Herein, we report a transition-metal-free protocol for the direct gem-difluoroallylation of β,γ-unsaturated α-amino nitrile-derived lithium reagents. The reaction proceeds via the in situ generation of β,γ-unsaturated α-amino nitrile lithium species, which react with gem-difluoroallylic ammonium salts with high regioselectivity. This selectivity is governed by the hard-soft acid-base (HSAB) principle, wherein the softness of the nucleophile is matched with that of the electrophile. The resulting products can be readily transformed into a diverse array of β-gem-difluoroallyl-substituted carboxylic acid derivatives. Notable features of this reaction include the absence of transition metals, the synthetic simplicity inherent in organolithium reagents, scalability to gram quantities, and good functional-group compatibility. This strategy offers an efficient approach to the synthesis of gem-difluoroallyl compounds.

Key words: β,γ-unsaturated α-aminonitriles, organolithium reagents, gem-difluoroallylic ammonium salts, gem-difluoroallylation