Using IR vibrations to quantitatively describe and predict site-selectivity in multivariate Rh-catalyzed C–H functionalization

Achieving selective C–H functionalization is a significant challenge that requires discrimination between many similar C–H bonds. Yet, reaction systems employing Rh(2)(DOSP)(4) and Rh(2)(BPCP)(4) were recently demonstrated to afford high levels of selectivity in the C–H insertion of carbenes into toluene-derived substrates. Herein, we explore the origin of this selectivity through a systematic analysis of substrate and reagent features that alter levels of selectivity from 20 : 1 to 1 : 610 for secondary (or tertiary)-to-primary benzylic C–H functionalization of toluene derivatives. Describing this variation using infrared vibrations and point charges, we have developed a mathematical model from which are identified features of the systems that determine levels of site-selectivity and are applied as predictive factors to describe the selectivity behavior of new substrate/reagent combinations.