun, Pri).221

O CO2Et

O

O

400 °C FVP

550 °C FVP

CO2Et

CO2Et

O

75%

75%

O

O

63

62

64

Scheme 22

OLi OEt

H R

O

Br O

CO2Et

FVP

R

THF, −100 °C

R

7−95%

Single isomer

66

65 R=

Bun,

Pri,

CO2Et

O

Ph, CH2=CH, 2-furyl, 3-furyl

Scheme 23

The thermal rearrangement of vinyloxiranes equipped with a chiral auxiliary group, such as 67, was studied by Steel,223 but only limited chiral induction was achieved because of the small energy difference in the corresponding transition states (equation 41). O Ph O

N

Ph

O 67

O

PhMe 180 °C

N

Ph

O +

68−72% O O

O

O

N

Ph

O :

O

+ O

Ph 33

O

:

O

O

N

Ph O

Ph 57

O O

N

Ph

O

+

Ph 6

O :

ð41Þ

Ph 4

The 2-vinyloxirane–2,5-dihydrofuran rearrangement is a transformation of interest for industrial applications.224,225 A combination of Lewis acids such as trialkyltin iodides,225 zinc halides,224 and iodide salts can be used as shown in Scheme 24. Njardarson226 found that Bis(hexafluoroacetylacetonato)copper(II) (Cu(hfacac)2) is a convenient catalyst for laboratory application of the rearrangement to a wide range of vinyloxiranes 70 to 2,5-dihydrofurans 71. The process occurs under milder conditions than those employed for the conventional thermal rearrangement. Complete stereoselectivity was observed in these rearrangements (equation 42).

Rearrangements of Vinylcyclopropanes, Divinylcyclopropanes, and Related Systems

1027

i or ii

O

O

68

69

i. LiCl*H2O 5 mass%, ZnCl2 3 mass%, NMP, 130 °C, 99%; ii. (n-C8H17)3(n-C18H37) P+I− 3.5 mass%, (n-C8H17)3 SnI 0.5 mass%, 100 °C, 94%

Scheme 24

R3

Cu(hfacac)2 1 mol% Toluene 150 °C

O

R1 R2

R2 R3 O

R1

70

ð42Þ

71

R1,3-alkyl, H R2 = p-MeC6H4, H, alkyl

Yield 59−97%

Radical addition of alkenes to vinyloxiranes to yield THFs is analogous to the similar reaction of vinylcyclopropanes (equation 43),227 with the same regio- and stereoselectivity, with a predominance of syn isomers having the regiochemistry indicated in 72.228 Radical polymerization of vinyloxiranes has also been reported.229 The rearrangements of vinyl thiiranes proceed in a similar fashion to those of vinyloxiranes. The general field of thermal rearrangements of three-membered heterocycles containing oxygen, sulfur, or nitrogen was reviewed.230 A vast majority of the literature on the rearrangements of vinyloxirane systems deals with those cases where Cope-like rearrangements of the divinyloxiranes are possible. The expansions of such systems to oxepins and further rearrangements and transmutations of, for example, vinylalkynyloxiranes to vinylcyclopropyl aldehydes have also been studied and reviewed.222,228,230 CO2But

Ph

t Ph2S2 1.05 equivalents Bu O2C

+

O

h, AIBN 34 mol% benzene

O

Ph

ð43Þ

47% 72

5.22.1.4.1.2 Nucleophilic opening Vinyloxiranes react with nucleophiles in three regiochemically distinct ways: with α, β, and vinylogous modes of opening. The subject has been of considerable interest in the context of acyclic stereoselection and generation of allylic alcohols in an iterative fashion. Cyclic vinyloxiranes react with organocuprates with inversion of configuration (anti) and in a vinylogous mode (equation 44), not by the expected SN2 reaction that simple oxiranes are known to undergo. This subject has recently been summarized.231,232 The conformation of cyclic vinyloxirane is restricted, whereas the acyclic vinyloxiranes, like vinylcyclopropanes, enjoy a conformational equilibrium, which determines the (E):(Z) ratio of the allylic alcohols that result from interactions with nucleophiles. For example, vinyloxirane 73 gave a E:Z ¼ 4:1 ratio of allylic alcohols 74 (equation 45) with Ph2Cu(CN)Li2, but a 7:2 ratio when (2-C5H5NCH2)2Cu(CN)Li2 was used.233

O

OH

RCuCNLi Et2O, −78 °C to > −40 °C

ð44Þ

R R = Ph 65% Me 95%

R2Cu(CN)Li2 O

R

OH

THF, −78 °C to > r.t. 74

73 R = Ph R= N

(E):(Z) = 3.4:1 (E):(Z) = 7:2

96% 73%

ð45Þ

1028

Rearrangements of Vinylcyclopropanes, Divinylcyclopropanes, and Related Systems

Although the 2,5-substitution pattern inherent in 76 is furnished through thermolytic rearrangements, the 2,3-isomer would result from an SN2′ opening of 75 to allylic iodide 77, which would cyclize to 2,3-functionalized dihydrofuran 78 (Scheme 25).221a,234 Only marginal results were obtained with vinyloxiranes under the conditions adapted from similar opening of vinylcyclopropanes with trimethylsilyl (TMS) iodide and titanium tetrachloride.235

−O

O CO2Et TMSI

500 °C R

O

FVP R

CO2Et

CO2Et

EtO2C

R R

I

R = Ph 95%

Trace 78

77

75

76

O

Scheme 25

Palladium-catalyzed nucleophilic opening of vinyloxiranes received attention in connection with the cis-dihydroxylation reported by Trost in 1985.236 However, Pd-catalyzed SN2′ addition of nucleophiles is not a predominant mode for vinyloxiranes. Baeckvall237 described opening of enantiomerically pure cis- and trans-vinyl epoxides 79 with NaNHTs in the presence of Pd (PPh3)4. The reaction proceeded with high regio- and stereoselectivity. OBn

NHTs TsNH2, NaNHTs

O 79a

R

Pd(PPh3)4 5 mol%, MeCN, 40 °C

BnO

ð46Þ

R

OH 67−86%

R=Me, Prn, Bun

OBn

NHTs TsNH2, NaNHTs

O

R

79b

Pd(PPh3)4 5 mol%, MeCN, 40 °C

ð47Þ

BnO R

OH 81−91%

Trost238 described a general approach for asymmetric opening of vinyloxiranes 80 with alcohols 81. Starting from racemic epoxides, it was possible to achieve dynamic resolution with a wide range of alcohols. The reaction was believed to proceed via a π-allyl palladium complex 82. In order to increase the nucleophilicity of the alcohol and change the reaction to an intramolecular mode triethylborane was added as cocatalyst. High enantiomeric excess (80–98%) was achieved. Trost239 also showed that under similar conditions the opening of vinyloxiranes can be achieved with nitrogen nucleophiles containing acidic N–H bonds, such as the case of phthalimide, in good yields and with high enantiomeric excess (up to 98% ee) (equation 49).

Pd2(dba)3*CHCl3 1 mol%, 33 3 mol%

HO O

+

80

Et3B 1 mol%, CH2Cl2, r.t.

81

Et Et B− O O Pd+

OH O

82

ð48Þ

83 83% ee 95%

O NH O

HO O

O

Pd(C3H5)2Cl2 2.5 mol%, 33 7.5 mol%, Cs2CO3, THF, r.t.

ð49Þ

N

HO HO

O

87%, 82% ee

Rearrangements of Vinylcyclopropanes, Divinylcyclopropanes, and Related Systems

1029

Vinyloxiranes also undergo opening with carbon nucleophiles. With soft nucleophiles and products formed via π-allyl metal intermediates, SN2′ addition can be expected, whereas hard nucleophiles tend to form products of SN2 addition. Certain methods can lead to the selective formation of either SN2 or SN2′ products depending on the conditions and additives. Trost240a studied the addition of soft carbon nucleophiles to a chiral vinyloxirane 84 and showed that the reaction proceeds smoothly with retention of configuration (equation 50). He and his group240b also described conditions for selective asymmetric SN2 opening of vinyloxiranes utilizing Pd-catalyzed conditions. Some alkynyl lithium salts can serve as soft nucleophiles and the mode of addition to the vinyloxirane can be controlled. A combination of copper salts and chiral phosphoramidite 48 (see Scheme 18) was utilized for the asymmetric resolution of cyclic vinyloxiranes 86 with alkyl zinc241 and alkyl aluminum reagents.242 Different ligands and sources of copper were studied (equation 51). Prn

+

SO2Ph

O

O

Prn

PhO2S

OH

85, THF reflux

O

84

Pd2(dba)3*CHCl3

ð50Þ

55%

Et O O P O

(No catalyst loading in original paper)

85

R +

i or ii

O

HO

n

n 86

HO

R

n

87

88

ð51Þ

i. n = 2, 33% ee 92% ratio 87:88 = 13:1 ii. n = 2, 50% ee 61% ratio 87:88 = 98:2

n = 1−3

i. Me2Zn Cu(OTf)2 3 mol%, 48 6 mol%, toluene, −70 °C ii. Me3Al CuTC 1 mol%, 48 2 mol%, THF, −70 °C

5.22.1.4.2

Cyclopropyl carbonyls

When the vinylcyclopropane system contains a heteroatom within the alkene portion, it is highly susceptible to rearrangements governed by donor–acceptor principles. Under appropriate conditions the ring closure of systems such as 89, in addition to normal diradical pathways, can occur by two additional mechanisms: unraveling of a cyclopropylcarbinyl cation system (path a) or the action of a lone pair of an additional donor atom (or a full anion) resembling the unraveling of a cyclopropylcarbinyl anion (path b; Scheme 26). Ideally, both processes can reinforce one another to lead easily to rearrangements of systems such as 90 to the corresponding 1,4-dicarbonyl compounds, reported as early as 1938 (Scheme 27).243 Recognition that the cyclopropylcarbinyl cation cleaves to provide additional unsaturation led to the methodology of acid- or base-catalyzed unraveling of systems of type 91 to the corresponding β,γ-unsaturated carbonyls (equation 52).244 Only one review on the topic of synthesis and reactivity of cyclopropyl carbonyls and imines has been published in the past 20 years.245 X

R

X

b Y

a R

Y

−X

−X

Y

+

R

+

Y

89 X = O, NR; R = alkyl, aryl, OR Scheme 26

NaOEt Br

CO2Et

CO2Et

22% EtO 90

Scheme 27

O KOH, H2O

OH

H O

R

1030

Rearrangements of Vinylcyclopropanes, Divinylcyclopropanes, and Related Systems

HO

R

R

R H+

R H

ð52Þ

OR O 50% for R=Ph

91

The above processes constitute the foundation on which Wenkert developed a general synthetic methodology applicable to terpenoid and alkaloid syntheses.47,48 The carbonyl can be viewed as a hetero-vinyl moiety participating in the overall (heterovinyl)-cyclopropane–cyclopentene rearrangement, as shown in Scheme 28, even though the mechanism involves the cyclopropylcarbinyl rearrangement. HO RO

H+

O

OR

+

RO

OR

Δ

O

OR O

O RO

RO Scheme 28

Either isomer of 92 was converted into dihydrofuran 93 on alumina as an alternative to acid-catalyzed conditions (equation 53).246 One methodology for α-methylene lactone synthesis relies on the solvolysis of cyclopropyl esters of type 94 to give α-methylene lactone 95 with Li2CO3 in dioxane (equation 54). The formation of the undesired diene 96 was diminished by the use of AgClO4.247 Al2O3 (on chromatography) O CO2Et

MeO

100%

EtO2C

OMe

O

ð53Þ

93

92

Br AgClO4

O O +

CO2Me dioxane, r.t. OMe 94

CO2Me

OMe

OMe

95 85%

96 15%

ð54Þ

Vinylcyclopropanes containing carboxylates react selectively through the agency of the carbonyl group in acid-catalyzed rearrangements, as shown in equation 55.248 It is noteworthy that neither of the two alternative pathways, the divinylcyclopropane Cope rearrangement of 97 or cyclopentene rearrangement(s), takes place. Further examples of carboxylate over vinyl selectivity are seen in the rearrangements of cyclopropanes 98 and 99 to the corresponding tetrahydrofuranones (Scheme 29).249 Trifluoroacetic acid (TFA) CO2But 97

CH2Cl2 100%

H O O

ð55Þ

H

Thermal rearrangements of various dibenzosemibullvalenes have been described.250 On heating, the compounds underwent clean rearrangements to the corresponding dihydrofurans 100. It is interesting to note that under direct irradiation the products are converted back to the starting cyclopropyl ketones, in contrast to direct photoconversion of cyclopropyl carbonyl to

Rearrangements of Vinylcyclopropanes, Divinylcyclopropanes, and Related Systems

O

O

1031

O

H

i O

O

CO2Et

O

39% H

98 O

i

O

CO2Et

98% CO2Et CO2Et i. (Me3SiO)2SO2, DCE, reflux 1 h

99 Scheme 29

gem-disubstituted dimethyl dihydrofurans,137 (equation 56; compare to Scheme 6). FVP was applied by de Meijere251 to produce complex diazepine products such as 101 (equation 57). Treatment of activated silylcyclopropyl ketones with acids252 in aprotic conditions or with excess of TMS triflate253 lead to conversion to the corresponding 2,3-dihydrofurans or cyclobutanones. Most substrates provided highest conversion with TMS triflate, as shown in Scheme 30 and Table 10. Ph

O o-DCB reflux

Ph

PhCO

R1

R1 PhCO

h

O

R2

R2

ð56Þ R1=H, R2=t-Bu R1=H, R2=COMe R1=COMe, R2=Me R1=COPh, R2=Me R1=p-ArOMe, R2=H

R N

100

200 °C >0.04 torr 85−91%

NH

O

R N

O O

O

ð57Þ

NH O 101

O R = CH2(C6H4)-p-OMe, CH2(C6H4)-p-Cl

R3 R2 R1

R3

R3 O

Conditions A, B, C

SiMe3

R1 R2

O 102

+ SiMe3 R2 R1

R1 = H, Me R2 = H, Me, Ph, (CH2)4 R3 = H, Me, (CH2)4

O 103

Conditions A H2SO4 THF/1,2-dimethoxyethane (DME) 60 °C Conditions B TfOH, DME, −20 °C Conditions C Me3SiOTf 1−5 equivalents, CH2Cl2, −78 °C Scheme 30

Table 10 1

2

3

Acid-catalyzed rearrangement of silyl cyclopropyl ketones (Scheme 30)

R ,R ,R

Conditions

Product (Yield %)

H, Ph, H Me, Me, H H, Ph, H H, Ph, H

A A B C

103 102 102 102

(70) (69) (75) (99)

1032

Rearrangements of Vinylcyclopropanes, Divinylcyclopropanes, and Related Systems

Theodorakis254 utilized the acid-catalyzed rearrangement of bicyclic systems to produce bicyclic lactones (equation 58). Lewis acids have also been used for similar rearrangements in order to stabilize opened, charged intermediates. Yadav255 and Johnson256 showed that 1-acyl-2-vinylcyclopropanes can be rearranged with Ni(cod)2256 or with a range of Lewis acids255 (equation 59). In analogy with the anion accelerated vinylcyclopropane–cyclopentene rearrangement, such as the one used in specionin synthesis (see Table 12 and ref. 381) cyclopropyl carbonyls masked as silyl enol ethers rearrange, via the corresponding enolate anions, as shown in equation 60 and described by Davies.257 The rearrangements proceed with good diastereoselectivity but with complete racemization in the absence of a chiral auxiliary. O

BunO

O

n MeSO3H Bu O

CO2Et

O

Acetone

ð58Þ

O 72%

O

CO2Et

TiCl4

EtO2C

CH2Cl2 −30 °C to r.t.

SiPh2But

ð59Þ

O t-BuPh2Si 70%

R1

R1

CO2R3 OTBS

−78 °C

R2O

R2O

R1 = H, Me R2 = Bu, Et R3 = Me, O

5.22.1.4.2.1

CO2Me

TBAF O

ð60Þ

Yield = 32−82% de 67−86%

O

Transient cyclopropyl carbonyls

Cyclopropane systems that contain donor and acceptor substituents on vicinal carbons are predisposed to undergo opening and rearrangement to more stable dihydrofuran moieties (equation 61). Suitable substrates can be generated by metalation of sulfonyl cyclopropanes such as 104123,258 and lithium salts can be quenched by acyl imidazoles (Im). On heating to room temperature, these compounds rearrange to dihydrofurans. Oxidation of cyclopropyl sulfides with electron-rich aryl substituents to the corresponding sulfones leads to rearrangement to dihydrofurans (equation 62).259 Upon insertion of carbenoid intermediates to electron-rich enol ethers derived from α,β-unsaturated ketones the resulting cyclopropane intermediates can undergo further rearrangement to dihydrofurans.260 SO2Ph i, ii

R1O

SO2Ph R3

2

R O

R1

R

1

SO2Ph R2O R1

O

O

R3

104

ð61Þ R1=n-C6H13CH=CH, R2=Me, R3=alkyl 63−78% 18−79% R1=OPh, R2=Ph, R3=alkyl, aryl

i. BuLi, −78 °C, THF; ii. R3COIm, −78 °C to r.t.

SO2Ph

SPh m-chloroperbenzoic acid R

O

0 °C to r.t., 16 h

R

O

R = 4-C6H4-Me, 4-C6H4-OMe 40−51%

ð62Þ

Rearrangements of Vinylcyclopropanes, Divinylcyclopropanes, and Related Systems 5.22.1.5 5.22.1.5.1

1033

Rearrangements of Vinylaziridines and Cyclopropyl Imines Rearrangement of vinylaziridines

Like vinyloxiranes, vinylaziridines are subject to a number of rearrangements that parallel the pathways available to vinylcyclopropanes. Unlike them, however, vinylaziridines undergo extremely well-controlled nucleophilic opening to furnish pyrrolines under nonthermolytic conditions. They are easily prepared from alkenes and azides via triazolines.261 Because of the valency of nitrogen there are two topographical isomers possible, 105 or 107, each leading to a different tautomer of pyrroline 106a or 106b, and an additional isomer, 3-pyrroline 108, available through cleavage of bond a in 107 (Scheme 31). This remarkable property of vinyl- aziridines translates into the selective preparation of all possible isomers of pyrroline, 1-, 2-, and 3-pyrroline, by careful “tuning” of the reactivity of 105 and 107 through substituent effects and the knowledge of probable reaction intermediates. Much of the thermal and photochemical behavior of vinylaziridines may be rationalized through either diradical or zwitterionic (azomethine ylide) intermediates. This subject has been thoroughly summarized.51,230,262,263

N

N

H N

106a

106b

H N

b

a

a

H N

a

105

b 107

108

Scheme 31

5.22.1.5.1.1 Thermal rearrangements of vinylaziridines Vinylaziridines such as 109 have been rearranged thermally to 3-pyrrolines (equation 63),264,265 presumably through one of the species 111. Substituents play an important role in the likelihood of these intermediates.266 The energy of activation for carbon– nitrogen bond cleavage has been estimated to be 12–14 kcal mol−1 (compared with 27 kcal mol−1 for cyclopropane).267 Vinylaziridines of type 112 (R¼ alkyl) furnish 1-pyrrolines 113 or, if X is another heteroatom, the corresponding heterocyclopentenes (equation 64).265,268 R N

100 °C

(During gas chromatography) N R

109

110

ð63Þ R N

or −

R N

+

or

R N

−

+

111

X

R N

Δ

N R X

X=CR2, O,S, NR 37−90% 112

ð64Þ

113

The competing reaction involves the formation of imines (presumably via diradicals and hydrogen migration), as proposed by Logothetis to account for the formation of imines in the thermolysis of aziridines.269 Imine formation is sometimes observed as a competing pathway in the thermolysis of N-substituted vinylaziridines270 and can also be rationalized by a process analogous to a [1,5] homodienyl shift.230,271,272 In cyclic systems with proper stereochemistry (endo) this process may predominate, as evidenced by the isolation of only the (E)-alkene 115 (R ¼ CO2Et; Scheme 32).271,272 Reaction of vinylaziridines 116 with NaI in refluxing acetone led to 3-pyrrolines 118 (Scheme 33).273,274 When the N-substituent contains an additional alkene as in the case of 119a, the possibility of an intervening Cope-like rearrangement will complicate pyrroline formation. The selectivity between these two pathways usually depends on the stereochemistry of the

1034

Rearrangements of Vinylcyclopropanes, Divinylcyclopropanes, and Related Systems

R

•

R N •

N

[1,5]

R

N

R

THF reflux

H

Benzene reflux

R=CO2Et 90%

N R=CO2Et 82%

116

R=H, CO2Et

114

115

Scheme 32

vinylaziridine, and the temperature of the rearrangement (higher temperatures favor the pyrroline formation as the Cope rearrangement is frequently reversible.) No cis/trans isomerization was observed in the case of 119a.275 The divinylaziridine rearrangement as well as the [1,5] shift pathways of vinylaziridines can be controlled according to the principles found valid with vinylcyclopropanes or vinyloxiranes. Some aspects of the rearrangements of vinylaziridines have been reviewed.23,45,230,263,276 I

NaI N

Acetone reflux

R R=allyl, aryl

or

−

116 R2

N R

N R

I

N R R=p-BrC6H491% 118

117 R3

R2 R3

R1 R1

−

N

N

Δ trans

H N

Δ

R1 R2

cis

R3 119a

60−65%

(Yield of azepines was not specified)

R1,2,3 = Me, H Scheme 33

Photochemical rearrangements have also been reported, as shown in equation 65.277,278 Transition-metal-catalyzed rearrangement [palladium(0)] of a dienylaziridine has been reported in one case,279 and a radical opening of a dienylaziridine led to pyrroline formation under the conditions of radical initiation with azobisisobutyronitrile (AIBN)/Ph3SnH (equation 66).280 For those vinylaziridines that contain additional unsaturation, the corresponding aza equivalent of a divinylcyclopropane Cope rearrangement is the usual pathway.281 The pyrroline–azepine pathways are usually controllable by determining temperature profiles for the reactions. Higher temperatures favor pyrroline formation. Compared to vinylcyclopropanes, vinylaziridines have not enjoyed wide applicability in synthetic schemes or for annulation before the discovery and development of [4+1] pyrroline annulation (Scheme 34).51,271,272,282–284 Activation of the dienes with EWGs proved necessary for the formation of vinylaziridines 121 (through intermediate triazolines and their thermal decomposition).284 Noteworthy is the selectivity in bond activation in 121 (Scheme 34). O 155 °C or N

N

ð65Þ

h (366 nm) MeOH O 79%

Ph3SnH N Ts

N Ts AIBN, 80 °C benzene

64%

ð66Þ

Rearrangements of Vinylcyclopropanes, Divinylcyclopropanes, and Related Systems

X

X

X CO2Et

120

X = H, OR

CO2Et

H

ii 89%

N

94%

N3

CO2Et

i

1035

N

121

122

i. PhMe, Δ; ii. 485 °C Scheme 34

Compounds of type 123 (Scheme 35) have been found to yield pyrrolines 125 through the vinylaziridine–pyrroline rearrangement of 124 (not isolated) in refluxing CHCl3 or THF, albeit in moderate yields (31–62%).285,286 The heteroatom substitution apparently accelerates the rearrangement. Somfai287 showed that vinylaziridines may be rearranged to 3-pyrrolines under microwave radiation in presence of salts such as LiI or NaI. Njardarson288 discovered that electron-deficient Cu(hfacac)2 can promote a smooth rearrangement of electron-deficient vinylaziridines to the corresponding 2,5-dyhydropyrroles (equation 67). He extended the scope of this rearrangement to enantiopure aziridines,289 in which the reaction proceeded with complete retention of optical purity unlike similar vinylcyclopropane–cyclopentene rearrangements. It is important to note that only electron-poor aziridines (R1 ¼ p-toluenesulfonate (Ts), p-nitrobenzenesulfonyl) can be transformed under such conditions.

X

X

X Reflux

N3

CHCl3

N

N 124

123 X = SPh,

OSiMe2But,

125 OCH(CH3)OEt

31−65%

Scheme 35

CO2Et N Ts

Cu(hfacac)2 5 mol% Toluene 150 °C

N Ts

CO2Et

ð67Þ

90%

5.22.1.5.1.2 Nucleophilic opening of vinylaziridines The mechanistic details of the nucleophilic opening of vinylaziridines are similar to those operating on vinyloxiranes. Whereas thermolysis of 127 leads to pyrrolizidine 130,271,272,284 likely through the agency of azomethine ylide 129, nucleophilic opening leads exclusively to 128 through intermediate allylic iodides 131, which are produced as mixtures of (E)- and (Z)-isomers but are converted into 128 through equilibration and recycling of the (Z)-isomer (Scheme 36).282 It was shown by Ibuka and coworkers in 1994290 that copper reagents can open acyclic vinylaziridines in a SN2′ fashion (Scheme 37). The same year Wipf291 succeeded in opening of N-acyl aziridines with cyanocuprates in the presence of BF3. High anti-selectivity was achieved (equation 68). Later Hudlicky292 applied similar conditions to the opening of cyclic vinylaziridine 132. The main product was formed as a result of selective syn-SN2′ addition. The predominance of the syn addition was explained by the high steric demand of the acetonide to proceed in anti-fashion (equation 69). Sweeney293 showed that 2,3-trans-3-aryl-2vinylaziridines can be opened with lithium dialkyl cuprates in exclusive SN2′ fashion (equation 70).

CO2Me N Ph

O

MeCu(CN)Li 1.2 equivalents BF3*Et2O, THF, −78 °C

CO2Me Ph

NH O 65%

ð68Þ

1036

Rearrangements of Vinylcyclopropanes, Divinylcyclopropanes, and Related Systems

CO2Et

CO2Et

i 85%

N3

91%

N

126

N

127

128

N+ −

N

CO2Et

CO2Et

129

130

CO2Et

CO2Et

CO2Et (Z )-isomer

Me3SiI N

CO2Et

ii

N

(Z )-isomer

N SiMe3 I

131

127

128

i. Toluene, Δ; ii. Me3SiI, CH2Cl2, −50 °C; Scheme 36

Me

R1

CO2Me

R1

i

R1 i

CO2Me

N Ts

N Ts

NHTs Me

R1

i N Ts

CO2Me

R1

CO2Me

R1

CO2Me

i

CO2Me

N Ts

NHTs Yield = 91−97% + 1−8% of SN2 product

R1 = H, Me

i. 3−4 equivalents Me3ZnLi/30 mol% CuCN or MeCu(CN)Li, THF, −78 °C

Scheme 37 R O

Ph2CuLi

O

THF, −78 °C to −40 °C

O TsN

O

O + O

R

ð69Þ

NHTs

NHTs 132

6%

38%

Bun Bun

2CuLi

Ph N

Et2O, −78 °C to r.t.

HN Ph2(O)P

R1

ð70Þ

P(O)Ph2 74%

The catalytic enantioselective opening of vinylaziridines in the presence of copper catalysts has been studied by Pineschi.294 During his work with cyclic vinyl epoxides (see Section 5.22.1.4.1.2), he discovered that cyclic 2-alkenyl N-carboxybenzyl (Cbz)protected aziridines can be opened by alkylzinc reagents in the presence of Cu(OTf)2/phoshoramidite ligands with an enantiomeric excess range of 5–83%. Without the ligand, there were unexpected amounts (50%) of the syn product observed, explained by the complexation of the copper with the Cbz group (equation 71). Comasseto295 screened different organometallic reagents and showed that higher order cuprates gave the best selectivity for SN2′ addition for cyclic and acyclic aziridines.

Rearrangements of Vinylcyclopropanes, Divinylcyclopropanes, and Related Systems

1037

R

R R2Zn Cu(OTf)2 3 mol%, 48 6 mol%, PhMe, −78 °C to >r.t.

NCbz

+

+

R NCBz

NCbz

NCbz

ð71Þ

Conversion 42−100%

R = Me, Et

5.22.1.5.1.3 Cycloadditions of vinylaziridines Alper296 showed that vinylaziridines can undergo cycloadditions with a variety of isocyanates, carbodiimides, and isothiocyanates with Pd(OAc)2/PPh3 as the catalytic system. The reaction proceeds via formation of a π–allylpalladium complex (Scheme 38, Table 11).

Pd(OAc)2 / PPh3, r.t.

R2

R1

X • Y

NR2

R1

Pd+

R1 N

− NR2

X Y a NAr NAr b O NAr c NAr S

Y X

R1 = H, alkyl R2 = alkyl

36−97%

Scheme 38 Table 11

Cycloaddition reaction of vinylaziridines with different unsaturated partners

X,Y

R1,R2

Yield (%)

O, PhN PhN, PhN PhN, S

c-C6H11, H c-C6H11, H c-C6H11, H

89 60 96

Yamamoto297 described similar cycloadditions with olefins activated by EWGs. The reaction proceeded with high yields but low diastereoselectivities, with ratios of cis to trans in the range of 23:77–55:45 (equation 72). E R1 N Ts

E E

E

Pd2(dba)3 5 mol%, P(p-FC6H4)3 40 mol%, THF, r.t.

R1 = aryl, H E = CN, SO2Ph

R N Ts 69−99%

ð72Þ

1

Trost298 described the first example of an enantioselective version of the cycloaddition of isocyanates to vinylaziridines in the presence of Pd(allyl)2Cl2/(R,R)-33. The reaction proceeded with good yields and in reasonable enantiomeric excess in the presence of an acidic additive such as acetic acid. Later the same group utilized this transformation in total synthesis.299 Alper300 discovered that similar reactivity can be achieved also with BINAP and CeCl3 as an additive (Scheme 39).

R2

R2 + NR1

R3NCO

i or ii

R3 N

N R1 O

Scheme 39

i. Pd(C3H7)2Cl22 mol%, 33 6 mol%, DCM AcOH 10 mol%, r.t.

R1=CH2aryl, Ts R2=H,Me R3=aryl

ii. Pd2(dba)3 2.5 mol%, BINAP 10 mol%, CeCl3 10 mol%, THF, r.t.

R1=Cy, But R2=H R3=aryl

52−99% ee 13−95%

58−85% ee 60−83%

1038

Rearrangements of Vinylcyclopropanes, Divinylcyclopropanes, and Related Systems

The first example of a palladium-catalyzed cycloaddition of carbon monoxide to vinylaziridines was described in 1991 by Ohfune (equation 73).301 Regardless of the configuration of the starting vinylaziridines, only the trans β-lactam was formed in moderate yield. Somfai and Tanner302 utilized this transformation in the synthesis of the carbapenem antibiotic (+)-PS-5. OBn BnO

Pd2(dba)3*CHCl3 20 mol%, PPh3 1.5 equivalents

ð73Þ

N

CO 1 atm, benzene

N Boc

O

tert-butoxycarbonyl

51%

Expanding this methodology to a broader scope of substrates, Aggarwal303 discovered that changing the solvent significantly alters the stereochemical outcome. He also discovered that silyl-substituted aziridines can produce δ-lactams as the only product of what seems to be a [5+1] cycloaddition, contrary to the typical reaction of such a system to produce β-lactams (Scheme 40).

R1 R2

R1 i O

N Ts

Ph

R2 = TMS 61%

N Ts

R2

N

i

Ts

+

O

R2 = aryl, Me

R1 = aryl

R2

R1 N Ts

O R

R1

59−79% +

2

N Ts

O

i. Pd2(dba)3*CHCl3 5 mol%, PPh3 60 mol%, CO 1 atm, PhMe, r.t. Scheme 40

Iron-mediated processes were described by Ley.304 Sonication of vinylaziridine with Fe2(CO)9 produces a stable iron complex that can be reduced and transformed to the β-lactam by oxidation with Me3NO (Scheme 41).

O R2

Fe(CO)3

R1

R4

Fe2(CO)9

R3

R2

R1 R2

Benzene, 30 °C, )))

N R3

R4

R3

71−77%

R1,2 = H, Me R3 = CO2Me, Bn R4 = H, Ac

R4

R1

N

N O

54−69%

Scheme 41

Louie305 discovered that a formal [5+2]-cycloaddition occurred up on heating electron-rich vinylaziridines with phenyl isocyanates in nonpolar solvents with formation of seven-membered cyclic ureas. Byproducts were five-membered ureas and oxazolidines. It has been shown that only trans-substituted aziridines form seven-membered cyclic ureas (equation 74). Recently Saito306 showed that a similar reaction can proceed at 0 °C with activated mesyl and tosyl isocyanates (equation 75).

O C N Ph +

Bn N

O 100 °C

Ph

Bn

N

N N

PhMe

Ph

O

Ph + Bn N

O

+

Bn N

N Ph

ð74Þ

Ph 41%

39%

Ph

9%

Ph

Rearrangements of Vinylcyclopropanes, Divinylcyclopropanes, and Related Systems

O C N SO2R1 + R2 N

O

R2

0 °C

N

N

1039

R1

CH2Cl2

R3

ð75Þ

R3

83−98% R1 = Me, 4-MeC6H4 2 n R = Bn,c-C6H13, Bu , 2,4-dimethoxyphenyl R3 = H, Me

Yudin307 described the reaction of N-unsubstituted vinylaziridines with dimethyl acetylenedicarboxylate (DMAD). The use of different solvents led to the formation of dihydroazepines or bicyclic 4,5-systems (Scheme 42).

MeO2C + HN

MeO2C

CO2Me

CO2Me

N

r.t.

MeO2C PhMe

CO2Me

N Ph

Ph

(No yield in paper)

Ph MeO2C H + N

CO2Me

Ph

N

DMSO

CO2Me CO2Me

Ph

H 70%

Scheme 42

The Ni(0)/NHC catalytic system developed by Louie308 was applied in the intramolecular cycloaddition reaction between alkynes and aziridines. In order to suppress the competing β-hydride shift, a large substituent on nitrogen was required. Screening of various ligands showed that the most efficient ones were SIPr and IMes (equation 76). O

O Ni(COD)2 5 mol% NHC 10 mol% benzene, 60 °C N conversion triphenylmethyl (Tr) 100% NHC It-Bu IMes IPr SIPr

5.22.1.5.2

O

O +

+

Tr

Tr

N Tr

a

b

c (ratio)

1 − − −

− 1 1 4

2 1 1

N

N

ð76Þ

−

Cyclopropyl imines

The cyclopropylimine–pyrroline rearrangement (Cloke rearrangement) has been known since 1929, long before the discovery of the parent vinylcyclopropane system.309 Rearrangements of cyclopropylimines have been studied recently in the context of the effects of heteroatom substitution on rearrangements of cyclopropanes.245 Dicyclopropylimine 133 rearranged to pyrroline 134 not to 2-pyrroline 137, the product expected from the accelerating effect of the amino substituent (Scheme 43). Further reaction and hydrolysis led to pyrrolizidone 136.310 The effects of substituents (N, S) were investigated on substrates shown in equation 77.247 Sulfur and nitrogen did not exert an effect of the magnitude expected from similar studies on vinylcyclopropanes. It may be attributed to the mechanistic duality of this rearrangement, which may involve nucleophilic opening followed by alkylation. The observed preference for the rearrangement of the less-substituted cyclopropane may have its roots in steric effects and the preference for the nucleophilic attack at the less-substituted site. Stevens obtained a different result.311,312 The piperidinyl-substituted cyclopropane in 138 rearranged on thermolysis in the presence of an acid with a nonnucleophilic counterion and gave pyrrole 139 up on further acid-catalyzed elimination (equation 78).311,312

1040

Rearrangements of Vinylcyclopropanes, Divinylcyclopropanes, and Related Systems

O NH4Cl

N NH

HBr

N

Xylene, Δ 78%

H3O

N

140 °C

N

51%

N

133

+

N

134

135

136

N HN 137 Scheme 43

N

H

R1

NH4Cl

R2

R1

N N R2

138a R1 = piperidinyl , R2 = H R1

R2

138b = piperidinyl, 138c R1 = H, R2 = SPh

N R1

SPh

+

Xylene

= SH

ð77Þ −

78% 69% 28%

− 22%

H R2

Xylene, Δ R1 = piperidinyl 138a 138b

R2

Me2O, HBF4 N H

ð78Þ

139 R2=H R2=SPh

32% 42%

Cyclopropyl imines are usually generated by reduction of nitriles or condensation of carbonyl compounds with amines.312,313 An alternative to this process involves the generation of cyclopropylimmonium salts such as 141 at room temperature from a cyanohydrin equivalent such as 140 (Scheme 44).314

N

+ LiBr AgBF4 1.5 equivalents N BF 4− DME, r.t. CN MeCN, r.t. 60% OAc OAc

140

+

N

Br −

OAc 141

Scheme 44

The rearrangement proceeds thermally under acid catalysis by HBr, NH4Cl, or via nucleophilic opening and reclosure as in the case of vinylaziridines. Sulfur substitution has been found effective in accelerating the rearrangement as well as serving as a site of further functionalization. This feature has been especially exhibited in the synthesis of pyrrolizidine and Amaryllidaceae alkaloids.312,313 The synthesis of cyclopropylimines was discussed in detail in a 2007 review.315 Their rearrangement takes place under conditions similar to those employed for vinylcyclopropane–cyclopentene rearrangements; high temperatures (300–500 °C) are sometimes required. Unsubstituted C-cyclopropyl imine is stable toward heating up to 650 °C in the absence of acid. When Wu316 studied the FVP of C-cyclopropyl imine, he discovered that N-acyl imines, with a stabilizing group on the cyclopropyl ring

Rearrangements of Vinylcyclopropanes, Divinylcyclopropanes, and Related Systems

1041

generated in situ, undergo rearrangement with moderate yields. In case of unsubstituted and alkyl-substituted cyclopropanes decomposition was observed (Scheme 45).

Ac N

R1 R2

400−500 °C 10−2

OAc

R1

R2

%

H Ph PhCO H

Ph H H CO2Me

37 38 21 35

R

R2

Ac N

1

torr

R1

R2

N Ac

Scheme 45

Kagabu317 discovered that gem-dihalosubstituted cyclopropyl imines produce heterocyclic compounds under thermal conditions and with different additives (bases, metal oxides, inorganic salts). In the case of N-benzyl (Bn) substituted imines, the main products were pyridines. Pyrroles were generated from N-alkyl-substituted imines and gem-difluoro cyclopentene (Scheme 46). Later the same group320b published a more extensive study showing that N-substituents without α-protons undergo rearrangements to pyrroles. The mechanism is believed to vary for different substrates. In case of gem-difluorocyclopentene, radical cleavage occurs. gem-Dichlorocyclopropyl imines undergo the rearrangement via cationic intermediates. De Meijere251 showed that this rearrangement can generate complex molecules starting from cyclopropyl ketimines (equation 79). Cl p-MeC6H4

Cl Cl

Ph

220 °C

N

+

Benzene

p-MeC6H4

Ph

N

p-MeC6H4

60% F

N 5%

Ph

F F

Ph

Ph N

170 °C Ph

+

N

Benzene

Ph

N

Ph 50%

12%

Scheme 46

R1 N

O

170−240 °C R2

> 0.04 torr

NH

HN

R1 N HN

50−70%

O

NH

R2

ð79Þ

O

O

N-Cyclopropyl imines undergo much smoother rearrangement. It has been shown by Campos and Rodriguez318 that with FVP a variety of unsubstituted and aryl-substituted cyclopropyl imines undergo rearrangement to 1-pyrrolines (equation 80). R1

Ar 3

R N

1

R

R2 R1,2 = H, Ph R3 = H, MePh Ar = Ph, furyl

350 °C 10−3 torr

R2

N

R3 Ar

ð80Þ

26−74%

Photochemical rearrangement has been shown to work only for N-cyclopropyl imines.315 The scope of substrates was investigated under direct irradiation and was shown to proceed with good to excellent yields (equation 81). The mechanism was shown to occur

1042

Rearrangements of Vinylcyclopropanes, Divinylcyclopropanes, and Related Systems

via diradical intermediates,319 but slow interconversion and control of chromophore excitation allowed greater stereoselectivity compared to thermal vinylcyclopropane–cyclopentene rearrangements. A further study320 described the influence of substituents and solvents. Complete selectivity toward the cyclopropylimine–dihydropyrrole rearrangement was shown (equation 82). R2

R2 R1

3

h MeCN

R N

R3 R1

R4

h

R3

R1

Ph

R1

R2

MeCN

R2

ð81Þ

50−98%

R1,2,3 = H, Me, Ph, CO2Bu R4 = Ph, trans-CH=CHPh

N

R4

N

N

R3

Ph

ð82Þ 1

R

R

2

3

R

70% 75%

Ph CHPh H H O OEt

Classical methods for the rearrangement of C-cyclopropyl imines (Cloke rearrangement)309 entail high temperatures and acidic conditions. A typical reaction involves heating of the substrate to 140 °C in the presence of NH4Cl;321 however, milder catalysts may be used, for example TMSCl and NaI,322 LiCl, LiI, and others. The generally accepted mechanism of the acid-catalyzed rearrangement is depicted in Scheme 47. The cyclopropyl iminium ion can also be generated with AgOTf (Scheme 48). Charged intermediates generated by alkylation of thioimidates were utilized for a similar rearrangement.323 The mechanism for opening and reclosure is similar to the Cloke rearrangement (Scheme 49). R2 N

R3

X−

A+X−

R1

R1

R2

A R N

X

R2

R1

R1

+

N R3 A

−A+X−

N R3

R2

Scheme 47

R1

R1 n N

OTf−

R2 AgOTf, THF

N+

R1

R2 LiBr

N+

CN R1 = H, CO2Et R2 = H, CH2CO2Et n = 1, 2, 3

R2 Br−

65−93%

Scheme 48

S NH2

R

MeI, acetone reflux I−

BnO2C

BnO2C

N SMe 99% Scheme 49

I NH2 R=CO Bn 2 SMe

Ph

+

S

NH2

a

b R

I R=Ph

NH2

Ph N

SMe 95%

SMe

Rearrangements of Vinylcyclopropanes, Divinylcyclopropanes, and Related Systems

1043

Wender324 used intermolecular cycloaddition of DMAD to cyclopropyl imines to produce dihydroazepines in high yields (equation 83). CO2Me +

MeO2C

N

CO2Me

R1

R2

ð83Þ

61−95%

R1, R2 = H, alkyl R3 = H, alkyl, Ph R4 = Bn, alkyl

5.22.1.6

R4 N CO2Me

R2

PhMe, 60 °C

R3 R1

R3

[Rh(CO)2Cl]2 5 mol%

R4

Miscellaneous Systems

It would be difficult to list all of the cases involving the various combinations of heteroatom substitution in a vinylcyclopropane system. It has been recognized that virtually any heteroatom or any degree of unsaturation can be incorporated into the parent vinylcyclopropane system for almost limitless variability in the type of products that can be expected on its rearrangements.52,325 The general transformations depicted in equation 84 have been summarized and reviewed18,230,326–329 in the context of the synthesis of five-membered heterocycles. Vinylcyclopropenes, methylenevinylcyclopropanes, and cyclopropylalkynes all undergo the requisite rearrangements to five-membered rings.9 The products are the corresponding cyclopentadienes or methylenecyclopentenes and their heteroatom analogs. These topics have been reviewed.9,13,18,329 The mechanism of these transformations ranges from diradical scission to carbene generation and rearrangement.18,329–331 Y X

ð84Þ

XY

General discussions and reviews of rearrangements of heterovinylcyclopropane systems with one heteroatom and two or more heteroatoms not discussed in the previous sections (Sections 5.22.1.4 and 5.22.1.5) are available.332,333 Their rearrangements are governed by principles discussed previously, that is, most stable diradical or ylide intermediate or the least-hindered site for nucleophilic attack in the case of nucleophilic openings. The electronegativity of the heteroatom and the conditions of rearrangement determine the regiochemistry of bond cleavage. With systems containing additional unsaturation, the divinylcyclopropane–Cope rearrangement remains a viable option (see Section 5.22.2).222 The use of vinylthiiranes as synthons for 2,5-dihydrothiophenes has been somewhat limited as they readily undergo thermal desulfurization to form dienes. Njardarson334 recently discovered that vinylthiiranes may be rearranged into 2,5-dihydrothiophenes under conditions similar to those described above for vinyloxiranes and vinylaziridines.

5.22.1.6.1

Isomerizations of oxyvinylcyclopropanes to cyclobutanones

Vinylcyclopropanes substituted with oxygen (or sulfur or selenium) are susceptible to ring expansion to the corresponding cyclobutanone derivatives in addition to the expected rearrangement to cyclopentene (Scheme 50). The oxycyclopropane can be viewed as a pseudo enol in those interactions with electrophiles that involve the vinyl group. The resulting cyclopropylcarbinyl system 142a will interact with nucleophiles either directly (path a) or through ring opening (path b; Scheme 51). The participation of either bond a or b in this opening will depend on the precise conformation of 142, which is in turn dependent on the nature of the cation and its solvation, as well as on the tendency of the cyclopropylcarbinyl cation 142a to unravel. When proper orbital overlap exists, one of these bonds will participate in opening the cyclopropane to yield 144, or it will act as an internal nucleophile in its migration (and concomitant ring expansion to 145). O E

OR

OR E+ 142

Scheme 50

This latter process was developed and extensively utilized by Trost in spirocyclobutanone annulation.19,20 A less common reaction of oxyvinylcyclopropanes involves normal electrophilic opening of the oxycyclopropane, as, for example, that occurring in the generation of the β-stannyl enone (equation 85).15

1044

Rearrangements of Vinylcyclopropanes, Divinylcyclopropanes, and Related Systems

OR

OR

Path b

OR Path a

Nu

+

Nu E 143

E

E 142a

144

O E 145 Scheme 51

O OH

Me3SnCl, Et3N DMSO, Et2O, r.t.

R

ð85Þ

Me3Sn R 50−70%

R=Ph, Me

Salaun showed that optically active silyl ethers of vinylcyclopropanols can be rearranged under mild conditions with BF3*Et2O with the retention of optical configuration (84–90% ee, equation 86).335 O

OSiMe2But BF3*Et2O cat. OH CH2Cl2, r.t. R

ð86Þ

R 76−80%

R=H, Et

Cha utilized the acid-catalyzed intramolecular cyclization of vinylcyclopropanols with tethered ω-aldehydes for the synthesis of polycyclic structures. Reactions proceed with good yield and diastereoselectivity. It was shown that, depending on the length of alkyl chain, different stereochemistry of the hydroxyl group can be observed (Scheme 52). 336

O PPTS CH2Cl2, r.t. m=1

n HO H 148a (n = 1) 91−99% 149b (n = 2) 91%

OH

147

PPTS CH2Cl2, r.t. m=2

n

O

m

O

m O

O

H OH

PPTS CH2Cl2, r.t. n = 2, m = 3

150 90%

n

O

Et2AlCl CH2Cl2, r.t. n = 2, m = 3

HO

149a (n = 1) 89% 149b (n = 2) 92%

151 97%

Scheme 52 PPTS, pyridinium p-toluenesulfonate.

Cha337 also explored Lewis acid intermolecular reaction of acetals with vinylcyclopropanols. In the case of α,β-alkenyl substrates good diastereoselectivity was observed (46:1), compared to modest diastereoselectivity (43:1) observed in case of alkyl and aryl acetals (equation 87). The chiral auxiliary (R,R)-(+)-hydrobenzoin 153 was used337b,c in the form of a chiral acetal to provide access to the enantiomerically pure products. O

O OTMS

TiCl4

R1O R2

+ R1O

n 152 n = 1, 2

R1 =

Me, Et,

CH2Cl2, −78 °C n Ph

R2 H

OR

154

Ph 153 R2=1°-alkyl, aryl, alkenyl

+

R2

n H

OR 155

1 2 n = 2, R1 = Me, R2 = CH2CH2Br n = 1, R = Me, R = = CH CH CH 2 3 82%, 154:155=3:1 95%, 154:155 = 1:5.2

ð87Þ

Rearrangements of Vinylcyclopropanes, Divinylcyclopropanes, and Related Systems

1045

Cationic rearrangements can be performed in the presence of transition-metal complexes. Seminal work on the enantioselective variant of such rearrangements was published by Trost.338 Reactions proceed in the presence of catalytic amounts of Pd(dba)2 and the chiral bidentate phosphine 158 via formation of the π-allylpalladium complex 156 and proceed with good yields to give chiral vinylcyclobutanones 157 (equation 88). Addition of base such as tetramethylguanidine (159) was shown to increase the ee but significantly lowered the rate of conversion. OH R1

OH

Pd2(dba)3 1 mol% /158

O R1 PdL+

PhMe, 159, r.t. R2O

R1

O

156

157

O

61% to > 95% yield ee 69−93%

R1 = Me, 1°-Alk, alkynyl, Ar R2 = Me, CH2CF3

Ph

ð88Þ

Ph

O

O NH

NH

HN N

PPh2 Ph2P

N

159

158

Gold339 and ruthenium340 were shown to promote rearrangements of alkynyl cyclopropanols to 2-alkylidenecyclobutanones. Triarylphoshine gold cationic species promoted the rearrangement of a wide range of substrates to E-alkene products 160 with high stereoselectivity. The indenyl ruthenium catalyst 161 promotes rearrangement to the sterically less favorable Z-alkene. A possible explanation of such an outcome is coordination of ruthenium to the R group in the proposed transitional state 162, as shown in equation 89. (p-CF3C6H4)3PAuCl 0.5−5 mol%

OH

O

AgSbF6, R 0.5−5 mol% R=H, I, SiMe , aryl CH2Cl2, r.t.

160 61−98%

3

Ru R

OH 161, 5 mol% Camphorsulfonic R acid 5 mol%, In(OTf)3 5 mol% THF, reflux R=SiMe3, SiEt3, SiPri3, COOEt, COOBn, COn-C6H14

R

O

162

Cl

R O

ð89Þ

68−98%

Ru PPh3 PPh3 161

Toste341 described enantioselective rearrangements in the presence of the cationic gold catalyst 164. Allenyl cyclopropanols yielded vinylcyclobutanones under these conditions (equation 90). OH • R 163 R=1°-alkyl, aryl

164 2.5 mol% NaBArF −30 °C, DCE

O R

(xylyl)2 P AuCl

MeO MeO

P AuCl (xylyl)2

165 61−99% ee 84−94%

ð90Þ

164

Electrophiles generated from alkynes on addition of gold catalysts were shown to undergo intramolecular annulation to produce [5.5.4] tricyclic systems.342 The outcome of the reaction can be somewhat controlled by variations in catalysts (equation 91).

1046

Rearrangements of Vinylcyclopropanes, Divinylcyclopropanes, and Related Systems OEt

Au-cat 3 mol%

R

+

X

CH2Cl2, r.t.

X

OEt X

R H

OEt

R H

166a O

166b

O

t

ð91Þ

Bu + But P Au-NCMe

X=C(CO2Me)2, NTs, R=H, Me

SbF6− AuCl Yield ratio 166a:166b

5.22.1.6.2

80% 30:1

81% 1:8

Radical reactions and cycloadditions of vinylcyclopropanes

Addition of free-radical species to vinylcyclopropane results either in the abstraction of a hydrogen atom from the cyclopropane or ring opening through the agency of the cyclopropylcarbinyl radical generated on the initial addition.12 Radical addition occurs with vinylcyclopropanes containing radical stabilizing group on the cyclopropane ring. There are two general types of reactivity derived from the radical activation of vinylcyclopropanes: the termination of a radical chain by a hydrogen atom source leading to an open-chain product or the addition of an unsaturated fragment A¼ B in a [3+2] manner leading to cyclic products (Scheme 53). Tin-, sulfur-, and silicon-based radicals add to the vinylcyclopropane system. A B

A B

X

−X

X XH −X H X Scheme 53

Regioselectivity of radical additions was observed in general and follows the same pattern as metal-catalyzed formal [3+2] cycloadditions. Feldman343 described radical activation of vinylcyclopropane rings with diphenyldisulfide under thermal and photolytic conditions. A mixture of syn and anti-isomers was formed. On introduction of an EWG to the cyclopropane ring, preferential formation of the syn product 169b was observed (equation 92). R1

R2

R3 +

R4

167

AIBN 20 mol%, h, benzene, reflux

168

R4

R4 Ph2S2

+ R1

R3

R2

R1 = Me, R2 = H, R3 = CO2But, R4 = OBun R1,2 = H, R3 = OBn, R4 = CO2Me

R1

R3 R2

169a

169b

3.3 1

1 1

ð92Þ Yield 94% 70%

Feldman344 performed a study on the addition of oxygen to the radical formed from vinylcyclopropanes (equation 93). A mixture of dioxolanes 171 was formed under mild conditions with good regioselectivity in some cases.

R

170

Ph2Se2 20 mol%, AIBN 10 mol% h, O2, 0 °C, MeCN

R = Ph R = CO2CH(CF3)2

O O

O O R 171a >10 <1

+

R

ð93Þ

171b <1 >10

Yield 63% 65%

Rearrangements of Vinylcyclopropanes, Divinylcyclopropanes, and Related Systems

1047

A study of intramolecular cyclizations showed345 that the regioselectivity can be affected by the electronic configuration of the linker X in compound 172 (Scheme 54); different types of bicyclic systems can be produced starting from the same type of vinylcyclopropane 172. O E

O E i or ii

X

O E +

X

X

R

R 172

R ii. E=CN, R=Me, X=CH2 74%

i. E=CN, R=CO2Et, X=NBn 63%

i. Ph2S2 1 equivalent, h sunlamp, PhCl, reflux; ii. AIBN cat., benzene, reflux Scheme 54

Free radical polymerization of substituted vinylcyclopropanes through both 1,2- and 1,5-type additions has also been reported.346,347 Radical macrocyclization–transannulation in polyene systems containing a vinylcyclopropane moiety provided efficient access to manifolds of polycyclic compounds. Pattenden developed a general approach to diverse analogs of the steroid skeleton. By varying the position of the initial site of radical formation and the position of the vinylcyclopropane moiety in polyene system different types of polycyclic structures could be formed. An unusual type of steroid, 174,348 can be formed starting from acyl selenoate 173. The estrone-type skeleton formation was studied, and conditions were found for the selective formation of 175 and 176.349 A similar type of skeleton of C-nor-D-homosteroid 177 was selectively prepared in moderate yield in one step (Scheme 55).350 CO2Me

CO2Me MeO2C

MeO2C i

H H

H

45%

PhSe O

O 174

173 H

H

H

ii H

25%

H

I 175

H

176 major

minor PhSe

H

i O

H

+ H

H

25% O

H 177

i. Bu3SnH, AIBN, PhH, Δ; ii. (Me3Si)3H, AIBN, PhH, Δ Scheme 55

5.22.1.6.3

[2,3] Rearrangements of vinylaziridines and vinyl epoxides

The first example of an aza-[2,3]-Wittig rearrangement of vinylaziridines was described by Somfai.351 It was shown that Nsubstituted aziridines with an anion-stabilizing group may be rearranged to piperidines on treatment with base. The best selectivity for formation of cis-disubstituted piperidines 179a was achieved when a carboxylic ester was the stabilizing group and lithium diisopropylamide (LDA) was used as a base (Scheme 56). Coldham352 described a similar system that showed the same tendency to produce cis-disubstituted piperidines. Vinyl epoxides can be rearranged in a similar [2,3] fashion via oxonium ylides. Only two examples have been published on this rearrangement.353,354 An oxonium ylide is produced on the attack by the metal carbenoid obtained from the decomposition of a diazo compound (equation 94).

1048

Rearrangements of Vinylcyclopropanes, Divinylcyclopropanes, and Related Systems

R1 R

3

Base

+

THF, −78 °C

N

R3

R2

+ R3

R2

N H

Me3Si

R1

R1 N H

179a

R2

R3

179b

N

180

R1=H, R3=But 178

179a

LDA BusLi KHMDS

179b

Yield

Only product R2=CO2But SiMe3 1.2 R2=

−

−

95%

1.8

1

95%

R2=CN

1

−

80%

6.6

Scheme 56

R1

N2CHCO2But O

5.22.1.6.4

+

O

Cu(hfacac)2, CH2Cl2, r.t.

−

ButO2C CO2

But

R1

O

ð94Þ

181 70%

Rearrangements of silavinylcyclopropanes

Thermal or photochemical355 generation of silylenes in the presence of 1,4-dienes leads to 3-silolene. Stable vinylsiliranes can be prepared in high yield under mild conditions from bulky silylenes.356 Such vinylsiliranes can be converted on heating to 3-silolene as shown in Scheme 57. It is unclear whether this reaction proceeds by a mechanism similar to the vinylcyclopropane–cyclopentene rearrangement or by decomposition to silylene and direct [4+1] cycloaddition. Computational studies for silylenes, germylenes, and hypothetical stannylenes have been performed.357

Thermal or photogeneration R1 Si R2

R3

R2 1 R Si

r.t.

+

R1,R2 = Me, Ar R3 = H, Me

3 Benzene R

160 °C, 12 days for R3 = H complete 100 °C, 5 h for R3 = Me conversion 105 °C Benzene

R3 Si

R1 R2

Scheme 57

Vinyl phosphirane can be generated via the addition of the corresponding phosphinidene complex to a diene.358 Rearrangement to the corresponding 3-phospholenes can occur under thermal conditions via a biradical intermediate similar to that in the vinylcyclopropane–cyclopentene rearrangement process, but such a rearrangement can also occur under CuCl catalysis as shown in Scheme 58. In the latter case the process possesses significant concerted features.359

105 °C only syn (OC)5W

P

Ph

64% CO2Me CuCl 60 mol% CO2Me

Scheme 58

benzene, 52 °C

W(CO)5 P Ph

+ P Ph (OC)5W 76% syn:anti = 60:40

(OC)5W

P

Ph

Rearrangements of Vinylcyclopropanes, Divinylcyclopropanes, and Related Systems 5.22.1.7

1049

Total Syntheses

The vinylcyclopropane–cyclopentene rearrangement and its heterocyclic variants have been featured in a number of general methods of synthesis, most notably those developed by Wenkert, Stevens, Hudlicky, and Wender. Most of these developments were discussed in the first edition of this work published in 1991 or in the review that appeared at the anniversary of Neureiter's discovery.485 The list of syntheses performed before 1991 includes the core of prostaglandin by Trost,360 aphidicolin by Trost,361 zizaene by Piers,362 hirsutene by Hudlicky,363 11-deoxyprostaglandin E2 by Salaün,364 α-vetispirene by Paquette,365 hinesol by Piers,366 isocomenic acid, isocomene, and β-isocomene by Hudlicky,367,368 jasmone and dihydrojasmone by Salaün,369 coriolin by Wender,370 spirovetivane by Salaün,371 silphinine by Wender,372 dicraenone by Salaun,373 antheridiogen-an by Corey,374 epiisocomene by Hudlicky,375 pentalenene by Hudlicky,376,377 pentalenic acid by Hudlicky,377 and retigeranic acid by Hudlicky.378 The use of these rearrangements in total synthesis continues and the tables below provide the update in accomplishments since the 1991 version (Tables 12–14).

Table 12

Vinylcyclopropane rearrangement in total synthesis

Starting material (SM)

OAc

TBSO

Conditions

Product

Bu2O, 190 °C

AcO

Target

References 379

O

CO2Me

OPMB

OH

TBSO

n-C5H11

n-C5H11

HO

PMBO

n-C5H11 Prostaglandin E2 methyl ester H

OH

hν, Toluene–petrol ether

OH

380

HH

H

(−) -Δ9 (12)capnellene

O

Tetra-n-butylammonium fluoride (TBAF), THF

O

O

O

HO H

381

O

O

TBSO O

H O CO2Et

CO2Et

OEt O

O

HO

H

H

HO

OEt

(−)-Specionin

HO

PPh3AuCl, AgBF4, dichloromethane (CH2Cl2)

O

382

H

H

H

H

Ventricos-7(13)-ene Me3SiO

TiCl4, CH2Cl2

MeO

O

O

383

Br

Br

OMe Pri

OMe Pri

H

CHO

Pri Cyathin B2

Heteroatom-containing analogs of vinylcyclopropanes used in total synthesis before 1991 include mysomine and apoferrosamine by Stevens,384 mesembrine by Stevens385 and Keely,386 shihunine by Breuer,387 aspidospermine by Stevens,388 joubertiamine by Stevens,389 elwesine by Stevens,390 14C-nicotine by Comes,391 sceletium alkaloid A-4 by Stevens,385c isoretronecanol and δ-coniceine by Stevens,392 ipalbidine and septicine by Stevens,393 supinidine by Hudlicky271,282 and Pearson,272 isoretronecanol and traceanthamidine by Hudlicky,282,284 mitomycin A by Maruyama,394 dihydroxyheliotridane, hastanecine, and

1050

Table 13

Rearrangements of heteroatom-containing analogs of vinylcyclopropanes in total synthesis

Starting material (SM)

Product

Target

NH4Cl, toluene, 140 °C

MeO2C

OH H

O

O

MeO2C

O

321

OH OH

N

N

References

N (+)-Crotanecine

NBn

Bn N

TMSCl, NaI

NO2

N

322,398

N H H

NO2

H

Dehydrotubifoline N

N

H

H

O

H O Strychnine

O

CO2Et

500 °C, 0.04 mbar

O

O Ph

399

O

Ph

O

CO2Et H

H O

O O (±)-Epiasarinin MeO

LiI, MeCN, μwave

MeO

MeO

OH

AcO

287

Ts N N Ts

N H (−)-Anisomycin (Continued )

Rearrangements of Vinylcyclopropanes, Divinylcyclopropanes, and Related Systems

O

Conditions

S

O

Cu(hfacac)2, 150 °C

S

CO2Et

3

3

CO2Et

HN

336

NH

S CO2Et

(±)-Biotin

R

MeO

TFA

OMe

MeO

R

HO

OMe

OH

400,401

O

R = H, O

N

O

(±) -Salviasperanol

N

S OBn

O

Cu(hfacac)2, 100 °C

MeO2C

MeO2C

O

OBn

402

O

OMe

OMe

O Core of Platensimycin

O

Cu(hfacac)2, 150 °C

Ph

OH

HO Ph

403

O

CO2Me

CO2Me

Ph

O CO2Me

(+)-Gonithalesdiol O

Cu(hfacac)2, 150 °C

OBn

HO

O

OH

OH

404

OMe

BnO

O (+)-Varitriol CO2But N

n-C6H13

Lithium diisopropylamide (LDA), THF, −78 °C

405

n-C6H13

N H

CO2

But

n-C6H13

N

Rearrangements of Vinylcyclopropanes, Divinylcyclopropanes, and Related Systems

O

Indolizidine 209D

1051

Cycloadditions in total synthesis

Starting material (SM)

Conditions

Product

HO

HO

References

H

H

H

OH

406

H

(+)-Dictamnol

O

[Rh(CO)2Cl]2, toluene, reflux

407

• H

H

OB

HO (+)-Aphanomol I

OBn O

O

[Rh(CO)2Cl]2, 1,2-dichloroethane (DCE)

408

OH

HO OH

CHO Core of (+)-Allocyathin B2 OH

OH

Fe(CO)5, i-PrOH, hν

OH

184

O

O

(−)-Delobanone BnO

OBn

[Rh(CO)2Cl]2, toluene, reflux

O

O

409

O

MeO2C MeO2C

MeO2C

H

H

CO2Me

Tremulenolide A TBDPSO

[(C8H10)Rh(COD)]

+

SbF− 6,

H

DCE

O

OTBDPS

410

O TBSO

TBSO

H

H

HOOC

CO2Me OAc

(−)-Pseudolaric acid B (Continued )

Rearrangements of Vinylcyclopropanes, Divinylcyclopropanes, and Related Systems

[Rh(CO)2Cl]2, toluene, reflux

•

Target

1052

Table 14

CpRu(MeCN)3PF6, CH2Cl2

HO

411

HO H

OTIPS

HO TIPSO

OH (+)-Frondosin A O

Fe(CO)5, i-PrOH, hν

O

O

O

412

O

(+)-Coronafacic acid

O Pd2(dba)3, dppe, THF

NO2 MeO2C NO2

CO2Me CO2Me

CO2Me

413

N

O2N NO2

CO2Me N H

O

Scandine PMB

N+

O−

4

PMBO

Yb(OTf)3

PMB

N 4

MeO2C

PMBO

CO2Me

O H

N

CO2Me CO2Me

O

414

O O (+)-Phyllantidine

Sn(OTf)2

O N Ts

O MeO2C

O

N CO2Me Ts BnO2C

CO2Bn

H N

415

O

OH

N O HO

OH

(+)-Isatisine A

OMe

OMe

Bu3SnH, AIBN

H

I H MeO

H H

H MeO (±)-Estrone

351

H

1053

MeO

O

Rearrangements of Vinylcyclopropanes, Divinylcyclopropanes, and Related Systems

CO2H

1054

Rearrangements of Vinylcyclopropanes, Divinylcyclopropanes, and Related Systems

trihydroxyheliotridane by Hudlicky,395,396 eburnamonine by Wenkert,397a dehydroaspidospermidine and quebrachamine by Wenkert,397b and ipomeamarone by Hudlicky221 (Tables 13 and 14).

5.22.2

Divinylcyclopropanes

5.22.2.1

Introduction

The facile thermal σ2s+π2s+π2s (Cope) rearrangement of cis-1,2-divinylcyclopropane 182 to 1,4-cycloheptadiene 183 was first reported in 1960 by Vogel.416 In his experiments, Vogel did not isolate 182, since, under the conditions of its formation (80 °C), 182 rearranges rapidly to 183. Indeed, it was not until more than a decade later that 182 was isolated and shown to rearrange to 183 with half-lives of approximately 90 s and 25 min at 35 °C417 and 11 °C,417,418 respectively.

182

184

183

Not unexpectedly, trans-1,2-divinylcyclopropane 184 is much more stable than the cis isomer 182 and is a readily isolable compound. Nevertheless, at elevated temperatures, for example, 190 °C, 184 undergoes smooth bond reorganization to provide 1,4-cycloheptadiene 183 in essentially quantitative yield.416a,c Thus, at the time the Cope rearrangement of 1,2-divinylcyclopropane systems was discovered,416 it was already clear that both cis and trans isomers could, in principle, serve as suitable substrates for the reaction. As it turns out, this is an important reaction characteristic, since, in most cases, it makes unnecessary the stereoselective preparation of either the cis or trans starting material. Since 1960, the thermolysis of 1,2-divinylcyclopropanes has been studied quite extensively to from a mechanistic point of view. However, particularly since 1975, synthetic applications of the rearrangement reaction have been explored, and these studies have shown that the reaction provides a versatile, effective method for the construction of functionalized mono-, bi-, and tricyclic substances.21,419 In this section, the mechanistic features of the rearrangement will be outlined briefly. The major portion of the discussion will deal with synthetic aspects of this interesting process.

5.22.2.2 5.22.2.2.1

Mechanistic Considerations Rearrangement pathways

It appears to be well accepted that the thermal rearrangement of cis-1,2-divinylcyclopropane 182 proceeds in a concerted fashion via a boat-like transition state, in which the vinyl groups lie over the three-membered ring.10,420,421 Thus, conformational orientation of 182 as shown in 182b (equation 95), followed by bond reorganization by way of a transition state represented by A, provides 1,4cycloheptadiene 183, in which both double bonds have cis stereochemistry. Concerted rearrangement of 182 via a chair-like transition state derived directly from conformation 182a would lead to the highly strained trans,trans-1,4-cycloheptadiene, and it is clear that such a pathway would be of a much higher energy than that involved in the conversion of 182b, via (A), into 183.

H

H 182a

H

H

182b

H

ð95Þ

H 183

A

The thermolytic transformation of trans-1,2-divinylcyclopropane 184 into 1,4-cycloheptadiene 183 probably proceeds via the pathway shown in equation 96. Homolytic cleavage of the cyclopropane ring of 184 provides the resonance stabilized diradical 185, which, in addition to reverting to 184, can undergo bond rotation and subsequent ring closure to give cis-1,2-divinylcyclopropane 182. The latter substance then rearranges, by way of conformation 182b, into 183.

H

H 184

H 185

ð96Þ

H

(182b)

183

Rearrangements of Vinylcyclopropanes, Divinylcyclopropanes, and Related Systems

1055

The energy of activation Ea for the overall conversion of 184 into 183 has been reported421,422 to be in the range 32.1– 34.3 kcal mol−1 (1 kcal≈4.2 kJ). In comparison, the data reported by Brown et al.417 and Schneider and Rau423 show that Ea for the rearrangement of 182 to 183 is approximately 19–20 kcal mol−1. Thus, for the conversion of 184 into 183, the rate-determining step is the isomerization of 184 into 182, presumably via the diradical 185. This characteristic is common to most of the known rearrangements of 1,2-divinylcyclopropane systems. That is, for a given pair of isomers, trans to cis isomerization is generally slower than Cope rearrangement of the cis isomer. However, it must be noted that there are exceptions to this generalization, since thermolysis of certain substituted cis-1,2-divinylcyclopropanes results only in cis-trans isomerization and not in sigmatropic rearrangement (vide infra). The mechanism of rearrangement has been studied by DFT methods. Fabian424 explored systems containing a heteroatom in the double bond 186. The activation barrier calculated for the known vinylcyclopropane carbaldehyde–dihydrooxepin rearrangement corresponded well with known data, 23.4 and 23 kcal mol−1, respectively. The barrier for rearrangement of cisdivinylcyclopropane, a strongly exothermic reaction, was calculated at 18.8 kcal mol−1. This result corresponds with experimental evidence that cis-divinylcyclopropane rearranges below room temperature. Substituents such as OH and CHO lower the activation barrier for rearrangement (equation 97). R2 R1 X

X

X R1

R2

R1

X R2

R1

186

ð97Þ

R2

X = CH2, O, S, NH R1,2 = H, OH, CHO

For systems 187 Zora calculated the barrier of rearrangement and nuclear independent chemical shifts (NICS) for the all-carbon skeleton425 and for heterocyclic analogs.426 It was shown that the activation barrier decreases in the series CH2oNHoOoPHoS, which can be justified by decreasing ring strain of the parent three-membered compounds (equation 98). ≠

X

X

X

ð98Þ

X

187 X = CH2, O, NH, NMe, NEt, PH, S

5.22.2.2.2

Substituent effects

Substituents attached to the terminal carbons of the vinyl groups can have a profound effect on the rate of the Cope rearrangement of cis-1,2-divinylcyclopropane systems, Schneider and Rau423 showed that the cis,cis,cis substrate 187 undergoes reversible cis-trans isomerization, 188 to 187, much faster than it undergoes Cope rearrangement to 189 (Scheme 59). In a related study, Baldwin and Ullenius427 reported that, at 165 °C, the 188:187 ratio at equilibrium is approximately 1:4. Furthermore, heating 187 at 178 °C for 4.2 h or 75 h gives, in addition to an equilibrium mixture of 188 and 187, minor (4%) or significant (35%) amounts of the Cope rearrangement product 189. Thus, although the sigmatropic bond reorganization of 188 is not precluded, the steric interactions present in the transition state (E; Scheme 59) make this a higher energy pathway than the isomerization of 188 to 187.

H

178 °C Fast

H 187

∪ ∩ ∪ ∩ ∩∪ H

178 °C H H 188

Slow

H H E

189

Scheme 59

Other studies have also qualitatively demonstrated the effect of substitution patterns on the ease of cis-divinylcyclopropane rearrangements. For example, at temperatures in the range 0–20 °C, the substrates 190–192 are readily transformed into the cycloheptadienes 193–195, respectively (Scheme 60).428–430 The rearrangement of 192 to 195 occurs with a half-life of approximately 50 min at 15 °C430 and is thus marginally slower than the thermal conversion of the parent cis- 1,2-divinylcyclopropane 182 into 1,4-cycloheptadiene 183 (Section 5.22.2.1).417,419 However, complete transformation of 196 into 193 requires heating at 75 °C for 5 h (Scheme 60),428 again demonstrating the notable rate-retarding effect of a cis-substituent.

1056

Rearrangements of Vinylcyclopropanes, Divinylcyclopropanes, and Related Systems

R R

0−20 °C

75 °C 5h

H

H

H

H

190 R = Bun 191 R = (E)-1-butenyl 192 R = (Z)-1-butenyl

193 R = Bun 194 R = (E)-1-butenyl 195 R = (Z)-1-butenyl

196

Scheme 60

The highly substituted cis-divinylcyclopropanes 199 and 200 do not undergo sigmatropic rearrangement at all.431 Apparently, the highly sterically congested nature of the transition states (F) precludes this possibility. Thermolysis of 199 and 200 at 170–180 °C produces only equilibrium mixtures of these substances and the corresponding trans isomers 197 and 198, respectively (Scheme 61).431

H

≠

∪ ∩

R

R

R R

R H H

H

197 R = H (75%) 198 R = Me (72%)

199 R = H (25%) 200 R = Me (28%)

∪ ∩ R∪ ∩ ∪ ∩

H H F R = H or Me

Scheme 61

5.22.2.2.3

Guide to preparation

There are a variety of methods for generating divinylcyclopropanes. Some are analogous to those used for the preparation of vinylcyclopropanes (vide supra). The following methods are unique to divinylcyclopropane systems, in particular cis-divinylcyclopropane systems. Some general approaches are presented in Scheme 62.

O 201

[M] 202 [M]

+

[M]

+

203

204 Scheme 62

Olefination of cyclopropyl aldehydes of general type 201432–434 provided access to a variety of substituted divinylclyclopropanes. Addition of cyclopropyl-containing organometallic reagents of general type 202 to appropriate electrophiles provided yet another means of access to the divinylcyclopropane core. These reagents include Cu,435 Zn,436 Zr,437, and Li438,439 derivatives. One of the most developed and general modern methods involves the addition of vinyl carbenoids of type 203 to a diene system. Early examples of use of such carbenoids include addition of Fischer-type carbenes of VI group metals. Harvey440 utilized insertion of these to alkynes. The vinylcarbenoid 205 formed in this way undergoes intramolecular cyclopropanation to the diene, which in turn rearranges to the cycloheptadiene system 206. The reaction proceeds in moderate yields in both electron-neutral and electron-poor diene systems (Scheme 63). A similar approach was utilized by the group of Iwasawa.441 Insertion of a tungsten complex into the enyne led to the formation of a vinyl carbenoid, which was subjected to cyclopropanation and rearrangement as shown in equation 99.

Rearrangements of Vinylcyclopropanes, Divinylcyclopropanes, and Related Systems

1057

MeO R3 R1 R1

M(CO)5

M(CO)5 PhMe

+

OMe reflux

R3

OMe

R1

R2

R1 R1

R3

R1 R1

R2

H

R1

H

R2 MeO

R3

R2

R1 = H, CO2Et R2 = H, CO2Me, CH=CHCO2Et R3 = Me, Bu M = Cr, Mo

10−40% 205

206

Scheme 63

OSiPri3

CO2Me CO2Me

OSiPri3 CO2Me H CO2Me

i 81%

Ph

Ph

ð99Þ H

i. 5 mol% W(CO)6 5 mol%, Et3N 10 mol%, h, 4 Å sieves, PhMe, r.t.

The addition of chromium carbene complexes to electron-rich dienes was studied by Barluenga.442 The reaction occurred under mild conditions and provided cis-divinylcyclopropanes with complete regio- and stereoselectivity. In some cases, the reaction required heating to 60 °C, and some trans-product was observed. Studies of reactions in the presence of chiral proline-based auxiliaries showed significant enantioinduction442b,c (Scheme 64, Table 15). Barluenga described similar reactivity for 2-azadiene systems,443 with preferential insertion into the CQN bond.

R1 R3

R1

Cr(CO)5

R2

R5

N R4

i R3 N R4

R6

R1

R6 R5

R2 R3

N R4

R5

R2

OMe

+

R6

H+

R1 R2 O

OMe

OMe

R6 R5 O

i. MeCN, 25 °C or THF, 60 °C Scheme 64

Table 15 1

Selected examples of addition of chromium carbenes to diene systems

2

R,R

R3, R4

R5, R6

Yield (%) (eea)

CH2OH, Me

NR3R4 ¼

H, Ph

65 , (95)

H, 2-furyl

82

N MeO CH2OMe, Me a

For chiral auxiliaries.

Me, Ph

1058

Rearrangements of Vinylcyclopropanes, Divinylcyclopropanes, and Related Systems

One of the most convenient methods for generating such carbenoids is by the decomposition of diazo compounds of type 207 in the presence of metal catalysts such as salts of rhodium and copper. The rhodium-based approach developed and studied by Davies has been the subject of several reviews.83,84,444–447 The advantage of this method is that it proceeds with high levels of stereoselectivity and the major product is a cis-divinylcyclopropane 209, which can undergo direct rearrangement to the cycloheptatriene skeleton (Scheme 65, Table 16). The regioselectivity of carbenoid insertion into acyclic dienes can be controlled somewhat by changing the substitution pattern. Preferential cyclopropanation occurred on the least substituted double bond. The reaction can be selectively performed on a cis-alkene in presence of the trans isomer. Better control can be achieved by substitution with electron-rich functionalities. R6 R10 R5 R1

N2

LnRh i

R4

R2

R1 R4

R2

R3

R9 R7 R8 208

R5 R8 R9

R3

R6

R7

R1

4 R10 R

207

R7

R2

R5 R6

ii

R1

R2 R8 R10 R4 R9 R3 210

R3

209 i. RhL, solvent; ii. Δ

Scheme 65

Table 16

Selected examples of addition of rhodium carbenes to diene systems

R1, R2, R3, R4

RhL, solvent

Yield (%) (eea)

Me, H, H, H

Rh2(OPiv)4 pentane

90

Me, H, H, CH¼CHPh

Rh2(OAc)4, CH2Cl2

80

Rh2(OAc)4, CH2Cl2

92

Rh2(S-DOSP)4, pentane

52 (98)

208

MeO

Et, H, H, CO2Et

Me3SiO Et, H, H, Ph a

For chiral version of the transformation.

In most cases, divinylcyclopropanes are transient species and cannot be isolated. Under the reaction conditions they tend to undergo subsequent transformation to cycloheptadienes 210; however, sterically congested divinylcyclopropanes can sometimes be isolated. A wide range of substrates has been studied. Cyclic dienes448, furans,449 pyrroles450 have been used; these open access to functionalized bicyclic systems including biologically active tropanes. The addition of metal carbenoids to an aromatic ring with disruption of aromaticity (Büchner reaction) leads to bicyclic norcaradiene structures.445,451 The reaction also proceeds under copper/rhodium catalysis from diazo compounds. In most cases the intermediate divinylcyclopropanes undergo immediate rearrangement to the corresponding cycloheptatriene system. Less common methods of preparation of divinylcyclopropanes include oxidative cyclization of allyl iron complexes. Donaldson452 discovered that vinyl Grignard reagents 211 can be stereoselectively added to a cationic iron complex such as 212. The product of such reaction, namely 213, can be oxidized by one-electron oxidants such as cerium ammonium nitrate (CAN) or H2O2. Oxidation of the complex leads to decomplexation of iron and rearrangement to cis-divinylcyclopropane 214. After reduction of the ester, this compound undergoes the rearrangement to cycloheptadiene 215 (Scheme 66). PF6− + MgBr MeO2C

211

H i +

Fe(CO)3

212

ii

iii, iv

51% MeO2C

Fe(CO)3 213

76% for 3 steps CO2Me

CH2OH

214

215

i. DCM, −78 °C; ii. H2O2, MeCN, r.t.; iii. LiAlH4, THF; iv. mesitylene, reflux Scheme 66

Rearrangements of Vinylcyclopropanes, Divinylcyclopropanes, and Related Systems

1059

Extrusion of SO2 from tricyclic sulfolanes 216 was explored by Aitken.453 Fused tricyclic sulfolanes produced the corresponding 7-membered-ring compounds up on FVP in moderate to good yields via formation of cis-divinylcyclopropanes (equation 100). Acyl-silanes of general type 217 undergo sequential Brook/Cope rearrangement on addition of dienolates 218 (Scheme 67) as was described by Takeda.454,455 Matsubara reported that vinylic 1,2-diketones 219 can be transformed into cis-divinylcyclopropanes with Zn carbenoids.456 The reaction proceeded with high stereoselectivity, and the transient divinyl species 167 underwent smooth rearrangements to cycloheptane diketone 221 (Scheme 68). Stephenson457 studied the utility of a photoredox catalyst in the reaction of cyclopropyl-centered radicals with alkynes. It was shown that radicals are formed under mild conditions and undergo an addition–Cope rearrangement sequence with good yield. The scope of substrates was somewhat limited as only propargylic amides 170 were found to participate in such reactions (equation 101).

O2S

X

i

X

X

216 i. 580 °C,

O SiMe2But

O

OLi

i

+

ButMe2SiO

O

−O

SiMe3

Me3Si

Me3Si

218

217

O−

ButMe2SiO

ButMe2Si

SiMe3

ð100Þ

X=O 55% NCO2Me 10% NCO2Et 14% CH2 80%

10−3 torr

73% i. THF −80 °C to −30 °C

Scheme 67

O

O R2

R1

R3

CH2(ZnI)2

IZnO

OZnI 25 °C

IZnO

OZnI

THF, −78 °C R1

219

R3

R2

R1

220

O

H+

R3 R2

O

R1

221

R3 R2

222

R1 = aryl, Me R2,3 = aryl, Me, H

47−98%

Scheme 68

O R1 R1

R1

O i

R1

Br N

O

N

R

N

R

ð101Þ

223 R1= Ph, 3-MeOC6H4, 4-MeC6H4, 4-FC6H4, 2-FC6H4,

69−88%

i. 1 mol% Ir(2-pyridin-2-ylphenyl)2(4,4′-di-tert-butyl-2,2′-bipyridine) PF6, Et3N, DMF, visible light

5.22.2.3 5.22.2.3.1

Monocyclic Divinylcyclopropanes Stereospecificity

Rearrangement of 224 from –10 to 30 °C provides quantitatively cis-6,7-dimethyl 1,4-cycloheptadiene 189.423 Furthermore, prolonged heating of 188 at 178 °C produces, in addition to the trans isomer 187, the same sigmatropic rearrangement product

1060

Rearrangements of Vinylcyclopropanes, Divinylcyclopropanes, and Related Systems

(189; Scheme 69).427 Other studies have shown that thermolyses (178 °C, 4.2 h) of substrates 225 and 226 give, in quantitative yields, the epimeric cycloheptadienes 189 and 228, respectively.427 Presumably, these transformations proceed by way of the corresponding cis-1,2-di(1-propenyl)cyclopropanes 224 and 227.427

H H

H

H

H

H 224

189

H

H

H

H

188

187

H H

225

R R′ H

75 °C, 5 h >95%

H 229 R = Bun, R′ = H 230 R = H, R′ = Bun

226

227

228

R R′ 231 R = Bun, R′ = H 232 R = H, R′ = Bun

H H

Scheme 69

Collectively, the results summarized above show that, with respect to the stereochemistry of appropriately substituted vinyl groups, the (reversible) trans to cis isomerization (e.g., 187 to 188; 224 to 225; 226 to 227) and the sigmatropic rearrangement of the cis-1,2-divinylcyclopropane systems (e.g., 224 or 188 to 189; 225 to 228) are completely stereospecific. In connection with carrying out stereoselective syntheses, the importance of this reaction characteristic is obvious. Indeed, the stereospecific nature of the Cope rearrangement of 1,2-divinylcyclopropanes has been demonstrated with substrates that are structurally more complex than those discussed above. Specific examples will be presented later in this chapter (see Sections 5.22.2.3–5.22.2.6).

5.22.2.3.2

Enantiospecificity

Relatively little work has been done in this area. In studies related to the total synthesis of the marine natural product (R)-(–)-dictyopterene C′ (231), Jaenicke and coworkers458 showed that the enantiomerically pure substrates 229 and 230 rearrange cleanly to the corresponding enantiomerically pure products 231 and 232, respectively (Scheme 69). Nonnatural (S)-(+)dictyopterene C′ (232) is also obtained by rearrangement of (1R,2S)-1-[(E)-1-hexenyl]-2-vinylcyclopropane (Scheme 69).459 These results show, not unexpectedly, that the Cope rearrangements of rather simply substituted cis-divinylcyclopropanes are enantiospecific. With monocyclic trans-1,2-divinylcyclopropanes, chirality transfer is, apparently, poor. Thermolysis of (+)-dictyopterene A (234) at 165 °C for 48 h and of (–)-dictyopterene B (235) at 103–108 °C for 40 h gives, in each case, a mixture of the two enantiomeric Cope rearrangement products, 231, 232 and 238, 241, respectively (Scheme 70).460 Although the uncertainty associated with the optical purities and (or) rotations of the various substances involved458,460 made a quantitative determination of the product ratios difficult, it is evident from the results that enantiomers 232 and 238 predominated marginally over 231 and 241, respectively. This observation has been rationalized461 by postulating that, in the intermediate diradical 236, the allyl system rotates more rapidly, to give 237, than the more bulky heptenyl or heptadienyl groups, to produce 239. Ring closure of 237 and 239, followed by bond reorganization of the (enantiomeric) cis-divinylcyclopropanes 233 and 240, produces the final products. Although further work in this area is desirable, it appears that in the Cope rearrangement of simple trans-divinylcyclopropanes, such as 234 and 235, enantioselectivity is poor. Despite the biradical character of the rearrangement, transfer of chirality can sometimes occur in more complex substrates, such as polycyclic systems. The enantioselective generation of divinylcyclopropanes is of utmost importance. Because of the concerted nature of the rearrangement, enantioselective cyclopropanation leads to chiral products, according to the well-studied transition state. Davies has expanded the scope of the insertion of vinyl carbenoids to an asymmetric version. Chiral auxiliaries have been utilized462 with some success, but the diastereomeric excess of products was not high (30%).

Rearrangements of Vinylcyclopropanes, Divinylcyclopropanes, and Related Systems

H

1061

H R

R R 237

232 R = Bun 238 R = (Z)-1-butenyl

233

R

R H H

HH

R R 234 R = Bun 235 R = (Z)-1-butenyl

236

239

240

R 231 R = Bun 241 R = (Z)-1-butenyl

Scheme 70

Later investigations focused on chiral rhodium catalysts. The use of amino acid-based rhodium dinuclear ligands such as 242 and 243 led to impressive levels of enantio- and regiocontrol. Low temperatures and nonpolar solvents such as pentane and toluene were required. O

Rh

R

O

Rh

N

O

Rh

O O

N

Rh

O

SO2

4

4

R R = adamantyl Rh2(S-PTAD)4 R = But Rh2(S-PTTL)4

R = But Rh2(S-TBSP)4 R = C12H25n Rh2(S-DOSP)4

243

242

Maguire studied the enantioselective copper-catalyzed Büchner reactions.463 Bis-oxazoline ligands 244 showed good enantioselectivity and yields for an intramolecular version of the Büchner cyclopropanation (equation 102). R2

R2

O i or ii N2

R1

R2 O

R1

i. CuPF6 5 mol%, 244 6 mol%, CH2Cl2, reflux ii. CuCl-NaBArF 5 mol%, 244 6 mol%, CH2Cl2, reflux

R1 O 62−97% ee 56−95% 46−57% ee 72−80%

ð102Þ

O

O N

N

Ph

Ph 244

5.22.2.3.3

Synthesis of functionalized cycloheptanes

The use of the Cope rearrangement of 1,2-divinylcyclopropanes for the synthesis of functionalized seven-membered rings has been illustrated in a number of studies. For example, thermolysis of 245 (mixture of cis and trans isomers), followed by cleavage of the enol silyl ether function in the resultant product 246 provides the natural product karahanaenone (247; Scheme 71).438a In this

1062

Rearrangements of Vinylcyclopropanes, Divinylcyclopropanes, and Related Systems

OSiMe3

OSiMe3

O H

i

H

O 245

O

MeO

H

OSiMe3 H

MeO

O

SPh iv

iii

O

OSiMe3 vii

MeO

247

vi

H 252

251

246

SPh

O

v

ii

O

MeO

H 248 cis 249 trans

250

253

254

i. 165−175 °C, PhH; ii. BunLi, THF; iii. cis, 25 °C; trans, 160 °C (70%); iv. HgCl2, H2O-MeCN (45%); v. Me3SiCl, Et3N, Et2O (100%); vi. 210 °C, PhH (96%); vii. KF, MeOH (95%) Scheme 71

case, as in many others, the fact that 245 was not stereochemically homogenous was of no consequence, since both isomers of 245 cleanly afford the same rearrangement product. Similarly, sigmatropic rearrangement of the isomers 248 and 249 and subsequent hydrolysis of the resultant vinyl sulfide 250 also produces karahanaenone (247).464 The efficient conversion of substrate 251 into the keto ester 254 via a route in which the Cope rearrangement of 252 played a key role has been reported.465 In an investigation related to the synthesis of substituted 4-cyclohepten-1-ones,466 the stereochemically homogenous cis-2vinylcyclopropyl ketones 255a–255d were converted cleanly into the enol silyl ethers 256 (Scheme 72). Thermolysis of the latter substances, followed by acid hydrolysis of the resultant products 257, gives excellent yields of the ketones 258a–258d. Interestingly, however, kinetic deprotonation of each of the cis-ketones 255e–255h is not regioselective. Treatment of these substrates with LDA–TBSCl provides mixtures of the enol silyl ethers 259 and 260, in ratios varying from 4:1 (substrate 255g) to 1:9 (substrate 255f). Fortunately, the trans-ketones 262e–262h give synthetically more satisfactory results, since these substances can be converted chemoselectively into the trans-divinylcyclopropanes 263. As expected, Cope rearrangements of compounds 262 require temperatures considerably higher than those employed for the conversion of 256 into 257. However, the reactions are clean and the products 264, obtained in good to excellent yields, are readily hydrolyzed to the ketones 258e–258h. H R R′

O

R i

H

OSiMe3

R′

H

H

255a-d

H

ii 85−96% from 183

R′

OSiMe3

R

256a-d

iii

R′

84−91%

R

257a-d

O

258a-d

a: R = Bun, R′ = H; b: R = Ph, R′ = H; c: R, R′ = (CH2)3; d: R, R′ = (CH2)4 H R R′

O

H

O H

iv

H

R

OSiButMe2 H H

261e-h

Me2ButSiO H R

H

262e-h

v

R′

H 260e-h

259e-h

>85% R′

H

+

>85% R′

H

255e-h H R R′

OSiButMe2

R

iv

R′

R

OSiButMe2 iii

60−91% from 189

R′

R

O

73−88% 263e-h

264e-h

e: R, R′ = (CH2)5; f: R, R′ = CH2CMe2(CH2)3; g: R, R′ = (CH2)6; h: R = But, R′ = H i. LDA, THF; Me3SiCI, Et3N; ii. 100−110 °C, 30 min; iii. HCI, H2O, MeOH; iv. LDA, THF; ButMe2SiCI, HMPA; v. 230 °C, 30−60 min Scheme 72

Rearrangements of Vinylcyclopropanes, Divinylcyclopropanes, and Related Systems

1063

In a study of Nakamura, an interesting application of the chemistry of the cyclopropenone acetal 265 was achieved (equation 103).437 Although this conversion was the only reported example of this novel process, it seems likely that the use of other functionalized and (or) stereochemically modified reagents would provide efficient syntheses of a wide variety of interestingly substituted seven-membered rings.

O

O

i, ii

O

O

O

67%

O

ð103Þ 265

5.22.2.4.1

Bun

Bun

Bun

I , (PPh3)4Pd, −70 °C to >r.t.

)2CuLi, THF −Et2O, −70 °C; ii. Bun

i. ( Bun

5.22.2.4

Bun

β-(2-Vinylcyclopropyl)-α,β-Unsaturated Ketones Synthesis of functionalized bicyclo[5.n.0]alkanes and related substances

The Cope rearrangement of 1,2-divinylcyclopropane systems in which one of the vinyl groups is part of an α,β-unsaturated ketone moiety has found considerable use in synthesis. A significant number of substrates have been prepared and subjected to thermal rearrangement and some of the products have been employed effectively for natural product syntheses. The reaction of 2-vinylcyclopropyllithium reagents with β-alkoxy enones has served well as a method for preparing β-(2vinylcyclopropyl) enones.438,439 For example, treatment of 266 with a mixture of cis-and trans-2-vinylcyclopropyllithium, followed by mild acid hydrolysis of the resultant products, provides the epimeric divinylcyclopropanes 267 and 268 (Scheme 73).439a Although 267 rearranges slowly at room temperature, the trans substrate 268 requires, as expected, elevated temperatures for rearrangement. Indeed, heating of the mixture of 267 and 268 at 170–180 °C provides 269 cleanly and efficiently.439a Thus, not unexpectedly, the stereoselective preparation of the requisite divinylcyclopropane substrates is unnecessary, since both 267 and 268 are readily converted into the same product 269. In a similar fashion, the enones 271–273 are smoothly transformed into the rearrangement products 270, 276 and 277, respectively.439a Under the rearrangement reaction conditions, the primary products 274 and 275, derived from 272 and 273, undergo isomerization to the more stable enones 276 and 277, respectively. EtO

O

O

i,ii

OEt

iii H

O

72% from 266

i−iii n

O

H 267 cis 268 trans

266

OEt

O

74%

269 n = 1 270 n = 2

271

O

H

i−iii R R

R = H, 77% R O R = Me, 73% R

272 R = H 273 R = Me

R R 274 R = H 275 R = Me

276 R = H 277 R = Me

i. 7:3 mixture of cis- and trans-2-vinylcyclopropyllithium, Et2O; ii. HCl, H2O; iii. 170−180 °C, PhH Scheme 73

Chemoselective Wittig reactions on keto aldehydes, such as 278 and 279, also provide substrates suitable for sigmatropic rearrangement.432,433 For example, treatment of 279 (mixture of epimers) with Ph3P¼ CHCO2Et provides the trans-divinylcyclopropane 280 (86%) and the keto ester 282 (8%), the latter being derived from room temperature Cope rearrangement of the initially formed intermediate 281 (Scheme 74).433 Thermolysis of 280 produces 282 quantitatively. The efficient conversions of 280 and 281 into the stereochemically homogenous keto ester 282 again illustrates the highly stereoselective nature of the sigmatropic rearrangement of cis- and trans-1,2-divinylcyclopropane systems. The reaction of cyclopropylcuprate reagents with β-iodo enones has proven to be a useful method for preparing β-(2-vinylcyclopropyl) enones. For example, reaction of 283 with the cuprate reagent 284 (7:3 mixture of cis and trans isomers, readily prepared from the corresponding mixture of 1-bromo-2-vinylcyclopropanes), followed by thermal rearrangement of the resultant product 285,

1064

Rearrangements of Vinylcyclopropanes, Divinylcyclopropanes, and Related Systems

O ii 100%

86% H

O

CO2Et

CO2Et

O

280

i CHO H

282

O

278 R = H 279 R = Me

CO2Et

8% H

H 281

i. Ph3P=CHCO2Et, THF, 20 °C; ii. 140 °C, xylene, 6 h Scheme 74

gives the ketone 286 (Scheme 75).467 Similarly, the substrates 287–289 are smoothly transformed into the bicyclic ketones 276, 269, and 270, whereas subjection of the (E)-2-(iodomethylene)cycloalkanones 290 and 291 to the same reaction sequence affords the corresponding spirodienones 292 and 293. Because the iodo enones are readily prepared from 1,3-dicarbonyl compounds468 and the cuprate reagent 284 is obtained via a separate synthetic route, the overall annulation sequences are convergent, short, and efficient. PhS(Li)Cu

O

O H

H

284, i, ii

ii

i

n

80%

I 283

I

O

O

284, i, ii n = 1, 84% I n = 2, 82% 288 n = 1 289 n = 2

287

286 n = 1 276 n = 2

285

n

75%

H

H

O

O

O

284

O I

n

n

269 n = 1 270 n = 2

284, i, ii n

n = 1, 64% n = 2, 77%

292 n = 1 293 n = 2

290 n = 1 291 n = 2

i. THF, −78 °C, 1 h; −20 °C, 1 h; 0 °C, 1−2 h; ii. Heat, 180 °C, 30−45 min Scheme 75

Cuprate methodology can also be used to prepare more highly substituted substrates. Thus, treatment of the 3-iodo-2cyclohexen-1-ones 287 and 289 with the epimeric, stereochemically homogenous cuprates 294 and 285 produces the divinylcyclopropanes 296–299 in excellent yields (equation 104).468

O

PhS(Li)Cu R

+

H

Et2O-THF H

I 287 R = H 289 R = Me

294 cis 295 trans

O R

−78 to 20 °C 2.5 h

H H

296 R = H, cis (88%) 297 R = Me, cis (76%) 298 R = H, trans (95%) 299 R = Me, trans (82%)

ð104Þ

Rearrangements of Vinylcyclopropanes, Divinylcyclopropanes, and Related Systems

1065

Rearrangement of the epimers 296 and 298 is, in each case, unexceptional (Scheme 76).468 Thermolysis of 296 in hexane provides the dienone 300, whereas heating either 296 or 300 at 110 °C (neat) affords the conjugated ketone 301. Although, as expected, rearrangement of 298 requires much higher temperatures, the same product 301 is formed in good yield. Presumably, this conversion proceeds by way of the stabilized diradical 302 and the cis-divinylcyclopropane 296. O

O

O

H

i H

ii

97%

H

300

296

301

iii 93%

O

O

•

H

296

•

59%

300

H 298

302

i. hexane, reflux, 4 h; ii. Heat, 110 °C, 10 min; iii. o-dichlorobenzene, 220 °C, 14 h Scheme 76

The cis substrate 297 represents an interesting case. Thermolysis of this material under a variety of conditions produces mixtures of 299 and 303, in which the latter substance nearly invariably predominates (Scheme 77).468 For example, heating of 297 in collidine at 140–150 °C gives 299 and 303 in a ratio of approximately 1:2. Under these and other thermolysis conditions, the trans-divinylcyclopropane 299 is stable. As mentioned in Section 5.22.2.2.2, Scheme 61, thermolysis of 199 at 180 °C does not result in Cope rearrangement but provides an equilibrium mixture of 199 and its epimer 197.431 Interestingly, in terms of steric congestion, the transition states for Cope rearrangement of 199 and 297, F and G, respectively, are similar (Scheme 77). Therefore, it is noteworthy that 297 does undergo sigmatropic rearrangement (albeit in competition with isomerization to 299), whereas 199 does not. In 297, of course, one of the substituted vinyl groups is part of an α,β-unsaturated ketone function and, apparently, this structural feature lowers the activation energy of the Cope rearrangement process. O

O H

O

i

H ∪ ∩ ∪ ∩

i H

H

≠

O 49%

H 303

G

297

299

H ii H 197

∪ ∩ H ∪ ∩

H

H

H

199

H

H F

i. Collidine, 140−150 °C, 43.5 h; ii. 180 °C, 3 h Scheme 77

The trans substrate 299 is quite resistant to thermal rearrangement. However, thermolysis of this substance at 220 °C (Scheme 78)468 provides the Cope rearrangement product 303 and the trienone 304, in a ratio of 1:4. Product 304 results from a [1,5] sigmatropic hydrogen migration, presumably via a transition state that can be represented by H.421,98 Interestingly, in the thermolysis of 299, the latter process is energetically more favorable than the alternative Cope rearrangement pathway. From a synthetic viewpoint, a comparison of the thermolyses of the epimers 297 and 299 (Schemes 77 and 78) illustrates the point, previously mentioned, that, in certain cases in which alternative modes of rearrangement are possible, the stereoselective

1066

Rearrangements of Vinylcyclopropanes, Divinylcyclopropanes, and Related Systems

O 20% O 303

i

H

≠

H

H 299

O

O

80%

304

(H) i. o-DCB, 220 °C, 16 h Scheme 78 o-DCB, 1,2-dichlorobenzene.

formation of the cis-divinylcyclopropane substrate is important. Thus, whereas thermal rearrangement of the cis substrate 297 provides the Cope rearrangement product 303 in reasonable yield, thermolysis of the trans isomer 299 does not.

5.22.2.5

Heterocyclic Divinylcyclopropanes

469,470

Somfai studied rearrangements of N-acylvinylaziridines. On their treatment with LiHMDS, the resulting enolate underwent a rearrangement to lactam 305 via a boat-like transition state leading to conservation of chirality in the sp2-sp3 transfer of stereochemical information (equation 105). R2

R2

R3 R4 N

LiHMDS THF, −78 °C

R1

O

R1

R2

R3

R3 R4

R4

N

R1

OLi

N H

ð105Þ

O

305 R1 = CH2OBn, Me, CH2CH2Ph R2,3 = H, Me, CH2OBn R4 = H, OBn, Me, NHBoc

Yield 60−85%

Müller described a Curtius–Cope rearrangement sequence.471 It is interesting to note that, despite the mostly concerted character of this rearrangement, some erosion of ee occurred in case of 306, probably because of participation of a biradical mechanism (equation 106). In case of the more substituted compound 307, complete conservation of stereoselectivity was observed (equation 107). Benzene, reflux

N3 O

O • N

Bun

Bun

Bun

O N

NH

Bun

ee = 90%

ð106Þ

60% ee 64%

306

H

O

O N •

BunOH reflux 92%

O • N

H

BunO

NH O

ð107Þ

307

N-Aryl vinylaziridines 308 can be rearranged to benzoazepines 309 on heating with silica gel. Gallo472 studied the formation of such aziridines and their pathways of rearrangement. In case of sterically encumbered aziridines or under strictly thermal conditions without silica gel, dihydropyrroles of type 310 are formed (equation 108).

Rearrangements of Vinylcyclopropanes, Divinylcyclopropanes, and Related Systems

R2 R1

R2 N Ar

R3

SiO2, benzene

R3 R4

R1

Ph

NH +

R4

65−80 °C

Ph

N

ð108Þ

O2N

308

NO2

Ar = 3,5-F3CC6H4, 4-NO2C6H4

310

309 R1,3=H,

R2,4=Me Single product 58%

5.22.2.6

1067

for R1,2=Ph, R3,4=H, Single product 70%

Total Syntheses

The divinylcyclopropane–cycloheptadiene rearrangement has not been featured in total syntheses as frequently as the vinylcyclopropane–cyclopentene rearrangement. Since the publication of the first edition of this work, only a few applications were reported. These are summarized in Table 17. For previous utilization of this rearrangement see the 1991 edition; notable accomplishments include the syntheses of β-himachalene by Piers473 and of confertine by Wender.474

Table 17

Total syntheses featuring the divinylcyclopropane–cycloheptadiene rearrangement

Starting material (SM)

Conditions

Product

Target

References 475

AcO O

H

AcO

O

O H

O

O Confertin A

MeO CO2Me

O

1,8-diazabicyclo[5.4.0] undec-7-ene (DBU)

MeO

HO

476

CO2Me

OTBS MeO OMe

O

MeO

O O

OTBS

HO

OMe

Hainanolidol N2

CO2Me

CO2Me Rh2(S-PTAD)4, −10 °C to reflux

O O

OTBS

OTBS

477

O O

O

(−) 5-epi-Vibsanin MeO2C

OMe

478

MeO CO2Me O

O H H

HO O (+)-Frondosin B (Continued )

1068

Rearrangements of Vinylcyclopropanes, Divinylcyclopropanes, and Related Systems

Table 17

Continued

Starting material (SM)

Conditions

O

Cs2CO3, 100 °C, 76%

N O

Product

Target

O

O O

479

N H

O

O

O

O

NH

O

O

References

RO

O

OMe O =R OH CO2Me

(−)-Deoxyharringtonine 480

O

MeO O

MeO

MeO

(−)-cis-7-Methoxycalamenene

MeO2C

Toluene-MeCN, 90 °C

H N

O O

481

O

MeO

NH

N

O

I

MeO2C

O (±)-Gelsemine

140 °C

O

O

O

O

O

482

H

H

O H

H (+)-5-epi-Tremulenolide CO2Me

Rh2(R-PTAD), hexanes, reflux

483

O

OSiMe2But H

H

H

N2 CO2Me

(+)-Barekoxide

OSiMe2But TMSO H

Toluene, 70 °C

484

O

O

O

O

5.22.3

O OPiv

N H

N OMe

N OMe

PivO H

O

HO

O

N H

O

Gelsemoxonine

Outlook

More than 50 years have passed since Neureiter's discovery of the vinylcyclopropane rearrangement. In the golden age of physical organic chemistry, 1950–70, this rearrangement and the divinylcyclopropane rearrangement were subjected to detailed

Rearrangements of Vinylcyclopropanes, Divinylcyclopropanes, and Related Systems

1069

mechanistic scrutiny. The applications of both rearrangements to synthesis followed shortly thereafter. Many useful and general methods were derived from these rearrangements and their heteroatom variants. The total synthesis community was also quick to recognize their value, as evidenced by many applications to the synthesis of natural products in both the terpene and alkaloid domains. After the publication of the chapters dealing with these two rearrangements in the first edition of Comprehensive Organic Synthesis in 1991 the frequency of applications in synthesis diminished, perhaps indicating the maturity of the methods. An update published in 2010485 as a tribute to Neureiter's historical contribution reported a few new applications that surfaced since 1991. Organometallic chemistry significantly changed the landscape of, especially, the chemistry of vinylcyclopropanes. The attention of the synthetic community has been more focused on the application of transition-metal catalysis especially in the design of new modes of reactivity, such as the higher order cycloadditions discovered by Wender and the redesign of old reactions under enantioselective conditions. The topology of these reactive substrates offers almost endless combinations of products when one considers the almost infinite combinatorial possibilities resulting from the incorporation of heteroatoms into the reactive manifold. Few of these combinations have been truly exploited in synthesis, and it is the authors' hope that the publication of this chapter will inspire interest in further development of some of the most fascinating transformations in organic synthesis.486,487

References 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32. 33. 34. 35. 36.

Baeyer, A. Chem. Ber. 1885, 18, 2269–2281. Perkin, W. H. J. Chem. Soc. 1885, 47, 801–855. Coulson, C. A.; Moffitt, W. E. J. Chem. Phys. 1947, 15, 151. Coulson, C. A.; Moffitt, W. E. Philos. Mag. 1949, 40, 1–35. (a) Walsh, A. D. Nature 1947, 159, 712–713. (b) Walsh, A. D. Trans. Faraday Soc. 1949, 45, 179–190. Dewar, M. J. S. J. Am. Chem. Soc. 1984, 106, 669–682. Cox, J. D.; Pilcher, G. Thermochemistry of Organic and Organometallic Compounds; Academic Press: London, 1970. Synder, R. G.; Schachtschneider, J. H. Spectrochim. Acta 1965, 21, 169–195. Egger, K. W.; Golden, D. M.; Benson, S. W. J. Am. Chem. Soc. 1964, 86, 5420–5424. Hudlicky, T.; Kutchan, T. M.; Naqvi, S. The Vinylcyclopropane-cyclopentene Rearrangement. In Organic Reactions; Kende, A. S., Ed.; Wiley: New York, 1985, Vol. 33, Chapter 2; pp 247–335. Mil'vitskaya, E. M.; Tarakanova, A. V.; Plate, A. F. Russ. Chem. Rev. (Engl. Transl.) 1976, 45, 469–478. Willcott, M. R.; Cargill, R. L., III; Sears, A. B. Prog. Phys. Org. Chem. 1972, 9, 25–98. Wong, H. N. C.; Hon, M. Y.; Tse, C. W.; et al. Chem. Rev. 1989, 89, 165–198. Rappoport, Z. The Chemistry of the Cyclopropyl Group; Wiley: New York, 1987. Salaun, J. R. Y. Rearrangements Involving the Cyclopropyl Group. In The Chemistry of the Cyclopropyl Group; Rappoport, Z., Ed.; Wiley: New York, 1987, Part 2; Chapter 13; pp 809–878, Salaün, J. Synthesis and Synthetic Applications of 1-Donor Substituted Cyclopropanes with Ethynyl, Vinyl and Carbonyl Groups. In Top. Curr. Chem.; de Meijere, A., Ed.; Springer: Berlin/Heidelberg, 1988, Vol. 144; pp 1–71. Reissig, H. U. Donor-acceptor-substituted Cyclopropanes: Versatile Building Blocks in Organic Synthesis. In Top. Curr. Chem.; de Meijere, A., Ed.; Springer: Berlin/ Heidelberg, 1988, Vol. 144; pp 73–135. Krief, A. Synthesis and Synthetic Applications of 1-Metallo-1-selenocyclopropanes and -Cyclobutanes and Related 1-etallo-1-silylcyclopropanes. In Top. Curr. Chem.; deMeijere, A., Ed.; Springer: Berlin/Heidelberg, 1987, Vol. 135; pp 1–75. Binger, P.; Büch, H. Cyclopropenes and Methylenecylopropanes as Multifunctional Reagents in Transition Metal Catalyzed Reactions. In Top. Curr. Chem.; de Meijere, A., Ed.; Springer: Berlin/Heidelberg, 1987, Vol. 135; pp 77–151. Trost, B. M. Acc. Chem. Res. 1974, 7, 85–92. Trost, B. Strain and Reactivity: Partners for Selective Synthesis. In Top. Curr. Chem.; de Meijere, A., Ed.; Springer: Berlin/Heidelberg, 1986, Vol. 133; pp 3–82. Reissig, H. U. Organic Synthesis via Cyclopropanes: Principles and Application. In The Chemistry of the Cyclopropyl Group; Rappoport, Z., Ed.; Wiley: New York, 1987, Part 1; pp 375–444. Baldwin, J. E. Chem. Rev. 2003, 103, 1197–1212. Hudlicky, T.; Becker, D. A.; Fan, R. L.; Kozhushkov, S. Vinylcyclopropane−cyclopentene Rearrangement. In Carbocyclic Three-membered Ring Compounds; Houben− Weyl, 1996, Vol. E 17c; pp 2538−2565. Baldwin, J. E.; Leber, P. A. Org. Biomol. Chem. 2008, 6, 36–47. Wang, S. C.; Tantillo, D. J. J. Organomet. Chem. 2006, 691, 4386–4392. Staley, S. W. J. Am. Chem. Soc. 1967, 89, 1532–1533. Tidwell, T. T. Conjugative and Substituent Properties of the Cyclopropyl Group. In The Chemistry of the Cyclopropyl Group; Rappoport, Z., Ed.; Wiley: New York, 1987, Part 1; pp 565–632. Carreira, L. A.; Towns, T. G.; Malloy, T. B. J. Am. Chem. Soc. 1978, 100, 385–388. Wiberg, K. B. Structures, Energies and Spectra of Cyclopropanes. In The Chemistry of the Cyclopropyl Group; Rappoport, Z., Ed.; Wiley: New York, 1987, Part 1; pp 1–26. Boche, G.; Walborsky, H. M. Cyclopropyl Radicals, Anion Radicals and Anions. In The Chemistry of the Cyclopropyl Group; Rappoport, Z., Ed.; Wiley: New York, 1987, part 1; pp 701–808. Hirao, T. Selective Transformations of Small Ring Compounds in Redox Reactions. In Small Ring Compounds in Organic Synthesis V; Meijere, A., Ed.; Springer: Berlin, Heidelberg, 1996, Vol. 178; pp 99–147. (a) Oxgaard, J.; Wiest, O. J. Am. Chem. Soc. 1999, 121, 11531–11537. (b) Oxgaard, J.; Wiest, O. Eur. J. Org. Chem. 2003, 2003, 1454–1462. (c) Donoghue, P. J.; Wiest, O. Chem. Eur. J. 2006, 12, 7018–7026. Houmam, A. Chem. Rev. 2008, 108, 2180–2237. (a) Stevenson, J. P.; Jackson, W. F.; Tanko, J. M. J. Am. Chem. Soc. 2002, 124, 4271–4281. (a) Chahma, M. h.; Li, X.; Phillips, J. P.; et al. J. Phys. Chem. A 2005, 109, 3372–3382. (b) Tanko, J. M.; Li, X.; Chahma, M. H.; Jackson, W. F.; Spencer, J. N. J. Am. Chem. Soc. 2007, 129, 4181–4192. Mathew, L.; Warkentin, J. J. Am. Chem. Soc. 1986, 108, 7981–7984.

1070

37. 38. 39. 40. 41. 42. 43. 44. 45. 46. 47. 48. 49. 50. 51. 52. 53. 54. 55. 56. 57. 58. 59. 60. 61. 62. 63. 64. 65. 66. 67. 68. 69. 70. 71. 72. 73. 74. 75. 76. 77. 78. 79. 80. 81. 82. 83. 84. 85. 86. 87. 88. 89. 90. 91. 92. 93. 94. 95. 96. 97. 98. 99. 100. 101. 102. 103. 104. 105.

Rearrangements of Vinylcyclopropanes, Divinylcyclopropanes, and Related Systems

Maillard, B.; Forrest, D.; Ingold, K. U. J. Am. Chem. Soc. 1976, 98, 7024–7026. Griller, D.; Ingold, K. U. Acc. Chem. Res. 1980, 13, 317–323. Ratier, M.; Pereyre, M.; Davies, A. G.; Sutcliffe, R. J. Chem. Soc., Perk. Trans. 2 1984, 1907–1915. Kochi, J. K.; Krusic, P. J.; Eaton, D. R. J. Am. Chem. Soc. 1969, 91, 1877–1879. Chen, K. S.; Edge, D. J.; Kochi, J. K. J. Am. Chem. Soc. 1973, 95, 7036–7043. Hehre, W. J. J. Am. Chem. Soc. 1973, 95, 2643–2646. Shono, T.; Nishiguchi, I. Tetrahedron 1974, 30, 2173–2181. Evans, D. A., ‘Consonant and Dissonant Relationships: An Organizational Model for Organic Synthesis’, unpublished (available from D. A. Evans, Harvard University). Hudlicky, T.; Reed, J. W. The Way of Synthesis: Evolution of Design and Methods for Natural Products; Wiley-VCH-Verlag: Weinheim, 2007; pp 186−190. Seebach, D. Angew. Chem. Int. Ed. 1979, 18, 239–258. Wenkert, E. Acc. Chem. Res. 1980, 13, 27–31. Wenkert, E. Heterocycles 1980, 14, 1703–1708. Trinajstic, N. Chemical Graph Theory; CRC Press: Cleveland, 1987; Vols. 1 and 2. Bertz, S. H. J. Am. Chem. Soc. 1981, 103, 3599–3601. Hudlicky, H.; RuLin, F.; Lovelace, T. C.; Reed, J. W. In Studies in Natural Product Chemistry, Stereoselective Synthesis; Atta-ur-Rahman, Ed.; Elsevier: Amsterdam, 1989, Vol. 3, Part B; p 3. Hudlicky, T.; Reed, J. W. personal communication. Combinatorial possibilities for the rearrangement were estimated. Buchert, M.; Reissig, H. U. Liebigs Annalen 1996, 1996 (12), 2007–2013. Reissig, H.-U.; Zimmer, R. Chem. Rev. 2003, 103, 1151–1196. Yu, M.; Pagenkopf, B. L. Tetrahedron 2005, 61, 321–347. Carson, C. A.; Kerr, M. A. Chem. Soc. Rev. 2009, 38, 3051–3060. Wendisch, D. In Methoden Org. Chem. (Houben–Weyl); Muller, E., Ed.; Thieme Verlag: Stuttgart, 1971, Vol. 4, Chapter 3; p 15. Tsuji, T.; Nishida, S. Preparation of Cyclopropyl Derivatives. In The Chemistry of the Cyclopropyl Group; Rappoport, Z., Ed.; Wiley: New York, 1987, Part 1; pp 307–374. Verhé, R.; de Kimpe, N. Synthesis and Reactivity of Electrophilic Cyclopropanes. In The Chemistry of the Cyclopropyl Group; Rappoport, Z., Ed.; Wiley: New York, 1987, Part 1; pp 445–564. Cowell, G. W.; Ledwith, A. Q. Rev. Chem. Soc. 1970, 24, 119–167. Doyle, M. P. Chem. Ind. (London) 1985, 22, 47. Doyle, M. P. Chem. Rev. 1986, 86, 919–939. Brookhart, M.; Studabaker, W. B. Chem. Rev. 1987, 87, 411–432. Kostikov, R. Zh. Vses. Khim. Ova. 1986, 31, 177, (Chem. Abstr., 1987, 106, 101 750g). Lautens, M.; Klute, W.; Tam, W. Chem. Rev. 1996, 96, 49–92. Kulinkovich, O. G.; Sviridov, S. V.; Vasilevski, D. A. Synthesis 1991, 234. Chaplinski, V.; de Meijere, A. Angew. Chem. Int. Ed. 1996, 35, 413–414. Bertus, P.; Szymoniak, J. Chem. Commun. 2001, 1792–1793. Sato, F.; Okamoto, S. Adv. Synth. Catal. 2001, 343, 759–784. Kulinkovich, O. G. Chem. Rev. 2003, 103, 2597–2632. Kulinkovich, O. G.; de Meijere, A. Chem. Rev. 2000, 100, 2789–2834. Bertus, P.; Szymoniak, J. Synlett 2007, 1346, 1356. Wolan, A.; Six, Y. Tetrahedron 2010, 66, 15–61. Wolan, A.; Six, Y. Tetrahedron 2010, 66, 3097–3133. Conia, J. M.; Salaun, J. R. Acc. Chem. Res. 1972, 5, 33–40. Conia, J. M.; Robson, M. J. Angew. Chem. Int. Ed. 1975, 14, 473–485. King, J. F.; Mayo, P. d.; McIntosh, C. L.; Piers, K.; Smith, D. J. H. Can. J. Chem. 1970, 48, 3704–3715. Trost, B. M.; Schinski, W. L.; Chen, F.; Mantz, I. B. J. Am. Chem. Soc. 1971, 93, 676–684. Lebel, H.; Marcoux, J. F.; Molinaro, C.; Charette, A. B. Chem. Rev. 2003, 103, 977–1050. Burke, S. D.; Grieco, P. A. Intramolecular Reaction of Diazocarbonyl Compounds. In Organic Reactions; Dauben, W. G., Ed.; Wiley: New York, 1979, Vol. 26, Chapter 2; pp 361–476. David, V.; Warnhoff, E. W. The Reactions of Diazoacetic Esters with Alkenes, Alkynes, Heterocyclic, and Aromatic Compound. In Organic Reactions; Dauben, W. G., Ed.; Wiley: New York, 1970, Vol. 18, Chapter 3; pp 217–402. Simmons, H. E.; Cairns, T. L.; Vladuchik, S. A.; Hoiness, C. M. In Organic Reactions; Dauben, W. G., Ed.; Wiley: New York, 1973, Vol. 20, Chapter 1; pp 1–132. Doyle, M. P.; Protopopova, M. N. Tetrahedron 1998, 54, 7919–7946. Davies, H. M. L.; Antoulinakis, E. G. In Organic Reactions; Overman, L. E., Ed.; Wiley: New York, 2001, Vol. 57, Chapter 1; pp 1–326. Johnson, C. R. Acc. Chem. Res. 1973, 6, 341–347. Trost, B. M.; Melvin, L. S., Jr. Sulfur Ylides; Academic Press: New York, 1975. Li, A.-H.; Dai, L.-X.; Aggarwal, V. K. Chem. Rev. 1997, 97, 2341–2372. Sun, X.-L.; Tang, Y. Acc. Chem. Res. 2008, 41, 937–948. Rubin, M.; Rubina, M.; Gevorgyan, V. Chem. Rev. 2007, 107, 3117–3179. Davies, H. M. L.; Clark, D. M.; Alligood, D. B.; Eiband, G. R. Tetrahedron 1987, 43, 4265–4270. Davies, H. M. L.; Hu, B. Tetrahedron Lett. 1992, 33, 455–456. Frey, H. M.; Walsh, R. Chem. Rev. 1969, 69, 103–124. Glass, D. S.; Boikess, R. S.; Winstein, S. Tetrahedron Lett. 1966, 7, 999–1008. Frey, H. M.; Solly, R. K. J. Chem. Soc. B 1970, 996–998. Ellis, R. J.; Frey, H. M. J. Chem. Soc. 1964, 5578–5583. Hudlicky, T.; Koszyk, F. J. Tetrahedron Lett. 1980, 21, 2487–2490. Ohloff, G. Tetrahedron Lett. 1965, 6, 3795–3800. Spangler, C. W. Chem. Rev. 1976, 76, 187–217. Piers, E.; Maxwell, A. R. Can. J. Chem. 1984, 62, 2392–2395. Gilbert, J. C.; Smith, K. R.; Klumpp, G. W.; Schakel, M. Tetrahedron Lett. 1972, 13, 125–128. Roth, W. R.; König, J. Liebigs Ann. Chem. 1965, 688, 28–39. Roberts, R. M.; Landolt, R. G.; Greene, R. N.; Heyer, E. W. J. Am. Chem. Soc. 1967, 89, 1404–1411. Bickelhaupt, F.; de Graaf, W. L.; Klumpp, G. W. Chem. Commun. 1968, 53–54. Schakel, M.; Klumpp, G. W. Recl. Trav. Chim. Pays-Bas 1973, 92, 605–608. Monti, S. A.; McAninch, T. W. Tetrahedron Lett. 1974, 15, 3239–3240.

Rearrangements of Vinylcyclopropanes, Divinylcyclopropanes, and Related Systems

106. 107. 108. 109. 110. 111. 112. 113. 114. 115. 116. 117. 118. 119. 120. 121. 122. 123. 124. 125. 126. 127. 128. 129. 130. 131. 132. 133. 134. 135. 136. 137. 138. 139. 140. 141. 142. 143. 144. 145. 146. 147. 148. 149. 150. 151. 152. 153. 154. 155.

156. 157. 158. 159. 160. 161. 162. 163. 164. 165. 166. 167. 168. 169. 170. 171.

1071

Govindan, S. V.; Hudlicky, T.; Koszyk, F. J. J. Org. Chem. 1983, 48, 3581–3583. Neureiter, N. J. Org. Chem. 1959, 24, 2044–2046. Vogel, E. Angew. Chem. 1960, 72, 4–26. Overberger, C. G.; Borchert, A. E. J. Am. Chem. Soc. 1960, 82, 1007–1008. Andrews, G. D.; Baldwin, J. E. J. Am. Chem. Soc. 1976, 98, 6705–6706. Carpenter, B. K. Preparation and Uses of Isotopically Labelled Derivatives. In The Chemistry of the Cyclopropyl Group; Rappoport, Z., Ed.; Wiley: New York, 1987, Part 2; pp 1027–1082. Newman-Evans, R. H.; Simon, R. J.; Carpenter, B. K. J. Org. Chem. 1990, 55, 695–711. Gajewski, J. J.; Olson, L. P. J. Am. Chem. Soc. 1991, 113, 7432–7433. McGaffin, G.; Grimm, B.; Heinecke, U.; et al. Eur. J. Org. Chem. 2001, 3559–3573. de Meijere, A.; Kozhushkov, Sergei I.; Faber, D.; et al. Eur. J. Org. Chem. 2001, 2001, 3607–3614. Ohta, A.; Dahl, K.; Raab, R.; Geittner, J.; Huisgen, R. Helv. Chim. Acta 2008, 91, 783–804. Mulzer, J.; Huisgen, R.; Arion, V.; Sustmann, R. Helv. Chim. Acta 2011, 94, 1359–1388. Lewis, D. K.; Charney, D. J.; Kalra, B. L.; et al. J. Phys. Chem. A 1997, 101, 4097–4102. Baldwin, J. E.; Bonacorsi, S. J. Am. Chem. Soc. 1993, 115, 10621–10627. Asuncion, L. A.; Baldwin, J. E. J. Am. Chem. Soc. 1995, 117, 10672–10677. Jug, K.; Kölle, C. J. Phys. Chem. B 1998, 102, 6605–6611. Sonawane, H. R.; Nanjundiah, B. S.; Nazeruddin, G. M. Tetrahedron Lett. 1992, 33, 1645–1646. Lee, P. H.; Kim, J. S.; Kim, Y. C.; Kim, S. Tetrahedron Lett. 1993, 34, 7583–7586. Kohmoto, S.; Nakayama, N.; Takami, J.-i.; et al. Tetrahedron Lett. 1996, 37, 7761–7764. Kassam, K.; Venneri, P. C.; Warkentin, J. Can. J. Chem. 1997, 75, 1256–1263. Kataoka, T.; Nakamura, Y.; Matsumoto, H.; et al. J. Chem. Soc., Perkin Trans. 1 1997, 309–316. Williams, M. C.; de Meijere, A. J. Chem. Soc., Perkin Trans. 1 1998, 3699–3702. Brandi, A.; Cicchi, S.; Brandl, M.; Kozhushkov, S. I.; de Meijere, A. Synlett 2001, 433–435. van Es, D. S.; Gret, N.; de Rijke, M.; et al. Tetrahedron 2001, 57, 3557–3565. Smart, B. E.; Krusic, P. J.; Roe, D. C.; Yang, Z.-Y. J. Fluorine Chem. 2002, 117, 199–205. Voigt, T.; Winsel, H.; de Meijere, A. Synlett 2002, 1362–1364. Boisvert, L.; Beaumier, F.; Spino, C. Org. Lett. 2007, 9, 5361–5363. Beaumier, F.; Dupuis, M.; Spino, C.; Legault, C. Y. J. Am. Chem. Soc. 2012, 134, 5938–5953. (a) Nendel, M.; Sperling, D.; Wiest, O.; Houk, K. N. J. Org. Chem. 2000, 65, 3259–3268. (b) Oxgaard, J.; Wiest, O. Eur. J. Org. Chem. 2003, 1454–1462. Sonawane, H. R.; Bellur, N. S.; Kulkarni, D. G.; Ahuja, J. R. Synlett 1993, 875–884. Waske, P. A.; Tzvetkov, N. T.; Mattay, J. Synlett 2007, 669–685. Armesto, D.; Ortiz, M. J.; Agarrabeitia, A. R. J. Org. Chem. 1999, 64, 1056–1060. Armesto, D.; Ramos, A.; Mayoral, E. P.; Ortiz, M. J.; Agarrabeitia, A. R. Org. Lett. 2000, 2, 183–186. Dinnocenzo, J. P.; Conlon, D. A. Tetrahedron Lett. 1995, 36, 7415–7418. Sutton, S. C.; Nantz, M. H.; Parkin, S. R. Organometallics 1993, 12, 2248–2257. Grossman, R. B.; Tsai, J.-C.; Davis, W. M.; Gutierrez, A.; Buchwald, S. L. Organometallics 1994, 13, 3892–3896. Corey, E. J.; Kigoshi, H. Tetrahedron Lett. 1991, 32, 5025–5028. Harvey, D. F.; Brown, M. F. Tetrahedron Lett. 1991, 32, 2871–2874. Satyanarayana, J.; Basaveswara Rao, M. V.; Ila, H.; Junjappa, H. Tetrahedron Lett. 1996, 37, 3565–3568. Davies, H. M. L.; Hu, B. J. Org. Chem. 1992, 57, 3186–3190. Davies, H. M. L.; Kong, N.; Churchill, M. R. J. Org. Chem. 1998, 63, 6586–6589. Grant, T. N.; West, F. G. J. Am. Chem. Soc. 2006, 128, 9348–9349. Grant, T. N.; West, F. G. Org. Lett. 2007, 9, 3789–3792. Zhang, F. Y.; Kulesza, A.; Rani, S.; Bernet, B.; Vasella, A. Helv. Chim. Acta 2008, 91, 1201–1218. Coscia, R. W.; Lambert, T. H. J. Am. Chem. Soc. 2009, 131, 2496–2498. Lingam, K. A. P.; Shanmugam, P.; Selvakumar, K. Synlett 2012, 278–284. (a) Hudlicky, T.; Koszyk, F. F.; Kutchan, T. M.; Sheth, J. P. J. Org. Chem. 1980, 45, 5020–5027. (b) Hudlicky, T.; Koszyk, F. J.; Dochwat, D. M.; Cantrell, G. L. J. Org. Chem. 1981, 46, 2911–2915. (c) Hudlicky, T.; Short, R. P. J. Org. Chem. 1982, 47, 1522–1527. Khusnutdinov, R. I.; Dzhemilev, U. M. J. Organomet. Chem. 1994, 471, 1–18. (a) Iwasawa, N.; Narasaka, K. Transition Metal Promoted Ring Expansion of Alkynyl- and Propadienylcyclopropanes. In Topics in Curr. Chem.; de Meijere, A., Ed.; Springer: Berlin/Heidelberg, 2000, Vol. 207; pp 69–88. (b) Rubin, M.; Rubina, M.; Gevorgyan, V. Chem. Rev. 2007, 107 (7), 3117–3179. (a) Grigg, R.; Hayes, R.; Sweeney, A. J. Chem. Soc. Chem. Commun. 1971, 1248–1249. (b) Salomon, R. G.; Salomon, M. F.; Kachinski, J. L. C. J. Am. Chem. Soc. 1977, 99, 1043–1054. (c) Pinke, P. A.; Stauffer, R. D.; Miller, R. G. J. Am. Chem. Soc. 1974, 96, 4229–4234. (d) Aris, V.; Brown, J. M.; Conneely, J. A.; Golding, B. T.; Williamson, D. H. J. Chem. Soc. Perkin Trans. 2 1975, 4–10. (e) Alcock, N. W.; Brown, J. M.; Conneely, J. A.; Williamson, D. H. J. Chem. Soc. Perkin Trans. 2 1979, 962–971. (f) Murakami, M.; Nishida, S. Chem. Lett. 1979, 8, 927–930. (g) Doyle, M. P.; Van Leusen, D. J. Org. Chem. 1982, 47, 5326–5339. Ryu, I.; Ikura, K.; Tamura, Y.; et al. Synlett 1994, 941–942. Hiroi, K.; Arinaga, Y.; Ogino, T. Chem. Lett. 1992, 21, 2329–2332. (b) Hiroi, K.; Arinaga, Y.; Ogino, T. Chem. Pharm. Bull. 1994, 42, 470–474. (a) Hiroi, K.; Arinaga, Y. Tetrahedron Lett. 1994, 35, 153–156. (b) Hiroi, K.; Yoshida, Y.; Kaneko, Y. Tetrahedron Lett. 1999, 40, 3431–3434. (c) Hiroi, K.; Suzuki, Y.; Kaneko, Y.; et al. Polyhedron 2000, 19, 525–528. Jun, C.-H.; Kang, J.-B.; Lim, Y.-G. Tetrahedron Lett. 1995, 36, 277–280. Hayashi, M.; Ohmatsu, T.; Meng, Y. P.; Saigo, K. Angew. Chem. Int. Ed. 1998, 37, 837–839. Shimizu, M.; Schelper, M.; Nagao, I.; et al. Chem. Lett. 2006, 35, 1222–1223. Hiroi, K.; Kato, F.; Oguchi, T.; Saito, S.; Sone, T. Tetrahedron Lett. 2008, 49, 3567–3569. Mauleόn, P.; Krinsky, J. L.; Toste, F. D. J. Am. Chem. Soc. 2009, 131, 4513–4520. Garayalde, D.; Gόmez-Bengoa, E.; Huang, X.; Goeke, A.; Nevado, C. J. Am. Chem. Soc. 2010, 132, 4720–4730. Suginome, M.; Matsuda, T.; Yoshimoto, T.; Ito, Y. Organometallics 2002, 21, 1537–1539. Zuo, G.; Louie, J. Angew. Chem. Int. Ed. 2004, 43, 2277–2279. Miura, T.; Sasaki, T.; Harumashi, T.; Murakami, M. J. Am. Chem. Soc. 2006, 128, 2516–2517. Wang, S. C.; Troast, D. M.; Conda-Sheridan, M.; et al. J. Org. Chem. 2009, 74, 7822–7833. Shimizu, I.; Ohashi, Y.; Tsuji, J. Tetrahedron Lett. 1985, 26, 3825–3828. Parsons, A. T.; Campbell, M. J.; Johnson, J. S. Org. Lett. 2008, 10, 2541–2544.

1072

Rearrangements of Vinylcyclopropanes, Divinylcyclopropanes, and Related Systems

172. (a) Jiao, L.; Ye, S.; Yu, Z.-X. J. Am. Chem. Soc. 2008, 130, 7178–7179. (b) Li, Q.; Jiang, G.-J.; Jiao, L.; Yu, Z.-X. Org. Lett. 2010, 12, 1332–1335. (c) Jiao, L.; Lin, M.; Yu, Z.-X. Chem. Commun. 2010, 46, 1059–1061. 173. Sherry, B. D.; Fürstner, A. Chem. Commun. 2009, 7116–7118. 174. Dieskau, A. P.; Holzwarth, M. S.; Plietker, B. J. Am. Chem. Soc. 2012, 134, 5048–5051. 175. Hiroi, K.; Yamada, A. Tetrahedron Asymmetry 2000, 11, 1835–1841. 176. Trost, B. M.; Morris, P. J. Angew. Chem. Int. Ed. 2011, 50, 6167–6170. 177. Mei, L.-Y.; Wei, Y.; Xu, Q.; Shi, M. Organometallics 2012, 31, 7591−7599. 178. (a) Sebelius, S.; Olsson, V. J.; Szabó, K. J. J. Am. Chem. Soc. 2005, 127, 10478–10479. (b) Sebelius, S.; Olsson, V. J.; Wallner, O. A.; Szabó, K. J. J. Am. Chem. Soc. 2006, 128, 8150–8151. 179. Sumida, Y.; Yorimitsu, H.; Oshima, K. Org. Lett. 2008, 10, 4677–4679. 180. Sierra, M. A.; Soderberg, B.; Lander, P. A.; Hegedus, L. S. Organometallics 1993, 12, 3769–3771. 181. (a) Iwasawa, N.; Owada, Y.; Matsuo, T. Chem. Lett. 1995, 24, 115–116. (b) Owada, Y.; Matsuo, T.; Iwasawa, N. Tetrahedron 1997, 53, 11069–11086. 182. Murakami, M.; Itami, K.; Ubukata, M.; Tsuji, I.; Ito, Y. J. Org. Chem. 1998, 63, 4–5. 183. Schulze, M. M.; Gockel, U. Tetrahedron Lett. 1996, 37, 357–358. (b) Schulze, M. M.; Gockel, U. J. Organomet. Chem. 1996, 525, 155–158. 184. Taber, D. F.; Bui, G.; Chen, B. J. Org. Chem. 2001, 66, 3423–3426. 185. Kurahashi, T.; de Meijere, A. Synlett 2005, 2619–2622. 186. Jiang, G.-J.; Fu, X.-F.; Li, Q.; Yu, Z.-X. Org. Lett. 2012, 14, 692–695. 187. Lin, M.; Li, F.; Jiao, L.; Yu, Z.-X. J. Am. Chem. Soc. 2011, 133, 1690–1693. 188. (a) Pellissier, H. Adv. Synth. Catal. 2011, 353, 189–218. (b) Wender, P. A.; Croatt, M. P.; Deschamps, N. M. 10.13 − C−C Bond Formation (Part 1) by Addition Reactions: Higher-order Cycloadditions. In Comprehensive Organometallic Chemistry III; Robert, H. C., Mingos, D. M. P., Eds.; Elsevier: Oxford, 2007, pp 603–647. (c) Wender, P. A.; Bi, F. C.; Gamber, G. G.; et al. Pure Appl. Chem. 2002, 74, 25–31. 189. Wender, P. A.; Takahashi, H.; Witulski, B. J. Am. Chem. Soc. 1995, 117, 4720–4721. 190. Wender, P. A.; Sperandio, D. J. Org. Chem. 1998, 63, 4164–4165. 191. Gilbertson, S. R.; Hoge, G. S. Tetrahedron Lett. 1998, 39, 2075–2078. 192. Wang, B.; Cao, P.; Zhang, X. Tetrahedron Lett. 2000, 41, 8041–8044. 193. Wender, P. A.; Williams, T. J. Angew. Chem. Int. Ed. 2002, 41, 4550–4553. 194. Wender, P. A.; Lesser, A. B.; Sirois, L. E. Angew. Chem. Int. Ed. 2012, 51, 2736–2740. 195. Wender, P. A.; Love, J. A.; Williams, T. J. Synlett 2003, 1295–1298. 196. Trost, B. M.; Toste, F. D.; Shen, H. J. Am. Chem. Soc. 2000, 122, 2379–2380. 197. Fürstner, A.; Majima, K.; Martín, R.; et al. J. Am. Chem. Soc. 2008, 130, 1992–2004. 198. Zuo, G.; Louie, J. J. Am. Chem. Soc. 2005, 127, 5798–5799. 199. Wender, P. A.; Glorius, F.; Husfeld, C. O.; Langkopf, E.; Love, J. A. J. Am. Chem. Soc. 1999, 121, 5348–5349. 200. Wender, P. A.; Husfeld, C. O.; Langkopf, E.; Love, J. A. J. Am. Chem. Soc. 1998, 120, 1940–1941. 201. Wender, P. A.; Husfeld, C. O.; Langkopf, E.; Love, J. A.; Pleuss, N. Tetrahedron 1998, 54, 7203–7220. 202. Wender, P. A.; Rieck, H.; Fuji, M. J. Am. Chem. Soc. 1998, 120, 10976–10977. 203. Wender, P. A.; Dyckman, A. J.; Husfeld, C. O.; Scanio, M. J. C. Org. Lett. 2000, 2, 1609–1611. 204. Wender, P. A.; Barzilay, C. M.; Dyckman, A. J. J. Am. Chem. Soc. 2000, 123, 179–180. 205. Wender, P. A.; Sirois, L. E.; Stemmler, R. T.; Williams, T. J. Org. Lett. 2010, 12, 1604–1607. 206. Wegner, H. A.; de Meijere, A.; Wender, P. A. J. Am. Chem. Soc. 2005, 127, 6530–6531. 207. Wender, P. A.; Haustedt, L. O.; Lim, J.; et al. J. Am. Chem. Soc. 2006, 128, 6302–6303. 208. Shintani, R.; Nakatsu, H.; Takatsu, K.; Hayashi, T. Chem. Eur. J. 2009, 15, 8692–8694. 209. Hudlicky, J. R.; Hopkins-Hill, J.; Hudlicky, T. Synlett 2011, 2891–2895. 210. Bisset, T.; Hudlicky, T., unpublished observations. 211. Vogel, E.; Günther, H. Angew. Chem. Int. Ed. 1967, 6, 385–401. 212. van Tamelen, E. E. J. Am. Chem. Soc. 1955, 77, 1704–1706. 213. Crawford, R. J.; Lutener, S. B.; Cockcroft, R. D. Can. J. Chem. 1976, 54, 3364–3376. 214. Eberbach, W.; Burchardt, B. Chem. Ber. 1978, 111, 3665–3698. 215. O'Sullivan, A.; Bischofberger, N.; Frei, B.; Jeger, O. Helv. Chim. Acta 1985, 68, 1089–1106. 216. Eberbach, W.; Roser, J. Tetrahedron 1986, 42, 2221–2234. 217. (a) Eberbach, W.; Trostmann, U. Chem. Ber. 1985, 118, 4035–4058. (b) Eberbach, W.; Trostmann, U. Chem. Ber. 1981, 114, 2979–3003. 218. Eberbach, W.; Roser, J. Tetrahedron Lett. 1987, 28, 2685–2688. 219. Paulson, D. R.; Tang, F. Y. N.; Sloane, R. B. J. Org. Chem. 1973, 38, 3967–3968. 220. (a) Bourelle-Wargnier, F.; Vincent, M.; Chuche, J. J. Org. Chem. 1980, 45, 428–435. (b) Bourelle-Wargnier, F.; Vincent, M.; Chuche, J. Tetrahedron Lett. 1978, 19, 283–286. 221. (a) Hudlicky, T.; Fleming, A.; Lovelace, T. C. Tetrahedron 1989, 45, 3021–3037. (b) Hudlicky, T.; Lovelace, T. C. Synth. Commun. 1990, 20, 1721–1732. 222. Hudlicky, T.; Rulin, F.; Reed, J. W.; Gadamasetti, K. G. Divinylcyclopropane−Cycloheptadiene Rearrangement. In Organic Reactions; Paquette, L. A., Ed.; Wiley: New York, 1992, Vol. 41, Chapter 1; pp 1–133. 223. Batsanov, A. S.; Byerley, A. L. J.; Howard, J. A. K.; Steel, P. G. Synlett 1996, 401–403. 224. Bobyleva L. I.; Krjukov S. I.; Abreimova M. A., et al. (JAROSLAVSKIJ GOSUDARSTVENNYJ TEKHNICHESKIJ UNIVERS); Method of Synthesis of 2,5-Dihydrofuran. RU Appl. 0117228, 1996. RU 2105004 C1 19980220 (1998). 225. Falling, S.; Monnier, J.; Phillips, G.; Kanel, J.; Godleski, S. Development of an Industrial Process for the Lewis Acid/Iodide Salt-Catalyzed Rearrangement of 3,4-Epoxy-1Butene to 2,5-Dihydrofuran. In Catalysis of Organic Reactions: Twenty-first Conference; Schmidt, S. R., Ed.; CRC Press: Boca Raton, 2007, pp 327–335. 226. Batory, L. A.; McInnis, C. E.; Njardarson, J. T. J. Am. Chem. Soc. 2006, 128, 16054–16055. 227. Feldman, K. S.; Romanelli, A. L.; Ruckle, R. E.; Miller, R. F. J. Am. Chem. Soc. 1988, 110, 3300–3302. 228. Feldman, K. S.; Fisher, T. E. Tetrahedron 1989, 45, 2969–2977. 229. Cho, I.; Lee, J.-Y. Makromol. Chem. Rapid Commun. 1984, 5, 263–267. 230. Braslavsky, S.; Heicklen, J. Chem. Rev. 1977, 77, 473–511. 231. Marshall, J. A.; Trometer, J. D.; Cleary, D. G. Tetrahedron 1989, 45, 391–402. 232. Olofsson, B.; Somfai, P. Vinylepoxides in Organic Synthesis. In Aziridines and Epoxides in Organic Synthesis; Yudin, A. K., Ed.; Wiley-VCH Gmbh: Weinheim, 2006, pp 315–347. 233. Lipshutz, B. H.; Wilhelm, R. S.; Kozlowski, J. A.; Parker, D. J. Org. Chem. 1984, 49, 3928–3938. 234. Hudlicky, T.; Fleming, A.; Radesca, L. J. Am. Chem. Soc. 1989, 111, 6691–6707. 235. Fleming, A.; Sinai-Zingde, G.; Natchus, M.; Hudlicky, T. Tetrahedron Lett. 1987, 28, 167–170.

Rearrangements of Vinylcyclopropanes, Divinylcyclopropanes, and Related Systems

1073

236. Trost, B. M.; Angle, S. R. J. Am. Chem. Soc. 1985, 107, 6123–6124. 237. Pettersson-Fasth, H.; Riesinger, S. W.; Baeckvall, J. E. J. Org. Chem. 1995, 60, 6091–6096. 238. (a) Trost, B. M.; McEachern, E. J.; Toste, F. D. J. Am. Chem. Soc. 1998, 120, 12702–12703. (b) Trost, B. M.; Tang, W.; Schulte, J. L. Org. Lett. 2000, 2, 4013–4015. (c) Trost, B. M.; Brown, B. S.; McEachern, E. J.; Kuhn, O. Chem.-Eur. J. 2003, 9, 4442–4451. (d) Trost, B. M.; Zhang, T. Org. Lett. 2006, 8, 6007–6010. 239. (a) Trost, B. M.; Krueger, A. C.; Bunt, R. C.; Zambrano, J. J. Am. Chem. Soc. 1996, 118, 6520–6521. (b) Trost, B. M.; Horne, D. B.; Woltering, M. J. Angew. Chem. Int. Ed. 2003, 42, 5987–5990. 240. (a) Trost, B. M.; Ceschi, M. A.; König, B. Angew. Chem. Int. Ed. 1997, 36, 1486–1489. (b) Trost, B. M.; Jiang, C. J. Am. Chem. Soc. 2001, 123, 12907–12908. 241. (a) Badalassi, F.; Crotti, P.; Macchia, F.; et al. Tetrahedron Lett. 1998, 39, 7795–7798. (b) Bertozzi, F.; Crotti, P.; Feringa, B. L.; Macchia, F.; Pineschi, M. Synthesis 2001, 483–486. 242. Equey, O.; Alexakis, A. Tetrahedron Asymmetry 2004, 15, 1531–1536. 243. Rambaud, R. Bull. Soc. Chim. Fr. 1938, 1552. 244. Julia, M.; Baillarge, M. Bull. Soc. Chim. Fr. 1966, 734–743. 245. De Simone, F.; Waser, J. Synthesis 2009, 3353–3374. 246. Alonso, M. E.; Morales, A. J. Org. Chem. 1980, 45, 4530–4532. 247. Hudrlik, P. F.; Chou, D. T. W.; Stephenson, M. A. J. Org. Chem. 1982, 47, 2987–2993. 248. Mueller, L. G.; Lawton, R. G. J. Org. Chem. 1979, 44, 4741–4742. 249. Morizawa, Y.; Hiyama, T.; Oshima, K.; Nozaki, H. Bull. Chem. Soc. Jpn. 1984, 57, 1123–1127. 250. Sajimon, M. C.; Ramaiah, D.; Muneer, M.; et al. J. Org. Chem. 1999, 64, 6347–6352. 251. Funke, C.; Es-Sayed, M.; de Meijere, A. Org. Lett. 2000, 2, 4249–4251. 252. Nakajima, T.; Segi, M.; Mituoka, T.; et al. Tetrahedron Lett. 1995, 36, 1667–1670. 253. Honda, M.; Naitou, T.; Hoshino, H.; et al. Tetrahedron Lett. 2005, 46, 7345–7348. 254. Kim, C.; Brady, T.; Kim, S. H.; Theodorakis, E. A. Synth. Commun. 2004, 34, 1951–1965. 255. Yadav, V. K.; Balamurugan, R. Org. Lett. 2001, 3, 2717–2719. 256. Bowman, R. K.; Johnson, J. S. Org. Lett. 2006, 8, 573–576. 257. Davies, H. M. L.; Ahmed, G.; Calvo, R. L.; Churchill, M. R.; Churchill, D. G. J. Org. Chem. 1998, 63, 2641–2645. 258. Pohmakotr, M.; Takampon, A.; Ratchataphusit, J. Tetrahedron 1996, 52, 7149–7158. 259. Bernard, A. M.; Frongia, A.; Piras, P. P.; Secci, F.; Spiga, M. Org. Lett. 2005, 7, 4565–4568. 260. Lund, E. A.; Kennedy, I. A.; Fallis, A. G. Can. J. Chem. 1996, 74, 2401–2412. 261. Scriven, E. F. V. Azides and Nitrenes, Reactivity and Utility; Academic Press: New York, 1984. 262. Lown, W. In 1,3-Dipolar Cycloaddition Chemistry; Padwa, A., Ed.; Wiley: New York, 1984, Vol. 1; p 663. 263. Ohno, H. Vinylaziridines in Organic Synthesis. In Aziridines and Epoxides in Organic Synthesis; Yudin, A., Ed.; Wiley-VCH: Weinheim, 2006, pp 37–71. 264. Atkinson, R. S.; Rees, C. W. Chem. Commun. 1967, 1232a, -1232a. 265. Mishra, A.; Rice, S. N.; Lwowski, W. J. Org. Chem. 1968, 33, 481–486. 266. Borel, D.; Gelas-Mialhe, Y.; Vessière, R. Can. J. Chem. 1976, 54, 1590–1598. 267. Gembitskii, P. A.; Loim, N. N.; Zhuk, D. S. Usp. Khim. 1966, 229. 268. Heine, H. W. Angew. Chem. Int. Ed. 1962, 1, 528–532. 269. Logothetis, A. L. J. Am. Chem. Soc. 1965, 87, 749–754. 270. Attia, M. E. M.; Gelas-Mialhe, Y.; Vessiere, R. Can. J. Chem. 1983, 61, 2126–2132. 271. Hudlicky, T.; Frazier, J. O.; Kwart, L. D. Tetrahedron Lett. 1985, 26, 3523–3526. 272. Pearson, W. H. Tetrahedron Lett. 1985, 26, 3527–3530. 273. Scheiner, P. J. Org. Chem. 1967, 32, 2628–2630. 274. Calcagno, M. A.; Schweizer, E. E. J. Org. Chem. 1978, 43, 4207–4215. 275. Sauleau, J.; Sauleau, A.; Huet, J. Bull. Soc. Chim. Fr. 1978, Part 2, 97–103. 276. Manisse, N.; Chuche, J. Tetrahedron 1977, 33, 2399–2406. 277. Schultz, A. G.; Dittami, J. P.; Myong, S. O.; Sha, C. K. J. Am. Chem. Soc. 1983, 105, 3273–3279. 278. Schultz, A. G.; Myong, S. O. J. Org. Chem. 1983, 48, 2432–2434. 279. Fugami, K.; Morizawa, Y.; Ishima, K.; Nozaki, H. Tetrahedron Lett. 1985, 26, 857–860. 280. Miura, K.; Fugami, K.; Oshima, K.; Utimoto, K. Tetrahedron Lett. 1988, 29, 1543–1546. 281. Pommelet, J. C.; Chuche, J. Can. J. Chem. 1976, 54, 1571–1581. 282. Hudlicky, T.; Sinai-zingde, G.; Seoane, G. Synth. Commun. 1987, 17, 1155–1163. 283. Hudlicky, T.; Seoane, G.; Lovelace, T. C. J. Org. Chem. 1988, 53, 2094–2099. 284. Hudlicky, T.; Frazier, J. O.; Seoane, G.; et al. J. Am. Chem. Soc. 1986, 108, 3755–3762. 285. Pearson, W. H.; Celebuski, J. E.; Poon, Y.-F.; Dixon, B. R.; Glans, J. H. Tetrahedron Lett. 1986, 27, 6301–6304. 286. Pearson, W. H.; Bergmeier, S. C.; Degan, S.; et al. J. Org. Chem. 1990, 55, 5719–5738. 287. Hirner, S.; Somfai, P. Synlett 2005, 3099–3102. 288. Brichacek, M.; Lee, D.; Njardarson, J. T. Org. Lett. 2008, 10, 5023–5026. 289. Brichacek, M.; Navarro Villalobos, M.; Plichta, A.; Njardarson, J. T. Org. Lett. 2011, 13, 1110–1113. 290. (a) Ibuka, T.; Nakai, K.; Habashita, H.; et al. Angew. Chem. Int. Ed. 1994, 33, 652–654. (b) Fujii, N.; Nakai, K.; Tamamura, H.; et al. J. Chem. Soc. Perkin Trans. 1 1995, 1359–1371. 291. (a) Wipf, P.; Fritch, P. C. J. Org. Chem. 1994, 59, 4875–4886. (b) Wipf, P.; Henninger, T. C. J. Org. Chem. 1997, 62, 1586–1587. (c) Wipf, P.; Henninger, T. C.; Geib, S. J. J. Org. Chem. 1998, 63, 6088–6089. 292. Hudlicky, T.; Tian, X.; Konigsberger, K.; Rouden, J. J. Org. Chem. 1994, 59, 4037–4039. 293. Cantrill, A. A.; Jarvis, A. N.; Osborn, H. M. I.; Ouadi, A.; Sweeney, J. B. Synlett 1996, 847–849. 294. Gini, F.; Del Moro, F.; Macchia, F.; Pineschi, M. Tetrahedron Lett. 2003, 44, 8559–8562. 295. Cunha, R. L. O. R.; Diego, D. G.; Simonelli, F.; Comasseto, J. V. Tetrahedron Lett. 2005, 46, 2539–2542. 296. Butler, D. C. D.; Inman, G. A.; Alper, H. J. Org. Chem. 2000, 65, 5887–5890. 297. Aoyagi, K.; Nakamura, H.; Yamamoto, Y. J. Org. Chem. 2002, 67, 5977–5980. 298. Trost, B. M.; Fandrick, D. R. J. Am. Chem. Soc. 2003, 125, 11836–11837. 299. Trost, B. M.; Fandrick, D. R. Org. Lett. 2005, 7, 823–826. 300. Dong, C.; Alper, H. Tetrahedron Asymmetry 2004, 15, 1537–1540. 301. Spears, G. W.; Nakanishi, K.; Ohfune, Y. Synlett 1991, 91–92. 302. Tanner, D.; Somfai, P. Bioorg. Med. Chem. Lett. 1993, 3, 2415–2418. 303. Fontana, F.; Tron, G. C.; Barbero, N.; et al. Chem. Commun. 2010, 46, 267–269.

1074

304. 305. 306. 307. 308. 309. 310. 311. 312. 313. 314. 315. 316. 317. 318. 319. 320. 321. 322. 323. 324. 325. 326. 327. 328. 329. 330. 331. 332. 333. 334. 335. 336. 337. 338. 339. 340. 341. 342. 343. 344. 345. 346. 347. 348. 349. 350. 351. 352. 353. 354. 355. 356. 357. 358. 359. 360. 361. 362. 363. 364.

Rearrangements of Vinylcyclopropanes, Divinylcyclopropanes, and Related Systems

Ley, S. V.; Middleton, B. Chem. Commun. 1998, 1995–1996. Zhang, K.; Chopade, P. R.; Louie, J. Tetrahedron Lett. 2008, 49, 4306–4309. Kanno, E.; Yamanoi, K.; Koya, S.; et al. J. Org. Chem. 2012, 77, 2142–2148. Baktharaman, S.; Afagh, N.; Vandersteen, A.; Yudin, A. K. Org. Lett. 2010, 12, 240–243. Zuo, G.; Zhang, K.; Louie, J. Tetrahedron Lett. 2008, 49, 6797–6799. Cloke, J. B. J. Am. Chem. Soc. 1929, 51, 1174–1187. (a) Wasserman, H. H.; Dion, R. P. Tetrahedron Lett. 1982, 23, 1413–1416. (b) Wasserman, H. H.; Dion, R. P. Tetrahedron Lett. 1983, 24, 3409–3412. Stevens, R. V.; Sheu, J. T. J. Chem. Soc. Chem. Commun. 1975, 682, -682. Stevens, R. V. Acc. Chem. Res. 1977, 10, 193–198. Stevens, R. V. Alcaloid Synthesis. In The Total Synthesis of Natural Products; ApSimon, J., Ed.; Wiley: New York, 1977, Vol. 3; p 439. Boeckman, R. K.; Jackson, P. F.; Sabatucci, J. P. J. Am. Chem. Soc. 1985, 107, 2191–2192. Soldevilla, A.; Sampedro, D. Org. Prep. Proced. Int. 2007, 39, 561–590. Wu, P.-L.; Wang, W.-S. J. Org. Chem. 1994, 59, 622–627. (a) Kagabu, S.; Ando, C.; Ando, J. J. Chem. Soc. Perkin Trans. 1 1994, 739–751. (b) Kagabu, S.; Tsuji, H.; Kawai, I.; Ozeki, H. Bull. Chem. Soc. Jpn. 1995, 68, 341–349. Campos, P. J.; Soldevilla, A.; Sampedro, D.; Rodriguez, M. A. Tetrahedron Lett. 2002, 43, 8811–8813. Sampedro, D.; Soldevilla, A.; Rodríguez, M. A.; Campos, P. J.; Olivucci, M. J. Am. Chem. Soc. 2004, 127, 441–448. Soldevilla, A.; Sampedro, D.; Campos, P. J.; Rodríguez, M. A. J. Org. Chem. 2005, 70, 6976–6979. Bennett, R. B.; Cha, J. K. Tetrahedron Lett. 1990, 31, 5437–5440. Rawal, V. H.; Michoud, C.; Monestel, R. J. Am. Chem. Soc. 1993, 115, 3030–3031. (a) Kuduk, S. D.; Ng, C.; Chang, R. K.; Bock, M. G. Tetrahedron Lett. 2003, 44, 1437–1440. (b) Chang, R. K.; DiPardo, R. M.; Kuduk, S. D. Tetrahedron Lett. 2005, 46, 8513–8516. Wender, P. A.; Pedersen, T. M.; Scanio, M. J. C. J. Am. Chem. Soc. 2002, 124, 15154–15155. Huisgen, R. 1,3-dipolar cycloaddition−introduction, survey, mechanism. In 1,3-Dipolar Cycloaddition Chemistry; Padwa, A., Ed.; Wiley: New York, 1984, Vol. 1, Chapter 1; p 53. Potts, K. T. Synthesis of Five-membered Rings with Two or More Heteroatoms. In Comprehensive Heterocyclic Chemistry; Katritzky, A. R., Rees, C. W., Eds.; Pergamon: Oxford, 1984, Vol. 5; pp 111–166. Bird, C. W.; Cheeseman, G. W. H. Synthesis of Five-membered Rings with One Heteroatom. In Comprehensive Heterocyclic Chemistry; Katritzky, A. R., Rees, C. W., Eds.; Pergamon: Oxford, 1984, Vol. 4; pp 89–153. Katritzky, A. R., Rees, C. W., Eds. Comprehensive Heterocyclic Chemistry; Pergamon: Oxford, 1984, Vol. 5; p 6. Baird, M. S. Functionalised Cyclopropenes as Synthetic Intermediates. In Top. Curr. Chem.; de Meijere, A., Ed.; Springer: Berlin/Heidelberg, 1988, Vol. 144; pp 137–209. Battiste, M. A.; Halton, B.; Kulig, M.; et al. J. Am. Chem. Soc. 1971, 93, 2327–2329. Padwa, A.; Woolhouse, A. D. Aziridines, Azirines and Fused-ring Derivatives. In Comprehensive Heterocyclic Chemistry; Katritzky, A. R., Rees, C. W., Eds.; Pergamon: Oxford, 1984, Vol. 7; pp 47–93. Bosshard, P.; Eugster, C. H. The Development of the Chemistry of Furans, 1952−1963. In Adv. Heterocycl. Chem.; Katritzky, A. R., Boulton, A. J., Eds.; Academic Press: New York, 1967, Vol. 7; pp 377−490. Campaigne, E. Thiophenes and their Benzo Derivatives: (iii) Synthesis and Applications. In Comprehensive Heterocyclic Chemistry; Katritzky, A. R., Rees, C. W., Eds.; Pergamon: Oxford, 1984, Vol. 4; pp 863–934. Rogers, E.; Araki, H.; Batory, L. A.; McInnis, C. E.; Njardarson, J. T. J. Am. Chem. Soc. 2007, 129, 2768–2769. Salaun, J.; Karkour, B.; Ollivier, J. Tetrahedron 1989, 45, 3151–3162. Youn, J.-H.; Lee, J.; Cha, J. K. Org. Lett. 2001, 3, 2935–2938. (a) Oh, H.-S.; Lee, H. I.; Cha, J. K. Org. Lett. 2002, 4, 3707–3709. (b) Oh, H.-S.; Cha, J. K. Tetrahedron Asymmetry 2003, 14, 2911–2917. (c) Lysenko, I. L.; Oh, H. S.; Cha, J. K. J. Org. Chem. 2007, 72, 7903–7908. Trost, B. M.; Yasukata, T. J. Am. Chem. Soc. 2001, 123, 7162–7163. Markham, J. P.; Staben, S. T.; Toste, F. D. J. Am. Chem. Soc. 2005, 127, 9708–9709. Trost, B. M.; Xie, J.; Maulide, N. J. Am. Chem. Soc. 2008, 130, 17258–17259. Kleinbeck, F.; Toste, F. D. J. Am. Chem. Soc. 2009, 131, 9178–9179. Jiménez-Núñez, E.; Claverie, C. K.; Nieto-Oberhuber, C.; Echavarren, A. M. Angew. Chem. Int. Ed. 2006, 45, 5452–5455. Feldman, K. S.; Romanelli, A. L.; Ruckle, R. E.; Jean, G. J. Org. Chem. 1992, 57, 100–110. (a) Feldman, K. S.; Simpson, R. E. J. Am. Chem. Soc. 1989, 111, 4878–4886. (b) Feldman, K. S.; Kraebel, C. M. J. Org. Chem. 1992, 57, 4574–4576. Bertrand, M. P.; Nouguier, R.; Archavlis, A.; Carrière, A. Synlett 1994, 09, 736–738. de Meijere, A.; Bagutski, V.; Zeuner, F.; et al. Eur. J. Org. Chem. 2004, 3669–3678. Feast, W. J.; Gimeno, M.; Kenwright, A. M. Macromolecules 2006, 39, 4076–4080. Handa, S.; Pattenden, G. Chem. Commun. 1998, 311–312. Pattenden, G.; Krishnakanth Reddy, L.; Walter, A. Tetrahedron Lett. 2004, 45, 4027–4030. Pattenden, G.; Stoker, D. A.; Winne, J. M. Tetrahedron 2009, 65, 5767–5775. (a) Åhman, J.; Somfai, P. J. Am. Chem. Soc. 1994, 116, 9781–9782. (b) Åhman, J.; Somfai, P. Tetrahedron Lett. 1996, 37, 2495–2498. (a) Coldham, I.; Collis, A. J.; Mould, R. J.; Rathmell, R. E. Tetrahedron Lett. 1995, 36, 3557–3560. (b) Coldham, I.; Collis, A. J.; Mould, R. J.; Rathmell, R. E. J. Chem. Soc. Perkin Trans. 1 1995, 2739–2745. Quinn, K. J.; Biddick, N. A.; DeChristopher, B. A. Tetrahedron Lett. 2006, 47, 7281–7283. Mack, D. J.; Batory, L. A.; Njardarson, J. T. Org. Lett. 2011, 14, 378–381. (a) Zhang, S.; Conlin, R. T. J. Am. Chem. Soc. 1991, 113, 4272–4278. (b) Moiseev, A. G.; Leigh, W. J. Organometallics 2007, 26, 6277–6289. Takeda, N.; Tokitoh, N.; Okazaki, R. Chem. Lett. 2000, 29, 622–623. Nag, M.; Gaspar, P. P. Organometallics 2009, 28, 5612–5622. (a) Lammertsma, K.; Hung, J. T.; Chand, P.; Gray, G. M. J. Org. Chem. 1992, 57, 6557–6560. (b) Hung, J. T.; Lammertsma, K. J. Org. Chem. 1993, 58, 1800–1803. van Eis, M. J.; Nijbacker, T.; deKanter, F. J. J.; et al. J. Am. Chem. Soc. 2000, 122, 3033–3036. Trost, B. M.; Kurozumi, S. Tetrahedron Lett. 1974, 15, 1929–1932. Trost, B. M.; Nishimura, Y.; Yamamoto, K. J. Am. Chem. Soc. 1979, 101, 1328–1330. Piers, E.; Banville, J. J. Chem. Soc. Chem. Commun. 1979, 1138–1140. (a) Hudlicky, T.; Kutchan, T. M.; Wilson, S. R.; Mao, D. T. J. Am. Chem. Soc. 1980, 102, 6351–6353. (b) Hudlicky, T.; Koszyk, F. F.; Kutchan, T. M.; Sheth, J. P. J. Org. Chem. 1980, 45, 5020–5027. Salaün, J.; Ollivier, J. Nouv. J. Chim. 1981, 5, 587.

Rearrangements of Vinylcyclopropanes, Divinylcyclopropanes, and Related Systems

1075

365. (a) Tu-Hsin, Y.; Paquette, L. A. Tetrahedron Lett. 1982, 23, 3227–3230. (b) Wells, G. J.; Yan, T. H.; Paquette, L. A. J. Org. Chem. 1984, 49, 3604–3609. (c) Paquette, L. A.; Yan, T. H.; Wells, G. J. J. Org. Chem.. 1984, 49, 3610–3617. 366. Piers, E.; Lau, C. K.; Nagakura, I. Can. J. Chem. 1983, 61, 288–297. 367. Short, R. P.; Revol, J. M.; Ranu, B. C.; Hudlicky, T. J. Org. Chem. 1983, 48, 4453–4461. 368. Ranu, B. C.; Kavka, M.; Higgs, L. A.; Hudlicky, T. Tetrahedron Lett. 1984, 25, 2447–2450. 369. Salaün, J.; Almirantis, Y. Tetrahedron 1983, 39, 2421–2428. 370. Wender, P. A.; Howbert, J. J. Tetrahedron Lett. 1983, 24, 5325–5328. 371. Barnier, J. P.; Salaün, J. Tetrahedron Lett. 1984, 25, 1273–1276. 372. Wender, P. A.; Ternansky, R. J. Tetrahedron Lett. 1985, 26, 2625–2628. 373. Ollivier, J.; Salaun, J. J. Chem. Soc. Chem. Commun. 1985, 1269–1270. 374. Corey, E. J.; Myers, A. G. J. Am. Chem. Soc. 1985, 107, 5574–5576. 375. (a) Kwart, L. D.; Tiedje, M.; Frazier, J. O.; Hudlicky, T. Synth. Commun. 1986, 16, 393–399. (b) Hudlicky, T.; Kwart, L. D.; Tiedje, M. H.; et al. Synthesis 1986, 716–727. 376. Hudlicky, T.; Natchus, M. G.; Sinai-Zingde, G. J. Org. Chem. 1987, 52, 4641–4644. 377. Hudlicky, T.; Sinai-Zingde, G.; Natchus, M. G.; Ranu, B. C.; Papadopolous, P. Tetrahedron 1987, 43, 5685–5721. 378. (a) Hudlicky, T.; Radesca-Kwart, L.; Li, L.-Q.; Bryant, T. Tetrahedron Lett. 1988, 29, 3283–3286. (b) Hudlicky, T.; Fleming, A.; Radesca, L. J. Am. Chem. Soc. 1989, 111, 6691–6707. 379. Murray, C. K.; Yang, D. C.; Wulff, W. D. J. Am. Chem. Soc. 1990, 112, 5660–5662. 380. Sonawane, H. R.; Nanjundiah, B. S.; Shah, V. G.; Kulkarni, D. G.; Ahuja, J. R. Tetrahedron Lett. 1991, 32, 1107–1108. 381. Hudlicky, T.; Natchus, M. J. Org. Chem. 1992, 57, 4740–4746. 382. Sethofer, S. G.; Staben, S. T.; Hung, O. Y.; Toste, F. D. Org. Lett. 2008, 10, 4315–4318. 383. Kim, K.; Cha, J. K. Angew. Chem. Int. Ed. 2009, 48, 5334–5336. 384. (a) Stevens, R. V.; Ellis, M. C. Tetrahedron Lett. 1967, 8, 5185–5188. (b) Stevens, R. V.; Ellis, M. C.; Wentland, M. P. J. Am. Chem. Soc. 1968, 90, 5576–5579. 385. (a) Stevens, R. V.; Wentland, M. P. Tetrahedron Lett. 1968, 9, 2613–2615. (b) Stevens, R. V.; Wentland, M. P. J. Am. Chem. Soc. 1968, 90, 5580–5583. (c) Stevens, R. V.; Lesko, P. M.; Lapalme, R. J. Org. Chem. 1975, 40, 3495–3498. 386. Keely, S. L.; Tahk, F. C. J. Am. Chem. Soc. 1968, 90, 5584–5587. 387. (a) Breuer, E.; Melumad, D. Tetrahedron Lett. 1969, 10, 3595–3596. (b) Breuer, E.; Zbaida, S. Tetrahedron 1975, 31, 499–504. 388. Stevens, R. V.; Fitzpatrick, J. M.; Kaplan, M.; Zimmerman, R. L. J. Chem. Soc. Chem. Commun. 1971, 857–858. 389. Stevens, R. V.; Lai, J. T. J. Org. Chem. 1972, 37, 2138–2140. 390. Stevens, R. V.; DuPree, L. E.; Loewenstein, P. L. J. Org. Chem. 1972, 37, 977–982. 391. Comes, R. A.; Core, M. T.; Edmonds, M. D.; Edwards, W. B.; Jenkins, R. W. J. Labelled Comp. Radiopharm. 1973, 9, 253–259. 392. Stevens, R. V.; Luh, Y.; Sheu, J.-T. Tetrahedron Lett. 1976, 17, 3799–3802. 393. Stevens, R. V.; Luh, Y. Tetrahedron Lett. 1977, 18, 979–982. 394. Naruta, Y.; Nagai, N.; Arita, Y.; Maruyama, K. J. Org. Chem. 1987, 52, 3956–3967. 395. Hudlicky, T.; Seoane, G.; Price, J. D.; Gadamasetti, K. G. Synlett 1990, 433–440. 396. Hudlicky, T.; Luna, H.; Price, J. D.; Rulin, F. J. Org. Chem. 1990, 55, 4683–4687. 397. (a) Wenkert, E.; Hudlicky, T.; Showalter, H. D. H. J. Am. Chem. Soc. 1978, 100, 4893–4894. (b) Wenkert, E.; Hudlicky, T. J. Org. Chem. 1988, 53, 1953–1957. 398. Rawal, V. H.; Iwasa, S. J. Org. Chem. 1994, 59, 2685–2686. 399. Aldous, D. J.; Dalençon, A. J.; Steel, P. G. Org. Lett. 2002, 4, 1159–1162. 400. Simmons, E. M.; Sarpong, R. Org. Lett. 2006, 8, 2883–2886. 401. Majetich, G.; Zou, G.; Grove, J. Org. Lett. 2007, 10, 85–87. 402. McGrath, N. A.; Bartlett, E. S.; Sittihan, S.; Njardarson, J. T. Angew. Chem. Int. Ed. 2009, 48, 8543–8546. 403. Brichacek, M.; Batory, L. A.; Njardarson, J. T. Angew. Chem. Int. Ed. 2010, 49, 1648–1651. 404. Brichacek, M.; Batory, L. A.; McGrath, N. A.; Njardarson, J. T. Tetrahedron 2010, 66, 4832–4840. 405. Åhman, J.; Somfai, P. Tetrahedron Lett. 1995, 36, 303–306. 406. Wender, P. A.; Fuji, M.; Husfeld, C. O.; Love, J. A. Org. Lett. 1999, 1, 137–140. 407. Wender, P. A.; Zhang, L. Org. Lett. 2000, 2, 2323–2326. 408. Wender, P. A.; Bi, F. C.; Brodney, M. A.; Gosselin, F. Org. Lett. 2001, 3, 2105–2108. 409. Ashfeld, B. L.; Martin, S. F. Tetrahedron 2006, 62, 10497–10506. 410. Trost, B. M.; Waser, J.; Meyer, A. J. Am. Chem. Soc. 2007, 129, 14556–14557. 411. Trost, B. M.; Hu, Y.; Horne, D. B. J. Am. Chem. Soc. 2007, 129, 11781–11790. 412. Taber, D. F.; Sheth, R. B.; Tian, W. J. Org. Chem. 2009, 74, 2433–2437. 413. Goldberg, A. F. G.; Stoltz, B. M. Org. Lett. 2011, 13, 4474–4476. 414. Carson, C. A.; Kerr, M. A. Angew. Chem. Int. Ed. 2006, 45, 6560–6563. 415. Karadeolian, A.; Kerr, M. A. J. Org. Chem. 2010, 75, 6830–6841. 416. (b) Vogel, E.; Ott, K.-H.; Gajek, K. Liebigs Ann. Chem. 1961, 644, 172–188. (c) Vogel, E. Angew. Chem. Int. Ed. 1963, 2, 1–11. (d) von E. Doering, W.; Roth, W. R. Tetrahedron 1963, 19, 715–737. 417. (a) Brown, J. M.; Golding, B. T.; Stofko, J. J. J. Chem. Soc. Chem. Commun. 1973, 319b–320. (b) Brown, J. M.; Golding, B. T.; Stofko, J. J. J. Chem. Soc. Perkin Trans. 2 1978, 436–441. 418. (a) Schneider, M. P.; Rebell, J. J. Chem. Soc. Chem. Commun. 1975, 283a. (b) Schneider, M. Angew. Chem. Int. Ed. 1975, 14, 707–708. 419. Hudlicky, T.; Fan, R. L.; Becker, D. A.; Kozhushkov, S. Formation of Seven-membered Rings: Divinylcyclopropane−cycloheptadiene Rearrangement. In Carbocyclic Threemembered Ring Compounds; Houben−Weyl: Stuttgart, 1996, Vol. E 17c; pp 2589−2622. 420. Rhoads, S. J.; Raulins, N. R. The Claisen and Cope Rearrangement. In Organic Reactions; Dauben, W. G., Ed.; Wiley: New York, 1975, Vol. 22, Chapter 1; pp 1–254. 421. Gajewski, J. J. C7H6−C7H12. Hydrocarbon Thermal Isomerizations, 2nd ed.; Academic Press: San Diego, 2004; pp 171−209. 422. Pickenhagen, W.; Näf, F.; Ohloff, G.; Müller, P.; Perlberger, J.-C. Helv. Chim. Acta 1973, 56, 1868–1874. 423. Schneider, M. P.; Rau, A. J. Am. Chem. Soc. 1979, 101, 4426–4427. 424. (a) Sperling, D.; Reissig, H.-U.; Fabian, J. Liebigs Ann. 1997, 2443–2449. (b) Sperling, D.; Reißig, H.-U.; Fabian, J. Eur. J. Org. Chem. 1999, 1107–1114. 425. (a) Ö zkan, I.;̇ Zora, M. J. Org. Chem. 2003, 68, 9635–9642. (b) Zora, M.; Ö zkan, l.;̈ Danıs- man, M. F. J. Mol. Struct.: THEOCHEM 2003, 636, 9–13. (c) Zora, M. J. Mol. Struct.: THEOCHEM 2004, 681, 113–116. 426. Zora, M. J. Org. Chem. 2005, 70 (15), 6018–6026. 427. Baldwin, J. E.; Ullenius, C. J. Am. Chem. Soc. 1974, 96, 1542–1547. 428. Ohloff, G.; Pickenhagen, W. Helv. Chim. Acta 1969, 52, 880–886. 429. Schneider, M.; Rau, A. Angew. Chem. Int. Ed. 1979, 18, 231–233.

1076

430. 431. 432. 433. 434. 435. 436. 437. 438. 439. 440. 441. 442. 443. 444. 445. 446. 447. 448. 449. 450. 451. 452.

453. 454. 455. 456. 457. 458. 459. 460. 461. 462. 463. 464. 465. 466. 467. 468. 469. 470. 471. 472. 473. 474. 475. 476. 477. 478. 479. 480. 481. 482. 483. 484. 485. 486. 487.

Rearrangements of Vinylcyclopropanes, Divinylcyclopropanes, and Related Systems

Schneider, M. P.; Goldbach, M. J. Am. Chem. Soc. 1980, 102, 6114–6116. Sasaki, T.; Eguchi, S.; Ohno, M. J. Org. Chem. 1972, 37, 466–469. Marino, J. P.; Kaneko, T. Tetrahedron Lett. 1973, 14, 3975–3978. Bradbury, R. H.; Gilchrist, T. L.; Rees, C. W. J. Chem. Soc. Perkin Trans. 1 1981, 3225–3233. Imogaï, H.; Bernardinelli, G.; Gränicher, C.; et al. Helv. Chim. Acta 1998, 81, 1754–1764. Nakamura, E.; Isaka, M.; Matsuzawa, S. J. Am. Chem. Soc. 1988, 110, 1297–1298. Piers, E.; Jean, M.; Marrs, P. S. Tetrahedron Lett. 1987, 28, 5075–5078. Thomas, E.; Kasatkin, A. N.; Whitby, R. J. Tetrahedron Lett. 2006, 47, 9181–9185. Marino, J. P.; Browne, L. J. Tetrahedron Lett. 1976, 17, 3245–3248. (a) Wender, P. A.; Filosa, M. P. J. Org. Chem. 1976, 41, 3490–3491. (b) Wender, P. A.; Hillemann, C. L.; Szymonifka, M. J. Tetrahedron Lett. 1980, 21, 2205–2208. (a) Harvey, D. F.; Lund, K. P. J. Am. Chem. Soc. 1991, 113, 5066–5068. (b) Harvey, D. F.; Grenzer, E. M.; Gantzel, P. K. J. Am. Chem. Soc. 1994, 116, 6719–6732. (a) Kusama, H.; Onizawa, Y.; Iwasawa, N. J. Am. Chem. Soc. 2006, 128, 16500–16501. (b) Onizawa, Y.; Hara, M.; Hashimoto, T.; Kusama, H.; Iwasawa, N. Chem. Eur. J. 2010, 16, 10785–10796. (a) Barluenga, J.; Aznar, F.; Martin, A.; et al. J. Chem. Soc. Chem. Commun. 1993, 319–321. (b) Barluenga, J.; Aznar, F.; Valdes, C.; et al. J. Am. Chem. Soc. 1993, 115, 4403–4404. (c) Barluenga, J.; Aznar, F.; Martin, A.; Vazquez, J. T. J. Am. Chem. Soc. 1995, 117, 9419–9426. (a) Barluenga, J.; Tomas, M.; Ballestros, A.; Santamaria, J.; Lopez-Ortiz, F. J. Chem. Soc. Chem. Commun. 1994, 321–322. (b) Barluenga, J.; Tomás, M.; Ballesteros, A.; et al. Chem. Eur. J. 1996, 2, 88–97. (c) Barluenga, J.; Tomás, M.; Ballesteros, A.; Santamaría, J.; Suárez-Sobrino, A. J. Org. Chem. 1997, 62, 9229–9235. Davies, H. M. L. Tetrahedron 1993, 49, 5203–5223. Ye, T.; McKervey, M. A. Chem. Rev. 1994, 94, 1091–1160. Davies, H. M. L. [3+4] Annulations Between Rhodium-Stabilized Vinylcarbenoids and Dienes. In Advances in Cycloaddition; Harmata, M., Ed.; JAI Press: Stamford, 1999, Vol. 5; pp 119–164. Davies, H. M. L.; Denton, J. R. Chem. Soc. Rev. 2009, 38, 3061–3071. Davies, H. M. L.; Saikali, E.; Clark, J. T.; Chee, E. H. Tetrahedron Lett. 1990, 31, 6299–6302. Davies, H. M. L.; Ahmed, G.; Churchill, M. R. J. Am. Chem. Soc. 1996, 118, 10774–10782. Davies, H. M. L.; Saikali, E.; Young, W. B. J. Org. Chem. 1991, 56, 5696–5700. Reisman, S. E.; Nani, R. R.; Levin, S. Synlett 2011, 2437–2442. (a) Wallock, N. J.; Donaldson, W. A. Org. Lett. 2005, 7, 2047–2049. (b) Wallock, N. J.; Bennett, D. W.; Siddiquee, T.; Haworth, D. T.; Donaldson, W. A. Synthesis 2006, 21, 3639–3646. (c) Pandey, R. K.; Wang, L.; Wallock, N. J.; Lindeman, S.; Donaldson, W. A. J. Org. Chem. 2008, 73, 7236–7245. (d) Gone, J. R.; Wallock, N. J.; Lindeman, S.; Donaldson, W. A. Tetrahedron Lett. 2009, 50, 1023–1025. (e) Lee, D. W.; Pandey, R. K.; Lindeman, S.; Donaldson, W. A. Org. Biomol. Chem. 2011, 9, 7742–7747. Aitken, R. A.; Cadogan, I. G. J.; Gosney, I. M. H. C.; McLaughlin, M. L.; Wyse, S. J. J. Chem. Soc. Perkin Trans. 1 1999, 605–614. (a) Takeda, K.; Takeda, M.; Nakajima, A.; Yoshii, E. J. Am. Chem. Soc. 1995, 117, 6400–6401. (b) Takeda, K.; Nakajima, A.; Yoshii, E. Synlett 1996, 8, 753–754. (c) Takeda, K.; Nakajima, A.; Takeda, M.; et al. J. Am. Chem. Soc. 1998, 120, 4947–4959. (a) Takeda, K.; Ohtani, Y. Org. Lett. 1999, 1, 677–680. (b) Takeda, K.; Sawada, Y.; Sumi, K. Org. Lett. 2002, 4, 1031–1033. (c) Sawada, Y.; Sasaki, M.; Takeda, K. Org. Lett. 2004, 6, 2277–2279. (d) Nakai, Y.; Kawahata, M.; Yamaguchi, K.; Takeda, K. J. Org. Chem. 2007, 72, 1379–1387. Takada, Y.; Nomura, K.; Matsubara, S. Org. Lett. 2010, 12, 5204–5205. Tucker, J. W.; Stephenson, C. R. J. Org. Lett. 2011, 13, 5468–5471. Schotten, T.; Boland, W.; Jaenicke, L. Tetrahedron Lett. 1986, 27, 2349–2352. Colobert, F.; Genet, J.-P. Tetrahedron Lett. 1985, 26, 2779–2782. (a) Moore, R. E.; Pettus, J. A. J. Am. Chem. Soc. 1971, 93, 3087–3088. (b) Moore, R. E.; Pettus, J. A.; Mistysyn, J. J. Org. Chem. 1974, 39, 2201–2207. Moore, R. E. Acc. Chem. Res. 1977, 10, 40–47. Davies, H. M. L.; Huby, N. J. S. Tetrahedron Lett. 1992, 33, 6935–6938. (a) O'Keeffe, S.; Harrington, F.; Maguire, A. R. Synlett 2007, 2367–2370. (b) O'Neill, S.; O'Keeffe, S.; Harrington, F.; Maguire, A. R. Synlett 2009, 2312–2314. Cairns, P. M.; Crombie, L.; Pattenden, G. Tetrahedron Lett. 1982, 23, 1405–1408. Marino, J. P.; Ferro, M. P. J. Org. Chem. 1981, 46, 1912–1914. Piers, E.; Burmeister, M. S.; Reissig, H.-U. Can. J. Chem. 1986, 64, 180–187. Piers, E.; Morton, H. E.; Nagakura, I.; Thies, R. W. Can. J. Chem. 1983, 61, 1226–1238. Piers, E.; Grierson, J. R.; Lau, C. K.; Nagakura, I. Can. J. Chem. 1982, 60, 210–223. Lindström, U. M.; Somfai, P. J. Am. Chem. Soc. 1997, 119, 8385–8386. Lindstrom, U. M.; Somfai, P. Chem. Eur. J. 2001, 7, 94–98. (a) Müller, P.; Imogai, H. Helv. Chim. Acta 1999, 82, 315–322. (b) Müller, P.; Toujas, J.-L.; Bernardinelli, G. Helv. Chim. Acta 2000, 83, 1525–1534. Fantauzzi, S.; Gallo, E.; Caselli, A.; et al. Chem. Eur. J. 2009, 15, 1241–1251. Piers, E.; Ruediger, E. H. Can. J. Chem. 1983, 61, 1239–1247. Wender, P. A.; Eissenstat, M. A.; Filosa, M. P. J. Am. Chem. Soc. 1979, 101, 2196–2198. Kennedy, M.; McKervey, M. A. J. Chem. Soc. Perkin Trans. 1 1991, 2565–2574. Frey, B.; Wells, A. P.; Rogers, D. H.; Mander, L. N. J. Am. Chem. Soc. 1998, 120, 1914–1915. Schwartz, B. D.; Denton, J. R.; Lian, Y.; Davies, H. M. L.; Williams, C. M. J. Am. Chem. Soc. 2009, 131, 8329–8332. Olson, J. P.; Davies, H. M. L. Org. Lett. 2008, 10, 573–576. Eckelbarger, J. D.; Wilmot, J. T.; Gin, D. Y. J. Am. Chem. Soc. 2006, 128, 10370–10371. McDowell, P. A.; Foley, D. A.; O'Leary, P.; Ford, A.; Maguire, A. R. J. Org. Chem. 2012, 77, 2035–2040. Fukuyama, T.; Liu, G. J. Am. Chem. Soc. 1996, 118, 7426–7427. Davies, H. M. L.; Doan, B. D. Tetrahedron Lett. 1996, 37, 3967–3970. Lian, Y.; Miller, L. C.; Born, S.; Sarpong, R.; Davies, H. M. L. J. Am. Chem. Soc. 2010, 132, 12422–12425. Shimokawa, J.; Harada, T.; Yokoshima, S.; Fukuyama, T. J. Am. Chem. Soc. 2011, 133, 17634–17637. Hudlicky, T.; Reed, J. W. Angew. Chem. Int. Ed. 2010, 49 (29), 4864–4876. Hudlicky, T.; Reed, J. W. Rearrangements of Vinylcyclopropanes and Related Systems. In Comprehensive Organic Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon: Oxford, 1991, Chapter 8.1; pp 899–970. Piers, E. Rearrangements of Divinylcyclopropanes. In Comprehensive Organic Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon: Oxford, 1991, Chapter 8.2; pp 971–998.