Determining Quantum Mechanical Methods Suitable for Quantitative Modeling of Hydrogen Atom Transfer by Halogen Atoms

Quantum mechanical methods for modeling hydrogen atom transfer by halogen reactions were systematically tested against experimental activation energies and regioselectivity data from modern synthetic organic reactions reported in the literature. For the practical and reliable predictions aimed at elucidating mechanisms or determining selectivity, an accurate description of saddle point energetics is critical, outweighing the benefits of explicit dynamical treatments or higher-level geometry optimizations. Among the methods evaluated, DLPNO-CCSD(T) single-point energies computed on M06-2X geometries achieve a practical predictive accuracy, with a mean absolute error of 0.6 kcal/mol in ΔΔ G ‡ . This is sufficient for predicting regioselectivity and assessing whether photoredox reactions proceed via HAT by free halogen atoms. The protocol delivers performance comparable to higher-level ab initio approaches using MP2 geometries, as well as to variational transition state theory treatments incorporating dynamical corrections, while maintaining computational efficiency. Single point energy calculations with CCSD(T) deliver excellent predictions, but high computational cost and applicability only to small systems limit the practical scope.