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

Abstract

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.

Highly selective single and multiple deuteration of unactivated C(sp3)-H bonds

“…This is a powerful method, but the preinstallation of an allylsulfonyl moiety on the nitrogen atom is crucial to successful initiation of the radical rearrangement to generate the N-centered radical and produce 1 equivalent of SO 2 and allylsulfides as the concomitant products. Thus we questioned if the more challenging free N-H contained amides are competent substrates for radical H/D exchange of remote C(sp 3 )-H bonds through proton-coupled electron transfer (PCET) 33 – 36 process. The key challenges to such reactions stem from concerns that the single electron oxidation of strong N-H bonds (100~110 kcal mol −1 ) 37 , 38 and the acidic protons in N-H moiety would prevent a high deuterium incorporation from D 2 O.…”

Electrochemical ammonium-cation-assisted pyridylation of inert N-heterocycles via dual-proton-coupled electron transfer

“…It is well known that electron-deficient pyridine derivatives are often modified into salts as radical acceptors for Minisci reactions due to their inherently negative electrode potential, which makes them difficult to activate ( Scheme 1 B) ( Proctor and Phipps, 2019 ). The dual-proton-coupled electron transfer strategy may provide a promising roadmap for this transformation ( Lehnherr et al., 2020 ; Murray et al., 2022 ; Tay et al., 2022 ). Although various elegant pyridylation strategies have been established in recent years by employing photocatalysis and metal or metal-free catalysis ( Huang et al., 2021 ; Kim et al., 2019 ; Novaes et al., 2021 ; Shen et al., 2021 ; Tong et al., 2021 ; Xu et al., 2021 ; Zhang et al., 2017a , 2017b , 2020 , 2021 ; Zhu et al., 2019 ).…”

Electrochemical Site-Selective Alkylation of Azobenzenes with (Thio)Xanthenes

“…In recent years, electrochemical synthesis has received increasing attention for its powerful ability to forge chemical bonds, presumably due to the advantages of no external stoichiometric chemical oxidants or reductants and milder conditions over the conventional approaches [ 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 ]. As a result, we speculate that electrochemistry maybe provides a unique opportunity to facilitate the functionalization of azobenzene.…”