The merger of photoredox catalysis with transition metal catalysis, termed metallaphotoredox catalysis, has become a mainstay in synthetic methodology over the past decade. Metallaphotoredox catalysis has combined the unparalleled capacity of transition metal catalysis for bond formation with the broad utility of photoinduced electron- and energy-transfer processes. Photocatalytic substrate activation has allowed the engagement of simple starting materials in metal-mediated bond-forming processes. Moreover, electron or energy transfer directly with key organometallic intermediates has provided novel activation modes entirely complementary to traditional catalytic platforms. This Review details and contextualizes the advancements in molecule construction brought forth by metallaphotocatalysis.

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Modern proximity labeling techniques have enabled significant advances in understanding biomolecular interactions. However, current tools primarily utilize activation modes that are incompatible with complex biological environments, limiting our ability to interrogate cell- and tissue-level microenvironments in animal models. Here, we report μMap-Red, a proximity labeling platform that uses a red-light-excited SnIV chlorin e6 catalyst to activate a phenyl azide biotin probe. We validate μMap-Red by demonstrating photonically controlled protein labeling in vitro through several layers of tissue, and we then apply our platform in cellulo to label EGFR microenvironments and validate performance with STED microscopy and quantitative proteomics. Finally, to demonstrate labeling in a complex biological sample, we deploy μMap-Red in whole mouse blood to profile erythrocyte cell-surface proteins. This work represents a significant methodological advance toward light-based proximity labeling in complex tissue environments and animal models.

Here we report the direct conversion of strong, aliphatic C(sp 3 )−H bonds into the corresponding alkyl sulfinic acids via decatungstate photocatalysis. This transformation has been applied to a diverse range of C(sp 3 )-rich scaffolds, including natural products and approved pharmaceuticals, providing efficient access to complex sulfur-containing products. To demonstrate the broad potential of this methodology for the divergent synthesis of pharmaceutically relevant molecules, procedures for the diversification of the sulfinic acid products into a range of medicinally relevant functional groups have been developed.

C-H functionalization of electron-deficient heteroarenes using commercial unactivated alkyl halides through reductive quenching photoredox catalysis was developed. Mainstream approaches rely on the use of an excess of strong acids that result in regioselectivities dictated by the innate effect of the protonated heteroarene, leaving the functionalization of other carbons unexplored. We report a mild method under basic conditions that allows access to previously underexplored regioselectivities by relying on a combination of conjugate and halogen  ortho-directing effects. Overall, this methodology gives quick access to a variety of alkylated heteroarenes that will be of interest to medicinal chemistry programs.