Principles of Proton-Coupled Electron Transfer Mediator Design

Author: Adillon, Enric Healey

Year: 2026

Degree: Dissertation (Ph.D.)

Advisor: Peters, Jonas C.

Committee Members: Agapie, Theodor; Nelson, Hosea M.; Gray, Harry B.; Peters, Jonas C.

Option: Chemistry

Abstract

This thesis explores a series of structurally related reagents for formal H-atom transfer reactions. The work builds upon a previous discovery that an aniline-appended cobaltocene complex, upon protonation and reduction, is capable of concerted proton-electron transfer which enables its use as an electrochemical mediator for a variety of unsaturated small molecule reduction reactions. Given its potent reactivity and simple design, the aniline- appended cobaltocene complex is a wonderful platform for structure-function studies, and accordingly, three distinct structure-function relationships are investigated.

Chapters 2 and 3 examine the reductive component by substituting cobaltocene for a main group reductant of a similar potential, diaryl-o-carborane. The o-carborane can be reduced and protonated to generate an N–H bond with a weak effective bond dissociation free energy of 31 kcal/mol. Crystal structures of the diaryl-o-carborane radical anions are disclosed. The reactivity of the singly reduced, protonated form of the diaryl-o-carborane towards substrates and towards proton reduction is discussed. Then, the synthesis, thermochemistry, and reactivity of a family of o-carborane PCET reagents is described. Cyclic voltammetry using acetophenone reduction as an indicator of concerted proton-electron transfer suggests that the thermochemical perturbations do not categorically change the reactivity.

The second section examines the bridging group that separates the redox and acid/base moieties. Across the series of four complexes, the PCET driving force remains relatively constant while the thermodynamic coupling is varied substantially. Kinetic measurements of PCET reduction reveal that the reaction proceeds by a rate-limiting CPET step in all cases, the rate of which is modestly varied across the series. In particular, the o-phenylene-bridged complex has the fastest PCET rate despite the least driving force, which is attributed to a stabilizing orbital interaction between cobaltocene and the substrate.

In Chapter 5, the synthesis of phosphonium-appended cobaltocene is disclosed as well as its PCET thermochemistry and reactivity with acetophenone. Despite substantially less driving force for PCET than its nitrogen congener, the phosphonium-cobaltocene complex is more reactive.