Azaaryl Alcohols as Latent Benzylic Nucleophiles in Pd-Catalyzed Regioselective Fluoroallylation of gem -Difluorinated Cyclopropanes

Abstract

Herein, we introduce a strategy wherein azaaryl tertiary alcohols serve as latent benzylic nucleophiles, enabling direct coupling with readily accessible gem-difluorinated cyclopropanes (gem-DFCPs) to afford α-fluoroallylated azaarenes in synthetically valuable yields. This protocol exhibits highly branched regioselectivity and broad substrate compatibility, thereby providing a new avenue for the introduction of valuable fluoroallyl moieties at the traditionally challenging α position of azaarenes. Mechanistic studies reveal that the tertiary alcohol moiety plays a critical role in enabling the cross-coupling process. Furthermore, density functional theory (DFT) calculations suggest that β-F elimination is likely the rate-determining step, while the observed regioselectivity originates from a favorable 3,3′-reductive elimination pathway.