Unveiling the Delicate Balance of Polarity and Strain Effect in Determining the Site-Selective Intramolecular Hydrogen Atom Transfers

Abstracting hydrogen atoms from different non-activated C(sp3)–H bonds to generate various carbon radicals provides an efficient way to further broaden the application of intramolecular hydrogen atom transfer (HAT) reactions. This study thoroughly explores the roles of kinetic factors (polarity and strain effects) and thermodynamic factors (bond dissociation energy) in affecting the reactivity of intramolecular HAT reactions, contributing to the rational design of suitable substrates. Furthermore, the site-selectivity, as represented by the barrier height difference (ΔΔG1, n–1, n′≠, where 1,n and 1,n′ denotes 1,n-HAT and 1,n′-HAT reaction) correlates reasonably well with local electrophilicity index difference (ΔΔω1,n–1,n′loc), demonstrating the vital role of polarity in achieving site-selective intramolecular HAT reactions. Additionally, strain effects are considered alongside polar effects to explain the observed site-selective products, offering fundamental kinetic insight into balancing these effects in determining the proper hydrogen atom engaged in the reaction.