STEREOCHEMICAL AND MECHANISTIC STUDIES ON CONJUGATE ADDITION OF ORGANOCUPRATES TO ACYCLIC ENONES AND ENOATES - SIMPLE RULE FOR DIASTEREOFACIAL SELECTIVITY

Systematic studies of organocuprate conjugate additions to three pairs of gamma-epimeric and geometrically isomeric gamma-chiral acyclic eno nes (1a, 2a; 1b, 2b; and 3, 4) and two pairs of gamma-chiral acyclic e noates (5, 6 and 7, 8) allowed us to generalize diastereofacial select ivity of these reactions. The diastereoselectivity depended on the dou ble-bond geometry, the configuration at the gamma-position, and the re action conditions. In reactions without activating additives, cuprate added to the si-face of the geometrically isomeric pair of E- and Z-en ones (1a and 2a) with high diastereoselectivity (98%), while their epi mers at the gamma-position (3 and 4) yielded re-facial adduct preferen tially (86-97%). Addition of TMSC1 and HMPA together not only accelera ted the addition reaction but also completely changed the pattern of p i-facial selectivity. In reactions containing those additives, cuprate s added to isomeric E- and Z-enones with reverse facial selectivity: E -enone la gave the si-facial adduct exclusively, whereas isomeric Z-en one 2a yielded the re-facial adduct with high selectivity(97%). Their gamma-epimers gave opposite results; namely, the E-isomer 3 reacted wi th re-facial selectivity (97%), while the Z-isomer 4 reacted with si-f acial selectivity (75%).;Under conditions where both TMSC1 and HMPA we re 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 sel ectivity of cuprate conjugate additions in which a possibility of Z-E isomerization of starting enones is taken into account as a crucial de terminant.