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 pKa 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 N-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.