Three-membered ring systems (2005)

81

Chapter 3.2

Three-membered ring systems (2005) Stephen C. Bergmeier and Damon D. Reed Department of Chemistry & Biochemistry, Ohio University, Athens, OH, USA [email protected] and [email protected]

3.2.1 INTRODUCTION Three-membered heterocyclic ring systems continue to receive attention from organic chemists. These heterocyclic ring systems provide a useful combination of reactivity, utility and stability. This review is not a comprehensive review but rather covers a selection of interesting and synthetically useful transformations. Some themes that have emerged in the past year include the use of supported reagents, aqueous reactions and solvent free reactions. The organization of this chapter follows that of previous years. Several reviews on specific topics in aziridine or epoxide chemistry have been published in the past year. Two recent reviews have focused on advances in the metal catalyzed asymmetric epoxidation. One review focuses on Cr and Mn(salen) complexes <05CRV1563>. The other review focuses on the broader topic of homogenous and heterogeneous asymmetric epoxidation reactions <05CRV1603>. The coverage of these reviews is roughly to the end of 2004. A review on the use of chiral auxiliaries in epoxidation reactions has been published <05SL1047>. The review focuses on the epoxidation of several select substrates. The use of enzymatic transformations including the opening of epoxides has been reviewed <05MI181>. A recent review has covered asymmetric ring opening reactions of epoxides <05MI1>. The synthesis and reactions of lithiated epoxides has been the subject of a recent review <05SL1359>. A review on the synthesis of α,β-diamino acids that covers some syntheses from aziridines has been published <05CRV3167>. 3.2.2 EPOXIDES 3.2.2.1 Preparation of Epoxides The development of methods for metal-catalyzed epoxidations continues at a rapid pace. Mechanistic studies of the Jacobsen-Katsuki epoxidation have rationalized the enantioselectivity as arising from a competition of approach vectors <05JA13672>. The development of Mn-catalyzed epoxidation methods have provided useful methods for the stereocontrolled epoxidation of olefins. Evidence for a peroxy-Mn complex as a key intermediate in high valent manganese catalyzed epoxidations has been proposed <05JA17170>. From a synthetic perspective, a Mn-porphyrin catalyst has been developed for erythroselective epoxidations <05JOC4226>. This epoxidation catalyzed by Mn-porphyrin is highly

82

S.C. Bergmeier and D.D. Reed

substrate dependent. As shown below, reaction of 1 with Mn(2,6-Cl2TPP)Cl and oxone provides a reasonable yield of erythro-2 when R = COOMe. However, when R = OTBS or OAc the yields drop precipitously. R Mn(2,6-Cl2TPP)Cl, oxone, NH4OAc Ph

O

CH3

1

Ph

R

O CH3

R

Ph

erythro-2 6 R = CO2Me, 70% yield R = OTBS, <5% yield 1 R = OAc, 35% yield

CH3 threo-2 1 1

The use of Ru catalysts for selective epoxidations has also been explored. The Ru(2,6Cl2TPP)CO catalyst with dichloropyridine N-oxide as the stoichiometric oxidant provides good levels of stereocontrol for the synthesis of threo-amino epoxides, 4 <05MI29>. The use of the manganese system, Mn(2,6-Cl2TPP)Cl, on amine 3 provides a 1.4:1 mixture of the 4erythro: 4-threo isomers in 88% yield after 1 hour <05JOC4226>. BocHN Ph

O

BocHN

Cl2PyNO, Ru(2,6-Cl2TPP)CO

Ph

3

32% yield >99% threo 4

The epoxidation of olefins has been reported using an interesting tri-pyridyl catalyst 7 <05OL987>. Yields of the corresponding epoxides are generally quite high. An advantage of this epoxidation system is the use of hydrogen peroxide as oxidant. Chiral Ru analogs of 7 were used to carry out asymmetric epoxidations in which the ee reached only 54%.

N O 5

30% H2O2 t-AMOH 7, 0.005 eq.

N

O

O

O

N

N

N Ru

O

O

O 6 81% yield

O

O 7

Methyltrioxorhenium (MTO) has proven to be a useful oxidant for a number of reactions. A problem with the use of MTO in epoxidation is the acidity of the reagent, which leads to diol formation. Several different methods have previously been reported in an attempt to solve this problem. The use of microencapsulated Lewis base adducts of MTO appears to be a good solution <05T1069>. Another modification of MTO is (PPh3)2[Re(NCS)6] with H2O2 as an oxidant <05TL339>. Janda and co-workers have found that the enantioselectivity of the Sharpless epoxidation reaction can be reversed when utilizing a tartrate ester of polyethylene glycol <05JOC1728>. The work described here is based on earlier reports <02CC118, 04JOC2042> in which conflicting results were obtained with PEG-tartrate esters. In the current study, the molecular weight of the polyethylene glycol used has a significant effect on which epoxide enantiomer is produced. Using the usual Sharpless epoxidation conditions on alcohol 8, the (2S,3S)

83

Three-membered ring systems (2005)

enantiomer, 9, was obtained in 96% ee. A number of polyethylene glycol esters of tartaric acid were then prepared and used in the epoxidation reaction. Polyethylene glycol up to a MW of 350 all gave the expected epoxide, 9. A polyethylene glycol of MW 550 gave an epoxide with an ee of only 5%, while the next higher MW polyethylene glycol, MW 750, gave epoxide 10 with an ee of 67%. Increasing the size of the polyethylene glycol to MW 2000 gave 10 in 75% ee. The rationale for this change in the preferred enantiomer is not clear but the authors have hypothesized that it may be due to a change in aggregation of the ligand to the metal. O

O

L-DIPT, 96% ee OH

OH 9

PEG-DIPT, MW 350 75% ee

OH

8

10 PEG-DIPT, MW 2000 75% ee

A method for the polymer supported epoxidation of olefins has been reported <05TL1643>. The resin supported phthalate, 11, was oxidized to peracid 12 through oxidation with H2O2 or a urea-H2O2 complex. The reaction was most conveniently carried out by mixing 11, the urea-H2O2 complex and the olefinic substrate. Simple filtration then provides a wide variety of epoxides in excellent yield. This reagent system provides all of the typical advantages of supported reagents as well as an improved safety profile of the supported peracid. O O

nO

11

R2

R1 13

O

O

30% H2O2 or O urea-H2O2 complex O

O 1) 11, urea-H2O2 complex 2) filtration R1 14

O n

O

CO2H O

12

OH

O

R2

R1 n-C6H13 Ph Ph CH2OH

Yields(%) R2 95 H 75 H 80 CH2OH 90 H

Walsh and co-workers have developed a one-pot method for the synthesis of hydroxyepoxides via an initial synthesis of an allylic alcohol followed by an asymmetric epoxidation <05JOC1262, 05JA14668, 05JA16416>. This reaction provides an improvement in overall yields over the typical kinetic resolution reaction. The method involves an initial asymmetric addition to the aldehyde followed by a diastereoselective epoxidation reaction. O O H 15

O

OH

ZnEt2, Ti(OiPr)4, O2, 17 16

90% yield 99% ee 20:1 dr (erythro:threo)

N OH 17

Several methods for the epoxidation of α,β-unsaturated carbonyl compounds have been reported. The use of amino acid derivatives or peptides as chiral ligands for epoxidation continues to be an active area of investigation. The use of silica bound poly-L-leucine, 21, with sodium percarbonate appears to be an excellent route to enantiomerically pure keto

84

S.C. Bergmeier and D.D. Reed

epoxides, 19 <05TL5665>. Interestingly, the diphenylprolinol/t-BuOOH system 22, provides enantioenriched ketoepoxides of opposite configuration, 20, albeit with lower enantiomeric excess <05OL2579>. The use of the related 3,5-(CF3)2Ph prolinol catalyst 23 with H2O2 as oxidant provides epoxy aldehyde 19 (R1 = Ph, R2 = H) in excellent yield and enantiomeric excess <05JA6964>. Significantly this is one of the few routes to epoxy aldehydes. O

O Catalyst

R1

R2 19 (2S,3R)

O R1

or

R2 18

O

Yields R1 = R2 = Ph, 94% yield, 93% ee (2S,3R) R1 = R2 = Ph, 72% yield, 75% ee (2R,3S) R1 = Ph, R2 = H, 80% yield, 96% ee (2S,3R) R1 = R2 = Ph, 95% yield, 99% ee (2S,3R) R1 = R2 = Ph, 99% yield, 97.6% ee (2R,3S)

21 22 23 24 25

O

R1

R2 20 (2R,3S)

CF3 Si-AMP-(L-Leu)n, Na2CO4 21

HN HO

OCH3 Br

N

N

HN

t-BuOOH 2

Ph

TMSO 22

F

O H

N

2

23

Br

O H

H2O2 CF3

OCH3

N

H2O2 24

HO HO

OH OH La(Oi-Pr)3, Ph3PO 25

The use of a variety of chiral catalysts for the asymmetric epoxidation of α,β-unsaturated ketones has produced some interesting results. The use of a bis-quinoline catalyst, 24, and H2O2 as oxidant provides the desired epoxide 19 <05AG(I)1383>. A heterogeneous version of Shibasaki’s BINOL catalyst provides a very nice method to overcome some of the disadvantages inherent in the use of polymer supported version of the BINOL catalysts <05AG(I)6362>. The heterogeneous catalyst 25 provided (2R,3S)-epoxide 20 in excellent yield and with high enantioselectivity. The use of polyethylene glycol supported BINOL catalyst for example, provides the expected epoxide in good yield but with only 45% ee <05MI59>. The Baylis-Hillman reaction is a highly useful and general method for the synthesis of allylic alcohols. A method to convert the product of a Baylis-Hillman reaction to an epoxidized α,β-unsaturated ketone has been reported <05TL8895>. Iodosobenzene and KBr

Three-membered ring systems (2005)

85

initiate the reaction through the oxidation of the allylic alcohol to ketone 27. The resulting α,β-unsaturated ketone is then epoxidized with PhIO. OH CO2Me

Ph

O

PhIO, KBr

CO2Me

Ph

26

O

PhIO

CO2Me O

Ph

27

85% yield

28

The epoxidation of gem-deactivated olefins is a vexing problem in organic chemistry. While the epoxidation of α,β-unsaturated carbonyl compounds is well studied, the inclusion of an additional electron stabilizing group makes epoxidation much more difficult. The use of m-CPBA/K2CO3 provides an excellent solution to this problem in the epoxidation of the sulfone ester 29 <05JOC4300>. O

O TolO2S

m-CPBA, K2CO3

O 29

TolO2S

OEt

O

O

30

OEt

77% yield

A report on selective epoxidations of α,β-unsaturated carboxylates that uses the hydrophobicity of the substrate and reagent to provide largely a single product <05JA10812>. Reaction of a mixture of two carboxylates, 31 and 32, with oxaziridine 33 provides 34 as the major product. While this is a mechanistic study and reactions were carried out to only 5% completion, it does suggest that high levels of chemoselectivity can be accomplished through hydrophobic interactions between reagent and substrate. BF4 O

O Ph

O

+ H3C

31

O 32

33 oxone D2O

N CH3 O

O

O

O

Ph

O

H3C

98.1 34

O O

1.9 35

The selective capture of one isomer of interconverting allylic azides by epoxidation has been investigated <05JA13444>. Allylic azides 36 and 37 exist as a 70:30 equilibrium mixture. Upon treatment with m-CPBA, one isomer, 36, can be captured as the epoxide 38. As might be expected, the more substituted double bond of the mixture is epoxidized. N3

N3

m-CPBA, K2CO3, H2O

O N3

(70:30) 36

37

85% yield

38

A very interesting sulfur ylide approach to epoxides has been reported <05JOC4166>. In this method, a catalytic amount (10 – 20 mol%) of a C2 symmetric thiolane, 40, with a controlled topology is used to generate ylide 41. Reaction with an aryl aldehyde provides epoxide 42 via a catalytic transfer of benzylidene in generally excellent yields with good ee.

86

S.C. Bergmeier and D.D. Reed

A Darzens reaction has been used to generate trans-epoxides <05SL842>. Reaction of electron deficient p-substituted benzylammonium chlorides with benzaldehyde provides the trans-epoxide 46 in excellent to moderate yield as a 99:1 mixture of trans:cis epoxides.

O

O CHO

O

O

O

200 mol% BnBr NaOH

Ph

S 42

S 39

66% yield trans/cis 90:10 R,R/S,S 97.5:2.5

40 41

N

Cl

O

N

KOt-Bu, PhCHO

N

Ph

N

F3C

46 F3C

43

100% yield

CF3

44 45

The ring closure of halohydrins to form epoxides is a well known reaction. The ability to generate enantiopure halohydridns has been addressed through a biocatalytic approach <05MI1827>. The biocatalytic hydrogen-transfer reduction of prochiral α-chloroketones has been reported using lyophilized cells of Rhodococcus ruber DSM 44541 to provide chlorohydrin 48 in 99% conversion and with 99% ee. A subsequent cyclization reaction then provides epoxide 49. A strategy that uses whole cells of R. ruber as a base stable biocatalyst at pH >12 yields the epoxide in a single step, again with 99% conversion and 99% ee. O Cl

OH C6H13

47

R. ruber lyophilized cells pH 7.5, 30 ˚C

Cl

C6H13 48

KOH pellets pH > 12 30 ˚C

O

H C6H13 49

R. ruber lyophilized cells KOH pellets, pH ~13 30 ˚C

Enzymatic approaches to epoxidation are potentially quite powerful in that they avoid harsh reaction conditions and can provide high levels of enantioselectivity. Monooxygenases catalyze the activation of molecular oxygen and its addition to a variety of substrates. Monooxygenases are cofactor-dependent enzymes which restrict their use in epoxidation reactions. The use of direct electrochemical regeneration of monooxygenases appears to be a solution to the use of these enzymes in epoxidation reactions <05JA6540>. This approach uses the FADH2-dependent oxygenase component (StyA) of styrene monooxygenase (StyAB) from Pseudomonas sp. VLB120 coupled with cathodic reoxidation to epoxidize a series of styrene derivatives with excellent enantioselectivities.

87

Three-membered ring systems (2005)

A problem with enzymatic reaction systems is the inherent substrate specificity of the enzyme. An interesting approach to enzymatic epoxidation has been reported that overcomes this limitation <05T6009>. This approach combines the in situ enzymatic generation of H2O2 with the broad substrate specificity of a catalytic chemical system. Glucose oxidase catalyzes the conversion of β-D-glucose to gluconolactone and H2O2. Reaction of an olefin with glucose oxidase provides the epoxide through reaction with the generated H2O2. Both water soluble olefins as well as hydrophobic olefins such as 50 can be epoxidized. Hydrophobic olefins require the use of an additive such as t-BuOH or SDS to solubilize the olefin in the reaction medium. The enzyme has been immobilized on silica gel as well. glucose oxidase 0.2 M glucose, O2 pH 7.0 phosphate 50 Additive 10% t-BuOH 5 mM SDS

O

51 % Conversion 45 65

3.2.2.2 Reactions of Epoxides The reactions of epoxides are largely exemplified by nucleophilic attack on the epoxide ring. Both carbon and heteroatom nucleophiles are widely used. The use of carbon nucleophiles provides an excellent route for the preparation of highly substituted alcohols. The literature is replete with examples of organolithium and Grignard reagents used to open epoxides. In recent years the use of additional metals (e.g. B, Al, Ti, Pd) to modulate the ring opening in interesting and useful ways has been reported. The reaction of cyclohexene oxide with aryllithium reagents in the presence of both a Lewis acid (BF3•OEt2) and a Lewis base (sparteine) provides the ring opened product in excellent yields with moderate enantioselectivity <05EJO1354>. Reaction always occurs at the (S)-carbon of the oxirane. Other meso-epoxides gave excellent yields but with a lower enantioselectivity. H N O

N OH H

ArLi, BF3•OEt2 52

Ar = 2-Me-Phenyl, 91% yield, 65% ee Ar = 4-OMe-Phenyl, 95% yield, 40% ee Ar = 3-CF3-Phenyl, 90% yield, 60% ee

Ar 53

Regiocontrol in the ring opening of unsymmetrical epoxides is synthetically important. The ring opening of epoxides at the more substituted carbon is generally difficult yet potentially valuable synthetic transformation. The use of titanium reagents provides one solution to this problem.

88

S.C. Bergmeier and D.D. Reed

OMOM

ClTi(OPh)3

O

HO OMOM

MgCl 54

55 O

ClTi(OPh)3 MgCl

t-BuO2C

46% yield

49% yield OH

t-BuO2C

56

57

The reaction of a wide variety of functionalized epoxides containing esters, amides and acetals with chlorotitanium triphenoxide and allylmagnesium chloride provides exclusive reaction at the more substituted carbon <05T6726>. The use of protected chiral epoxides, 54 and 56, with the same reagent system provides a facile route into chiral quaternary centers, 55 and 57. The use of organoaluminum reagents also provides a useful solution to the regioselective ring opening of epoxides <05TL797>. The use of diethylpropynylalane with diastereomeric epoxides will provide different ring-opened products depending on the relative stereochemistry of the alcohol and epoxide. The anti-hydroxy epoxide, 58, leads to nucleophilic ring-opening at the carbon distal to the alcohol to provide 59. The syn-hydroxy epoxide, 60, provides the product of nucleophilic ring opening at the proximal carbon of the epoxide providing 61 in 39% yield.

AlEt2 TIPSO OH

78% yield 89:11

TIPSO

O

OH

OH

59

58

OH AlEt2

TIPSO OH

O

39% yield 15:85

TIPSO OH

60

61

Epoxides of α,β-unsaturated ketones can undergo a ring opening/arylation reaction under Heck conditions <05JOC4720>. Epoxide 62 undergoes an initial Pd-catalyzed rearrangement to a 1,2-cyclohexanedione which then undergoes a Heck arylation reaction to form 63. O

O O

62

Pd(OAc)2, PPh3, i-Pr2NEt Δ or MW Ar Br

OH Ar

Ar = 3-(NMe2)-Ph, 71% yield Ar = 4-(CF3)-Ph, 33% yield Ar = 4-(acetyl)-Ph, 40% yield Ar = Ph, 72% yield

63

Epoxides derived from 1,6-anhydro-β-D-glucopyranose undergo a quite interesting rearrangement to generate substituted allylic alcohols <05EJO2841, 05EJO4557>. Treatment of epoxide 64 with MeLi and CuCN initiates an epoxide to allylic alcohol rearrangement to

89

Three-membered ring systems (2005)

generate intermediate 65. Intramolecular delivery of the methyl group provides the final product 66 in 92% yield.

O

O

O H

B

O

MeLi CuCN

64

O 92% yield

O OTs Li Cu Me Me 65

OTs

O

O

HO

Me 66

Control of SN2 versus SN2’ additions to vinyl epoxides continues to be of interest. The usual group of alkynyl lithium reagents generally provided a mixture of the SN2 and SN2’ products <05EJO3946>. However when lithio-ethoxyacetylene was used, the SN2 product 68 was the major product (98:2). Changing the metal to aluminum provided a shift to the SN2’ product 69 in a similar 98:2 ratio as a mixture of E and Z-isomers. OH EtO Li BF3•OEt2

OTBS

62% yield SN2/SN2' 98:2

68 OEt

OTBS

O 67

EtO

AlEt2

EtO

OH OTBS

55% yield SN2'/SN2 98:2 E/Z 70:30

69

An alternate approach to regiocontrol in the ring opening of unsaturated epoxides is found in the initial ring opening of unsaturated epoxides with a transition metal prior to a coupling reaction <05MI5260, 05TL6705>. The reaction of vinylepoxide 70 with pincer catalyst 73 and an arylboronic acid provides the SN2’ product 71 in an 11:1 ratio.

73, PhB(OH)2

O 70

Ph HO

Ph

HO

PhSe 72

71 94% yield

Pd Cl 73

SePh

Propargylic oxiranes can undergo a similar SN2’ type reaction <05TL6705>. Ring opening of oxirane 74 with palladium followed by coupling to an aryl boronic acid provides the allenic alcohol 75 as a single stereoisomer.

90

S.C. Bergmeier and D.D. Reed

Pd(PPh3)4

CH3

OH

B(OH)2

•

O

75

CH3

Ph

O

74

92% yield

Ph

Ph

Pd2(dba)3•CHCl3, dppb

54% yield O

HO

CH3

76 CH3

The reaction of the same propargylic oxirane with a different catalyst and nucleophile provides radically different product <05TL3669>. Treatment of 74 with a phenol in the presence of a Pd2(dba)3 provides 76, the product of simple addition across the triple bond. It is interesting to note that no reaction of the epoxide ring occurs. The intramolecular ring opening of oxiranes with carbon nucleophiles is an excellent method for the construction of a number of novel molecules. A tandem base-promoted ringopening/Brook rearrangement/allylic alkylation of silyl epoxides provides the silyl enol ether 81 in very good yield <05JOC10515>. Reactions in which the cyclopropane derivatives are formed have also been reported <05T3349>. O

NaHMDS

CN

t-BuMe2Si

O t-BuMe2Si

77

O t-BuMe2Si

CN

78

t-BuMe2SiO CN

79

t-BuMe2SiO

R X

R = H, 73% yield R = Me, 63% yield

CN

80

CN

81 R

The acid catalyzed rearrangement of epoxides to form an aldehyde or ketone is a useful and commonly used reaction <05TL1269, 05T2541, 05JOC10747, 05TL89, 05JOC6537>. An interesting application of this reaction involves the in situ rearrangement of an epoxide to an aldehyde followed by reaction with an allenylstannane, 84, to generate alkyne 85 <05JOC6541>. None of the products that might arise from reaction of the allenylstannane with the epoxide were observed. Fused ring epoxides (e.g. cyclohexene oxide) were unreactive. OH O O

BF3•OEt2

Ph

CHO

Bu3Sn TMS

Ph 82

83

•

N

O

O

Ph 84

Ph

TMS

Ph

85

N

Ph

79% yield syn/anti >95:5

O Ph

Another interesting variation on this common rearrangement involves trapping the intermediate oxonium ion with an external nucleophile <05TL2311>. Treatment of epoxide 86 with ZrCl4 and a homoallylic alcohol generates intermediate 87. Cyclization and trapping

91

Three-membered ring systems (2005)

of the carbocation with chloride provides the isolated product 89. A number of homoallylic alcohols and epoxides were examined to provide a number of examples of 89 in excellent yields.

O

ZrCl4

O

Ph

Ph

Ph

Ph

Ph

Ph ZrCl3

O

Ph

O

Ph

87% yield

87 86

Cl 88

HO

89

The ruthenium-catalyzed cyclization of epoxy iodoalkynes shows a very intriguing solvent dependence <05OL1745>. The authors rationalize this solvent dependence as a result of two different ruthenium intermediates. In a polar solvent such as DMF an iodovinylidene species is formed followed by attack of the epoxide oxygen to eventually lead to naphthalene 91 in 88% yield. A nonpolar solvent such as benzene favors the formation of a p-iodoalkyne ruthenium species. Attack of this species by the epoxide oxygen leads to formation of oxepin derivative 92 in 78% yield. O TpRuPPh3(CH3CN)2PF6

O OH

90

I DMF (yields) Benzene (yields)

I 91 88% 12%

I 92 1% 78%

Radical cyclizations of epoxides initiated by Ti are versatile reactions for the formation of carbocycles and heterocycles <05JA14911>. While not truly a nucleophilic ring opening, these reactions provide similar products as a typical nucleophile ring opening reaction. The titanium-catalyzed intramolecular cyclization of 93 was studied <05S1405>. The use of sulfoximines and phosphine oxides as the leaving group (LG) were examined. The sulfoximines proved to be more difficult to prepare and gave poorer yields in the cyclization reaction than the corresponding phosphine oxides. Ts N

O

R2

LG 93

R

1

O LG = R1 = R2 = Me 40% yield S TsN p-Tol

Ts N

Cp2TiCl2, Mn HO 94

R1

R2

O P LG = Ph Ph

R1 = R2 = Me 80% yield

The metal catalyzed ring opening of epoxides followed by reaction with CO or CO2 to form β-lactones and carbonates is a useful reaction that continues to attract attention. In an expansion of previous work, Coates and co-workers have developed an improved catalyst, 99, for the carbonylation of epoxides <05JA11426>. These reaction conditions are compatible with a wide variety of side chains, including those bearing Lewis basic functionality. Interestingly, the cyclopentene oxide 97 was readily converted to the β-lactone 98 in excellent yield.

92

S.C. Bergmeier and D.D. Reed

O O

O

99, 900 psi CO

O

R R

95

96 R = Et, 99% yield R = t-Bu, 99% yield R = CH2OTBS, 99% yield R = CH2OCH2CHCH2, 88% yield R = CH2OAc, 99% yield

N

N Cr N

N

O

O

99, 900 psi CO 99% yield

O

O 98

97

Co(CO)4

99, [(OEP)Cr(THF)2][Co(CO)4]

An interesting reaction for the synthesis of cyclopropanes makes use of a tungsten carbonyl compound as the electrophile <05JOC5852>. An initial conjugate addition of lithiated epoxide 101 onto tungsten carbonyl 102 leads to intermediate 103, which then does an intramolecular ring opening of the epoxide to provide cyclopropane 104. H3CO

O

W(CO)5 O

Ph 100

s-BuLi, TMEDA

73% yield

O

Ph Li 101

HO Ph Ph 104

Ph

Ph

OCH3

Ph

102

103

W(CO)5

pyridine N-oxide

OCH3

HO Ph Ph 105

O

W(CO)5 Li

83% yield

OCH3

α-Lithiated epoxides constitute an alternative to carbenes for a variety of reactions. The homo-dimerization of α-lithiated epoxides has been found to provide an excellent route to 1,4-diols <05OL2305>. R

O

OH LTMP

R

R 106

107

OH

R = t-Bu, 86% yield R = CH2OTr, 51% yield R = cC6H11, 51% yield (+ 26% of the cis isomer) R = n-C5H11, 43% yield (+ 19% of the cis isomer)

Vicinal amino alcohols are highly useful molecules. Vicinal amino alcohols find use as synthetic intermediates, ligands for metal catalyzed reactions, and as biologically interesting molecules. It is not surprising that considerable effort has gone into the synthesis of useful vicinal amino alcohols as well as the development of new and improved methods for their synthesis. Pericàs and coworkers have elucidated a facile and inexpensive route to determining the enantiomeric excess of primary amines. A regioselective and enantioselective epoxide ring opening of 108 with BF3 followed by lithium tert-butoxide catalyzed epoxide closure yielded 109, which was utilized as a resolution reagent. Through the use of 20 mol% of 109 relative to an amine, an ee determination could be performed on 110 via NMR without further purification <05OL3829>.

93

Three-membered ring systems (2005)

O OTs

Ph

NH2

1. BF3•OEt2 70% yield 2. t-BuOLi, THF 90-100% yield

F Ph

108

O

R1

F

R1 R2 LiClO4, THF MW, 75 °C

Ph OH 110

109

N H

R2

The microenvironment created by cyclodextrins can be used to overcome the low reactivity of epoxides. Rao and coworkers have shown that in situ formation of an epoxide/β-cyclodextrin complex in water, followed by amine addition yields regioselective epoxide openings <05SL506>. Several substituted epoxides and aromatic amines were examined with isolated yields in the range of 80-90%. NH2

O OH

Ph HN

β-CD, H2O, rt,

OH

92% yield

OH 111

112

Most methods for the ring-opening of epoxides require some type of acid catalyst. A potentially very useful ring-opening process has been reported that takes place in water and requires no catalyst <05OL3649>. In this reaction, the epoxide and amine are simply mixed in water for 5 – 24 hours and the resulting β-amino alcohol, 114, is then isolated in excellent yields. It is worth noting that aliphatic amines will preferentially react in the presence of aryl amines in this reaction system. O H2O, rt, R2

113

H N

R1

HO

R1 N R2

114

R1 R2 Yield(%) -(CH2)492 -(CH2)593 H n-Bu 84 Et Et 86

The search for improved catalytic systems for epoxide opening reactions has yielded a number of methods to improve this reaction. The use of 10 mol% of Cu(BF4)2 has been found to catalyze the ring-opening of epoxides with amines under solvent free conditions <05TL2675>. Both aliphatic and aromatic amines provide excellent yields of the β-amino alcohols. Scandium triflate has also been found to catalyze the ring-opening of epoxides with both aromatic and aliphatic amines in the absence of solvent <05TL9029>.

94

S.C. Bergmeier and D.D. Reed

O

PhNH2

R1

PhHN

R2

OH

R1

R2

O

116

115

Sm I

O 117

R1, R2 (CH2)4 (CH2)4 (CH2)4 (CH2)4 (CH2)4 Ph, Ph

Reference <05TL2675> <05TL9029> <05TL8229> <05MI93> <05OL1023> <05OL4593>

Catalyst %Yield (ee) Cu(BF4)2 97 Sc(OTf)3 92 BiCl3 89 Ce-W10O36 100 117 79 (91) 118 89 (91)

N

N

OH

HO

Sc(OSO3C12H25)3

118

The use of BiCl3 is an interesting catalyst for the opening of epoxides with aryl amines <05TL8299>. When the ring opening reaction is carried out in acetonitrile, a chlorohydrin is the primary product. Changing the solvent to cyclohexane provides excellent yields of the βamino alcohol 116. Ammonium decatungstocerate (IV) polyoxometalate has been shown to be an effective heterogeneous catalyst for the ring opening of epoxides with arylamines <05MI93>. The conversion of meso epoxides to β-amino alcohols in high enantiomeric excess continues to be a rich area of research. The samarium binol catalyst 117, generates β-amino alcohols in excellent yield with good asymmetric induction (91%) <05OL1023>. The combination of a chiral bipyridal ligand and scandium tris(dodecylsulfate), 118, provides a method to open meso epoxides in water <05OL4593>. This catalytic system provides the amino alcohols in excellent yield and with good enantioselectivity. A one-pot epoxidation/azide-opening sequence has been developed <05JA2147>. A samarium-BINOL-Ph3AsO complex is used as a catalyst for enantioselective epoxidations of α,β-unsaturated amides. Upon addition of TMSN3 a new samarium azide complex is generated which regioselectively opens the epoxide to form 120. This method has also been extended to thiols and cyanide. O

N3 Sm(O-i-Pr)3, (S)-BINOL, Ph3As=O (1:1:1) Me3SiN3, TBHP in decane, THF, MS 4A, rt

N

O N

99% yield 99% ee

OH

119

120

The syn-opening of epoxides is a challenging reaction pathway to access. The use of arylborates, 122, may provide a general non-catalyzed route to such a reaction manifold <05CC1426>. Treatment of epoxide 121 with borate 122 provides 123 in 63% yield. The reaction occurs through an initial activation of the epoxide with the boron followed by synnucleophilic attack of the phenolic oxygen. This reaction occurs with some N-Boc aziridines as well although both syn and anti-opened products are obtained. OH O O

63% yield

O BOn-Bu

OH

O 121

122

123

Three-membered ring systems (2005)

95

Carboxylic acids are well known nucleophiles for opening epoxides and aziridines. Recently the stereoselective epoxide ring opening has also been achieved via palladium catalyzed formal 1,4 addition <05TL7243>. OH

O AcOH, Pd(Ph3)4

AcO OTES

OTES Ph

Ph

Ph

67% yield 94% ds

Ph 125

124

A tandem aldol/intramolecular enol cyclization of epoxyaldehydes to form α-furyl carbinols, 127, has been reported <05TL5467>. Only isopropyl methyl ketones or t-butyl methyl ketones have been shown to work in this reaction. The corresponding N-Boc aziridine aldehyde 127 (X = N-Boc) has also been used to generate an α-amino furan in excellent yield. H

X Bu2BOTf/DIPEA, DCM, 0 °C to 25 °C

X n-Pr

CHO

O

126

n-Pr

O

X Yield (%) O 71 N-Boc 72

127

3.2.3 AZIRIDINES 3.2.3.1 Preparation of Aziridines A general solution for the formation of aziridines by addition of nitrogen across an olefin has yet to be firmly established. Several examples of the transition metal mediated aziridination of olefins have been reported in the past year. The use of the rhodium catalyst, Rh2(cap)4, TsNH2 and NBS provides a number of aziridines in good to excellent yields <05OL2787>. Another rhodium catalyst, Rh2(pfm)4, (pfm = perfluorobutyramide) has been shown to catalyze the aziridination of olefins using TsNH2 and PhI(OAc)2 <05TL4031>. An advantage of the Rh2(pfm)4 catalyst system is the reported ability to use a variety of sulfonamides (e.g. nosyl, trichloroethoxysulfonyl) in the aziridination reaction. A cobalt porphyrin catalyst system that uses bromamineT as the nitrogen source provides excellent yields of aziridines <05OL3191>. A simple copper complex has been shown to catalyze aziridination as well <05JOC4833>. This reaction system uses PhINTs as the nitrogen F source and requires a borate, NaBAr 4, to remove the anionic ligands creating a coordinatively unsaturated cationic copper species. A key feature of all of these methods is that the olefinic substrate is the limiting reagent. This is an important feature of being able to use these methods in synthetically significant settings.

96

S.C. Bergmeier and D.D. Reed Ts N

R2

R1

R1

128 Catalyst

129

R2

Yield (%)

1 mol% Rh2(cap)4, NBS, TsNH2

R1 1 mol% Rh2(pfm)4, PhI(OAc)2, TsNH2

N Rh

R1 = Ph, R2 = H, 77% = n-C4H9,

R2

= H, 77%

R1 = Ph, R2 = H, 73%

Rh2(cap)4

R1 = n-C3H7, R2 = CH3, 44% 5 mol% Co(TDClPP), bromamine T

R1 = Ph, R2 = H, 83%

5 mol% (py)2CuCl2, NaBArF4, PhINTs

R1 = Ph, R2 = H, 97%

O Rh

R1 = n-C7H15, R2 = H, 56% R1 = n-C4H9, R2 = H, 49%

A rhodium-catalyzed route to bicyclic aziridines 131 from N-tosyloxycarbamates has been reported <05JA14198>. Several olefins were tested in this intramolecular process with yields ranging between 62-79%. O O O

N H

OTs

K2CO3, Rh2(OAc)4, Acetone, 25 °C

H

O

N

79% yield 131

130

The use of N-aminophthalimide as a nitrogen source in aziridination reactions has been examined. One of the problems associated with N-aminophthalimide as a nitrogen source is the need for a strong oxidant. The use of electrochemical catalysis with N-amino phthalimide has proved to be an effective and mild route for aziridination <05JOC932>. Both electronrich and electron-poor substrates worked well in this reaction.

MeO2C O

N

+ 1.80 V (vs Ag), MeCN, rt, NEt3H+ OAcCO2Me

NH2 132

O

O

133

N

O

92% yield trans

N MeO2C

134

CO2Me

The synthesis of aziridines from imines and sulfur ylides has been reviewed in previous editions of PHC and is a well-known reaction. A current study reveals that telluronium ylides add to α,β-unsaturated imines through a Michael addition-elimination to the olefin followed by a second equivalent of telluronium ylide addition to the imine, which subsequently eliminates to form aziridines 137 and 138 in a ratio of 13:1 <05JA12222>.

97

Three-membered ring systems (2005) Ph 1. NaHMDS

Te TMS

2. Ph

N

135

Ph Ph N

Ph

Ph N

TMS

TMS

TMS

136

137

TMS

138

82% yield 137/138 13:1

A new example of the aza-Payne rearrangement has been used to prepare βhydroxyaziridines <05OL3267>. The epoxy imine 139, is prepared by a sequential epoxidation and imination. Reaction of 139 with a series of alkyl lithium reagents initially adds to the imine which then does an aza-Payne rearrangement to form the hydroxyaziridine 140. While the method generally suffers from poor yields, the one step nature of the transformation lends greatly to its appeal. OH O N

t-Bu

R-Li N

139

140

R t-Bu

R = Me, 35% yield R = n-Bu, 47% yield R = Ph, 65% yield R = PhC≡C, 33% yield

3.2.3.2 Reactions of Aziridines In the synthesis of poison-frog alkaloid (-)-205B, a three-component Linchpin coupling was used to form a complex intermediate, 144, in a single step <05OL3247>. Lithiation of 141 followed by addition of epoxide 142, warming the reaction and then addition of aziridine in THF and DME to trigger the Brook rearrangement leads to 144. 1. t-BuLi, Et2O, -78 °C → -45 °C 2. Et2O, -78 °C → -20 °C S

S

3. THF/DME, -78 °C → 0 °C

OBPS

S

N Ts O

TBS O

O

O

142

141

O

OBPS

S OTBS NHTs

53% yield 144

143

The homologation of aziridines to allylic amines is an attractive process to a very useful class of molecules. Reaction of N-protected aziridines with excess dimethylsulfonium methylide provides the homologated allylic amines in excellent yields <05OL3295>. H 3C SO2t-Bu N R

145

S CH2 (300 mol%)

NHSO2t-Bu

H 3C R

146

R = CH2OTr, 90% yield R = (CH2)2CHCH2, 99% yield R = (CH2)4Cl, 98% yield R = CH2Ph, 99% yield

98

S.C. Bergmeier and D.D. Reed

The gadolinium•149 complex was used to catalyze the enantioselective desymmetrization of an assortment of aziridines <05JA11252>. The substitution on the nitrogen was critical to obtaining optimal yields and enantioselectivity. The use of N-tosyl aziridine gave 148 in only 24% ee while changing to the p-nitrobenzoyl gave 148 with an 87% ee. Aziridines have also been opened through the use of nucleophilic catalysis <05OL3509>. Several nucleophilic catalysts were examined for the preparation of cyanoamides, 148, and the optimal choice was TMEDA (20 mol%). This represents a significant departure from the more typical acid catalysis used for aziridine ring opening.

N R 147

H N

Gd(Oi-Pr), TMSCN, 149 R = Ts, 58% yield, 24% ee R = 4-NO2-PhCO, 94% yield 87% ee or

Ph R

Ph

CN 148

P O HO

O

O

F

HO

F

149

TMEDA, KCN, R = Ts, 57% yield

1,2-Diamines are another highly useful class of molecules with potent biological activity and use as synthetic intermediates and metal ligands. The ring-opening reactions of aziridines with amines and azide provides a facile route for the synthesis of 1,2-diamines. The use of microwave induced Montmorillonite K-10 clay catalyzed opening of tosylaziridines provides an environmentally friendly route to 1,2-diamines 151 and 152 <05TL2083>. In general, these ring-opening reactions are regioselective with both arylamines and aliphatic amines participating equally well. Particularly interesting is the opening of aziridine 150 (R1 = Me, R2 = CO2Me) at the most substituted carbon to provide diamino ester 151. Ts R1 R3 Yield (%) R2 3HN 3 TsHN R NHTs NHR 97 N MW, K-10 H Me Ph R1 93 H Me PhCH R3-NH2 2 R1 R2 R1 R2 R2 PhCH2 92 H Ph 150 85 151 152 Ph Me CO2Me

Ratio (151:152) only 152 10:90 90.10 only 151

A dynamic kinetic asymmetric transformation (DYKAT) of racemic vinyl aziridine 153 yielded the enantiopure imidazolidinone 154 <05OL823>. This transformation was the initial step in a total synthesis of (+)-pseudodistomin D. (η3-C3H5PdCl)2, 155 DMB N AcOH, DCM

DMB N

O N DMB

O

O NH HN

O 153

154 O OCN

88% yield 94% ee

PPh2 Ph2P 155

The ring opening of unactivated aziridines is difficult due to the inertness of these ring systems. The use of AlCl3 to catalyze the ring opening of aziridine 156 by NaN3 has proven

99

Three-membered ring systems (2005)

surprisingly effective <05TL4407>. The authors report complete inversion at the carbon bearing the azide. Given the acidic reaction conditions, it is also interesting to note that the reaction was carried out on a several hundred gram scale without any difficulties! Me

Ph N

Ph

H

AlCl3 (cat.), NaN3, EtOH:H2O (50:50), pH 4

Me

CO2Et

N H

86% yield N3

CO2Et 156

157

The silicon β-effect has been exploited to convert aziridines to 2-imidazolines and oxazolidines <05JA16366>. This reaction presumably goes through siliranium ion 159, which can then react with an electrophile to form 160 or 161. It has also been shown that zinc dihalides are effective in catalyzing the formation of 160, but require elevated temperatures <05TL4103>. SiPh2t-Bu N Me

MeCN Ts N

SiPh2t-Bu

BF3•Et2O DCM, rt

F3B

O O S N

p-Tol

158

N Ts 160, 90% yield

SiPh2t-Bu

SiPh2t-Bu R 159

O

EtCHO

Et N Ts 161, 90% yield cis/trans 67:33

An interesting copper catalyzed phenol opening of aziridine 163 yielded an intermediate, 164, for the synthesis of ustiloxin D <05OL5325>. This reaction is quite unique in that the phenol is reacting at a highly congested carbon and that none of the SN2’ addition is observed. OBn

CO2Bn

HO Boc

N Ns

N 162

O

O

OH

OBn N H

CO2t-Bu

CuOAc DBU Toluene

O Ns

CO2Bn

HO 163

Boc

NH

N

N H

CO2t-Bu

90% yield

164

In a very neat reaction sequence, N-methylaziridines have been shown to be useful directing groups for ortho-metallation <05OL3749>. Reaction of 165 with s-BuLi followed by trapping with a carbonyl compound provides alcohol 167. Subsequent intramolecular aziridine ring opening provides isobenzofuran derivative 168.

100

S.C. Bergmeier and D.D. Reed

CH3 N

OH

CH3

Li

N

s-BuLi, -78 °C

acetone

165

167

166 O

NHCH3

TFA

CH3 N

95% yield

168

Ring-opening reactions of aziridines (and epoxides) typically require the use of a Lewis acid to catalyze the reaction. β-Cyclodextrins (β-CD) are very useful in creating microenvironments in which aziridines can be opened using mild conditions. The reaction of aziridines with β-CD and sulfur nucleophiles such as thiocyanate <05SL489> or thiophenols <05TL6437> provides a mild route to such ring-opened compounds. TsHN

Ts N

SPh

β-CD, H2O, PhSH, 50 °C

β-CD, H2O, KSCN, rt

TsHN

SCN

78% yield

90% yield 169

170

171

Several thiazolidines were synthesized via titanium tetrachloride catalytic cyclization <05JOC227>. The reaction proceeds via an intramolecular attack on the nitrile by the aziridine nitrogen to provide bicyclic aziridinium intermediate 173. Subsequent ring opening by chloride yields thiazolidine 174. O Cl

N 172

N

Cl 1. TiCl4, MeCOCl, DCM, rt 2. NaHCO3, rt

N

NH

SCN Ar

Cl N

Me 96% yield

S 174

S

Cl 173

An interesting SN2/formal [3+2] cycloaddition route for the synthesis of substituted indolizidines has been reported <05OL5545>. This reaction requires both an electron withdrawing group on the alkyne and an aromatic ring on the aziridine. The reaction goes through an initial N-alkylation of the aziridine with iodide 175 followed by a Michael addition/rearrangement to generate indolizidines 179 - 181.

101

Three-membered ring systems (2005) H N

176

Ph racemic K2CO3, MeCN, 60°C, 24hr

95% yield racemic

179 Ph

EtO2C

>99% ee Ph K2CO3, MeCN, 50°C, 16hr

I

OBn N

H N

177

CO2Et

Ph

EtO2C

BnO

92% yield >99% ee N 180

175

Cl K2CO3, MeCN, 65°C, 24hr H N

178

83% yield 94% ee

EtO2C

95% ee

181

N Cl

The regioselective oxidation of aziridines to α-tosylamino ketones has been accomplished via N-Bromosuccinimide (NBS) and cerium(IV) ammonium nitrate <05TL4111>. Both styryl aziridines, 182, and aliphatic aziridines, 184, have been oxidized. A related report uses β-cyclodextrins in addition to NBS to catalyze the same transformation <05TL1299>. These reaction conditions also work well for epoxides to provide the corresponding α-hydroxy ketones. Ts N Ph

O

CH3CN:H2O (9:1), CAN, NBS

NHTs

Ph 182

92% yield

183

184

O

CH3CN:H2O (9:1), CAN, NBS

N Ts

185

H NHTs

84% yield

The transformation of aziridines that do not involve ring opening are rare due to the reactivity of the aziridine ring. Considering the somewhat more difficult synthesis of aziridines (relative to epoxides), the ability to convert one aziridine into another represents a significant expansion of the scope of any aziridine synthesis. The deprotection of N-protected aziridines continues to be a problematic process. Many methods used to deprotect N-protected aziridines results in cleavage of the aziridine ring. The use of ozone to deprotect N-benzhydryl aziridines, 186, has been reported <05OL2201>. While the yields of this method were modest, this is an important new method for such deprotections. Ph

Ph N

Ph

CO2Et 186

1. O3, DCM, -78 °C 2. NaBH4, MeOH

H N Ph

60% yield CO2Et

187

102

S.C. Bergmeier and D.D. Reed

The Darzens reaction of the oxazoline 188 with a series of aldimines has been shown to form aziridine 190 in good yields and diastereoselectivity <05T3251>. Deprotonation of the aziridine to form the aziridinyl anion and subsequent reaction with an electrophile provides the highly substituted aziridines 191 in moderate yields. The diphenylphosphinyl group on the nitrogen provides optimal yields in the lithiation reaction.

1. LDA, -98 °C, THF

N Cl

O

2.

188

Ph

Me

Me

191

E

Electrophile Yield (%) 50 MeI 58 BnBr 24 PHCHO

H

66% yield dr 90:10

189

s-BuLi, -98 °C TMEDA Electrophile

N POPh2 N Ph O

O P Ph Ph N

N POPh2 N Ph O

190

Terminal aziridines were deprotonated with LTMP and directly treated with a variety of electrophiles to provide substituted aziridines, 193 <05OL1153>. In all cases, the products had the trans geometry about the aziridine ring. Related work on the lithiation of carboxylate substituted aziridines <05AG(I)6169> and aziridinium ions <05MI1294> was also reported.

THF, -78 °C, Electrophile

O S O N C5H11

H

O S O N C5H11

N Li

192

Electrophile TMSCl PhCHO DMF CO2

R 193

Yield (%) 86 38 63 63

R SiMe3 CHOHPh CHO CO2Me

2-Aziridinemethanols were resolved using porous ceramic (Toyonite)-immobilized lipase (PS-C II) <05JOC1369>. This report is significant in that few examples of the lipasecatalyzed reaction for such 2-aziridinemethanols having two stereogenic centers at β– and γcarbons are known, and none of these types of resolutions with aziridine derivatives without N-protection have been reported. Ph

H N

H

Me OH

Me 194

H N

Ph

OH H

195

lipase PS-C II Acetone -40 °C

Me

H N

Ph

OAc H

Ph

H N

H OH

Me

196

197

90% ee

87% ee

Kimpe et. al., have found that (2-bromomethyl)-N-alkyl aziridines react with organocuprate reagents to provide largely the product of bromide displacement, 199 <05SL931>. Most aliphatic organocuprates (e.g. R = Me, n-Bu) provide good yields of the displacement product 199. When R = allyl, the sole product is 200 (40%), presumably via a competing electron transfer or metal-halogen exchange reaction which then leads to ring opening.

103

Three-membered ring systems (2005) Ph

Ph R2CuLi, Et2O

N Br

R

198

Yield (199:200) R 76:0 Me 54:10 n-Bu

N H

R

N

200

199

Aziridine 2-carboaldimines, 201, have been used to provide ready access to a variety of diamines <05T9281>. A number of nucleophiles were added to imine 201 to provide products 202 and 203. Grignard reagents and a ketene silyl acetal added to the imine in very good yields when catalyzed with BF3•OEt2. The Strecker product, R = CN, was obtained in very good yield but with only moderate diastereoselectivity by reaction with TMSCN and BF3•OEt2. Ph

PMB N

Me

N

Ph

BF3•OEt2 Nucleophile

Me

Ph

PMB N

HN

Me

PMB N

HN

R H

R

H

201 Nucleophile MeMgBr TMSCN OMe

H

202 Yield (%) Ratio (202:203) 86 99:1 99 69:31

203 R CH3 CN CO2Me

87 OTMS

In addition to the nucleophilic addition reactions of 201 shown above, the imine can also participate in cycloaddition reactions <05T9281>. Keto-piperidine 205 could be prepared in very good yield through a Diels Alder reaction of 201 with Danishefsky’s diene. The observed stereoselectivity was rationalized through a chelation controlled transition state with re-face preference. Ph Me

PMB N

N

BF3•OEt2 OMe OTMS

H

204

Ph PMB N N Me O H 205

201

Ph PMB N N Me 81% yield 71:29

O H 206

3.2.4 REFERENCES 04JOC2042 05AG(I)1383 05AG(I)6169 05AG(I)6362 05CC118 05CC1426 05CRV1563 05CRV1603 05CRV3167 05EJO1354 05EJO2841 05EJO3946

H.-C. Guo, X.-Y. Shi, X. Wang, S.-Z. Liu, M. Wang, J. Org. Chem. 2004, 69, 2042. S.-s. Jew, J.-H. Lee, B.-S. Jeong, M.-S. Yoo, M.-J. Kim, Y.-J. Lee, J. Lee, S.-h. Choi, K. Lee, M.S. Lah, H.-g. Park, Angew. Chem. Int. Ed. 2005, 44, 1383. A.P. Patwardhan, V.R. Pulgam, Y. Zhang, W.D. Wulff, Angew. Chem. Int. Ed. 2005, 44, 6169. X. Wang, L. Shi, M. Li, K. Ding, Angew. Chem. Int. Ed. 2005, 44, 6362. H. Guo, X. Shi, Z. Qiao, S. Hou, M. Wang, J. Chem. Soc., Chem. Commun. 2002, 118. M. Pineschi, F. Bertolini, R.M. Haak, P. Crotti, F. Macchia, J. Chem. Soc., Chem. Commun. 2005, 1426. E.M. McGarrigle, D.G. Gilheany, Chem. Rev. 2005, 105, 1563. Q.H. Xia, H.Q. Ge, C.P. Ye, Z.M. Liu, K.X. Su, Chem. Rev. 2005, 105, 1603. A. Viso, R.F.d.l. Pradilla, A. Garcia, A. Flores, Chem. Rev. 2005, 105, 3167. E. Vrancken, A. Alexakis, P. Mangeney, Eur. J. Org. Chem. 2005, 1354. K. Krohn, D. Gehle, U. Floerke, Eur. J. Org. Chem. 2005, 2841. P. Restorp, P. Somfai, Eur. J. Org. Chem. 2005, 3946.

104 05EJO4557 05JA2147 05JA6540 05JA6964 05JA10812 05JA11252 05JA11426 05JA12222 05JA13444 05JA13672 05JA14198 05JA14668 05JA14911 05JA16366 05JA16416 05JA17170 05JOC227 05JOC932 05JOC1262 05JOC1369 05JOC1728 05JOC4166 05JOC4226 05JOC4300 05JOC4720 05JOC4833 05JOC5852 05JOC6537 05JOC6541 05JOC10515 05JOC10747 05MI1 05MI29 05MI59 05MI93 05MI181 05MI1294 05MI1827 05MI5260 05OL823 05OL987 05OL1023 05OL1153 05OL1745 05OL2201 05OL2305 05OL2579 05OL2787 05OL3191 05OL3247 05OL3267 05OL3295 05OL3509 05OL3649 05OL3749

S.C. Bergmeier and D.D. Reed

K. Krohn, D. Gehle, U. Floerke, Eur. J. Org. Chem. 2005, 4557. S.-y. Tosaki, R. Tsuji, T. Ohshima, M. Shibasaki, J. Am. Chem. Soc. 2005, 127, 2147. F. Hollmann, K. Hofstetter, T. Habicher, B. Hauer, A. Schmid, J. Am. Chem. Soc. 2005, 127, 6540. M. Marigo, J. Franzen, T.B. Poulsen, W. Zhuang, K.A. Jorgensen, J. Am. Chem. Soc. 2005, 127, 6964. M.R. Biscoe, R. Breslow, J. Am. Chem. Soc. 2005, 127, 10812. T. Mita, I. Fujimori, R. Wada, J. Wen, M. Kanai, M. Shibasaki, J. Am. Chem. Soc. 2005, 127, 11252. J.A.R. Schmidt, E.B. Lobkovsky, G.W. Coates, J. Am. Chem. Soc. 2005, 127, 11426. J.-C. Zheng, W.-W. Liao, Y. Tang, X.-L. Sun, L.-X. Dai, J. Am. Chem. Soc. 2005, 127, 12222. A.K. Feldman, B. Colasson, K.B. Sharpless, V.V. Fokin, J. Am. Chem. Soc. 2005, 127, 13444. P. Fristrup, B.B. Dideriksen, D. Tanner, P.-O. Norrby, J. Am. Chem. Soc. 2005, 127, 13672. H. Lebel, K. Huard, S. Lectard, J. Am. Chem. Soc. 2005, 127, 14198. A.R. Kelly, A.E. Lurain, P.J. Walsh, J. Am. Chem. Soc. 2005, 127, 14668. J. Justicia, J.L. Oller-López, A.G. Campaña, J.E. Oltra, J.M. Cuerva, E. Buñuel, D.J. Cárdenas, J. Am. Chem. Soc. 2005, 127, 14911. V.K. Yadav, V. Sriramurthy, J. Am. Chem. Soc. 2005, 127, 16366. S.-J. Jeon, H. Li, P.J. Walsh, J. Am. Chem. Soc. 2005, 127, 16416. G. Yin, M. Buchalova, A.M. Danby, C.M. Perkins, D. Kitko, J.D. Carter, W.M. Scheper, D.H. Busch, J. Am. Chem. Soc. 2005, 127, 17170. M. D'Hooghe, A. Waterinckx, N. De Kimpe, J. Org. Chem. 2005, 70, 227. T. Siu, C.J. Picard, A.K. Yudin, J. Org. Chem. 2005, 70, 932. A.E. Lurain, P.J. Carroll, P.J. Walsh, J. Org. Chem. 2005, 70, 1262. T. Sakai, Y. Liu, H. Ohta, T. Korenaga, T. Ema, J. Org. Chem. 2005, 70, 1369. N.N. Reed, T.J. Dickerson, G.E. Boldt, K.D. Janda, J. Org. Chem. 2005, 70, 1728. M. Davoust, J.-F. Brière, P.-A. Jaffrès, P. Metzner, J. Org. Chem. 2005, 70, 4166. W.-K. Chan, M.-K. Wong, C.-M. Che, J. Org. Chem. 2005, 70, 4226. J.L.G. Ruano, C. Fajardo, A. Fraile, M.R. Martin, J. Org. Chem. 2005, 70, 4300. A. Svennebring, N. Garg, P. Nilsson, A. Hallberg, M. Larhed, J. Org. Chem. 2005, 70, 4720. F. Mohr, S.A. Binfield, J.C. Fettinger, A.N. Vedernikov, J. Org. Chem. 2005, 70, 4833. V. Capriati, S. Florio, R. Luisi, F.M. Perna, J. Barluenga, J. Org. Chem. 2005, 70, 5852. X.-M. Deng, X.-L. Sun, Y. Tang, J. Org. Chem. 2005, 70, 6537. C. de Los Rios, L.S. Hegedus, J. Org. Chem. 2005, 70, 6541. S. Okugawa, H. Masu, K. Yamaguchi, K. Takeda, J. Org. Chem. 2005, 70, 10515. A. Barbero, P. Castreño, G. Fernández, F.J. Pulido, J. Org. Chem. 2005, 70, 10747. I.M. Pastor, M. Yus, Current Org. Chem. 2005, 1. L. Sun, C.-P. Du, J. Qin, J.-S. You, M. Yang, X.-Q. Yu, J. Mol. Catal. A-Chem. 2005, 234, 29. G. Kumaraswamy, N. Jena, M.N.V. Sastry, G.V. Rao, K. Ankamma, J. Mol. Catal. A-Chem. 2005, 230, 59. V. Mirkhani, S. Tangestaninejad, B. Yadollahi, L. Alipanah, Catal. Lett. 2005, 101, 93. K. Faber, W. Kroutil, Curr. Opin. Chem. Biol. 2005, 9, 181. C. Gaebert, J. Mattay, M. Toubartz, S. Steenken, B. Mueller, T. Bally, Chem. Eur. J. 2005, 11, 1294. T.M. Poessl, B. Kosjek, U. Ellmer, C.C. Gruber, K. Edegger, K. Faber, P. Hildebrandt, U.T. Bornscheuer, W. Kroutil, Adv. Synth. Catal. 2005, 347, 1827. J. Kjellgren, J. Aydin, O.A. Wallner, I.V. Saltanova, K.J. Szabo, Chem. Eur. J. 2005, 11, 5260. B.M. Trost, D.R. Fandrick, Org. Lett. 2005, 7, 823. M.K. Tse, M. Klawonn, S. Bhor, C. Doebler, G. Anilkumar, H. Hugl, W. Maegerlein, M. Beller, Org. Lett. 2005, 7, 987. F. Carree, R. Gil, J. Collin, Org. Lett. 2005, 7, 1023. D.M. Hodgson, P.G. Humphreys, J.G. Ward, Org. Lett. 2005, 7, 1153. M.-Y. Lin, S.J. Maddirala, R.-S. Liu, Org. Lett. 2005, 7, 1745. A.P. Patwardhan, Z. Lu, V.R. Pulgam, W.D. Wulff, Org. Lett. 2005, 7, 2201. D.M. Hodgson, C.D. Bray, N.D. Kindon, Org. Lett. 2005, 7, 2305. A. Lattanzi, Org. Lett. 2005, 7, 2579. A.J. Catino, J.M. Nichols, R.E. Forslund, M.P. Doyle, Org. Lett. 2005, 7, 2787. G.-Y. Gao, J.D. Harden, X.P. Zhang, Org. Lett. 2005, 7, 3191. A.B. Smith III, D.-S. Kim, Org. Lett. 2005, 7, 3247. J.L. Bilke, M. Dzuganova, R. Fröhlich, E.-U. Würthwein, Org. Lett. 2005, 7, 3267. D.M. Hodgson, M.J. Fleming, S.J. Stanway, Org. Lett. 2005, 7, 3295. S. Minakata, Y. Okada, Y. Oderaotoshi, M. Komatsu, Org. Lett. 2005, 7, 3509. N. Azizi, M.R. Saidi, Org. Lett. 2005, 7, 3649. V. Capriati, S. Florio, R. Luisi, B. Musio, Org. Lett. 2005, 7, 3749.

Three-membered ring systems (2005)

05OL3829 05OL4593 05OL5325 05OL5545 05S1405 05SL489 05SL506 05SL842 05SL931 05SL1047 05SL1359 05T1069 05T2541 05T3251 05T3349 05T6009 05T6726 05T9281 05TL89 05TL339 05TL797 05TL1269 05TL1299 05TL1643 05TL2083 05TL2311 05TL2675 05TL3669 05TL4031 05TL4103 05TL4111 05TL4407 05TL5467 05TL5665 05TL6437 05TL6705 05TL7243 05TL8229 05TL8895 05TL9029

105

S. Rodríguez-Escrich, D. Popa, C. Jimeno, A. Vidal-Ferran, M.A. Pericàs, Org. Lett. 2005, 7, 3829. S. Azoulay, K. Manabe, S. Kobayashi, Org. Lett. 2005, 7, 4593. P. Li, C.D. Evans, M.M. Joullié, Org. Lett. 2005, 7, 5325. W. Zhu, G. Cai, D. Ma, Org. Lett. 2005, 7, 5545. D. Leca, K. Song, M. Albert, M.G. Goncalves, L. Fensterbank, E. Lacote, M. Malacria, Synthesis 2005, 1405. M.S. Reddy, M. Narender, K.R. Rao, Synlett 2005, 489. K. Surendra, N.S. Krishnaveni, K.R. Rao, Synlett 2005, 506. T. Kimachi, H. Kinoshita, K. Kusaka, Y. Takeuchi, M. Aoe, M. Ju-ichi, Synlett 2005, 842. M. D'Hooghe, M. Rottiers, R. Jolie, N. De Kimpe, Synlett 2005, 931. W. Adam, A. Zhang, Synlett 2005, 1047. V. Capriati, S. Florio, R. Luisi, Synlett 2005, 1359. R. Saladino, A. Andreoni, V. Neri, C. Crestini, Tetrahedron 2005, 61, 1069. T. Komiyama, Y. Takaguchi, A.T. Gubaidullin, V.A. Mamedov, I.A. Litvinov, S. Tsuboi, Tetrahedron 2005, 61, 2541. R. Luisi, V. Capriati, S. Florio, P.D. Cunto, B. Musio, Tetrahedron 2005, 61, 3251. A. Mordini, D. Peruzzi, F. Russo, M. Valacchi, G. Reginato, A. Brandi, Tetrahedron 2005, 61, 3349. K.-H. Tong, K.-Y. Wong, T.H. Chan, Tetrahedron 2005, 61, 6009. T. Tanaka, K. Hiramatsu, Y. Kobayashi, H. Ohno, Tetrahedron 2005, 61, 6726. H.-Y. Noh, S.-W. Kim, S.I. Paek, H.-J. Ha, H. Yunc, W.K. Leed, Tetrahedron 2005, 61, 9281. Y. Kita, S. Matsuda, R. Inoguchi, J.K. Ganesh, H. Fujioka, Tetrahedron Lett. 2005, 46, 89. S. Dinda, S.R. Chowdhury, K.M.A. Malik, R. Bhattacharyya, Tetrahedron Lett. 2005, 46, 339. R. Tirado, G. Torres, W. Torres, J.A. Prieto, Tetrahedron Lett. 2005, 46, 797. M. Fujita, M. Shindo, K. Shishido, Tetrahedron Lett. 2005, 46, 1269. M.S. Reddy, M. Narender, K.R. Rao, Tetrahedron Lett. 2005, 46, 1299. C. Ghiron, L. Nannetti, M. Taddei, Tetrahedron Lett. 2005, 46, 1643. U.K. Nadirm, A. Singh, Tetrahedron Lett. 2005, 46, 2083. J.S. Yadav, K. Rajasekhar, M.S.R. Murty, Tetrahedron Lett. 2005, 46, 2311. A. Kamal, R. Ramu, M.A. Azhar, G.B.R. Khanna, Tetrahedron Lett. 2005, 46, 2675. M. Yoshida, Y. Morishita, M. Ihara, Tetrahedron Lett. 2005, 46, 3669. G.F. Keaney, J.L. Wood, Tetrahedron Lett. 2005, 46, 4031. M.K. Ghorai, K. Das, A. Kumar, K. Ghosh, Tetrahedron Lett. 2005, 46, 4103. K. Surendra, N.S. Krishnaveni, K. Rama Rao, Tetrahedron Lett. 2005, 46, 4111. Y. Kim, H.-J. Ha, K. Han, S.W. Ko, H. Yun, H.J. Yoon, M.S. Kimd, W.K. Leeb, Tetrahedron Lett. 2005, 46, 4407. G. Righi, R. Antonioletti, S. Ciambrone, F. Fiorini, Tetrahedron Lett. 2005, 46, 5467. H. Yi, G. Zou, Q. Li, Q. Chen, J. Tang, M.-y. He, Tetrahedron Lett. 2005, 46, 5665. M. Somi Reddy, M. Narender, Y.V.D. Nageswar, K.R. Rao, Tetrahedron Lett. 2005, 46, 6437. M. Yoshida, H. Ueda, M. Ihara, Tetrahedron Lett. 2005, 46, 6705. S. Yoshida, M. Asano, Y. Kobayashi, Tetrahedron Lett. 2005, 46, 7243. A. McCluskey, S.K. Leitch, J. Garner, C.E. Caden, T.A. Hill, L.R. Odell, S.G. Stewart, Tetrahedron Lett. 2005, 46, 8229. B. Das, H. Holla, K. Venkateswarlu, A. Majhi, Tetrahedron Lett. 2005, 46, 8895. A.T. Placzek, J.L. Donelson, R. Trivedi, R.A. Gibbs, S.K. De, Tetrahedron Lett. 2005, 46, 9029.