C–H functionalization reactions are playing an increasing role in the preparation and modification of complex organic molecules, including pharmaceuticals, agrochemicals and polymer precursors. In recent years, there have been many reports of radical C–H functionalization reactions initiated by hydrogen-atom transfer and proceeding via open-shell radical intermediates. These methods introduce strategic opportunities to functionalize C(sp3)–H bonds. Examples include synthetically useful advances in radical-chain reactivity and biomimetic radical-rebound reactions. A growing number of reactions, however, have been found to proceed via radical relay, whereby hydrogen-atom transfer generates a diffusible radical that is functionalized by a separate reagent or catalyst. The latter methods provide the basis for versatile C–H cross-coupling methods with diverse partners. In this Review, we highlight recent examples of radical-chain and radical-rebound methods to provide context for a survey of emerging radical-relay methods, which greatly expand the scope and utility of intermolecular C(sp3)–H functionalization and cross coupling.
This is a preview of subscription content
Subscribe to Journal
Get full journal access for 1 year
only 9,27 € per issue
All prices are NET prices.
VAT will be added later in the checkout.
Tax calculation will be finalised during checkout.
Get time limited or full article access on ReadCube.
All prices are NET prices.
He, J., Wasa, M., Chan, K. S. L., Shao, Q. & Yu, J.-Q. Palladium-catalyzed transformations of alkyl C–H bonds. Chem. Rev. 117, 8754–8786 (2017).
Jazzar, R., Hitce, J., Renaudat, A., Sofack-Kreutzer, J. & Baudoin, O. Functionalization of organic molecules by transition-metal-catalyzed C(sp3)–H activation. Chem. Eur. J. 16, 2654–2672 (2010).
Saint-Denis, T. G., Zhu, R.-Y., Chen, G., Wu, Q.-F. & Yu, J.-Q. Enantioselective C(sp3)–H bond activation by chiral transition metal catalysts. Science 359, eaao4798 (2018).
Gupta, A., Kumar, J., Rahaman, A., Singh, A. K. & Bhadra, S. Functionalization of C(sp3)–H bonds adjacent to heterocycles catalyzed by earth abundant transition metals. Tetrahedron 98, 132415 (2021).
Davies, H. M. L. & Manning, J. R. Catalytic C–H functionalization by metal carbenoid and nitrenoid insertion. Nature 451, 417–424 (2008).
Doyle, M. P., Duffy, R., Ratnikov, M. & Zhou, L. Catalytic carbene insertion into C–H bonds. Chem. Rev. 110, 704–724 (2010).
Roizen, J., Harvey, M. E. & Du Bois, J. Metal-catalyzed nitrogen-atom transfer methods for the oxidant of aliphatic C–H bonds. Acc. Chem. Res. 45, 911–922 (2012).
Yi, H. et al. Recent advances in radical C–H activation/radical cross-coupling. Chem. Rev. 117, 9016–9085 (2017).
Zhang, C., Li, Z.-L., Gu, Q.-S. & Liu, X.-Y. Catalytic enantioselective C(sp3)–H functionalization involving radical intermediates. Nat. Commun. 12, 475 (2021).
Studer, A. & Curran, D. P. Catalysis of radical reactions: a radical chemistry perspective. Angew. Chem. Int. Ed. 55, 58–102 (2016).
Labinger, J. A. & Bercaw, J. E. Understanding and exploiting C–H bond activation. Nature 417, 507–514 (2002).
Sheldon, R. A. & Kochi, J. K. Metal-Catalyzed Oxidations of Organic Compounds: Mechanistic Principles and Synthetic Methodology Including Biochemical Processes (Academic, 1981).
Hermans, I., Spier, E. S., Neuenschwander, U., Turrà, N. & Baiker, A. Selective oxidation catalysis: opportunities and challenges. Top. Catal. 52, 1162–1174 (2009).
Quinn, R. K. et al. Site-selective aliphatic C–H chlorination using N-chloroamides enables a synthesis of chlorolissoclimide. J. Am. Chem. Soc. 138, 696–702 (2016).
Schmidt, V. A., Quinn, R. K., Brusoe, A. T. & Alexanian, E. J. Site-selective aliphatic C–H bromination using N-bromoamides and visible light. J. Am. Chem. Soc. 136, 14389–14392 (2014).
Czaplyski, W. L., Na, C. G. & Alexanian, E. J. C–H xanthylation: a synthetic platform for alkane functionalization. J. Am. Chem. Soc. 138, 13854–13857 (2016).
Tanwar, L., Börgel, J. & Ritter, T. Synthesis of benzylic alcohols by C–H oxidation. J. Am. Chem. Soc. 141, 17983–17988 (2019).
Huang, X. & Groves, J. T. Beyond ferryl-mediated hydroxylation: 40 years of rebound mechanism and C–H activation. J. Biol. Inorg. Chem. 22, 185–207 (2017).
Huang, X. & Groves, J. T. Taming azide radicals for catalytic C–H azidation. ACS Catal. 6, 751–759 (2016).
Clark, J. R., Feng, K., Sookezian, A. & White, M. C. Manganese-catalysed benzylic C(sp3)–H amination for late-stage functionalization. Nat. Chem. 10, 583–591 (2018).
Lovering, F., Bikker, J. & Humblet, C. Escape from flatland: increasing saturation as an approach to improving clinical success. J. Med. Chem. 52, 6752–6756 (2009).
Blakemore, D. C. et al. Organic synthesis provides opportunities to transform drug discovery. Nat. Chem. 10, 383–394 (2018).
Guillemard, L., Kaplaneris, N., Ackermann, L. & Johansson, M. J. Late-stage C–H functionalization offers new opportunities in drug discovery. Nat. Rev. Chem. 5, 522–545 (2021).
Wolff, M. E. Cyclization of N-halogenated amines (the Hofmann-Löffler reaction). Chem. Rev. 63, 55–64 (1963).
Statement, L. M., Nakafuku, K. M. & Nagib, D. A. Remote C–H functionalization via selective hydrogen atom transfer. Synthesis 50, 1569–1586 (2018).
Sarkar, S., Cheung, K. P. S. & Gevorgyan, V. C–H functionalization reactions enabled by hydrogen atom transfer to carbon-centred radicals. Chem. Sci. 11, 12974–12993 (2020).
Nodwell, M. B. et al. Direct photocatalytic fluorination of benzylic C–H bonds with N-fluorobenzenesulfonimide. Chem. Commun. 51, 11783–11786 (2015).
Pitts, C. R., Ling, B., Woltornist, R., Liu, R. & Lectka, T. Triethylborane-initiated radical chain fluorination: a synthetic method derived from mechanistic insight. J. Org. Chem. 79, 8895–8899 (2014).
Pitts, C. R. et al. Direct, catalytic monofluorination of sp3 C–H bonds: a radical-based mechanism with ionic selectivity. J. Am. Chem. Soc. 136, 9780–9791 (2014).
Bloom, S. et al. Iron(II)-catalyzed benzylic fluorination. Org. Lett. 15, 1722–1724 (2013).
Buss, J. A., Vasilopoulos, A., Golden, D. L. & Stahl, S. S. Copper-catalyzed functionalization of benzylic C–H bonds with N-fluorobenzenesulfonimide: switch from C–N to C–F bond formation promoted by a redox buffer and Brønsted base. Org. Lett. 22, 5749–5752 (2020).
Bloom, S. et al. A polycomponent metal-catalyzed aliphatic, allylic, and benzylic fluorination. Angew. Chem. Int. Ed. 51, 10580–10583 (2012).
Xia, J.-B., Zhu, C. & Chen, C. Visible light-promoted metal-free C–H activation: diarylketone-catalyzed selective benzylic mono- and difluorination. J. Am. Chem. Soc. 135, 17494–17500 (2013).
Halperin, S. D., Fan, H., Chang, S., Martin, R. E. & Britton, R. A convenient photocatalytic fluorination of unactivated C–H bonds. Angew. Chem. Int. Ed. 53, 4690–4693 (2014).
Bloom, S., McCann, M. & Lectka, T. Photocatalyzed benzylic fluorination: shedding “light” on the involvement of electron transfer. Org. Lett. 16, 6338–6341 (2014).
Carestia, A. M., Ravelli, D. & Alexanian, E. J. Reagent-dictated site selectivity in intermolecular aliphatic C–H functionalizations using nitrogen-centred radicals. Chem. Sci. 9, 5360–5365 (2018).
MacMillan, A. J. et al. Practical and selective sp3 C–H bond chlorination via aminium radicals. Angew. Chem. Int. Ed. 60, 7132–7139 (2021).
Xiang, M. et al. Visible light-catalyzed benzylic C–H bond chlorination by a combination of organic dye (Acr+-Mes) and N-chlorosuccinimide. J. Org. Chem. 85, 9080–9087 (2020).
Ozawa, J. & Kanai, M. Silver-catalyzed C(sp3)–H chlorination. Org. Lett. 19, 1430–1433 (2017).
Quiclet-Sire, B. & Zard, S. Z. The xanthate route to amines, anilines, and other nitrogen compounds. A brief account. Synlett 27, 680–701 (2016).
Huang, X. & Groves, J. T. Oxygen activation and radical transformations in heme proteins and metallophorphyrins. Chem. Rev. 118, 2491–2553 (2018).
Leising, R. A., Norman, R. E. & Que, L. Jr. Alkane functionalization by non-porphyrin iron complexes: mechanistic insights. Inorg. Chem. 29, 2553–2555 (1990).
Chen, K., Costas, M. & Que, L. Jr. Spin state tuning of non-heme iron-catalyzed hydrocarbon oxidations: participation of FeIII–OOH and FeV=O intermediates. J. Chem. Soc. Dalton Trans. 5, 672–679 (2002).
Kim, J., Kim, C., Harrison, R. G., Wilkinson, E. C. & Que, L. Jr. Fe(TPA)-catalyzed alkane hydroxylation can be a metal-based oxidation. J. Mol. Catal. A Chem. 117, 83–89 (1997).
Chen, K. & Que, L. Jr Stereospecific alkane hydroxylation by non-heme iron catalysts: mechanistic evidence for an FeV=O active species. J. Am. Chem. Soc. 123, 6327–6337 (2001).
Costas, M., Tipton, A. K., Chen, K., Jo, D.-H. & Que, L. Jr. Modeling Rieske dioxygenases: the first example of iron-catalyzed asymmetric cis-dihydroxylation of olefins. J. Am. Chem. Soc. 123, 6722–6723 (2001).
Kim, C., Chen, K., Kim, J. & Que, L. Jr Stereospecific alkane hydroxylation with H2O2 catalyzed by an iron(II)–tris(2-pyridylmethyl)amine complex. J. Am. Chem. Soc. 119, 5964–5965 (1997).
Costas, M. & Que, L. Jr Ligand topology tuning of iron-catalyzed hydrocarbon oxidations. Angew. Chem. Int. Ed. 41, 2179–2181 (2002).
Chen, M. S. & White, M. C. A predictably selective aliphatic C–H oxidation reaction for complex molecule synthesis. Science 318, 783–787 (2007).
St John, P., Guan, Y., Kim, Y., Kim, S. & Paton, R. S. Prediction of homolytic bond dissociation enthalpies for organic molecules at near chemical accuracy with sub-second computational cost. Nat. Commun. 11, 2328 (2020).
Chen, M. S. & White, M. C. Combined effects on selectivity in Fe-catalyzed methylene oxidation. Science 327, 566–571 (2010).
Gormisky, P. E. & White, M. C. Catalyst-controlled aliphatic C–H oxidations with a predictive model for site-selectivity. J. Am. Chem. Soc. 135, 14052–14055 (2013).
Howell, J. M., Feng, K., Clark, J. R., Trzepkowski, L. J. & White, M. C. Remote oxidation of aliphatic C–H bonds in nitrogen-containing molecules. J. Am. Chem. Soc. 137, 14590–14593 (2015).
Osberger, T. J., Rogness, D. C., Kohrt, J. T., Stepan, A. F. & White, M. C. Oxidative diversification of amino acids and peptides by small-molecule iron catalysis. Nature 537, 214–219 (2016).
Dantignana, V. et al. Chemoselective aliphatic C–H bond oxidation enabled by polarity reversal. ACS Cent. Sci. 3, 1350–1358 (2017).
Borrell, M., Gil-Caballero, S., Bietti, M. & Costas, M. Site-selective and product chemoselective aliphatic C–H bond hydroxylation of polyhydroxylated substrates. ACS Catal. 10, 4702–4709 (2020).
Zhao, J., Nanjo, T., de Luca, E. C. & White, M. C. Chemoselective methylene oxidation in aromatic molecules. Nat. Chem. 11, 213–221 (2019).
Milan, M., Bietti, M. & Costas, M. Highly enantioselective oxidation of nonactivated aliphatic C–H bonds with hydrogen peroxide catalyzed by manganese complexes. ACS Cent. Sci. 3, 196–204 (2017).
White, M. C., Doyle, A. G. & Jacobsen, E. N. A synthetically useful, self-assembling MMO mimic system for catalytic alkene epoxidation with aqueous H2O2. J. Am. Chem. Soc. 123, 7194–7195 (2001).
Oloo, W. N. & Que, L. Jr Bioinspired nonheme iron catalysts for C–H and C=C bond oxidation: insights into the nature of the metal-based oxidants. Acc. Chem. Res. 48, 2612–2621 (2015).
Kal, S., Xu, S. & Que, L. Jr Bio-inspired nonheme iron oxidation catalysis: involvement of oxoiron(V) oxidants in cleaving strong C–H bonds. Angew. Chem. Int. Ed. 59, 7332–7349 (2020).
Liu, W. & Groves, J. T. Manganese catalyzed C–H halogenation. Acc. Chem. Res. 48, 1727–1735 (2015).
Liu, W. et al. Oxidative aliphatic C–H fluorination with fluoride ion catalyzed by a manganese porphyrin. Science 337, 1322–1325 (2012).
Li, G., Dilger, A. K., Cheng, P. T., Ewing, W. R. & Groves, J. T. Selective C–H halogenation with a highly fluorinated manganese porphyrin. Angew. Chem. Int. Ed. 57, 1251–1255 (2018).
Liu, W. et al. Site-selective 18F fluorination of unactivated C–H bonds mediated by a manganese porphyrin. Chem. Sci. 9, 1168–1172 (2018).
Huang, X., Bergsten, T. M. & Groves, J. T. Manganese-catalyzed late-stage aliphatic C–H azidation. J. Am. Chem. Soc. 137, 5300–5303 (2015).
Huang, X. et al. Alkyl isocyanates via manganese-catalyzed C–H activation for the preparation of substituted ureas. J. Am. Chem. Soc. 139, 15407–15413 (2017).
Ishii, Y., Sakaguchi, S. & Iwahama, T. Innovation of hydrocarbon oxidation with molecular oxygen and related reactions. Adv. Synth. Catal. 343, 393–427 (2001).
Sterckx, H., Morel, B. & Maes, B. U. W. Catalytic aerobic oxidation of C(sp3)–H bonds. Angew. Chem. Int. Ed. 58, 7946–7970 (2019).
Ishii, Y., Iwahama, T., Sakaguchi, S., Nakayama, K. & Nishiyama, Y. Alkane oxidation with molecular oxygen using a new efficient catalytic system: N-hydroxyphthalimide (NHPI) combined with Co(acac)n (n = 2 or 3). J. Org. Chem. 61, 4520–4526 (1996).
Hruszkewycz, D. P., Miles, K. C., Thiel, O. R. & Stahl, S. S. Co/NHPI-mediated oxygenation of benzylic C–H bonds in pharmaceutically relevant molecules. Chem. Sci. 8, 1282–1287 (2017).
Cooper, J. C., Luo, C., Kameyama, R. & Van Humbeck, J. F. Combined iron/hydroxytriazole dual catalytic system for site selective oxidation adjacent to azaheterocycles. J. Am. Chem. Soc. 140, 1243–1246 (2018).
Gaster, E., Kozuch, S. & Pappo, D. Selective aerobic oxidation of methylarenes to benzaldehydes catalyzed by N-hydroxyphthalimide and cobalt(II) acetate in hexafluoropropan-2-ol. Angew. Chem. Int. Ed. 56, 5912–5915 (2017).
Schultz, D. M. et al. Oxyfunctionalization of the remote C–H bonds of aliphatic amines by decatungstate photocatalysis. Angew. Chem. Int. Ed. 56, 15274–15278 (2017).
Wu, W. et al. (nBu4N)4W10O32-catalyzed selective oxygenation of cyclohexane by molecular oxygen under visible light irradiation. Appl. Catal. B Environ. 164, 113–119 (2015).
Laudadio, G. et al. Selective C(sp3)–H aerobic oxidation enabled by decatungstate photocatalysis in flow. Angew. Chem. Int. Ed. 57, 4078–4082 (2018).
Lee, J. M., Park, J., Cho, S. H. & Chang, S. Cu-facilitated C–O bond formation using N-hydroxyphthalimide: efficient and selective functionalization of benzyl and allylic C–H bonds. J. Am. Chem. Soc. 130, 7824–7825 (2008).
Guo, Z., Jin, C., Zhou, J. & Su, W. Copper(II)-catalyzed cross dehydrogenative coupling reaction of N-hydroxyphthalimide with alkanes and ethers via unactivated C(sp3)–H activation at room temperature. RSC Adv. 6, 79016–79019 (2016).
Zhang, X., Yang, H. & Tang, P. Transition-metal-free oxidative aliphatic C–H azidation. Org. Lett. 17, 5828–5831 (2015).
Kim, K., Lee, S. & Hong, S. H. Direct C(sp3)–H cyanation enabled by highly active decatungstate photocatalyst. Org. Lett. 23, 5501–5505 (2021).
Sarver, P. J., Bissonnette, N. B. & MacMillan, D. W. C. Decatungstate-catalyzed C(sp3)–H sulfinylation: rapid access to diverse organosulfur functionality. J. Am. Chem. Soc. 143, 9737–9743 (2021).
Schirmer, T. E., Rolka, A. B., Karl, T. A., Holzhausen, F. & König, B. Photocatalytic C–H trifluoromethylthiolation by the decatungstate anion. Org. Lett. 23, 5729–5733 (2021).
Capaldo, L. & Ravelli, D. Decatungstate as direct hydrogen atom transfer photocatalyst for SOMOphilic alkynylation. Org. Lett. 23, 2243–2247 (2021).
Mao, R., Bera, S., Turla, A. C. & Hu, X. Copper-catalyzed intermolecular functionalization of unactivated C(sp3)–H bonds and aliphatic carboxylic acids. J. Am. Chem. Soc. 143, 14667–14675 (2021).
Bentley, K. W., Dummit, K. A. & Van Humbeck, J. F. A highly site-selective radical sp3 C–H amination of azaheterocycles. Chem. Sci. 9, 6440–6445 (2018).
Hu, A., Guo, J.-J., Pan, H. & Zuo, Z. Selective functionalization of methane, ethane, and higher alkanes by cerium photocatalysis. Science 361, 668–672 (2018).
An, Q. et al. Cerium-catalyzed C–H functionalizations of alkanes utilizing alcohols as hydrogen atom transfer agents. J. Am. Chem. Soc. 142, 6216–6226 (2020).
Yang, Q. et al. Photocatalytic C–H activation and the subtle role of chlorine radical complexation in reactivity. Science 372, 847–852 (2021).
Ryu, I. et al. Efficient C–H/C–N and C–H/C–CO–N conversion via decatungstate-photoinduced alkylation of diisopropyl azodicarboxylate. Org. Lett. 15, 2554–2557 (2013).
Bonassi, F., Ravelli, D., Protti, S. & Fagnoni, M. Decatungstate photocatalyzed acylations and alkylations in flow via hydrogen atom transfer. Adv. Synth. Catal. 357, 3687–3695 (2015).
Wan, T. et al. Accelerated and scalable C(sp3)–H amination via decatungstate photocatalysis using a flow photoreactor equipped with high-intensity LEDs. ACS Cent. Sci. 8, 51–56 (2022).
Giese, B. Formation of CC bonds by addition of free radicals to alkenes. Angew. Chem. Int. Ed. Engl. 22, 753–764 (1983).
Crespi, S. & Fagnoni, M. Generation of alkyl radicals: from the tyranny of tin to the photon democracy. Chem. Rev. 120, 9790–9833 (2020).
Kanegusuku, A. L. G. & Roizen, J. L. Recent advances in photoredox-mediated radical conjugate addition reactions: an expanding toolkit for the Giese reaction. Angew. Chem. Int. Ed. 60, 2–36 (2021).
Treacy, S. M. & Rovis, T. Copper-catalyzed C(sp3)–H bond alkylation via photoinduced ligand-to-metal charge transfer. J. Am. Chem. Soc. 143, 2729–2735 (2021).
Kang, Y. C., Treacy, S. M. & Rovis, T. Iron-catalyzed photoinduced LMCT: a 1° C–H abstraction enables skeletal rearrangements and C(sp3)–H alkylation. ACS Catal. 11, 7442–7449 (2021).
Angioni, S. et al. Tetrabutylammonium decatungstate (chemo)selective photocatalyzed, radical C–H functionalization in amides. Adv. Synth. Catal. 350, 2209–2214 (2008).
Yamada, K. et al. Photocatalyzed site-selective C–H to C–C conversion of aliphatic nitriles. Org. Lett. 17, 1292–1295 (2015).
Fukuyama, T. et al. Photocatalyzed site-selective C(sp3)–H functionalization of alkylpyridines at non-benzylic positions. Org. Lett. 19, 6436–6439 (2017).
Fukuyama, T., Nishikawa, T. & Ryu, I. Site-selective C(sp3)–H functionalization of fluorinated alkanes driven by polar effects using a tungstate photocatalyst. Eur. J. Org. Chem. 2020, 1424–1428 (2020).
Laudadio, G. et al. C(sp3)–H functionalizations of light hydrocarbon using decatungstate photocatalysis in flow. Science 369, 92–96 (2020).
Roberts, B. P. Polarity-reversal catalysis of hydrogen-atom abstraction reactions: concepts and applications in organic chemistry. Chem. Soc. Rev. 28, 25–35 (1999).
Lei, G., Xu, M., Chang, R., Funes-Ardoiz, I. & Ye, J. Hydroalkylation of unactivated olefins via visible-light-driven dual hydrogen atom transfer catalysis. J. Am. Chem. Soc. 143, 11251–11261 (2021).
Minisci, F., Bernardi, R., Bertini, F., Galli, R. & Perchinummo, M. Nucleophilic character of alkyl radicals — VI: a new convenient selective alkylation of heteroaromatic bases. Tetrahedron 27, 3575–3579 (1971).
Proctor, R. S. J. & Phipps, R. J. Recent advances in Minisci-type reactions. Angew. Chem. Int. Ed. 58, 13666–13699 (2019).
Leonov, D. & Elad, D. Ultraviolet- and γ-ray-induced reactions of nucleic acid constituents. Reactions of purines with ethers and dioxolane. J. Org. Chem. 39, 1470–1473 (1974).
Deng, G., Ueda, K., Yanagisawa, S., Itami, K. & Li, C.-J. Coupling of nitrogen heteroaromatics and alkanes without transition metals: a new oxidative cross-coupling at C–H/C–H bonds. Chem. Eur. J. 15, 333–337 (2009).
Xia, R., Niu, H.-Y., Qu, G.-R. & Guo, H.-M. CuI controlled C–C and C–N bond formation of heteroaromatics through C(sp3)–H activation. Org. Lett. 14, 5546–5549 (2012).
Shao, X., Wu, X., Wu, S. & Zhu, C. Metal-free radical-mediated C(sp3)–H heteroarylation of alkanes. Org. Lett. 22, 7450–7454 (2020).
Tzirakis, M. D., Lykakis, I. N. & Orfanopoulos, M. Decatungstate as an efficient photocatalyst in organic chemistry. Chem. Soc. Rev. 38, 2609–2621 (2009).
Quattrini, M. C. et al. Versatile cross-dehydrogenative coupling of heteroaromatics and hydrogen donors via decatungstate photocatalysis. Chem. Commun. 53, 2335–2338 (2017).
De Waele, V., Poizat, O., Fagnoni, M., Bagno, A. & Ravelli, D. Unraveling the key features of the reactive state of decatungstate anion in hydrogen atom transfer (HAT) photocatalysis. ACS Catal. 6, 7174–7182 (2016).
Ravelli, D., Fagnoni, M., Fukuyama, T., Nishikawa, T. & Ryu, I. Site-selective C–H functionalization by decatungstate anion photocatalysis: synergistic control by polar and steric effects expands the reaction scope. ACS Catal. 8, 701–703 (2018).
Li, G.-X., Hu, X., He, G. & Chen, G. Photoredox-mediated Minisci-type alkylation of N-heteroarenes with alkanes with high methylene selectivity. ACS Catal. 8, 11847–11853 (2018).
Lee, W., Jung, S., Kim, M. & Hong, S. Site-selective direct C–H pyridylation of unactivated alkanes by triplet excited anthraquinone. J. Am. Chem. Soc. 143, 3003–3012 (2021).
Shu, C., Noble, A. & Aggarwal, V. K. Metal-free photoinduced C(sp3)–H borylation of alkanes. Nature 586, 714–719 (2020).
Kharasch, M. S. & Sosnovsky, G. The reactions of t-butyl perbenzoate and olefins–a stereospecific reaction. J. Am. Chem. Soc. 80, 756 (1958).
Kharasch, M. & Fono, A. Radical substitution reactions. J. Org. Chem. 23, 325–326 (1958).
Kochi, J. K. Copper salt-catalyzed reaction of butenes with peresters. J. Am. Chem. Soc. 84, 774–784 (1962).
Muzart, J. Enantioselective copper-catalyzed allylic acetoxylation of cyclohexene. J. Mol. Catal. 64, 381–384 (1991).
Andrus, M. B., Argade, A. B., Chen, X. & Pamment, M. G. The asymmetric Kharasch reaction. Catalytic enantioselective allylic acyloxylation of olefins with chiral copper(I) complexes and tert-butyl perbenzoate. Tetrahedron Lett. 36, 2945–2948 (1995).
Gokhale, A. S., Minidis, A. B. E. & Pfaltz, A. Enantioselective allylic oxidation catalyzed by chiral bisoxazoline-copper complexes. Tetrahedron Lett. 36, 1831–1834 (1995).
Kawasaki, K., Tsumura, S. & Katsuki, T. Enantioselective allylic oxidation using biomimetic tris(oxazolines)-copper(II) complex. Synlett 1995, 1245–1246 (1995).
Andrus, M. B. & Zhou, Z. Highly enantioselective copper–bisoxazoline-catalyzed allylic oxidation of cyclic olefins with tert-butyl p-nitroperbenzoate. J. Am. Chem. Soc. 124, 8806–8807 (2002).
Corey, E. J. & Lee, J. Enantioselective total synthesis of oleanolic acid, erythrodiol, β-amyrin, and other pentacyclic triterpenes from a common intermediate. J. Am. Chem. Soc. 115, 8873–8874 (1993).
Neukirch, H. et al. Improved anti-inflammatory activity of three new terpenoids derived, by systematic chemical modifications, from the abundant triterpenes of the flowery plant calendula officinalis. Chem. Biodivers. 2, 657–671 (2005).
García-Cabeza, A. L. et al. Allylic oxidation of alkenes catalyzed by a copper–aluminum mixed oxide. Org. Lett. 16, 1598–1601 (2014).
García-Cabeza, A. L. et al. Optimization by response surface methodology (RSM) of the Kharasch–Sosnovsky oxidation of valencene. Org. Process Res. Dev. 19, 1662–1666 (2015).
Gephart, R. T. et al. Reaction of CuI with dialkyl peroxides: CuII-alkoxides, alkoxy radicals, and catalytic C–H etherification. J. Am. Chem. Soc. 134, 17350–17353 (2012).
Tran, B. L., Driess, M. & Hartwig, J. F. Copper-catalyzed oxidative dehydrogenative carboxylation of unactivated alkanes to allylic esters via alkenes. J. Am. Chem. Soc. 136, 17292–17301 (2014).
Kohmura, Y., Kawasaki, K. & Katsuki, T. Benzylic and allylic amination. Synlett 12, 1456–1458 (1997).
Pelletier, G. & Powell, D. A. Copper-catalyzed amidation of allylic and benzylic C–H bonds. Org. Lett. 8, 6031–6034 (2006).
Powell, D. A. & Fan, H. Copper-catalyzed amination of primary benzylic C–H bonds with primary and secondary sulfonamides. J. Org. Chem. 75, 2726–2729 (2010).
Wiese, S. et al. Catalytic C–H amination with unactivated amines through copper(II) amides. Angew. Chem. Int. Ed. 49, 8850–8855 (2010).
Tran, B. L., Li, B., Driess, M. & Hartwig, J. F. Copper-catalyzed intermolecular amidation and imidation of unactivated alkanes. J. Am. Chem. Soc. 136, 2555–2563 (2014).
Zheng, Y.-W., Narobe, R., Donabauer, K., Yabukov, S. & König, B. Copper(II)-photocatalyzed N–H alkylation with alkanes. ACS Catal. 10, 8582–8589 (2020).
Borduas, N. & Powell, D. A. Copper-catalyzed oxidative coupling of benzylic C–H bonds with 1,3-dicarbonyl compounds. J. Org. Chem. 73, 7822–7825 (2008).
Song, Z.-Q. et al. Photoredox oxo-C(sp3)–H bond functionalization via in situ Cu(I)-acetylide catalysis. Org. Lett. 22, 832–836 (2020).
Vasilopoulos, A., Zultanski, S. L. & Stahl, S. S. Feedstocks to pharmacophores: Cu-catalyzed oxidative arylation of inexpensive alkylarenes enabling direct access to diarylalkanes. J. Am. Chem. Soc. 139, 7705–7708 (2017).
Xie, W., Heo, J., Kim, D. & Chang, S. Copper-catalyzed direct C–H alkylation of polyfluoroarenes by using hydrocarbons as an alkylating source. J. Am. Chem. Soc. 142, 7487–7496 (2020).
Ni, Z. et al. Highly regioselective copper-catalyzed benzylic C–H amination by N-fluorobenzenesulfonimide. Angew. Chem. Int. Ed. 51, 1244–1247 (2012).
Zhang, W. et al. Enantioselective cyanation of benzylic C–H bonds via copper-catalyzed radical relay. Science 353, 1014–1018 (2016).
Xiao, H. et al. Copper-catalyzed late-stage benzylic C(sp3)–H trifluoromethylation. Chem 5, 940–949 (2019).
Suh, S.-E. et al. Site-selective copper-catalyzed azidation of benzylic C–H bonds. J. Am. Chem. Soc. 142, 11388–11393 (2020).
Sharma, A. & Hartwig, J. F. Metal-catalyzed azidation of tertiary C–H bonds suitable for late-stage functionalization. Nature 517, 600–604 (2015).
Margrey, K. A., Czaplyski, W. L., Nicewicz, D. A. & Alexanian, E. J. A general strategy for aliphatic C–H functionalization enabled by organic photoredox catalysis. J. Am. Chem. Soc. 140, 4213–4217 (2018).
Liu, S. et al. Copper-catalyzed oxidative benzylic C(sp3)–H amination: direct synthesis of benzylic carbamates. Chem. Commun. 56, 13013–13016 (2020).
Wang, A., DeOliveira, C. C. & Emmert, M. Non-directed, copper catalyzed benzylic C–H amination avoiding substrate excess. Preprint at ChemRxiv https://doi.org/10.26434/chemrxiv.8792243.v2 (2019).
Jiang, C., Chen, P. & Liu, G. Copper-catalyzed benzylic C–H bond thiocyanation: enabling late-stage diversifications. CCS Chem. 2, 1884–1893 (2020).
Suh, S.-E., Nkulu, L. E., Lin, S., Krska, S. W. & Stahl, S. S. Benzylic C–H isocyanation/amine coupling sequence enabling high-throughput synthesis of pharmaceutically relevant ureas. Chem. Sci. 12, 10380–10387 (2021).
Vasilopoulos, A., Golden, D. L., Buss, J. A. & Stahl, S. S. Copper-catalyzed C–H fluorination/functionalization sequence enabling benzylic C–H cross coupling with diverse nucleophiles. Org. Lett. 22, 5753–5757 (2020).
Champagne, P. A. et al. Enabling nucleophilic substitution reactions of activated alkyl fluorides through hydrogen bonding. Org. Lett. 15, 2210–2213 (2013).
Champagne, P. A., Benhassine, Y., Desroches, J. & Paquin, J.-P. Friedel–Crafts reaction of benzyl fluorides: selective activation of C–F bonds as enabled by hydrogen bonding. Angew. Chem. Int. Ed. 53, 13835–13839 (2014).
Hemelaere, R., Champagne, P. A., Desroches, J. & Paquin, J.-F. Faster initiation in the Friedel–Crafts reaction of benzyl fluorides using trifluoroacetic acid as activator. J. Fluorine Chem. 190, 1–6 (2016).
Hamel, J.-D. & Paquin, J.-F. Activation of C–F bonds α to C–C multiple bonds. Chem. Commun. 54, 10224–10239 (2018).
Lopez, M. A., Buss, J. A. & Stahl, S. S. Cu-catalyzed site-selective benzylic chlorination enabling net C–H coupling with oxidatively sensitive nucleophiles. Org. Lett. 24, 597–601 (2022).
Jin, J. et al. Copper(I)-catalyzed site-selective C(sp3)–H bond chlorination of ketones, (E)-enones and alkylbenzenes by dichloramine-T. Nat. Commun. 12, 4065 (2021).
Fawcett, A., Keller, M. J., Herrera, Z. & Hartwig, J. F. Site selective chlorination of C(sp3)–H bonds suitable for late-stage functionalization. Angew. Chem. Int. Ed. 60, 8276–8283 (2021).
Li, J. et al. Site-specific allylic C–H bond functionalization with a copper-bound N-centered radical. Nature 574, 516–521 (2019).
Zhou, J., Jin, C., Li, X. & Su, W. Copper-catalyzed oxidative esterification of unactivated C(sp3)–H bonds with carboxylic acids via cross dehydrogenative coupling. RCS Adv. 5, 7232–7236 (2015).
Hu, H. et al. Copper-catalyzed benzylic C–H coupling with alcohols via radical relay enabled by redox buffering. Nat. Catal. 3, 358–367 (2020).
Chen, S.-J., Golden, D. L., Krska, S. W. & Stahl, S. S. Copper-catalyzed cross-coupling of benzylic C–H bonds and azoles with controlled N-site selectivity. J. Am. Chem. Soc. 143, 14438–14444 (2021).
Ivanova, A. E. et al. Ambident polyfluoroalkyl-substituted pyrazoles in the methylation reactions. J. Fluorine Chem. 195, 47–56 (2017).
Huang, A. et al. Regioselective synthesis, NMR, and crystallographic analysis of N1-substituted pyrazoles. J. Org. Chem. 82, 8864–8872 (2017).
Zhang, W., Chen, P. & Liu, G. Copper-catalyzed arylation of benzylic C–H bonds with alkylarenes as the limiting reagents. J. Am. Chem. Soc. 139, 7709–7712 (2017).
Zhang, W., Wu, L., Chen, P. & Liu, G. Enantioselective arylation of benzylic C–H bonds by copper-catalyzed radical relay. Angew. Chem. Int. Ed. 58, 6425–6429 (2019).
Fu, L., Zhang, Z., Chen, P., Lin, Z. & Liu, G. Enantioselective copper-catalyzed alkynylation of benzylic C–H bonds via radical relay. J. Am. Chem. Soc. 142, 12493–12500 (2020).
Li, Z., Cao, L. & Li, C.-J. FeCl2-catalyzed selective C–C bond formation by oxidative activation of a benzylic C–H bond. Angew. Chem. Int. Ed. 46, 6505–6507 (2007).
Xia, Q., Chen, W. & Qiu, H. Direct C–N coupling of imidazoles and benzylic compounds via iron-catalyzed oxidative activation of C–H bonds. J. Org. Chem. 76, 7577–7582 (2011).
Kumar, J., Suresh, E. & Bhadra, S. Catalytic direct α-amination of arylacetic acid synthons with anilines. J. Org. Chem. 85, 13363–13374 (2020).
Karimov, R. R., Sharma, A. & Hartwig, J. F. Late stage azidation of complex molecules. ACS Cent. Sci. 2, 715–724 (2016).
Ye, Y.-H., Zhang, J., Wang, G., Chen, S.-Y. & Yu, X.-Q. Cobalt-catalyzed benzylic C–H amination via dehydrogenative-coupling reaction. Tetrahedron 67, 4649–4654 (2011).
Tang, S., Wang, P., Li, H. & Lei, A. Multimetallic catalysed radical oxidative C(sp3)–H /C(sp)–H cross-coupling between unactivated alkanes and terminal alkynes. Nat. Commun. 7, 11676 (2016).
Liu, D., Liu, C., Li, H. & Lei, A. Direct functionalization of tetrahydrofuran and 1,4-dioxane: nickel-catalyzed oxidative C(sp3)–H arylation. Angew. Chem. Int. Ed. 52, 4453–4456 (2013).
Liu, D. et al. Nickel-catalyzed selective oxidative radical cross-coupling: an effective strategy for inert Csp3–H functionalization. Org. Lett. 17, 998–1001 (2015).
Vasilopoulos, A., Krska, S. W. & Stahl, S. S. C(sp3)–H methylation enabled by peroxide photosensitization and Ni-mediated radical coupling. Science 372, 398–403 (2021).
Schönherr, H. & Cernak, T. Profound methyl effects in drug discovery and a call for new C–H methylation reactions. Angew. Chem. Int. Ed. 52, 12256–12267 (2013).
Xu, P., Guo, S., Wang, L. & Tang, P. Silver-catalyzed oxidative activation of benzylic C–H bonds for the synthesis of difluoromethylated arenes. Angew. Chem. Int. Ed. 126, 6065–6068 (2014).
Yang, H. et al. Silver-promoted oxidative benzylic C–H trifluoromethoxylation. Angew. Chem. Int. Ed. 57, 13266–13270 (2018).
Skubi, K. L., Blum, T. R. & Yoon, T. P. Dual catalysis strategies in photochemical synthesis. Chem. Soc. Rev. 116, 10035–10074 (2016).
Twilton, J. et al. The merger of transition metal and photocatalysis. Nat. Rev. Chem. 1, 0052 (2017).
Shaw, M. H., Twilton, J. & MacMillan, D. W. C. Photoredox catalysis in organic chemistry. J. Org. Chem. 81, 6898–6926 (2016).
Levin, M. D., Kim, S. & Toste, F. D. Photoredox catalysis unlocks single-electron elementary steps in transition metal catalyzed cross-coupling. ACS Cent. Sci. 2, 293–301 (2016).
Matsui, J. K., Lang, S. B., Heitz, D. R. & Molander, G. A. Photoredox-mediated routes to radicals: the value of catalytic radical generation in synthetic methods development. ACS Catal. 7, 2563–2575 (2017).
McAtee, R. C., McClain, E. J. & Stephenson, C. R. J. Illuminating photoredox catalysis. Trends Chem. 1, 111–125 (2019).
Chan, A. Y. et al. Metallaphotoredox: the merger of photoredox and transition metal catalysis. Chem. Rev. 122, 1485–1542 (2022).
Capaldo, L., Ravelli, D. & Fagnoni, M. Direct photocatalyzed hydrogen atom transfer (HAT) for aliphatic C–H bonds elaboration. Chem. Rev. 122, 1875–1924 (2022).
Leibler, I. N.-M., Tekle-Smith, M. A. & Doyle, A. A general strategy for C(sp3)–H functionalization with nucleophiles using methyl radical as a hydrogen atom abstractor. Nat. Commun. 12, 6950 (2021).
Zhang, Y. et al. A photoredox-catalyzed approach for formal hydride abstraction to enable a general Csp3–H fluorination with HF. Chem Catalysis 2, 292–308 (2022).
Li, G.-X. et al. A unified photoredox-catalysis strategy for C(sp3)–H hydroxylation and amidation using hypervalent iodine. Chem. Sci. 8, 7180–7185 (2017).
Michaudel, Q., Thevenet, D. & Baran, P. S. Intermolecular Ritter-type C–H amination of unactivated sp3 carbons. J. Am. Chem. Soc. 134, 2547–2550 (2012).
Kiyokawa, K., Takemoto, K. & Minakata, S. Ritter-type amination of C–H bonds at tertiary carbon centers using iodic acid as an oxidant. Chem. Commun. 52, 13082–13085 (2016).
Maeda, B., Sakakibara, Y., Murakami, K. & Itami, K. Photoredox-catalyzed benzylic esterification via radical-polar crossover. Org. Lett. 23, 5113–5117 (2021).
Meng, Q.-Y., Schirmer, T. E., Berger, A. L., Donabauer, K. & König, B. Photocarboxylation of benzylic C–H bonds. J. Am. Chem. Soc. 141, 11393–11397 (2019).
Berger, A. L., Donabauer, K. & König, B. Photocatalytic carbanion generation from C–H bonds–reductant free Barbier/Grignard-type reactions. Chem. Sci. 10, 10991–10996 (2019).
Bosnidou, A. E. & Muñiz, K. Intermolecular radical C(sp3)–H amination under iodine catalysis. Angew. Chem. Int. Ed. 58, 7485–7489 (2019).
Romine, A. M. et al. Easy access to the copper(III) anion [Cu(CF3)4]−. Angew. Chem. Int. Ed. 54, 2745–2749 (2015).
Guo, S., AbuSalim, D. I. & Cook, S. P. Aqueous benzylic C–H trifluoromethylation for late-stage functionalization. J. Am. Chem. Soc. 140, 12378–12382 (2018).
He, J., Nguyen, T. N., Guo, S. & Cook, S. P. Csp3–H trifluoromethylation of unactivated aliphatic systems. Org. Lett. 23, 702–705 (2021).
Choi, G., Lee, G. S., Park, B., Kim, D. & Hong, S. H. Direct C(sp3)–H trifluoromethylation of unactivated alkanes enabled by multifunctional trifluoromethyl copper complexes. Angew. Chem. Int. Ed. 60, 5467–5474 (2021).
Sarver, P. J. et al. The merger of decatungstate and copper catalysis to enable aliphatic C(sp3)–H trifluoromethylation. Nat. Chem. 12, 459–467 (2020).
Shaw, M. H., Shurtleff, V. W., Terrett, J. A., Cuthbertson, J. D. & MacMillan, D. W. C. Native functionality in triple catalytic cross-coupling: sp3 C–H bonds as latent nucleophiles. Science 352, 1304–1308 (2016).
Le, C., Liang, Y., Evans, R. W., Li, X. & MacMillan, D. W. C. Selective sp3 C–H alkylation via polarity-match-based cross-coupling. Nature 547, 79–83 (2017).
Zhang, X. & MacMillan, D. W. C. Direct aldehyde C–H arylation and alkylation via the combination of nickel, hydrogen atom transfer, and photoredox catalysis. J. Am. Chem. Soc. 139, 11353–11356 (2017).
Twilton, J. et al. Selective hydrogen atom abstraction through induced bond polarization: direct α-arylation of alcohols through photoredox, HAT, and nickel catalysis. Angew. Chem. Int. Ed. 57, 5369–5373 (2018).
Ma, Z.-Y. et al. Sulfonamide as photoinduced hydrogen-atom transfer catalyst for regioselective alkylation of C(sp3)–H bonds adjacent to heteroatoms. Org. Lett. 23, 474–479 (2021).
Perry, I. B. et al. Direct arylation of strong aliphatic C–H bonds. Nature 560, 70–75 (2018).
Berger, M., Goldblatt, I. L. & Steel, C. Photochemistry of benzaldehyde. J. Am. Chem. Soc. 95, 1717–1725 (1973).
Dórman, G., Nakamura, H., Pulsipher, A. & Prestwich, G. D. The life of pi star: exploring the exciting and forbidden worlds of the benzophenone photophore. Chem. Rev. 116, 15284–15398 (2016).
Shen, Y., Gu, Y. & Martin, R. sp3 C–H arylation and alkylation enabled by the synergy of triplet excited ketones and nickel catalysts. J. Am. Chem. Soc. 140, 12200–12209 (2018).
Dewanji, A., Krach, P. E. & Rueping, M. The dual role of benzophenone in visible-light/nickel photoredox-catalyzed C–H arylations: hydrogen-atom transfer and energy transfer. Angew. Chem. Int. Ed. 58, 3566–3570 (2019).
Zhang, L. et al. The combination of benzaldehyde and nickel-catalyzed photoredox C(sp3)–H alkylation/arylation. Angew. Chem. Int. Ed. 58, 1823–1827 (2019).
Si, X., Zhang, L. & Hashmi, S. K. Benzaldehyde- and nickel-catalyzed photoredox C(sp3)–H alkylation/arylation with amides and thioethers. Org. Lett. 21, 6329–6332 (2019).
Heitz, D. R., Tellis, J. C. & Molander, G. A. Photochemical nickel-catalyzed C–H arylation: synthetic scope and mechanistic investigations. J. Am. Chem. Soc. 138, 12715–12718 (2016).
Shields, B. J. & Doyle, A. G. Direct C(sp3)–H cross-coupling enabled by catalytic generation of chlorine radicals. J. Am. Chem. Soc. 138, 12719–12722 (2016).
Nielsen, M. K. et al. Mild, redox-neutral formylation of aryl chlorides through the photocatalytic generation of chlorine radicals. Angew. Chem. Int. Ed. 56, 7191–7194 (2017).
Chang, X., Lu, H. & Lu, Z. Enantioselective benzylic C–H arylation via photoredox and nickel dual catalysis. Nat. Commun. 10, 3549 (2019).
Cheng, X., Li, T., Liu, Y. & Lu, Z. Stereo- and enantioselective benzylic C–H alkenylation via photoredox/nickel dual catalysis. ACS Catal. 11, 11059–11065 (2021).
Joe, C. L. & Doyle, A. G. Direct acylation of C(sp3)–H bonds enabled by nickel and photoredox catalysis. Angew. Chem. Int. Ed. 55, 4040–4043 (2016).
Ahneman, D. T. & Doyle, A. G. C–H functionalization of amines with aryl halides by nickel-photoredox catalysis. Chem. Sci. 7, 7002–7006 (2016).
Novaes, L. F. et al. Electrocatalysis as an enabling technology for organic synthesis. Chem. Soc. Rev. 50, 7941–8002 (2021).
Chen, N. & Xu, H.-C. Electrochemical generation of nitrogen-centered radicals for organic synthesis. Green Synth. Catal. 2, 165–178 (2021).
Masui, M., Hara, S., Ueshima, T., Kawagushi, T. & Ozaki, S. Anodic oxidation of compounds having benzylic or allylic carbon and α-carbon to hetero atom using N-hydroxyphthalimide as a mediator. Chem. Pharm. Bull. 31, 4209–4211 (1983).
Masui, M., Hosomi, K., Tsuchida, K. & Ozaki, S. Electrochemical oxidation of olefins using N-hydroxyphthalimide as a mediator. Chem. Pharm. Bull. 33, 4798–4802 (1985).
Masui, M., Hara, S. & Ozaki, S. Anodic oxidation of amides and lactams using N-hydroxyphthalimide as a mediator. Chem. Pharm. Bull. 34, 975–979 (1986).
Nutting, J. E., Rafiee, M. R. & Stahl, S. S. Tetramethylpiperidine N-oxyl (TEMPO), phthalimide N-oxyl (PINO), and related N-oxyl species: Electrochemical properties and their use in electrocatalytic reactions. Chem. Rev. 118, 4834–4885 (2018).
Horn, E. J. et al. Scalable and sustainable electrochemical allylic C–H oxidation. Nature 533, 77–81 (2016).
Mo, Y. & Jensen, K. F. Continuous N-hydroxyphthalimide (NHPI)-mediated electrochemical aerobic oxidation of benzylic C–H bonds. Chem. Eur. J. 24, 10260–10265 (2018).
Kawamata, Y. et al. Scalable, electrochemical oxidation of unactivated C–H bonds. J. Am. Chem. Soc. 139, 7448–7451 (2017).
Saito, M. et al. N-ammonium ylide mediators for electrochemical C–H oxidation. J. Am. Chem. Soc. 143, 7859–7867 (2021).
Rafiee, M., Wang, F., Hruszkewycz, D. P. & Stahl, S. S. N-hydroxyphthalimide-mediated electrochemical iodination of methylarenes and comparison to electron-transfer-initiated C–H functionalization. J. Am. Chem. Soc. 140, 22–25 (2018).
Hayashi, R., Shimizu, A. & Yoshida, J. The stabilized cation pool method: metal- and oxidant-free benzylic C–H/aromatic C–H cross-coupling. J. Am. Chem. Soc. 138, 8400–8403 (2016).
Zhu, Y. et al. A promising electro-oxidation of methyl-substituted aromatic compounds to aldehydes in aqueous imidazole ionic liquid solutions. J. Electroanal. Chem. 751, 105–110 (2015).
Das, A., Nutting, J. E. & Stahl, S. S. Electrochemical C–H oxygenation and alcohol dehydrogenation involving Fe-oxo species using water as the oxygen source. Chem. Sci. 10, 7542–7548 (2019).
Robinson, S. G., Mack, J. B. C., Alektiar, S. N., Du Bois, J. & Sigman, M. S. Electrochemical ruthenium-catalyzed C–H hydroxylation of amine derivatives in aqueous acid. Org. Lett. 22, 7060–7063 (2020).
Meyer, T. H., Samanta, R. C., Del Vecchio, A. & Ackermann, L. Mangana(III/IV)electro-catalyzed C(sp3)–H azidation. Chem. Sci. 12, 2890–2897 (2021).
Niu, L. et al. Manganese-catalyzed oxidative azidation of C(sp3)–H bonds under electrophotocatalytic conditions. J. Am. Chem. Soc. 142, 17693–17702 (2020).
This work was supported by funding from the NIH (R35 GM134929).
The authors declare no competing interests.
Peer review information
Nature Reviews Chemistry thanks S. Bagley and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Golden, D.L., Suh, SE. & Stahl, S.S. Radical C(sp3)–H functionalization and cross-coupling reactions. Nat Rev Chem 6, 405–427 (2022). https://doi.org/10.1038/s41570-022-00388-4