Incorporation of C(sp3)-Rich Benzene Bioisosteres via Iron-Catalyzed Photoelectrochemical Decarboxylative C−H Functionalization

Abstract

The bioisosteric replacement of benzenes in pharmaceuticals can foster their physicochemical properties. Moreover, an increased three-dimensional character of drug candidates is associated with a higher success rate in clinical studies. Therefore, strategies for the installation of C(sp3)-rich benzene bioisosteres continue to be of great demand. However, previous methods for the incorporation of bioisosteric motifs via C−C coupling using readily available, stable, and atom-economic reagents are scarce, rely on multi-step syntheses of prefunctionalized substrates and require expensive/toxic catalysts. In sharp contrast, we herein describe a versatile iron-catalyzed photoelectrochemical approach for the installation of a plethora of benzene bioisosteres through decarboxylative C−H functionalization with the aid of bench-stable, commercially available building blocks. Our strategy featured broad functional group tolerance, including late-stage diversification of pharmaceuticals, thereby significantly expanding the viable chemical space.