Electrochemical Benzylic C-H Functionalization with Isocyanides

We report the challenging direct carbamoylation or cyanation of benzylic C(sp3)-H bonds with an isocyanide via an electrochemical process giving rise to structures that are encountered in several biologically relevant compounds and drugs. This transformation proceeds under mild conditions without the need for any external oxidant and avoids the necessity to start from a prefunctionalized benzylic substrate or the deployment of the cation pool method. The anodic oxidation of the benzylic position and the subsequent addition of the isocyanide lead to the formation of a C-C bond and to a nitrilium cation that hydrolyzes to yield alpha-aryl acetamide derivatives, whereas the elimination of a t-butyl cation delivers alpha-aryl acetonitrile derivatives.

Automated summary

In this study, we report the direct carbamoylation or cyanation of benzylic C(sp3)-H bonds via an electrochemical process, leading to the formation of structures found in biologically relevant compounds and drugs. This transformation occurs under mild conditions without the need for external oxidants or prefunctionalized substrates.