EFFICIENT CATALYTIC ENANTIOSELECTIVE REACTION OF A GLYCINE CATION EQUIVALENT WITH MALONATE ANIONS VIA PALLADIUM CATALYSIS

The enantioselective alkylation of Schiff base acetates 1 with malonat e types of stabilized carbon nucleophiles in the presence of a stable palladium source Pd(OAc)(2) and the chiral ligand (+)-BINAP was develo ped. The product 2, a protected beta-carboxyaspartic acid (ASA), was o btained in up to 85% enantiomeric excess by varying the ester protecti ng group on the substrate. The nature of the nucleophile has a signifi cant effect on the enantioselectivity in this (2-aza-pi-allyl)palladiu m system. While a rapid chemical conversion was achieved with Schiff b ase benzoates 5, the enantioselectivity was insensitive to the leaving group used. An optically active substrate (51% ee) gave the same leve l of enantioselectivity as that obtained from the racemate. Temperatur e effects on the reaction were also studied; the best selectivity was obtained at 0 degrees C. A laboratory-scale reaction of the reactive n ucleophile KCH(COOCH3)(2) with the tert-butyl ester substrate 1c gave, following a single recrystallization, product 2c with 95.5% ee in an overall chemical yield of 62%.