Pierce, ME; Parsons, RL; Radesca, LA; Lo, YS; Silverman, S; Moore, JR; Islam, Q; Choudhury, A; Fortunak, JMD; Nguyen, D; Luo, C; Morgan, SJ; Davis, WP; Confalone, PN; Chen, CY; Tillyer, RD; Frey, L; Tan, LS; Xu, F; Zhao, DL; Thompson, AS; Corley, EG; Grabowski, EJJ; Reamer, R; Reider, PJ
A highly enantioselective and practical synthesis of the HIV-1 reverse transcriptase inhibitor efavirenz (1) is described. The synthesis proceeds 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) to p-methoxybenzyl-protected ketoaniline 3a mediated by (1R,2S)-N-pyrrolidinylnorephedrine lithium alkoxide (5a) establishes the stereogenic center in the target with a remarkable level of stereocontrol.