Hole Catalysis of Cycloaddition Reactions: How to Activate and Control Oxidant Upconversion in Radical-Cationic Diels-Alder Reactions

Abstract

In order to use holes as catalysts, the oxidized product should be able to transfer the hole to a fresh reactant. For that, the hole-catalyzed reaction must increase the oxidation potential along the reaction path, i.e., lead to "hole upconversion." If this thermodynamic requirement is satisfied, a hole injected via one-electron oxidation can persist through multiple propagation cycles and serve as a true catalyst. This work provides guidelines for the rational design of hole-catalyzed Diels-Alder (DA) reactions, the prototypical cycloaddition. After revealing the crucial role of hyperconjugation in the absence of hole upconversion in the parent DA reaction, we show how upconversion can be reactivated by proper substitution. For this purpose, we computationally evaluate the contrasting effects of substituents at the three possible positions in the two reactants. The occurrence and magnitude of hole upconversion depend strongly on the placement and nature of substituents. For example, donors at C1 in 1,3-butadiene shift the reaction to the hole-upconverted regime with an increased oxidation potential of up to 1.0 V. In contrast, hole upconversion in C2-substituted 1,3-butadienes is activated by acceptors with the oxidation potential increase up to 0.54 V. Dienophile substitution results in complex trends because the radical cation can be formed at either the dienophile or the diene. Hole upconversion is always present in the former scenario (up to 0.65 V). Finally, we report interesting stereoelectronic effects that can activate or deactivate upconversion via a conformational change.