Photocatalytic ketone synthesis: recent advances in radical-based approaches from carboxylic acids and derivatives

Abstract

Ketones are widely recognized as privileged structural motifs in organic synthesis due to their unique dual reactivity profile, serving as versatile electrophiles in numerous carbon–carbon and carbon–heteroatom bond-forming transformations. Their ubiquitous presence in pharmacologically active compounds, advanced materials, and agrochemicals further underscores their synthetic importance. Consequently, the design of novel catalytic platforms enabling efficient construction of structurally diverse ketones from readily available precursors represents a significant challenge in contemporary synthetic methodology. Carboxylic acids and derivatives, owing to their natural abundance, low cost, and exceptional structural variability, are an ideal class of starting materials for such transformations. The integration of these compounds with photocatalysis enables their transformation into ketones through radical-based reaction strategies, offering distinct advantages over conventional two-electron reaction systems by circumventing their inherent limitations.

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Shengbiao Yang

Shengbiao Yang obtained his B.Sc. degree (2015) from Liaocheng University Dongchang College and PhD degree (2021) from Northeast Normal University under the supervision of Prof. Qian Zhang. From 2022 to 2024, he was a lecturer at Qilu University of Technology. Since 2024, he has been an associate professor at the Qilu Institute of Technology. His research area is organic synthesis methodology, mainly including multicomponent reactions, transition-metal-catalyzed reactions and free radical chemistry.

Xiaochen Wang

Xiaochen Wang obtained her B.Sc. degree (2017) under the supervision of Prof. Zhiyu Dou from the Changchun University of Science and Technology. She then pursed an M.Sc. degree in 2018 under the supervision of Prof. Qingmin Wang at Nankai University and obtained her PhD degree in 2024. Currently, she is a lecturer at Shanxi Medical University. Her research focuses on photoredox catalyzed radical chemistry.

Lan Bao

Lan Bao was born in Inner Mongolia Province, China. She received her B.Sc. degree from Inner Mongolia Minzu University, China, in 2015. She received her M.Sc. degree in Physical Chemistry from Inner Mongolia Minzu University, China, in 2018. She received her PhD in Organic Chemistry from Shandong Normal University under the supervision of Prof. Xianxiu Xu in 2023. Currently, she is an associate professor at the Qilu Institute of Technology. Her research focuses on organic synthesis methodology through green synthesis to achieve the construction of thick rings, spiral rings, large rings, and natural products via one-pot methods.

Tianzhen Wang

Dr Tianzhen Wang obtained his PhD from Wuhan University in 2022 and is currently an associate professor at the Qilu Institute of Technology. His research primarily focuses on molecular computational simulation, heat and mass transfer, water treatment and related fields. In recent years, he has published multiple SCI-indexed papers and participated in several national/provincial-level scientific research projects, corporate technology development initiatives, and international design projects.

Lingang Wu

Lingang Wu received his BSc degree from Shandong Agricultural University in 2014. He then pursued his MSc degree in 2016 under the supervision of Prof. Bin Fu at China Agricultural University. In 2020, he obtained his PhD degree under the supervision of Professor Qingmin Wang from Nankai University. Presently, he is a lecturer at Liaocheng University, and his research primarily focuses on cycloaddition reactions and photoredox catalyzed radical chemistry.

Qingmin Wang

Dr Qingmin Wang is currently a professor at the State Key Laboratory of Elemento-Organic Chemistry, Nankai University. He obtained his BSc degree (1994) from Lanzhou University and PhD degree (2000) from Nankai University under the supervision of Prof. Runqiu Huang. His research interests mainly focus on the isolation, total synthesis, structural optimization, and bioactivity studies of natural products and environmentally friendly green synthesis reactions through photocatalysis and electrocatalysis.

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1. Introduction

The concise forging of the ketone structural unit from feedstock chemicals represents the state of the art in synthetic chemistry as they are extremely common in natural products and pharmaceutical compounds.^1–4 The ketone moiety also serves as a highly versatile reaction center in organic synthesis.^5,6 The classic methods for synthesizing ketone compounds include the following: oxidation processes, such as the oxidation of alcohols, oxidation of alkyl side chains on aromatic rings, oxidation of alkenes, and oxidation after the hydration of alkynes; hydrolysis of dihaloalkanes; transition-metal-catalyzed carbonylation reactions involving carbon monoxide;^7–9 reactions of acyl electrophiles with organometallic reagents (such as Grignard reagents) or electron-rich aromatic rings (Friedel–Crafts reaction, catalyzed by Brønsted or Lewis acids);^10–13 and metal-catalyzed cross-coupling reactions of acyl electrophiles with nucleophilic reagents^14–18 or electrophilic reagents¹⁹ (Fig. 1). However, in these traditional methods, the key step of ketone formation is achieved through a two-electron transfer process or a reductive elimination process involving metal intermediates. The need for cautious operations and substrate pre-functionalization not only compromise functional group tolerance and synthetic flexibility but also fail to meet the escalating need for late-stage modification of complex target molecules such as those found in proteins or within living cells under mild conditions.

Fig. 1 Classic methods for synthesizing ketone compounds.

In contrast, radical-mediated reactions offer the advantages of mild conditions, simple operation, and good functional group compatibility. Photoredox catalysis employing visible light has emerged as a valuable platform for the design of unique one electron-transfer pathways that can be used to construct structurally diverse ketones using simple, inexpensive substrates.^20–27

Carboxylic acids and their derivatives are characterized by their low cost, wide availability, structural diversity, and stability.^28–30 Consequently, radical reactions employing these compounds as starting materials have become a powerful strategy for constructing complex molecules with diverse biological activities.^31,32 Leveraging single-electron transfer processes enabled by photoredox catalysis, novel synthetic approaches employing carboxylic acids as fundamental building blocks have been developed for ketone synthesis. These significant advancements can be categorized into three main types based on the acyl precursor: ketone synthesis via α-keto acids, via carboxylic acids, and via carboxylic acid derivatives (Fig. 2).

Fig. 2 Photocatalytic generation of ketones from carboxylic acids and their derivatives.

2. Acyl radicals generated via α-keto acids

When serving as radical precursors, α-keto acids primarily undergo single-electron oxidation to generate acyl radicals. Subsequently, these acyl radicals can participate in radical addition/coupling reactions or, under transition metal catalysis, couple with electrophilic reagents (Fig. 3).

Fig. 3 Oxidative generation of radicals from α-keto acids.

2.1 Radical addition/coupling reactions

In 2015, the Fu and Shang group³³ reported the generation of an acyl anion equivalent by photoredox catalysis from α-keto acid for addition to various Michael acceptors, including α,β-unsaturated esters, ketones, amides, aldehydes, nitriles, and sulfones under mild conditions. Mechanistic studies indicated that irradiation of the photocatalyst with blue light generates an excited state, which is reduced by the α-keto acid to generate an acyl radical. This acyl radical can be trapped by a Michael acceptor to generate an enolate radical, which may oxidize the reduced photocatalyst to complete the catalytic cycle and deliver the 1,4-addition product after protonation. The employed substrates mainly comprise aromatic and heteroaromatic α-ketocarboxylic acids (Fig. 4).

Fig. 4 Photoredox catalyzed decarboxylative 1,4-addition of α-ketocarboxylic acid.

In 2017, Zhu and co-workers³⁴ utilized a similar mechanism to achieve a domino-fluorination–protodefluorination decarboxylative cross-coupling reaction between α-keto acids and styrenes via photoredox catalysis. The key to the success of this method is the formation of the C–F bond through trapping of a carbon-centered radical intermediate, effectively suppressing side reactions during the styrene radical functionalization process. The employed substrates also mainly encompass aromatic and heteroaromatic α-ketocarboxylic acids (Fig. 5). By changing the acceptors to methacryloyl benzamide, a decarboxylative acyl radical acylation/cyclization cascade reaction can occur for accessing acylated isoquinoline-1,3(2H,4H)-dione derivatives.³⁵ And the construction of acylated heterocyclic derivatives can also be achieved via the same process.³⁶ In 2022, the Smith and Zysman-Colman group reported a metal-free, dual NHC/photoredox catalytic system using the MR-TADF photocatalyst DiKTa for the modular synthesis of unsymmetric 1,4-diketones via α-keto acid-derived acyl radicals under mild conditions.³⁷

Fig. 5 Photoredox catalyzed decarboxylative cross-coupling combined with radical fluorination.

Further deuterium incorporation at the β-position of the ketone was also accomplished by the Liang group using the readily available pyrimidopteridine N-oxide (BuPPTNO) photocatalyst,³⁸ delivering the corresponding β-deuterio ketones in excellent yields with 86–97% D-labelling efficiency. Almost simultaneously, two independent groups^39,40 disclosed visible-light protocols for decarboxylative ring-opening of vinylcyclopropanes with α-keto acids to afford β,γ-alkenyl ketones (Fig. 6).

Fig. 6 Decarboxylative allylation of vinylcyclopropanes with α-keto acids.

In 2023, the Jana group⁴¹ used the same process to produce acyl radicals, enabling the installation of two carbon-based fragments across a styrene double bond in a single step (Fig. 7). By merging a photoredox cycle with either radical–radical coupling or a radical-to-polar switch, this protocol selectively delivers β-acylated products bearing either a benzyl or a carboxyl handle at the α-position. The reactions proceed under mild, transition-metal-free conditions, tolerate a broad range of substituents, and can be scaled up under natural sunlight, providing a concise synthetic route to complex γ-keto acids and related scaffolds. A mild Cr/photoredox dual-catalyzed protocol⁴² enables the decarboxylative coupling of α-keto acids with benzylic Katritzky salts under blue-light irradiation, furnishing diverse ketones through a radical cross-coupling pathway in the absence of olefins.

Fig. 7 β-Acylative divergent alkene difunctionalization with Katritzky salt/CO₂.

In 2018, the Shah group⁴³ reported a photoredox protocol that converts α-keto acids in situ from terminal arylacetylenes directly into acyl radicals via oxidative cleavage, enabling rapid Minisci-type acylation of electron-deficient heteroarenes. The method avoids toxic tin reagents, harsh conditions, and excess acyl sources, and is compatible with alkyl, halo, ether and CF₃ substituents.

Hypervalent iodine reagents have also been introduced into the corresponding acyl radical generation process. In 2015, Chen and co-workers⁴⁴ developed a decarboxylative ynonylation using dual hypervalent iodine(III) reagents/photoredox catalysis to construct ynones, ynamides, and ynoates with a broad substrate scope under mild reaction conditions (Fig. 8a). This process is achieved directly using BI-alkyne as the substrate. Both aromatic and aliphatic α-keto acids proved to be viable substrates in this transformation, yielding the corresponding products efficiently. In parallel, the Wang group⁴⁵ reported a sunlight-driven decarboxylative alkynylation of α-keto acids with bromoacetylenes catalyzed by hypervalent iodine reagents (Fig. 8b). Under sunlight irradiation, the homolytic cleavage of the intermediate formed via the reaction between BI-OH and an α-keto acid generates an iodanyl radical and an acyl radical. The iodanyl radical subsequently reacts with bromoacetylene, yielding BI-alkyne and a bromine radical. Concurrently, the acyl radical undergoes addition with BI-alkyne, forming a vinyl radical intermediate, which then liberates the desired ynone product. Notably, this transformation exhibits a broad substrate scope as the α-keto acid component is not restricted to aryl-substituted variants—aliphatic α-keto acids also participate effectively in the reaction. The Chen group⁴⁶ also reported a visible-light-driven acyl radical Smiles rearrangement under mild, metal-free conditions, wherein biaryl ethers bearing α-ketoacids are converted into hydroxybenzophenones in a single step by dual catalysis with an acridinium photocatalyst (Acr-Mes⁺ClO₄⁻) and a recyclable hypervalent iodine(III) reagent (BIOAc). The protocol tolerates electron-rich and electron-poor aryl rings, aldehydes, halides, nitro, and other functional groups, proceeds in neutral aqueous media, and has been demonstrated on a gram scale.

Fig. 8 Hypervalent iodine-promoted radical addition of aryl α-keto acids to alkynes.

Subsequently, the Wang group⁴⁷ exploited a similar mechanistic pathway using hypervalent iodine reagents to convert α-keto acids into acyl radicals, which then undergo radical addition/cyclization/oxidation with radical acceptors to afford ketone products (Fig. 9a). In 2017, the Duan group⁴⁸ utilized a similar intermediate to generate acyl radicals under the photocatalysis of the organic dye rhodamine B. The acyl radical subsequently undergoes addition and ring expansion of vinylcyclobutanol to furnish the corresponding 1,4-diketones (Fig. 9b). By changing the acceptor to N-benzylacrylamides, functionalized γ-ketoamides and 2-azaspiro[4.5]decanes can be synthesized in one pot in good to excellent yields via an acyl radical-triggered cascade involving a 1,4-HAT and dearomative spirocyclization reaction through the same mechanism.⁴⁹

Fig. 9 Hypervalent iodine-promoted radical addition of aryl α-keto acids to alkenes.

In 2021, the Jin group presented a photocatalyst- and oxidant-free method for synthesizing acylated quinazolinones through visible-light-induced decarboxylative radical acylation/cyclization of unactivated alkenes with α-keto acids (Fig. 10), utilizing a substrate self-sensitized energy transfer process under mild conditions.⁵⁰

Fig. 10 Acylation/cyclization of unactivated alkenes with α-keto acid.

In 2025, Wu and coworkers⁵¹ reported the first chromium(II) decarboxylative alkyl acylation reaction by utilizing the stability of metal−ligand coordination and the instability of the metal-to-ligand charge transfer (MLCT) excited state to dissociate the ligand (Fig. 11). Chromium(II) chloride (CrCl₂) serves as the sole chromium source in this reaction. In situ coordination with α-keto acids generates a low-valent Cr(II)–ligand complex that undergoes MLCT excitation, providing both the acyl radical (via ligand decarboxylation) and the oxidized Cr(III) center required for subsequent SET/HAT activation of alkanes or Hantzsch esters.

Fig. 11 Chromium-catalyzed decarboxylative alkyl acylation.

2.2 Transition-metal-catalyzed coupling reactions with electrophiles

In 2015, MacMillan and co-workers⁵² reported the pioneering work on photoredox/nickel dual-catalyzed decarboxylative coupling of keto acids with aryl halides (iodides/bromides) to afford ketones. Notably, this dual catalytic system demonstrated remarkable efficiency for both aromatic and aliphatic keto acids, producing the corresponding ketone products in good to excellent yields. The mild reaction conditions allowed for a broad substrate scope, significantly expanding the applications of visible-light photocatalysis combined with transition-metal catalysis in organic synthesis. Mechanistic studies revealed that the nickel (0) species, generated via reduction of nickel(I) by the excited photocatalyst, undergoes oxidative addition with the aryl halide. Subsequent capture of the acyl radical (formed through single-electron oxidation and decarboxylation of the keto acid) followed by reductive elimination delivers the final ketone product (Fig. 12). And acyl radicals can also be generated from α-keto acids using inexpensive and commercially available 2-chloro-thioxanthen-9-one as the photoredox catalyst.⁵³

Fig. 12 Photoinduced nickel-catalyzed coupling of keto acids with aryl halides.

In the same year, the Fu and Shang group⁵⁴ disclosed a related photoredox/palladium-catalyzed decarboxylative arylation of keto acids with aryl halides to generate aromatic ketones and amides at room temperature. The reaction delivered moderate to good yields for ketone acids bearing electron-donating groups, while the yields dropped significantly in the presence of electron-withdrawing groups. The reaction mechanism was similar to that proposed by the MacMillan group, with the key step being the palladium valence change mediating the oxidative addition and reductive elimination processes (Fig. 13).

Fig. 13 Photoinduced palladium-catalyzed coupling of keto acids with aryl halides.

Parallel to these developments, directing group-assisted C–H functionalization emerged as an alternative strategy. The Wang group⁵⁵ developed a room temperature decarboxylative ortho acylation of acetanilides with α-keto acids via an eosin Y/Pd dual catalytic system. This operationally simple protocol employed molecular oxygen as the terminal oxidant to achieve selective ortho-acylation of acetanilide derivatives with excellent functional group tolerance (Fig. 14a). Subsequently, the same group⁵⁶ extended this methodology by replacing eosin Y with acridinium perchlorate as the photocatalyst, enabling efficient ortho-acylation of azobenzenes to access diverse aryl ketone derivatives (Fig. 14b).

Fig. 14 Visible light-mediated palladium-catalyzed direct C–H acylation.

In 2024, the Cho group⁵⁷ reported a dual photoredox/nickel protocol that converts α-keto acids and 1,1-disubstituted allenes into 1,4-diones in one step (Fig. 15). Acyl radicals generated by photocatalysis sequentially add to Ni(I) and migrate into the allene, followed by a second acyl capture and reductive elimination through a Ni(I)–Ni(III) cycle. The reaction tolerates diverse aryl and functionalized keto acids, operates under visible light at room temperature, and is scalable.

Fig. 15 Radical diacylation of allenes with ketoacids.

3. Acyl radicals generated via carboxylic acids

Carboxylic acids have also been widely used as versatile acyl sources, primarily through three distinct pathways: (1) direct decarboxylation of carboxylic acids to generate radicals, which are subsequently captured by carbon monoxide to form acyl radicals; (2) activation of carboxylic acids to form reactive intermediates that undergo single-electron reduction or bond cleavage to generate acyl radicals; and (3) generation of acyl anion radicals through photocatalysis in combination with N-heterocyclic carbene (NHC) catalysis. The third category has already been extensively reviewed in many excellent articles,^58–69 and will not be elaborated here (Fig. 16).

Fig. 16 Oxidative generation of radicals from carboxylic acids.

3.1 Direct decarboxylation of carboxylic acids

In 2015, the Lu and Xiao research group⁷⁰ reported photocatalytic decarboxylative alkynylations of carboxylic acids with alkynyl hypervalent iodine reagents under a carbon monoxide atmosphere. The transformation proceeds through single-electron oxidation of carboxylic acid by the excited state of the photocatalyst to generate an alkyl radical, which is subsequently trapped by CO to form an acyl radical. This newly generated radical then undergoes addition to the alkynyl hypervalent iodine species, followed by cleavage of the I–O bond to afford the corresponding ynones as products. Notably, both cyclic and acyclic aliphatic carboxylic acids demonstrated excellent reactivity in this process (Fig. 17).

Fig. 17 Decarboxylative carbonylative alkynylation reaction.

3.2 Activation of carboxylic acids to form acyl radicals

In 2015, Wallentin and co-workers⁷¹ reported the first redox-neutral approach for the mild visible-light-mediated tandem acylarylation of olefins by employing the activating agent dimethyl dicarbonate (DMDC) to generate an anhydride in situ from a carboxylic acid. The anhydride was reduced and decarboxylated by the photocatalyst to produce the corresponding acyl radical, which subsequently undergoes selective radical addition to olefin followed by ring-closing oxidation to yield the desired product. In 2017, the same group⁷² reported a three-component reaction that exploited two electronically distinct radical acceptors to achieve precise control over the reaction sequence, thereby accomplishing intermolecular 1,2-acylalkylation of alkenes (Fig. 18).

Fig. 18 Generation of acyl radicals using DMDC as an activator.

Building on the idea of using in situ generated anhydrides as precursors for acyl radicals, the Zhu group^73–75 reported three examples of this type of reaction in 2017. These included: (1) the generation of acyl radicals employing tris(trimethylsilyl)silane (TMS₃Si-H) as a hydrogen atom source, followed by addition to olefins and reduction to yield the corresponding ketones; (2) using the same system to reduce the generated acyl radicals to aldehydes; and (3) transferring the acyl addition reaction intramolecularly to produce a series of fluorenone derivatives.

In 2018, the Zhu and Xie group⁷⁶ pioneered the integration of phosphorus radical chemistry with photocatalysis. The excited photocatalyst is able to undergo single-electron transfer (SET) oxidation with Ph₃P to form the triphenylphosphine radical cation, which could trigger the proposed radical deoxygenation. The resulting radical cation reacts with the carboxylate anion to generate a phosphoryl radical, which undergoes β-selective C(acyl)–O bond cleavage to generate the corresponding acyl radical. The acyl radicals generated in this way then engage in hydroacylation reactions with alkenes or imines present in the system, yielding a diverse array of hydroacylated products under mild reaction conditions with a broad substrate scope (Fig. 19).

Fig. 19 Generation of acyl radicals using PPh₃ as an activator.

This innovative methodology has since been widely adopted by the scientific community,^77–83 demonstrating broad utility in both intermolecular transformations and intramolecular cyclizations. The operational simplicity and mild conditions of this system have enabled the late-stage functionalization of numerous biologically active molecules.

Building upon this foundation, in 2020, the same group⁸⁴ introduced nickel catalysis into the system, achieving a cross-electrophile coupling between aromatic carboxylic acids and organic bromides, enabled by a photoredox/nickel and phosphoranyl radical synergistic combination, enabling electrophilic cross-coupling between aromatic acids and aryl/alkyl bromides (Fig. 20a). This advancement provided direct access to a wide array of structurally diverse ketones with excellent functional group compatibility from readily available starting materials. In 2021, a photoredox/nickel dual catalytic system was also developed by the same group to achieve hydroacylation of ethylene with aromatic carboxylic acids under mild conditions (Fig. 20b), overcoming radical polarity-mismatch challenges through nickel-mediated radical trapping to afford valuable ketones in up to 92% yield.⁸⁵

Fig. 20 Photoredox/nickel-catalyzed reaction between an acid and aryl bromides or ethylene.

In 2022, the Chu and Sun group⁸⁶ developed a visible-light-induced photocatalytic strategy for the synthesis of flavonoids through the deoxygenative/cyclization reaction of salicylic acid derivatives with aryl acetylene using diphenyl sulfide as an O-transfer reagent (Fig. 21). Mechanistically, photo-excited Mes-Acr-Me⁺* oxidizes Ph₂S to the sulfide radical cation, which activates the carboxylate via S–O interaction and induces β-selective C–O cleavage to generate an acyl radical. This radical adds to the aryl alkyne to give a vinyl radical that undergoes 6-endo cyclization onto the phenol oxygen, followed by deprotonation to deliver the flavonoid.

Fig. 21 Deoxygenation/cyclization of salicylic acid derivatives and aryl acetylene.

4. Acyl radicals generated via derivatives of carboxylic acids

In addition to the aforementioned carboxylic acid precursors, various carboxylic acid derivatives have also been established as effective precursors for acyl radical generation, including anhydrides, acyl halides, thioesters, and amide derivatives, among others. Some elegant reports on transition-metal-catalyzed oxidative addition of carboxylic acid to achieve enantioselective C(sp³)–H acylation, wherein a C–H bond is converted into a C–C bond, have not been included in this review (Fig. 22).^87–89

Fig. 22 Enantioselective C(sp³)–H acylation.

4.1 Acyl radical generation from anhydrides

In addition to the in situ formation of anhydrides from carboxylic acids in the presence of DMDC, the direct use of anhydrides is also a method for generating acyl radicals. In 2016, the Wallentin group⁹⁰ reported the use of easily available symmetric aromatic carboxylic anhydrides as a direct acyl source for the tandem radical acylarylation and tandem acylation/semipinacol rearrangement of olefins under photocatalytic conditions (Fig. 23a). Their study revealed that while electron-deficient aromatic anhydrides reacted efficiently under the standard conditions, Lewis acid activation became necessary when employing electron-rich aromatic or heteroaromatic carboxylic anhydrides to achieve productive transformations. Similar to the reaction system proposed by the Wallentin group, the Ye group⁹¹ reported in 2017 the use of aromatic symmetric carboxylic anhydrides or mixed anhydrides (generated in situ) as precursors for acyl radicals to construct 1,4-dicarbonyl compounds via acyl Michael addition. Anhydrides bearing electron-withdrawing or moderately electron-donating groups can both react in this system (Fig. 23b). This advancement addressed a key limitation of the earlier methodology by expanding the range of viable anhydride substrates without requiring additional Lewis acid activation for electron-rich systems.

Fig. 23 Acyl radical formation from carboxylic anhydride precursors.

4.2 Acyl radical generation from acyl halides

Acyl chlorides are versatile intermediates that are widely employed as electrophilic acylating reagents in organic synthesis. However, traditional acylation reactions using these compounds typically require harsh reaction conditions and exhibit significant sensitivity to the electronic properties of substrate functional groups, resulting in a limited substrate scope. Conventionally, research on acyl halide reagents have predominantly focused on acyl bromides and chlorides, with relatively less attention to acyl fluorides.

The photoredox generation of acyl radicals from acyl halides mainly occurs through three mechanisms: first, direct single-electron reduction of acyl halides to yield the corresponding acyl radicals; second, photochemical/N-heterocyclic carbene (NHC) co-catalysis to produce acyl anion radicals for subsequent acylation reactions (not elaborated here); and third, transition metal-mediated oxidative addition/reductive elimination processes; however, for acyl chlorides, this process does not involve electron transfer and is not within the scope of the current discussion.

The van der Kerk group⁹² reported an early example of the formation of an acyl radical intermediate from acyl chloride in 1957. Under their reaction conditions, triphenyltin chloride and benzaldehyde were generated. In 1960, the Kuivila group⁹³ systematically studied the reaction between triphenyltin hydride and benzoyl chloride, and in 1966,⁹⁴ they further demonstrated that the system involved the generation of acyl radicals. In 1981, the Kagan group⁹⁵ reported the formation of acyl radicals from acyl chloride through single-electron transfer with SmI₂, which were subsequently reduced to acyl anions.

It was not until 2017 that photoredox catalysis was employed for the single-electron reduction of acyl chloride to generate acyl radicals. The Xu group⁹⁶ reported the first synthetic method for converting benzoyl chloride into a benzoyl radical, which then reacted with 1,7-enynes to form diverse fused pyran derivatives with a broad substrate scope in high yields (Fig. 24). The reaction mechanism primarily involves single-electron reduction of the acyl chloride by the excited-state photocatalyst to generate the acyl radical. The nucleophilic acyl radical starts the radical cyclization process by attacking the carbon−carbon double bond of 1,7-enyne; the vinyl radical intermediate that is formed by an intramolecular radical addition is oxidized by the photocatalyst to form a vinyl cation. The vinyl cation is attacked by the carbonyl oxygen of the acyl group to form an oxonium cation. Deprotonation of this ion yields the desired product.

Fig. 24 Synthesis of fused pyran derivatives via acyl chlorides.

In the same year, the same group⁹⁷ reported that acyl radical intermediates could also undergo intermolecular cyclization and oxidation to produce quaternary 3,3-dialkyl 2-oxindole derivatives through a similar mechanism, which expands the current substrate scope in this field (Fig. 25). Upon switching the radical acceptor to 2-aryl indoles,⁹⁸ the acyl-radical engages in a visible-light-promoted cascade cyclization, furnishing indolo[2,1-a]isoquinolin-6-ones in good to excellent yields. Acylation of enol acetates with acyl chlorides can also be achieved.⁹⁹

Fig. 25 Synthesis of 3,3-dialkyl 2-oxindole derivatives via acyl chlorides.

Acyl radicals generated from acyl chlorides can also directly undergo addition reactions with alkynes. In 2017, the Tang group¹⁰⁰ synthesized a series of 3-acylspiro[4,5]trienones through a site-selective carbonylation reaction of N-(p-methoxyaryl)propiolamides with acyl chloride. The p-methoxy group on the aromatic ring was crucial for product formation, with benzoyl chlorides bearing alkyl, methoxy, and halogen substituents as well as thiophene acyl chlorides all successfully reacting to afford the corresponding products. The proposed reaction mechanism involves the generation of acyl radicals through photocatalytic single-electron reduction of acyl chlorides, followed by a tandem radical addition, radical cyclization and dearomatization to form a cyclic radical intermediate. This intermediate is then attacked by an H₂O molecule in the presence of 2,6-dimethylaniline to form a radical anion intermediate. After the loss of the methoxy radical, the intermediate is oxidized by the photocatalyst to yield the final product (Fig. 26).

Fig. 26 Synthesis of 3-acylspiro[4,5]trienones via acyl chlorides.

In 2018, the Tang group¹⁰¹ further extended the use of this type of acyl radical precursor to the one-pot construction of diverse 3-acylcoumarins with high efficiency and selectivity. Benzoyl chlorides substituted with methyl, methoxy, and halogen groups, as well as thiophene acyl chloride, were well tolerated. However, benzoyl chlorides substituted with alkyl, vinyl, and electron-withdrawing groups were not compatible with this system (Fig. 27).

Fig. 27 Synthesis of 3-acylcoumarins via acyl chlorides.

In 2018, the Yang and Xiang group¹⁰² developed the conjugate addition between aroyl chloride and various Michael acceptors upon using Hantzsch ester (HEH) as a reductant, achieving the preparation of 1,4-dicarbonyl compounds. They further transformed these 1,4-dicarbonyl compounds into highly substituted pyrroles, demonstrating the synthetic utility of this method (Fig. 28).

Fig. 28 Synthesis of 1,4-dicarbonyl compounds via acyl chlorides.

In 2019, the Liu and Ngai group¹⁰³ developed a photoredox-catalyzed β-selective aroylation of alkenes using aroyl chlorides, where the key additive 2,6-di-tert-butyl-4-methylpyridine (DTBMP) enhanced efficiency via a proton-coupled electron transfer (PCET) mechanism, enabling the late-stage synthesis of α,β-unsaturated ketones with broad functional group tolerance (Fig. 29a). The reaction proceeds through a radical intermediate and a 1,3-chlorine shift, avoiding over-aroylation and isomerization side reactions. In 2023, the Ritter group¹⁰⁴ developed a nickel/photoredox-catalyzed chloroacylation of terminal alkenes with acyl chlorides to synthesize α-branched enones, where chlorine radicals generated in situ from acyl chlorides are regioselectively added to alkenes, followed by nickel-mediated acylation and HCl elimination (Fig. 29b). Although these two transformations do not proceed directly via acyl radicals, the mechanistic insights have inspired subsequent developments in the field.

Fig. 29 Reaction between acyl chloride and olefin.

In 2020, Oh and coworkers¹⁰⁵ reported a Friedel–Crafts-type chloroacylation of alkenes to β-chloroketones under photocatalytic conditions. In this system, the addition of the acyl radical to the double bond of a styrene derivative generates benzyl radical species that could be stabilized by an adjacent phenyl group, which is then oxidized to the benzylic cation species that reacts with the chloride anion released from the reduction of the acyl chloride, yielding the corresponding β-chloroketone compounds. The reaction conditions are mild and compatible with both cyclic and acyclic olefins, as well as aryl and heteroaryl acyl chlorides (Fig. 30). The same mechanism can be applied to other acceptors to afford the corresponding ketone derivatives.^106–108

Fig. 30 Synthesis of β-chloroketone compounds via acyl chlorides.

In the same year, the Melchiorre group¹⁰⁹ reported a visible-light mediated, metal-free protocol that uses commercial potassium ethyl xanthate (or a related dithiocarbamate) as a nucleophilic organic catalyst to generate acyl radicals from readily available acyl chlorides (Fig. 31). The xanthate anion attacks the carbonyl electrophile, forming a light-absorbing acyl-xanthate (or carbamoyl-xanthate) intermediate. Blue-LED irradiation cleaves the weak C–S bond of this intermediate, releasing the nucleophilic acyl radical and a sulfur-centered xanthyl radical. The acyl radical adds to an electron-deficient olefin, producing an electrophilic radical that abstracts a hydrogen atom from γ-terpinene, yielding the final product.

Fig. 31 Generation of acyl radicals using a nucleophilic organic catalyst.

In 2022, a metal-free protocol that generates acyl radicals directly from acyl chlorides by visible-light excitation of a transient charge-transfer complex (CTC) formed between the carbonyl and a Lewis base (DIPEA or DABCO) was reported by the Chen and Wang group.¹¹⁰ The resulting acyl radicals engage with isocyanides, methacrylamides, alkenes, alkynes, enynes, and other π-systems to deliver >10 classes of acylated heterocycles in moderate to excellent yields under mild, photocatalyst-free conditions (Fig. 32).

Fig. 32 Metal-free generation of an acyl radical via CTC.

In 2023, the research group of Kang and Qu¹¹¹ reported the use of the organic small-molecule photocatalyst CBZ6 as a redox-neutral photocatalyst for visible light-promoted generation of an acyl radical and the following oxidation of the desired benzyl radical to the benzyl cationic intermediate (Fig. 33). This enables intermolecular alkoxyacylation of olefins, providing a concise and practical method for the synthesis of β-functionalized ketones.

Fig. 33 Synthesis of β-alkoxyketones via acyl chlorides.

In 2024, the Paul and Guin group¹¹² developed a dual nickel/photoredox catalytic system for the anti-Markovnikov chlorocarbonylation of unactivated alkenes, enabling the synthesis of β-keto primary chlorides through a chlorine radical (Cl˙) transfer mechanism (Fig. 34). The protocol features mild conditions, broad substrate scope (tolerating esters, halides, and acid-labile groups), and scalability (demonstrated by 1.5 g-scale synthesis). Although this transformation does not proceed through a single-electron transfer (SET) process involving acyl chlorides, this work complements prior acylation strategies by providing direct access to synthetically valuable β-chloroketones from simple olefins and acyl chlorides.

Fig. 34 Synthesis of β-keto primary chlorides by selective chlorocarbonylation of olefins.

In 2025, the Yu and Duan group¹¹³ reported the synthesis of α,β-unsaturated ketones via visible-light or sunlight-induced excited-state copper-catalyzed acylation of olefins with acyl chlorides. This method employs a masking strategy to effectively prevent side reactions, including double acylation, Z/E isomerization, and [2 + 2] cycloaddition. The proposed reaction mechanism is as follows: under light irradiation, Cu(I) is excited to form an excited-state copper complex, which then reduces the acyl chloride, generating Cu(II) and an acyl radical. The acyl radical subsequently adds to the olefin, followed by halide transfer to form a β-chloroketone intermediate. This intermediate undergoes HCl elimination in the presence of DBU to yield the desired product (Fig. 35). The identical mechanism is equally operative when α-CF₃ alkenes are employed as substrates, delivering the corresponding β-CF₃-enones in good to excellent yields.¹¹⁴

Fig. 35 Synthesis of α,β-unsaturated ketones via acyl chlorides.

In 2023, the Wang and Chen group¹¹⁵ reported a photoinduced N-heterocyclic nitrenium (NHN)-catalyzed single-electron reduction of acyl fluorides to generate acyl radicals for the synthesis of carbonyl phenanthridines (Fig. 36). This method uses NHN iodide salt as a photoredox catalyst, Et₃N as a base, and blue light irradiation to convert stable acyl fluorides into acyl radicals, which then react with 2-isocyanobiaryls via a cascade cyclization to afford phenanthridine derivatives. The key step is the NHN radical donating an electron to the acyl fluoride, cleaving the C–F bond to release F⁻ and generate an acyl radical.

Fig. 36 Reductive cyclization of acyl fluorides to phenanthridines.

In 2025, the Miura group¹¹⁶ reported a photoinduced nickel-catalyzed 1,2-acylcyanation of styrenes using acyl fluorides and TMSCN (Fig. 37). The reaction proceeds via ligand-to-metal charge transfer (LMCT) in a nickel(II) acyl fluoride complex, generated in situ from Ni(cod)₂ and Tol-BINAP, where photoexcitation of the Ni(II)–acyl bond leads to homolytic cleavage, releasing an acyl radical. This radical adds regioselectively to the styrene double bond, forming a benzylic radical, which is then trapped by a nickel(I) cyanide complex to afford the 1,2-acylcyanation product after reductive elimination, regenerating the Ni(0) catalyst. The method tolerates diverse acyl fluorides and styrenes, including late-stage functionalization of natural products, and avoids decarbonylation or β-hydride elimination side reactions.

Fig. 37 1,2-Acylcyanation of styrenes via acyl radicals from acyl fluorides.

4.3 Acyl radical generation from thioesters

In 2017, the Gryko group¹¹⁷ reported a vitamin B₁₂-mediated reaction that enabled the generation of acyl radicals from stable and readily available 2-S-pyridyl thioesters. Mechanistic studies suggested that the acyl radical likely originated from the homolytic cleavage of the carbon–cobalt bond under visible light. The acyl radicals then undergo Giese-type acylation with activated olefins, and the resulting radical intermediate was reduced by zinc and protonated by ammonium chloride to yield the final ketone product. Mechanistic experiments also indicated that NH₄Cl serves as the proton source, as evidenced by the generation of deuterated products when ND₄Cl was used in place of NH₄Cl (Fig. 38).

Fig. 38 Vitamin B₁₂-catalysed generation of acyl radicals from 2-S-pyridyl thioesters.

In 2020, the same group¹¹⁸ reported that heptamethyl cobyrinate (a vitamin B12 derivative) enables consecutive generation of both alkyl and acyl radicals from a single 2-S-pyridyl thioester reagent. The mechanism is similar to that reported in a previous work.

In 2018, the McErlean group¹¹⁹ utilized thioesters as precursors for acyl radicals and conducted intramolecular or intermolecular hydroacylation of olefins under photocatalytic conditions by controlling the reaction conditions. When 10 equivalents of tributylamine and formic acid were used, the acyl radical undergoes intramolecular addition to the olefin, generating the corresponding chromenone and indanone derivatives. In contrast, when 2 equivalents of tributylamine and an olefin (such as cyclohexene or allyltrimethylsilane) were used without formic acid, intermolecular hydroacylation occurs, yielding the corresponding products (Fig. 39).

Fig. 39 Indirect acyl radical generation from thioesters.

A unique feature of this reaction is that the acyl radicals are generated from aryl and alkyl thioesters in an indirect fashion under photoredox conditions.¹²⁰ The mechanism involves the single-electron oxidation of tributylamine by the excited-state photocatalyst to form the tributylammonium radical cation. Subsequently, the iodobenzene moiety of the thioester is reduced by the photocatalyst to generate a phenyl radical, which attacks the sulfur of the thioester to form dihydrobenzothiophene and an acyl radical. The acyl radical is then captured by the olefin to form an alkyl radical intermediate, which abstracts a hydrogen atom from the tributylammonium radical cation to yield the desired product, thus completing the catalytic cycle (Fig. 40).

Fig. 40 The mechanism of indirect acyl radical generation from thioesters.

In 2023, Shi and coworkers¹²¹ reported that bench-stable S-trifluoromethyl thioesters serve as bifunctional reagents for the simultaneous installation of acyl and –SCF₃ groups onto unsaturated systems (Fig. 41). Under photoredox/copper dual catalysis, alkenes undergo 1,2-acyl-trifluoromethylthiolation to give β-trifluoromethylthiolated ketones; 1,3-enynes engage in 1,4-addition to deliver δ-trifluoromethylthiolated β-allenyl ketones. The protocol tolerates diverse functional groups and has been extended to late-stage modification of complex molecules and to alternative fluoroalkyl/aryl radical precursors. Base-assisted addition–elimination of the S-trifluoromethyl thioester generates the SCF₃⁻ anion and a bisacyl-carbonate; the excited photocatalyst oxidizes the latter to release an acyl radical. The radical adds to the unsaturated substrate, and the ensuing carbon-centered radical is captured by a CF₃SCu(II) species formed from SCF₃⁻/Cu(I). Reductive elimination from the resulting Cu(III) intermediate furnishes the product and closes both photoredox and copper cycles.

Fig. 41 Trifluoromethylthio-acylation of alkenes.

4.4 Acyl radical generation from N-acyl derivatives

In 2020, the Hong group¹²² reported the first direct acylation of unactivated aliphatic C(sp³)–H bonds using N-acylsuccinimide as acyl surrogates through a dual catalysis strategy involving metallaphotoredox catalysis (Fig. 42). The key innovation is the synergistic activation of two challenging bonds: the N-acylsuccinimide C–N bond and the unactivated aliphatic C(sp³)–H bond, enabling the synthesis of ketones from simple substrates under mild conditions without external oxidants. The mechanism involves an unusual pathway where C–H activation occurs prior to the oxidative addition of the acyl substrate. Specifically, the Ni^II precatalyst is oxidized to a Ni^III species by photocatalyst, which undergoes hydrogen atom transfer to form a cyclohexyl-bound Ni^III complex. This complex is then reduced to a Ni^I species, followed by oxidative addition to form a Ni^III complex, which undergoes reductive elimination to yield the final ketone product. This sequence avoids the formation of an unstable acylnickel(II) species, explaining the superior reactivity of N-acylsuccinimides compared to more reactive acyl donors like acyl chlorides.

Fig. 42 Synthesis of ketones via N-acylsuccinimide.

In 2021, the Opatz group¹²³ reported a dual catalysis strategy for ketone synthesis from carboxylic acid derivatives using visible-light photoredox and nickel catalysis (Fig. 43). The method employs Hantzsch ester (HE) as a cheap, green, and potent photoreductant that facilitates radical generation and participates in the nickel catalytic cycle to regenerate the active species. This dual role of HE enables the coupling of a wide variety of radicals with acyl moieties. Mechanistic studies revealed that Ni(II) is first reduced by HE to form the active Ni(0) species, which undergoes oxidative addition with N-acylsaccharin to form an intermediate. This intermediate captures a radical generated through an electron donor–acceptor (EDA) complex between HE and the redox-active ester (RAE), leading to the formation of a highly reactive Ni(III) species that undergoes reductive elimination to yield the ketone product. The Ni(I) species is then reduced back to Ni(0) by photoexcited HE, completing the catalytic cycle.

Fig. 43 Synthesis of ketones via N-acylsaccharin.

4.5 Acyl radical generation from ester derivatives

In 2024, the Liu group¹²⁴ reported a mild photochemical protocol using inexpensive triazine esters as bench-stable acyl radical precursors (Fig. 44). Under blue-light irradiation with Ir(ppy)₃ as a reductive photocatalyst, the esters deliver aryl acyl radicals that participate in Giese-type addition with N-arylmethacrylamides, followed by intramolecular cyclization, furnishing hydroxyl-functionalized oxindoles.

Fig. 44 Synthesis of ketones via triazine esters.

5. Conclusion and outlook

As complements to traditional two-electron reaction modes, single-electron reaction pathways have revitalized the synthesis of ketones. This review has focused on the photocatalytic generation of ketones from carboxylic acids and their derivatives, categorizing these processes based on the precursors of the acyl radicals. This approach not only offers distinct advantages such as mild reaction conditions, step economy, and broad functional group tolerance but also significantly expands the scope of substrates and functional group compatibility compared with two-electron reaction systems.

Despite these achievements, challenges remain in improving the substrate scope (particularly for aliphatic acids), enhancing selectivity in intermolecular couplings, and reducing reliance on stoichiometric additives. Future efforts should focus on developing more sustainable catalytic systems (e.g., Earth-abundant metals like Cu or Fe, economical and low-cost organic photocatalysts or metal-free catalysis), integrating emerging techniques like flow photochemistry, and expanding applications to complex molecular architectures. By addressing these challenges, photocatalytic ketone synthesis will continue to evolve as a robust platform for streamlined and environmentally friendly carbonylative transformations.

Conflicts of interest

There are no conflicts to declare.

Data availability

No primary research results and no new data were generated or analysed as part of this review.

Acknowledgements

We are grateful for financial support from the project ZR2023QB036 supported by the Natural Science Foundation of Shandong Province and the project QIT24TP019 supported by the Research Program of Qilu Institute of Technology.

References

1. J.-C. Wang, S.-S. Ng and M. J. Krische, Catalytic Diastereoselective Synthesis of Diquinanes from Acyclic Precursors, J. Am. Chem. Soc., 2003, 125, 3682–3683.
2. R. Tomita, Y. Yasu, T. Koike and M. Akita, Combining Photoredox-Catalyzed Trifluoromethylation and Oxidation with DMSO: Facile Synthesis of α-Trifluoromethylated Ketones from Aromatic Alkenes, Angew. Chem., Int. Ed., 2014, 53, 7144–7148.
3. D. C. Fabry, J. Zoller, S. Raja and M. Rueping, Combining Rhodium and Photoredox Catalysis for C-H Functionalizations of Arenes: Oxidative Heck Reactions with Visible Light, Angew. Chem., Int. Ed., 2014, 53, 10228–10231.
4. A. Noble, S. J. McCarver and D. W. C. MacMillan, Merging Photoredox and Nickel Catalysis: Decarboxylative Cross-Coupling of Carboxylic Acids with Vinyl Halides, J. Am. Chem. Soc., 2015, 137, 624–627.
5. J. Otera, Modern Carbonyl Chemistry, Wiley-VCH, 2000.
6. L. Wu, Z. Wang, Y. Qiao, L. Xie and Q. Wang, Photoexcited nitroarenes for alkylation of quinoxalin-2(1H)-ones, Chem. Commun., 2024, 60, 11311–11314.
7. B. Gabriele, R. Mancuso and G. Salerno, Oxidative carbonylation as a powerful tool for the direct synthesis of carbonylated heterocycles, Eur. J. Org. Chem., 2012, 6825–6839.
8. X.-F. Wu, H. Neumann and M. Beller, Palladium-catalyzed oxidative carbonylation reactions, ChemSusChem, 2013, 6, 229–241.
9. R. K. Dieter, Reaction of acyl chlorides with organometallic reagents: A banquet table of metals for ketone synthesis, Tetrahedron, 1999, 55, 4177–4236.
10. M. Rueping and B. J. Nachtsheim, A Review of new developments in the Friedel–Crafts alkylation−from green chemistry to asymmetric catalysis, Beilstein J. Org. Chem., 2010, 6, 6–29.
11. G. Sartori and R. Maggi, Use of solid catalysts in Friedel–Crafts acylation reactions, Chem. Rev., 2006, 106, 1077–1104.
12. M. M. Heravi, V. Zadsirjan, P. Saedi and T. Momeni, Applications of Friedel–Crafts reactions in total synthesis of natural products, RSC Adv., 2018, 8, 40061–40163.
13. J. A. Milligan, J. P. Phelan, S. O. Badir and G. A. Molander, Alkyl carbon−carbon bond formation by nickel/photoredox cross-coupling, Angew. Chem., Int. Ed., 2019, 58, 6152–6163.
14. C. Joe and A. Doyle, Direct acylation of C(sp³)-H bonds enabled by nickel and photoredox catalysis, Angew. Chem., Int. Ed., 2016, 55, 4040–4043.
15. C. C. Le and D. W. C. MacMillan, Fragment couplings via CO₂ extrusion recombination: expansion of a classic bond-forming strategy via metallaphotoredox, J. Am. Chem. Soc., 2015, 137, 11938–11941.
16. R. Takise, K. Muto and J. Yamaguchi, Cross−coupling of aromatic esters and amides, Chem. Soc. Rev., 2017, 46, 5864–5888.
17. J. Buchspies and M. Szostak, Recent advances in acyl suzuki cross-coupling, Catalysts, 2019, 9, 53–75.
18. T. Moragas, A. Correa and R. Martin, Metal-catalyzed reductive coupling reactions of organic halides with carbonyl-type compounds, Chem. – Eur. J., 2014, 20, 8242–8258.
19. C. K. Prier, D. A. Rankic and D. W. C. MacMillan, Visible light photoredox catalysis with transition metal complexes: applications in organic synthesis, Chem. Rev., 2013, 113, 5322–5363.
20. A. Banerjee, Z. Lei and M. Y. Ngai, Acyl Radical Chemistry via Visible-Light Photoredox Catalysis, Synthesis, 2019, 303–333.
21. N. Chalotra, S. Sultan and B. A. Shah, Recent Advances in Photoredox Methods for Ketone Synthesis, Asian J. Org. Chem., 2020, 9, 863–881.
22. L.-N. Guo, H. Wang and X.-H. Duan, Recent advances in catalytic decarboxylative acylation reactions via a radical process, Org. Biomol. Chem., 2016, 14, 7380–7391.
23. C. Raviola, S. Protti, D. Ravelli and M. Fagnoni, Photogenerated acyl/alkoxycarbonyl/carbamoyl radicals for sustainable synthesis, Green Chem., 2019, 21, 748–764.
24. M. Roy, B. Sardar, I. Mallick and D. Srimani, Generation of alkyl and acyl radicals by visible-light photoredox catalysis: direct activation of C–O bonds in organic transformations, Beilstein J. Org. Chem., 2024, 20, 1348–1375.
25. Y. Zhang, Y. Zhang, J. Lin, Z. Li and H. Huang, Radical acylation: concepts, synthetic applications and directions, Org. Chem. Front., 2023, 10, 1056–1085.
26. B. Yang and R.-Y. Tang, Direct synthesis of dialkyl ketones from deoxygenative cross-coupling of carboxylic acids and alcohols, Chem. Sci., 2024, 15, 18405–18410.
27. Y.-Z. Liu, Y. Jiang, J.-L. Zhang, Y. Mei, D.-J. Li and F. Pan, Photocatalyzed radical multicomponent alkylacylation of [1.1.1]propellane to synthesize 1,3-disubstituted BCP ketones, Org. Chem. Front., 2023, 10, 4616–4622.
28. J. Xuan, Z. G. Zhang and W.-J. Xiao, Visible-Light-Induced Decarboxylative Functionaliza tion of Carboxylic Acids and Their Derivatives, Angew. Chem., Int. Ed., 2015, 54, 15632–15641.
29. H. Huang, K. Jia and Y. Chen, Radical Decarboxylative Functionalizations Enabled by Dual Photoredox Catalysis, ACS Catal., 2016, 6, 4983–4988.
30. S. B. Beil, T. Q. Chen, N. E. Intermaggio and D. W. C. MacMillan, Carboxylic Acids as Adaptive Functional Groups in Metallaphotoredox Catalysis, Acc. Chem. Res., 2022, 55, 3481–3494.
31. E. Scott, F. Peter and J. Sanders, Biomass in the manufacture of industrial products—the use of proteins and amino acids, Appl. Microbiol. Biotechnol., 2007, 75, 751–762.
32. P. Gallezot, Conversion of biomass to selected chemical products, Chem. Soc. Rev., 2012, 41, 1538–1558.
33. G.-Z. Wang, R. Shang, W.-M. Cheng and Y. Fu, Decarboxylative 1,4-addition of α-oxocarboxylic acids with Michael acceptors enabled by photoredox catalysis, Org. Lett., 2015, 17, 4830–4833.
34. M. Zhang, J. Xi, R. Ruzi, N. Li, Z. Wu, W. Li and C. Zhu, Domino-fluorination–protodefluorination enables decarboxylative cross-coupling of α-oxocarboxylic acids with styrene via photoredox catalysis, J. Org. Chem., 2017, 82, 9305–9311.
35. Y. Su, R. Zhang, W. Xue, X. Liu, Y. Zhao, K.-H. Wang, D. Huang, C. Huo and Y. Hu, Visible-light-promoted acyl radical cascade reaction for accessing acylated isoquinoline 1,3(2H,4H)-dione derivatives, Org. Biomol. Chem., 2020, 18, 1940–1948.
36. H.-L. Zhu, F.-L. Zeng, X.-L. Chen, K. Sun, H.-C. Li, X.-Y. Yuan, L.-B. Qu and B. Yu, Acyl Radicals from α-Keto Acids: Metal-Free Visible-Light-Promoted Acylation of Heterocycles, Org. Lett., 2021, 23, 2976–2980.
37. C. Prentice, J. Morrison, E. Zysman-Colman and A. D. Smith, Dual NHC/photoredox catalytic synthesis of 1,4 diketones using an MR-TADF photocatalyst (DiKTa), Chem. Commun., 2022, 58, 13624–13627.
38. F. Gao, Z. Y. Liao, Y. H. Ye, Q. H. Yu, C. Yang, Q.-Y. Luo, F. Du, B. Pan, W.-W. Zhong and W. Liang, Photomediated Hydro(deutero) acylation of Olefins by Decarboxylative Addition of α-Oxocarboxylic Acids, J. Org. Chem., 2024, 89, 2741–2747.
39. C. Jagadeesh, M. Patel, S. Hazra, S. Mondal, A. B. Melkani and J. Saha, Site-Selective Acylation of Vinylcyclopropanes under Visible-Light Photocatalysis, Asian J. Org. Chem., 2025, 14, e202400325.
40. Z. Bai, Y. Sa, X. He, H. Du and D. Kong, Visible-light-mediated decarboxylative allylation of vinylcyclopropanes with α-keto acids toward β,γ-alkenyl ketones, Org. Biomol. Chem., 2025, 23, 5783–5787.
41. S. Nandi, P. Das, S. Das, S. Mondal and R. Jana, Visible-light-mediated β-acylative divergent alkene difunctionalization with Katritzky salt/CO₂, Green Chem., 2023, 25, 3633–3643.
42. J. Cao, Y. Liu, Z. Wang and L. Liu, Cr-mediated photocatalytic decarboxylative coupling of alpha-oxo acids with benzylic pyridinium salts, Org. Chem. Front., 2024, 11, 3242–3249.
43. S. Sultan, M. Rizvi, J. Kumar and B. Shah, Acyl Radicals fromTerminal Alkynes:Photoredox-Catalyzed Acylation of Heteroarenes, Chem. – Eur. J., 2018, 24, 10617–10620.
44. H. Huang, G. Zhang and Y. Chen, Dual Hypervalent Iodine(III) Reagents and photoredox catalysis enable decarboxylative ynonylation under mild conditions, Angew. Chem., Int. Ed., 2015, 54, 7872–7976.
45. T. Hui, H.-J. Li, W.-Q. Ji and L. Wang, Sunlight-driven decarboxylative alkynylation of α-keto acids with bromoacetylenes by hypervalent iodine reagent catalysis: a facile approach to ynones, Angew. Chem., Int. Ed., 2015, 54, 8374–8377.
46. J. Li, Z. Liu, S. Wu and Y. Chen, Acyl Radical Smiles Rearrangement To Construct Hydroxybenzophenones by Photoredox Catalysis, Org. Lett., 2019, 21, 2077–2080.
47. W. Ji, H. Tan, M. Wang, P. Li and L. Wang, Photocatalyst-free hypervalent iodine reagent catalyzed decarboxylative acylarylation of acrylamides with a-oxocarboxylic acids driven by visible-light irradiation, Chem. Commun., 2016, 52, 1462–1465.
48. J.-J. Zhang, Y.-B. Cheng and X.-H. Duan, Metal-free oxidative decarboxylative acylation/ring expansion of vinylcyclobutanols with α-keto acids by visible light photoredox catalysis, Chin. J. Chem., 2017, 35, 311–315.
49. C. S. Nishad, A. Kumar, K. Kaur and B. Banerjee, Visible-Light-Mediated Cascade 1,4-Hydrogen Atom Transfer versus Dearomative Spirocyclization of N-Benzylacrylamides: Divergent Access to Functionalized γ-Ketoamides and 2-Azaspiro[4.5]decanes, J. Org. Chem., 2025, 90, 1411–1425.
50. B. Sun, R. Shi, K. Zhang, X. Tang, X. Shi, J. Xu, J. Yang and C. Jin, Photoinduced homolytic decarboxylative acylation/cyclization of unactivated alkenes with a-keto acid under external oxidant and photocatalyst free conditions: access to quinazolinone derivatives, Chem. Commun., 2021, 57, 6050–6053.
51. Y. Liu, Y.-Y. Cheng, J. X. Yu, C. Wang, H.-L. Hu, G. Liang, F.-X. Li, H.-Y. Hou, X.-N. Guo, C.-H. Tung and L.-Z. Wu, Chromium(II)-Catalyzed Decarboxylative Alkyl Acylation under Visible Light Irradiation, Org. Lett., 2025, 27, 6777–6782.
52. L.-L. Chu, J.-M. Lipshultz and D. W. C. MacMillan, Merging photoredox and nickel catalysis: the direct synthesis of ketones by the decarboxylative arylation of α-oxo acids, Angew. Chem., Int. Ed., 2015, 54, 7929–7933.
53. D.-L. Zhu, Q. Wu, D. J. Young, H. Wang, Z.-G. Ren and H.-X. Li, Acyl Radicals from α-Keto Acids Using a Carbonyl Photocatalyst: Photoredox-Catalyzed Synthesis of Ketones, Org. Lett., 2020, 22, 6832–6837.
54. W.-M. Cheng, R. Shang, H.-Z. Yu and Y. Fu, Room-temperature decarboxylative couplings of α-oxocarboxylates with aryl halides by merging photoredox with palladium catalysis, Chem. – Eur. J., 2015, 21, 13191–13195.
55. C. Zhou, P. Li, X. Zhu and L. Wang, Merging photoredox with palladium catalysis: decarboxylative ortho-acylation of acetanilides with α-oxocarboxylic acids under mild reaction conditions, Org. Lett., 2015, 17, 6198–6201.
56. N. Xu, P. Li, Z. Xie and L. Wang, Merging Visible-light photocatalysis and palladium catalysis for C−H acylation of azo- and azoxybenzenes with α-keto Acids, Chem. – Eur. J., 2016, 22, 2236–2242.
57. S. D. Tambe, H. S. Hwang, E. Park and E. J. Cho, Dual Photoredox and Nickel Catalysis in Regioselective Diacylation: Exploring the Versatility of Nickel Oxidation States in Allene Activation, Org. Lett., 2024, 26, 4147–4151.
58. K. Liu, M. Schwenzer and A. Studer, Radical NHC Catalysis, ACS Catal., 2022, 12, 11984–11999.
59. R. Song, Z. Jin and R. Y. Chi, NHC-catalyzed covalent activation of heteroatoms for enantioselective reactions, Chem. Sci., 2021, 12, 5037–5043.
60. K.-Q. Chen, H. Sheng, Q. Liu, P.-L. Shao and X.-Y. Chen, N-heterocyclic carbene-catalyzed radical reactions, Sci. China: Chem., 2021, 64, 7–16.
61. Q.-Z. Li, R. Zeng, B. Han and J.-L. Li, Single-Electron Transfer Reactions Enabled by N-Heterocyclic Carbene Organocatalysis, Chem. – Eur. J., 2021, 27, 3238–3250.
62. T. Ishii, K. Nagao and H. Ohmiya, Recent advances in N-heterocyclic carbene-based radical catalysis, Chem. Sci., 2020, 11, 5630–5636.
63. L. Dai and S. Ye, Recent advances in N-heterocyclic carbene-catalyzed radical reactions, Chin. Chem. Lett., 2021, 32, 660–667.
64. M. N. Hopkinson and A. Mavroskoufis, Photo-NHC Catalysis: Accessing Ketone Photochemistry with Carboxylic Acid Derivatives, Synlett, 2021, 95–101.
65. A. V. Bay and K. A. Scheidt, Single-electron carbene catalysis in redox processes, Trends Chem., 2022, 4, 277–290.
66. J. Liu, X. Xing, J. Huang, L. Lu and W. Xiao, Light opens a new window for N-heterocyclic carbene catalysis, Chem. Sci., 2020, 11, 10605–10613.
67. X. Wang, S. Wu, R. Yang, H. Song, Y. Liu and Q. Wang, Recent advances in combining photo- and N-heterocyclic carbene catalysis, Chem. Sci., 2023, 14, 13367–13383.
68. H. Cai, X. Yang, S. Ren and Y. R. Chi, Radical Reactions with N-HeterocyclicCarbene (NHC)-Derived Acyl Azoliums for Access to Multifunctionalized Ketones, ACS Catal., 2024, 14, 8270–8293.
69. S. Tian, M. Chen, Y. Tang, K. Cheng, G. C. Tsui and Q. Wang, Acylmonofluoromethylation of alkenes via dual NHC/photoredox catalysis, Org. Chem. Front., 2023, 10, 6124–6130.
70. Q.-Q. Zhou, W. Guo, W. Ding, X. Wu, X. Chen, L.-Q. Lu and W. J. Xiao, Decarboxylative Alkynylation and Carbonylative Alkynylation of carboxylic acids enabled by visible-light photoredox catalysis, Angew. Chem., Int. Ed., 2015, 54, 11196–11199.
71. G. Bergonzini, C. Cassani and C.-J. Wallentin, Acyl radicals from aromatic carboxylic acids by means of visible-light photoredox catalysis, Angew. Chem., Int. Ed., 2015, 54, 14066–14069.
72. F. Pettersson, G. Bergonzini, C. Cassani and C.-J. Wallentin, Redox-neutral dual functionalization of electron-deficient alkenes, Chem. – Eur. J., 2017, 23, 7444–7447.
73. M. Zhang, R. Ruzi, J. Xi, N. Li, Z. Wu, W. Li, S. Yu and C. Zhu, Photoredox-catalyzed hydroacylation of olefins employing carboxylic acids and hydrosilanes, Org. Lett., 2017, 19, 3430–3433.
74. M. Zhang, N. Li, X. Tao, R. Ruzi, S. Yu and C. Zhu, Selective reduction of carboxylic acids to aldehydes with hydrosilane via photoredox catalysis, Chem. Commun., 2017, 53, 10228–10231.
75. R. Ruzi, M. Zhang, K. Ablajan and C. Zhu, Photoredox-catalyzed deoxygenative intramolecular acylation of biarylcarboxylic acids: access to fluorenones, J. Org. Chem., 2017, 82, 12834–12839.
76. M. Zhang, J. Xie and C. Zhu, A general deoxygenation approach for synthesis of ketones from aromatic carboxylic acids and alkenes, Nat. Commun., 2018, 9, 3517–3526.
77. J. A. Rossi-Ashton, A. K. Clarke, W. P. Unsworth and R. J. K. Taylor, Phosphoranyl radical fragmentation reactions driven by photoredox catalysis, ACS Catal., 2020, 10, 7250–7261.
78. L. Zhang, X. Yu, S. Ouyang, C. Zhu, W. Li and J. Xie, Synthesis β-Trifluoromethylated Ketones by Photocatalyzed Deoxygenative Coupling of Aromatic Acids with α-CF₃-Substituted Styrenes, Eur. J. Org. Chem., 2024, e202400392.
79. W.-H. Tang, L.-Y. Wu, Q.-Q. Zhou and J.-P. Wan, Photoredox catalytic phosphine-mediated deoxygenative alkynylation of carboxylic acids with alkynyl sulfones for alkynone synthesis, Org. Chem. Front., 2025, 12, 2340–2345.
80. E. E. Stache, A. B. Ertel, T. Rovis and A. G. Doyle, Generation of Phosphoranyl Radicals via Photoredox Catalysis Enables Voltage−Independent Activation of Strong C−O Bonds, ACS Catal., 2018, 8, 11134–11139.
81. H. Jiang, G. Mao, H. Wu, Q. An, M. Zuo, W. Guo, C. Xu, Z. Sun and W. Chu, Synthesis of dibenzocycloketones by acyl radical cyclization from aromatic carboxylic acids using methylene blue as a photocatalyst, Green Chem., 2019, 21, 5368–5373.
82. L. Zhang, Y. Li, Z. Guo, Y. Li, N. Li, W. Li, C. Zhu and J. Xie, Photoredox deoxygenative allylation of carboxylic acids via selective 1,6−addition of acyl radicals to electron–deficient 1,3−dienes, Chin. J. Catal., 2023, 50, 215–221.
83. L. Zheng, P.-J. Xia, Q.-L. Zhao, Y.-E. Qian, W.-N. Jiang, H.-Y. Xiang and H. Yang, Photocatalytic Hydroacylation of Alkenes by Directly Using Acyl Oximes, J. Org. Chem., 2020, 85, 11989–11996.
84. R. Ruzi, K. Liu, C. Zhu and J. Xie, Upgrading ketone synthesis direct from carboxylic acids and organohalides, Nat. Commun., 2020, 11, 3312–3320.
85. L. Zhang, S. Chen, H. He, W. Li, C. Zhu and J. Xie, Photoredox/nickel-catalyzed hydroacylation of ethylene with aromaticacids, Chem. Commun., 2021, 57, 9064–9067.
86. X. Fan, C. He, M. Ji, X. Sun, H. Luo, C. Li, H. Tong, W. Zhang, Z. Sun and W. Chu, Visible light-induced deoxygenation/cyclization of salicylic acid derivatives and aryl acetylene for the synthesis of flavonoids, Chem. Commun., 2022, 58, 6348–6351.
87. X. Shu, L. Huan, Q. Huang and H. Huo, Direct Enantioselective C(sp3)−H Acylation for the Synthesis of α-Amino Ketones, J. Am. Chem. Soc., 2020, 142, 19058–19064.
88. L. Huan, X. Shu, W. Zu, D. Zhong and H. Huo, Asymmetric benzylic C(sp3)−H acylation via dual nickel and photoredox catalysis, Nat. Commun., 2021, 12, 3536–3543.
89. X. Shu, D. Zhong, Q. Huang, L. Huan and H. Huo, Site- and enantioselective cross-coupling of saturated N-heterocycles with carboxylic acids bycooperativeNi/photoredoxcatalysis, Nat. Commun., 2023, 14, 125–134.
90. G. Bergonzini, C. Cassani, H. Lorimer-Olsson, J. Hçrberg and C.-J. Wallentin, Visible-light-mediated photocatalytic difunctionalization of olefins by radical acylarylation and tandem acylation/semipinacol rearrangement, Chem. – Eur. J., 2016, 22, 3292–3295.
91. S. Dong, G. Wu, X. Yuan, C. Zou and J. Ye, Visible-light photoredox catalyzed hydroacylation of electron-deficient alkenes: carboxylic anhydride as an acyl radical source, Org. Chem. Front., 2017, 4, 2230–2234.
92. G. J. M. van der Kerk and J. G. Noltes, Investigations on organo-tin compounds. VII† the addition of organo-tin hydrides to olefinic double bonds, J. Appl. Chem., 1957, 7, 356–365.
93. H. G. Kuivila, Notes- reduction of phthalyl and succinyl dichlorides with tri-n-butyltin hydride. Cyclization of γ-oxoacyl chlorides, J. Org. Chem., 1960, 25, 284–285.
94. H. G. Kuivila and E. J. Jr Walsh, The reaction of acyl halides with organotin hydrides. The mechanism of aldehyde formation, J. Am. Chem. Soc., 1966, 88, 571–576.
95. P. Girard, R. Couffignal and H. B. Kagan, An easy coupling of acid chlorides into α-diketones promoted by diiodosamarium, Tetrahedron Lett., 1981, 22, 3959–3960.
96. C.-G. Li, G.-Q. Xu and P.-F. Xu, Synthesis of fused pyran derivatives via visible-light-induced cascade cyclization of 1,7-enynes with acyl chlorides, Org. Lett., 2017, 19, 512–515.
97. S.-M. Xu, J.-Q. Chen, D. Liu, Y. Bao, Y.-M. Liang and P.-F. Xu, Aroyl chlorides as novel acyl radical precursors via visible-light photoredox catalysis, Org. Chem. Front., 2017, 4, 1331–1335.
98. Y.-L. Wei, J.-Q. Chen, B. Sun and P.-F. Xu, Synthesis of indolo[2,1-a]isoquinoline derivatives via visible-light-induced radical cascade cyclization reactions, Chem. Commun., 2019, 55, 5922–5925.
99. R. Kumar, Harsha and N. Jain, Photoredox Assisted Net-Neutral Radical-Polar Crossover α Acylation of Enol Acetates with Acyl Chlorides: Access to 1,3 Diketones, Adv. Synth. Catal., 2025, 367, e202500007.
100. Y. Liu, Q.-L. Wang, C.-S. Zhou, B.-Q. Xiong and K.-W. Tang, Visible-light-mediated ipso-carboacylation of alkynes: synthesis of 3-acylspiro[4,5]trienones from N-(p-Methoxyaryl)propiolamides and acyl chlorides, J. Org. Chem., 2018, 83, 2210–2218.
101. Y. Liu, Q.-L. Wang, C.-S. Zhou, B.-Q. Xiong, P.-L. Zhang, S.-J. Kang, C.-A. Yang and K. W. Tang, Visible-light-mediated cascade difunctionalization/cyclization of alkynoates with acyl chlorides for synthesis of 3-acylcoumarins, Tetrahedron Lett., 2018, 59, 2038–2041.
102. C. M. Wang, D. Song, P. J. Xia, J. Wang, H.-Y. Xiang and H. Yang, Visible-light-promoted synthesis of 1,4-dicarbonyl compounds via conjugate addition of aroyl chlorides, Chem. – Asian J., 2018, 13, 271–274.
103. Z. Lei, A. Banerjee, E. Kusevska, E. Rizzo, P. Liu and M.-Y. Ngai, Selective Aroylation of Activated Alkenes by Photoredox Catalysis, Angew. Chem., Int. Ed., 2019, 58, 7318–7323.
104. J. Kim, S. Müller and T. Ritter, Synthesis of α-Branched Enones via Chloroacylation of Terminal Alkenes, Angew. Chem., Int. Ed., 2023, 62, e202309498.
105. D. V. Patil, H. Y. Kim and K. Oh, Visible light-promoted Friedel–Crafts-type chloroacylation of alkenes to β-chloroketones, Org. Lett., 2020, 22, 3018–3022.
106. Y. Liu, Z. Chen, Q.-L. Wang, P. Chen, J. Xie, B.-Q. Xiong, P.-L. Zhang and K.-W. Tang, Visible Light-Catalyzed Cascade Radical Cyclization of N-Propargylindoles with Acyl Chlorides for the Synthesis of 2-Acyl-9H-pyrrolo[1,2-a]indoles, J. Org. Chem., 2020, 85, 2385–2394.
107. P.-F. Huang, J.-L. Fu, J.-J. Huang, B.-Q. Xiong, K.-W. Tang and Y. Liu, Photoredox radical cyclization reaction of o-vinylaryl isocyanides with acyl chlorides to access 2,4-disubstituted quinolines, Org. Biomol. Chem., 2024, 22, 513–520.
108. W.-H. Rao, Q. Li, Y.-G. Li, L.-L. Jiang, M.-X. Yue, G.-D. Zou and X. Cao, Visible-Light Photoredox-Catalyzed Acyl Lactonization of Alkenes with Acyl Chlorides, Eur. J. Org. Chem., 2023, e202300191.
109. E. D. P. Beato and P. Melchiorre, Photochemical generation of acyl and carbamoyl radicals using a nucleophilic organic catalyst: applications and mechanism thereof, Chem. Sci., 2020, 11, 6312–6324.
110. L. Bao, Z.-X. Wang and X.-Y. Chen, Metal-Free Generation of Acyl Radical via Photoinduced Single Electron Transfer from Lewis Base to Acyl Chloride, Org. Lett., 2022, 24, 8223–8227.
111. F.-T. Cen, Y. Sun, J.-P. Qu and Y.-B. Kang, Photocatalytic Redox-Neutral Alkoxyacylation of Alkenes, Org. Lett., 2023, 25, 8997–9001.
112. B. Khatua, A. Ghosh, A. K. Ray, N. Banerjee, J. Dey, A. Paul and J. Guin, Photocatalytic Synthesis of β-Keto Primary Chlorides by Selective Chlorocarbonylation of Olefins, Angew. Chem., Int. Ed., 2024, 63, e202402849.
113. X. Yang, Y. Xiao, Y. Yin, H. Li, J. Du, X. Li, W. Duan and L. Yu, Visible-light or sunlight photoredox-catalyzed β-selective acylation of alkenes to access α,β-unsaturated ketones, Org. Chem. Front., 2025, 12, 1543–1549.
114. Y. Zhou, Q. Jiang, Y. Cheng, M. Hu, X.-H. Duan and L. Liu, Photoredox-Catalyzed Acylchlorination of α-CF₃ Alkenes with Acyl Chloride and Applicationas Masked Access to β-CF₃-enones, Org. Lett., 2024, 26, 2656–2661.
115. L. Bao, Z.-X. Wang and X.-Y. Chen, Photoinduced N-Heterocyclic Nitrenium-Catalyzed Single Electron Reduction of Acyl Fluorides for Phenanthridine Synthesis, Org. Lett., 2023, 25, 565–568.
116. N. Oku, R. Saeki, Y. Doi, K. Yamazaki and T. Miura, 1,2-Acylcyanation of Styrenes by Photoinduced Nickel Catalysis to Generate Acyl Radicals from Acyl Fluorides, Org. Lett., 2025, 27, 3361–3367.
117. M. Ociepa, O. Baka, J. Narodowiec and D. Gryko, Light-driven Vitamin B₁₂-catalysed generation of acyl radicals from 2-S-pyridyl thioesters, Adv. Synth. Catal., 2017, 359, 3560–3565.
118. A. Potrząsaj, M. Ociepa, O. Baka, G. Spólnik and D. Gryko, Vitamin B12 Enables Consecutive Generation of Acyl and Alkyl Radicals from One Reagent, Eur. J. Org. Chem., 2020, 1567–1571.
119. A. R. Norman, M. N. Yousif and C. McErlean, Photoredox-catalyzed indirect acyl radical generation from thioesters, Org. Chem. Front., 2018, 5, 3267–3298.
120. D. Crich and Q. Yao, Generation of acyl radicals from thiolesters by intramolecular homolytic substitution at sulfur, J. Org. Chem., 1996, 61, 3566–3570.
121. Z. Zhang, Y. Tian, X. Li, Z. Wang, R. Liu, P. Chen, X. Li, J. Dai and D. Shi, S-Trifluoromethyl thioesters as bifunctional reagents for acyl-trifluoromethylthiolation of alkenes and 1,3-enynes via photoredox/copper dual catalysis, Green Chem., 2023, 25, 2723–2729.
122. G. S. Lee, J. Won, S. Choi, M.-H. Baik and S. H. Hong, Synergistic Activation of Amides and Hydrocarbons for Direct C(sp3)–H Acylation Enabled by Metallaphotoredox Catalysis, Angew. Chem., Int. Ed., 2020, 59, 16933–16942.
123. J. Brauer, E. Quraishi, L. M. Kammer and T. Opatz, Nickel-Mediated Photoreductive Cross Coupling of Carboxylic Acid Derivatives for Ketone Synthesis, Chem. – Eur. J., 2021, 27, 18168–18174.
124. T. Wang, Y.-Y. Zong, W.-Z. Feng, L. Z. Wu and Q. Liu, Visible-Light-Mediated Generation of Acyl Radicals from Triazine Esters, J. Org. Chem., 2023, 88, 12698–12708.

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Footnote

† Co-first authors.

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