Electrocatalytic Oxidative Coupling of CO with Amines toward Symmetrical and Asymmetrical Urea Derivatives

Urea derivatives have broad applications in the pharmaceutical and agricultural industries. Existing synthetic routes involve toxic reagents and multistep processes and operate at harsh conditions. In this work, we report an electrocatalytic oxidative coupling strategy capable of synthesizing urea derivatives from CO and amines under mild conditions in one pot. A Faradaic efficiency of up to 77% could be achieved in the C-N coupling reaction for the formation of 1,3-di-<i>tert</i>-butylurea. In situ spectroscopic and kinetic investigations reveal that the oxidative C-N coupling reaction proceeds via an Eley-Rideal mechanism, in which surface-adsorbed CO first couples with amines to form corresponding isocyanate intermediates followed by a nucleophilic attack. Generality and potential of this electrosynthetic approach are demonstrated by the synthesis of a broad range of symmetrical and asymmetrical urea derivatives with high selectivity, including active medical ingredients such as pimavanserin and a soluble epoxide hydrolase inhibitor.