The first catalytic highly enantioselective alkylation of Ketimines-A Novel approach to Optically Active Quaternary alpha-Amino Acids

摘要

A series of novel ketimines with intrinsic protecting group anchoring was synthesized and alowed 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 rangeing from 34% up to 95% ee.The catalyst was studied by ~1h NMR spectroscopy and X-ray crystallography,and a dynamic equilibrium of two species was identified in solutions.These are a homochiral 1:2 methal-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,simulataneous coordination of the imino electrophile and a single molecule of H_2O 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.