Uncovering an IS-PC2ET Mechanism that Facilitates I(III)-to-I(V) Oxidation: an Experimental and Computational Study

Proton-coupled electron transfer (PCET) plays a central role in oxidative iodine chemistry. In this study, we show that 2-iodobenzoic acid (<b>1</b>) is readily oxidized by Oxone to generate the I(V) species IBX, while 2-iodo-1,3-benzenedicarboxylic acid (<b>8</b>) is only oxidized to the I(III) species iodosodilactone (<b>12</b>). Density functional theory (DFT) calculations reveal that the oxidation of both substrates follows an inner-sphere two-electron transfer (IS-2ET) mechanism, in which push-pull interactions facilitate the process. While the initial I(I)-to-I(III) step proceeds with comparable activation barriers for both <b>1</b> and <b>8</b>, the subsequent I(III)-to-I(V) oxidation is significantly less favorable for <b>8</b>, with a barrier of 44.9 kcal/mol compared to 24.7 kcal/mol for <b>1</b>. For compound <b>1</b>, oxidation proceeds via an I(III) intermediate, iodosobenzoic acid (IBA), bearing an OH ligand. We found that IBA is oxidized to IBX with a moderate activation barrier when the reaction proceeds via an inner-sphere proton-coupled two-electron transfer (IS-PC2ET), in which deprotonation of the OH group precedes two-electron transfer to Oxone. In contrast, compound <b>12</b> lacks an OH ligand and cannot undergo IS-PC2ET, rendering further oxidation inaccessible. These findings reveal a distinct subclass of PCET mechanisms and provide guiding principles for designing iodine-based oxidants capable of accessing the I(V) state under mild conditions.