title: Catalytic asymmetric synthesis of an HIV integrase inhibitor.
abstract: An efficient synthesis of HIV integrase inhibitor (S)-(-)-1 via a unique asymmetric hydrogenation of a mixture of imines/enamine 5a-5b/5c is described. Hydrogenation of the imines/enamine by a Rh(I)-Josiphos complex afforded 6 in 90% yield and 90% ee. Amide formation completed the synthesis of 1 in 58% overall yield from 2, which is readily available from 3,4-dihydro-2H-pyran in a seven-step sequence. A deuterium labeling study suggests the asymmetric hydrogenation proceeds predominantly via the enamine tautomer.
authors.affiliation: Department of Process Research, Merck Research Laboratories, P.O. Box 2000, Rahway, New Jersey 07065, USA.
authors.forename: Yong-Li
authors.initials: YL
authors.lastname: Zhong
authors.forename: Shane W
authors.initials: SW
authors.lastname: Krska
authors.forename: Hua
authors.initials: H
authors.lastname: Zhou
authors.forename: Robert A
authors.initials: RA
authors.lastname: Reamer
authors.forename: Jaemoon
authors.initials: J
authors.lastname: Lee
authors.forename: Yongkui
authors.initials: Y
authors.lastname: Sun
authors.forename: David
authors.initials: D
authors.lastname: Askin
mesh_terms: D000588:Amines / Q000737:chemistry; D002384:Catalysis; D019427:HIV Integrase; D019428:HIV Integrase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D006865:Hydrogenation; D007097:Imines / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D000588:Amines; D019428:HIV Integrase Inhibitors; D007097:Imines; D019427:HIV Integrase