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

Abstract

Hypervalent iodine (HVI) compounds are 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 dearomatize electron-poor phenols for the first time. To 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 2-iodoxybenzoic acid (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 disfavor 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. It was identified that trapping in situ-generated triflic acid is a key role played by the bidentate bipyridine ligands in Bi(N)-HVIs as this serves to minimize the decomposition of the ortho-quinone product.

Discovery of Periodinane Oxy-Assisted (POA) Oxidation Mechanism in the IBX-Controlled Oxidative Dearomatization of Pyrroles Mediated by Acetic Acid

“…This mechanism commences with a hypervalent twist to give a less stable isomer 7 , a species that is more reactive toward reductive elimination than the more stable isomer 3 . From a molecular orbital perspective, it has been demonstrated that the twist increases the oxidation potency of an iodine­(V) oxidant. − Next, we propose that pyrrole coordinates to the empty coordination site within 7 ( trans to the OAc ligand), thereby setting the stage for the first redox process. The reduction of iodine­(V) to iodine­(III) occurs by the transfer of two electrons from the coordinated pyrrole to the I–OAc σ* antibonding orbital (lowest unoccupied molecular orbital (LUMO) of 7 ) via transition structure TS 8 promoted by the nucleophilic attack of the iodine­(V) oxy ligand at the C2-position of the pyrrole.…”

“…This product then undergoes a substitution reaction with acetic acid and forms a thermodynamically more stable product 2b . The proposed mechanism for the second redox process is analogous to the oxidation of phenols by iodine­(III) reagents, which have been reported previously. , Comparison of our newly proposed POA oxidation mechanism with the more conventional proposal (Figures and ) reveals that the former is ∼25 kcal/mol more favorable than the latter. For the POA oxidation mechanism, the first reductive elimination step via TS 8 ii , which features an overall activation free energy of 20.6, is the rate-determining step.…”

“…The energy of the key transition structure associated with this pathway ( TS′ 8 i ) is computed to be 5.5 kcal/mol greater than TS 8 i (Figure ), indicating that this pathway is energetically unfavorable. This finding can be explained by the intrinsic instability of the π-complex 8′ in which two relatively strong electron donor ligands (oxy and acetate) occupy trans positions, resulting in TS′ 8 i lying at higher energy than its counterpart TS 8 i ; it has been demonstrated that the presence of strong electron donor ligands in a trans position lowers the stability of hypervalent iodine complexes. ,, …”

“…This finding can be explained by the intrinsic instability of the π-complex 8′ in which two relatively strong electron donor ligands (oxy and acetate) occupy trans positions, resulting in TS′ 8 i lying at higher energy than its counterpart TS 8 i ; it has been demonstrated that the presence of strong electron donor ligands in a trans position lowers the stability of hypervalent iodine complexes. 9, 10,12 Another alternative is that the carboxylate group, rather than the oxy ligand, serves as the nucleophilic promoter in the first reductive elimination step (Figure 7b). We found that the key transition structure in this case (TS″ 8 i ) has greater energy than TS 8…”

Remote Stereoelectronic Effects in Pyrrolidone- and Caprolactam-Substituted Phenols: Discrepancies in Antioxidant Properties Evaluated by Electrochemical Oxidation and H-Atom Transfer Reactivity

“…This process is typically related to the ArO–H BDE (bond dissociation energy). − Both PT-ET, stepwise proton-transfer-electron-transfer, and ET-PT, stepwise electron-transfer-proton-transfer, are two-step reactions, where the former is related to ArO–H acidity and ionization potential and the latter is related to oxidation potential. Even more diverse scenarios exist when multiple H-atoms are removed from one molecule. − …”