Nickel-Catalyzed Electroreductive 3'-C Arylation and Alkenylation of Cordycepin Derivatives.

A nickel-catalyzed electroreductive cross-electrophile coupling of 3'-bromocordycepin derivatives with aryl, heteroaryl, and alkenyl iodides is disclosed. Under mild electrochemical conditions, C(sp3)-C(sp2) bonds are directly constructed at the 3' position of the ribose framework with excellent stereoselectivity, affording the desired products as single diastereomers and enabling modular access to diverse 3'-C-arylated and alkenylated cordycepin analogues. By replacing stoichiometric metal reductants with cathodic reduction, this protocol is compatible with nucleoside substrates bearing multiple polar functional groups and exhibits good functional group tolerance. X-ray crystallographic analysis, DFT calculations, and cyclic voltammetry experiments provide support for the stereochemical assignment of the products and a plausible nickel-catalyzed electroreductive coupling mechanism.