Asymmetric Grignard Synthesis of Tertiary Alcohols through Rational Ligand Design

Abstract

A simple, general and practical method is reported for highly enantioselective construction of tertiary alcohols through the direct addition of organomagnesium reagents to ketones. Discovered by rational ligand design based on a mechanistic hypothesis, it has an unprecedented broad scope. It utilizes a new type of chiral tridentate diamine/phenol ligand that is easily removed from the reaction mixture. It is exemplified by application to a formal asymmetric synthesis (>95:5 d.r.) of vitamin E.

Keywords: Grignard synthesis; asymmetric synthesis; tertiary alcohols; tridentate ligands; vitamin E.