Organic Hydride/Acid Pairs Acting as a Type of Thermodynamic-Capability-Regulated Two-Hydrogen-Atom Donors in Multisite Proton-Coupled Electron Transfer Reactions

Organic hydride/acid pairs (XH/HB pairs) serve as two-hydrogen-atom multisite proton-coupled electron transfer (MS-PCET) reagents. Their thermodynamic capabilities can be precisely regulated through the selection of different organic hydrides and acids. Crucially, the organic hydride radical cations (XH^•+), generated after the initial MS-PCET step, play a key role. XH^•+ quenches subsequent highly active radical intermediates via hydrogen atom transfer (HAT) to form desired products or activate additional unsaturated substrates. Therefore, the hydrogen-atom-donating Gibbs free energies of XH^•+ and the two-hydrogen-atom-donating Gibbs free energies of XH/HB pairs are valuable parameters. These two parameters enable a more comprehensive and objective evaluation of the thermodynamic capabilities of XH/HB pairs as two-hydrogen-atom-donating reductive MS-PCET reagents. The results demonstrate that the thermodynamic two-hydrogen-atom-donating capability of XH/HB pairs can be regulated across an exceptionally wide range of 143.2 kcal/mol. This is achieved by selecting XH with varying hydricities and HB with different acidities. Specifically, when a specific XH is used, the thermodynamic capability can be regulated across a range of 77.0 kcal/mol through acid selection. Conversely, with a fixed HB, the choice of XH enables regulation across 66.2 kcal/mol. This study establishes a fundamental thermodynamic database and provides a predictive framework for the rational design of metal-free, tunable, two-hydrogen-atom-donating reductive MS-PCET reagents in synthetic applications.