DFT-Based Comparison between Mechanistic Aspects of Amine and Alcohol Oxidation Mediated by IBX

Abstract

Density functional theory was utilized to investigate plausible mechanisms for amine and alcohol oxidation by an iodine­(V) hypervalent reagent (IBX). In this contribution, we found that amine and alcohol oxidation both proceed by similar mechanisms. The reactions initiate from ligand exchange to give four coordinate intermediates followed by a redox process giving an iodine­(III) species and oxidized substrates. Interestingly, for both the ligand-exchange and the redox steps a hypervalent twist is required for the reaction to proceed via an energetically more accessible route. The ligand-exchange process was found to be mediated by a proton-shuttling agent such as water, a second IBX, or a second substrate. While the ligand-exchange step for both amine and alcohol occurs with almost identical activation energy (particularly when water is considered as the shuttling agent), the redox step for the amine takes place with much lower activation energy than that for the alcohol. Finally, we ascertained that five coordinate amide iodine­(V) complexes are unreactive toward redox reactions due to the fact that in such cases two electrons from the coordinated amide are required to occupy a 3c–4e σ* orbital which is too high in energy to be reachable.

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

“…This is consistent with the shorter I–OTf bond distance within 21_OTf (2.252 Å) in comparison to the equivalent bond in 20 (2.412 Å) (Figure ). It is established that a hypervalent twist must take place for the iodine oxidant to be sufficiently reactive toward the redox process. , The corresponding twist occurs by overcoming an activation barrier of 8.4 kcal/mol via TS 21–22_ OTf , which forms 22_OTf . The approach of the ortho -carbon of the phenolate to the oxo ligand in 22_OTf promotes the first redox process via an associative mechanism to afford 23_OTf .…”

The Mechanistic Perspective of IV Iodoxolones

“…In 2019, Chipman et al. used DFT to compare 1° alcohol and 1° amine oxidation, finding the onset to ligand exchange occurs via a common, base assisted proton shuttle mechanism, the 1° amine variant of which commences in Scheme 74 [54] . The Gibbs free activation energy for proton migration from substrate to the oxo ligand of 3 decreases as the nucleophile approaches the iodine(V) centre.…”

“…In 2019, Chipman et al used DFT to compare 1°alcohol and 1°amine oxidation, finding the onset to ligand exchange occurs via a common, base assisted proton shuttle mechanism, the 1°amine variant of which commences in Scheme 74. [54] The Gibbs free activation energy for proton migration from substrate to the oxo ligand of 3 decreases as the nucleophile approaches the iodine(V) centre. The phenyl and oxo groups of 3 are too strong trans-influencing to allow their trans position to be occupied, so an approach of amine to iodine(V) from the position trans to the hydroxyl group is favoured.…”

“…[53] The most stable conformation of a four-coordinate iodine(V) compound is conventionally the one that best accommodates the trans influencing properties of the ligands. [54] Series 1 shows the complete set of IBX 3 and Ac-IBX 6 ligands, arranged in descending order of trans influence:…”

“…Suresh correlated trans influence of I III ligands with their inductive nature [53] . The most stable conformation of a four‐coordinate iodine(V) compound is conventionally the one that best accommodates the trans influencing properties of the ligands [54] . Series 1 shows the complete set of IBX 3 and Ac‐IBX 6 ligands, arranged in descending order of trans influence: …”