Repositioning Proton and Electron Donors in a Family of Proton-Coupled Electron Transfer Mediators.

Reagents for reductive PCET often tether an acid and a reductant with a bridging moiety, lowering the effective molecularity of PCET to substrates. The effect of this connecting group on the thermodynamics and kinetics of PCET, however, is not systematically understood. To interrogate the role of the bridge in a well-defined system, we measured PCET rates from a set of anilinium-appended cobaltocene complexes to a series of aryl ketones. Synthesis of four cobaltocene PCET mediators, including one via late-stage Pd-catalyzed cross-coupling of a cobaltocenium salt, enabled systematic variation of the covalent bridge between the cobaltocene electron donor and anilinium proton donor. Measurements of electron and proton transfer equilibria show that the overall PCET driving force is minimally perturbed. Kinetic analysis establishes that aryl ketone reduction by our PCET mediators proceeds by a concerted mechanism in all cases, despite substantial variations in the thermodynamic coupling. Notably, a complex containing an o-phenylene bridge exhibits the fastest PCET rate despite having the least driving force, a result attributed to stabilizing orbital interactions between the ketone substrate and the cyclopentadienyl ligand of the mediator.