Work

Regio‐ and Stereospecific Copper‐Catalyzed S N 2’ Substitution Reaction of Propargyl Esters with Polyfluoroaryl Zinc Reagents

Year: 2025

Type: article

Abstract: Copper‐catalyzed S N 2' substitution reactions of chiral propargyl compounds provides an efficient synthetic method for chiral allenes that have widespread applications in pharmaceuticals and artificial functional materials. However, compared with the S N 2' reaction catalyzed by palladium, ruthenium, and other noble metals, the development of S N 2' reaction catalyzed by copper is relatively delayed due to its sensitivity to steric hindrance. Herein we reported a highly selective copper‐catalyzed S N 2' substitution reaction through the use of weakly nucleophilic zinc reagents. A wide variety of polyfluoroaryl allenes bearing an assortment of functional groups (36 examples) are compatible with this catalysis system. It is worth noting that chiral polyfluoroaryl allenes can also be efficiently constructed from chiral propargyl esters via this S N 2' reaction. A series of mechanism verification experiments and DFT calculations also provide a basis for the reaction mechanism and the stereo‐model of chiral transfer. Moreover, the preparation of other valuable polyfluoroarene containing compounds from polyfluoroaryl allenes also proves the synthetic utility of this methodology.

Source: Helvetica Chimica Acta

DOI: 10.1002/hlca.202500135