Nickel‐Catalyzed Four‐Component Carbonylation of Ethers and Olefins: Direct Access to γ‐Oxy Esters and Amides

Multi‐component carbonylation of olefins, a reaction that installs both a carbon–carbon(heteroatom) bond and a carbonyl group across the double bond, is an attractive strategy for alkene functionalization. Herein, we developed a novel nickel‐catalyzed four‐component carbonylation of olefins with ethers under low CO gas pressure. Using alcohols and amines as the reaction partner, diverse γ‐oxy‐substituted esters and amides were produced in good yields with excellent functional group tolerance. Notably, Naftidrofuryl, a medicine for the treatment of cerebrovascular disease (CVD), can be synthesized by this process straightforwardly. A new nickel‐catalyzed four‐component carbonylation of ethers with olefins to synthesize γ‐substituted carbonyl compounds has been developed. A variety of γ‐substituted carbonyl compounds were produced in excellent yields under 1 atm pressure of CO. Notably, this strategy has been successfully applied to the one‐step synthesis of the drug molecule Naftidrofuryl, which is a medicine for the treatment of cerebrovascular disease (CVD).