Modular Synthesis of Fully-Substituted and Configuration-Defined Alkyl Vinyl Ethers Enabled by Dual-Functional Copper Catalysis

Abstract

Here we present a modular, chemo-, regio-, and stereoselective synthesis of fully-substituted and configuration-defined alkyl vinyl ethers (AVEs) using simple chemical feedstocks. The distinctive approach involves the chemo- and regioselective functionalization of the CF₂ unit in gem-difluorinated cyclopropanes with O-H and C-H nucleophiles in a specific order. The resulting highly functionalized cyclopropanyl ethers then undergo a stereoselective ring-opening process to produce fully-substituted and configuration-defined AVEs. These AVEs are rarely accessible through conventional methods and are easily transformable. Mechanistic experiments indicate that the success of this method relies on the use of dual-functional copper catalysis, which is involved in both the functionalization of the CF₂ unit and the subsequent ring-opening process.

Keywords: Alkyl Vinyl Ethers; Copper Catalysis; C−C Bond Activation; C−F Bond Functionalization; gem-Difluorinated Cyclopropanes.