Modular Synthesis of Fully-Substituted and Configuration-Defined Alkyl Vinyl Ethers Enabled by Dual-Functional Copper
Zhong-Tao Jiang1, Zhengzhao Chen1, Ying Xia1
1West China School of Public Health and West China Fourth Hospital, West China-PUMC C.C. Chen Institute of Health, and State Key Laboratory of Biotherapy, Sichuan University, 610041, Chengdu, China.
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.
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