Unprecedented catalytic asymmetric reduction of N-H imines.
[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.
Gosselin
Francis
F
Department of Process Research, Merck Frosst Centre for Therapeutic Research, 16711 route transcanadienne, Kirkland, Québec, Canada. francis_gosselin@merck.com
O'Shea
Paul D
PD
Roy
Stéphanie
S
Reamer
Robert A
RA
Chen
Cheng-Yi
CY
Volante
Ralph P
RP
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
D000588:Amines; D007097:Imines; D006859:Hydrogen; D009584:Nitrogen