Unprecedented enantioselective reduction of N-unsubstituted imines: Catalytic asymmetric synthesis of trifluoromethylated amines

ORGN 793

Francis Gosselin, francis_gosselin@merck.com1, Paul D. O'Shea1, Stéphanie Roy1, Robert Reamer2, Cheng-yi Chen, cheng_chen@merck.com2, and Ralph P. Volante2. (1) Department of Process Research, Merck Frosst Centre for Therapeutic Research, 16711 route transcanadienne, Kirkland, QC H9H 3L1, Canada, (2) Department of Process Research, Merck Research Laboratories, PO Box 2000, P.O.Box 2000, Rahway, NJ 07065
The reductive amination of trifluoromethyl ketones is plagued by the formation of stable tetrahedral adducts that often fail to undergo dehydration to the corresponding imines. We have found that addition of LiN(SiMe3)2 to trifluoromethyl ketones at rt leads to smooth formation of the corresponding N-TMS-ketimines. Solvolysis of the N-Si bond of N-TMS-ketimines in MeOH leads to formation of stable, isolable N-unsubstitued ketimine E/Z isomers along with a methanol adduct. These three-component mixtures undergo a highly unprecedented asymmetric reduction under oxazaborolidine catalysis with catecholborane as hydride source. This methodology was applied to the first catalytic asymmetric synthesis of trifluoromethylated amines in 72-95% yield and 75-98% ee.
 

Asymmetric Reactions, Molecular Recognition, Self Assembly, Bioorganic Chemistry, Process R&D
8:00 PM-10:00 PM, Wednesday, 16 March 2005 Convention Center -- Hall D, Poster

Division of Organic Chemistry

The 229th ACS National Meeting, in San Diego, CA, March 13-17, 2005