Novel synthesis of alpha-trifluoromethylated alpha-amino acid derivatives from gamma-hydroxy-alpha-fluoro-alpha-trifluoromethyl carboxamides.

On treatment with an organoaluminum reagent such as trimethylaluminum or DIBAL-H, gamma-hydroxy-alpha-fluoro-alpha-trifluoromethyl carboxamides (1) give a single diastereomer of alpha-amino-alpha-trifluoromethyl-gamma-lactones (2), which are a ring-closed form of gamma-hydroxy-alpha-trifluoromethyl-alpha-amino acids. This intriguing reaction results from intramolecular replacement of the fluorine atom on the alpha-carbon atom with the nitrogen atom of the amide group, which occurs in an SN2 manner. [reaction: see text]