One or More CC Bond(s) by Pericyclic Processes

1.17 One or More C1C Bond(s) by Pericyclic Processes HAMISH McNAB University of Edinburgh, UK 0[06[0 INTRODUCTION

660

0[06[1 FORMATION OF MONOENES BY RETRO!ENE AND RELATED REACTIONS 0[06[1[0 Cleava`e of One C0H and One C0C Bond 0[06[1[1 Cleava`e of One C0H and One C0O Bond 0[06[1[1[0 Pyrolysis of acetates and related esters 0[06[1[1[1 Pyrolysis of xanthate esters 0[06[1[1[2 Other concerted pyrolytic eliminations 0[06[1[2 Cleava`e of One C0H and One C0S Bond\ includin` Pyrolysis of Sulfoxides 0[06[1[3 Cleava`e of One C0H and One C0Se Bond*Pyrolysis of Selenoxides 0[06[1[4 Cleava`e of One C0H and One C0N Bond\ includin` the Cope Elimination 0[06[2 FORMATION OF MONOENES BY RETRO!CYCLOADDITION REACTIONS 0[06[2[0 Retro ð1¦1Ł Cycloadditions 0[06[2[1 Retro ð3¦1Ł Cycloadditions "Retro!DielsÐAlder Reactions# 0[06[3 FORMATION OF DIENES AND POLYENES

661 661 662 662 664 666 667 679 671 673 673 674 676 678 689

0[06[3[0 Retro!cycloaddition Reactions 0[06[3[1 Retro!cheletropic Reactions

0[06[0 INTRODUCTION This chapter is concerned with the creation of the C1C unit by retro!pericyclic cleavage reactions\ with emphasis on their synthetic utility[ Retro!sigmatropic!shift processes\ which are considered _rst\ are characterised by cleavage of one C0H and one C0X bond to create the alkene\ whereas the retro!cycloaddition reactions which form the next section of the chapter are characterised by cleavage of two C0C "or C0X# bonds[ Formation of dienes and polyenes are considered separately\ and include a consideration of retro!cheletropic reactions[ Concerted rearrangements are covered in Chapters 0[98 and 0[07[ Within each section\ the mechanism and stereochemistry of the process under consideration will be covered\ together with an assessment of the scope\ limitations and reaction conditions^ _nally\ some examples of applications to the syntheses of natural and unnatural products will be given[ The majority of the relevant reactions are thermal eliminations\ which may be carried out preparatively either in solution or in the gas phase[ Most chemists have an intuitive {feel| for solution temperature conditions\ but the same cannot be said for gas phase reactions\ where the contact time of the substrate in the hot zone is the most important parameter[ This chapter will describe as {~ow pyrolyses| those reactions which are carried out at atmospheric pressure "often in a stream of nitrogen# by feeding the substrate\ either neat or in solution\ down a heated tube packed with glass helices[ Contact times under these conditions are generally of the order of a few seconds[ In contrast\ 660

C1C Bond"s# by Pericyclic Processes

661

{~ash vacuum pyrolysis| "FVP# involves vacuum distillation of the substrate through a heated tube\ and contact times are generally a few milliseconds[ Clearly\ much higher temperatures are needed for FVP and\ as a general rule\ a reaction which proceeds at 079>C in solution may well require in excess of 799>C under FVP conditions\ with ~ow pyrolyses taking place at intermediate tempera! tures[

0[06[1 FORMATION OF MONOENES BY RETRO!ENE AND RELATED REACTIONS The general reactions under consideration are shown in Equations "0# and "1#[ Equation "0# involves hydrogen transfer via a six!membered ring transition state and is formally a ð1ss ¦1ss ¦1psŁ reaction[ In certain cases where X and Y are carbon!containing groups\ the formation of the by! product X1Y0ZH may also be synthetically useful[ Equation "1# is isoelectronic with Equation "0#\ but involves a _ve!membered ring transition state ð1ss ¦1ss ¦1vsŁ[ A number of general reviews are available "e[g[\ ð58AG"E#445\ 82S548Ł#\ which include examples of the generation of C0heteroatom double bonds by this mechanism[ H

ZH

Z

X Y

+

(1)

Y

X

H +

X

+

Y–

X YH

(2)

0[06[1[0 Cleavage of One C0H and One C0C Bond Apart from the intramolecular case which results in a rearrangement\ the {all!carbon| retro!ene reaction "Equation "0#^ XYZC# is of little synthetic value ð82S548Ł[ In part\ this is due to a mechanistic dichotomy in which concerted and homolytic cleavage mechanisms are in competition and which therefore leads to mixtures of products[ In the gas phase pyrolysis of hex!0!ene\ for example\ retro!ene cleavage is most important at lower temperatures\ with radical _ssion of the C!20C!3 bond being predominant at high temperatures ð68MI 006!90Ł[ Simple ketones decompose on pyrolysis under ~ow conditions to give alkenes "Equation "0#^ ZO#\ but they require temperatures ca[ 049>C higher than the corresponding acetates "see Section 0[06[1[1[0# for comparable conversion ð67JOC0310Ł\ and therefore the reaction is seldom used syn! thetically[ Decarboxylation of carboxylic acids containing b\g!unsaturation "Equation "2## forms a special case of Equation "0#\ in which the {useful| product is the HZ0Y1X fragment ðB!68MI 006!91\ B!79MI 006!90Ł[ Pyrolyses are carried out at 239>C in solution "boiling phenanthrene# ð53JCS2786Ł or at ca[ 319>C in the gas phase under ~ow conditions ð54JCS5191Ł[ The reaction takes place with a wide variety of substituted acids\ including cyclic examples ð56JCS"B#446Ł\ but it does not appear to have been exploited in synthesis[ O O

H

X

Z Y

ZH CO2

+

X

Y

(3)

Facile decarboxylation of b!ketoacids and 0\2!diacids ð40QR020Ł is familiar as a key step in the acetoacetic ester and malonic ester syntheses of methyl ketones and carboxylic acids\ respectively\ in which the initially formed enol tautomerises to the _nal product "Scheme 0#[ In practice\ the reaction may only require heating of the acid for a few hours in re~uxing aqueous acid solution ð32OSC"1#305Ł\ or heating at 014Ð029>C in the absence of solvent ð32OSC"1#82Ł[

662

Monoenes by Retro!ene and Related Reactions O

H

H O CO2

R1

O

+

O

O R1

R1

R2

R2

R2

R1 = Me or OH; R2 = alkyl Scheme 1

0[06[1[1 Cleavage of One C0H and One C0O Bond These cleavage processes are an important group of preparatively useful reactions "Equation "0#^ XO# which di}er in the nature of the other heteroatoms "Y\Z#[ Most have the overall e}ect of accomplishing an alcohol dehydration\ by _rst modifying the alcohol function and then performing a pyrolytic syn!elimination ð59CRV320Ł[ The e.ciency of both of these steps is therefore important in the synthetic applicability of the various methods[

0[06[1[1[0 Pyrolysis of acetates and related esters Many reviews of this topic "Equation "0#^ XZO# are available ð59CRV320\

60MI 006!90\

B!68MI 006!91\ B!79MI 006!90\ 80COS0900Ł[

This reaction is traditionally carried out in the gas phase under ~ow conditions\ with temperatures of 499Ð414>C recommended for preparative purposes ð59CRV320Ł[ FVP conditions are also e}ective\ but require slightly higher temperatures "599Ð699>C#[ The mechanism has been extensively studied ðB!68MI006!91Ł[ The syn!nature of the elimination was suspected for many years before it was elegantly proved by pyrolyses of the speci_cally labelled acetates "0# and "1#\ which lead to deuterium incorporation into\ and deuterium exclusion from\ the alkene product\ respectively "Scheme 1# ð42JA5900\ 61JCS"P1#054Ł[ These results have been applied to the conformational analysis of steroids "ð40JCS0937Ł and references therein#[ H

O

flow

Ph D

Ph

O

Ph

+ HOAc 400 °C 74%

D

Ph

(1) H

O

flow

Ph H

D

Ph (2)

O

Ph

+ DOAc 400 °C 61%

Ph

Scheme 2

The regioselectivity of the elimination is dependent on a number of factors\ including statistical e}ects\ thermodynamic stability of the products "arising from steric e}ects# and electronic e}ects\ and the overall stereochemical outcome can be rather modest[ Statistical e}ects dominate the pyrolyses of simple alkyl acetates^ for example\ but!1!yl acetate gives a 46 ] 32 ratio of but!0!ene to but!1!enes\ close to the statistical ratio of 59 ] 39 ð52RTC0012Ł "Equation "3##[ Steric e}ects promote the formation of the "E#! rather than the "Z#!alkenes if either is possible "Equation "3## and may cause a slight reduction in the amount of terminal alkene in competitive situations[ Cycloalkyl acetates generally form the alkene unexceptionally^ however\ with large ring sizes\ both "E#! and "Z#!alkenes are formed "Equation "4## ð44JA0990Ł[ The formation of a double bond endo! to a ring is generally favoured relative to the exo!isomer\ due to the greater reduction in eclipsing interactions in the former case ðB!68MI 006!91Ł "e[g[\ Equation "5# ð48JA540Ł#[ Conjugative stabilisation of the product appears to be unimportant^ even the acetate "2# gives just a 0 ] 0 mixture of conjugated and unconjugated dienes "Equation "6## ð58MI 006!90Ł[ Large ring lactones\ which can accommodate the required transition state\ undergo corresponding thermal rearrangement to give v!unsaturated carboxylic acids ð66JOC2784Ł[

C1C Bond"s# by Pericyclic Processes

663

flow

+

(4)

+

380–440 °C

OAc

57%

28%

15%

OAc flow

(5)

+ 500 °C

69%

19%

flow

(6)

+ OAc

450 °C

0–16%

84–100%

OAc 'reactor'

+

(7)

300 °C

(3)

50%

50%

Electronic factors are now recognised as being dominant in governing the rate and direction of alkene formation[ The reaction is aided by electron donation at C!0\ such that the order of reactivity is tertiary×secondary×primary\ even allowing for statistical correction "e[g[\ the relative rates of ethyl\ isopropyl and t!butyl acetates are 0 ] 17[7 ] 2204 ð64JCS"P1#0914Ł#[ The reaction is aided by electron withdrawing groups at C!1\ such that pyrolysis of "E#!methyl 1!acetoxycyclo! hexanecarboxylate gave the 0!alkene almost exclusively "Equation "7## ð48JA1015Ł[ Bulky electron donating "alkyl# substituents at this position can also cause a small rate enhancement due to {steric acceleration| ð65JCS"P1#179Ł\ which reaches a maximum factor of 02 for a t!butyl group relative to a hydrogen atom[ CO2Me OAc

flow

CO2Me

CO2Me

+

(8)

435 °C

97%

3%

The reaction is also accelerated by electron!withdrawing groups at the carbonyl carbon atom^ formates\ chloroacetates\ chloroformates and other functional groups such as carbonates and carbamates "see Section 0[06[1[1[2# are therefore all in principle more e.cient than acetates ðB!68MI 006!91Ł\ although the e}ect is often small ð52JCS0135Ł[ However\ cyclohexyl tri~uoroacetate is some 08 times more reactive than the corresponding acetate ð58JCS"B#076\ 61RTC2Ł[ From a synthetic point of view\ these reactions are attractive despite the relatively high tem! peratures involved\ because of the ready availability of starting materials\ and because of the absence of any acidic or basic reagents which might promote rearrangements[ At a practical level\ the use of benzoates rather than acetates has the advantage that benzoic acid crystallises at the exit point of the furnace\ well away from the more volatile alkene ð77MI 006!90Ł[ The gas!phase\ short contact time conditions are particularly e}ective for the synthesis of alkenes which readily polymerise or decompose unless kept in the cold[ Examples include the generation of reactive dihydrofurans ð76TL0408\ 82AJC0210Ł or dihydrothiophenes ð75JOC002Ł "Scheme 2#^ in both monocyclic cases the isolated yield from the pyrolysis step was ×74)[ Acetate pyrolysis continues to be employed as a key step in natural product syntheses[ It was used selectively by Klaver et al[ en route to the alkaloid peduncularine "3#\ when anionic or cationic eliminations failed "Scheme 3# ð78JA1477Ł[ The exo!cyclic methylene groups of longifolene "4# ð89JA3598\ 82JOC1075Ł and sinularene "5# ð68AJC0708Ł were introduced by classic {~ow| pyrolysis methodology using benzene or toluene solutions of the substrates "Scheme 4#[

664

Monoenes by Retro!ene and Related Reactions FVP

OSiMe2But AcO

OSiMe2But

510 °C, 0.02 torr

O

O

FVP

OAc

S

400 °C, 0.0001 torr

S

OH

OH FVP

OAc O

550 °C, 0.2 torr

O H

O

O H

Scheme 3

AcO Pri

N

AcO OAc

Pri

FVP

Pri

N

N

600 °C, 0.05 torr

O

O

N H (4) Scheme 4

OAc

flow 525 °C, benzene

(5)

flow

OAc

450 °C

(6) Scheme 5

0[06[1[1[1 Pyrolysis of xanthate esters This method follows the general mechanism of Equation "0# "XO\ YC0SR\ ZS#^ invariably the S!methyl derivatives are used[ As well as the reviews cited in the previous subsection\ a specialised account of this transformation*the Chugaev reaction*is available ð51OR"01#46Ł[ The reaction is aided by greater nucleophilicity in the atom Z ðB!68MI 006!91Ł and so\ not surprisingly\ xanthates are more reactive than acetates and the reaction may be carried out under relatively mild conditions[ Possible thermal isomerisation of the alkene is therefore minimised[ Typically\ the pure xanthate is heated to ca[ 049>C for a few hours either at atmospheric pressure or under vacuum^ the product may distil out or remain in the pyrolysis ~ask[ If the xanthate distils without decomposition\ the elimination can be e}ected by dropwise addition to a high boiling point solvent such as diphenyl ether or biphenyl ð51OR"01#46Ł[ Two disadvantages of this method vis!a! vis ester pyrolysis are that xanthates are more di.cult to prepare than acetates and that the products are frequently contaminated with sulfur!containing impurities "which are traditionally removed by treatment with metallic sodium# ð51OR"01#46Ł[ The syn!stereochemistry of the process was established by Cram ð38JA2772Ł "e[g[\ Equation "8##\ and this was applied to assign the con_guration of terpene hydroxyl groups in the early days of conformational analysis ð38JCS1063Ł[ The involvement of the C1S sulfur atom in the elimination

C1C Bond"s# by Pericyclic Processes

665

has been proved by 23S and 03C isotope e}ects ð50CJC237Ł[ Statistical\ thermodynamic and steric factors again govern the direction of the elimination ð51OR"01#46Ł\ and complex mixtures will result if a variety of decomposition pathways are open "cf[ Section 0[06[1[1[0#[ Where a comparison has been made\ the results have been found to be closely similar to those of the corresponding acetate\ bearing in mind that the reaction conditions are substantially di}erent ð59CRV320Ł[ Again\ the formation of "E#!alkenes is favoured over "Z#!alkenes in competitive situations[ "Z#!Cycloalkenes are formed when the ring size is smaller than eight carbon atoms ð51OR"01#46Ł\ but the proportion of "E#!isomer increases the larger the ring size ð44JA0990Ł[ The preference for endo! rather than exo! elimination in cyclic cases is apparently less marked than for the corresponding acetate ð59CRV320Ł[ Electron withdrawing groups attached to sulfur further accelerate the reaction ð42JA1007Ł[ Ph

H

Ph

S

O

180 °C

(9)

SMe

Xanthate pyrolysis is still used substantially in synthesis[ At a simple level\ b!02C!labelled styrene was prepared in 19) yield by pyrolysis of the xanthate derived from labelled phenethyl alcohol ð76JA442Ł[ A comparison of acetate\ tosylate and xanthate pyrolysis as a means of preparing tens of grams of 5!chlorohex!0!ene has shown that the last method is preferred\ with yields of 64Ð79) being obtained routinely by FVP at 414>C ð78JOC4700Ł[ Applications in propellane ð76TL1684\ 89JA117Ł and triquinancene chemistry ð89TL2398\ 81JOC4010Ł have also been published since the late 0879s\ including a spectacular triple!Chugaev process "Equation "09## which takes place in 80) yield when carried out at 119Ð129>C in hexamethylphosphoramide "HMPA# ð89TL2398\ 81JOC4010Ł[ OCS2Me 220 °C

(10)

OCS2Me HMPA 91%

OCS2Me

A number of applications in natural product synthesis may be cited[ Pyrolysis of the xanthate "6# in biphenyl solution at 109>C gave an 79) yield of the alkene "7# en route to racemic lindestrene "Scheme 5# ð74TL5282Ł[ The method is compatible with the presence of remote chiral centres\ and the alkene function of the alkaloid "−#anisomycin "8# was introduced by xanthate pyrolysis in o!dichlorobenzene "Equation "00##^ the 3\4!dehydropyrrolidine isomer was also obtained as a minor by!product ð78H"18#0750Ł[ Not surprisingly\ heating the xanthate "09# at its sublimation temperature "109>C# gave regiospeci_c formation of the dihydropyran "00# in high yield "Equation "01##^ structure "00# has been proposed as a potential intermediate in yohimbine alkaloid synthesis ð75JOC2912Ł[ In other cases\ a comparison of xanthate and selenoxide methods has come out in favour of the latter methodology ð89JOC3940Ł[ MeS2CO

O

O O

Ph2, 210 °C

O

16 h 80%

H CO2Me

O H CO2Me

(7)

H

(8) Scheme 6

MeS2CO

OMe H

OMe 180 °C

H

N

N

CO2Bn

R R = CO2Bn → R =H (9)

(11)

666

Monoenes by Retro!ene and Related Reactions O

O

H

MeS2CO H

H

Ph3CO

H

210 °C

OMe

(12)

H

93%

Ph3CO

(10)

OMe (11)

0[06[1[1[2 Other concerted pyrolytic eliminations Wide structural variation is possible\ and some examples have been summarised ð80JOC735Ł^ Taylor has made extensive studies of the mechanistic e}ects of changing the heteroatoms "e[g[\ ð80JCS"P1#0692Ł and earlier papers in the series#[ Important factors include the nucleophilicity of Z and the electronegativity of Y "or of atoms attached to Y#\ both of which aid the reaction "Equation "0## ðB!68MI 006!91Ł[ However\ these variations have\ as yet\ not signi_cantly displaced the traditional acetate or xanthate methods for preparative purposes[ The heteroatom Z is not required for a successful pyrolytic elimination\ and indeed simple vinyl ethers "01# "Equation "0#^ XO# can be pyrolysed in a ~ow system at atmospheric pressure ð66JOC2788Ł\ to give alkenes at a comparable rate to the corresponding acetate\ although the product distribution is slightly altered "Equation "0#^ XO# ð71JCS"P1#0068\ 77JCS"P1#626Ł[

O (12)

1!Alkoxypyridines "02# ð71JCS"P1#0064Ł and related heterocycles ð75JCS"P1#0144Ł undergo a similar decomposition "Equation "0#^ XO\ ZN#[

O

N

(13)

Other examples of substrates with two heteroatoms which give alkenes in a similar manner to ester pyrolyses are thionacetates "03# "and the isomeric thioacetates "04## ð62JCS"P1#0182\ 64JCS"P1#206Ł and benzimidates "05# ð55TL5168Ł\ whereas examples related to xanthates include the carbonates "06# ð61JCS"P1#815\ 61JCS"P1#0633\ 61JCS"P1#1248\ 72JCS"P1#180Ł and thiocarbonates "07#[ Within the series of carbonates and their possible sulfur analogues\ the following order of reactivity has been found ð77JCS"P1#066Ł] PhOCSOR×PhOCO1R×PhSCSOR×PhSCO1R×PhOCS1R×PhSCS1R× PhOCOSR×PhSCOSR[ The major rate change occurs when OR is replaced by SR\ with the change from carbonyl to thiocarbonyl producing a relatively small e}ect ð77JCS"P1#066Ł[ S

O

NPh

O

S

O

(14)

(15)

(16)

Ph

O O (17)

S OR

O

OR

(18)

The ~ow pyrolysis of carbamates "08# ð62AJC0148Ł has attracted some attention[ Empirically\ N\N!dimethylcarbamates require similar conditions to those of acetates\ but their diphenyl ana! logues react at rather lower temperatures ð70JOC1793Ł[ In one useful application\ decomposition of the carbamate "19# at the temperature of re~uxing carbon tetrachloride "09 h# gave an 79) yield of the silole "10# "Equation "02## ð72TL2410Ł^ the method was much superior to earlier methods of dehydration[ A study of N!aryl!O!alkylselenocarbamate "11# pyrolysis has been made ð83T528Ł[

C1C Bond"s# by Pericyclic Processes

667

Conditions are mild "79>C in chloroform solution#\ but the syn!elimination is complicated by a competing bimolecular "E1# mechanism[ S O

Se NR2

O

(19)

O

CCl4

NHPh O

Si Me

NHAr

(22)

(13)

10 h

Me

Si Me

(20)

Me

(21)

Similar eliminations have been observed from phosphate "12#\ phosphinate "13# or sulfonate "14# esters[ Phosphates are much more reactive than the corresponding acetate owing to the greater electronegativity of the phosphorus atom ð50JOC735Ł\ and the rate spread for alkyl diphenyl! phosphinates "primary ] secondary ] tertiary0 ] 399 ] 095# is much greater than for the cor! responding acetates ð64JCS"P1#0914Ł[ O O

P

O

OR OR

O

(23)

P

O

Ph Ph

(24)

O

S

R O

(25)

Tosylates have been found to be more reactive than either acetates or xanthates in 0\2!eliminations in the adamantane series ð61JCS"P0#1422Ł[ Like benzoates\ they have the added practical advantage for FVP that the co!product condenses at a position in the trap\ well away from the alkene\ allowing facile separation ð78JOC4700Ł[ As an alternative to gas!phase methods\ 7!quinolylsulfonates or 1!pyridylsulfonates have been found to decompose cleanly at ca[ 049>C to give good to excellent yields of simple alkenes ð78JOC278Ł[

0[06[1[2 Cleavage of One C0H and One C0S Bond\ including Pyrolysis of Sulfoxides The cleavage of C0S bonds in ester!type pyrolyses is well known "Equation "0#^ XS\ etc[#[ Examples include thioacetates "04# and S!alkyldimethylthiocarbamates "15#\ which show standard eliminations to give alkenes "79Ð87) on a 099 mg scale# upon FVP at 459>C ð76JOC2577Ł^ these compounds are less reactive than their O!alkyl isomers[ O S

NMe2 (26)

Pyrolysis of sulfoxides has long been known to give alkenes\ but the reaction has only been developed as a useful synthetic method since the mid 0869s ð67ACR342\ 67CRV252\ 67S602\ 80COS0900Ł[ The availability of the precursors and the mild conditions required for the elimination are two major attractions of this method "and for the related application of selenoxide pyrolysis "Section 0[06[1[3##[ In particular\ it provides a three!step route from ketones or esters to their a\b!unsaturated analogues by sequential sulfenylation\ oxidation and thermolysis "Scheme 6# ð67CRV252Ł[ The thermolysis step usually takes place in solution in the temperature range 14Ð029>C\ with S!arylsulfoxides decom! posing at the lower temperatures and S!alkylsulfoxides decomposing at the higher temperatures in the range ð67ACR342Ł[ Electron!withdrawing groups on the S!aryl ring also accelerate the reaction

668

Monoenes by Retro!ene and Related Reactions

ð67CL430Ł[ The method is also useful for the preparation of the sulfenic acid co!products ð80COS0900Ł[ Sul_nate esters "16# show similar elimination reactions ð69JCS"C#70Ł[ –O

SR3 R2

R1

[O]

R2

R1

O

+

SR3 heat

R2

R1

O

O R2

R1

R3SOH

+ O Scheme 7

+

S

O–

OMe (27)

The standard syn!stereochemistry of the process for acyclic examples was established by Kings! bury and Cram ð59JA0709Ł and the solvent independence of the reaction rate is consistent with a concerted mechanism[ Isotope e}ect studies suggest that the hydrogen transfer occurs via a linear transition state ð67JA1791\ 67JA2816Ł[ Acyclic alkenes are produced with "E# stereochemistry ð62JA5739\ 64JOC037Ł[ Fragmentation takes place towards the most acidic b!hydrogen atom\ and the order of reactivity quoted by Trost ð67ACR342Ł is as follows] C1C0CH1 ×C2C0CH1 ×ArCH1 ½ CH2 ×CH1 ×CH[ The elimination takes place away from b!hydroxy groups to give allylic alcohols "Scheme 7# ð67TL3892Ł] the equivalent reaction of selenoxides "Section 0[06[1[3# is more useful in practice[ Where no other reaction is possible\ pyrolysis of b!hydroxysulfoxides gives ketones via their enol tautomers ð64TL1730Ł[ Chirality at the sulfoxide group can also have an e}ect on the regiochemistry\ especially in sterically hindered situations where alternative b!hydrogen atoms have similar acidities ð56JCS"C#421\ 69JCS"C#722\ 65JCS"P0#348Ł[ Early attempts to obtain optically active alkenes by the use of homochiral sulfoxides have met with only limited success ð56JOC1948Ł[ As found for acetate and xanthate pyrolysis\ endo!cyclic rather than exo!cyclic elimination takes place in _ve! and six!membered cyclic systems "Equation "03# and Scheme 8\ where LDA is lithium diisopropylamide# ð62JA5739\ 64JOC037\ 66HCA1277Ł[ OH

140 °C

OH + –O

SR OH Scheme 8

O– +

SMe 120 °C

O O

O 95%

+

O

O

(14)

O 87:13

As the elimination step takes place under such mild conditions\ the synthetic utility of sulfoxide eliminations is primarily dependent on the availability of the precursors[ The route to a\b!unsatu! rated carbonyl compounds "Scheme 6# can be extended by regiospeci_c alkylation*either at the sul_de or the sulfoxide stage ð67S602Ł*to give a combined alkylationÐelimination sequence "e[g[\ Scheme 8# ð66HCA1277Ł[ Dimsyl anion methodology can be used as a route to isolated terminal alkenes\ although the thermolysis temperatures are comparatively high "e[g[\ Scheme 09# ð53JOC1588Ł[

C1C Bond"s# by Pericyclic Processes

679 O

O SPh

O +

i, LDA, MeI

70 °C

SPh O–

ii, mcpba

Scheme 9

O– NaCH2S(O)Me C15H31

OTs

DMSO

DMSO

S+

C15H31

C15H31

reflux

Scheme 10

In some applications from the late 0879s\ vinyl ~uorides have been obtained from a!~uoro! sulfoxides ð76TL2890Ł^ for the corresponding b!~uoro derivatives elimination takes place away from the ~uorine atom to give a high yield of an allylic ~uoride "Equation "04## ð81JOC603Ł[ Dimethyldioxirane has been advocated for oxidising sterically hindered sul_des to the sulfoxide prior to the elimination\ for which traditional reagents are ine}ective ð82T6856Ł[ In the _eld of natural product synthesis\ sulfoxide elimination has been employed in routes to avermectin ð76TL3848Ł and azadirachtin ð76TL110\ 80T5702Ł subunits "Scheme 00# "see also Chapters 0[02 and 0[03#[ F +

F

80 °C

Me

S

(15) 20 h 95%

O–

CO2Me

HO

HO

SPh

CO2Me

mcpba

O

110 °C 94%

H

OMe

OSiMe2But +

SPh O–

O H

OMe

OSiMe2But

110 °C 92%

O

O H

H Scheme 11

0[06[1[3 Cleavage of One C0H and One C0Se Bond*Pyrolysis of Selenoxides Selenoxide elimination is the most recently developed method to be considered in this chapter\ and it occurs under the mildest conditions\ with the {pyrolysis| frequently taking place in solution between 9>C and room temperature "Equation "1#^ XSe#[ On average\ temperatures for the elimination are 49Ð019>C lower than those required for sulfoxide pyrolysis ð67T0938Ł[ Alkenes which are sensitive to nucleophiles\ polymerisation\ enolisation and thermal degradation can be prepared e.ciently by this method[ Flexible routes to the selenide precursors are available from ketones\ esters\ epoxides or by substitution reactions\ which enhance the synthetic utility of the method\ and these lead to a\b!unsaturated carbonyl compounds\ allylic alcohols or terminal alkenes\ respectively[ Reviews have been published ð67T0938\ B!75MI 006!90\ 80COS0900Ł[ Detailed practical considerations are discussed by Clive ð67T0938Ł\ and applications to natural product synthesis are summarised by Paulmier ðB!75MI 006!90Ł[ The reaction is carried out by oxidation of a selenide precursor "usually a phenylselenide# and

670

Monoenes by Retro!ene and Related Reactions

the elimination then takes place directly without isolation of the selenoxide[ A range of possible reagents may be employed\ but hydrogen peroxide or meta!chloroperoxybenzoic acid are used most commonly ð67T0938Ł[ The formation of terminal unconjugated alkenes from primary selenides is slow\ although it can be encouraged by incorporating an electron withdrawing group into the phenyl ring of the selenide ð64JOC836\ 79TL4926Ł[ Since the precursors are easily made from alcohols ð65JOC0374Ł\ this provides an alternative to acetate and related pyrolyses for primary alcohol dehydration[ The generation of acyclic enones is particularly rapid[ Often\ an excess of the oxidising agent is employed to destroy the selenenic acid co!product\ which could otherwise react with the alkene "particularly terminal alkenes# or undergo competing disproportionation reactions ð67JOC0578Ł[ The selenenic acid can also be destroyed by addition of a secondary amine to convert it into a selenenamide ð65JOC1492Ł\ a strategy which is particularly useful when cyclic enones are formed ð64JA4323Ł[ The mild conditions employed\ compared with sulfoxides "and amine oxides#\ are due to the longer Se0O and Se0C bond lengths and to the greater polarisation of the Se0O bond ð70JA0121Ł[ The syn!nature of the elimination was established in 0869 using a steroid example ð69JCS"D#75Ł\ and later con_rmed for acylic cases ð62TL0868Ł[ As usual\ "E#!alkenes are obtained predominantly ð63TL1168Ł\ although almost equal amounts of "E#! and "Z#!a\b!unsaturated nitriles may be obtained[ In most cyclic systems a "Z#!alkene is produced\ but for large "−01!membered# rings either pure "E#! isomer or mixtures of "E#! and "Z#!isomers may be obtained ð67T0938Ł[ As with sulfoxide! or acetate!type pyrolysis\ endo!alkene formation is favoured over exo!elimination for both _ve! and six!membered rings\ although in some cases the preference may not be very great "Scheme 01# ð62JA4702Ł[ Where possible\ the fragmentation occurs away from a b!electronegative substituent "particularly oxygen atoms# "e[g[\ Equation "05## ð63JOC318Ł\ and this provides an e.cient and highly e}ective synthetic route to allylic alcohols[ Decomposition takes place towards allylic or benzylic centres to give the conjugated product ð62JA4702\ 62TL0868\ 64JA2149Ł^ conditions are par! ticularly mild in these cases ð64JA4323Ł[ The direction of the elimination is also a}ected by statistical factors\ and if these are in opposition to the above e}ects then the overall regioselectivity may not be very good[ H2O2, MeOH

O

67:23

O

O

+

SePh

80:20 H2O2, AcOH, THF, H2O, < 25 °C

Scheme 12

SePh OH

H2O2 25 °C

(16)

+ OH

OH > 99:1

Partly because of the availability of precursors\ selenoxide eliminations are particularly e}ective for the synthesis of a\b!unsaturated carbonyl compounds\ and for allylic alcohols ð62JA1586Ł and related compounds ð80COS0900Ł via enolate selenenylation and epoxide ring opening\ respectively[ These methods are of signi_cant importance in contemporary organic synthesis\ and frequently appear in multistep syntheses of natural products[ Thus the reaction has been employed in quassinoid chemistry "Equation "06## ð83JOC200Ł\ where it was found that removal of the phenylselenenic acid co!product was simply e}ected by addition of sodium bicarbonate[ Cases of a\b!unsaturated car! bonyl compounds being produced include formation of a!alkylidene!b!lactones "17# ð82JOC211Ł "which can be transformed into allenes by b!lactone thermolysis "Section 0[06[2[0## and a subunit "18# of the streptogramin antibiotics "Scheme 02# ð78JOC2877Ł[ Some exo!methylene heterocyclic

C1C Bond"s# by Pericyclic Processes

671

compounds have been prepared via selenoxide intermediates "e[g[\ Equation "07## ð82JOC0238Ł[ Allylic alcohol formation has been employed in key steps en route to symbioramide "29# ð83LA30Ł\ valienamine "20# ð81TL0914Ł and coriolin "21# ð82LA0022Ł "Scheme 03# "see also Chapter 0[03#[ O

O H2O2, EtOH, NaHCO3

H PhSe

O-TBDMS

H

O

O

H2O2

SePh

O-TBDMS

H

O

O

(17)

H

25 °C 82%

25 °C

(28)

O-TBDMS

O-TBDMS i, LiNPri2, PhSeBr ii, H2O2 70%

CO2Me

CO2Me (29) Scheme 13

EtO2C

EtO2C H2O2

SePh Ph

O

20 °C, 25 h 71%

(18) Ph

O

0[06[1[4 Cleavage of One C0H and One C0N Bond\ including the Cope Elimination Alkenes may be formed by pyrolysis of suitable amides "Equation "0#^ XNR\ ZO#[ Although the temperatures required are higher "ca[ 099>C# than those for the corresponding acetate ð59CRV320Ł\ similar isomer distributions are obtained ð48JA540Ł[ Kinetic data for amides and the corresponding thioamides "Equation "0#^ XN\ ZS# are available ð78JCS"P1#468\ 89JCS"P1#1076Ł[ In a cyclic example\ facile elimination of isobutene from N!t!butylpyridazin!2!ones at 699>C under FVP conditions has been observed ð71JCS"P0#0734Ł[ Disulfonimides "22# can also be pyrolysed neat at 059Ð199>C to give alkenes in up to 88) yield[ The most important reaction type in this section is the Cope elimination "Equation "1#^ XNR#\ for which specialised reviews are available ð59OR206\ 82S152Ł in addition to more general surveys ð59CRV320\ 80COS0900Ł[ The method presents an alternative to the more widely used Hofmann elimination of quaternary ammonium hydroxides\ and has certain advantages in terms of ease of manipulation and lack of product isomerisation[ However\ the Meisenheimer rearrangement to form N\N\O!trisubstituted hydroxylamines may compete ð82S152Ł[ As with the related sulfoxide and selenoxide eliminations\ the reaction is normally carried out with a mixture of amine and oxidising agent without puri_cation of the amine oxide[ After destruction of the excess oxidising agent\ the reaction mixture is concentrated and the crude material is pyrolysed for a few minutes at 099Ð039>C "e[g[\ ð42JA2101Ł#[ These conditions are signi_cantly more severe than those required for sulfoxide and particularly selenoxide eliminations[ Both the alkene and the hydroxylamine by!product distil from the reaction mixture and are separated by treatment with acid[ Signi_cant rate enhancements can be observed if the elimination is carried out in DMSO solution ð51JA0623Ł[ The syn!stereochemistry of the elimination has been frequently established "e[g[\ Equation "08# ð62JOC0631Ł#\ but isotope e}ects suggest that there may be subtle di}erences in the mechanism in

672

Monoenes by Retro!ene and Related Reactions OH OH O-TBDMS

( )13

OH

H2O2

( )13

25 °C

( )14

HO O-TBDMS H

O

N

SePh ( )13

HO (30) BnO

BnO i, PhSeNa ii, mcpba, 45 °C

BnO

86%

O

BnO

BnO

BnO

HO

BnO

BnO

O

HO

BnO

HO

BnO

HO OH

NH2 OH (31) HO

O

i, PhSeNa

O

O

H

O

O O

ii, H2O2, EtOH, 78 °C, 4 h

O H

HO

H

O

H OH (32)

Scheme 14

NO2 O 2S R

N

SO2

NO2 (33)

DIGLYME solution "nonlinear hydrogen transfer via a bent transition state# and DMSO solution "linear hydrogen transfer\ possibly incorporating a molecule of solvent# ð67JA1791\ 67JA2816\ 70JA3549Ł[ 03 C!Isotope e}ects indicate that extensive rupture of both the C0N and the C0H bonds has taken place at the transition state\ with relatively little C1C character ð72JA2603Ł[ In aliphatic systems\ the direction of elimination qualitatively resembles that found for esters\ with the number of hydrogen atoms on b!positions being the major factor ð59CRV320\ 59OR206Ł^ the formation of "E#! alkenes is again favoured if both "E# and "Z# isomers can be obtained ð59CRV320\ 59OR206Ł[ In medium!sized rings "−nine!membered# "E#!alkenes are obtained exclusively ð42JA2101\ 44JA0517Ł[ A striking di}erence compared with the results of ester\ sulfoxide or selenoxide pyrolyses is that a double bond exo! to a six!membered ring is obtained in preference to the endo!isomer "Equation "19## ð46JA3618Ł[ This may be due to the more severe constraints of the _ve!membered ring transition state with relatively short C0N bonds\ which requires a quasi!boat form in the cyclohexane ring for endo!elimination[ Five! and seven!membered ring analogues give more of the endo!cyclic alkene ð46JA3618Ł[

C1C Bond"s# by Pericyclic Processes

673

O– +

NMe2

110 °C

(19)

D

+

D

160 °C

NMe2

+

(20)

O– 97.2:2.8

Applications of the Cope elimination to synthesis have been rare[ Following earlier work in thiete dioxide chemistry ð53JOC2020Ł\ Woolhouse et al[ obtained the conjugated thiete "23# exclusively by heating a sample of the amine oxide "24# at 89>C "Scheme 04# ð82JHC762Ł^ the isomeric thiete "25# is thought to be formed initially\ which then isomerises under the reaction conditions[ In a highly stereoselective\ convergent synthesis of racemic trichodiene "26#\ a Cope elimination was used in the _nal step to introduce the exo!cyclic alkene function "Equation "10## ð73JOC2769Ł[ Examples of intramolecular ring cleavage by Cope elimination have been published with simple heterocycles ð59JA3545Ł and the work has been extended to alkaloid chemistry in the mid 0879s ð73JCS"P0#0690\ 74H"12#2974Ł "see also Chapters 0[02 and 0[03#[ +

O–

N

H

H 90 °C

SO2 (35)

SO2

SO2

(36)

(34)

Scheme 15

NMe2 mcpba

(21)

distil at 1.5 torr

(37)

0[06[2 FORMATION OF MONOENES BY RETRO!CYCLOADDITION REACTIONS 0[06[2[0 Retro ð1¦1Ł Cycloadditions Thermal cycloreversions of this type "Equation "11## would formally be ð1ss ¦1saŁ processes and hence many of these reactions occur thermally by diradical mechanisms ð75T1024Ł and are not considered in detail here[ The incorporation of a carbonyl group in the four!membered ring apparently increases the likelihood of a "stereospeci_c# concerted process taking place under thermal conditions[ The topic has been reviewed ð71AG"E#114Ł[ W X

Z

W

Y

X

+

Z Y

(22)

Mechanistic aspects of the formation of alkenes by cyclobutane pyrolysis have been reviewed by Gajewski ðB!70MI 006!91Ł and Brown ðB!79MI 006!90Ł\ and the weight of evidence is in favour of diradical intermediates ð83TL1564Ł[ In contrast\ the thermal decomposition of simple cyclobutanones is probably concerted and proceeds with the retention of stereochemistry predicted for such a mechanism ð61JA6124Ł[ Under photochemical conditions\ even simple cyclobutanes would be expected to undergo concerted fragmentation^ one example is shown in Equation "12# ð64TL0224Ł[

674

Monoenes by Retro!Cycloaddition Reactions O

Ph

O

Ph hν

+

N

Ph

Ph

Me

(23) N Me

The photochemical formation of oxetanes followed by thermal cracking in the opposite sense ð62CC263Ł has been employed as a synthetic method for a\v!enones ð64CC195Ł^ this is probably another diradical process ð66CRV362Ł[ The facile loss of carbon dioxide from b!lactones is well established ð0772CB1197Ł and has been reviewed "e[g[\ ð73CHEC"6#252\ 82S330Ł[ The process is of synthetic value for the two!step conversion of 2!hydroxycarboxylic acids into alkenes\ and since these precursors can be readily obtained from ketones the method is a viable alternative to the Wittig reaction for the conversion of ketones into alkenes[ Experimental conditions include heating in water ð47JA2474Ł\ or heating at 039Ð059>C either neat ð61JA1999Ł or in solution ð82JOC211Ł\ or FVP at 399>C ð80JOC4671Ł[ The decomposition is accelerated by electron donating substituents at the 3!position\ although it is a}ected little by substituents at the 2!position ð73CHEC"6#252Ł[ The precise mechanism of the reaction is a matter for debate ð82S330Ł\ but the syn!nature of the elimination was con_rmed in 0855 "Equation "13## ð55JOC3932Ł[ This feature\ together with the absence of isomerisation\ is particularly important for synthetic applications ð61JA1999Ł[ The method has been used as a route to enol ethers ð62CJC870\ 68S277Ł\ and applications to the synthesis of allenes are also noteworthy ð80JOC4671\ 82JOC211Ł[ In exceptional cases where a highly strained alkene would result\ the cycloreversion may take place in the opposite sense to give a keto!ketene ð75JA6010Ł[ O

H

100 °C

+ CO2

O

H Ar

(24)

Ar

Simple b!lactams can decompose thermally to give isocyanates and alkenes ð48RTC440Ł\ although the alternative mode of fragmentation to ketene and imine may take place with appropriate substituents ð52JA2413Ł and under photochemical conditions ð57CB1558Ł[ Upon FVP at 599>C "01 torr# reaction takes place to give alkenes with almost complete retention of stereochemistry "Equation "14## ð69JA0652Ł[ This reaction does not appear to have been used synthetically[ O

H H

FVP

N

+

(25)

600 °C

H 99.3:0.7

0[06[2[1 Retro ð3¦1Ł Cycloadditions "Retro!DielsÐAlder Reactions# This ð1ps ¦1ss ¦1ssŁ reaction "Equation "15## has been used extensively as a preparative route to either monoenes\ dienes "Section 0[06[3[0# or other multiply bonded functional groups containing heteroatoms[ For the preparation of alkenes "Equation "15#^ YZC#\ the transformation almost always involves cleavage of two C0C single bonds "i[e[\ UXC#[ It can be carried out in solution\ usually at temperatures in excess of 049>C ð80COS"4#440Ł\ although in appropriate cases acceleration by cation\ anion or radical substitution has been predicted ð67T0766Ł[ Indeed\ oxy! anionic substitution may cause the reaction to proceed rapidly at room temperature "Equation "16## ð79TL1688Ł[ Cycloreversion of endo!adducts may be substantially faster than that of exo!adducts ð67JOC407Ł[ Increasingly\ FVP methods are employed to accomplish the transformation for neutral species\ using temperatures in the range 399Ð599>C ð80COS"4#440Ł[ Cyclopentadiene or anthracene adducts ""27# and "28#\ respectively# have been commonly used as alkene precursors[ The former has the advantage that its low molecular weight causes the precursor "and the cyclopentadiene co! product# to be relatively volatile and it is commonly used for complex alkenes\ although relatively high temperatures may be required[ In contrast\ anthracene is less volatile and condenses near the exit point of the furnace^ it is often used for simple alkenes from which it is readily separated[

C1C Bond"s# by Pericyclic Processes

675

V W

U

Z

heat

Y

X

W

U

t1

H O–

Z

+

(26)

Y

X

MeO2C

25 °C

MeO2C MeO2C

V

(27)

+

< 1 min

/2

MeO2C

H

O– R2 R1

R1 R2

(38)

(39)

These methods have been used to prepare a wide range of both simple and functionalised alkene systems\ and some typical examples are given below[ In many cases reactive alkenes are released at a late stage of a synthesis and so the DielsÐAlder adduct serves as a protecting group[ A number of comprehensive reviews of retro!DielsÐAlder processes are available\ covering mechanistic features ð57CRV304\ 79AG"E#668Ł\ preparative aspects ð67T08\ 74S010\ 80COS"4#440Ł and application to natural product synthesis ð76S196Ł[ The vinylimidazole "39# is a good example of a simple alkene best prepared by retro!DielsÐAlder reactions[ A yield of 74Ð89) is claimed for ~ow pyrolysis "methanol solution# at 499>C "Equation "17## ð72AG"E#459Ł[ The method is also useful for releasing sensitive a\b!unsaturated carbonyl functionality[ The example shown in Equation "18# is noteworthy\ since the chiral centres and the alcohol protecting group are both una}ected\ despite the apparently severe conditions of the retro! DielsÐAlder reaction ð75TL2400Ł[ Zwanenburg and co!workers have used FVP methodology "499>C# to generate the alkene unit of cyclopentenones "e[g[\ Equation "29#\ which are important inter! mediates in the synthesis of quinane natural products^ once again\ optically active products can be obtained under these conditions "e[g[ ð76TL246\ 83TL1676Ł#[ A large number of methylidenemalonic esters have been generated in situ by reaction of malonic ester with formaldehyde\ trapped with anthracene\ and then released again by pyrolysis of the adducts "30# in solution at 199Ð149>C in the presence of maleic anhydride "which reacts with the anthracene formed#[ For most esters\ yields are in the 39Ð59) range ð77JOC3748Ł[ Natural products containing an allylic alcohol unit*such as "31#\ a ~avour component of mushrooms*have been made in high enantiomeric purity by a method which requires an FVP cycloreversion to create the alkene function "Scheme 05# ð76TL072Ł[

N

FVP

+

(28) N

500 °C

N

H N

H (40)

Ph

FVP

Ph

+ 500 °C

O

O

O-TMS R1 H

R2

R1

O-TMS R2

FVP

+

(30)

500 °C

O

(29)

O

676

Dienes and Polyenes R1O2C

CO2R2

(41)

O-TMS

O-TMS

FVP

+ 660 °C

OH

(42) Scheme 16

The retro!DielsÐAlder cleavage of anthracene cycloadducts has been used very e}ectively by Ripoll and co!workers ð74S010Ł to generate unstable or highly reactive tautomers such as enols ð68NJC084Ł\ simple enamines ð79T1386Ł or vinyl phosphines ð79T1386Ł\ as shown in Equation "20#[ In many cases\ these products were trapped or were characterised by spectroscopy at low temperatures[ X X

FVP

+

(31)

660 °C

X = OH, NH2, PH2, etc.

In certain cases where strained alkenes may be formed\ an alternative free!radical ring expansion may take place rather than the retro!DielsÐAlder process[ Certain cyclopropeneÐanthracene adducts\ for example\ have been shown to behave in this way ð83CC778Ł[

0[06[3 FORMATION OF DIENES AND POLYENES The methods described in the previous sections have been applied*often unexceptionally*to generate dienes and polyenes\ and some typical examples of each will be given below[ The major advantage of these methods vis!a!vis ionic eliminations is that the reactions usually proceed with a notable lack of isomerisation\ and so nonconjugated alkenes can often be obtained if desired[ Standard ~ow pyrolysis of an acetone solution of the diacetate "32# gave the diene "33# in up to 74) yield on a 149 g scale "Equation "21## ð76JOC4923Ł[ Trahanovsky and co!workers have made extensive application of ester pyrolysis under FVP conditions as a route to heteroaromatic analogues of o!xylylenes "e[g[\ ð70JA5580\ 75JOC3197Ł#[ The mechanism may involve a direct d!elimination\ or a ð2\2Ł!sigmatropic shift of the ester function prior to standard b!elimination "Scheme 06#[ These xylylenes are stable at −59>C but form dimers at room temperature[ AcO

OAc flow

O

O

(43)

460 °C

(32) O

O

(44)

C1C Bond"s# by Pericyclic Processes

677 OCOPh

FVP

dimers 635 °C

O

O Scheme 17

Facile Chugaev eliminations can take place instead of the expected reduction when appropriate xanthate!type compounds are heated to 79Ð009>C in the presence of tributyltin hydride ð82JA1157Ł[ Allylic alcohols have been transformed into conjugated dienoic esters by a one!pot process involving sequential ortho!ester exchange\ ð2\2Ł!sigmatropic shift and sulfoxide pyrolysis "Scheme 07# ð80JOC5870Ł[ Although mixtures of isomers may be obtained\ the method has been usefully applied in synthesis ð89JOC2856\ 80JOC3228Ł[ In a more esoteric application\ a quadruple sulfoxide elimination was employed to generate four alkene units in the novel cyclophane "34# "Equation "22## ð80AG"E#0062Ł[ The use of sulfoxide and particularly selenoxide pyrolysis to give conju`ated dienes is complicated by the possibility of a competitive ð1\2Ł!sigmatropic shift to give the isomeric sulfenate or selenenate\ respectively "Scheme 08#\ which may be trapped to give an allylic alcohol ð63ACR036Ł[ As a result of the reversibility of the process in the case of sulfur\ the diene may also be obtained if desired ð71JOC3790Ł\ especially if the S!aryl ring contains electron!withdrawing groups which accel! erate the elimination ð67CL430Ł[ With selenoxides\ the equilibrium lies much further towards the selenenate\ and dienes have only been obtained in a few special cases and in modest yield ð72JA1492Ł[ +

OH

Ph

+

S O–

OEt

100 °C

H+

Ph

OEt OEt

O

+

S –O

Ph

+

S

45–95%

CO2Et

4–18 h

OEt

CO2Et

–O

Scheme 18

SOMe

MeOS

300 °C

(33)

SOMe

MeOS

(45)

Ph +

S O– P(OMe)3

OSPh

OH

Scheme 19

The Cope elimination has been employed to prepare penta!0\3!diene and allylbenzene^ both were obtained in the absence of their conjugated isomers penta!0\2!diene and b!methylstyrene\ respectively ð46JA859Ł[ Although the overall yield is often high\ isomerisation may be a problem in

678

Dienes and Polyenes

amine oxide pyrolysis ð81TL1350Ł\ and traditional Hofmann elimination can be more selective[ A spontaneous {sila!Cope| elimination\ leading speci_cally to a "Z#\"Z#!diene\ has been reported to take place under particularly mild conditions ð71JA6555Ł[ 0[06[3[0 Retro!cycloaddition Reactions Photochemical cleavage of cyclobutanes has been used to achieve some spectacular syntheses of unnatural target molecules such as bullvalene "Equation "23## ð53CB2039Ł\ and*in conjunction with matrix isolation*reactive polyenes such as pentalenes ð62AG"E#226Ł and cyclobutadienes ð63AG"E#314Ł have been obtained[

hν

(34)

The pyrolytic cleavage of b!lactones has been employed as a convenient route to arene oxides and related dihydroaromatic compounds ð67JA241Ł\ since the precursors can be easily obtained in a few steps from benzoic acid[ The retro!DielsÐAlder reaction can be used to release a single alkene of a diene "or polyene# unit[ The general conditions of the reaction are described in Section 0[06[2[1\ and a typical example is shown in Equation "24# ð75TL0334Ł[ MeO2C

FVP

+

(35)

550 °C

MeO2C

CO2Me CO2Me

100%

Clearly\ dienes can also be generated directly by utilising the other product of the retro!DielsÐ Alder process "Equation "15#^ UVWXC#[ When the {diene| released forms part of a benzenoid system\ the reactions may be especially facile[ Much variation in the precursor structure is possible\ and useful syntheses have been developed in which the diene is formed by cleavage of either two C0C bonds\ or one C0C bond together with a C0O or C0N bond\ or by cleavage of two C0N bonds[ By way of illustration\ some typical examples of each of these classes are given below[ The retro!DielsÐAlder cleavage of ethylene from 0\3!epoxytetrahydronaphthalenes "35# under FVP conditions has been developed into a highly e.cient synthesis of the highly reactive iso! benzofuran system "Equation "25## ð70MI 006!90Ł[ The parent compound\ which is a useful DielsÐ Alder diene\ can be accumulated in quantitative yield at a rate of 4Ð09 g h−0 from a commercially available precursor ð61CC236Ł[ FVP

O

O

650 °C

+

(36)

(46)

Cycloadducts derived from a!pyrones "e[g[\ "36## acting as dienes often lose CO1 under the conditions of their formation to generate diene products by cleavage of one C0C and one C0O bond "e[g[\ Scheme 19# ð61TL3540Ł[ When the original dienophile is an alkyne\ substituted benzene systems are obtained directly "e[g[\ ð76T4134Ł#[ O O

–CO2

150 °C

+ O

O

O

MeO2C

CO2Me

O

(47) Scheme 20

MeO2C

H

O

C1C Bond"s# by Pericyclic Processes

689

In a similar fashion to the examples in the preceding paragraph\ retro!DielsÐAlder cleavage of one C0C and one C0N bond "usually as RCN#\ or two C0N bonds "usually as N1# frequently takes place in situ following cycloaddition reactions of azines and alkynes\ leaving an alternative heteroaromatic system as the _nal product of the reaction[ Typical examples of the many possibilities are given in Scheme 10 ð62LA326\ 63LA0089Ł[ This area of heterodiene reactions has been com! prehensively reviewed ð72T1758Ł[ CO2Et

CO2Et Et2N

MeCN

N

+

N

NEt2

N

20 min 90%

CO2Me N

N

N

N

CO2Me

+

MeO2C

140 °C, 15 h

N

53%

N

CO2Me

CO2Me

CO2Me CO2Me CO2Me

Scheme 21

0[06[3[1 Retro!cheletropic Reactions Retro!cheletropic processes are applicable to the stereospeci_c formation of conjugated dienes "Equation "26##[ The extruded group "X# is most often CO\ N1 or SO1[ The cleavage of SO1 from 2!sulfolenes is of particular importance in synthesis\ and this topic has been reviewed ð82PHC0Ł[ Both the thermal extrusion of sulfur dioxide from "37# ð55JA1746\ 55JA1747Ł and of nitrogen from "38# ð55JA0224Ł have been shown to take place stereospeci_cally with disrotatory motions of the terminal methylene groups "e[g[\ Scheme 11#[ Carbon monoxide extrusion is particularly important when an aromatic product is formed ð56TL3834Ł[

SO2

(37)

X +

X

–SO2

–N2

155 °C

(48)

+

–

N N

(49) Scheme 22

The formation of butadiene derivatives by pyrolysis of 2!sulfolenes takes place readily at 099Ð 049>C in solution or in a sealed tube\ at 249>C under ~ow conditions\ or at ca[ 499>C by FVP[ The _rst conditions may be used to generate a reactive diene in situ in the presence of a dienophile\ whereas the last conditions are often more e.cient for the isolation of the diene itself[ 0!Substituted or 0\3!disubstituted butadienes can be made by alkylation of the sulfolene at its acidic a!positions prior to the pyrolysis\ although special conditions must be used to avoid the ring opening of the anion to butadienyl sul_nate[ Therefore\ nonnucleophilic bases have been used so that the anion may be generated in the presence of the alkylating agent ð75JCS"P0#0928Ł[ Alternatively\ the protection and subsequent pyrolytic "FVP# release of the sulfolene as a formal DielsÐAlder adduct has the signi_cant advantage that alkylation"s# take place exclusively on the exo!face and therefore lead to a stereospeci_c diene synthesis "Equation "27## ð71TL2166Ł[ This method has been employed exten! sively by Bloch et al[ as a route to insect sex pheromones "e[g[\ ð72TL0136\ 75T3864Ł#[ 1!Trimethyl! silylsulfolene can be used to achieve a\a!dialkylation and hence give a potential route to 0\0!disubstituted butadienes ð76CC823Ł[

680

Dienes and Polyenes FVP

R2

+ 600 °C

SO2

R2

R1

(38)

R1

Reaction of the anion derived from 2!methyl!2!sulfolene with prenyl or geranyl bromides followed by extrusion of SO1 has been reported as a stereo! and regioselective means of introducing an isoprene unit onto an existing skeleton ð73CC0212Ł[ Many functionalised 1!substituted butadienes have been obtained by pyrolysis of the corresponding 2!substituted sulfolene[ For example\ 1!trimethylsilylbuta!0\2!diene was generated by sealed!tube "059>C# pyrolysis of the appropriate sulfolene\ and underwent in situ DielsÐAlder reaction with dimethyl acetylenedicarboxylate "DMAD# ð76JOC133Ł[ In applications of sulfolene pyrolysis to alkaloid synthesis\ the butadiene released is often in place to undergo an intramolecular DielsÐAlder reaction and hence create a new six!membered ring[ Two examples are given in Scheme 12 ð79JOC2261\ 83TL0960Ł^ in the _rst of these\ the heteroene component was also generated by a pyrolytic method[ O TMS-O

O-TMS

N H SO2

390 °C

N

O

OAc

H N N

110 °C

O N MeO C 2 H

SO2

3.5 h 79%

O N

H

CO2Me

H (E):(Z) 4:1 Scheme 23

Pyrolysis of 1\6!dihydrothiepin!0\0!dioxides "49# leads to 0\2\4!trienes by an analogous concerted process ð58JA4571Ł[

SO2 (50)

Copyright

#

1995, Elsevier Ltd. All R ights Reserved

Comprehensive Organic Functional Group Transformations