Cyanoethylations and Michael additions. V. The synthesis of allylic cyclohexenols by γ-cyanoethylation of α,β-unsaturated aldehydes and ketones. Part V

It is shown that the cyanoethylation of 3β-acetoxy-21-methyl-5α-pregn-17-en-21-one results in part in the addition of acrylonitrile to the γ-position, with concomitant cyclization, and that therefore the cyclo-γ-cyanoethylations of α,β-unsaturated carbonyl compounds reported previously were not confined to aldehydes. However, the main reaction products of the conjugated ketone were α-cyanoethylated derivatives. A variation of the reaction time did not affect the proportion of α- and γ-cyanoethylated products; the implications of this finding on mechanistic considerations are discussed; in particular, an explanation based on the assumption of an equilibrium between reactants and α- and γ-cyanoethylated products is ruled out. It is shown that the γ-additions observed, particularly in the case of α,β-unsaturated aldehydes, are not due to steric hindrance, neither to an abnormal charge distribution in the anion. It is further shown that in the presence of base the propionitrile moiety of oxygen-cyanoethylated α,β-unsaturated aldehydes with a suitable geometry is transferred to the γ-position of the original aldehyde and that cyclization occurs so that the same products are obtained from such cyano-enol ethers as in the direct cyanoethylation of the free aldehydes. On the basis of this finding, a mechanism for the cyclo-γ-cyanoethylations of α,β-unsaturated carbonyl compounds, involving such a transfer reaction, can be tentatively proposed.