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^α deprotonation) and introduce a replacement for it. This alternative route commences with α-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 (ΔG = −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 α-hydride elimination is calculated to be the rate-determining step with an overall activation free energy of ∼24 kcal/mol.