Concerted proton-coupled electron transfer is a key mechanism of substrate activation in biological redox catalysis. However, its applications in organic synthesis remain largely unexplored. Herein, we report the development of a new catalytic protocol for ketyl-olefin coupling and present evidence to support concerted proton-coupled electron transfer being the operative mechanism of ketyl formation. Notably, reaction outcomes were correctly predicted by a simple thermodynamic formalism relating the oxidation potentials and pKa values of specific Bronsted acid/reductant combinations to their capacity to act jointly as a formal hydrogen atom donor.

Catalytic ketyl-olefin cyclizations enabled by proton-coupled electron transfer.

Hydrogen Peroxide as a Sustainable Energy Carrier: Electrocatalytic Production of Hydrogen Peroxide and the Fuel Cell.

Synthesis, DNA-binding and DNA-mediated luminescence quenching of Ru(II) polypyridine complexes

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.

Photochemical and Electrochemical Applications of Proton-Coupled Electron Transfer in Organic Synthesis.

Electron-transfer properties of high-valent metal-oxo complexes

An acid-stable NADH model compound, 10-methyl-9,10-dihydroacridine (AcrH2) and 1,1′-dimethylferrocene [Fe(C5H4Me)2] are oxidized by dioxygen in the presence of HClO4 in acetonitrile and water. The acid-catalysed two-electron and four-electron reductions of dioxygen by AcrH2 and [Fe(C5H4Me)2], respectively, take place more efficiently in the heterogeneous systems using solid acid catalysts [alumina, silica–alumina, HY-type zeolite, and solid superacids (ZrO2 and Fe2O3 treated with H2SO4)] activated by calcination at various temperatures. Mechanisms of both the homogeneous and heterogeneous reduction of dioxygen by AcrH2 and [Fe(C5H4Me)2] are discussed.

Reduction of dioxygen by an NADH model compound and 1,1′-dimethylferrocene catalysed by acids in homogeneous and heterogeneous systems

Acid catalysed multi-electron reduction of nitrobenzene derivatives by an acid-stable NADH analogue, 10-methyl-9,10-dihydroacridine, occurs efficiently under mild conditions in the presence of perchloric acid in acetonitrile. Observation of CIDNP spectra as well as detailed kinetic studies on the acid catalysed reduction of nitrobenzene derivatives by AcrH2 and on the acid catalysed electron transfer from the excited state of [Ru(bpy)3]2+ to nitrobenzene derivatives has revealed that the multi-electron reduction of nitrobenzene derivatives by AcrH2 proceeds via acid catalysed electron transfer radical-chain reactions in which hydrogen transfer from AcrH2 to radicals produced by the acid catalysed one-electron reduction of nitrobenzene derivatives is the rate determining propagation step.

Multi-electron reduction of nitrobenzene derivatives by an acid-stable NADH analogue via acid-catalysed electron transfer radical-chain reactions

Various ketones are readily reduced by an acid-stable NADH model compound, 10-methylacridan (AcrH2), in the presence of perchloric acid in acetonitrile. Rates of the acid-catalyzed reduction of ket...

Acid-Catalyzed Reduction of Ketones by an NADH Model Compound and the Relation with Acid-Catalyzed Photoinduced Electron-Transfer Reactions

Acid-catalysed multi-electron reduction of nitrobenzene derivatives by a dihydronicotinamide adenine dinucleotide (NADH) model compound proceeds efficiently under mild conditions in the presence of perchloric acid in acetonitrile.

Acid-catalysed multi-electron reduction of nitrobenzene derivatives by a dihydronicotinamide adenine dinucleotide (NADH) model compound, 9,10-dihydro-10-methylacridine

Makoto Chiba

Papers

Reduction of dioxygen by an NADH model compound and 1,1′-dimethylferrocene catalysed by acids in homogeneous and heterogeneous systems

Multi-electron reduction of nitrobenzene derivatives by an acid-stable NADH analogue via acid-catalysed electron transfer radical-chain reactions

Acid-Catalyzed Reduction of Ketones by an NADH Model Compound and the Relation with Acid-Catalyzed Photoinduced Electron-Transfer Reactions

Acid-catalysed multi-electron reduction of nitrobenzene derivatives by a dihydronicotinamide adenine dinucleotide (NADH) model compound, 9,10-dihydro-10-methylacridine