Applications of Proton-Coupled Electron Transfer in Organic Synthesis

Abstract

Proton-coupled electron transfer (PCET) reactions are a kind of unconventional redox reactions, which exhibit special reactivities and selectivities due to their unique interdependent electron-proton transfer mechanisms. There are three possible pathways of PCET processes, including stepwise electron transfer followed by proton transfer (ETPT), proton transfer followed by electron transfer (PTET), and concerted pathway in which electron and proton transfer synchronously (CEPT), avoiding intermediates with high energy. These reactions have been playing a key role in numerous areas in organic chemistry, inorganic chemistry, bioorganic chemistry, organometallic and material chemistry, including the redox processes in natural and artificial systems, such as the activation for small molecules. Recently, the application of PCET reactions in organic synthesis has received a great deal of attentions and interests. Being accompanied by the development of electrochemical methods and photocatalysts, more and more novel reactions in electrochemistry and photochemistry involve PCET processes have been reported. Applying these electrochemical and photochemical methods, the activation of X-H bond has been achieved via PCET processes, including C-H bond, N-H bond, P-H bond, S-H bond or O-H bond. Thus, based on these crucial processes, a number of vital structures and fundamental frameworks can be synthesized, and various synthetic building blocks and natural products have been attained. For example, pharmaceutical building blocks like 2°-piperidines can be cyanated at their α-position; substituted dimeric pyrroloindolines such as (-)-calycanthidine, (-)-chimonanthine, and (-)-psychotriasine have also been successfully synthesized via PCET mechanism. Moreover, not only the products of reduction of multiple bonds (C＝ Y bond such as C＝C bond, C＝N bond and C＝O bond), but also the products of self/cross-coupling have been achieved via PCET mechanism. In this review, the recent applications and developments of PCET mechanism in organic synthesis are summarized, including new catalyst systems and new reagents, especially with electrochemical and photochemical methodologies. The future of this area has also been demonstrated from both experimental and theoretical aspects. Keywords proton-coupled electron transfer; organic synthesis; radical reactions; functionalization

Molecular Mechanism of the Mononuclear Copper Complex‐Catalyzed Water Oxidation from Cluster‐Continuum Model Calculations

“…As shown in Scheme 2, the calculated p K a of 3 2 is around 11, while the calculated H 2 O→OH − ligand exchange has an exothermicity of 7.2 kcal mol −1 , indicating both pathways are feasible, but the latter pathway could be more favorable at the experimental pH of 11.5. In the third pathway (III), the formation of .+ L−Cu II −OH − may transpire via the proton‐coupled electron transfer, a prevalent process in electrochemical reactions [91–98] . However, such a process is associated with a redox potential of 1.39 V and thus less unfavorable compared to the pathway 3 2 → 3 3′ .…”

“…In the third pathway (III), the formation of * + LÀ Cu II À OH À may transpire via the proton-coupled electron transfer, a prevalent process in electrochemical reactions. [91][92][93][94][95][96][97][98] However, such a process is associated with a redox potential of 1.39 V and thus less unfavorable compared to the pathway 3 2! 3 3'.…”

Decoupled Photoelectrochemical Cerium-Catalyzed Oxydichlorination of Alkynes: Slow Releasing of Chloride Ions and Chlorine Radicals

“…As an efficient merger of photoredox catalysis (PRC) and synthetic organic electrochemistry (SOE), synthetic photoelectrochemistry (PEC) has been illustrated as a sustainable synthetic platform for novel transformations in organic synthesis over the past decade. − Featuring a wide redox window (−4.5 to 4.5 eV), mild conditions, “traceless” redox agents, and energy saving, PEC is deemed as a new frontier for single electron transfer (SET) and used as a combined “upconversion” technology for the energy transfer from photons and electrons to reactants. − A key issue for PEC is the exploitation and selection of photoelectrocatalysts with their redox and photophysical properties to precisely match the reactants. Despite the fact that a series of photo-responsive redox mediators including cyclopropenium ions, triarylamines, naphthalene-imides, and some other aromatics − were developed (Figure ), metal-based ones are often being ignored and rarely reported in PEC. − In fact, benefiting from versatile properties including ligand-to-metal charge transfer (LMCT), − metal-to-ligand charge transfer (MLCT), and proton-coupled electron transfer (PCET), − metal-based catalysts have been widely used in SET chemistry. , …”

Photoredox-Catalyzed and Copper(II) Salt-Assisted Radical Addition/Hydroxylation Reaction of Alkenes, Sulfur Ylides, and Water

“…To our knowledge, the use of sulfur ylides to generate the corresponding carbon radicals is still unknown . We envisioned that, in principle, the marriage of visible-light photoredox and proton-coupled electron transfer (PCET) might provide a new platform for controlled conversion of sulfur ylides to the corresponding carbon radicals (Scheme c). Note that since the work of Kellogg on photocatalytic SET-reduction of α-bromo carbonyl compounds, α-carbonyl alkyl bromides have been widely explored as precursors to access various α-carbonyl carbon radicals in many C–C bond-forming reactions .…”