Cathodic Radical Cyclisation of Aryl Halides Using a Strongly-Reducing Catalytic Mediator in Flow

Abstract

Electro-reductive radical cyclisation of aryl halides affords the corresponding hetero- and carbo-cycles in an undivided flow reactor equipped with steel and carbon electrodes using an organic mediator. A dissolving metal anode is not needed, and the mediator can be employed in a sub-stoichiometric amount (0.05 equiv), increasing the practical utility of cathodic radical cyclisation. The methodology is applied to O-, N-, and C-tethers, yielding tricyclic fused and spiro systems. In the absence of mediator, the major pathway is hydrogenolysis of the C−X bond, a 2 e− process occurring at the cathode. Predominance of the radical pathway in presence of a strongly reducing mediator (M) is consistent with homogeneous electron-transfer in a reaction layer detached from the cathode surface, where the flux of M.− leaving the electrode is such that little aryl halide reaches the cathode.