Electronic and Torsional Effects on Hydrogen Atom Transfer from Aliphatic C–H Bonds: A Kinetic Evaluation via Reaction with the Cumyloxyl Radical

A kinetic study on the hydrogen atom transfer (HAT) reactions from the aliphatic C–H bonds of a series of 1-Z-pentyl, 1-Z-propyl, and Z-cyclohexyl derivatives and of a series of N-alkylamides and N-alkylphthalimides to the electrophilic cumyloxyl radical (CumO^•) has been carried out. With 1-pentyl and 1-propyl derivatives, α-CH₂ activation toward CumO^• is observed for Z = Ph, OH, NH₂, and NHAc, as evidenced by an increase in k_H as compared to the unsubstituted alkane substrate. A decrease in k_H has been instead measured for Z = OAc, NPhth, CO₂Me, Cl, Br, and CN, indicative of α-CH₂ deactivation with HAT that predominantly occurs from the most remote methylenic site. With cyclohexyl derivatives, α-CH activation is only observed for Z = OH and NH₂, indicative of torsional effects as an important contributor in governing the functionalization selectivity of monosubstituted cyclohexanes. In the reactions of N-alkylamides and N-alkylphthalimides with CumO^•, the reactivity and selectivity patterns parallel those observed in the oxidation of the same substrates with H₂O₂ catalyzed by manganese complexes, supporting the hypothesis that both reactions proceed through a common HAT mechanism. The implications of these findings and the potential of electronic, stereoelectronic, and torsional effects as tools to implement selectivity in C–H oxidation reactions are briefly discussed.