Rationalizing the regioselectivity of azolation of benzylic C-H bonds under photoredox catalysis

Abstract

A Density Functional Theory (DFT) study was performed to evaluate the reaction mechanism of the C-N bond formation under an integrated Hydrogen Atom Transfer / Radical Polar Crossover photoredox catalytic cycle. The regioselective activation of a model substrate, including three reactive positions (3º benzylic C-H bond, 2º benzylic C-H bond and primary C-Cl bond) was addressed to distinguish among the radical C-H activation mechanism and the standard SN2 reaction. We demonstrated that activation of tertiary benzylic C-H bond is the most favored and forms exclusively the experimentally observed product. In addition, the whole photoredox catalytic cycle, including the outer sphere electron transfer steps, was characterized computationally.