Synthesis of Efavirenz

Significance

Efavirenz is a reverse transcriptase inhibitor that is used in the treatment of HIV. A ­salient feature of the Merck synthesis of efavirenz (route A) is the asymmetric alkynylation of the ­ketone A mediated by the chiral chaperone C, which provides the adduct E in 95% yield and er > 99:1 (C. Y. Chen, R. D. Richard, L. Tan WO9851676, 1998, example 11). Carreira and co-workers have shown that the mol ratio of the chiral chaperone C could be reduced from 1.5 equivalents (route A) to 0.3 (route B) by spiking the reaction with 0.18 equivalent of the enantiopure product E at the ­outset.