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 electrochemi-cally 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, exhibit-ing 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 al-kyne-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.(c) 2023, Dalian Institute of Chemical Physics, Chinese Academy of Sciences. Published by Elsevier B.V. All rights reserved.