Direct asymmetric reductive amination.
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.
Steinhuebel
Dietrich
D
Department of Process Research, Merck & Co., Inc., P.O. Box 2000, Rahway, New Jersey 07065, USA. dietrich_steinhuebel@merck.com
Sun
Yongkui
Y
Matsumura
Kazuhiko
K
Sayo
Noboru
N
Saito
Takao
T
D000577:Amides / Q000737:chemistry*; D000586:Amination; D002384:Catalysis; D015394:Molecular Structure; D010084:Oxidation-Reduction; D017975:Ruthenium Compounds / Q000737:chemistry*; D013237:Stereoisomerism
D000577:Amides; D017975:Ruthenium Compounds