Activation and Deactivation of Benzylic C-H Bonds Guided by Stereoelectronic Effects in Hydrogen Atom Transfer from Amides and Amines to Alkoxyl Radicals

Kinetic and product studies on the reactions of tert-alkoxyl radicals with secondary and tertiary alkanamides bearing benzylic alpha-C H bonds, isoindoline, tetrahydroisoquinoline and the corresponding N-acetyl derivatives were carried out. Product studies on the reactions with the tert-butoxyl radical (tBuO*) point toward exclusive HAT from the benzylic alpha-C H bonds. Comparison of the kH values measured for reaction with the cumyloxyl radical (CumO*) with those obtained previously for the corresponding reactions of N-alkyl- and N,N-dialkylalkanamides, are indicative of a lack of benzylic activation and the operation of steric and stereoelectronic effects. Compared to N-methyl and N-ethyl groups, the presence of N-benzyl groups increases the barrier required to reach the optimal conformation for HAT, where the alpha-C H bond to be cleaved is perpendicular to the plane of the amide, precluding concurrent overlap with the phenyl p-system. When the benzylic alpha-C H bonds are in a conformation that allows for optimal overlap with both the phenyl p-system and the amide p-system or amine nitrogen lone pair, as in the isoindoline and tetrahydroisoquinoline derivatives, increases in kH that exceed 2-orders of magnitude were observed, highlighting the strong contribution provided by stereoelectronic activation to these HAT processes.