Electrochemical Oxidative Radical Polar Crossover Route to 1,4-Keto Carboxylates Mediated by Anchimeric Assistance

Abstract

The 1,4-keto carboxylate scaffold is present in the structure of many biologically relevant compounds. To date, there are only a branch of methods to prepare them, using either transition metal catalysts, or noncommercially available and sensitive starting materials. Herein, we describe a sustainable electrochemical methodology starting from commercially available and highly stable 1,3-diketones and alkenes to prepare 1,4-keto aryl and alkyl carboxylates in a highly efficient manner, without the need of an external catalyst or harsh reaction conditions. This electrochemical oxidative radical polar crossover transformation presents a broad scope, is compatible with many functional groups, and can even be applied in flow chemistry. In addition, the key stabilization of the intermediate carbocation by anchimeric assistance allows a high diastereo- and regio-control of the reaction. Moreover, the utility of these 1,4-keto carboxylates was demonstrated in several derivatizations and applications in the late-stage functionalization of bioactive compounds.

Keywords: 1,4‐keto carboxylate; anchimeric assistance; cross‐polar‐reaction; electrochemistry; radical chemistry.