DOUBLE ASYMMETRIC-SYNTHESIS BY ASYMMETRIC CATALYTIC CARBONYL-ENE TYPEREACTION WITH CHIRAL ENE COMPONENTS - ASYMMETRIC CATALYTIC SYNTHESIS OF ASPARTYL DIPEPTIDE SWEETENER

Double asymmetric induction is described in the carbonylene type react ion of glyoxylate (2) with chiral ene components, (-)-beta-pinene (3a) or (+)-alpha-fenchene (3b), catalyzed by chiral titanium complex (1) derived from optically pure binaphthol (BINOL) and (i-PrO)(2)TiCl2. By (S)-BINOL-Ti catalyst (1) and (-)-beta-pinene (3a), the usual ene pat hway is favored to provide the homoallylic alcohol products (4a) in ex tremely high levels of 11S selectivity. By (R)-BINOL-Ti catalyst (1), however, the Friedel-Crafts type reaction leading to the allylic alcoh ols (4b) becomes favorable to exhibit high levels of 11R selectivity. By contrast, in double asymmetric reaction with (+)-alpha-fenchene (3b ), (5)- and (R)-BINOL-Ti (1) catalysts provide mainly the allylic alco hol products (5b) in extremely high levels of 11S and 11R selectivity, respectively, The (11R)-allylic alcohol 5b thus obtained is converted to the alpha-amino ester (6), the key intermediate of aspartyl dipept ide sweeteners, via double asymmetric hydrogenation catalyzed by chira l BINAP-Ru complex. The effective mutual kinetic resolution of (Z)- an d (E)-mixture 5b is attained by the racemic mixture of (5)- and (R)-BI NAP-Ru catalyst to provide exo-8 in high stereoselectivity.