Total synthesis of (R,R,R)-γ-tocopherol through Cu-catalyzed asymmetric 1,2-addition

Abstract

Based on the asymmetric copper-catalyzed 1,2-addition of Grignard reagents to ketones, (R,R,R)-γ-tocopherol has been synthesized in 36 % yield over 12 steps (longest linear sequence). The chiral center in the chroman ring was constructed with 73 % ee by the 1,2-addition of a phytol-derived Grignard reagent to an α-bromo enone prepared from 2,3-dimethylquinone.

Keywords: (R,R,R)-γ-tocopherol; 1,2-addition; asymmetric catalysis; natural product synthesis; vitamin E.