Convenient asymmetric synthesis of beta-trifluoromethyl-beta-amino acid, beta-amino ketones, and gamma-amino alcohols via Reformatsky and Mannich-type reactions from 2-trifluoromethyl-1,3-oxazolidines.
The stereoselective syntheses of beta-trifluoromethyl-beta-amino ester, beta lactams, and beta-amino ketones starting from an oxazolidine derived from trifluoroacetaldehyde hemiacetal and (R)-phenylglycinol are reported. The Mannich-type reaction involving a chiral fluorinated iminium ion occurred in a good yield and with a higher stereoselectivity (dr up to 96:4) than that of the Reformatsky-type reaction. This straightforward strategy was applied to the short syntheses of (R)-3-amino-4,4,4-trifluorobutanoic acid, a series of novel enantiopure unprotected fluorinated beta-amino ketones, and their corresponding gamma-amino alcohols.
Laboratoire Réactions Sélectives et Applications, UMR CNRS 6519, Université de Reims-Champagne-Ardenne, Faculté des Sciences, BP 1039, 51687 Reims Cedex 2, France.
Florent
F
Huguenot
Thierry
T
Brigaud
D000596:Amino Acids / Q000138:chemical synthesis*; D000605:Amino Alcohols / Q000138:chemical synthesis*; D007659:Ketones / Q000138:chemical synthesis*; D010080:Oxazoles / Q000737:chemistry*; D013237:Stereoisomerism
D000596:Amino Acids; D000605:Amino Alcohols; D007659:Ketones; D010080:Oxazoles