Origin of Regioselectivity in C–H Bond Scission by Radicals: Quantitatively Predicting Effect of Electrophilicity Using Adamantane

Abstract Hydrogen abstraction is a key step in the oxidation of saturated hydrocarbons and the functionalization of C–H groups via hydrogen atom transfer. To evaluate and predict the regioselectivity of active species in these reactions, adamantane has long been utilized as a probe molecule. The yield ratio of tertiary and secondary functionalized products is a parameter used to evaluate the electrophilicity of the active species; electrophilic active species preferentially abstract hydrogen atoms from tertiary C–H groups. However, the fundamental origin of this selectivity remains elusive because the tertiary and secondary C–H groups in adamantane have very similar electron density and bond strength. Herein, this work clarifies the reactivity of C–H bonds in hydrogen abstraction reactions through theoretical calculations using adamantane as a representative probe molecule, providing the quantitative scale that reproduces the regioselectivity using the electrophilicity and bond dissociation energy of active species. Quantum calculations clarify that electrophilic radicals withdraw electrons from adamantane during the abstraction of hydrogen atoms, thus passing through a mechanism similar to that of proton-coupled electron transfer. Compared with secondary C–H groups, tertiary C–H groups more easily donate electrons while their bonds are stretched. This is the essential cause providing selectivity. Because of the characteristically low ionization energy of adamantane and similar dissociation energy of its C–H bonds, this compound is indeed suitable for evaluating the electrophilicity of active species.