Enantioselective addition of diethylzinc to aldehydes catalyzed by chiral amino alcohols. Substituent effect and nonlinear effect

A new series of chiral β-amino alcohols derived from (S)-leucine, valine, and phenylalanine have been synthesized and evaluated as chiral catalysts for the enantioselective addition of diethylzinc to aldehydes. The β-amino alcohol (1c) possessing a isobutyl substituent and two phenethyl substituents on the carbinol carbon atom was found to be an efficient and optimal ligand to catalyze the diethylzinc addition with high enantioselectivity (up to 97% ee) and good yield. Furthermore, a strong (+)-nonlinear effect (asymmetric amplification) was observed in the enantioselective catalysis, providing high level of enantioselection (93% ee) by use of ligand 1c in 20% ee.