Palladium-Catalyzed Fluoroallylation of Aldimine Esters With gem-Difluorocyclopropanes: Synthesis of Fluorinated α-Amino Acid Derivatives

Abstract

Traditional approaches to α-C─H bond functionalization of aldimine esters heavily rely on bimetallic catalysis. In this work, we report a method for the fluoroallylation of aldimine esters using gem-difluorocyclopropanes under single palladium catalysis. This strategy enables the diversity-oriented synthesis of various fluorinated α-amino acid derivatives in good to excellent yields. The key fluorinated aldimine esters were formed via sequential α-C─H deprotonation and fluoroallylation. Subsequent in situ acidic hydrolysis afforded the corresponding free amino acid esters, while reduction with NaBH₄ delivered N-protected amino acid esters.