Catalytic Asymmetric Construction of Tertiary Carbon Centers Featuring an α-Difluoromethyl Group with CF2H-CH2-NH2 as the Building Block

We report here for the first time a novel difluoromethylated ketimine building block condensed by thioisatin and difluoroethylamine, offering efficient access to a broad range of enantioenriched products bearing difluoroethylamine units (27 examples, <= 98% yield, >99% ee) in the presence of quinine-derived squaramide. Further transformation of the intermediate would generate a variety of versatile functional blocks like a-difluoromethyl amines, beta-amino acid, and beta-diamine with retention of the enantiomeric excess at the difluoromethyl-bound carbon.

Automated summary

A novel difluoromethylated ketimine building block was synthesized for the first time by condensation of thioisatin and difluoroethylamine, providing efficient access to enantioenriched products with difluoroethylamine units. Further transformation of the intermediate led to the generation of versatile functional blocks while retaining the enantiomeric excess at the difluoromethyl-bound carbon.