Direct Hydroxylarylation of Benzylic Carbon (sp3/sp2/sp) via Radical-involved Paired Electrochemical Cascade Reaction

Precisely regulating the chemoselectivity of free radicals and inhibiting their side reactions has always been one of the most difficult challenges in organic chemistry. Based on the full utilization of stability and philicity of free radicals, we have achieved a Radical-involved Paired Electrochemical Cascade Reaction (RPECR), which is also the first example of catalyst-free direct hydroxyarylation of unactivated benzylic carbon (sp3/sp2/sp). In detail, transient benzylic radical species generated by direct anodic oxidation of inexpensive and readily available alkyl/alkenyl/alkynylbenzenes undergo cascade transformations to couple with persistent radical anion obtained from cathodic reduction, yielding the large steric hindered high-value-added secondary and tertiary benzylic alcohols. Mechanistic studies, including divided-cell experiments, isotope labeling, free radical trapping, electron paramagnetic resonance (EPR), reaction kinetics, and cyclic voltammetry, strongly support the proposed RPECR process. Gram-scale synthesis and diversification of drug derivative have visualized the tremendous potential of this protocol for practical applications.