Asymmetric syntheses of 1-aryl-2,2,2-trifluoroethylamines via diastereoselective 1,2-addition of arylmetals to 2-methyl-N-(2,2,2-trifluoroethylidene)propane-2-sulfinamide.
Condensation of N-tert-butanesulfinamide (S)-1 with trifluoroacetaldehyde hydrate 2a afforded 2-methyl-N-(2,2,2-trifluoroethylidene)propane-2-sulfinamide 3. Without isolation and purification, imine 3 was added to various aryllithium reagents to give highly diastereomerically enriched adducts 5a-g. Acidic methanolysis of 5a-g provided the desired 1-aryl-2,2,2-trifluoroethylamine hydrochloride compounds 6a-g. [reaction: see text].
Truong
Vouy Linh
VL
Department of Medicinal Chemistry, Merck Frosst Centre for Therapeutic Research, 16711 Trans Canada Highway, Kirkland, Québec H9H 3L1, Canada. vouylinh_truong@merck.com
Ménard
Madeleine S
MS
Ménard
Madelaine S
MS
Dion
Isabelle
I
D002851:Chromatography, High Pressure Liquid; D005021:Ethylamines / Q000138:chemical synthesis*; D006845:Hydrocarbons, Fluorinated / Q000138:chemical synthesis* / Q000737:chemistry; D007097:Imines / Q000138:chemical synthesis; D007202:Indicators and Reagents; D009942:Organometallic Compounds / Q000737:chemistry; D013237:Stereoisomerism; D013452:Sulfonium Compounds / Q000737:chemistry*
C518435:2-methyl-N-(2,2,2-trifluoroethylidene)propane-2-sulfinamide; D005021:Ethylamines; D006845:Hydrocarbons, Fluorinated; D007097:Imines; D007202:Indicators and Reagents; D009942:Organometallic Compounds; D013452:Sulfonium Compounds