Stereoselectivity Shapiro reaction

The advantage of the Shapiro over Bamford-Stevens Reaction is, that the resulting dianion does not tend to rearrange, which can occur with intermediate carbenes and carbenium ions. However, the Shapiro reaction does not lead to high stereoselectivity between the -/Z-isomers. 

Geometrical stereoselectivity can often be achieved in the condensation of unsymmetrical ketones 8 with tosylhydrazine l,2 and this feature means Shapiro reactions direct from an unsymmetrical ketone 8 via E-9 lead to the less substituted vinyllithium 11. On the other hand, a sequential alkylation-Shapiro sequence from a starting symmetrical hydrazone 12 will reliably form the more substituted vinyllithium 14 via Z-9 Retention of Z stereochemistry in Z-9 is dependent on its re-use almost immediately on standing, for example, Z-9 (R = vinyl) equilibrates to an 85 15 ratio E Z-9J ... 

Usable vinyllithiums are obtained if (a) ortholithiation-resistant hydrazones derived from triisopropylphenylsulfonylhydrazine 15 are used,9 and (b) if the Shapiro reaction is carried out in a TMEDA-hexane mixture, which avoids protonation of the vinyllithium.10 For example, 16 forms stereoselectively from 15, with steric hindrance directing formation of the E hydrazone. The dianion of 16 decomposes at 0 °C to yield the vinyllithium 17 which reacts with electrophiles to yield products such as 18.11... 

The application of the aliphatic Friedel-Crafts reaction (chapter 5) to alkynes is a stereoselective approach to vinyl-lithiums that forms a bridge between the Shapiro reaction and the next section-hydrometallation. Acid chlorides 64 react with alkynes under Lewis acid catalysis to give E-P-chloroenones -65 stereoselectively. The chlorine can be replaced by more reactive iodine by conjugate substitution.11... 

As noted above, the classical Shapiro reaction requires the use of >2 equiv of base to effect the conversion of an arylsulfonylhydrazone to an alkene. However, in recent work Yamamoto has described a catalytic version of the Shapiro reaction that employs aziridinyl hydrazones and is effective with only 5-30 mol% of added base.21 As shown above, treatment of hydrazone 34 with 5 mol% of LDA affords a 93% isolated yield of 35 with >99 1 stereoselectivity. This reaction is believed to proceed via metalation of 34 with LDA to yield 36. This intermediate decomposes with loss of styrene and nitrogen to provide vinyllithium reagent 37, which is protonated by diisopropylamine, regenerating the LDA base. Unfortunately this method is not amenable to the capture of the intermediate vinyllithium species with electrophiles. 

A Shapiro reaction reduces the ketone 74 into the allylic alcohol 75. After Jones oxidation, the y-lactone 76 is alkylated stereoselectively at Cll to give the target molecule 65. 

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. 

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