Iodine Activation of Alcohols: A Computational Study

A DFT study aimed at unravelling the origin of catalytic activity of iodine in reaction with alcohols is presented. Computed free energies for generation of the O–I complexes from the separated reactants are around 3 kcal/mol and solvation increases endoergicity by ca. 1 kcal/mol. Calculations suggest that halogen bond formation between I2 and alcohols does not lead to strong activation of the hydroxyl as a leaving group, although solvent has a notable effect in lowering endoergicity for carbocation formation. Model tertiary alcohols exhibited β-proton abstraction following breaking of the C–O bond, while model secondary and primary alcohols experienced an earlier β-proton abstraction, synchronic with the C–O bond cleavage. Consistent with computed natural bond orbital charges, benzylic and propargylic alcohols underwent iodide anion quenching at the para position of phenyl and C-3, respectively.