Tunable Multisite Proton-Coupled Electron Transfer Mediators: Distinct Pathways for Substrate Reduction Versus Competing Hydrogen Evolution

Proton-coupled electron transfer (PCET) reagents have emerged as powerful tools for transferring net H atoms to organic substrates from relatively weak X-H bonds. One advantage of employing PCET reagents is the tunability of the X-H bond strength by independently varying their redox potential and/or p<i>K</i>_a for selective substrate reductions; however, the rational development of modular catalytic PCET reagents based on these features remains underdeveloped. Here, we address important mechanistic questions relevant to a dimethylaniline-appended cobaltocene PCET mediator that our lab has previously introduced. Specifically, we examine where protonation occurs within the reactive Co(II, NH)⁺ intermediate of a Brønsted-base modified cobaltocene mediator, whether substrate reduction and hydrogen evolution reaction (HER) proceed by a common or bifurcated mechanistic pathway, and how the redox, acid-base, and structural properties of PCET mediators can dictate their reactivity and selectivity. We show that substrate compatibility can be tuned and, via a model study with <i>N</i>-aryl imine substrates, provide data pointing to a multisite PCET (MS-PCET) pathway. Moreover, we rigorously characterize the site of protonation in the reactive reduced, protonated form of the mediator, and through kinetic analysis establish that the pathway for undesired competing HER is fundamentally different and involves Cp-ring protonation. Our findings point to a high degree of flexibility in the design of reductive PCET mediators.