A Continuum of Proton-Coupled Electron Transfer Reactivity

Abstract

Proton-coupled electron transfer (PCET) covers a wide range of reactions involving the transfer(s) of electrons and protons. The best-known PCET reaction, hydrogen atom transfer (HAT), has been studied in detail for more than a century. HAT is generally described as the concerted transfer of a hydrogen atom (H^• ≡ H⁺ + e^-) from one group to another, Y + H-X → Y-H + X, but a strict definition of HAT has been difficult to establish. Distinctions are more challenging when the transfer of "H^•" involves e^- and H⁺ that transfer to/from spatially distinct sites or even completely separate reagents (multiple-site concerted proton-electron transfer, MS-CPET). MS-CPET reactivity is increasingly proposed in biological and synthetic contexts, and some reactions typically described as HAT more resemble MS-CPET. Despite that HAT and MS-CPET reactions "look different," we argue here that these reactions lie on a reactivity continuum, and that they are governed by many of the same key parameters. This Account walks the reader across this PCET reactivity continuum, using a series of studies to show the strong similarities of reactions that move protons and electrons in seemingly different ways. To prepare for our stroll, we describe the thermochemical and kinetic frameworks for HAT and MS-CPET. The driving force for a solution HAT reaction is most easily discussed as the difference in the bond dissociation free energies (BDFEs) of the reactants and products. BDFEs can be analyzed as sums of electron and proton transfer steps and can therefore be obtained from p K_a and E° values. Even though MS-CPET reactions do not make and break H-X bonds in the same way as HAT, the same thermochemical description can be used with the introduction of an effective BDFE (BDFE_eff). The BDFE_eff of a reductant/acid pair is the free energy of that pair to form H^•, which can be obtained from p K_a and E° values in an analogous fashion to a standard BDFE. When the PCET thermochemistry is known, HAT and PCET rate constants can be understood and often predicted using linear free energy relationships (the Brønsted catalysis law) and Marcus theory type approaches. After this background, we walk the reader through a continuum of PCET reactivity. Our journey begins with a study of metal-mediated HAT from hydrocarbon substrates to a metal-oxo complex and travels to the MS-CPET end of the reactivity spectrum, involving the transfer of H⁺ and e^- from the hydroxylamine TEMPOH to two completely separate molecules. These examples, and those in between, are all analyzed within the same thermodynamic and kinetic framework. A description of the first examples of MS-CPET with C-H bonds uses the same framework and highlights the importance of hydrogen bonding and preorganization. The examples and analyses show that the reactions along the PCET continuum are more similar than they are different, and that attempts to divide these reactions into subcategories can obscure much of the essential chemistry. We hope that developing the many common features of these reactions will help experts and newcomers alike to explore exciting new territories in PCET reactivity.

Figure 1.

Marc theory description of reactions where the intersection of the parabolic reactant and product free energy surfaces gives the free energy of the transition state (ΔG^‡) in terms of ΔG° and the intrinsic barrier λ, eq 4.

Figure 2.

(A) HAT from toluene to Ru^IVO²⁺. (B) Graph showing the dependence of rate constants (ln(k_HAT)) on driving force (ln(k_eq)) for oxidations of hydrocarbons by Ru^IVO²⁺. Data from ref .

Figure 3.

CPET reactions with acid/base sites distant from the metal center. Estimated metal-to-basic atom distances are given in the boxes at right. (A) Transfer of 1e⁻/1H⁺ from Ru^II(acac)₂(py-imH) to TEMPO. (B) Transfer of 1e⁻/1H⁺ from TEMPOH to Ru-pyCO₂⁻ (n = 0) and RupyPhCO₂⁻ (n = 1) yields the reduced Ru^II/carboxylic acid complex. (C) Transfer of 1e⁻/1H⁺ from TEMPOH to iron porphyrin complexes with carboxylate oxygen atoms distant from the iron center.

Figure 4.

(A) MS-CPET oxidation of phenol-base compounds. (B) Phenol-pyridines HOArCH₂pyX. (C) Plot of log(k) vs log(K_eq) for the reaction of different HOArCH₂pyX with various [N(C₆H₄Y)₃]^+• Parts (B) and (C) reproduced with permission from ref . Copyright 2012 American Chemical Society.

Figure 5.

(A) MS-CPET from TEMPOH to pyridine bases and ferrocenium (Fc⁺) oxidants. (B) Plot of ln(k_{MS CPET}) vs ln(K_eq). Part (B) reproduced with permission from ref . Copyright 2017 American Chemical Society.

Figure 6.

(A) MS-CPET oxidation of the fluorenyl-benzoate 1⁻. (B) Plot of log(k_MS-CPET) vs log(K_eq). Part (A) reproduced and part (B) adapted with permission from ref . Copyright The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC) http://creativecommons.org/licenses/bync/4.0/.

Scheme 1.

Illustrations of Concerted Proton-Electron Transfer (CPET) Reactions: (A) “Canonical HAT “; (B) Separated; and (C) Multiple Site

Scheme 2.. Thermodynamic Cycles (Square Schemes) and Equations for BDFEs of (A) a Single PCET Reagent and (B) a Reductant/Acid Paira^a

^aThe C_G,sol constant is in essence ΔG°(H⁺ + e⁻→ H) in solvent “sol”. Adapted with permission from ref . Copyright 2012 Royal Society of Chemistry.