Stereochemical and Mechanistic Studies on Conjugate Addition of Organocuprates to Acyclic Enones and Enoates: Simple Rule for Diastereofacial Selectivity

Abstract

Systematic studies of organocuprate conjugate additions to three pairs of γ-epimeric and geometrically isomeric γ-chiral acyclic enones (1a, 2a; 1b, 2b; and 3, 4) and two pairs of γ-chiral acyclic enoates (5, 6 and 7, 8) allowed 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 si-face of the geometrically isomeric pair of E- and Z-enones (1a and 2a) with high diastereoselectivity (98%), while their epimers at the γ-position (3 and 4) yielded re-facial adduct preferentially (86−97%). Addition of TMSCl and HMPA together 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: E-enone 1a gave the si-facial adduct exclusively, whereas isomeric Z-enone 2a yielded the re-facial adduct with high selectivity (97%). Their γ-epimers gave opposite results; namely, the E-isomer 3 reacted with re-facial selectivity (97%), while the Z-isomer 4 reacted with si-facial selectivity (75%). Under conditions where both TMSCl and HMPA were present, even the enoates (5−8) reacted efficiently with similarly reverse and high facial selectivity. On the basis of these results, we postulate a general and clear-cut rule to predict diastereofacial selectivity of cuprate conjugate additions in which a possibility of Z−E isomerization of starting enones is taken into account as a crucial determinant.