The direct functionalization of C-H bonds is one of the most desirable strategies for molecular synthesis in organic chemistry. The abundance of such bonds in most organic substrates usually renders their selective activation a daunting task, forcing the synthetic chemist to follow long and expensive routes to accomplish it.
In the last years, experiments have evinced that selective C-H activation is feasible. The empirical approach to these achievements, however, pinpoints the lack of a theory that is both accessible and reliable to quantitatively predict the outcome of such reactions.
In this talk, I will present the latest results from our group in the field of C-H activation. In our theoretical framework, selectivity can be understood and tailored by gauging the influence of the reduction potentials and acidity constants of the reacting species in the C-H cleavage step. The computational design of selective C-H activation reactions will be illustrated, deriving guidelines that we foresee will find applications in de novo synthesis and late-stage functionalization chemistry.