Visible-light induced direct C(sp³)–H functionalization: recent advances and future prospects

Abstract

The direct activation of inert saturated C–H bonds for selective functionalization has long been a significant challenge in organic synthesis. The past few decades have witnessed the emergence of visible-light-induced synthesis, which also offers a new platform for achieving direct C(sp³)–H functionalization under mild conditions. Due to the tremendous research effort devoted to this, various novel visible-light-driven protocols have been established, enabling the efficient and sustainable preparation of value-added molecules from readily available alkane feedstocks. Inspired by the recent breakthroughs, herein we summarize the latest methodologies reported from the second half of 2021 to the first half of 2024, with a particular emphasis on the formation of C–P, C–B, C–S bonds, etc., along with some efforts in asymmetric C–H functionalization, to reveal the current trends and the existing challenges in this rapid-developing field.

---

Jia-Lin Tu

Jialin Tu was born in Hubei Province, China, in 1996. He obtained his degree in Medicinal Chemistry from Soochow University in 2021. In the same year, he joined the research group of Professor Wujiong Xia at the Harbin Institute of Technology, focusing on the applications of iron photocatalysis in C–H activation and decarboxylation reactions, as well as photoelectrocatalysis.

Yining Zhu

Yining Zhu was born in Zhejiang Province, China, in 1997. He obtained his B.S. in Materials Chemistry at Harbin Institute of Technology in 2019. He joined the research group of Professor Wujiong Xia in 2021 at the Harbin Institute of Technology, with a research focus on iron photocatalysis for C–H activation and decarboxylation.

Pengcheng Li

Pengcheng Li was born in Shandong Province, China, in 1989. He obtained his degree in Inorganic Chemistry from Yantai University in 2017. He joined the research group of Professor Wujiong Xia in 2018 at the Harbin Institute of Technology, with a research focus on transition metal photocatalysis for C–H activation.

Binbin Huang

Binbin Huang obtained his bachelor's degree from Zhejiang University in 2014. Later, he acquired both his master's (2016) and PhD (2021) degrees under the supervision of Prof. Wujiong Xia at Harbin Institute of Technology. After graduation, he took a position in Beijing Normal University at Zhuhai. His research interest mainly focuses on the development of sustainable organic synthetic protocols that are enabled by photo- and electrochemical methods.

---

1. Introduction

The selective activation of inert C(sp³)–H bonds poses a significant challenge in organic synthesis, due to the high bond dissociation energies (BDEs) of saturated C–H bonds and their ubiquity in organic molecules (Scheme 1a).¹ The precise conversion of alkanes into value-added products in a more sustainable and step-economical way is always of paramount appeal, and therefore, direct C–H activation is often dubbed the “Holy Grail” of organic synthesis.² The development of efficient methodologies for C–H activation holds the potential to profoundly influence the field of organic synthesis, by which chemists can streamline the synthesis of complex molecules, reduce the reliance on prefunctionalized starting materials, and minimize the waste generation.³

Scheme 1 Background information for this review.

Over the past few decades, visible-light-induced organic synthesis has attracted considerable research attention and is regarded as an emerging green, efficient, and economical synthetic methodology,⁴ which also offers a new avenue for achieving direct C(sp³)–H functionalization.⁵ In 2021, Wu^5a and Fagnoni^5b independently disclosed their own comprehensive accounts on the advances in visible-light-induced C–H functionalization, showcasing the prospects for overcoming the inherent challenges via hydrogen atom transfer (HAT) processes. Based on the pathways leading to the generation of HAT reagents (generally induced by visible light irradiation), the related C–H activation research can be classified into two broad categories:⁵ direct HAT processes (exemplified by photosensitizers such as eosin Y,⁶ TBADT,⁷ and benzophenone,⁸ which upon photoexcitation and intersystem crossing can directly abstract hydrogen atoms from alkanes) and indirect HAT processes (e.g., the visible-light-excited iron chloride species could not abstract the hydrogen atom, but the chlorine radical generated via a ligand-to-metal charge transfer process serves as the real powerful HAT reagent).⁹

Despite the significant progress in visible-light-induced C(sp³)–H activation that has been documented in these elegant reviews, the field continues to evolve rapidly, and promising new discoveries and advancements have been reported.¹⁰ From the second half of 2021 to the first half of 2024, breakthroughs in visible-light-induced C(sp³)–H functionalization have been achieved, particularly with the rise of photoinduced ligand-to-metal charge transfer (LMCT) processes¹¹ and photoelectrocatalytic systems,¹² which are also the catalytic patterns to be highlighted in this review (Scheme 1b). Photocatalytic C–H functionalization using inexpensive metals such as iron,⁹ copper,¹³ cerium,¹⁴ bismuth¹⁵ and titanium¹⁶ has been deepened. Apart from the homolytic cleavage of metal chlorides under photoinduced LMCT or single-electron oxidation of chlorides, Shi's group pioneered the generation of chlorine radicals using electron donor–acceptor complexes.^10b For direct C(sp³)–H phosphorylation, Hu^17a and Xia^17b independently reported their photocatalytic systems to address the long-standing challenge, producing trivalent phosphines direct from economical hydrocarbons, which hold the potential to serve as versatile ligands in organic synthesis.¹⁸ Alkyl boronates are widely utilized as practical synthetic intermediates in cross-coupling reactions, which can be accessed by Aggarwal's metal-free photoinduced C(sp³)–H borylation.¹⁹ Building on Aggarwal's pioneering work, several groups have made notable advancements in this challenging transformation by means of visible-light photocatalysis or photoelectrocatalysis.²⁰ Furthermore, progress has also been achieved in C(sp³)–H sulfurization through different visible-light-mediated pathways,^20a,21 which is driven by the ubiquitous presence of sulfur-containing moieties in pharmaceutical compounds and natural products.²²

To further propel the development of this field and complement the earlier reviews,⁵ this review will systematically summarize the recent advances in visible-light (mainly purple light around 370–390 nm) induced C(sp³)–H functionalization over the past three years, and several UV-light (<370 nm) enabled strategies are also included. It is noteworthy that while the remote C(sp³)–H activation strategies represent significant strides in visible-light-enabled organic synthesis, these reactions often require tailored substrate structures to facilitate radical migration,²³ which therefore would only be briefly addressed in the subsequent discussions. The review is categorized by the diverse C–X (X = hetero atom) bonds formed directly from unactivated C(sp³)–H, with a particular emphasis on the formation of C–P, C–B, and C–S bonds, among others. Additionally, concerning the significance of asymmetric synthesis,^5g we also highlight some of the latest achievements (mainly reported after 2023) in visible-light-enabled enantioselective C(sp³)–H functionalization in an independent section. The scope of this review is presented in Scheme 1c. We believe that these recent examples along with the discussion will not only underscore the transformative potential of visible-light-induced organic synthesis in C(sp³)–H activation, but also provide crucial perspectives for advancing sustainable and efficient chemical processes.

2. C(sp³)–H phosphorylation

The construction of C–P bonds is of immense importance in organic synthesis and the pharmaceutical chemistry.²⁴ From a synthetic perspective, phosphorus ligands play a crucial role in catalytic reactions, and phosphorus-containing compounds are pivotal in drug development,²⁵ as exemplified by certain antibiotics²⁶ and anticancer agents.²⁷ Moreover, phosphorus-containing compounds find extensive applications as pesticides and herbicides, bolstering agricultural productivity.²⁸ Recent methods for C–P bond formation primarily involve transition metal catalysis using copper,²⁹ nickel,³⁰ or palladium.³¹ Moreover, systems for radical phosphorylation have been developed using highly reactive radical precursors such as alkyl halides, N-hydroxyphthalimide (NHPI) esters, and Katritzky salts, to react with diphosphates or chlorophosphates.³² However, these methods are ineffective for the direct phosphorylation of inert C(sp³)–H bonds, and their photocatalytic counterparts typically work on specific positions, such as benzylic positions³³ and α-positions adjacent to nitrogen atoms.³⁴ In late 2023, Wu et al. developed a visible-light-induced remote C(sp³)–H phosphonylation of aliphatic amines,³⁵ but this substrate-specific method lacks generality for broader applications. Consequently, developing a robust method for the phosphorylation of simple alkane C(sp³)–H bonds remains a significant endeavor.

In 2023, Hu^17a and Xia^17bet al. almost simultaneously reported the first visible-light-induced, iron-catalyzed direct C(sp³)–H phosphorylation of unactivated alkanes (Scheme 2). Exemplified by the work of Xia and Guo (Scheme 2b),^17b the reaction is facilitated by a photoinduced Fe-LMCT process under 390 nm light irradiation, and demonstrates a broad substrate scope, showing compatibility with simple alkanes containing halide, ketone, ester, nitrile, ether, thioether, and silane moieties. The visible-light-mediated C(sp³)–H phosphorylation reaction proceeds through a series of key steps. Upon visible-light excitation, the iron(III) complex undergoes an intramolecular LMCT process, generating a reduced iron(II) complex and a highly reactive chlorine radical (Cl˙). The chlorine radical then engages in an HAT process with the C–H bond of alkane 1, producing an alkyl radical intermediate 1′. This carbon-centered radical subsequently adds onto chlorodiphenylphosphine 2 to form intermediate 10, which rapidly undergoes a single-electron-transfer (SET) process with the iron(II) complex, yielding the desired C(sp³)–H phosphorylation product 3 and completing the catalytic cycle of the iron catalyst.

Scheme 2 Visible-light-induced C(sp³)–H phosphorylation of hydrocarbons.

Shortly thereafter, Huang and Zhu et al. reported a similar photoinduced, iron-LMCT catalyzed C(sp³)–H phosphorylation reaction (Scheme 3).³⁶ Apart from monochlorophenyl phosphines, dichlorophenyl phosphines 12 and even phosphorus trichloride can be used as the phosphating reagents, resulting in dialkylated or trialkylated trivalent phosphorus derivatives. By adding hydrogen peroxide or elemental sulfur after the reaction, pentavalent phosphorus compounds can be obtained with O- or S-incorporation.

Scheme 3 Iron-catalyzed C(sp³)–H phosphorylation via photoinduced LMCT.

3. C(sp³)–H borylation

The vacant p-orbital of boron atoms enables the formation of stable σ bonds with carbon atoms. This imparts unique reactivity to boron-containing compounds, rendering them invaluable in organic synthesis,³⁷ particularly as substrates in Suzuki coupling reactions,³⁸ which have significantly advanced the related fields. Significant strides have been made in transition metal/iridium-catalyzed C–H borylation³⁹ and radical pathways for C–B bond formation.⁴⁰ Notably, the Aggarwal group has contributed to the metal-free, visible-light-induced C–H borylation of alkanes, employing a reactive reagent B-chlorocatecholborane (Cl-Bcat) as the chloride source in combination with an alkoxyphthalimide.¹⁹ Subsequently, visible-light-mediated remote C(sp³)–H borylation has also emerged, albeit relying on specialized precursors, thus posing certain limitations in generality.⁴¹ Consequently, developing a general, mild and cost-effective catalytic system for the construction of C–B bonds from inert alkanes still remains a formidable challenge.

In 2023, Xia and Guo et al. reported an visible-light-mediated, iron-catalyzed C(sp³)–H borylation reaction, wherein the direct photoexcitation of ferrous chloride (FeCl₂) enables the generation of reactive chlorine radicals by LMCT (Scheme 4).^20a These radicals undergo intermolecular HAT processes with simple alkanes for following functionalization with bis(catecholato)diboron (B₂cat₂, 22). The reaction shows broad substrate compatibility, accommodating functionalities such as halides, carbonyls, nitriles, amides, and sulfonamides, making it applicable for the late-stage modification of pharmaceutical molecules and natural products. Notably, this strategy exhibits excellent terminal selectivity.

Scheme 4 C(sp³)–H borylation via photoinduced LMCT.

The mechanism of this photoinduced iron-catalyzed C(sp³)–H borylation is proposed as follows (Scheme 5):^20a upon excitation, ferric chloride undergoes an intramolecular LMCT process, generating reduced iron(II) species and a chlorine radical. The latter rapidly undergoes HAT with the C(sp³)–H substrate 21, releasing alkyl radical 21′. This intermediate reacts with the ligand-stabilized B₂(cat)₂ to form the desired alkyl boronic ester 29, which is further transformed into the final stabilized product 23 by treatment with pinacol and triethylamine. The N-fluorobenzene sulfonamide (NFSI) serves as a single-electron oxidant to convert iron(II) to iron(III) complex.

Scheme 5 Mechanism of the C(sp³)–H borylation via photoinduced LMCT.

In 2023, the Dai research group reported a photoinduced, copper-mediated alkane C(sp³)–H borylation reaction using ultraviolet light (365 nm) and stoichiometric cupric chloride, offering an alternative method for the synthesis of alkyl boronic esters (Scheme 6).^20b The reaction mechanism is proposed as follows: upon excitation, the excited state CuCl₂ undergoes an LMCT process to generate chlorine radicals. These radicals then undergo HAT with alkane 30, generating alkyl radical 30′. The alkyl radical interacts with B₂cat₂ to form intermediate 32, which further reacts with CuCl₂ to produce unstable borylated product 33. The next treatment with Et₃N and pinacol affords the stable product 31.

Scheme 6 Photoinduced C(sp³)–H borylation of alkanes via copper(II) chloride.

Shortly thereafter, the group of Aggarwal and Nobel reported a copper-catalyzed C(sp³)–H borylation of non-activated alkanes under visible-light irradiation and external oxidant-free conditions (Scheme 7).^20c Notably, the authors discovered that under CuCl₂ catalysis, B₂cat₂ and H₂O undergo a dehydrogenation process to generate the key intermediate O(Bcat)₂39, an efficient alkyl radical borylating reagent. The reaction demonstrates excellent generality, is applicable to a variety of complex alkane structures, and provides alkyl boronic esters with outstanding selectivity. The authors conducted detailed mechanistic studies, confirming the presence of the hypothesized electrophilic borylating reagent 39 during the reaction. They proposed that the HAT agent is either chlorine radicals or a Cl-radical-boron ‘ate’ complex 40 formed by the interaction of chlorine radical with 39. This finding serves as crucial evidence for explaining the reaction's excellent regioselectivity.

Scheme 7 Copper-mediated photocatalytic dehydrogenative C(sp³)–H borylation of alkanes.

In recent years, driven by the rapid development of both organic photocatalysis^4,5 and electrocatalysis,⁴² organic photoelectrocatalysis has garnered increasing attention, providing a new paradigm for achieving selective and sustainable transformations.¹² For example, in 2020, the Xu research group developed a photoelectrocatalytic dehydrogenative cross-coupling of heteroarenes with aliphatic C–H bonds.⁴³ This reaction utilized electrical energy to oxidize chloride ions to molecular chlorine, and light energy to further generate chlorine radicals for the desired C–H activation process. Building upon this work, the group of Xia and Guo developed a photoelectrochemical C(sp³)–H borylation, providing a significant extension of chloride-mediated C–H functionalization in photoelectrochemical systems (Scheme 8).⁴⁴

Scheme 8 Photoelectrochemical C(sp³)–H borylation of alkanes.

In 2024, Lu^20d and Ackermann^20e independently reported their protocols of photoelectrochemically driven iron-catalyzed C(sp³)–H borylation (Scheme 9). These reactions merge iron photochemistry with electrochemical systems, conveniently transforming inexpensive alkanes into high-value alkyl boronic ester derivatives without the need for external chemical oxidants.

Scheme 9 Photoelectrochemically driven, iron-catalyzed C(sp³)–H borylation of alkanes.

Exemplified by Lu's work,^20d the proposed mechanism involves the formation of [FeCl₄]⁻ from FeCl₃ and chloride anions in solution. When exposed to purple LED light, the excited *[FeCl₄]⁻ undergoes an LMCT process, resulting in the generation of a chloride radical, which then abstracts a hydrogen atom from alkane 54, forming alkyl radical 54′ and regenerating [FeCl₄]⁻ by anodic oxidation. At the same time, B₂cat₂ is reduced at the cathode, forming a radical anion, which then reacts with the alkyl radical to yield the C(sp³)–H borylation product 55. Additionally, direct interaction between the alkyl radical and B₂cat₂ can also produce the borylated product with H₂ evolution (Scheme 10).

Scheme 10 Mechanism of photoelectrochemically driven C(sp³)–H borylation.

Traditional HAT reactions typically require stoichiometric HAT precursors or harsh conditions, and the site-selective modifications of simple alkanes are generally elusive. Recently, Hu et al. reported a novel photocatalytic strategy for direct C(sp³)–H borylation (Scheme 11).^20f This iron-catalyzed reaction enables a highly selective borylation of terminal C(sp³)–H bonds in substrates with small steric hindrance, including unbranched alkanes, offering a new avenue for selective C–H bond functionalization. A reversible HAT process is revealed by the mechanistic studies, and a key boron-sulfoxide complex 62 is proposed to contribute to the regioselectivity. The selectivity can be primarily attributed to two major aspects: (1) steric hindrance plays a crucial role, where di-phenyl sulfoxide (59, R = Ph) facilitates the preferential borylation of terminal radicals due to their lower steric hindrance. Reactions at secondary positions are completely suppressed, due to the obstructive nature of the phenyl ring structure towards radical attacks, making terminal radicals 58′′′ more easily accessible to the reaction center. (2) The reversible HAT process is another key factor. During the process, BcatOH-sulfoxide 60 undergoes a reversible reaction with unreacted secondary alkyl radicals 58′ or 58′′ to regenerate alkane 58, preventing them from reacting with B₂cat₂, thereby enhancing the selectivity.

Scheme 11 Terminal-selective C(sp³)–H borylation through intermolecular radical sampling.

4. C(sp³)–H sulfurization

Sulfur is an essential element for life, and is widely present in various crucial biomolecules, such as amino acids (cysteine and methionine),⁴⁵ coenzyme A,⁴⁶ and vitamins (biotin).⁴⁷ The formation and cleavage of C–S bonds play a pivotal role in enzyme-catalyzed reactions, serving as the core of numerous biological processes.⁴⁸ By constructing and manipulating C–S bonds, molecules with specific biological activities can be developed, which holds significant potential for drug design and biochemical research.⁴⁹

In recent years, driven by the emergence of organic photocatalysis, significant advancements have been made in the construction of C–S bonds.⁵⁰ However, direct C(sp³)–H sulfurization reactions have only recently emerged in the studies of simple alkanes.⁵¹ The following content will provide a detailed overview of these research developments, primarily focusing on C(sp³)–H thioetherification, C(sp³)–H sulfinylation, and C(sp³)–H sulfonylation.

In 2021, Larionov and coworkers reported a novel photoinduced C(sp³)–H sulfinylation reaction mediated by sodium metabisulfite (Na₂S₂O₅), enabling the direct installation of sulfinates onto inert aliphatic C–H bonds under the irradiation of 300 nm UV-light in aqueous media (Scheme 12).⁵² This method exhibits excellent selectivity for monosulfination by keeping a low SO₂ concentration and forming stable sulfinate salts in situ. The mechanism of the C(sp³)–H sulfination reaction proceeds as follows: upon photon absorption, the dissolved sulfur dioxide undergoes an intersystem crossing (ISC) to the reactive triplet state ³SO₂*. It then abstracts a hydrogen atom from alkane 66, generating an alkyl radical 66′ and a hydroxy sulfonyl radical. The alkyl radical is subsequently trapped by SO₂ to form intermediate 66′′, which then reacts with the hydroxy sulfonyl radical to produce an alkyl sulfinic acid 75. This unstable compound is further converted to the corresponding alkyl sulfinate sodium salt 67 in the presence of Na₂SO₃. By one more facile step, this protocol enables the direct conversion of aliphatic C–H bonds to other classes of organosulfur compounds, including sulfonamides, sulfonyl fluorides, and sulfones.

Scheme 12 Photoinduced C(sp³)–H sulfinylation and further sulfonylation.

In 2022, Gong et al. reported a novel C(sp³)–H sulfonylation method employing a conjugated polycyclic quinone as a direct HAT photocatalyst, inexpensive copper salt as oxidant, and sulfinate salts as the sulfonylating reagents (Scheme 13).⁵³ This approach efficiently converts various toluene derivatives and cycloalkanes into value-added sulfone products 78. The proposed mechanism unfolds as follows: upon photoexcitation, the conjugated quinone chromophores undergo an intersystem crossing to their triplet excited state, which exhibits ambiphilic radical characteristics. In this activated form, the quinone can engage in an HAT process from C(sp³)–H bonds in alkane substrates 76, thereby generating alkyl radical intermediates 76′. Meanwhile, the copper catalytic cycle facilitates the formation of sulfone products 78via a sequence of ligand exchange, oxidative addition and reductive elimination steps.

Scheme 13 Photoinduced C(sp³)–H sulfonylation using conjugated quinone and copper salt.

Over the past several decades, the synthesis of organochalcogen compounds has aroused great interest in the synthetic community.⁵⁴ In 2022, Laulhé et al. reported a photoinduced C–H chalcogenation (thioetherification and selenoetherification) reaction using readily available dichalcogenides via an Fe-LMCT process (Scheme 14).⁵⁵ This method is applicable to Boc- and mesyl-protected amines, nitriles, halides, and sulfonylamides, exhibiting moderate to excellent yields for secondary and tertiary amides, offering a complementary strategy for the sulfurization of N-alkylamides and (thio)ethers in current synthetic chemistry.

Scheme 14 Photoinduced C(sp³)–H chalcogenation of amide derivatives and ethers via Fe-LMCT.

The synthesis of sulfoxides has long been challenging. In 2021, Bi and co-workers discovered an intriguing transformation: in the presence of acyl chlorides, sodium benzenesulfinate can be converted into sulfinyl sulfones.⁵⁶ By means of such a strategy, Larionov reported the first visible-light-enabled decarboxylative sulfinylation.⁵⁷ Furthermore, the direct C(sp³)–H sulfinylation of inert alkanes has seen developments. In 2023, Xia and Guo et al. developed an iron-induced selective C(sp³)–H thioetherification and C(sp³)–H sulfinylation using sodium benzenesulfinate/acyl chloride systems (Scheme 15).^20a

Scheme 15 Iron-photocatalyzed C(sp³)–H thioetherification and sulfinylation.

In the same year, Zheng and Wu reported a photoinduced direct C(sp³)–H sulfinylation mediated by tetrakis(tetrabutylammonium) decatungstate (TBADT), which exhibits excellent site-selectivity and is applicable to the late-stage modification of complex molecules (Scheme 16).⁵⁸ The sulfone intermediate 97 in this reaction originates from the reaction between sodium arylsulfinate 96 and (Boc)₂O. Additionally, it is also demonstrated in this work that secondary and tertiary aldehydes can be converted to the corresponding sulfone products through decarbonylative sulfonylation.

Scheme 16 Photocatalytic C(sp³)–H sulfinylation mediated by decatungstate salts.

Meanwhile, building upon their previous research, Xia, Guo and coworkers reported another advancement in iron photocatalysis (Scheme 17).²¹ By altering the reaction atmosphere (N₂ or air), they successfully utilized sulfinyl sulfones 108 to achieve selective C(sp³)–H thioetherification or sulfinylation of inert alkanes. Additionally, the introduction of a 1,4-diazabicyclo[2.2.2]octane bis(sulfur dioxide) adduct (DABSO)/NFSI combination during the reaction facilitated the transformation of alkanes into the corresponding sulfonyl fluorides 112.

Scheme 17 Selective C(sp³)–H sulfinylation via photomediated Fe-catalysis.

At the end of 2023, the Ryu research group reported a photocatalytic C(sp³)–H thiolation by a double S_H2 strategy using sulfinyl sulfones 114 as sulfur sources and TBADT as the photocatalyst (Scheme 18a).⁵⁹ Subsequently, they expanded the substrate scope to aldehydes, in which they found that a CO atmosphere can effectively limit the extent of decarbonylation of acyl radicals (Scheme 18b).⁶⁰ Soon after, Xia and Yang et al. also reported similar reactions using more easily available sulfinate salts 118 and acetyl chloride as reagents (Scheme 18c).⁶¹ Interestingly, under a standard nitrogen atmosphere, thioether products 115 are obtained as the major products, while under glovebox conditions, this reaction predominantly yields sulfoxide products 119.

Scheme 18 Decatungstate as an HAT reagent for the photochemical synthesis of thioethers and thioesters.

The proposed mechanism for this selective precursor formation in Xia and Yang's work is presented in Scheme 19.⁶¹ Initially, sodium p-toluenesulfinate 120 reacts with acetyl chloride to generate mixed anhydride 121, which further converts into the sulfoxide precursor 122 under glovebox conditions with an extremely low oxygen and moisture content (Path A).⁵⁶ However, in less rigorously moisture- and oxygen-free conditions, the unstable intermediate 122 would readily transform into 123, which undergoes subsequent steps to deliver the thioether precursor 125 (Path B). Next, these precursors are further engaged in the corresponding C(sp³)–H sulfurization reactions.

Scheme 19 Proposed mechanism for the selective formation of thioether and sulfoxide precursors.

In 2023, Maiti and Lahiri developed a transition-metal-free C(sp³)–H thiolation using thioxanthone as the photosensitizer, which plays a dual role of both hydrogen atom transfer and a photoinduced energy transfer agent, enabling the smooth conversion of various toluenes as well as unactivated alkanes (Scheme 20a).^62a Concurrently, Zhong et al. employed 4-CzIPN as the photosensitizer for the oxidative generation of bromine radical under 450 nm visible-light irradiation, which serves as the HAT reagent for selectively activating the α-C–H bonds of ethers 129 for thioetherification with reagent 130 (Scheme 20b).^62b

Scheme 20 Transition-metal-free photoinduced hydrogen atom transfer-assisted C(sp³)–H thiolation.

Disulfide bonds are of significant biological importance in maintaining a protein structure, regulating protein aggregation, and drug delivery.⁶³ The synthesis of asymmetric disulfides is challenging and often requires harsh conditions. In 2022, the Studer group developed a protocol utilizing decatungstate photocatalysis and tetrasulfides 133 as radical disulfurization agents to transform aliphatic C(sp³)–H bonds and aldehyde C(sp²)–H bonds into the corresponding –C–S–S– moieties (Scheme 21).⁶⁴ By using this strategy, a series of valuable asymmetric dialkyl disulfides 134 as well as acyl alkyl disulfides were successfully prepared. Furthermore, the application of this method in the late-stage modification of drugs and natural products is elegantly demonstrated.

Scheme 21 Synthesis of asymmetric disulfides via photoinduced C(sp³)–H activation.

Sulfinamide structures are prevalent in pharmacologically active molecules,⁶⁵ yet examples of the sulfinamidation via direct C–H activation of inert alkanes are still lacking. Recently, Hu and Wei et al. reported the application of iron photocatalysis in the direct sulfinamidation of alkanes, enabling the rapid synthesis of high-value sulfonamides 138 from simple hydrocarbons and sulfinylamines 137 (Scheme 22).⁶⁶ The proposed mechanism proceeds as follows: the photoexcited *[Fe(III)Cl₄]⁻ undergoes LMCT to form a reduced Fe(II) species and a chlorine radical. The chlorine radical serves as an HAT reagent to interact with the C(sp³)–H bond of 136, generating alkyl radical 136′, which is subsequently trapped by sulfinylamine 137 to form aminosulfinyl radical 148. This intermediate then undergoes SET with the Fe(II) species to generate intermediate 149, completing the Fe-catalytic cycle. Finally, intermediate 149 undergoes protonation to yield the corresponding target product 138. Further transformation to sulfonimidate esters 139 with alcohol nucleophiles is also demonstrated viable using PhIO as the oxidant.

Scheme 22 Iron photocatalysis for sulfinamide synthesis from alkanes.

Very recently, Noël's group introduced a photomediated approach to harness an HAT process for the activation of volatile alkanes under flow conditions (Scheme 23).⁶⁷ Gaseous alkanes such as isobutane, butane, propane, ethane, and methane can be activated under the standard conditions in 34–52 bar pressure, forming nucleophilic radicals to react with SO₂ to produce the corresponding sulfinates 151, which are further converted into sulfones 152 upon treatment with alkyl bromide and base.

Scheme 23 C(sp³)–H sulfinylation of light hydrocarbons with sulfur dioxide via HAT photocatalysis in flow.

Chlorine radical has been recognized as a potent HAT reagent for inert C–H bond activation.⁶⁸ The established methods for photoinduced chlorine radical generation primarily involve three approaches: photoinduced LMCT processes of metal chlorides,¹¹ oxidation of chloride ions by excited-state photosensitizers⁶⁹ and the photochemical decomposition of hydrochloric acid to produce molecular chlorine, which subsequently yields chlorine radicals.^43,44 Recently, Shi's group introduced a new strategy for generating chlorine radicals through an electron donor–acceptor (EDA) complex formed by hydrochloric acid and the S(IV)=O group of sulfinates (Scheme 24).^10b By means of this approach, chlorine radicals effectively activate C(sp³)–H bonds and react with diverse radical acceptors. In the case of sodium benzenesulfinate 165 as the acceptor, under visible-light irradiation, chloride ions undergo a proton-coupled electron transfer (PCET) process with the internal S(IV)=O group of EDA complex 166, generating chlorine radicals and simultaneously producing sulfur radical intermediate 167. The protonation and dehydration of intermediate 167 forms radical 168, which undergoes subsequent dimerization and rearrangement to deliver sulfinylsulfone intermediate 170. On the other hand, the chlorine radical can also abstract hydrogen atoms from alkane 171 to generate alkyl radical 171′, which then attacks sulfinylsulfone 170 to yield the desired thioetherification product 172via two possible pathways. Additionally, when heterocyclic compounds are employed as the radical acceptors, the reaction solvent is replaced with dimethyl sulfoxide (DMSO), utilizing its S(IV)=O structure to form similar key EDA complexes.

Scheme 24 Photoinduced versatile aliphatic C–H functionalization via an electron donor–acceptor complex.

5. C(sp³)–H heteroarylation

Different from traditional C(sp²)–H functionalization reactions,⁷⁰ C(sp³)–H heteroarylation reactions directly link the C(sp³) of alkanes with hetero aromatic groups containing nitrogen, oxygen, sulfur, and other heteroatoms, effectively constructing diverse heterocyclic compounds.⁷¹ Minisci-type reactions, as a versatile tool for synthesizing substituted N-heteroarenes, have advanced with the development of photoredox catalysis and the emergence of a wider range of radical precursors, providing new opportunities for the functionalization of complex heteroaromatic frameworks.⁷² Achieving C(sp³)–H Minisci reactions with unactivated alkanes is an especially appealing goal.⁷³ Moreover, sulfonyl-substituted pyrimidine and benzothiazole derivatives can act as radical acceptors for arylation, offering novel approaches for incorporating heterocyclic fragments into molecules.⁷⁴ Furthermore, exploiting the oxidation of carbon radicals at the α-position of an oxygen atom to carbocation centers enables nucleophilic attack by nitrogen-containing heterocycles,⁷⁵ thereby constructing a variety of N-containing heterocyclic compounds. In the following sections, we will highlight the recent advancements in C(sp³)–H heteroarylation using these strategies.

In 2021, the Li research group developed a UV-light-mediated dehydrogenative Minisci alkylation, enabling the coupling of various heterocyclic compounds with strong aliphatic C–H bonds, demonstrating its applicability to access various complex heterocycles (Scheme 25).^69c This study employed cobaloxime complex [Co(dmgH)₂(py)]Cl as a terminal oxidant and heterocyclic substrates 180 as photosensitizers. In the mechanistic proposal, the protonated heterocycle (180-H⁺) first undergoes excitation under visible light, facilitating the oxidation of chloride ions to chlorine radicals via an SET process. The chlorine radical serves as the HAT reagent, activating alkane 179 to alkyl radical 179′, while simultaneously forming radical intermediate [180-H]˙. Subsequently, alkyl radical 179′ adds onto intermediate 180-H⁺ to form intermediate 191. Concurrently, the trivalent Co-complex oxidizes radical intermediate [180-H]˙ back to its initial state, reducing itself to a divalent cobalt species. This cycle promotes the catalytic turnover of cobalt and facilitates the formation of the target product 181 through interaction with intermediate 191 and subsequent deprotonation.

Scheme 25 Photoinduced dehydrogenative Minisci alkylation.

In 2023, Tong, Jian and coworkers developed a green method using iron trichloride as a photoinduced LMCT catalyst for the direct functionalization of unactivated C(sp³)–H alkanes (Scheme 26).⁷⁶ The reaction proceeds smoothly under an air atmosphere, and is compatible with a variety of heterocycles including quinolines, benzothiazoles, and quinoxalines.

Scheme 26 Minisci alkylation via photo-induced Fe-LMCT.

To further propel advances in HAT photocatalysis for C(sp³)–heteroarylation, Noël's group reported the employment of decatungstate to enable the selective hydrogen abstraction of C(sp³)–Hs at the α-position to oxygen or nitrogen atoms, thereby generating carbon-centered radical intermediates (Scheme 27a).^75a These carbon radicals are subsequently oxidized to carbocations by tert-butyl hydroperoxide (TBHP), which are then engaged in nucleophilic addition by N-heteroaryl coupling partners. In 2022, the group of Ni and Mao disclosed a similar strategy utilizing chlorine radicals generated via photoinduced Fe-LMCT as the HAT reagent, with an external oxidant di-tert-butyl peroxide (DTBP) to facilitate the reaction (Scheme 27b).^75b Building upon these precedents, in 2023, Noël and colleagues incorporated the photoinduced Fe-LMCT manifold into an electrochemical setup in flow. This chemical oxidant-free photoelectrochemical LMCT approach not only enables the catalytic turnover of the iron species through anodic oxidation, but also facilitates the oxidation of α-oxy radical intermediates (Scheme 27c).^75c Notably, this reaction manifests broad substrate scope, permitting the incorporation of diverse nitrogen-containing heterocycles at the α-position of ethers, thereby providing a promising strategy for sustainable C(sp³)–H heteroarylation.

Scheme 27 Nucleophilic approaches to achieve C(sp³)–H heteroarylation.

In 2023, Xu and Deng et al. reported a novel TBADT-catalyzed method for the hydroxyalkylation or alkylation of N-heteroaromatics with aldehydes or alkanes in aqueous solution (Scheme 28).⁷⁷ This reaction employs methanesulfonyl-substituted benzothiazoles 201 as the radical acceptors. Notably, when aldehydes 200 are used as the reaction partners, the formation of ketones 205 does not terminate the reaction. Instead, it further proceeds into another HAT process with H⁺[TBADT]⁻, ultimately yielding the desired hydroxyalkylated heteroaromatic product 203.

Scheme 28 Photoinduced hydroxyalkylation of N-heteroaromatics with alkanes and aldehydes.

Given the importance of pyrimidine as a component of genetic material and its widespread presence in pharmaceutical molecules, introducing pyrimidine rings into inert alkanes possesses a significant appeal.⁷⁸ In 2017, Murafuji et al. reported a visible-light-induced C–H pyrimidination reaction using benzophenone as an HAT catalyst, but the substrate scope seems to be limited to saturated heterocycles containing O, N, and S heteroatoms.^78d At the end of 2023, Xia and Yang et al. reported a visible-light-driven, iron-catalyzed C(sp³)–H pyrimidination reaction (Scheme 29).⁷⁹ This method is applicable not only to simple alkanes but also to ethers, esters, and even free alcohols, exhibiting a significantly broadened scope.

Scheme 29 C(sp³)–H heteroarylation via photoinduced Fe-LMCT.

6. C(sp³)–H acylation

Ketones are prevalent in nature, existing among many significant biomolecules, including steroid hormones and fragrances.⁸⁰ Apart from conventional redox synthesis, reagents such as β-keto acids⁸¹ and α-keto acids⁸² facilitate the incorporation of carbonyl groups into molecular frameworks. Recently, the integration of N-heterocyclic carbene (NHC) catalysis with photoredox catalysis for the synthesis of ketones via acyl radical cross-coupling has garnered considerable attention.⁸³ However, achieving the acylation of simple alkanes remains a formidable challenge. The following section will focus on some recent research progress in this area.

In 2021, Huo's group disclosed an asymmetric benzylic C–H acylation for the synthesis of chiral α-aryl ketones 222, utilizing an Ir/Ni dual catalytic system under mild photoirradiation conditions (Scheme 30a).^84a Dimethyl dicarbonate (DMDC) is employed as the activating agent for carboxylic acids 220 to generate mixed anhydride in situ. The key step of this reaction is the generation of bromine radicals from bromide anions through single-electron oxidation enabled by iridium photoredox catalysis, which act as HAT reagents for the subsequent activation of benzylic C–H bonds. In 2023, they further developed a regio- and enantioselective N-α-acylation reaction for saturated N-heterocycles with a dual catalytic system, for the construction of chiral α-acylated amine derivatives 224 under blue-light irradiation (Scheme 30b).^84b In this reaction, chlorine radicals generated through a photoinduced LMCT process with high-valent nickel chloride act as the HAT reagent. These two methods represent convenient and efficient approaches for the straightforward synthesis of enantioenriched carbonyl compounds.

Scheme 30 Direct enantioselective acylation of benzylic C(sp³)–H bonds with carboxylic acids.

In 2022, Xia and Pan et al. reported a direct acylation of inert C(sp³)–H bonds (Scheme 31).⁸⁵ This strategy utilizes decatungstate NaDT to activate alkanes and employs CF₃-modified phenylsulfonyl ketone oximes 225 as the acylating reagents. The CF₃-modified phenylsulfonyl group is found to significantly enhance the electrophilicity of the imine and lower the C–S bond cleavage energy, thereby facilitating the transformation. This method exhibits excellent site selectivity and a broad substrate scope, including late-stage functionalization of complex natural products.

Scheme 31 Direct acylation of inert C(sp³)–H bonds using decatungstate and phenylsulfonyl ethanone oximes.

Radical imidazolium ions as substitutes of stable acyl radicals have attracted considerable attention, and the related studies have shown significant progress.⁸⁶ In 2023, Scheidt and Gutierrez's research group discovered that, upon visible-light excitation, acyl imidazolium ions 232* readily undergo intersystem crossing to generate triplet diradical species 234 (Scheme 32).⁸⁷ This species can serve as an HAT agent, activating the specific C–H bonds (such as α-C–Hs of nitrogen atoms and benzylic C–Hs) to form alkyl radicals. Alkyl radical 231′ is then engaged in selective cross-coupling with radical intermediate 235 to produce the desired acylated products 233 upon further treatment with a base.

Scheme 32 Photoinduced C(sp³)–H acylation via azolium-promoted intermolecular HAT.

As an inexpensive and abundant rare earth element, cerium has opened up new avenues for its applications in sustainable chemical synthesis.⁸⁸ At the end of 2023, based on their previous work, Scheidt and co-workers disclosed a novel photoinduced, cerium-catalyzed acylation employing azolium salts 232 as the acyl sources, enabling the direct functionalization of unactivated C(sp³)–H bonds (Scheme 33).⁸⁹ This protocol is successfully applied to a variety of C–H bonds, including cyclic and acyclic alkanes, demonstrating its potential utility in practical synthesis.

Scheme 33 Photoinduced cerium-catalyzed C(sp³)–H acylation.

The proposed reaction mechanism is illustrated in Scheme 34.⁸⁹ The whole process begins with the photoexcitation of [Ce^IIICl₆]³⁻ formed from Ce^IIICl₃, generating a potent single-electron reductant species *[Ce^IIICl₆]³⁻, which subsequently reduces the acyl azolium salt 232 to form radical intermediate 250. Meanwhile, the high-valent [Ce^IVCl₆]²⁻ species is also produced, which undergoes an LMCT process, leading to the formation of the [Ce^IIICl₅]²⁻ complex and a highly reactive chlorine radical. The chlorine radical efficiently abstracts a hydrogen atom from alkane 171, producing alkyl radical 171′ to couple with radical 250 to form the tertiary azolyl intermediate 251. Under basic conditions, 251 ejects carbine 252 to finally yield the desired ketone product 242.

Scheme 34 The mechanism of photoinduced cerium-catalyzed C(sp³)–H acylation.

7. Other types of C(sp³)–H functionalization

In this section, we will introduce the recent advances in C(sp³)–H activation for the construction of C(sp³)–C(sp³) bonds, C(sp³)–N bonds, and some other related transformations.⁹⁰ Some of this work is derived from earlier seminal studies, while other portions represent pioneering efforts. We will selectively highlight several representative and significant developments.

It is well-known that methane is an abundant and inexpensive organic carbon source in nature, while also being one of the major contributors to the global greenhouse effect. Consequently, the activation of the C–H bonds in methane holds significant economic and environmental value.⁹¹ However, the high bond dissociation energy of 105 kcal mol⁻¹ for the C–H bonds in methane, coupled with the poor solubility of gaseous alkanes in most solvents, has made methane activation a formidable challenge.⁹² In 2022, the research group led by Jin employed an iron-catalyzed strategy for generating chlorine radicals, achieving the direct functionalization of methane, and some heavier gaseous alkanes (Scheme 35).⁹³ The theoretical calculations reveal that the photoexcitation of the acetonitrile complex of iron chloride is the “rate-determining step”, while the C–H activation process is merely the “product-determining step”. This work may bring novel ideas for feedstock upgrading and catalyst design.

Scheme 35 UV-light-enabled, iron-catalyzed methane functionalization.

Allylation represents an important and practical transformation for the construction of C(sp³)–C(sp³) bonds.⁹⁴ In 2022, Fañanás-Mastral et al. reported a light-driven, decatungstate and copper cooperatively catalyzed allylation of alkanes with simple allylic chlorides (Scheme 36).⁹⁵ The photoexcited decatungstate anion acts as an HAT agent, activating alkane 171 to generate nucleophilic carbon-centered radical 171′, which subsequently engages in a nucleophilic substitution (S_H2′) reaction with activated allylic π-olefin-copper complexes 258 to afford the desired products 257. This strategy enables an efficient allylation of various chemical feedstocks and natural products.

Scheme 36 Photoinduced, decatungstate-copper co-catalyzed allylation of alkanes.

In 2023, Lu's group developed a Cu/Cr dual-catalytic system for converting aliphatic C–H bonds into nucleophiles under visible-light irradiation, which then interact with aldehydes 261 to access aryl alkyl alcohols 262 (Scheme 37).⁹⁶ The mechanistic studies indicate that the direct redox reaction between Cu(I) and Cr(III) seems unfavorable. In their proposed mechanism, aromatic aldehyde 261 acts not only as a substrate but also as a photosensitizer to undergo photoexcitation, and the excited 261* participates in the following HAT process to produce radical 260′ and facilitate the copper catalytic cycle, meanwhile generating intermediate 263. On the other hand, ketyl radical 263 reduces Cr(III) to Cr(II), enabling its rapid coupling with alkyl radical 260′ to form organometallic intermediate 264 for subsequent nucleophilic addition process.

Scheme 37 Coupling reaction between aldehydes and alkanes via photoinduced LMCT.

Recently, Barham and Tian et al. developed a novel photoelectrochemical carboamidation reaction utilizing styrenes and unactivated alkanes without the need for external oxidants (Scheme 38).⁹⁷ TBADT is employed as the photocatalyst, generating the active species wO by photoexcitation and subsequent decay, which is a strong HAT reagent for the C(sp³)–H activation of alkane 266. The resulting alkyl radical 266′ adds onto styrene 267 to afford benzylic radical 269, which is then oxidized via either direct or indirect anodic oxidation to access benzylic cation 270. The further Ritter-type amidation provides final product 268. The reaction exhibits good functional group tolerance for both styrenes and alkanes, addressing limitations in prior reports to electron-poor olefin trapping partners and mono-functionalization.

Scheme 38 Photoelectrochemical carboamidation of styrenes using unactivated alkanes.

In 2022, Wang et al. reported a novel method employing a cost-effective tungsten photocatalyst for the C(sp³)–N coupling reaction between unactivated simple hydrocarbons and nitrobenzenes (Scheme 39a).^98a In parallel, advancements in C(sp³)–H amidation reactions have also been made. In 2020, König et al. developed an innovative photoinduced copper(II)-peroxide catalytic system to achieve N–H bond alkylation, enabling the activation of stable C(sp³)–H bonds to react with a wide range of (sulfon)amides and N-heterocyclic nucleophiles.^98b In 2021, Murakami's group applied iridium photoredox catalysis combined with nickel catalysis for the synthesis of amides from inert alkanes and isocyanatess.^98c In 2022, Bao et al. reported a photoinduced decatungstate/nickel catalytic strategy for the direct intermolecular C(sp³)–H amidation of unactivated alkanes, ketones, ethers, amines, and aldehydes, with dioxazolones 274 as the sources of amide moieties (Scheme 39b).^98d Concurrently, Wang and colleagues described a similar photodriven tungsten/nickel dual-catalytic system that enables both C(sp³)–H amination and amidation of inert alkanes (Scheme 39c).^98e

Scheme 39 Decatungstate-mediated photochemical C(sp³)–N bond construction.

The reaction mechanism of Wang's work is proposed as follows (Scheme 40):^98e under UV-light irradiation, decatungstate undergoes intersystem crossing to generate an excited triplet state, which acts as an HAT reagent to activate the inert C–H bond of alkane 271, forming a reduced photosensitizer and alkyl radical 271′. The alkyl radical 271′ is then captured by Ni⁰ to form alkyl–Ni^I species 278, which, upon coordination with oxazolones 274, forms complex 279. Further nitrene insertion and protonation of 279 ultimately yield the desired amide product 275.

Scheme 40 Proposed mechanism for decatungstate-mediated C(sp³)–N bond construction.

8. Asymmetric C(sp³)–H functionalization

The selective functionalization of C–H bonds has long been an appealing yet challenging task in organic synthesis. Of particular interest are methods that directly convert the ubiquitous C(sp³)–H bonds into new C–C or C–X bonds with high chemoselectivity, regioselectivity, and especially stereoselectivity.⁹⁹ In recent years, significant advancements have been made in asymmetric photocatalytic C(sp³)–H bond activation, which circumvent the need for harsh reaction conditions or pre-functionalization, thereby enabling more step-economical and atom-economical synthesis.^5g,84,100 The latest research progress in this field has showcased the powerful capability of C–H activation chemistry in constructing molecular complexity and has provided opportunities for developing new efficient and sustainable synthetic strategies. In this section, we will highlight the latest representative work (mainly studies reported after 2023) on asymmetric photocatalytic C(sp³)–H functionalization for the reference of researchers in related fields.

In 2023, Kong, Wang, and colleagues reported an enantioselective C(sp³)–H arylation/alkenylation of saturated oxygen-containing heterocycles 281 at their O-α-positions (Scheme 41).¹⁰¹ A diaryl ketone which upon photoexcitation acts as a direct HAT agent is employed as the photocatalyst, along with a nickel catalyst and a chiral PHOX ligand, to achieve this directing-group-free asymmetric C(sp³)–H functionalization. This method is applicable to various saturated O-heterocyclic systems and a wide range of aryl and alkenyl bromides, providing an efficient route to high-value chiral oxygen heterocycles 283, and demonstrating the immense potential and broad prospects of synergistic photocatalysis and nickel catalysis in asymmetric C–H functionalization reactions.

Scheme 41 Synergistic nickel and photocatalysis strategies in asymmetric C(sp³)–H arylation and alkenylation.

In 2023, Gong and Hirao et al. developed a visible-light-induced, copper-catalyzed atom transfer radical coupling (ATRC) that enables the asymmetric oxidative functionalization of alkenes, facilitating the effective synthesis of diverse chiral lactones with high enantioselectivity via aliphatic C–H activation (Scheme 42).¹⁰² The proposed mechanism is initiated with the photoinduced homolysis of DTBP to generate tert-butoxy radicals, which abstract a hydrogen atom from alkane 284, affording alkyl radical 284′. This radical subsequently undergoes radical addition to the copper(II) complex 287, yielding key intermediate 288. A series of cyclization steps ultimately furnish the lactone product 286 while simultaneously releasing the copper(I) species. Regeneration of the active copper(II) complex 287 occurs through oxidation of copper(I) by another tert-butoxy radical, followed by ligand exchange with substrate 285, thereby closing the catalytic cycle. As revealed by density functional theory (DFT) calculations and mechanistic experiments, the enantioselectivity originates from the asymmetric C–O bond formation, and the rate-determining step is the cyclization step from 289 to 286.

Scheme 42 Photoinduced copper-catalyzed ATRC for the asymmetric synthesis of chiral lactones.

In 2023, Kramer, Lian and colleagues disclosed a dual copper and photocatalytic system for the enantioselective radical amidation and amination of benzylic C–H bonds (Scheme 43).¹⁰³ This catalytic system integrates a Cu-catalyst with a chiral ligand, an Ir-photocatalyst, and peroxide DTBP oxidant, demonstrating a broad substrate scope with excellent functional group tolerance.

Scheme 43 Enantioselective intermolecular radical amidation and amination of benzylic C–H bonds via dual copper and photocatalysis.

Recently, Feng, Liu, and colleagues developed an innovative photocatalytic C(sp³)–H functionalization for the asymmetric synthesis of privileged α-chiral alkyl phosphines 295 (Scheme 44).¹⁰⁴ This protocol employs a synergistic catalytic system combining an organic photocatalyst with a chiral Lewis acid catalyst. Under visible-light irradiation, the asymmetric addition of various C(sp³)–H containing reagents, including sulfides, amines, alkenes, and toluene derivatives, to α-substituted vinylphosphine oxides 294 is efficiently realized. Through this approach, structurally diverse α-chiral alkyl phosphine compounds can be synthesized, exhibiting excellent chemoselectivity, regioselectivity, and stereoselectivity. Mechanistic studies reveal that the excited-state photocatalyst oxidizes C(sp³)–H substrate 293via single-electron transfer, generating a radical cation, which subsequently forms radical 293′ through proton transfer (PT). This carbon radical then adds onto Lewis acid-activated vinylphosphine oxide 296, followed by single-electron reduction and protonation steps to yield the final product 295.

Scheme 44 Visible-light-induced C(sp³)–H radical functionalization for asymmetric synthesis of α-chiral alkyl phosphine.

In 2024, the Wang group reported a visible-light-induced asymmetric α-amino C(sp³)–H functionalization of N-sulfonyl benzylic amines 299 with aldehydes 300 to access enantioenriched β-amino alcohols 301 (Scheme 45).¹⁰⁵ A triple catalytic system is adopted involving photoredox catalysis, HAT catalysis, and chromium catalysis. Upon irradiation, the excited-state Ir(III)* undergoes SET with quinuclidine, generating a nitrogen radical cation with HAT capability. Due to H-bonding interaction, this radical cation would selectively abstract a hydrogen atom from the α-position of the nitrogen atom in 299, forming radical intermediate 299′. This radical intermediate then adds onto the aldehyde-Cr(II)/L complex 302, forming enantioenriched alkoxy intermediate 303. The dissociation of the Cr–O bond releases the desired product 301 and the Cr(III)/L complex, which can oxidize Ir(II) back to Ir(III), thereby closing both the iridium and chromium catalytic cycles.

Scheme 45 Asymmetric α-amino C(sp³)–H functionalization via photoredox and chromium catalysis.

In early 2024, Nevado and colleagues introduced a dual nickel/photoredox catalysis strategy that employs a chiral nickel complex with pyridine-oxazoline ligands as a catalyst under mild conditions (Scheme 46).¹⁰⁶ This approach facilitates the direct coupling of simple alkyl arenes 304 with isocyanates 305, yielding chiral α-aryl amides with high yields and excellent enantioselectivity. The proposed reaction mechanism encompasses three synergistic catalytic cycles: the photoredox cycle, bromine radical HAT cycle and nickel catalytic cycle.

Scheme 46 Direct asymmetric functionalization of benzylic C–H bonds via dual nickel/photoredox catalysis for the synthesis of chiral α-aryl amides.

Chiral sulfoxides and the related compounds are important chemical reagents with excellent asymmetric induction capabilities, which have been employed to enable the synthesis of various chiral compounds.¹⁰⁷ In 2024, Masson and Neuville et al. reported a sustainable visible-light-mediated method for the stereoselective radical alkylation of chiral N-sulfinyl imines 308 with simple alkanes 307, utilizing TBADT as the photocatalyst (Scheme 47).¹⁰⁸ The chiral sulfoxide not only serves as a substrate but also acts as a chiral inducer: the hydrogen bond between the sulfinyl-oxygen and the imine hydrogen of 310 (R¹ = mesityl) shields the Re-face, and therefore, alkyl radical 307′ would attack from the less-hindered Si-face to form the enantioenriched N-centered radical intermediate 311.

Scheme 47 TBADT-mediated photocatalytic stereoselective radical alkylation of chiral N-sulfinyl imines.

Recently, Nevado and colleagues reported a novel asymmetric three-component dicarbofunctionalization reaction of alkenes, which combines photomediated hydrogen atom transfer with nickel-catalyzed radical relay (Scheme 48).¹⁰⁹ The proposed reaction mechanism goes as follows: under 390 nm light irradiation, TBADT is excited to the excited state TBADT*, which then abstracts a hydrogen atom from alkane 313, generating carbon-centered radical 313′ and singly reduced decatungstate species. Subsequently, this carbon-centered radical adds onto olefin 314, forming radical intermediate 317, which is further captured by Ni(0), forming an alkyl–Ni(I) species 318. Next, this alkyl–Ni(I) intermediate undergoes oxidative addition with aryl bromide 315, yielding an alkyl–Ni(III)–aryl intermediate 319. In the next reductive elimination step, the target difunctionalized product 316 is delivered, along with a Ni(I) species. Finally, the Ni(I) species undergoes single-electron transfer with the singly reduced decatungstate to regenerate Ni(0) and decatungstate, completing the entire catalytic cycle. The alternative pathway via the combination of 320 and 317, and subsequent single-electron reduction to access 318 is also proposed. This protocol provides important insights for the future development of asymmetric multicomponent reactions involving C(sp³)–H activation.

Scheme 48 Asymmetric three-component difunctionalization via photomediated HAT and nickel catalysis.

Studies employing aryl radicals as HAT reagents in C–H activation have been relatively unexplored.¹¹⁰ Recently, Gong, Han, and co-workers have reported a breakthrough in this area, by developing a photoinduced palladium-catalyzed three-component enantioselective carboamination reaction of dienes with a modified BINAP-type chiral ligand (Scheme 49).¹¹¹ In this novel strategy, 2-bromo-1,5-di-tert-butyl-3-methylbenzene (ArBr) is screened out to serve as both an oxidant to oxidize the photoexcited Pd(0) species, and a precursor of aryl radical as an HAT reagent for C(sp³)–H activation. Remarkably, this protocol can accommodate a diverse array of alkane substrates, including toluene derivatives, ethers, amines, esters, and ketones, enabling the efficient synthesis of various pivotal chiral allylamines with exceptional enantioselectivitiy (up to 99% ee).

Scheme 49 Photoinduced Pd-catalyzed enantioselective carboamination of dienes.

Very recently, Huo and colleagues reported an important breakthrough, wherein photoredox and nickel catalysis are combined to achieve the enantioselective alkylation of α-amino C(sp³)–H bonds (Scheme 50).¹¹² This reaction employs two independent catalytic cycles for the activation of C–H bonds and subsequent asymmetric coupling, and exhibits a broad substrate scope, enabling methylation, deuteromethylation, and other alkylation reactions on various cyclic and acyclic amine compounds while tolerating a wide range of functional groups. The use of in situ generated bromine radicals as HAT reagents avoids the potential compatibility issues associated with external HAT reagents and harsh conditions. Bromine radicals herein are produced through the single-electron oxidation of bromide anions by the excited photocatalyst, which subsequently abstract hydrogen atoms from amine substrate 328 to generate α-amino radical 328′. Concurrently, the photocatalyst reduces carboxylic acid derivative 327 to form another alkyl radical. These two carbon radicals undergo asymmetric cross-coupling under the effect of the chiral nickel catalyst to yield C(sp³)–C(sp³) coupling product 329. This modular design allows for the independent control of radical generation and asymmetric cross-coupling, thereby achieving high efficiency and selectivity.

Scheme 50 Enantioselective α-amino C(sp³)–H alkylation via dual photoredox and nickel catalysis.

9. Summary and outlook

Photoinduced direct C(sp³)–H functionalization has seen rapid development in recent years, providing a novel pathway for the straightforward synthesis of complex organic molecules from readily available alkane feedstocks under sustainable conditions. Researchers have expanded the repertoire of both reaction types and substrate scopes within this field through the development of new photosensitizers, catalytic cycles, as well as reaction systems. Particularly noteworthy is the increasing application of cost-effective metals such as iron and copper as photoinduced LMCT catalysts, laying a solid foundation for more economical synthetic processes. Additionally, the emerging photoelectrochemical synthesis offers a promising opportunity for achieving more selective and sustainable transformations by replacing chemical oxidants with a precisely controlled electric current. Furthermore, photochemical strategies have made it possible to directly construct carbon–heteroatom bonds (such as C–P, C–B, C–S) under very mild conditions, which is elusive by means of traditional methods, providing new avenues for the sustainable synthesis of value-added molecules containing these important linkages.

While the scope of alkane partners has been greatly expanded, the high addition amount greatly limits the application of these protocols in practical synthesis, particularly in the functionalization of complex C(sp³)–H sources. Therefore, developing new methods which employ alkanes as the limiting reagents are highly desirable. In addition to pursuing reaction universality, realizing photocatalytic enantioselective C(sp³)–H functionalization is also a key objective, which has still been in its infancy. Currently, the application of chiral ligands and pre-installation of auxiliaries are the major strategies for achieving stereoselectivity control, while the innovative design of new chiral photosensitizers/catalysts can also be anticipated. Looking ahead, the future research will likely continue to focus on developing new photocatalytic systems to expand reaction types and substrate scopes, and on further exploring the mechanisms for novel reaction discovery.

Data availability

No primary research results, software or code have been included and no new data were generated or analysed as part of this review.

Conflicts of interest

There are no conflicts to declare.

Acknowledgements

The authors are grateful for the financial support from Beijing Normal University (No. 310432105), and Harbin Institute of Technology (Shenzhen).

References

1. Y.-R. Luo, Comprehensive Handbook of Chemical Bond Energies, CRC Press, Boca Raton, 2007.
2. (a) M. Galeotti, M. Salamone and M. Bietti, Electronic control over site-selectivity in hydrogen atom transfer (HAT) based C(sp³)–H functionalization promoted by electrophilic reagents, Chem. Soc. Rev., 2022, 51, 2171–2223; (b) R. Yazaki and T. Ohshima, Recent strategic advances for the activation of benzylic C–H bonds for the formation of C–C bonds, Tetrahedron Lett., 2019, 60, 151225; (c) J. Li, C.-Y. Huang and C.-J. Li, Cross-dehydrogenative coupling of unactivated alkanes, Trends Chem., 2022, 4, 479–494; (d) Y. Wang, P. Hu, J. Yang, Y.-A. Zhu and D. Chen, C–H bond activation in light alkanes: a theoretical perspective, Chem. Soc. Rev., 2021, 50, 4299–4358; (e) D. L. Golden, S.-E. Suh and S. S. Stahl, Radical C(sp³)–H functionalization and cross-coupling reactions, Nat. Rev. Chem., 2022, 6, 405–427; (f) R. Ge, Z. Xu, K. Yang and H. Ge, Transition-metal-catalyzed C(sp³)–H bond fluorination reactions, Chem. Catal., 2024, 4, 101009; (g) J.-Z. Li, L. Mei, X.-C. Yu, L.-T. Wang, X.-E. Cai, T. Li and W.-T. Wei, C-centered radical-initiated cyclization by directed C(sp³)–H oxidative functionalization, Org. Chem. Front., 2022, 9, 5726–5757; (h) K. Ohmatsu and T. Ooi, Catalytic acceptorless dehydrogenative coupling mediated by photoinduced hydrogen-atom transfer, Nat. Synth., 2023, 2, 209–216; (i) J. Kaur and J. P. Barham, Site-Selective C(sp³)–H Functionalizations Mediated by Hydrogen Atom Transfer Reactions via α-Amino/α-Amido Radicals, Synthesis, 2022, 1461–1477.
3. (a) H. Chen, T. Tang, C. A. Malapit, Y. S. Lee, M. B. Prater, N. S. Weliwatte and S. D. Minteer, One-Pot Bioelectrocatalytic Conversion of Chemically Inert Hydrocarbons to Imines, J. Am. Chem. Soc., 2022, 144, 4047–4056; (b) P. Bellotti, H.-M. Huang, T. Faber and F. Glorius, Photocatalytic Late-Stage C–H Functionalization, Chem. Rev., 2023, 123, 4237–4352; (c) L. Sun, D. Zhao, K. Sun, F. Liu, S. Yang, S. Chen and X. Wang, Photo/Electrochemical-Mediated C(sp³)–H Bond Functionalization of (Thio)Ethers, Eur. J. Org. Chem., 2024, e202400057; (d) L. Dai, Y.-Y. Chen, L.-J. Xiao and Q.-L. Zhou, Intermolecular Enantioselective Benzylic C(sp³)–H Amination by Cationic Copper Catalysis, Angew. Chem., Int. Ed., 2023, 62, e202304427; (e) L. Ge, H. Wang, Y. Liu and X. Feng, Asymmetric Three-Component Radical Alkene Carboazidation by Direct Activation of Aliphatic C–H Bonds, J. Am. Chem. Soc., 2024, 146, 13347–13355.
4. (a) N. A. Romero and D. A. Nicewicz, Organic Photoredox Catalysis, Chem. Rev., 2016, 116, 10075–10166; (b) L. Marzo, S. K. Pagire, O. Reiser and B. König, Visible-Light Photocatalysis: Does It Make a Difference in Organic Synthesis?, Angew. Chem., Int. Ed., 2018, 57, 10034–10072; (c) A. Y. Chan, I. B. Perry, N. B. Bissonnette, B. F. Buksh, G. A. Edwards, L. I. Frye, O. L. Garry, M. N. Lavagnino, B. X. Li, Y. Liang, E. Mao, A. Millet, J. V. Oakley, N. L. Reed, H. A. Sakai, C. P. Seath and D. W. C. MacMillan, Metallaphotoredox: The Merger of Photoredox and Transition Metal Catalysis, Chem. Rev., 2022, 122, 1485–1542; (d) P. P. Singh, P. K. Singh and V. Srivastava, Visible light metallaphotoredox catalysis in the late-stage functionalization of pharmaceutically potent compounds, Org. Chem. Front., 2023, 10, 216–236.
5. (a) H. Cao, X. Tang, H. Tang, Y. Yuan and J. Wu, Photoinduced intermolecular hydrogen atom transfer reactions in organic synthesis, Chem. Catal., 2021, 1, 523–598; (b) L. Capaldo, D. Ravelli and M. Fagnoni, Direct Photocatalyzed Hydrogen Atom Transfer (HT) for Aliphatic C–H Bonds Elaboration, Chem. Rev., 2022, 122, 1875–1924; (c) Á. Velasco-Rubio, P. Martínez-Balart, A. M. Álvarez-Constantino and M. Fañanás-Mastral, C–C bond formation via photocatalytic direct functionalization of simple alkanes, Chem. Commun., 2023, 59, 9424–9444; (d) L. Chang, S. Wang, Q. An, L. Liu, H. Wang, Y. Li, K. Feng and Z. Zuo, Resurgence and advancement of photochemical hydrogen atom transfer processes in selective alkane functionalizations, Chem. Sci., 2023, 14, 6841–6859; (e) L. Revathi, L. Ravindar, W.-Y. Fang, K. P. Rakesh and H.-L. Qin, Visible Light-Induced C−H Bond Functionalization: A Critical Review, Adv. Synth. Catal., 2018, 360, 4652–4698; (f) L. Capaldo and D. Ravelli, Hydrogen Atom Transfer (HAT): A Versatile Strategy for Substrate Activation in Photocatalyzed Organic Synthesis, Eur. J. Org. Chem., 2017, 2056–2071; (g) X. Chen and S. Kramer, Photoinduced transition-metal-catalyzed enantioselective functionalization of non-acidic C(sp³)-H bonds, Chem. Catal., 2024, 4, 100854.
6. (a) X.-Z. Fan, J.-W. Rong, H.-L. Wu, Q. Zhou, H.-P. Deng, J. D. Tan, C.-W. Xue, L.-Z. Wu, H.-R. Tao and J. Wu, Eosin Y as a Direct Hydrogen-Atom Transfer Photocatalyst for the Functionalization of C−H Bonds, Angew. Chem., Int. Ed., 2018, 57, 8514–8518; (b) D.-M. Yan, Q.-Q. Zhao, L. Rao, J.-R. Chen and W.-J. Xiao, Eosin Y as a Redox Catalyst and Photosensitizer for Sequential Benzylic C−H Amination and Oxidation, Chem. – Eur. J., 2018, 24, 16895–16901; (c) J. Inoa, G. Dominici, R. Eldabagh, J. J. I. V. Foley and Y. Xing, Synthetic Applications and Computational Perspectives on Eosin Y Induced Direct HAT Process, Synthesis, 2021, 2183–2191.
7. (a) B.-C. Hong and R. R. Indurmuddam, Tetrabutylammonium decatungstate (TBADT), a compelling and trailblazing catalyst for visible-light-induced organic photocatalysis, Org. Biomol. Chem., 2024, 22, 3799–3842; (b) M. D. Tzirakis, I. N. Lykakis and M. Orfanopoulos, Decatungstate as an efficient photocatalyst in organic chemistry, Chem. Soc. Rev., 2009, 38, 2609–2621; (c) P. P. Singh, S. Sinha, P. Gahtori, S. Tivari and V. Srivastava, Recent advances of decatungstate photocatalyst in HAT process, Org. Biomol. Chem., 2024, 22, 2523–2538; (d) Z. Yuan and R. Britton, Development and application of decatungstate catalyzed C–H ¹⁸F- and ¹⁹F-fluorination, fluoroalkylation and beyond, Chem. Sci., 2023, 14, 12883–12897.
8. (a) M.-J. Zhou, L. Zhang, G. Liu, C. Xu and Z. Huang, Site-Selective Acceptorless Dehydrogenation of Aliphatics Enabled by Organophotoredox/Cobalt Dual Catalysis, J. Am. Chem. Soc., 2021, 143, 16470–16485; (b) Q. Hu, S. Song, T. Zeng, L. Wang, Z. Li, J. Wu and J. Zhu, 1,3-Butadiene Dicarbofunctionalization Enabled by the Dual Role of Diaryl Ketone in Photo-HAT/Chromium Catalysis, Org. Lett., 2024, 26, 1550–1555; (c) H. Kang, L. Tan, J.-T. Han, C.-Y. Huang, H. Su, A. Kavun and C.-J. Li, Acceptorless cross-dehydrogenative coupling for C(sp³)-H heteroarylation mediated by a heterogeneous GaN/ketone photocatalyst/photosensitizer system, Commun. Chem., 2023, 6, 181.
9. Selected reviews and articles: (a) X.-Y. Yuan, C.-C. Wang and B. Yu, Recent advances in FeCl₃-photocatalyzed organic reactions via hydrogen-atom transfer, Chin. Chem. Lett., 2024, 35, 109517; (b) Z.-Y. Dai, S.-Q. Zhang, X. Hong, P.-S. Wang and L.-Z. Gong, A practical FeCl₃/HCl photocatalyst for versatile aliphatic C–H functionalization, Chem. Catal., 2022, 2, 1211–1222; (c) Y. Jin, Q. Zhang, L. Wang, X. Wang, C. Meng and C. Duan, Green Chem., 2021, 23, 6984–6989; (d) Y. Jin, L. Wang, Q. Zhang, Y. Zhang, Q. Liao and C. Duan, Photo-induced direct alkynylation of methane and other light alkanes by iron catalysis, Green Chem., 2021, 23, 9406–9411.
10. (a) A. Matsumoto and K. Maruoka, Design of Organic Radical Cations as Potent Hydrogen-Atom Transfer Catalysts for C−H Functionalization, Asian J. Org. Chem., 2024, 13, e202300580; (b) Z. Wang, C.-X. Yan, R. Liu, X. Li, J. Dai, X. Li and D. Shi, Photo-induced versatile aliphatic C–H functionalization via electron donor–acceptor complex, Sci. Bull., 2024, 69, 345–353; (c) E. Mao and D. W. C. MacMillan, Late-Stage C(sp³)–H Methylation of Drug Molecules, J. Am. Chem. Soc., 2023, 145, 2787–2793.
11. (a) Y. Abderrazak, A. Bhattacharyya and O. Reiser, Visible-Light-Induced Homolysis of Earth-Abundant Metal-Substrate Complexes: A Complementary Activation Strategy in Photoredox Catalysis, Angew. Chem., Int. Ed., 2021, 60, 21100–21115; (b) F. Juliá, Ligand-to-Metal Charge Transfer (LMCT) Photochemistry at 3d-Metal Complexes: An Emerging Tool for Sustainable Organic Synthesis, ChemCatChem, 2022, 14, e202200916; (c) S. Gavelle, M. Innocent, T. Aubineau and A. Guérinot, Photoinduced Ligand-to-Metal Charge Transfer of Carboxylates: Decarboxylative Functionalizations, Lactonizations, and Rearrangements, Adv. Synth. Catal., 2022, 364, 4189–4230.
12. Selected reviews and articles: (a) J. P. Barham and B. König, Synthetic Photoelectrochemistry, Angew. Chem., Int. Ed., 2020, 59, 11732–11747; (b) H. Huang, K. A. Steiniger and T. H. Lambert, Electrophotocatalysis: Combining Light and Electricity to Catalyze Reactions, J. Am. Chem. Soc., 2022, 144, 12567–12583; (c) L. Li, Y. Yao and N. Fu, Trinity of electrochemistry, photochemistry, and transition metal catalysis, Chem. Catal., 2024, 4, 100898; (d) Z. Shen, J.-L. Tu and B. Huang, Unleashing the potentiality of metals: synergistic catalysis with light and electricity, Org. Chem. Front., 2024, 11, 4024–4040; (e) Q. Wan, X.-D. Wu, Z.-W. Hou, Y. Ma and L. Wang, Organophotoelectrocatalytic C(sp²)–H alkylation of heteroarenes with unactivated C(sp³)–H compounds, Chem. Commun., 2024, 60, 5502–5505; (f) M. Tao, Q. Feng, K. Gong, X. Yang, L. Shi, Q. Chang and D. Liang, Photoredox streamlines electrocatalysis: photoelectrosynthesis of polycyclic pyrimidin-4-ones through carbocyclization of unactivated alkenes with malonates, Green Chem., 2024, 26, 4199–4208; (g) X.-L. Lai and H.-C. Xu, Photoelectrochemical Asymmetric Catalysis Enables Enantioselective Heteroarylcyanation of Alkenes via C–H Functionalization, J. Am. Chem. Soc., 2023, 145, 18753–18759; (h) K. Gong, Y. Ma, P. Yu, S. Gao, Y. Li, D. Liang, S. Sun and B. Wang, Self- or Acridinium-Catalyzed Electrophotosynthesis of Thiocyanato Heterocycles from Activated Alkenes, Adv. Synth. Catal., 2024, 366, 2352–2362; (i) H. He, C.-M. Pan, Z.-W. Hou, M. Sun and L. Wang, Organocatalyzed Photoelectrochemistry for the Generation of Acyl and Phosphoryl Radicals through Hydrogen Atom-Transfer Process, J. Org. Chem., 2024, 89, 7531–7540.
13. Selected articles: (a) S. M. Treacy and T. Rovis, Copper Catalyzed C(sp³)–H Bond Alkylation via Photoinduced Ligand-to-Metal Charge Transfer, J. Am. Chem. Soc., 2021, 143, 2729–2735; (b) Y. He, C. Tian, G. An and G. Li, β-C(sp³)−H chlorination of amide derivatives via photoinduced copper charge transfer catalysis, Chin. Chem. Lett., 2024, 35, 108546.
14. Selected articles: (a) X.-L. Lai, M. Chen, Y. Wang, J. Song and H.-C. Xu, Photoelectrochemical Asymmetric Catalysis Enables Direct and Enantioselective Decarboxylative Cyanation, J. Am. Chem. Soc., 2022, 144, 20201–20206; (b) C.-Y. Cai, X.-L. Lai, Y. Wang, H.-H. Hu, J. Song, Y. Yang, C. Wang and H.-C. Xu, Photoelectrochemical asymmetric catalysis enables site- and enantioselective cyanation of benzylic C–H bonds, Nat. Catal., 2022, 5, 943–951.
15. (a) D. Birnthaler, R. Narobe, E. Lopez-Berguno, C. Haag and B. König, ACS Catal., 2023, 13, 1125–1132; (b) J. Dong, Z. Tang, L. Zou, Y. Zhou and J. Chen, Visible light-induced hydrogen atom transfer trifluoromethylthiolation of aldehydes with bismuth catalyst, Chem. Commun., 2024, 60, 742–745; (c) J. Patra, A. M. Nair and C. M. R. Volla, Expedient radical phosphonylations via ligand to metal charge transfer on bismuth, Chem. Sci., 2024, 15, 7136–7143.
16. (a) M. Yamane, Y. Kanzaki, H. Mitsunuma and M. Kanai, Titanium(IV) Chloride-Catalyzed Photoalkylation via C(sp³)–H Bond Activation of Alkanes, Org. Lett., 2022, 24, 1486–1490; (b) X. Peng, Y. Hirao, S. Yabu, H. Sato, M. Higashi, T. Akai, S. Masaoka, H. Mitsunuma and M. Kanai, A Catalytic Alkylation of Ketones via sp³ C–H Bond Activation, J. Org. Chem., 2023, 88, 6333–6346; (c) J.-L. Tu and B. Huang, Titanium in photocatalytic organic transformations: current applications and future developments, Org. Biomol. Chem., 2024 10.1039/D4OB01152J.
17. (a) G.-D. Xia, Z.-K. Liu, Y.-L. Zhao, F.-C. Jia and X.-Q. Hu, Radical Phosphorylation of Aliphatic C–H Bonds via Iron Photocatalysis, Org. Lett., 2023, 25, 5279–5284; (b) W. Shi, P.-F. Zhong, X.-K. Qi, C. Yang, L. Guo and W. Xia, Photoinduced ligand-to-iron charge transfer enabled C(sp³)–H phosphorylation of hydrocarbons, Green Chem., 2023, 25, 7817–7824.
18. (a) S. Roediger, S. U. Leutenegger and B. Morandi, Nickel-catalysed diversification of phosphine ligands by formal substitution at phosphorus, Chem. Sci., 2022, 13, 7914–7919; (b) H. Pellissier, TADDOL-derived phosphorus ligands in asymmetric catalysis, Coord. Chem. Rev., 2023, 482, 215079.
19. C. Shu, A. Noble and V. K. Aggarwal, Metal-free photoinduced C(sp³)–H borylation of alkanes, Nature, 2020, 586, 714–719.
20. (a) J.-L. Tu, A.-M. Hu, L. Guo and W. Xia, Iron-Catalyzed C(Sp³)–H Borylation, Thiolation, and Sulfinylation Enabled by Photoinduced Ligand-to-Metal Charge Transfer, J. Am. Chem. Soc., 2023, 145, 7600–7611; (b) W. Fang, H.-Q. Wang, W. Zhou, Z.-W. Luo and J.-J. Dai, Photoinduced C(sp³)–H borylation of alkanes mediated by copper(II) chloride, Chem. Commun., 2023, 59, 7108–7111; (c) R. Sang, W. Han, H. Zhang, C. M. Saunders, A. Noble and V. K. Aggarwal, Copper-Mediated Dehydrogenative C(sp³)–H Borylation of Alkanes, J. Am. Chem. Soc., 2023, 145, 15207–15217; (d) Y. Cao, C. Huang and Q. Lu, Photoelectrochemically driven iron-catalysed C(sp³)−H borylation of alkanes, Nat. Synth., 2024, 3, 537–544; (e) W. Wei, B. Wang, L. Homölle Simon, J. Zhu, Y. Li, T. von Münchow, I. Maksso and L. Ackermann, Photoelectrochemical Iron-Catalyzed C(sp³)–H Borylation of Alkanes in a Position-Selective Manner, CCS Chem., 2024, 6, 1430–1438; (f) M. Wang, Y. Huang and P. Hu, Terminal C(sp³)–H borylation through intermolecular radical sampling, Science, 2024, 383, 537–544.
21. A.-M. Hu, J.-L. Tu, M. Luo, C. Yang, L. Guo and W. Xia, An iron-catalyzed C–S bond-forming reaction of carboxylic acids and hydrocarbons via photo-induced ligand to metal charge transfer, Org. Chem. Front., 2023, 10, 4764–4773.
22. (a) M. Wang and X. Jiang, Prospects and Challenges in Organosulfur Chemistry, ACS Sustainable Chem. Eng., 2022, 10, 671–677; (b) X. Wang, J. Meng, D. Zhao, S. Tang and K. Sun, Synthesis and applications of thiosulfonates and selenosulfonates as free-radical reagents, Chin. Chem. Lett., 2023, 34, 107736; (c) E. Skolia, P. L. Gkizis and C. G. Kokotos, Aerobic Photocatalysis: Oxidation of Sulfides to Sulfoxides, ChemPlusChem, 2022, 87, e202200008.
23. Selected reviews and articles: (a) W. Guo, Q. Wang and J. Zhu, Visible light photoredox-catalysed remote C–H functionalisation enabled by 1,5-hydrogen atom transfer (1,5-HAT), Chem. Soc. Rev., 2021, 50, 7359–7377; (b) J. Zhang and M. Rueping, Metallaphotoredox catalysis for sp³ C–H functionalizations through hydrogen atom transfer (HAT), Chem. Soc. Rev., 2023, 52, 4099–4120; (c) S. Sarkar, S. Wagulde, X. Jia and V. Gevorgyan, General and selective metal-free radical α-C–H borylation of aliphatic amines, Chem, 2022, 8, 3096–3108; (d) J. Wang, Q. Xie, G. Gao, H. Li, W. Lu, X. Cai, X. Chen and B. Huang, Selective N-α-C–H alkylation of cyclic tertiary amides via visible-light-mediated 1,5-hydrogen atom transfer, Org. Chem. Front., 2023, 10, 4394–4399; (e) L. Zeng, C.-H. Xu, X.-Y. Zou, Q. Sun, M. Hu, X.-H. Ouyang, D.-L. He and J.-H. Li, Iodoarene-directed photoredox β-C(sp³)–H arylation of 1-(o-iodoaryl)alkan-1-ones with cyanoarenes via halogen atom transfer and hydrogen atom transfer, Chem. Sci., 2024, 15, 6522–6529; (f) J. Wang, Q. Xie, G. Gao, G. Wei, X. Wei, X. Chen, D. Zhang, H. Li and B. Huang, Visible-light-mediated synthesis of polysubstituted pyrroles via C_Ar-I reduction triggered 1,5-hydrogen atom transfer process, Org. Chem. Front., 2024, 11, 4522–4528; (g) J. Lu, K. Yuan, J. Zheng, H. Zhang, S. Chen, J. Ma, X. Liu, B. Tu, G. Zhang and R. Guo, Photoinduced Electron Donor Acceptor Complex-Enabled α-C(sp³)-H Alkenylation of Amines, Angew. Chem., Int. Ed., 2024 DOI:10.1002/anie.202409310.
24. Selected reviews and articles: (a) S. P. M. Ung, V. A. Mechrouk and C.-J. Li, Shining Light on the Light-Bearing Element: A Brief Review of Photomediated C–H Phosphorylation Reactions, Synthesis, 2020, 1003–1022; (b) N. Sbei, G. M. Martins, B. Shirinfar and N. Ahmed, Electrochemical Phosphorylation of Organic Molecules, Chem. Rec., 2020, 20, 1530–1552; (c) Y. Jian, M. Chen, B. Huang, W. Jia, C. Yang and W. Xia, Visible-Light-Induced C(sp²)–P Bond Formation by Denitrogenative Coupling of Benzotriazoles with Phosphites, Org. Lett., 2018, 20, 5370–5374; (d) C. Wang, Q. Ge, C. Xu, Z. Xing, J. Xiong, Y. Zheng and W.-L. Duan, Photoinduced Copper-Catalyzed C(sp³)–P Bond Formation by Coupling of Secondary Phosphines with N-(Acyloxy)phthalimides and N-Fluorocarboxamides, Org. Lett., 2023, 25, 1583–1588; (e) N. B. Bissonnette, N. Bisballe, A. V. Tran, J. A. Rossi-Ashton and D. W. C. MacMillan, Development of a General Organophosphorus Radical Trap: Deoxyphosphonylation of Alcohols, J. Am. Chem. Soc., 2024, 146, 7942–7949.
25. (a) J. B. Rodriguez and C. Gallo-Rodriguez, The Role of the Phosphorus Atom in Drug Design, ChemMedChem, 2019, 14, 190–216; (b) A. O. Kolodiazhna and O. I. Kolodiazhnyi, Chiral Organophosphorus Pharmaceuticals: Properties and Application, Symmetry, 2023, 15, 1550.
26. (a) F. L. Weisenborn, J. L. Bouchard, D. Smith, F. Pansy, G. Maestrone, G. Miraglia and E. Meyers, The Prasinomycins: Antibiotics containing Phosphorus, Nature, 1967, 213, 1092–1094; (b) M. Kuemin and W. A. van der Donk, Structure–activity relationships of the phosphonateantibiotic dehydrophos, Chem. Commun., 2010, 46, 7694–7696.
27. (a) J. R. Idle and D. Beyoğlu, Ifosfamide - History, efficacy, toxicity and encephalopathy, Pharmacol. Ther., 2023, 243, 108366; (b) E. Hughes, M. Scurr, E. Campbell, E. Jones, A. Godkin and A. Gallimore, T-cell modulation by cyclophosphamide for tumour therapy, Immunology, 2018, 154, 62–68.
28. (a) R. Kaur and D. Goyal, Toxicity and degradation of the insecticide monocrotophos, Environ. Chem. Lett., 2019, 17, 1299–1324; (b) Y. Iwata, G. E. Carman and F. A. Gunther, Worker environment research: methidathion applied to orange trees, J. Agric. Food Chem., 1979, 27, 119–129.
29. H. Zhang, X.-Y. Zhang, D.-Q. Dong and Z.-L. Wang, Copper-catalyzed cross-coupling reactions for C–P bond formation, RSC Adv., 2015, 5, 52824–52831.
30. A. A. Zagidullin, I. y. F. Sakhapov, V. A. Miluykov and D. G. Yakhvarov, Nickel Complexes in C-P Bond Formation, Molecules, 2021, 26, 5283.
31. U. S. Kanchana, E. J. Diana, T. V. Mathew and G. Anilkumar, Palladium- Catalyzed C−P Bond Forming Reactions: An Overview, ChemistrySelect, 2021, 6, 1579–1588.
32. (a) D. Peng, S. Zhang, W. Fan, Y. Wen and S. Li, Zn-Mediated Scalable Synthesis of Trifluoromethylphosphines from Phosphine Chlorides and CF₃Br, Org. Lett., 2023, 25, 3892–3897; (b) S. Jin, G. C. Haug, V. T. Nguyen, C. Flores-Hansen, H. D. Arman and O. V. Larionov, Decarboxylative Phosphine Synthesis: Insights into the Catalytic, Autocatalytic, and Inhibitory Roles of Additives and Intermediates, ACS Catal., 2019, 9, 9764–9774; (c) P. B. Arockiam, U. Lennert, C. Graf, R. Rothfelder, D. J. Scott, T. G. Fischer, K. Zeitler and R. Wolf, Chem. – Eur. J., 2020, 26, 16374–16382; (d) P. Cui, S. Li, X. Wang, M. Li, C. Wang and L. Wu, Visible-Light-Promoted Unsymmetrical Phosphine Synthesis from Benzylamines, Org. Lett., 2022, 24, 1566–1570.
33. Selected articles: (a) Q. Xue, J. Xie, H. Jin, Y. Cheng and C. Zhu, Highly efficient visible-light-induced aerobic oxidative C–C, C–P coupling from C–H bonds catalyzed by a gold(III)-complex, Org. Biomol. Chem., 2013, 11, 1606–1609; (b) M. Liu, J. Zhu, X. Jiang, X. Yang and Q. Chen, Visible light irradiated photocatalytic C(sp³)–H phosphorylation of xanthenes and 9,10-dihydroacridines with P(O)–H compounds, Org. Biomol. Chem., 2023, 21, 6488–6492.
34. Selected articles: (a) M.-J. Yi, T.-F. Xiao, W.-H. Li, Y.-F. Zhang, P.-J. Yan, B. Zhang, P.-F. Xu and G.-Q. Xu, Organic photoredox catalytic α-C(sp³)–H phosphorylation of saturated aza-heterocycles, Chem. Commun., 2021, 57, 13158–13161; (b) R. Wang, J. Wang, Y. Zhang, B. Wang, Y. Xia, F. Xue, W. Jin and C. Liu, Electrochemical Oxidative Phosphorylations of Glycine Derivatives with R₂P(O)−H-Containing Compounds via C(sp³)−H Functionalisation, Adv. Synth. Catal., 2023, 365, 900–905; (c) S. Wang, X. Sha, Z. Wu, B. Su, S. Zheng, C. Jiang and H. Lu, Eur. J. Org. Chem., 2024, e202400461.
35. Z. Lei, W. Zhang and J. Wu, Photocatalytic Hydrogen Atom Transfer-Induced Arbuzov-Type α-C(sp³)–H Phosphonylation of Aliphatic Amines, ACS Catal., 2023, 13, 16105–16113.
36. H. Liu, K. Wang, S. Ye, Q. Zhu and H. Huang, Iron-catalyzed C(sp³)–H phosphorylation via photoinduced LMCT, Org. Chem. Front., 2024, 11, 2027–2032.
37. (a) K. Duan, X. Yan, Y. Liu and Z. Li, Recent Progress in the Radical Chemistry of Alkylborates and Alkylboronates, Adv. Synth. Catal., 2018, 360, 2781–2795; (b) J. Carreras, A. Caballero and P. J. Pérez, Alkenyl Boronates: Synthesis and Applications, Chem. – Asian J., 2019, 14, 329–343.
38. (a) P. Tian and R. Tong, In-water oxidative Suzuki coupling of arenes and arylboronic acids using H₂O₂ as a terminal oxidant, Green Chem., 2023, 25, 1345–1350; (b) P. Basnet, S. Thapa, D. A. Dickie and R. Giri, The copper-catalysed Suzuki–Miyaura coupling of alkylboron reagents: disproportionation of anionic (alkyl)(alkoxy)borates to anionic dialkylborates prior to transmetalation, Chem. Commun., 2016, 52, 11072–11075; (c) K. K. Das, S. Mahato, D. Ghorai, S. Dey and S. Panda, Photoredox Suzuki coupling using alkyl boronic acids and esters, Org. Chem. Front., 2024, 11, 854–863.
39. Selected reviews and articles: (a) Z.-T. Jiang, B.-Q. Wang and Z.-J. Shi, Transition Metal Catalyzed Direct Oxidative Borylation of C–H Bonds, Chin. J. Chem., 2018, 36, 950–954; (b) J. Hu, J. Lv and Z. Shi, Emerging trends in C(sp³)–H borylation, Trends Chem., 2022, 4, 685–698; (c) R. Kawazu, T. Torigoe and Y. Kuninobu, Iridium-Catalyzed C(sp³)−H Borylation Using Silyl-Bipyridine Pincer Ligands, Angew. Chem., Int. Ed., 2022, 61, e202202327.
40. G. Yan, D. Huang and X. Wu, Recent Advances in C–B Bond Formation through a Free Radical Pathway, Adv. Synth. Catal., 2018, 360, 1040–1053.
41. (a) S. Sarkar, S. Wagulde, X. Jia and V. Gevorgyan, General and selective metal-free radical α-C–H borylation of aliphatic amines, Chem, 2022, 8, 3096–3108; (b) J. He and S. P. Cook, Metal-free, photoinduced remote C(sp³)–H borylation, Chem. Sci., 2023, 14, 9476–9481.
42. (a) C. Ma, P. Fang, Z.-R. Liu, S.-S. Xu, K. Xu, X. Cheng, A. Lei, H.-C. Xu, C. Zeng and T.-S. Mei, Recent advances in organic electrosynthesis employing transition metal complexes as electrocatalysts, Sci. Bull., 2021, 66, 2412–2429; (b) X. Cheng, A. Lei, T.-S. Mei, H.-C. Xu, K. Xu and C. Zeng, Recent Applications of Homogeneous Catalysis in Electrochemical Organic Synthesis, CCS Chem., 2022, 4, 1120–1152; (c) B. Huang, Z. Sun and G. Sun, Recent progress in cathodic reduction-enabled organic electrosynthesis: Trends, challenges, and opportunities, eScience, 2022, 2, 243–277.
43. P. Xu, P.-Y. Chen and H.-C. Xu, Scalable Photoelectrochemical Dehydrogenative Cross-Coupling of Heteroarenes with Aliphatic C-H Bonds, Angew. Chem., Int. Ed., 2020, 59, 14275–14280.
44. P.-F. Zhong, J.-L. Tu, Y. Zhao, N. Zhong, C. Yang, L. Guo and W. Xia, Photoelectrochemical oxidative C(sp³)−H borylation of unactivated hydrocarbons, Nat. Commun., 2023, 14, 6530.
45. (a) B. M. Colovic, M. V. Vasic, M. D. Djuric and Z. D. Krstic, Sulphur-containing Amino Acids: Protective Role Against Free Radicals and Heavy Metals, Curr. Med. Chem., 2018, 25, 324–335; (b) F. Blachier, M. Andriamihaja and A. Blais, Sulfur-Containing Amino Acids and Lipid Metabolism, J. Nutr., 2020, 150, 2524S–2531S; (c) S. Youssef-Saliba and Y. Vallée, Sulfur Amino Acids: From Prebiotic Chemistry to Biology and Vice Versa, Synthesis, 2021, 2798–2808.
46. (a) A. Guarneri, W. J. H. van Berkel and C. E. Paul, Alternative coenzymes for biocatalysis, Curr. Opin. Biotechnol., 2019, 60, 63–71; (b) I. Di Meo, M. Carecchio and V. Tiranti, Inborn errors of coenzyme A metabolism and neurodegeneration, J. Inherited Metab. Dis., 2019, 42, 49–56.
47. (a) J. Zempleni, Uptake, localization, and noncarboxylase roles of biotin, Annu. Rev. Nutr., 2005, 25, 175–196; (b) D. M. Mock, Biotin: From Nutrition to Therapeutics, J. Nutr., 2017, 147, 1487–1492.
48. (a) K. Scherlach, W. Kuttenlochner, D. H. Scharf, A. A. Brakhage, C. Hertweck, M. Groll and E. M. Huber, Structural and Mechanistic Insights into C−S Bond Formation in Gliotoxin, Angew. Chem., Int. Ed., 2021, 60, 14188–14194; (b) S. Zhou, W.-J. Wei and R.-Z. Liao, QM/MM Study of the Mechanism of the Noncanonical S-Cγ Bond Scission in S-Adenosylmethionine Catalyzed by the CmnDph2 Radical Enzyme, Top. Catal., 2022, 65, 517–527; (c) X. Chen and B. Li, How nature incorporates sulfur and selenium into bioactive natural products, Curr. Opin. Chem. Biol., 2023, 76, 102377.
49. (a) Z.-W. Chen, R. Bai, P. Annamalai, S. S. Badsara and C.-F. Lee, The journey of C–S bond formation from metal catalysis to electrocatalysis, New J. Chem., 2022, 46, 15–38; (b) C. Shen, P. Zhang, Q. Sun, S. Bai, T. S. A. Hor and X. Liu, Recent advances in C–S bond formation via C–H bond functionalization and decarboxylation, Chem. Soc. Rev., 2015, 44, 291–314; (c) S. Huang, M. Wang and X. Jiang, Ni-catalyzed C–S bond construction and cleavage, Chem. Soc. Rev., 2022, 51, 8351–8377; (d) J. Corpas, S.-H. Kim-Lee, P. Mauleón, R. G. Arrayás and J. C. Carretero, Beyond classical sulfone chemistry: metal- and photocatalytic approaches for C–S bond functionalization of sulfones, Chem. Soc. Rev., 2022, 51, 6774–6823; (e) U. S. Kanchana, E. J. Diana and T. V. Mathew, Recent Trends in Nickel-Catalyzed C−S Bond Formation, Asian J. Org. Chem., 2022, 11, e202200038.
50. Selected reviews and articles: (a) J. Zhu, W.-C. Yang, X.-d. Wang and L. Wu, Photoredox Catalysis in C–S Bond Construction: Recent Progress in Photo-Catalyzed Formation of Sulfones and Sulfoxides, Adv. Synth. Catal., 2018, 360, 386–400; (b) X. Li, M. Jiang, J. Zuo, X. Song, J. Lv and D. Yang, Anti-Markovnikov ring-opening of sulfonium salts with alkynes by visible light/copper catalysis, Sci. China: Chem., 2023, 66, 791–798; (c) S. Zhong, Z. Zhou, F. Zhao, G. Mao, G.-J. Deng and H. Huang, Deoxygenative C–S Bond Coupling with Sulfinates via Nickel/Photoredox Dual Catalysis, Org. Lett., 2022, 24, 1865–1870; (d) V. Srivastava, P. K. Singh, A. Srivastava and P. P. Singh, Recent application of visible-light induced radicals in C–S bond formation, RSC Adv., 2020, 10, 20046–20056.
51. Selected articles: (a) P. J. Sarver, N. B. Bissonnette and D. W. C. MacMillan, Decatungstate-Catalyzed C(sp³)–H Sulfinylation: Rapid Access to Diverse Organosulfur Functionality, J. Am. Chem. Soc., 2021, 143, 9737–9743; (b) T. Li, K. Liang, J. Tang, Y. Ding, X. Tong and C. Xia, A photoexcited halogen-bonded EDA complex of the thiophenolate anion with iodobenzene for C(sp³)–H activation and thiolation, Chem. Sci., 2021, 12, 15655–15661.
52. S. Jin, G. C. Haug, R. Trevino, V. D. Nguyen, H. D. Arman and O. V. Larionov, Photoinduced C(sp³)–H sulfination empowers the direct and chemoselective introduction of the sulfonyl group, Chem. Sci., 2021, 12, 13914–13921.
53. S. Zhang, S. Cao, Y.-M. Lin, L. Sha, C. Lu and L. Gong, Photocatalyzed site-selective C(sp³)-H sulfonylation of toluene derivatives and cycloalkanes with inorganic sulfinates, Chin. J. Catal., 2022, 43, 564–570.
54. Selected reviews and articles: (a) C.-S. Wang, Y. Xu, S.-P. Wang, C.-L. Zheng, G. Wang and Q. Sun, Recent advances in selective mono-/dichalcogenation and exclusive dichalcogenation of C(sp²)–H and C(sp³)–H bonds, Org. Biomol. Chem., 2024, 22, 645–681; (b) K. Sun, X. Wang, C. Li, H. Wang and L. Li, Recent advances in tandem selenocyclization and tellurocyclization with alkenes and alkynes, Org. Chem. Front., 2020, 7, 3100–3119; (c) B. Huang, Y. Li, C. Yang and W. Xia, Three-component aminoselenation of alkenes via visible-light enabled Fe-catalysis, Green Chem., 2020, 22, 2804–2809; (d) M. Zhang, Z. Luo, X. Tang, L. Yu, J. Pei, J. Wang, C. Lu and B. Huang, Electrochemical selenocyclization of 2-ethynylanilines with diselenides: Facile and efficient access to 3-selenoindoles, Org. Biomol. Chem., 2023, 21, 8918–8923; (e) B. Huang, X. Tang, J. Yuan, M. Zhang, Z. Luo, J. Wang and C. Lu, Visible-light induced selenocyclization of 2-ethynylanilines under ambient conditions: simple FeBr₃ as a dual-functional catalyst, Org. Biomol. Chem., 2024, 22, 6198–6204.
55. B. Niu, K. Sachidanandan, M. V. Cooke, T. E. Casey and S. Laulhé, Photoinduced C(sp³)–H Chalcogenation of Amide Derivatives and Ethers via, Ligand-to-Metal Charge-Transfer, Org. Lett., 2022, 24, 4524–4529.
56. Z. Wang, Z. Zhang, W. Zhao, P. Sivaguru, G. Zanoni, Y. Wang, E. A. Anderson and X. Bi, Synthetic exploration of sulfinyl radicals using sulfinyl sulfones, Nat. Commun., 2021, 12, 5244.
57. V. D. Nguyen, G. C. Haug, S. G. Greco, R. Trevino, G. B. Karki, H. D. Arman and O. V. Larionov, Decarboxylative Sulfinylation Enables a Direct, Metal-Free Access to Sulfoxides from Carboxylic Acids, Angew. Chem., Int. Ed., 2022, 61, e202210525.
58. H. Tan, C. Zhang, Y. Deng, M. Zhang, X. Cheng, J. Wu and D. Zheng, Photoinduced Radical Sulfinylation of C(sp³)–H Bonds with Sulfinyl Sulfones, Org. Lett., 2023, 25, 2883–2888.
59. N. Taniguchi, M. Hyodo, L.-W. Pan and I. Ryu, Photocatalytic C(sp³)–H thiolation by a double SH₂ strategy using thiosulfonates, Chem. Commun., 2023, 59, 14859–14862.
60. L.-W. Pan, N. Taniguchi, M. Hyodo and I. Ryu, CO-Boosted Protocol for the Photocatalytic C-H Thiolation of Aldehydes Using Phenylthiobenzenesulfonate, Eur. J. Org. Chem., 2024, 27, e202400138.
61. P. Li, J.-L. Tu, A.-M. Hu, L. Guo, C. Yang and W. Xia, Photoinduced decatungstate-catalyzed C(sp³)–H thioetherification by sulfinate salts, Org. Biomol. Chem., 2024, 22, 3420–3424.
62. (a) J. Grover, G. Prakash, C. Teja, G. K. Lahiri and D. Maiti, Metal-free photoinduced hydrogen atom transfer assisted C(sp3)–H thioarylation, Green Chem., 2023, 25, 3431–3436; (b) C.-M. Zhu, R.-B. Liang, Y. Xiao, W. Zhou, Q.-X. Tong and J.-J. Zhong, B Metal-free and site-selective α-C–H functionalization of tetrahydrofuran enabled by the photocatalytic generation of bromine radicals, Green Chem., 2023, 25, 960–965.
63. (a) C. M. A. Gangemi, E. D'Agostino, M. C. Aversa, A. Barattucci and P. M. Bonaccorsi, Sulfoxides and disulfides from sulfenic acids: Synthesis and applications, Tetrahedron, 2023, 143, 133550; (b) X. Chen, W. Shao and G.-J. Deng, Nickel-Catalyzed Deoxygenative Disulfuration of Alcohols to Access Unsymmetrical Disulfides, ACS Catal., 2024, 14, 6451–6461.
64. J. Zhang and A. Studer, Decatungstate-catalyzed radical disulfuration through direct C-H functionalization for the preparation of unsymmetrical disulfide, Nat. Commun., 2022, 13, 3886.
65. Selected reviews and articles: (a) R. Ghomashi, S. Ghomashi, H. Aghaei and R. A. Massah, Recent Advances in Biological Active Sulfonamide based Hybrid Compounds Part A: Two-Component Sulfonamide Hybrids, Curr. Med. Chem., 2023, 30, 407–480; (b) S. Shoaib Ahmad Shah, G. Rivera and M. Ashfaq, Recent Advances in Medicinal Chemistry of Sulfonamides. Rational Design as Anti-Tumoral, Anti-Bacterial and Anti-Inflammatory Agents, Mini-Rev. Med. Chem., 2013, 13, 70–86; (c) N. M. M. Yousif, B. A. A.-R. El-Gazzar, N. H. Hafez, A. A. Fayed, A. ElRashedy and M. N. Yousif, Recent Advances in the Chemistry and Biological Activity of Sulfonamide Derivatives, Mini-Rev. Med. Chem., 2022, 19, 695–707; (d) Y. Chen, P. R. D. Murray, A. T. Davies and M. C. Willis, Direct Copper-Catalyzed Three-Component Synthesis of Sulfonamides, J. Am. Chem. Soc., 2018, 140, 8781–8787; (e) J.-L. Tu, W. Tang, S.-H. He, M. Su and F. Liu, Acceptorless dehydrogenative amination of alkenes for the synthesis of N-heterocycles, Sci. China: Chem., 2022, 65, 1330–1337.
66. G.-D. Xia, R. Li, L. Zhang, Y. Wei and X.-Q. Hu, Iron-Catalyzed Photochemical Synthesis of Sulfinamides from Aliphatic Hydrocarbons and Sulfinylamines, Org. Lett., 2024, 26, 3703–3708.
67. D. Nagornîi, F. Raymenants, N. Kaplaneris and T. Noël, C(sp³)–H sulfinylation of light hydrocarbons with sulfur dioxide via hydrogen atom transfer photocatalysis in flow, Nat. Commun., 2024, 15, 5246.
68. (a) S. Bonciolini, T. Noël and L. Capaldo, Synthetic Applications of Photocatalyzed Halogen-Radical Mediated Hydrogen Atom Transfer for C−H Bond Functionalization, Eur. J. Org. Chem., 2022, e202200417; (b) M. Sadeghi, C(sp³)-H Functionalization Using Chlorine Radicals, Adv. Synth. Catal., 2024, 366, 2898–2918.
69. (a) M. Wu, Z. Wu, H. T. Ang, B. Wang, T. Liu, S. Wu, Z. Lei, M. W. Liaw, S. Chanmungkalakul, C.-L. K. Lee, X. Liu, Y. Lu and J. Wu, Enhanced Reactivity of Acridinium Perchlorate: Harnessing Redox Mediators for Trace Chloride Activation in Hydrogen Atom Transfer Photocatalysis, ACS Catal., 2024, 14, 9364–9373; (b) P. Jia, Q. Li, W. C. Poh, H. Jiang, H. Liu, H. Deng and J. Wu, Light-Promoted Bromine-Radical-Mediated Selective Alkylation and Amination of Unactivated C(sp³)–H Bonds, Chem, 2020, 6, 1766–1776; (c) C.-Y. Huang, J. Li and C.-J. Li, A cross-dehydrogenative C(sp³)−H heteroarylation via photo-induced catalytic chlorine radical generation, Nat. Commun., 2021, 12, 4010.
70. (a) J. Li, J. Zhao and T.-P. Loh, Photoredox-Catalyzed C(sp²)–H Bond Functionalization Reactions: A Short Account, Synlett, 2023, 840–850; (b) U. Dutta, S. Maiti, T. Bhattacharya and D. Maiti, Arene diversification through distal C(sp²)−H functionalization, Science, 2021, 372, 5992; (c) J. Luo and Q. Fu, Aldehyde-Directed C(sp²)−H Functionalization under Transition-Metal Catalysis, Adv. Synth. Catal., 2021, 363, 3868–3878.
71. (a) E. N. Pinter, Z. S. Sheldon, A. Modak and S. P. Cook, Fluorosulfonamide-Directed Heteroarylation of Aliphatic C(sp³)–H Bonds, J. Org. Chem., 2023, 88, 4757–4760; (b) G.-X. Li, X. Hu, G. He and G. Chen, Photoredox-mediated remote C(sp³)–H heteroarylation of free alcohols, Chem. Sci., 2019, 10, 688–693; (c) R. Chi, G.-Y. Xu, Z.-A. Liu, D.-C. Li, W.-Z. Duan, J.-M. Dou, Q.-X. Yao, H.-W. Wang and Y. Lu, RhIII–Catalyzed Direct Heteroarylation of Unactivated C(sp³)–H with N-Heteroaryl Boronates, J. Org. Chem., 2024, 89, 6749–6758; (d) X. Wu, H. Zhang, N. Tang, Z. Wu, D. Wang, M. Ji, Y. Xu, M. Wang and C. Zhu, Metal-free alcohol-directed regioselective heteroarylation of remote unactivated C(sp³)–H bonds, Nat. Commun., 2018, 9, 3343; (e) L. Xuan, R. Du, P. Lei, W. Zhao, L. Tan, C. Ni, H. Wang, Q. Yan, W. Wang and F. Chen, Remote C(sp³)–H heteroarylation of N-fluorocarboxamides with quinoxalin-2(1H)-ones under visible-light-induced photocatalyst-free conditions, Green Chem., 2022, 24, 9475–9481; (f) Y. Wei, X. Wu and C. Zhu, Radical Heteroarylation of Alkenes and Alkanes via Heteroaryl -Migration, Synlett, 2022, 1017–1028.
72. (a) X. Zhang, S. Li, F. Qiu, H. T. Ang, J. Wu and P. Jia, Photocatalyzed Minisci-type reactions for late-stage functionalization of pharmaceutically relevant compounds, Green Chem., 2024, 26, 3595–3626; (b) R. S. J. Proctor and R. J. Phipps, Recent Advances in Minisci-Type Reactions, Angew. Chem., Int. Ed., 2019, 58, 13666–13699; (c) W. Wang and S. Wang, Recent Advances in Minisci-type Reactions and Applications in Organic Synthesis, Curr. Org. Chem., 2021, 25, 894–934; (d) Y. Sun, X. Wu, Z. Cao and C. Zhu, Multipurpose sulfoximine-mediated radical γ-heteroarylation of unactivated C(sp³)-H bonds, Sci. China: Chem., 2023, 66, 1435–1442; (e) W. Jia, Y. Jian, B. Huang, C. Yang and W. Xia, Photoredox-Catalyzed Decarboxylative C–H Acylation of Heteroarenes, Synlett, 2018, 1881–1886; (f) Z. Zhang, F. Cheng, X. Ma, K. Sun, X. Huang, J. An, M. Peng, X. Chen and B. Yu, Decatungstate-photocatalyzed direct acylation of N-heterocycles with aldehydes, Green Chem., 2024, 26, 7331–7336.
73. (a) A. C. Colgan, R. S. J. Proctor, D. C. Gibson, P. Chuentragool, A. S. K. Lahdenperä, K. Ermanis and R. J. Phipps, Hydrogen Atom Transfer Driven Enantioselective Minisci Reaction of Alcohols, Angew. Chem., Int. Ed., 2022, 61, e202200266; (b) H. Li, J. Tong, Y. Zhu, C. Jiang, P. Liu and P. Sun, Electrochemical Minisci reaction via, HAT-driven α-C(sp³)–H functionalization of alcohols, Green Chem., 2022, 24, 8406–8411; (c) C.-L. Zeng, H. Wang, D. Gao, Z. Zhang, D. Ji, W. He, C.-K. Liu, Z. Yang, Z. Fang and K. Guo, CF₃SO₂Na-Mediated Visible-Light-Induced Cross-Dehydrogenative Coupling of Heteroarenes with Aliphatic C(sp³)–H Bonds, Org. Lett., 2022, 24, 3244–3248; (d) L. Mantry and P. Gandeepan, Visible-Light-Induced PhI(OAc)₂-M ediated Alkylation of Heteroarenes with Simple Alkanes and Ethers, J. Org. Chem., 2024, 89, 6539–6544; (e) D.-S. Li, T. Liu, Y. Hong, C.-L. Cao, J. Wu and H.-P. Deng, Stop-Flow Microtubing Reactor-Assisted Visible Light-Induced Hydrogen-Evolution Cross Coupling of Heteroarenes with C(sp³)–H Bonds, ACS Catal., 2022, 12, 4473–4480; (f) L. Laze, B. Quevedo-Flores, I. Bosque and J. C. Gonzalez-Gomez, Org. Lett., 2023, 25, 8541–8546.
74. (a) Z.-J. Wang, S. Zheng, J. K. Matsui, Z. Lu and G. A. Molander, Desulfonative photoredox alkylation of N-heteroaryl sulfones – an acid-free approach for substituted heteroarene synthesis, Chem. Sci., 2019, 10, 4389–4393; (b) S. Kamijo, K. Kamijo and T. Murafuji, Synthesis of Alkylated Pyrimidines via Photoinduced Coupling Using Benzophenone as a Mediator, J. Org. Chem., 2017, 82, 2664–2671; (c) N. P. Ramirez, T. Lana-Villarreal and J. C. Gonzalez-Gomez, Direct Decarboxylative Allylation and Arylation of Aliphatic Carboxylic Acids Using Flavin-Mediated Photoredox Catalysis, Eur. J. Org. Chem., 2020, 1539–1550.
75. (a) T. Wan, L. Capaldo, G. Laudadio, A. V. Nyuchev, J. A. Rincón, P. García-Losada, C. Mateos, M. O. Frederick, M. Nuño and T. Noël, Decatungstate-Mediated C(sp³)–H Heteroarylation via Radical-Polar Crossover in Batch and Flow, Angew. Chem., Int. Ed., 2021, 60, 17893–17897; (b) H. Ni, C. Li, X. Shi, X. Hu and H. Mao, Visible-Light-Promoted Fe(III)-Catalyzed N–H Alkylation of Amides and N-Heterocycles, J. Org. Chem., 2022, 87, 9797–9805; (c) D. I. Ioannou, L. Capaldo, J. Sanramat, J. N. H. Reek and T. Noël, Accelerated Electrophotocatalytic C(sp³)−H Heteroarylation Enabled by an Efficient Continuous-Flow Reactor, Angew. Chem., Int. Ed., 2023, 62, e202315881.
76. Z.-T. Pan, L.-M. Shen, F. W. Dagnaw, J.-J. Zhong, J.-X. Jian and Q.-X. Tong, Minisci reaction of heteroarenes and unactivated C(sp³)–H alkanes via a photogenerated chlorine radical, Chem. Commun., 2023, 59, 1637–1640.
77. J. Xu, L. Liu, Z.-C. Yan, Y. Liu, L. Qin, N. Deng and H.-J. Xu, Photocatalyzed hydroxyalkylation of N-heteroaromatics with aldehydes in the aqueous phase, Green Chem., 2023, 25, 2268–2273.
78. (a) E. Vitaku, D. T. Smith and J. T. Njardarson, Analysis of the Structural Diversity, Substitution Patterns, and Frequency of Nitrogen Heterocycles among U.S. FDA Approved Pharmaceuticals, J. Med. Chem., 2014, 57, 10257–10274; (b) K. A. Jacobson, M. F. Jarvis and M. Williams, Purine and Pyrimidine (P2) Receptors as Drug Targets, J. Med. Chem., 2002, 45, 4057–4093; (c) M. Watanabe, H. Koike, T. Ishiba, T. Okada, S. Seo and K. Hirai, Synthesis and Biological Activity of Methanesulfonamide Pyrimidine- and N-Methanesulfonyl Pyrrole-Substituted 3,5-Dihydroxy-6-heptenoates, a Novel Series of HMG-CoA Reductase Inhibitors, Bioorg. Med. Chem., 1997, 5, 437–444; (d) S. Kamijo, K. Kamijo and T. Murafuji, Synthesis of Alkylated Pyrimidines via Photoinduced Coupling Using Benzophenone as a Mediator, J. Org. Chem., 2017, 82, 2664–2671.
79. P. Li, J.-L. Tu, H. Gao, C. Shi, Y. Zhu, L. Guo, C. Yang and W. Xia, FeCl₃-Catalyzed C(sp³)−H Heteroarylation Enabled by Photoinduced Ligand-to-Metal Charge Transfer, Adv. Synth. Catal., 2024, 366, 220–224.
80. (a) H. Su, B. Wang and S. Shaik, Quantum-Mechanical/Molecular-Mechanical Studies of CYP11A1-Catalyzed Biosynthesis of Pregnenolone from Cholesterol Reveal a C–C Bond Cleavage Reaction That Occurs by a Compound I-Mediated Electron Transfer, J. Am. Chem. Soc., 2019, 141, 20079–20088; (b) F. M. Bickelhaupt and I. Fernández, What defines electrophilicity in carbonyl compounds, Chem. Sci., 2024, 15, 3980–3987; (c) M. dos Santos Costa, A. L. P. de Meireles and E. V. Gusevskaya, Aerobic Palladium-Catalyzed Oxidations in the Upgrading of Biorenewables: Oxidation of β-Ionone and α-Ionone, Asian J. Org. Chem., 2017, 6, 1628–1634; (d) D. McGinty, C. S. Letizia and A. M. Api, Fragrance material review on 3-methyl-1-cyclopentadecanone, Food Chem. Toxicol., 2011, 49, 120–125.
81. S. Mao, K. Chen, G. Yan and D. Huang, β-Keto Acids in Organic Synthesis, Eur. J. Org. Chem., 2020, 525–538.
82. (a) F. Penteado, E. F. Lopes, D. Alves, G. Perin, R. G. Jacob and E. J. Lenardão, α-Keto Acids: Acylating Agents in Organic Synthesis, Chem. Rev., 2019, 119, 7113–7278; (b) W. Shi, C. Yang, L. Guo and W. Xia, Photo-induced decarboxylative hydroacylation of α-oxocarboxylic acids with terminal alkynes by radical addition–translocation–cyclization in water, Org. Chem. Front., 2022, 9, 6513–6519.
83. (a) S.-C. Ren, X. Yang, B. Mondal, C. Mou, W. Tian, Z. Jin and Y. R. Chi, Carbene and photocatalyst-catalyzed decarboxylative radical coupling of carboxylic acids and acyl imidazoles to form ketones, Nat. Commun., 2022, 13, 2846; (b) M. J. Rourke, C. T. Wang, C. R. Schull and K. A. Scheidt, Acyl Azolium–Photoredox-Enabled Synthesis of β-Keto Sulfides, ACS Catal., 2023, 13, 7987–7994; (c) Q.-Y. Meng, L. Lezius and A. Studer, Benzylic C−H acylation by cooperative NHC and photoredox catalysis, Nat. Commun., 2021, 12, 2068; (d) S.-C. Ren, W.-X. Lv, X. Yang, J.-L. Yan, J. Xu, F.-X. Wang, L. Hao, H. Chai, Z. Jin and Y. R. Chi, Carbene-Catalyzed Alkylation of Carboxylic Esters via Direct Photoexcitation of Acyl Azolium Intermediates, ACS Catal., 2021, 11, 2925–2934; (e) X. Wang, B. Zhu, Y. Liu and Q. Wang, Combined Photoredox and Carbene Catalysis for the Synthesis of α-Amino Ketones from Carboxylic Acids, ACS Catal., 2022, 12, 2522–2531; (f) K. Liu and A. Studer, Direct α-Acylation of Alkenes via N-Heterocyclic Carbene, Sulfinate, and Photoredox Cooperative Triple Catalysis, J. Am. Chem. Soc., 2021, 143, 4903–4909.
84. (a) L. Huan, X. Shu, W. Zu, D. Zhong and H. Huo, Direct Asymmetric Functionalization of C-H Bonds via Dual Nickel/Photoredox Catalysis for the Synthesis of Chiral α-Aryl Amides, Nat. Commun., 2021, 12, 3536; (b) X. Shu, D. Zhong, Q. Huang, L. Huan and H. Huo, Site- and enantioselective cross-coupling of saturated N-heterocycles with carboxylic acids by cooperative Ni/photoredox catalysis, Nat. Commun., 2023, 14, 125.
85. Q. Liu, Y. Ding, Y. Gao, Y. Yang, L. Gao, Z. Pan and C. Xia, Decatungstate Catalyzed Photochemical Acetylation of C(sp³)–H Bonds, Org. Lett., 2022, 24, 7983–7987.
86. (a) A. V. Bay and K. A. Scheidt, Single-electron carbene catalysis in redox processes, Trends Chem., 2022, 4, 277–290; (b) A. A. Bayly, B. R. McDonald, M. Mrksich and K. A. Scheidt, High-throughput photocapture approach for reaction discovery, Proc. Natl. Acad. Sci. U. S. A., 2020, 117, 13261–13266.
87. J. L. Zhu, C. R. Schull, A. T. Tam, Á. Rentería-Gómez, A. R. Gogoi, O. Gutierrez and K. A. Scheidt, Photoinduced Acylations via Azolium-Promoted Intermolecular Hydrogen Atom Transfer, J. Am. Chem. Soc., 2023, 145, 1535–1541.
88. (a) Y. Chen, X. Wang, X. He, Q. An and Z. Zuo, Photocatalytic Dehydroxymethylative Arylation by Synergistic Cerium and Nickel Catalysis, J. Am. Chem. Soc., 2021, 143, 4896–4902; (b) Q. An, Y.-Y. Xing, R. Pu, M. Jia, Y. Chen, A. Hu, S.-Q. Zhang, N. Yu, J. Du, Y. Zhang, J. Chen, W. Liu, X. Hong and Z. Zuo, Identification of Alkoxy Radicals as Hydrogen Atom Transfer Agents in Ce-Catalyzed C–H Functionalization, J. Am. Chem. Soc., 2023, 145, 359–376.
89. J. Cao, J. L. Zhu and K. A. Scheidt, Photoinduced cerium-catalyzed C–H acylation of unactivated alkanes, Chem. Sci., 2024, 15, 154–159.
90. Selected recent articles, not individually featured: (a) R. Pilli, K. Selvam, B. S. S. Balamurugan, V. Jose and R. Rasappan, C(sp³)–C(sp³) Coupling of Cycloalkanes and Alkyl Halides via Dual Photocatalytic Hydrogen Atom Transfer and Nickel Catalysis, Org. Lett., 2024, 26, 2993–2998; (b) Y. Chen, B. Yang, Q.-Y. Li, Y.-M. Lin and L. Gong, Selectfluor-enabled photochemical selective C(sp³)–H(sulfonyl)amidation, Chem. Commun., 2023, 59, 118–121; (c) E. Montinho-Inacio, D. Bouchet, W.-Y. Ma, P. Retailleau, L. Neuville and G. Masson, Decatungstate-Photocatalyzed Diastereoselective Dearomative Hydroalkylation of Indoles, Eur. J. Org. Chem., 2024, e202400248; (d) K.-L. Wang, H.-T. Ji, Q.-H. Peng, J. Jiang, L.-J. Ou and W.-M. He, decatungstate-photocatalyzed radical cascade alkylation/cyclization of isocyanides with simple alkanes, ethers and ketones, Green Synth. Catal., 2024 DOI:10.1016/j.gresc.2024.01.003; (e) C.-X. Yang, D.-G. Liu, L.-J. Li, Y.-X. Zhang, X.-R. Xia, H. Jiang and W.-M. Cheng, Light-induced FeCl₃-catalyzed selective benzyl C−H chlorination with trifluoromethanesulfonyl chloride, Adv. Synth. Catal., 2023, 365, 4144–4149; (f) Z. Song, J. Bai, D. Qi, L. Guo, C. Yang and W. Xia, Photo-Induced Synthesis of Functionalized γ-Lactams via Iron-Catalyzed LMCT Cascade, Adv. Synth. Catal., 2024, 366, 1972–1977; (g) H. E. Askey, J. D. Grayson, J. D. Tibbetts, J. C. Turner-Dore, J. M. Holmes, G. Kociok-Kohn, G. L. Wrigley and A. J. Cresswell, Photocatalytic Hydroaminoalkylation of Styrenes with Unprotected Primary Alkylamines, J. Am. Chem. Soc., 2021, 143, 15936–15945; (h) J. Gui, M. Sun, H. Wu, J. Li, J. Yang and Z. Wang, Direct benzylic C–H difluoroalkylation with difluoroenoxysilanes by transition metal-free photoredox catalysis, Org. Chem. Front., 2022, 9, 4569–4574; (i) X. Zhang and R. Zeng, Neutrally photoinduced MgCl₂-catalyzed alkenylation and imidoylation of alkanes, Org. Chem. Front., 2022, 9, 4955–4961; (j) X. Zhang, S. Ning, Y. Li, Y. Xiong and X. Wu, Hydrogen Atom Transfer for C(sp³)−H Functionalization Enabled by Photoredox/Thianthrene/Methanol Synergistic Catalysis, ChemCatChem, 2023, 15, e202300311.
91. (a) L. Sun, Y. Wang, N. Guan and L. Li, Methane Activation and Utilization: Current Status and Future Challenges, Energy Technol., 2020, 8, 1900826; (b) X. Wang, N. Luo and F. Wang, Advances and Challenges of Photocatalytic Methane C–C Coupling, Chin. J. Chem., 2022, 40, 1492–1505.
92. (a) Y. Tian, L. Piao and X. Chen, Research progress on the photocatalytic activation of methane to methanol, Green Chem., 2021, 23, 3526–3541; (b) F. Nkinahamira, R. Yang, R. Zhu, J. Zhang, Z. Ren, S. Sun, H. Xiong and Z. Zeng, Current Progress on Methods and Technologies for Catalytic Methane Activation at Low Temperatures, Adv. Sci., 2023, 10, 2204566.
93. Q. Zhang, S. Liu, J. Lei, Y. Zhang, C. Meng, C. Duan and Y. Jin, Iron-Catalyzed Photoredox Functionalization of Methane and Heavier Gaseous Alkanes: Scope, Kinetics, and Computational Studies, Org. Lett., 2022, 24, 1901–1906.
94. J.-F. Han, P. Guo, X.-G. Zhang, J.-B. Liao and K.-Y. Ye, Recent advances in cobalt-catalyzed allylic functionalization, Org. Biomol. Chem., 2020, 18, 7740–7750.
95. P. Martínez-Balart, B. L. Tóth, Á. Velasco-Rubio and M. Fañanás-Mastral, Direct C–H Allylation of Unactivated Alkanes by Cooperative W/Cu Photocatalysis, Org. Lett., 2022, 24, 6874–6879.
96. P. Peng, Y. Zhong, C. Zhou, Y. Tao, D. Li and Q. Lu, Unlocking the Nucleophilicity of Strong Alkyl C–H Bonds via Cu/Cr Catalysis, ACS Cent. Sci., 2023, 9, 756–762.
97. S. Schmid, S. Wu, I. Dey, M. Domański, X. Tian and J. P. Barham, Photoelectrochemical Heterodifunctionalization of Olefins: Carboamidation Using Unactivated Hydrocarbons, ACS Catal., 2024, 14, 9648–9654.
98. (a) Q. Wang, S. Ni, X. Wang, Y. Wang and Y. Pan, Visible-light-mediated tungsten-catalyzed C-H amination of unactivated alkanes with nitroarenes, Sci. China: Chem., 2022, 65, 678–685; (b) Y.-W. Zheng, R. Narobe, K. Donabauer, S. Yakubov and B. König, Copper(II)-Photocatalyzed N–H Alkylation with Alkanes, ACS Catal., 2020, 10, 8582–8589; (c) T. Kawasaki, K. Yamazaki, R. Tomono, N. Ishida and M. Murakami, Photoinduced Carbamoylation of C(sp³)–H Bonds with Isocyanates, Chem. Lett., 2021, 50, 1684–1687; (d) S. Zhou, T. Liu and X. Bao, Direct intermolecular C(sp³)–H amidation with dioxazolones via, synergistic decatungstate anion photocatalysis and nickel catalysis: A combined experimental and computational study, J. Catal., 2022, 415, 142–152; (e) Q. Wang, S. Ni, L. Yu, Y. Pan and Y. Wang, Photoexcited Direct Amination/Amidation of Inert Csp³−H Bonds via, Tungsten–Nickel Catalytic Relay, ACS Catal., 2022, 12, 11071–11077.
99. (a) S. Cheng, Q. Li, X. Cheng, Y.-M. Lin and L. Gong, Recent Advances in Asymmetric Transformations of Unactivated Alkanes and Cycloalkanes through Direct C–H Functionalization, Chin. J. Chem., 2022, 40, 2825–2837; (b) S. Zhang, S. Dong, X. Cheng, Z. Ye, L. Lin, J. Zhu and L. Gong, Chiral polycyclic benzosultams from photocatalytic diastereo- and enantioselective benzylic C–H functionalization, Org. Chem. Front., 2022, 9, 6853–6860; (c) X. Cheng, T. Li, Y. Liu and Z. Lu, Stereo- and Enantioselective Benzylic C–H Alkenylation via Photoredox/Nickel Dual Catalysis, ACS Catal., 2021, 11, 11059–11065; (d) J. Xu, Z. Li, Y. Xu, X. Shu and H. Huo, Stereodivergent Synthesis of Both Z- and E-Alkenes by Photoinduced, Ni-Catalyzed Enantioselective C(sp³)–H Alkenylation, ACS Catal., 2021, 11, 13567–13574.
100. (a) Y. Tan, Y. Yin, S. Cao, X. Zhao, G. Qu and Z. Jiang, Conjugate addition-enantioselective protonation to forge tertiary stereocentres α to azaarenes via cooperative hydrogen atom transfer and chiral hydrogen-bonding catalysis, Chin. J. Catal., 2022, 43, 558–563; (b) H. Yu, T. Zhan, Y. Zhou, L. Chen, X. Liu and X. Feng, Visible-Light-Activated Asymmetric Addition of Hydrocarbons to Pyridine-Based Ketones, ACS Catal., 2022, 12, 5136–5144; (c) Z.-Y. Dai, Z.-S. Nong, S. Song and P.-S. Wang, Asymmetric Photocatalytic C(sp³)–H Bond Addition to α-Substituted Acrylates, Org. Lett., 2021, 23, 3157–3161; (d) L. Feng, X. Chen, N. Guo, Y. Zhou, L. Lin, W. Cao and X. Feng, Visible-light-induced chemo-, diastereo- and enantioselective α-C(sp³)–H functionalization of alkyl silanes, Chem. Sci., 2023, 14, 4516–4522; (e) W. Zhang, X. Shu, L. Huan, B. Cheng and H. Huo, Enantioselective β-C(sp³)–H arylation of amides via synergistic nickel and photoredox catalysis, Org. Biomol. Chem., 2021, 19, 9407–9409; (f) X. Shu, D. Zhong, Y. Lin, X. Qin and H. Huo, Modular Access to Chiral α-(Hetero)aryl Amines via Ni/Photoredox-Catalyzed Enantioselective Cross-Coupling, J. Am. Chem. Soc., 2022, 144, 8797–8806.
101. S. Xu, Y. Ping, W. Li, H. Guo, Y. Su, Z. Li, M. Wang and W. Kong, Enantioselective C(sp³)–H Functionalization of Oxacycles via Photo-HAT/Nickel Dual Catalysis, J. Am. Chem. Soc., 2023, 145, 5231–5241.
102. Y. Jin, L.-F. Fan, E. W. H. Ng, L. Yu, H. Hirao and L.-Z. Gong, Atom Transfer Radical Coupling Enables Highly Enantioselective Carbo-Oxygenation of Alkenes with Hydrocarbons, J. Am. Chem. Soc., 2023, 145, 22031–22040.
103. X. Chen, Z. Lian and S. Kramer, Enantioselective Intermolecular Radical Amidation and Amination of Benzylic C−H Bonds via Dual Copper and Photocatalysis, Angew. Chem., Int. Ed., 2023, 62, e202217638.
104. Z. Tan, Y. Liu and X. Feng, Photoredox-catalyzed C(sp³)-H radical functionalization to enable asymmetric synthesis of α-chiral alkyl phosphine, Sci. Adv., 2024, 10, eadn9738.
105. H. Hu, Z. Shi, X. Guo, F.-H. Zhang and Z. Wang, A Radical Approach for Asymmetric α-C–H Addition of N-Sulfonyl Benzylamines to Aldehydes, J. Am. Chem. Soc., 2024, 146, 5316–5323.
106. S. Cuesta-Galisteo, J. Schörgenhumer, C. Hervieu and C. Nevado, Dual Nickel/Photoredox-Catalyzed Asymmetric Carbamoylation of Benzylic C(sp³)−H Bonds, Angew. Chem., Int. Ed., 2024, 63, e202313717.
107. (a) S. Otocka, M. Kwiatkowska, L. Madalińska and P. Kiełbasiński, Chiral Organosulfur Ligands/Catalysts with a Stereogenic Sulfur Atom: Applications in Asymmetric Synthesis, Chem. Rev., 2017, 117, 4147–4181; (b) G. Diaz-Muñoz, I. L. Miranda, S. K. Sartori, D. C. de Rezende and M. Alves Nogueira Diaz, Use of chiral auxiliaries in the asymmetric synthesis of biologically active compounds: A review, Chirality, 2019, 31, 776–812.
108. M. Leone, J. P. Milton, D. Gryko, L. Neuville and G. Masson, TBADT-Mediated Photocatalytic Stereoselective Radical Alkylation of Chiral N-Sulfinyl Imines: Towards Efficient Synthesis of Diverse Chiral Amines, Chem. – Eur. J., 2024, 30, e202400363.
109. X. Hu, I. Cheng-Sánchez, W. Kong, G. A. Molander and C. Nevado, Nickel-catalysed enantioselective alkene dicarbofunctionalization enabled by photochemical aliphatic C–H bond activation, Nat. Catal., 2024, 7, 655–665.
110. (a) J. Kang, H. S. Hwang, V. K. Soni and E. J. Cho, Direct C(sp³)–N Radical Coupling: Photocatalytic C–H Functionalization by Unconventional Intermolecular Hydrogen Atom Transfer to Aryl Radical, Org. Lett., 2020, 22, 6112–6116; (b) L. Caiger, H. Zhao, T. Constantin, J. J. Douglas and D. Leonori, The Merger of Aryl Radical-Mediated Halogen-Atom Transfer (XAT) and Copper Catalysis for the Modular Cross-Coupling-Type Functionalization of Alkyl Iodides, ACS Catal., 2023, 13, 4985–4991.
111. X.-Y. Ruan, D.-X. Wu, W.-A. Li, Z. Lin, M. Sayed, Z.-Y. Han and L.-Z. Gong, Photoinduced Pd-Catalyzed Enantioselective Carboamination of Dienes via Aliphatic C–H Bond Elaboration, J. Am. Chem. Soc., 2024, 146, 12053–12062.
112. J. Li, B. Cheng, X. Shu, Z. Xu, C. Li and H. Huo, Enantioselective alkylation of α-amino C(sp³)−H bonds via photoredox and nickel catalysis, Nat. Catal., 2024 DOI:10.1038/s41929-024-01192-7.

---