Total Synthesis of (R, R, R)-γ-Tocopherol through Cu-Catalyzed Asymmetric 1,2-Addition

Based on the asymmetric copper-catalyzed 1,2-addition of Grignard reagents to ketones, (R,R,R)--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 -bromo enone prepared from 2,3-dimethylquinone.