C–H Functionalization

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 the Nicewicz Group, researchers in the group, as published in JACS, 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, the group members 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.

Group members anticipate that the knowledge of reactivity and selectivity obtained through this predictive model will allow these methodologies to find wide application in late-stage functionalization of biologically active compounds.