Structural and Medium Effects on the Reactions of the Cumyloxyl Radical with Intramolecular Hydrogen Bonded Phenols. The Interplay Between Hydrogen-Bonding and Acid-Base Interactions on the Hydrogen Atom Transfer Reactivity and Selectivity

A time-resolved kinetic study on the reactions of the cumyloxyl radical (CumO•) with intramolecularly hydrogen bonded 2-(1-piperidinylmethyl)phenol (1) and 4-methoxy-2-(1-piperidinylmethyl)-phenol (2) and with 4-methoxy-3-(1-piperidinylmethyl)phenol (3) has been carried out. In acetonitrile, intramolecular hydrogen bonding protects the phenolic O−H of 1 and 2 from attack by CumO• and hydrogen atom transfer (HAT) exclusively occurs from the C−H bonds that are α to the piperidine nitrogen (α-C−H bonds). With 3 HAT from both the phenolic O−H and the α-C−H bonds is observed. In the presence of TFA or Mg(ClO4)2, protonation or Mg2+ complexation of the piperidine nitrogen removes the intramolecular hydrogen bond in 1 and 2 and strongly deactivates the α-C−H bonds of the three substrates. Under these conditions, HAT to CumO• exclusively occurs from the phenolic O−H group of 1−3. These results clearly show that in these systems the interplay between intramolecular hydrogen bonding and Brønsted and Lewis acid−base interactions can drastically influence both the HAT reactivity and selectivity. The possible implications of these findings are discussed in the framework of the important role played by tyrosyl radicals in biological systems.