Diastereoselectivity and mechanism of conjugate addition of organocuprates to γ-chiral acyclic enones and enoates

Abstract

Systematic studies of organocuprate conjugate additions to γ-chiral acyclic enones and enoates, which have two alkyl substituents at γ-position, led us to generalize diastereofacial selectivity of these reactions. The diastereoselectivity depended on the double-bond geometry, the configuration at the γ -position, and the reaction conditions. In reactions without activating additives, cuprate added to the same face of isomeric E- and Z-enones with high diastereoselectivity. Addition of TMSCI together with HMPA not only accelerated the addition reaction but also completely changed the pattern of π-facial selectivity. In reactions containing those additives, cuprates added to isomeric E- and Z-enones with reverse facial selectivity. Under the latter conditions, even the enoates reacted efficiently with similarly reverse and high facial selectivity. On the basis of these results, we postulated a general rule to predict diastereofacial selectivity of cuprate conjugate additions to γ-alkyl compounds. This rule was demonstrated to be applicable to other γ-chiral compounds with γ-alkoxy, γ-phenyl, or γ-ureido substituent.