Diastereoselective Reductive Amination of Aryl Trifluoromethyl Ketones and α-Amino Esters

• Published in: Angewandte Chemie (International ed.) Vol. 46; no. 11; pp. 1839 - 1842
• Main Authors: Hughes, Greg, Devine, Paul N., Naber, John R., O'Shea, Paul D., Foster, Bruce S., McKay, Daniel J., Volante, R. P.
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 01.01.2007; WILEY‐VCH Verlag; Wiley
• Subjects: Aluminum Compounds; amines; Amines - chemistry; amino acids; Amino Acids - chemistry; Chemistry; Chemistry, Multidisciplinary; Chromatography, High Pressure Liquid; diastereoselectivity; Esters - chemical synthesis; fluorine; Indicators and Reagents; Ketones - chemistry; Lithium Compounds; Magnetic Resonance Spectroscopy; Models, Molecular; Oxidation-Reduction; Physical Sciences; reduction; Science & Technology; Stereoisomerism; PARTIALLY-MODIFIED RETRO; ASYMMETRIC-SYNTHESIS; REAGENTS; ACIDS; RETENTION; IMINES; amino acids; amines; diastereoselectivity; STEREOSELECTIVE SYNTHESIS; CHIRAL FLUOROORGANIC COMPOUNDS; ALCOHOLS; CATHEPSIN-K; reduction; fluorine
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.200603745

Reductionist art: Careful choice of the reducing agent in the reductive amination of trifluoromethyl ketones with α‐amino esters allows stereoselective access, from the imine formed, to either the R,S or S,S diastereomers of the resulting amino acids. Whereas NaBH4 affords the R,S diastereomers, Zn(BH4)2 affords the S,S diastereomers (see scheme), which can be easily converted into potent cathepsin K inhibitors.