A novel L-neopentylglycine derivative as auxiliary for copper-catalyzed asymmetric Michael reactions

L-Neopentylglycine diethylamide (4a) was prepared from the new unnatural amino acid L-neopentylglycine (1). The utilization of amide 4a as a chiral auxiliary in the copper(II)-catalyzed asymmetric Michael reaction was investigated in comparison with L-valine diethylamide (4b). Cyclic beta-oxocarboxylates 7 react with 4a and 4b to give the respective enaminoesters 8, which were converted with methyl vinyl ketone (9) in the presence of 10 mol% Cu(OAc)(2) (.) H2O at room temperature in acetone to yield the optically active Michael addition products (R)-10a, b with high selectivity independent of the starting enamine. In the case of the seven-membered beta-oxocarboxylate 7c, however, the valine-derived enamine 8f led to higher enantioselectivity for product 10c. Despite the bulkiness of the neopentyl group, the isopropyl group with an a-branch has a better stereoinducing effect. (C) 2003 Wiley-Liss, Inc.