STEREOCHEMICAL ASPECTS IN THE ASYMMETRIC MICHAEL ADDITION OF CHIRAL IMINES TO SUBSTITUTED ELECTROPHILIC ALKENES

The Michael-type addition of chiral imines, derived from racemic alpha -substituted cyclanones and optically active 1-phenylethylamine, to el ectrophilic alkenes, in neutral conditions, constitutes one of the mos t efficient methods for the stereocontrolled construction of quaternar y carbon centers. In order to create an additional stereogenic center at the alpha- or beta-position to the quaternary one, the behavior of a variety of alpha and beta-substituted alkenyl accepters was examined . In general, these additions are highly regioselective, the alkylatio n taking place predominantly, if not exclusively, at the more substitu ted alpha-side of the imine function; however, in some cases (electrop hilic alkenes 28 and 49), significant amounts (10-15%) of regioisomeri c adducts were obtained. With the exception of methyl propiolate 52, a remarkable control of the absolute configuration of the adducts were always observed with these Michael accepters. According to the general rule we have previously proposed, the alkylation process takes place preferentially on the less hindered pi-face of the more substituted se condary enamine, in tautomeric equilibrium with the starting imine. An excellent diastereocontrol was always obtained by using the present a lpha and beta-substituted alkenes. These stereochemical outcomes can b e interpreted by invoking that the reaction proceeds through a compact approach of the reactants, the hydrogen atom at the nitrogen center o f the enamine being transferred to the alpha-vinylic carbon atom of th e acceptor, concertedly with the creation of the C-C bond. In this res pect the ''endo-approach'' 58, in which the electron-withdrawing group of the acceptor faced to the nitrogen atom of the enamine (case of ac cepters 10, methyl methacrylate, 24, 28, 43, 47, and 49) largely preva ils over the ''exo-approach'' 59 (case of acceptor 38). This predomina nt ''endo-preference'' can be reasonably interpreted in terms of a coo perative effect between steric and stereoelectronic factors.