DFT Mechanistic Investigation into BF3-Catalyzed Alcohol Oxidation by a Hypervalent Iodine(III) Compound

Density functional theory (DFT) at the SMD/M06-2X/def2-TZVP//SMD/M06-2X/LANL2DZ,6-31G(d) level was employed to explore mechanistic aspects of BF3-catalyzed alcohol oxidation using a hypervalent iodine(III) compound, [ArI(OAc)(2)], to yield aldehydes/ketones as the final products. The reaction is composed of two main processes: (i) ligand exchange and (ii) the redox reaction. Our study for 1-propanol discovered that ligand exchange is preferentially accelerated if BF3 first coordinates to the alcohol. This coordination increases the acidity of the alcohol hydroxyl proton, resulting in ligand exchange between the iodane and the alcohol proceeding via a concerted interchange associative mechanism with an activation free energy of 10 kcal/mol. For the redox process, the calculations rule out the feasibility of the conventional mechanism (alkoxy C-alpha deprotonation) and introduce a replacement for it. This alternative route commences with alpha-hydride elimination of the alkoxy group promoted by BF3 coordination, which yields a BF3-stabilized aldehyde/ketone product and the iodane [ArI(OAc)(H)]. The ensuing iodane is extremely reactive toward reductive elimination to give ArI + HOAc in a highly exergonic fashion (Delta G = -62.1 kcal/mol). The reductive elimination reaction is the thermodynamic driving force for the alcohol oxidation to be irreversible. Consistent with the kinetic isotope effect reported experimentally, the alpha-hydride elimination is calculated to be the rate-determining step with an overall activation free energy of similar to 24 kcal/mol.