Oxidation of Electron-Deficient Phenols Mediated by Hypervalent Iodine(V) Reagents: Fundamental Mechanistic Features Revealed by a DFT-Based Investigation

Hypervalent iodine(V) (HVI) compounds are highly efficient reagents for the double oxidative dearomatization of electron-rich phenols to o-quinones. We recently reported that an underexplored class of iodine(V) reagents possessing bidentate bipyridine ligands, termed Bi(N)-HVIs, could efficiently dearomatize electron-poor phenols for the first time. To better understand the fundamental mechanistic basis of this unique reactivity, density functional theory (DFT) was utilized. In this way, different pathways were explored to determine why Bi(N)-HVIs are capable of facilitating these challenging transformations while more traditional hypervalent species, such as IBX cannot. Our calculations reveal that the first redox process is the rate-determining step, the barrier of which hinges on the identity of the ligands bound to the iodine(V) center. This crucial process is composed of three steps: (a) ligand exchange, (b) hypervalent twist, and (c) reductive elimination. We found that strong coordinating ligands disfavour these elementary steps and, for this reason, HVIs bearing such ligands cannot oxidize the electron-poor phenols. In contrast, the weakly coordinating triflate ligands in Bi(N)-HVIs allow for the kinetically favorable oxidation of such phenols {e.g., G‡ = ~22 kcal/mol where Bi(N) = Bi(4-CO2Etbipy)}. It was also identified that trapping triflic acid, which is generated in situ, is a key role played by the basic bidentate bipyridine ligands in Bi(N)-HVIs as this serves to minimize decomposition of the sensitive ortho-quinone product.