Catalytic enantioselective organozinc addition toward optically active tertiary alcohol synthesis

Abstract

A highly enantioselective organozinc (R2Zn) addition to a series of aldehydes and ketones was developed based on conjugate Lewis acid-Lewis base catalysis. Optically active secondary and tertiary alcohols were obtained in high yields with high enantioselectivities without Ti(IV) compounds. Bifunctional chiral 3,3'-diphosphoryl-BINOL ligands were designed and prepared through a phospho-Fries rearrangement as a key step. On the other hand, bifunctional chiral phosphoramide ligands were designed and prepared from L-valine. Mechanistic studies were performed by X-ray analyses of Zn(II) cluster and chiral ligands, a 31P NMR experiment on Zn(II) complexes, and stoichiometric reactions with some chiral or achiral Zn(II) complexes to propose a transition state assembly that includes monomeric active intermediates.