Regioselective Electrochemical Oxidative Radical Ortho-(4 + 2)/Ipso-(3 + 2) Cyclization

Achieving regioselectivity in radical cyclization reactions is of central importance, yet extremely challenging. Although Baldwin's rules provided guidance on the addition of radical species with alkenes/alkynes, the ortho-/ipso-selectivity of the cyclic reaction between radical species (especially alkyl and alkenyl radical) and aryl groups is still ambiguous. Herein, we develop an electrochemically enabled regioselective ortho-(4 + 2)/ipso-(3 + 2) cyclization of alkyl/alkenyl radicals with aryl groups, which provides a series of tetrahydronaphthalene and spirocarbocycle derivatives, exhibiting a broad substrate scope and functional group tolerance. Alkyl/alkenyl radicals are generated by Cp2Fe-mediated electrochemical oxidative radical addition of benzylic malonates with alkenes and alkynes. The method avoids the use of chemical oxidant/base/noble metal, the pre-functionalization of substrates, and the over-oxidation of compounds. Theoretical studies reveal that the dominant factor promoting the alkene-preferred ortho-addition is the favorable interaction energy; the alkyne-preferred ipso-addition regioselectivity is controlled by the distortion energy. Notably, this strategy is regarded as an important supplement to Baldwin's rules for radical cyclization.