Umpolung Reactivity of Difluoroenol Silyl Ethers with Amines and Amino Alcohols. Application to the Synthesis of Enantiopure α-Difluoromethyl Amines and Amino Acids

Difluoroenol silyl ethers, produced in situ from acylsilanes and CF₃TMS, react as electrophiles with amines to give difluoroimines, via the corresponding hemiaminal adduct, as evidenced by ¹⁹F NMR spectroscopy. Reaction with (R)-phenylglycinol led to 2-difluoromethyloxazolidines. After separation of the diastereomers, reduction with LAH and Strecker-type synthesis gave enantiopure α-difluoromethylamines and α-difluoromethyl-α-amino acids, respectively.