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.

Oxidative cross-coupling has developed into a robust method for carbon–carbon (C–C), carbon–heteroatom (C–X), and heteroatom–heteroatom (X–Y) bond formation. Despite considerable advances in this field, the traditional oxidative cross-coupling reactions usually employ stoichiometric amounts of chemical oxidants to clean up surplus electrons from substrates to form new chemical bonds. Organic electrosynthesis is recognized as an environmentally benign and particularly powerful synthetic platform. Recent advancements have revealed that radical-involved electrochemical oxidative cross-coupling reactions can be achieved under exogenous-oxidant-free conditions. This tutorial review provides an overview of the most recent developments in electrochemical oxidative cross-coupling with hydrogen evolution involving radicals. Emphasis is mainly placed on synthetic and mechanistic aspects. We hope that this tutorial review can promote the development of radical chemistry, electrochemistry, and oxidative cross-coupling reactions.

Recent advances in electrochemical oxidative cross-coupling with hydrogen evolution involving radicals

Electrochemical multicomponent synthesis of 4-selanylpyrazoles under catalyst- and chemical-oxidant-free conditions

There is a resurgence of interests in organic electrochemistry, which is generally accepted as a green synthetic tool. In this context, many electrochemical methods have been developed in the past decade to access various nitrogen-centered radicals (NCRs) from readily available precursors in a controlled fashion, enabling the rapid development of many NCR-mediated new reactions for the construction of nitrogen-containing organic compounds. In this review, recent advances in the chemistry of electrochemically generated NCRs are critically highlighted, based on the electrochemical strategies for their formation and the types of NCRs. Focus is put on the mechanism for the electrochemical generation of different NCRs and their synthetic applications.

Electrochemical generation of nitrogen-centered radicals for organic synthesis

https://pubs.rsc.org/en/content/articlepdf/2020/gc/d0gc01324b

Zi-Chen Wang

Papers

Electrochemical intramolecular C–H/N–H functionalization for the synthesis of isoxazolidine-fused isoquinolin-1(2H)-ones

Electrochemically enabled rhodium-catalyzed [4 + 2] annulations of arenes with alkynes

Metal-Free Catalyzed Cyclization of N-Methoxybenzamides to Construct Quaternary Carbon-Containing Isoindolinones