The first catalytic highly enantioselective alkylation of ketimines--a novel approach to optically active quaternary alpha-amino acids.

A series of novel ketimines with intrinsic protecting group anchoring was synthesized and allowed to react with various silylketene acetals in the presence of 5-10 mol % of a chiral Zn(OTf)(2)-(R,R)-Ph-pybox-aqua complex. The corresponding optically active quaternary alpha-amino acid derivatives were obtained in high yields and with enantioselectivities ranging from 34 % up to 95 % ee. The catalyst was studied by (1)H NMR spectroscopy and X-ray crystallography, and a dynamic equilibrium of two species was identified in solution. These are a homo-chiral 1:2 metal-ligand complex and a 1:1 metal-ligand complex, of which the latter is expected to be the actual catalyst of the diastereo- and enantioselective reaction. A strong positive nonlinear effect was observed due to the formation of a catalytically inactive 1:2 metal-ligand hetero-chiral complex. On the basis of DFT calculations and the absolute stereochemistry of the products, simultaneous coordination of the imino electrophile and a single molecule of H(2)O to the chiral Lewis acid complex is proposed. Coordination of the imine-nitrogen atom in the axial position of an octahedral complex can account for the facial selectivity as well as the diastereoselectivity observed.