Predictive Model for Site-Selective Aryl and Heteroaryl C–H Functionalization via Organic Photoredox Catalysis

Direct C–H functionalization of aromatic compounds is a useful synthetic strategy that has garnered much attention because of its application to pharmaceuticals, agrochemicals, and late-stage functionalization reactions on complex molecules. On the basis of previous methods disclosed by our lab, we sought to develop a predictive model for site selectivity and extend this aryl functionalization chemistry to a selected set of heteroaromatic systems commonly used in the pharmaceutical industry. Using electron density calculations, we were able to predict the site selectivity of direct C–H functionalization in a number of heterocycles and identify general trends observed across heterocycle classes.