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1. Remote C–H Functionalization via Selective Hydrogen Atom Transfer

   https://doi.org/10.1055/s-0036-1591930  

   Stateman, Leah; Nakafuku, Kohki; Nagib, David (April 2018, Synthesis)

   The selective functionalization of remote C–H bonds via intramolecular hydrogen atom transfer (HAT) is transformative for organic synthesis. This radical-mediated strategy provides access to novel reactivity that is complementary to closed-shell pathways. As modern methods for mild generation of radicals are continually developed, inherent selectivity paradigms of HAT mechanisms offer unparalleled opportunities for developing new strategies for C–H functionalization. This review outlines the history, recent advances, and mechanistic underpinnings of intramolecular HAT as a guide to addressing ongoing challenges in this arena. 1 Introduction 2 Nitrogen-Centered Radicals 2.1 sp3 N-Radical Initiation 2.2 sp2 N-Radical Initiation 3 Oxygen-Centered Radicals 3.1 Carbonyl Diradical Initiation 3.2 Alkoxy Radical Initiation 3.3 Non-alkoxy Radical Initiation 4 Carbon-Centered Radicals 4.1 sp2 C-Radical Initiation 4.2 sp3 C-Radical Initiation 5 Conclusion 

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2. Simple amination of polystyrene via radical sp3 C–H imination

   https://doi.org/10.1039/D4PY01021C  

   Hu, Mengnan; He, Lizhe; Comito, Robert J (December 2024, Polymer Chemistry)

   We report the mild functionalization of polystyrene with primary amines and other nitrogen groups through sp3 C–H imination. This process significantly increases hydrophilicity without deterioration of molecular weight or thermal properties, and provides a handle for further covalent modification. This work will enable the upcycling and diversification of commodity polyolefins. 

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3. Recent applications of C–H functionalization in complex natural product synthesis

   https://doi.org/10.1039/C8CS00716K  

   Abrams, Dylan J.; Provencher, Philip A.; Sorensen, Erik J. (November 2018, Chemical Society Reviews)

   In this review, recent examples featuring C–H functionalization in the synthesis of complex natural products are discussed. A focus is given to the way in which C–H functionalization can influence the logical process of retrosynthesis, and the review is organized by the type and method of C–H functionalization. 

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4. Photoinduced C(sp ³ )–H sulfination empowers the direct and chemoselective introduction of the sulfonyl group

   https://doi.org/10.1039/D1SC04245A  

   Jin, Shengfei; Haug, Graham C.; Trevino, Ramon; Nguyen, Viet D.; Arman, Hadi D.; Larionov, Oleg V. (October 2021, Chemical Science)

   Direct installation of the sulfinate group by the functionalization of unreactive aliphatic C–H bonds can provide access to most classes of organosulfur compounds, because of the central position of sulfinates as sulfonyl group linchpins. Despite the importance of the sulfonyl group in synthesis, medicine, and materials science, a direct C(sp 3 )–H sulfination reaction that can convert abundant aliphatic C–H bonds to sulfinates has remained elusive, due to the reactivity of sulfinates that are incompatible with typical oxidation-driven C–H functionalization approaches. We report herein a photoinduced C(sp 3 )–H sulfination reaction that is mediated by sodium metabisulfite and enables access to a variety of sulfinates. The reaction proceeds with high chemoselectivity and moderate to good regioselectivity, affording only monosulfination products and can be used for a solvent-controlled regiodivergent distal C(sp 3 )–H functionalization. 

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5. Sulfenylnitrene-mediated nitrogen-atom insertion for late-stage skeletal editing of N -heterocycles

   https://doi.org/10.1126/science.adp0974  

   Ghosh, Bidhan; Kafle, Prakash; Mukherjee, Rishav; Welles, Randall; Herndon, Deacon; Nicholas, Kenneth M; Shao, Yihan; Sharma, Indrajeet (January 2025, Science)

   Given the prevalence of nitrogen-containing heterocycles in commercial drugs, selectively incorporating a single nitrogen atom is a promising scaffold hopping approach to enhance chemical diversity in drug discovery libraries. We harness the distinct reactivity of sulfenylnitrenes, which insert a single nitrogen atom to transform readily available pyrroles, indoles, and imidazoles into synthetically challenging pyrimidines, quinazolines, and triazines, respectively. Our additive-free method for skeletal editing employs easily accessible, benchtop-stable sulfenylnitrene precursors over a broad temperature range (−30 to 150°C). This approach is compatible with diverse functional groups, including oxidation-sensitive functionalities such as phenols and thioethers, and has been applied to various natural products, amino acids, and pharmaceuticals. Furthermore, we have conducted mechanistic studies and explored regioselectivity outcomes through density functional theory calculations. 

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