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1. Photoredox catalysis on unactivated substrates with strongly reducing iridium photosensitizers

   https://doi.org/10.1039/D0SC06306A  

   Shon, Jong-Hwa; Kim, Dooyoung; Rathnayake, Manjula D.; Sittel, Steven; Weaver, Jimmie; Teets, Thomas S. (January 2021, Chemical Science)

   null (Ed.)

   Photoredox catalysis has emerged as a powerful strategy in synthetic organic chemistry, but substrates that are difficult to reduce either require complex reaction conditions or are not amenable at all to photoredox transformations. In this work, we show that strong bis-cyclometalated iridium photoreductants with electron-rich β-diketiminate (NacNac) ancillary ligands enable high-yielding photoredox transformations of challenging substrates with very simple reaction conditions that require only a single sacrificial reagent. Using blue or green visible-light activation we demonstrate a variety of reactions, which include hydrodehalogenation, cyclization, intramolecular radical addition, and prenylation via radical-mediated pathways, with optimized conditions that only require the photocatalyst and a sacrificial reductant/hydrogen atom donor. Many of these reactions involve organobromide and organochloride substrates which in the past have had limited utility in photoredox catalysis. This work paves the way for the continued expansion of the substrate scope in photoredox catalysis. 

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2. Cooperative Photometallobiocatalysis: Nonheme Fe Enzyme‐Catalyzed Enantioconvergent Radical Decarboxylative Azidation, Thiocyanation, and Isocyanation of Redox‐Active Esters

   https://doi.org/10.1002/anie.202506361  

   Zhao, Liu‐Peng; Lin, Ken; Xie, Pei‐Pei; Liu, Huichong; Xiang, Hengye; Liu, Xin; Zhao, Yunlong; Liu, Peng; Yang, Yang (July 2025, Angewandte Chemie International Edition)

   Abstract Cooperative catalysis with an enzyme and a small‐molecule photocatalyst has recently emerged as a potentially general activation mode to advance novel biocatalytic reactions with synthetic utility. Herein, we report cooperative photobiocatalysis involving an engineered nonheme Fe enzyme and a tailored photoredox catalyst to achieve enantioconvergent decarboxylative azidation, thiocyanation, and isocyanation of redox‐active esters via a radical mechanism. We repurposed and further evolved metapyrocatechase (MPC), a nonheme Fe extradiol dioxygenase not previously studied in new‐to‐nature biocatalysis, for the enantioselective C─N₃, C─SCN, and C─NCO bond formation via an enzymatic Fe─X intermediate (X═N₃, NCS, and NCO). A range of primary, secondary, and tertiary alkyl radical precursors were effectively converted by our engineered MPC, allowing the syntheses of organic azides, thiocyanates, and isocyanates with good to excellent enantiocontrol. Further derivatization of these products furnished valuable compounds including enantioenriched amines, triazoles, ureas, and SCF₃‐containing products. DFT and MD simulations shed light on the mechanism as well as the binding poses of the alkyl radical intermediate in the enzyme active site and the π‐facial selectivity in the enantiodetermining radical rebound. Overall, cooperative photometallobiocatalysis with nonheme Fe enzymes provides a means to develop challenging asymmetric radical transformations eluding small‐molecule catalysis. 

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3. Advancing Organic Photoredox Catalysis: Mechanistic Insight through Time-Resolved Spectroscopy

   https://doi.org/10.1021/acs.jpclett.4c00895  

   Huxter, Vanessa M (July 2024, The Journal of Physical Chemistry Letters)

   The rapid development of light-activated organic photoredox catalysts has led to the proliferation of powerful synthetic chemical strategies with industrial and pharmaceutical applications. Despite the advancement in synthetic approaches, a detailed understanding of the mechanisms governing these reactions has lagged. Time-resolved optical spectroscopy provides a method to track organic photoredox catalysis processes and reveal the energy pathways that drive reaction mechanisms. These measurements are sensitive to key processes in organic photoredox catalysis such as charge or energy transfer, lifetimes of singlet or triplet states, and solvation dynamics. The sensitivity and specificity of ultrafast spectroscopic measurements can provide a new perspective on the mechanisms of these reactions, including electron-transfer events, the role of solvent, and the short lifetimes of radical intermediates. 

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4. Photoredox Product Selectivity Controlled by Persistent Radical Stability

   https://doi.org/10.1021/acs.joc.3c00490  

   Stevenson, Bernard G.; Gironda, Cameron; Talbott, Eric; Prascsak, Amanda; Burnett, Nora L.; Kompanijec, Victoria; Nakhamiyayev, Roman; Fredin, Lisa A.; Swierk, John R. (May 2023, The Journal of Organic Chemistry)

   The use of photoredox catalysis for the synthesis of small organic molecules relies on harnessing and converting the energy in visible light to drive reactions. Specifically, photon energy is used to generate radical ion species that can be harnessed through subsequent reaction steps to form a desired product. Cyanoarenes are widely used as arylating agents in photoredox catalysis because of their stability as persistent radical anions. However, there are marked, unexplained variations in product yields when using different cyanoarenes. In this study, the quantum yield and product yield of an α-aminoarylation photoredox reaction between five cyanoarene coupling partners and N-phenylpyrrolidine were characterized. Significant discrepancies in cyanoarene consumption and product yield suggested a chemically irreversible, unproductive pathway in the reaction. Analysis of the side products in the reaction demonstrated the formation of species consistent with radical anion fragmentation. Electrochemical and computational methods were used to study the fragmentation of the different cyanoarenes and revealed a correlation between product yield and cyanoarene radical anion stability. Kinetic modeling of the reaction demonstrates that cross-coupling selectivity between N-phenylpyrrolidine and the cyanoarene is controlled by the same phenomenon present in the persistent radical effect. 

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5. The Photoredox Paradox: Electron and Hole Upconversion as the Hidden Secrets of Photoredox Catalysis

   https://doi.org/10.1021/jacs.4c10422  

   Alabugin, Igor V; Eckhardt, Paul; Christopher, Kimberley M; Opatz, Till (October 2024, Journal of the American Chemical Society)

   Although photoredox catalysis is complex from a mechanistic point of view, it is also often surprisingly efficient. In fact, the quantum efficiency of a puzzlingly large portion of photoredox reactions exceeds 100% (i.e., the measured quantum yields (QYs) are >1). Hence, these photoredox reactions can be more than perfect with respect to photon utilization. In several documented cases, a single absorbed photon can lead to the formation of >100 molecules of the product, behavior known to originate from chain processes. In this Perspective, we explore the underlying reasons for this efficiency, identify the nature of common catalytic chains, and highlight the differences between HAT and SET chains. Our goal is to show why chains are especially important in photoredox catalysis and where the thermodynamic driving force that sustains the SET catalytic cycles comes from. We demonstrate how the interplay of polar and radical processes can activate hidden catalytic pathways mediated by electron and hole transfer (i.e., electron and hole catalysis). Furthermore, we illustrate how the phenomenon of redox upconversion serves as a thermodynamic precondition for electron and hole catalysis. After discussing representative mechanistic puzzles, we analyze the most common bond forming steps, where redox upconversion frequently occurs (and is sometimes unavoidable). In particular, we highlight the importance of 2-center-3-electron bonds as a recurring motif that allows a rational chemical approach to the design of redox upconversion processes. 

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