A Novel, Highly Enantioselective Ketone Alkynylation Reaction Mediated by Chiral Zinc Aminoalkoxides

Abstract
Kilogram-scale synthesis of the HIV reverse transcriptase inhibitor efavirenz was achieved by means of a highly enantioselective alkynylation of prochiral ketones 1 with alkynyllithium or alkynylmagnesium reagents in the presence of chiral zinc aminoalkoxides as mediators. With the achiral auxiliary 2,2,2-trifluoroethanol (R3=CF3CH2), the efavirenz precursor 2 (R1=H, R2=cyclopropyl) was obtained with an ee of 99.2%.

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