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 a-bromo enone prepared from 2,3-dimethylquinone.