title: Direct asymmetric reductive amination.
abstract: Asymmetric reductive amination of beta-keto amides catalyzed by the chiral catalyst Ru(OAc)(2)((R)-dm-segphos) produces unprotected beta-amino amides with high yields and high enantioselectivities (94.7-99.5% ee). This "one-pot" methodology is general in substrate scope and has been successfully employed to produce sitagliptin with 99.5% ee and 91% assay yield. The excellent reaction efficiency is attributed to the remarkable tolerance to high concentrations of ammonium ion, the high chemoselectivity, and the high enantioselectivity (99.5% ee) of the Ru catalyst system.
authors.affiliation: Department of Process Research, Merck & Co., Inc., P.O. Box 2000, Rahway, New Jersey 07065, USA. dietrich_steinhuebel@merck.com
authors.forename: Dietrich
authors.initials: D
authors.lastname: Steinhuebel
authors.forename: Yongkui
authors.initials: Y
authors.lastname: Sun
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Matsumura
authors.forename: Noboru
authors.initials: N
authors.lastname: Sayo
authors.forename: Takao
authors.initials: T
authors.lastname: Saito
mesh_terms: D000577:Amides / Q000737:chemistry*; D000586:Amination; D002384:Catalysis; D015394:Molecular Structure; D010084:Oxidation-Reduction; D017975:Ruthenium Compounds / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D000577:Amides; D017975:Ruthenium Compounds