PRACTICAL ASYMMETRIC-SYNTHESIS OF EFAVIRENZ (DMP-266), AN HIV-1 REVERSE-TRANSCRIPTASE INHIBITOR

A highly enantioselective and practical synthesis of the HIV-1 reverse transcriptase inhibitor efavirenz (1) is described. The synthesis pro ceeds in 62% overall yield in seven steps from 4-chloroaniline (6) to give efavirenz (1) in excellent chemical and optical purity. A novel, enantioselective addition of Li-cyclopropyl acetylide (4a) top-methoxy benzyl-protected ketoaniline 3a mediated by (1R,2S)-N-pyrrolidinylnore phedrine lithium alkoxide (5a) establishes the stereogenic center in t he target with a remarkable level of stereocontrol.