Vinyllithiums cyclization

Vinyllithium cyclizations. The vinyl lithiums formed from trisylhydrazones (9, 486) can participate in intramolecular cyclizations. This anionic cyclization is presently limited to formation of five-membered rings. It has the advantage of greater stereoselectivity than a corresponding radical cyclization. 

Tius and co-workers elegantly applied a variant of the Nazarov reaction to the preparation of cyclopentenone prostaglandins (Scheme 19.39) [46]. Moreover, it was demonstrated that the chirality of non-racemic allenes is transferred to an sp3-hybridized carbon atom. Preparation of allenic morpholinoamide 214 and resolution of the enantiomers by chiral HPLC provided (-)- and (+)-214. Compound (-)-214 was exposed to the vinyllithium species 215 to afford a presumed intermediate which was not observed but spontaneously cyclized to give (+)- and (—)-216 as a 5 1 mixture. Compound (+)-216 was obtained with an 84% transfer of chiral information and (-)-216 was obtained in 64% ee. The lower enantiomeric excess of (—)-216 indicates that some Z to E isomerization took place. This was validated by the conversion of 216 to 217, where the absolute configuration was established. The stereochemical outcome of this reaction has been explained by conrotatory cyclization of 218 in which the distal group on the allene rotates away from the alkene to give 216. 

The Shapiro reaction provides a convenient, easy and straightforward method to convert ketones into a plethora of olefinic substances in high yields. Many of these vinyllithium derivatives are useful for further synthetic manipulations. No attempt is made in this chapter to cover all the applications of the Shapiro reaction and only few representative examples will be described. A variety of polyolefins such as 119, used for cation olefin cyclization, can be stereospecifically formed in a concise and modular approach in a single step from the components shown in equation 42 via the Shapiro reaction . 

Treatment of functionalized vinyllithium, 28, with allylmaghesium bromide in the presence of zinc bromide leads to a stereoselectively substituted, metallated cyclopropane, 29, via a tandem metalla-Claisen-cyclization reaction (equation 48 )M. The produced cyclo-... 

Although the chemistry of anionic cyclizations of organolithium moieties derived from acetylenic systems has been less investigated38, studies of some acetylenic alkyllithiums, e.g. 131 (formed from 130), have shown that the ring closure proceeds in a regiospecific and highly stereoselective syw-fashion to give exocyclic vinyllithiums 132 (Scheme 43). 

The exocyclic vinyllithium (132, R = H) produced by cyclization of a 5-hexynyllithium could be trapped by reaction with electrophiles to deliver synthetically useful functionalized derivatives, e.g. 133, in good to excellent isolated yields (60-90%). The stereochemical requirements for the preferred 5-exo ring closures of 5-hexynyllithium are in agreement with a chair-like transition state complex. 

By simple incorporation of a leaving group at the distal propargylic position of the acetylenic vinyllithium, the cyclization methodology described was slightly modified to allow preparation of otherwise relatively inaccessible exocyclic, conjugated allenenes (s-annulated 1,2,4-trienes)108. Thus, the vinyllithium 142 generated from bromide 141 cyclizes via 143 to afford the five-membered exocyclic allenene 144 in 97% isolated yield (Scheme 46). 

The cascade sequence that affords bicyclic systems fails with the lithium derivatives of 2-bromo-iV,iV-diallylaniline. The methodology is useful for the synthesis of 3-substituted indolines and indoles, but the substrate undergoes only one anionic cyclization. Alkenyl vinyllithiums and alkenyl aryllithiums have also been employed in the preparation of alkylidenecyclopentanes and indanes. The intramolecular addition of vinyllithium reagents... 

B. Cyclization Reaction of Heteroatom-substituted Olefinic Vinyllithiums... 

C. Cyclization Reaction of Acetylenic Allenyl Lithiums, Vinyllithiums and... 

The first vinyllithium carbolithiation reaction was reported by Chamberlin and Bloom15, who showed that Shapiro-derived organolithium 10 cyclized onto a terminal alkene giving stereoselectively (>50 1) bicyclic compounds 11, after treatment with electrophiles (Scheme 4). The intermediate alkyllithiums 12 are generated via a 5-exo-trig cyclization reaction from 10, which undergo the carbolithiation reaction at approximately the same rate as reported by Bailey for the simple parent compound 5-hexenylIithium, i.e. with a half-life of a few minutes at 0 °C. 

The kinetics of the cyclization reaction of 5-hexynyllithiums 19 was also studied showing that (6-phenyl-5-hexynyl)lithium (19, R = Ph) has a half-life of ca 6 min at —50.6 °C, whereas cyclization reaction of 5-decynyllithium (19, R = Bu) is some 106 times slower. The rather dramatic increase in the rate of cyclization on going from an alkyl-substituted 5-hexyn-l-yllithium to a phenyl-substituted substrate is most likely a consequence of a reduction in A// due to stabilization of the incipient vinyllithium product by the phenyl group19. It is also interesting to note that the 5-exo-dig cyclization reaction of 19 (R = Bu) is slower than the corresponding 5-exo-trig carbolithiation reaction of 5-hexenyllithium. 

Although an energetically less favourable sp2 to sp3 carbanion transformation is involved in these processes, both aryllithium and vinyllithium cyclizations onto alkenes are successful. Moreover, cyclization reactions of vinyllithiums, rather than alkyllithiums, would also incorporate additional functionality (an alkene) into the product, allowing the preparation of alkylidenecycloalkanes with control of the alkene stereochemistry. 

In this context we have recently reported that A-2-bromoallyl-iV-(3-functionalized) allylamines 315 undergo, after formation of the corresponding vinyllithiums, intramolecular carbolithiation processes giving rise to functionalized methylenepyrrolidines 316 in good yields. We have shown that a moderately activating group at the terminal position of the double bond favours the cyclization reaction and we have presented the first... 

On the other hand, the cyclization reaction of a vinyllithium onto an acetylenic unit provides an efficient route to five- and six-membered bis-exocyclic 1,3-dienes, which react stereoselectively with a wide range of dienophiles157. The 5-exo carbolithiation reaction of vinyllithiums 369, derived from the corresponding vinyl bromides, is syw-stereospecific giving, after hydrolysis, the /(-isomer of five-membered outer-ring dienes 370 and tolerates aryl-, silyl- or alkyl-substituents at the distal acetylenic carbon (Scheme 97). However, the alkyl-substituted alkynes are far more resistant to rearrangement than the aryl- or silyl-substrates and the addition of TMEDA and longer reaction times are needed for the latter... 

A complementary approach, developed by Paquette, - uses substituted acryloyl chlorides as addends in reaction with structii ly embellished vinylsilanes. A general route to the vinylsilanes (87) was found in the silylation of vinyllithiums generated by the Shapiro reaction.The acylation with acryloyl chlorides takes place readily with aluminum trichloride to afford the divinyl ketones which are subsequently cyclized with tin tetrachloride. The Nazarov cyclization products were formed as a mixture of double tend isomers (equation 47). The best results were obtained with p,p-dimethylacryloyl chloride. Crotonyl chloride could be employed, but acryloyl chloride proved impractical. This metl owes much of its utility to the regiocontroUed synthesis of Ae vinylsilmes, thereby clearly establishing the loci of cyclopentannulation. 

The cyclization of a 4-substituted-5-hexenyllithium proceeds also by a 5> n-addition of the CHj-Li moiety to the triple bond (Scheme 7-11). By contrast, vinyllithium compounds bearing aryl or silyl substituents on the lithiated sp carbon are known to undergo facile cis-trans isomerization [15]. 

The formation of products derived from a formally cmti addition in the 6-exo-dig cyclization is seen as a consequence of equilibrium of an initially formed Z-vinyllithium to the E-isomer under the conditions of the cyclization reaction [15]. 

Five-menibered ring synthesis via cyclization of vinyllithium derivatives... 

The title transfonnation involves a much less energetically favorable sp to sp- conversion in addition to the favorable n to a-bond conversion. However, the vinyllithium species 78 underwent cyclization to 79 at approximately the same rate as reported by Bailey [13] for the sp organolithium derivative, with a half-life of a few minutes at 0 °C [77] (Scheme 7-70). Here again, the diastereoselectivity of this carbocyclization was investigated in detail... 

An extension of this intramolecular carbolithiation was recently disclosed for the preparation of bis-exocyclic 1,3-dienes by the 5-exo-dig cyclization of (5-acetylenic vinyllithiums. Through subsequent Diels-Alder chemistry, they serve as useful precursors of polycyclic ring systems [14a] (Scheme 7-13). 

Vinyllithiums have been shown to undergo also an efficient anionic 6-exo-dig cyclization to form a bis-exocyclic 1,3-diene in good yield [24] (Scheme 7-25). 

Sulfide has also been involved in a new two-step annulation method which featured stereospecific formation of three contiguous asymmetric centers. It was found that the lithium dienolate of the vinyl-ogous ester (6a) reacts rapidly with the a-thiophenyl butenolide (6b) to provide the corresponding adduct as a single diastereoisomer. Subsequent addition of vinyllithium, acidification and cyclization gave the tricyclic lactone (Scheme 30). 

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