Regiochemistry Shapiro reaction

The Shapiro reaction has been particularly useful for cyclic ketones, but the scope of the reaction also includes acyclic systems. In the case of unsymmetrical acyclic ketones, questions of both regiochemistry and stereochemistry arise. 1-Octene is the exclusive product from 2-octanone.207... 

It appears that the lithiation site is determined by the geometry of the C=N bond. When a second (third ) lithiation is induced, it occurs on the same side as the first - and this is now the more crowded side 46. The regiochemistry is determined by the C=N bond but the stereochemistry remains as before. When the Shapiro reaction is allowed to go to completion, by warming to 0 °C, the unsymmetrical Z-vinyl lithium Z-47 is produced. This is the isomer that cannot be made by the Shapiro reaction from the methyl ketone 48. 

In most cases the regiochemistry of the Shapiro reaction is controlled by steric factors, with the second metalation occurring at the less-substituted a-carbon atom of the hydrazone.2 For example, a-methyl ketone 10 was transformed to disubstituted alkene 11 in 69% yield as a single regioisomer via conversion to a tosylhydrazone followed by treatment with -BuLi. However, the regiochemical outcome of Shapiro reactions involving a,p-unsaturated hydrazones is difficult to predict in the absence of data obtained from reactions of structurally related substrates, as the second metalation can occur at either the a - or y-position. 

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