Elizabeth A. McLoughlin

We present here a review of the photochemical and electrochemical applications of multi-site proton-coupled electron transfer (MS-PCET) in organic synthesis. MS-PCETs are redox mechanisms in which both an electron and a proton are exchanged together, often in a concerted elementary step. As such, MS-PCET can function as a non-classical mechanism for homolytic bond activation, providing opportunities to generate synthetically useful free radical intermediates directly from a wide variety of common organic functional groups. We present an introduction to MS-PCET and a practitioner's guide to reaction design, with an emphasis on the unique energetic and selectivity features that are characteristic of this reaction class. We then present chapters on oxidative N-H, O-H, S-H, and C-H bond homolysis methods, for the generation of the corresponding neutral radical species. Then, chapters for reductive PCET activations involving carbonyl, imine, other X═Y π-systems, and heteroarenes, where neutral ketyl, α-amino, and heteroarene-derived radicals can be generated. Finally, we present chapters on the applications of MS-PCET in asymmetric catalysis and in materials and device applications. Within each chapter, we subdivide by the functional group undergoing homolysis, and thereafter by the type of transformation being promoted. Methods published prior to the end of December 2020 are presented.

The accumulation of persistent plastic waste in the environment is widely recognized as an ecological crisis. New chemical technologies are necessary both to recycle existing plastic waste streams into high-value chemical feedstocks and to develop next-generation materials that are degradable by design. Here, we report a catalytic methodology for the depolymerization of a commercial phenoxy resin and high molecular weight hydroxylated polyolefin derivatives upon visible light irradiation near ambient temperature. Proton-coupled electron transfer (PCET) activation of hydroxyl groups periodically spaced along the polymer backbone furnishes reactive alkoxy radicals that promote chain fragmentation through C–C bond β-scission. The depolymerization produces well-defined and isolable product mixtures that are readily diversified to polycondensation monomers. In addition to controlling depolymerization, the hydroxyl group modulates the thermomechanical properties of these polyolefin derivatives, yielding materials with diverse properties. These results demonstrate a new approach to polymer recycling based on light-driven C–C bond cleavage that has the potential to establish new links within a circular polymer economy and influence the development of new degradable-by-design polyolefin materials.

Electrochemical and chemical studies reveal that the amido complex (PNH_xP)Fe(CO)(H)(X) (FeN 1, x = 0, X = 0; Fe(H)(NH) 2, x = 1, X = H; PNHP = bis[2-(diisopropylphosphino)ethyl]amine) is active for the electrocatalytic oxidation of isopropanol. At room temperature, the amido FeN 1 dehydrogenates isopropanol to form acetone. The resulting amino hydride complex Fe(H)(NH) 2 is subsequently oxidized by one electron at a low potential (−0.74 V versus ferrocene/ferrocenium, Fc^0/+) in tetrahydrofuran. In the presence of strong base (phosphazene base P₂-Et, Et-N = P₂(dma)₅, P2), this oxidation process becomes a two-electron, two-proton process that regenerates FeN 1. FeN 1 is active for the electrooxidation of isopropanol in the presence of strong base (i.e., P2) with an onset potential near −1 V versus Fc^0/+. By cyclic voltammetry, fast turnover frequencies of 1.7 s^–1 for isopropanol oxidation are achieved with FeN 1. Controlled potential electrolysis studies confirm that the product of isopropanol electrooxidation is acetone, generated with high Faradaic efficiency (∼100%).

The synthesis, structural characterization, and electrochemical behavior of the neutral Mn(azpy)(CO)₃(Br) 4 (azpy = 2-phenylazopyridine) complex is reported and compared with its structural analogue Mn(bipy)(CO)₃(Br) 1 (bipy = 2,2′-bipyridine). 4 exhibits reversible two-electron reduction at a mild potential (−0.93 V vs Fc^+/0 in acetonitrile) in contrast to 1, which exhibits two sequential one-electron reductions at −1.68 V and −1.89 V vs Fc^+/0 in acetonitrile. The key electronic structure differences between 1 and 4 that lead to disparate electrochemical properties are investigated using a combination of Mn–K-edge X-ray absorption spectroscopy (XAS), Mn–Kβ X-ray emission spectroscopy (XES), and density functional theory (DFT) on 1, 4, their debrominated analogues, [Mn(L)(CO)₃(CH₃CN)][CF₃SO₃] (L = bipy 2, azpy 5), and two-electron reduced counterparts [Mn(bipy)(CO)₃][K(18-crown-6)] 3 and [Mn(azpy)(CO)₃][Cp₂Co] 6. The results reveal differences in the distribution of electrons about the CO and bidentate ligands (bipy and azpy), particularly upon formation of the highly reduced, formally Mn(−1) species. The data show that the degree of ligand noninnocence and resulting redox-activity in Mn(L)(CO)₃ type complexes impacts not only the reducing power of such systems, but the speciation of the reduced complexes via perturbation of the monomer–dimer equilibrium in the singly reduced Mn(0) state. This study highlights the role of redox-active ligands in tuning the reactivity of metal centers involved in electrocatalytic transformations.

Cobalt(III) hydrides, formed via protonation of basic cobalt(I) centers, have long been recognized as key intermediates in the electrocatalytic reduction of protons to hydrogen. An understanding of the structural and electronic factors that govern their formation is key to developing more efficient and potent catalysts. A combination of Co K-edge X-ray absorption spectroscopy, extended X-ray absorption fine structure, density functional theory (DFT), and time-dependent DFT methods have been used to investigate several cyclopentadienyl (Cp) Co(III)L (L = ligand) species and their two-electron reduced Co(I) analogues. The results reveal that when L is strongly π-accepting, the reduced species demonstrates strong backbonding between the electron-rich Co(I) center and the ligand L, resulting in a weakly basic Co center that does not protonate to form a Co(III)–H. In contrast, a weakly π-accepting or σ-donating ligand system results in an electron-rich Co(I) center, which is readily protonated to form a Co(III)–H. This study reveals the strength of a combined X-ray spectroscopy/theory method in understanding the role of ligands in tuning the electronic structure and subsequent reactivity of the metal center.

Protonation of the Co(I) phenylazopyridine (azpy) complex [CpCo(azpy)] 2 occurs at the azo nitrogen of the 2-phenylazopyridine ligand to generate the cationic Co(I) complex [CpCo(azpyH)]⁺ 3 with no change in oxidation state at Co. The N–H bond of 3 exhibits diverse hydrogen transfer reactivity, as studies with a variety of organic acceptors demonstrate that 3 can act as a proton, hydrogen atom, and hydride donor. The thermodynamics of all three cleavage modes for the N–H bond (i.e., proton, hydride, and hydrogen atom) were examined both experimentally and computationally. The N–H bond of 3 exhibits a pK_a of 12.1, a hydricity of ΔG°_H– = 89 kcal/mol, and a bond dissociation free energy (BDFE) of ΔG°_H• = 68 kcal/mol in CD₃CN. Hydride transfer from 3 to the trityl cation (ΔG°_H– = 99 kcal/mol) is exergonic but takes several hours to reach completion, indicating that 3 is a relatively poor hydride donor, both kinetically and thermodynamically. Hydrogen atom transfer from 3 to 2,6-di-tert-butyl-4-(4′-nitrophenyl)phenoxyl radical (^tBu₂NPArO·, ΔG°_H• = 77.8 kca/mol) occurs rapidly, illustrating the competence of 3 as a hydrogen atom donor.

Octahedral ruthenium complexes [RuX(CNN)(dppb)] (1, X = Cl; 2, X = H; CNN = 2-aminomethyl-6-tolylpyridine, dppb = 1,4-bis(diphenylphosphino)butane) are highly active for the transfer hydrogenation of ketones with isopropanol under ambient conditions. Turnover frequencies of 0.88 and 0.89 s^–1 are achieved at 25 °C using 0.1 mol % of 1 or 2, respectively, in the presence of 20 equiv of potassium t-butoxide relative to catalyst. Electrochemical studies reveal that the Ru–hydride 2 is oxidized at low potential (−0.80 V versus ferrocene/ferrocenium, Fc^0/+) via a chemically irreversible process with concomitant formation of dihydrogen. Complexes 1 and 2 are active for the electrooxidation of isopropanol in the presence of strong base (potassium t-butoxide) with an onset potential near −1 V versus Fc^0/+. By cyclic voltammetry, fast turnover frequencies of 3.2 and 4.8 s^–1 for isopropanol oxidation are achieved with 1 and 2, respectively. Controlled potential electrolysis studies confirm that the product of isopropanol electrooxidation is acetone, generated with a Faradaic efficiency of 94 ± 5%.