title: Unprecedented catalytic asymmetric reduction of N-H imines.
abstract: [Reaction: see text] Addition of lithium bis(trimethylsilyl)amide to perfluorinated ketones 1a-j affords (E)-N-TMS-ketimines 2a-j that are reduced in situ to afford racemic perfluoromethylated amine hydrochloride salts 3a-j in 54-97% yields. Solvolysis of the N-Si bond in MeOH leads to formation of bench-stable, isolable N-H imine Z/E isomer mixtures along with a methanol adduct. Enantioselective reduction of these three-component mixtures provides the first catalytic asymmetric synthesis of trifluoromethylated amines in 72-95% yields and 75-98% ee.
authors.affiliation: Department of Process Research, Merck Frosst Centre for Therapeutic Research, 16711 route transcanadienne, Kirkland, Québec, Canada. francis_gosselin@merck.com
authors.forename: Francis
authors.initials: F
authors.lastname: Gosselin
authors.forename: Paul D
authors.initials: PD
authors.lastname: O'Shea
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Roy
authors.forename: Robert A
authors.initials: RA
authors.lastname: Reamer
authors.forename: Cheng-Yi
authors.initials: CY
authors.lastname: Chen
authors.forename: Ralph P
authors.initials: RP
authors.lastname: Volante
mesh_terms: D000588:Amines / Q000737:chemistry*; D002384:Catalysis; D006859:Hydrogen / Q000737:chemistry* / Q000378:metabolism; D006860:Hydrogen Bonding; D007097:Imines / Q000737:chemistry*; D009584:Nitrogen / Q000737:chemistry* / Q000378:metabolism; D010084:Oxidation-Reduction; D013237:Stereoisomerism
chemical_list: D000588:Amines; D007097:Imines; D006859:Hydrogen; D009584:Nitrogen