Recent advances in the intermolecular addition of carbonyloxy radicals to alkenes

Abstract

Oxygen-centered radicals are highly reactive intermediates that serve key roles in radical-mediated organic transformations. Carbonyloxy radicals, a distinct subset of oxygen-centered radicals, not only exhibit the general reactivity patterns of oxygen-centered species, such as hydrogen atom transfer (HAT) and β-scission, but also demonstrate unique behaviors attributed to their electrophilic ester group. In this review, we summarize recent progress in the intermolecular addition of aryl and alkoxy carbonyloxy radicals to alkenes through different precursors of carbonyloxy radicals. These transformations highlight novel esterification reactions, in which generally alcohols react with carboxylic acids, acyl chlorides, or acid anhydrides. We aim to inspire further exploration into the innovative esterification reactions enabled by carbonyloxy radical chemistry.

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Jun Pan

Jun Pan was born in Hefei, China. She studied pharmaceutical engineering at Chuzhou University, where she completed her Bachelor's degree in 2018. Subsequently, she earned her MS degree from the Shanghai Institute of Technology in 2021. Currently, she is pursuing her PhD under the supervision of Prof. Zhiping Li and Prof. Leiyang Lv at Renmin University of China (RUC). Her research focuses on the photocatalytic synthesis of organic peroxides.

Yuting Feng

Yuting Feng was born in Sichuan, China. She studied pharmaceutical engineering at Beijing University of Chemical Technology, where she completed her Bachelor's degree in 2022. Currently, she is pursuing her PhD under the supervision of Prof. Zhiping Li and Prof. Leiyang Lv at Renmin University of China (RUC). Her research focuses on the photocatalytic synthesis of organic peroxides and synthesis of biologically active natural products.

Huijun Qian

Huijun Qian was born in Yangzhou, China. He studied chemical engineering and technology at Changzhou University where completed his Bachelor's degree. Currently, he is pursuing his PhD work under the guidance of Prof. Zhiping Li and Prof. Leiyang Lv at Renmin University of China (RUC). His current work focuses on the activation of inert bonds.

Leiyang Lv

Leiyang Lv received his PhD degree from Renmin University of China (RUC) in 2017 under the guidance of Prof. Zhiping Li. After three years as a postdoctoral fellow with Prof. Chao-Jun Li at McGill University, he joined RUC as Outstanding Young Scholar. His research interests focus on the development of new catalytic systems to construct functional molecules, especially fluorinated ones, as well as sustainable organic synthesis.

Zhiping Li

Zhiping Li started his independent research work at Renmin University of China (RUC) as an associate professor in 2006 and was promoted to full professor in 2009. His research interests include the development of synthetic methodologies, especially focusing on iron-catalyzed oxidative C–H bond transformation, organic peroxides investigation, and synthesis of biologically active natural products.

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1. Introduction

Oxygen-containing compounds including alcohols, ethers, aldehydes, ketones, carboxylic acids, esters, and others are fundamental in chemistry. Their syntheses are thus of great significance in various industries, pharmaceuticals, and biological processes. From the point of view of reaction mechanisms, the introduction of an oxygen-containing group into an organic molecule can be achieved through an ionic reaction or a radical reaction. The former has been broadly used, while the latter is less adopted. The important reason lies in the fact that oxygen-centered radicals are highly reactive intermediates and it is hard to control the selectivity of these radicals. Oxygen-centered radicals play critical roles in various radical-mediated transformations.^1–4 Representative examples include pollutant degradation via the Fenton reaction,^5–8 industrial phenol/acetone production in the cumene process,^9–11 lipid peroxidation^12–14 and antioxidant inhibition,^15,16 and ribonucleotide reduction catalyzed by class I ribonucleotide reductases.¹⁷ From the structural perspective, oxygen-centered radicals can be categorized into singlet oxygen (¹O₂), hydroxy (˙OH), alkoxy (˙OR), peroxy (˙OOR), carbonyloxy (˙OCOR), alkoxy carbonyloxy (˙OCO₂R), phenoxy radical (˙OAr) and nitroxy (˙ONRR′) radicals, etc. (Scheme 1).^18–26 The thermodynamic stability of oxygen-centered radicals can be determined by the bond dissociation energy (BDE) of the O–H bond in the corresponding alcohols.^27–31 Hydroxy and alkoxy radicals (˙OR) exhibit extreme reactivity and fleeting lifetimes in solution-phase reactions. In contrast, phenoxy radicals, such as those derived from antioxidants like α-tocopherol and butylated hydroxytoluene (BHT), demonstrate moderate stability and radical-scavenging and antioxidative activities.³² Nitroxy radicals, exemplified by (2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO), are both kinetically and thermally stable, enabling ambient storage and shipping.^33–35

Scheme 1 Categories of oxygen-centered radicals.

Carbonyloxy radicals, including aryl, alkyl, and alkoxy derivatives, have garnered significant attention due to the unique reactivity imparted by their carbonyl moiety (Scheme 2).³⁶ In 1858, Brodie synthesized the first organic peroxide benzoyl peroxide (BPO), which could undergo homolytic scission to generate benzoyl radicals.³⁷ A significant advance came in 1911 when Wieland demonstrated that thermolysis of bis(triphenylmethyl) peroxide proceeds via alkoxy radical intermediates en route to tetraphenyldiphenoxyethane, offering early mechanistic insights into the reactivity of peroxide-derived radicals.³⁸ Building on these seminal observations, carbonyloxy radicals and alkoxy radicals have evolved into important synthetic intermediates, orchestrating a broad portfolio of C–C and C–heteroatom bond-forming reactions. Their central role is epitomized by the Barton reaction, a paradigmatic 1,5-hydrogen atom transfer reaction that remains a touchstone in modern radical methodology.^39,40 Carbonyloxy radicals can be generated from an array of precursors: oxidation of carboxylic acids, homolysis or single-electron reduction of organic peroxides, hypervalent iodine(III) compounds, N-hydroxyphthalimide (NHPI), and oxime carbonates or esters, as well as reduction of carbonyloxy pyridinium salts, etc.^41,42

Scheme 2 Various precursors for the generation of carbonyloxy radicals discussed in this review.

Beyond the general properties of oxygen-centered radicals, carbonyloxy radicals exhibit distinctive reactivity modes, as summarized in Scheme 3.^43,44 Aliphatic carboxyloxy radicals undergo rapid decarboxylation (k = 10⁹ s⁻¹) to generate alkyl radicals, a transformation that has found widespread application in organic synthesis.^45,46 In contrast, the decarboxylation rates of aryl carboxyloxy radicals (k = 10⁶ s⁻¹) and alkoxy carboxyloxy radicals (k = 10³ s⁻¹) are markedly slower.⁴⁷ This kinetic disparity provides a valuable opportunity to retain the “CO₂” group in synthetic contexts (path a). Nevertheless, the reactivity of aryl carboxyloxy radicals remains constrained by their instability and O-centered electrophilicity. These radicals undergo rapid hydrogen atom transfer (HAT, k = 10⁷ s⁻¹) either from the reaction media to regenerate aryl carboxylic acids or from the substrates to enable aliphatic C–H functionalization (path b).⁴⁸ Consequently, aryl carboxyloxy radicals have traditionally been limited to intramolecular radical additions or annulations (path c).⁴⁹ Recent breakthroughs, however, demonstrate that intermolecular additions of carboxyloxy radicals to unsaturated systems are viable through careful selection of radical precursors and reaction conditions, offering a practical method for constructing new C–O bonds (path d).

Scheme 3 Typical reactivities of carbonyloxy radicals.

The prior reviews have mainly covered the first three pathways.^50–57 This review focuses on recent advances in intermolecular additions of aryl and alkoxy carbonyloxy radicals to alkenes, delivering various multisubstituted ester compounds (path e). The discussion is organized by precursor type, and we hope this overview will guide the development of efficient catalytic systems and valuable transformations of carbonyloxy radical chemistry.

Photocatalytic organic synthesis leverages photoexcited states of organic or transition-metal catalysts to enable precise energy transfer, generating high-energy redox-active intermediates (e.g., radicals or radical ions) that activate inert bonds (e.g., C–H, C–X) under mild reaction conditions, bypassing the need for high temperatures or harsh conditions.^58,59 This protocol not only enables selective bond formation with exceptional regio- and stereo-control but also exhibits broad substrate scope and functional-group tolerance.⁶⁰ Notably, the triplet energies (E_T) and excited-state redox potentials of these photocatalysts are summarized, providing convenience for researchers to study visible-light photocatalysis (Fig. 1).^61–63

Fig. 1 Photocatalysts in this review along with the triplet energies (E_T, kcal mol⁻¹) and excited-state redox potentials (E_1/2(PC*/PC⁻), E_1/2(PC⁺/PC*), V vs. SCE, SCE = saturated calomel electrode).

2. Carboxylic acids as carbonyloxy radical precursors

In 2013, Zhu and coworkers reported a metal-free regioselective dioxygenation of unactivated alkenes by using benzoic acids and tert-butyl hydroperoxide (TBHP) (Scheme 4).⁶⁴ The key innovation is the ⁿBu₄NI/TBHP system, which converts benzoic acids into benzoyloxy radicals under ambient conditions—an activation manifold that previously required either stoichiometric transition metals or harsh conditions. The substrate scope of this protocol was broad, a series of alkenes, including styrenes bearing either electron-donating or -withdrawing substituents, α-methylstyrene, 1,1-diphenylethylene, as well as aromatic carboxylic acids reacted smoothly, furnishing the vicinal acyloxy-hydroxyl products in good yields.

Scheme 4 ⁿBu₄NI-catalyzed regioselective difunctionalization of unactivated alkenes with carboxylic acids.

Mechanistic insight was obtained via several control experiments. Replacing the benzoic acid with 3-chloroperoxybenzoic acid still delivered the dioxygenated product, corroborating the intermediacy of an acyloxy radical. In contrast, the reaction of α-methylstyrene with sodium 4-chlorobenzoate was completely inhibited, ruling out nucleophilic attack by the carboxylate anion. Addition of the radical scavenger BHT (2,6-di-tert-butyl-4-methylphenol) totally suppressed the transformation, confirming a radical pathway. Therefore, the authors propose a catalytic cycle that is initiated by single-electron oxidation of I⁻ with TBHP to generate ^tBuO˙ and ^tBuOO˙ radicals. The latter abstracts a hydrogen atom from the carboxylic acid to give the benzoyloxy radical, which then selectively adds to the terminal of the alkene. The resulting benzylic radical is further oxidized to a carbocation and trapped by water, delivering the dioxygenated product. When handling these reactive intermediates, particularly peroxides, precautions must be taken due to their tendency to decompose explosively upon impact, heat, or irradiation.⁶⁵

3. Aryl diacetyl peroxides as carbonyloxy radical precursors

In 2015, Buchwald and coworkers reported an example of the radical reaction of dibenzoyl peroxide with 4-phenyl-4-pentenoic acid under a Cu(MeCN)₄PF₆ catalytic system, and subsequent intramolecular cyclization afforded two lactone products (Scheme 5).⁶⁶ The diacyloxylation product B (29% yield, 65% ee) arose from the addition of a benzoyloxy radical, generated through Cu(I)-catalyzed single-electron reduction of dibenzoyl peroxide. In comparison, the oxyarylation product C (40% yield, 66% ee) was formed via the phenyl radical addition, derived from spontaneous decarboxylation of the benzoyloxy radical intermediate. The competitive reactivities of these two pathways led to the simultaneous formation of both lactones. Notably, the rapid Cu(I)-mediated reduction of peroxides generated a high concentration of radical species. Manganese, used as a mild reducing agent, played a pivotal role in regenerating the active Cu(I) from the oxidized Cu(II), thereby minimizing the unproductive radical–radical termination events and enhancing the overall reaction efficiency.

Scheme 5 Cu-catalyzed radical diacyloxylation and decarboxylative oxyalkylation.

In 2021, Bao and coworkers reported an unprecedented copper-catalyzed radical enantioselective 1,4-oxycyanation of 1,3-enynes using diacetyl peroxides and trimethylsilyl cyanide (TMSCN) (Scheme 6).⁶⁷ The chiral bisoxazoline (BOX) ligand was identified as the optimal choice for enantioselectivity control, with the reaction proposed to proceed via an outer-sphere radical group transfer pathway. 1,3-Enynes bearing halogen atom, alkyl chain, haloalkyl chain, hydroxyl group, ester or cyclopropyl substituents afforded enantioenriched allenes in moderate yields with enantiomeric ratios (er) of calc. 90 : 10. However, enantioselectivity was absent when the 1,3-enyne lacked an aryl substituent. Additionally, peroxides attached with electron-donating or electron-withdrawing phenyl groups served as effective substrates, enabling the efficient synthesis of chiral allenes.

Scheme 6 Copper-catalyzed asymmetric radical 1,4-difunctionalization of 1,3-enynes.

Mechanistic studies, including carbocation trapping and radical clock experiments (Scheme 7a and b), provided evidence for an allenyl radical pathway over an allenyl cation alternative. The failure of alkyl 1,3-enyne and DFT calculations revealed a π–π interaction between the allenyl radical and the aryl ring of the BOX ligand, governing axial enantioselectivity. Linear correlations between ligand and product enantiomeric excesses (ee) implicated a monomeric copper(II) complex as the active catalyst. Furthermore, quantitative deprotection of the benzoyloxy group in the allenyl alcohol product preserved enantiomeric purity (Scheme 7c). Moreover, enantioenriched allenes could undergo central-to-axial chirality transfer to afford 3,6-dihydro-2H-pyrans bearing a quaternary stereocenter (Scheme 7d).

Scheme 7 Control experiments and synthetic transformations.

In 2021, Bao and coworkers further developed the copper-catalyzed oxycyanation of alkenes by using aryl diacyl peroxides and TMSCN (Scheme 8).⁶⁸ The reaction demonstrated broad substrate scope, accommodating styrene derivatives, 1,1-disubstituted alkenes, acyclic and cyclic 1,2-disubstituted vinylarenes, terminal and internal aliphatic alkenes, and even estrone-derived alkenes, all of which afforded the corresponding oxycyanation products in moderate to good yields. Additionally, a series of aryl diacyl peroxides proved effective in generating the desired oxycyanation products under the optimized conditions.

Scheme 8 Copper-catalyzed oxycyanation of alkenes with BPO and TMSCN.

The authors proposed the following mechanistic pathway (Scheme 9). A Cu(I) species (A) undergoes single-electron transfer (SET) with an aryl diacetyl peroxide to generate a Cu(II) species (B) and a benzoyl radical. The latter is intercepted by an alkene to afford a more stable benzyl radical (C). Concurrently, the Cu(II) species (B) undergoes ligand exchange with TMSCN to form a cyanide-bound Cu(II) species (D). Subsequent cyano transfer from D to the benzyl radical (C) occurs via either a radical-adduct intermediate (E) or through Cu(III) species (F) reductive elimination, thus delivering the oxycyanation product.

Scheme 9 Proposed mechanism of copper-catalyzed oxycyanation of alkenes.

Furthermore, the same group extended their studies to asymmetric oxycyanation (Scheme 10). Using a Cu(OAc)₂ catalyst combined with a chiral bisoxazoline ligand, they achieved high enantioselectivity (up to 91 : 9 er) for aromatic alkenes. However, aliphatic alkenes failed to exhibit enantiomeric excess under the same conditions.

Scheme 10 Copper-catalyzed asymmetric oxycyanation of alkenes.

4. Hypervalent iodine(III) as carbonyloxy radical precursors

Benziodoxole-alkynes (BI-alkynes) have been reported in the literature as the atom-efficient bifunctional reagents in the difunctionalization of alkenes. In 2024, Chen and coworkers reported a photocatalytic oxyalkynylation of unactivated alkenes using hypervalent iodine(III) reagents, specifically acetoxylbenziodoxole (BI-OAc) and BI-alkyne. This protocol enables the efficient synthesis of a variety of β-alkynyl alcohols with high anti-Markovnikov regioselectivity under mild conditions (Scheme 11).⁶⁹ The scope of this reaction is broad, accommodating various mono-, di-, and tri-substituted alkenes, including unactivated olefins, electron-rich enol ethers, and enamides. Notably, the reaction tolerates diverse functional groups such as hydroxyl, phthalimide, amide, and piperidine. Additionally, late-stage modifications of bioactive molecules, including isopulegol, ibuprofen and Boc-D-PHG-OH derivative, were successfully demonstrated.

Scheme 11 Photocatalytic oxyalkynylation of unactivated alkenes with hypervalent iodine(III) reagents.

Mechanistic studies, including cyclic voltammetry, radical trapping, radical clock, quantum yield, and fluorescence quenching experiments, revealed that BI radicals are generated via energy transfer between BI-OAc and the photocatalyst, and the reaction proceeds via a radical chain mechanism. Key evidence against radical cation intermediates is the regioselective addition of the aryl carboxyl group to β-pinene, and subsequent bridge bond cleavage (Scheme 12a). The transformation was scalable to the gram scale, affording the oxyalkynylation product in 66% yield (1.02 g), followed by the Sonogashira cross-coupling with phenylacetylene to afford the internal alkyne in 56% yield (Scheme 12b). Based on these findings, the authors proposed a plausible reaction mechanism (Scheme 12c). The triplet-excited photocatalyst (Ir^III*) undergoes energy transfer with BI-OAc to generate an acetic acid radical and the BI radical A, which rapidly isomerizes to the carbonyloxy radical B. Radical B then selectively adds to the less substituted terminal of the alkene, forming a more stable carbon-centered radical intermediate C. Subsequent coupling of C with BI-alkyne affords the oxyalkynylated product and generates the BI radical to propagate the catalytic cycle.

Scheme 12 Mechanistic studies and gram-scale synthesis.

5. NHPI esters as carbonyloxy radical precursors

In recent years, photoinduced single-electron reduction of redox-active esters, such as N-hydroxyphthalimide (NHPI) esters, has gained significant attention for generating radicals. The formation of acroyloxy or phthalimidyl radicals is determined by the relative electronegativity of the acroyloxy group and phthalimidyl fragment. Compared to N-centered radicals, O-centered radicals like alkyloxy and acroyloxy radicals are more electrophilic and reactive, which complicates the control of the reaction selectivity.

In 2021, Lu and coworkers reported an enantioselective oxocyanation of alkenes using 2,6-difluorophenyl carboxylic acid-derived NHPI ester (^2FPhCO₂NPhth) as the carbonyloxy radical precursor through the merging of copper and photoredox catalysis (Scheme 13).⁷⁰ The excess copper/ligand ratio (5/1) is crucial for selectively generating acroyloxy radicals. The serine-derived bisoxazoline ligand also significantly enhances reaction efficiency and enantioselectivity. The ester group in the ligand helps stabilize the copper species and increases the rigidity of the transition state. An array of substrates, including electron-rich and electron-deficient styrenes, and heteroaryl derivatives, afforded oxycyanation products with moderate to good yields and high enantioselectivities. Notably, this protocol enabled chemoselective oxycyanation of the aryl alkene moiety in the presence of both aryl and aliphatic alkenes. β-Methyl styrene afforded a single diastereomer with moderate yield and enantioselectivity, while cyclic 1,2-disubstituted alkenes (e.g. indene, 1,2-dihydronaphthalene) provided the desired products but with low enantiocontrol. Vinylbenzenes derived from natural products, such as α-amino acid, camphorsulfonic acid, estrone, and dehydrocholic acid, could undergo this transformation smoothly, highlighting the potential of this protocol for late-stage functionalization.

Scheme 13 Photocatalytic oxocyanation of alkenes with NHPI ester.

The authors conducted several control experiments to elucidate the reaction mechanism. A radical clock experiment using vinylcyclopropane as the substrate produced the 1,5-oxocyanation product in 52% yield with 95% ee, indicating a radical-involved pathway (Scheme 14a). Electron paramagnetic resonance (EPR) spectra, recorded using 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) as a spin trap, detected the formation of a DMPO-spin adduct, confirming the generation of benzoyloxyl radical (Scheme 14b). Additionally, control experiments with mesitylene as a radical acceptor demonstrated that the TMS cation plays a critical role in the formation of the benzoyloxyl radical (Scheme 14c). The proposed mechanism starts with the coordination of the TMS cation to the carbonyl group of the NHPI ester, forming complex A (Scheme 14d). Subsequent SET reduction of complex A generates an aroyloxyl radical, which is trapped by styrene to generate radical intermediate B. The addition of B to the ligand/Cu^II(CN) complex produces the high valent Cu^III species C. Reductive elimination of C delivers the desired oxycyanation product. Notably, the oxygen-centered radical is highly reactive and readily abstracts a hydrogen atom from the reaction system. Therefore, increasing the reaction concentration favors the desired intermolecular radical oxocyanation process.

Scheme 14 Control experiments and proposed mechanism.

6. Oxime esters or carbonates as carbonyloxy radical precursors

6.1 Two-component reactions

In 2021, Glorius and coworkers reported a novel photosensitized oxyimination reaction of unactivated alkenes with bifunctional oxime carbonates (Scheme 15).⁷¹ Thioxanthone functions as a photosensitizer to initiate triplet–triplet energy transfer (EnT), which promotes homolytic cleavage of the N–O bond in oxime carbonates, resulting in the generation of a carbonyloxy radical and an imino radical. The carbonyloxy radical preferentially adds to the terminal position of the alkene, followed by coupling with the long-lived imino radical to afford the 1,2-amino alcohol products in a highly regioselective manner. This transition-metal-free photocatalytic protocol exhibits complementary regioselectivity compared to Sharpless aminohydroxylation. Notably, the method proved compatible with diverse alkenes, including monosubstituted, 1,2-disubstituted, 1,1-disubstituted, trisubstituted, and complex alkenes.

Scheme 15 Photocatalytic oxyimination of unactivated alkenes with oxime carbonates.

The synthetic utility of this protocol was highlighted by its application in the synthesis of naturally occurring leucinol and isoleucinol, which are derived from two different isomers of methyl-1-pentene. This oxyimination reaction was successfully scaled up to 7.0 mmol (1.5 g), and downstream diversifications, including acidic/basic hydrolysis, reduction, and cyclization, have been demonstrated to underscore the method's practicality (Scheme 16). In 2023, Lan and coworkers performed density functional theory (DFT) calculations and revealed that the stronger electrophilicity of alkoxycarbonyloxyl leads to its preferential addition to styrene, and differences in the concentrations of the alkoxycarbonyloxyl radical and iminyl radical determine the chemoselectivity of this cross-coupling reaction.⁷²

Scheme 16 Synthetic utility of the photocatalytic oxyimination.

In 2021, Han and coworkers reported a similar oxyimination reaction of unactivated alkenes using benzophenone-derived oxime carbonates in the presence of the EnT photocatalyst [Ir(dFCF₃ppy)₂(dtbbpy)]PF₆ (Scheme 17a–c).⁷³ Intriguingly, the selective formation of anti-Markovnikov hydro-oxygenation products was observed when 1-phenylethyl-based ketoxime carbonates were tested. Mechanistic studies revealed that the stability of iminyl radicals was the key factor governing the divergent reactivity between hydro- and oxy-imination pathways (Scheme 18). Specifically, the addition of a carbonyloxyl radical to the alkene generates carbon-centered radical C, which subsequently undergoes coupling with the persistent diphenyl iminyl radical A to afford the oxyimination product. It is noteworthy that in the case of 1-phenylethyl-derived ketoxime carbonates, carbon radical C selectively abstracts a hydrogen atom (HAT) from the solvent due to the rapid decomposition of the resultant iminyl radical B.

Scheme 17 Photocatalytic oxyimination reaction of alkenes.

Scheme 18 Visible-light-induced intermolecular oxyimination of alkenes.

Interestingly, Sawamura, Shimizu, and coworkers subsequently reported a visible-light-induced oxyimination of alkenes that obviated the need for exogenous photocatalysts (Scheme 17d).⁷⁴ Central to this transformation was the fluorenone oxime scaffold, which functioned as a photoredox-active sensitizer. Upon blue LED (λ_max = 460 nm) irradiation, fluorenone oxime carbonates underwent photoexcitation to generate both iminyl and alkoxy radicals, which were subsequently intercepted by alkenes to afford the desired oxyimination products. Notably, analogous scaffolds such as benzophenone and anthracenone oximes proved ineffective, underscoring the unique photophysical properties of fluorenone oximes via visible-light catalysis.

In 2023, Zhan and coworkers reported an analogous oxyimination of alkenes using diarylketone-derived oxime carbonates under EnT photocatalyst, namely 2,4,5,6-tetrakis (2,7-dibromo-9H-carbazol-9-yl) isophthalonitrile (2,7-Br-4CzIPN, E_T = 62.1 kcal mol⁻¹) (Scheme 17e).⁷⁵ The reaction accommodates monosubstituted alkenes, as well as sterically demanding di- and tri-substituted styrenes bearing electron-donating or -withdrawing groups, delivering oxyimination products in moderate to good yields. Notably, unactivated alkenes, enamide, and vinyl ether were also engaged efficiently. Besides, this protocol could also be extended to the aminocarboxylation and amidylimination of alkenes.

In 2021, Huo and coworkers reported a visible-light-induced intermolecular vicinal O–N difunctionalization reaction of styrenes using oxime esters as bifunctional reagents under energy-transfer (EnT) catalysis (Scheme 18).⁷⁶ Among the oximes tested, 4,4′-dimethoxybenzophenone oxime ester exhibited optimal performance, delivering the highest yield of the desired product. This protocol demonstrated excellent compatibility with diverse functional groups, including esters, halides, boronic esters, and sulfonamides. Notably, alkyl oxime esters underwent rapid decarboxylation to afford carboimidation products. α-Methyl- and β-methyl-styrenes also participated efficiently, affording the desired products in 73% and 67% yields, respectively. Bioactive substrates such as estrone and ibuprofen derivatives were also applicable in this transformation.

To showcase the synthetic utility of this method, the oxime ester was hydrolyzed under acidic conditions to generate an amino ester derivative, which could be further converted into an anticancer agent via reductive amination. Mechanistic studies revealed that EnT-mediated homolytic cleavage of the N–O bond in oxime ester A generated iminyl radical B and acyloxy radical C. Iminyl radical B is more persistent than acyloxy radical C, thus the regioselective additions of B and C to alkenes afforded the oxyimination products.

In 2023, Xia and coworkers also reported a few examples of similar photocatalytic oxyimination of alkenes using oxime esters as bifunctional reagents under EnT catalysis (Scheme 19).⁷⁷ The transformation was restricted to thiophene, thiazole, and electron-deficient carbonyloxy radicals, likely due to their relatively lower decarboxylation rates under the reaction conditions. The method's mild reaction conditions, operational simplicity, scalability, and efficient flow reaction collectively underscore its significant promise for further application.

Scheme 19 Ultraviolet-mediated oxyimination of alkenes.

In 2023, Huo and coworkers further disclosed a visible-light-mediated protocol for the anti-Markovnikov hydro-oxygenation of unactivated alkenes using oxime esters as carbonyloxy radical precursors (Scheme 20).⁷⁸ This protocol demonstrated broad substrate scope, accommodating a diverse array of linear, cyclic, and sterically demanding tri- or tetra-substituted alkenes with varied chain lengths, ring sizes, and functional groups, to afford the corresponding ester products in moderate to excellent yields. Furthermore, this protocol was successfully applied to the late-stage functionalization of natural products and pharmaceutical agents. The practicability of this transformation was validated by a gram-scale experiment, after which hydrolysis of the ester afforded the anti-Markovnikov alcohol product in 82% yield.

Scheme 20 Visible-light-induced anti-Markovnikov hydroesterification of unactivated alkenes.

6.2 Three-component reactions

On the basis of the well-developed radical-involved 1,2-difunctionalization of a single olefin, in 2022, Glorius and coworkers further reported the radical relay 1,4-oxyimination of two electronically differentiated olefins with oxime carbonates via an EnT strategy (Scheme 21).⁷⁹ The design of this reaction was particularly ingenious as it orchestrated the formation of three distinct chemical bonds (C–O, C–C, and C–N) in a single operation, thereby enabling rapid access to a diverse array of structurally complex 1,4-oxyimination products, which can be readily converted into valuable biologically relevant δ-hydroxyl-α-amino acids. The substrate scope encompassed a wide range of unactivated and electron-rich olefins, including simple ethylene, sterically hindered trisubstituted and tetrasubstituted olefins, and various Michael acceptors, generally delivering moderate to good yields. Notably, the reaction tolerates a variety of functional groups and heterocycles, demonstrating excellent functional-group compatibility. Moreover, the generated diverse 1,4-oxyimination products could also be converted into biologically significant δ-hydroxyl-α-amino acids. Experimental and theoretical studies suggested that the reaction proceeds via a radical chain mechanism, initiated by EnT-mediated homolytic N–O bond cleavage of the oxime carbonate to generate N-centered iminyl and O-centered alkoxycarbonyloxyl radicals. The transient O-centered radical selectively adds to the electron-richer olefin, followed by a nucleophilic addition to a Michael acceptor. Computational studies support the proposed mechanism, revealing the importance of polarity matching and the persistent radical effect in achieving high selectivity.

Scheme 21 Visible-light-induced radical relay 1,4-oxyimination of two electronically differentiated olefins with oxime carbonates.

In 2023, Glorius and coworkers presented the development of a visible-light-catalyzed three-component 1,2,5-trifunctionalization reaction of alkenes, enabling the modular, one-step synthesis of densely functionalized scaffolds (Scheme 22).⁸⁰ The method addressed key limitations of existing radical 1,5-difunctionalizations by employing readily available bifunctional reagents (oxime carbonates, N-sulfonyl ketimines, imines) in combination with two distinct alkenes (allylboronic esters and Michael acceptors or electron-deficient styrenes). The authors simultaneously introduced three different functional groups via the selective one-step installation of four bonds, utilizing a 1,2-boron shift and leveraging radical polarities and stabilities. This approach overcomes the limitations of previous methods by offering backbone modularity during the functionalization reaction and broadening the scope of functional groups that can be introduced at the 2-position, making it particularly suitable for medicinal chemistry applications. The substrate scope of this reaction encompasses a wide range of oxime carbonates, N-sulfonyl ketimines, imines, and alkenes, delivering products in moderate to good yields, often exceeding 70%. Notably, the reaction tolerates various sensitive functional groups and can be performed metal-free, showcasing its versatility, including those bearing halides, esters, silyl groups, and sulfonyl fluorides (enabling downstream SuFEx click chemistry). The proposed mechanism was that homolytic cleavage of the bifunctional reagent generated a persistent iminyl radical and a transient electrophilic radical via energy transfer. Then, an electrophilic radical was added to the allylboronic ester, triggering a key 1,2-boron shift that forms a stabilized tertiary alkyl radical. The nucleophilic radical subsequently adds to the Michael acceptor, and termination occurs via radical recombination with the iminyl radical.

Scheme 22 Visible-light-induced three-component 1,2,5-trifunctionalization reaction of alkenes.

In 2024, Xia and coworkers revealed a novel and selective 1,4-oxyimination methodology across C=C and N=N bonds utilizing photocatalysis to synthesize structurally diverse N–N–N triazane derivatives (Scheme 23, left).⁸¹ This method was characterized by its atom-economical and modular approach, enabling the effective coupling of bifunctional precursors with olefins and diazenes through radical-mediated processes. The researchers employed precise control over the radical properties of these precursors and the electronic characteristics of the substrates to achieve high chemoselectivity. The generality of this 1,4-oxyamination reaction was explored with a wide range of olefins and diazenes under optimized conditions. It was found that both unactivated and electron-rich activated alkenes could participate effectively in the transformation, producing the corresponding oxyimination products. Then, the effectiveness of difunctional reagents was investigated by using 1,1-diethyl ethylene and dibenzyl azodicarboxylate as partners. It was demonstrated that a variety of oxime esters reacted efficiently, resulting in the successful synthesis of the corresponding products with moderate to high yields. Additionally, the scope of diazenes was thoroughly investigated, revealing that various azodicarboxylate esters could be used successfully, leading to products with yields of up to 64%.

Scheme 23 Visible-light-induced 1,4-oxyimination of alkenes across C=C and N=N/C=S bonds.

Mechanistic studies indicated that the process likely proceeded via an excited-state energy-transfer mechanism initiated by photoinduced interaction between the oxime carbonate and 2-iPr-TX, followed by homolytic cleavage of the weak N–O bond to generate oxygen-centered and iminyl radicals. These radicals then undergo sequential addition and cross-coupling reactions to form the final triazane product. Overall, this study presented a versatile tool for constructing complex molecular architectures with potential applications in medicinal chemistry, showcasing remarkable substrate flexibility and functional-group tolerance.

Shortly afterwards, Xia and coworkers developed a novel photocatalytic radical relay strategy for the efficient and regioselective 1,4-difunctionalization of carbon–sulfur (C=S) double bonds in isothiocyanates, marking the first instance of radical-mediated dual-functionalization of X–Y type unsaturated bonds (Scheme 23, right).⁸² This approach enabled the synthesis of complex linear molecules containing C–O, C–N, and C–S bonds in a single operation, surpassing traditional methods that rely on thiourea intermediates or harsh conditions. The reaction employed a three-component system involving an oxygen-centered radical precursor (oxime ester), unactivated alkenes, and isothiocyanates, with a proposed similar triple-step radical relay mechanism. The method demonstrated broad substrate compatibility, including over 60 diverse substrates, such as functionalized alkenes, isothiocyanates with varied substituents (alkyl, halogen, trifluoromethyl), and complex molecules like menthol and cholesterol derivatives, and achieved yields of up to 93%. Mechanistic studies, including radical trapping experiments, HRMS analysis, and control reactions, confirmed the radical relay pathway and highlight the critical role of energy transfer and electronic matching between radicals and receptors. The research not only advances the fields of bifunctionalization and remote difunctionalization but also provides a versatile platform for constructing heteroatom-rich molecules with applications in pharmaceuticals, materials science, and diversity-oriented synthesis. The study underscores the importance of electronic complementarity in controlling selectivity, offering theoretical insights for designing future radical-based reactions.

7. Alkoxycarbonyloxylpyridinium salts as carbonyloxy radical precursors

In 2022, Glorius and coworkers explored a photocatalytic anti-Markovnikov hydro-oxygenation of unactivated alkenes, complementing the established hydroboration/oxidation protocol (Scheme 24).⁸³ The alkoxycarbonyloxylpyridinium salts released a highly reactive alkoxycarbonyloxyl radical upon [Ir–F] catalyst system reduction and 2-phenylmalononitrile served as the most effective reagent for H atom abstraction and radical chain propagation. The substrate scope of this hydro-oxygenation protocol was explored extensively. Both linear and cyclic alkenes with varying chain lengths, ring sizes, and substitution patterns were successfully transformed into the desired products with high yields and selectivities. Notably, valuable terpene structures like camphene and lithocholic acid were also converted into the corresponding carbonate products. The [Ir–F] photocatalysts were activated by blue light, which transferred electrons to pyridinium salts to generate ethoxycarbonyloxyl radicals. Subsequently, this radical selectively added to the terminal carbon of alkenes, which is a thermodynamically favored step as confirmed by DFT forming a β-radical intermediate. Next, the 2-phenylmalononitrile served as the hydrogen atom donor (HAD) to rapidly terminate the intermediate via hydrogen transfer, producing the carbonate product while enabling a radical chain through HAD-derived species, which Stern–Volmer studies verified direct reagent–photocatalyst interactions. The synergy of selective radical addition and efficient HAT-driven termination enabled mild, precise anti-Markovnikov functionalization.

Scheme 24 Visible-light-initiated hydro-oxygenation of unactivated alkenes.

In 2024, Wu and coworkers addressed the visible light-promoted intermolecular oxycarbonylation reaction of unactivated alkenes using oxygen-centered radicals and carbon monoxide, marking a significant advancement in oxygen-centered radical chemistry (Scheme 25).⁸⁴ The pyridinium salt generated alkoxycarbonyloxy radicals for direct addition to unactivated alkenes under mild photoredox conditions, overcoming traditional selectivity challenges associated with highly reactive oxygen radicals. Substrate scope demonstrated broad applicability to mono- and di-substituted alkenes, including styrene derivatives with electron-donating or -withdrawing groups, heterocyclic systems (e.g., pyridine, thiophene), and linear, cyclic and internal alkenes, yielding products in moderate to good efficiency toward aromatic and heteroaromatic substituents. A plausible mechanism involved the reduction of alkoxycarbonyloxypyridinium salts by the excited photocatalyst, leading to the formation of alkoxycarbonyloxy radicals. These radicals add to the alkene, forming a new carbon radical, which subsequently traps carbon monoxide to produce the acyl radical. Intramolecular rearrangement and SET oxidation then yield the final product. This method broadens the scope of intermolecular oxygen functionalization of alkenes and highlights the potential of carbon monoxide in organic synthesis.

Scheme 25 Visible-light-promoted intermolecular oxycarbonylation reaction of unactivated alkenes.

8. Conclusion and perspectives

Oxygen-centered radicals are playing an increasingly important role in the synthesis of oxygen-containing compounds, attracting great attention from synthetic chemists. This review summarized the recent advances in intermolecular addition of aryl and alkoxy carbonyloxy radicals to alkenes, underscoring the strategic innovations that now enable the synthesis of multisubstituted esters. The innate electrophilicity imparted by the adjacent carbonyl group endows carbonyloxy radicals with reactivity paradigms that diverge markedly from those of conventional oxygen-centered radicals. A versatile arsenal of radical precursors—ranging from simple carboxylic acids to bench-stable NHPI esters, hypervalent iodine(III) reagents, aryl diacetyl peroxides, oxime carbonates, and alkoxycarbonyloxylpyridinium salts—has been deployed, each offering distinct properties and advantages in terms of functional-group tolerance, substrate scope, and operational simplicity. The pronounced electrophilic character of the carbonyloxy radicals not only dictates facile addition to p-systems but also underpins the exquisite regio- and stereo-control via the catalytic system design. Looking forward, the synergistic combination of carbonyloxy radical chemistry with photoredox, electrochemical, and biocatalytic strategies is envisioned to broaden the boundaries of the radical field and unlock radical cascades and streamline access to architecturally complex, bioactive scaffolds that remain challenging to construct by traditional methods.

Author contributions

J. P. and Y. F. contributed equally to this paper. All authors contributed to the review and editing of the original manuscript.

Conflicts of interest

There are no conflicts to declare.

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.

Acknowledgements

We gratefully acknowledge the National Natural Science Foundation of China (No. 22571320, 22571319, 22201300), the Beijing Natural Science Foundation (No. 2252010), and the Outstanding Innovative Talents Cultivation Funded Programs 2023 of Renmin University of China.

References

1. L. Chang, Q. An, L. Duan, K. Feng and Z. Zuo, Alkoxy Radicals See the Light: New Paradigms of Photochemical Synthesis, Chem. Rev., 2022, 122, 2429–2486.
2. J. J. Orlando, G. S. Tyndall and T. J. Wallington, The Atmospheric Chemistry of Alkoxy Radicals, Chem. Rev., 2003, 103, 4657–4690.
3. P. J. Ziemann and R. Atkinson, Kinetics, products, and mechanisms of secondary organic aerosol formation, Chem. Soc. Rev., 2012, 41, 6582–6605.
4. Y. Zhu, H. Wang, P. Shu, K. Zhang and Q. Wang, Recent Advances on Alkoxy Radicals-Mediated C(sp³)—H Bond Functionalization via 1,5-Hydrogen Atom Transfer, Chin. J. Org. Chem., 2024, 44, 1–17.
5. Y. Liu and J. Wang, Multivalent metal catalysts in Fenton/Fenton-like oxidation system: A critical review, Chem. Eng. J., 2023, 466, 143147–143169.
6. T. Zhang, B. Huang, H. Huang, A. Yan, S. Lu and X. Qian, Visible light boosted Fenton-like reaction of carbon dot-Fe(III) complex: Kinetics and mechanism insights, Chin. Chem. Lett., 2025, 36, 110885.
7. E. Brillas, I. Sirés and M. A. Oturan, Electro-Fenton Process and Related Electrochemical Technologies Based on Fenton's Reaction Chemistry, Chem. Rev., 2009, 109, 6570–6631.
8. S. You, R. Li, H. Lu, L. Hou, X. Xu and Y. Shang, Modulation of the structures and properties of iron-carbon composites by different small molecular carbon sources for Fenton-like reactions, Chin. Chem. Lett., 2025, 36, 110955.
9. Z. Li, R. Chen, W. Xing, W. Jin and N. Xu, Continuous Acetone Ammoximation over TS-1 in a Tubular Membrane Reactor, Ind. Eng. Chem. Res., 2010, 49, 6309–6316.
10. E. Brillas, I. Sirés and M. A. Oturan, Electro-Fenton Process and Related Electrochemical Technologies Based on Fenton's Reaction Chemistry, Chem. Rev., 2009, 109, 6570–6631.
11. L. Sun, D. Wang, Y. Li, B. Wu, Q. Li, C. Wang, S. Wang and B. Jiang, Fully conversing and highly selective oxidation of benzene to phenol based on MOFs-derived CuO@CN photocatalyst, Chin. Chem. Lett., 2023, 34, 107490.
12. Y. Zheng, J. Sun, Z. Luo, Y. Li and Y. Huang, Emerging mechanisms of lipid peroxidation in regulated cell death and its physiological implications, Cell Death Dis., 2024, 15, 859.
13. K. X. Huang, Y. B. Feng, W. Yao, L. X. Yang, F. Wang, H. B. Li, S. Zeng, J. X. Gong, M. H. Hu, Y. Zhao, X. M. Wu, X. K. Li and J. Qu, Evaluation of lipid peroxidation inhibition and free radical scavenging abilities of 5,6,7-trimethoxy dihydroflavonols, Chin. Chem. Lett., 2009, 20, 1187–1190.
14. Q. Lu, L. Zhang, Z. Chen, J. Lv, J. Gao, X. Li, H. Li, W. Shi, X. Li and H. Ma, A lipid droplet-targeting fluorescence probe for monitoring of lipid peroxidation in ferroptosis and non-alcoholic fatty liver disease, Chin. Chem. Lett., 2025, 36, 110620.
15. M. Canakdag, M. Feizi-Dehnayebi, S. Kundu, D. Sahin, İ. Ö. İlhan, S. K. Alhag, L. A. Al-Shuraym and S. Akkoc, Comprehensive evaluation of purine analogues: Cytotoxic and antioxidant activities, enzyme inhibition, DFT insights, and molecular docking analysis, J. Mol. Struct., 2025, 1323, 140798.
16. M. N. Asghar, Q. Alam and S. Augusten, Fluphenazine hydrochloride radical cation assay: A new, rapid and precise method to determine in vitro total antioxidant capacity of fruit extracts, Chin. Chem. Lett., 2012, 23, 1271–1274.
17. M. Bennati, F. Lendzian, M. Schmittel and H. Zipse, Spectroscopic and theoretical approaches for studying radical reactions in class I ribonucleotide reductase, Biol. Chem., 2005, 386, 1007–1022.
18. C. Banoun, E. Magnier and G. Dagousset, Recent Uses of Photogenerated Oxygen-Centered Radicals in Intermolecular C–O Bond Formation, Synlett, 2024, 268–278.
19. F.-S. He, S. Ye and J. Wu, Recent Advances in Pyridinium Salts as Radical Reservoirs in Organic Synthesis, ACS Catal., 2019, 9, 8943–8960.
20. J. Spanget-Larsen, M. Gil, A. Gorski, D. M. Blake, J. Waluk and J. G. Radziszewski, Vibrations of the Phenoxyl Radical, J. Am. Chem. Soc., 2001, 123, 11253–11261.
21. C. Anastasi, M. G. Sanderson, P. Pagsberg and A. Sillesen, Reaction of atomic oxygen with some simple alkenes. Part 2.—Reaction pathways involving ethene, propene and (E)-but-2-ene at atmospheric pressure, J. Chem. Soc., Faraday Trans., 1994, 90, 3625–3631.
22. N. A. Porter, A Perspective on Free Radical Autoxidation: The Physical Organic Chemistry of Polyunsaturated Fatty Acid and Sterol Peroxidation, J. Org. Chem., 2013, 78, 3511–3524.
23. J.-F. Poon and D. A. Pratt, Recent Insights on Hydrogen Atom Transfer in the Inhibition of Hydrocarbon Autoxidation, Acc. Chem. Res., 2018, 51, 1996–2005.
24. L. M. Smith, H. M. Aitken and M. L. Coote, The Fate of the Peroxyl Radical in Autoxidation: How Does Polymer Degradation Really Occur?, Acc. Chem. Res., 2018, 51, 2006–2013.
25. R. A. Sheldon and I. W. C. E. Arends, Organocatalytic Oxidations Mediated by Nitroxyl Radicals, Adv. Synth. Catal., 2004, 346, 1051–1071.
26. F. Recupero and C. Punta, Free Radical Functionalization of Organic Compounds Catalyzed by N-Hydroxyphthalimide, Chem. Rev., 2007, 107, 3800–3842.
27. B. Wei, D. Xie, S. Lai, Y. Jiang, H. Fu, D. Wei and B. Han, Electrochemically Tuned Oxidative [4 + 2] Annulation and Dioxygenation of Olefins with Hydroxamic Acids, Angew. Chem., Int. Ed., 2021, 60, 3182–3188.
28. L. R. Mahoney, G. D. Mendenhall and K. U. Ingold, Calorimetric and equilibrium studies on some stable nitroxide and iminoxy radicals. Approximate oxygen-hydrogen bond dissociation energies in hydroxylamines and oximes, J. Am. Chem. Soc., 1973, 95, 8610–8614.
29. S. J. Blanksby and G. B. Ellison, Bond Dissociation Energies of Organic Molecules, Acc. Chem. Res., 2003, 36, 255–263.
30. F. G. Bordwell and G. Z. Ji, Effects of structural changes on acidities and homolytic bond dissociation energies of the hydrogen-nitrogen bonds in amidines, carboxamides, and thiocarboxamides, J. Am. Chem. Soc., 1991, 113, 8398–8401.
31. S. Chiba and H. Chen, sp³ C–H oxidation by remote H-radical shift with oxygen- and nitrogen-radicals: a recent update, Org. Biomol. Chem., 2014, 12, 4051–4060.
32. E. Tsui, H. Wang and R. R. Knowles, Catalytic generation of alkoxy radicals from unfunctionalized alcohols, Chem. Sci., 2020, 11, 11124–11141.
33. P. G. Wang, M. Xian, X. Tang, X. Wu, Z. Wen, T. Cai and A. J. Janczuk, Nitric Oxide Donors: Chemical Activities and Biological Applications, Chem. Rev., 2002, 102, 1091–1134.
34. E. R. Lopat'eva, I. B. Krylov, B. Yu and A. O. Terent'ev, N-Oxyl Radicals in Oxidative C=C Bonds, Asian J. Org. Chem., 2025, 14, e202400503.
35. D. Leifert and A. Studer, Organic Synthesis Using Nitroxides, Chem. Rev., 2023, 123, 10302–10380.
36. B. Abel, J. Assmann, M. Buback, C. Grimm, M. Kling, S. Schmatz, J. Schroeder and T. Witte, Ultrafast Decarboxylation of Carbonyloxy Radicals: Influence of Molecular Structure, J. Phys. Chem. A, 2003, 107, 9499–9510.
37. A. Baeyer and V. Villiger, Einwirkungen des Caro'schen Reagents auf Ketone, Ber. Dtsch. Chem. Ges., 1899, 32, 3625–3633.
38. H. Wieland, Über Triphenylmethyl-peroxyd., Ein Beitrag zur Chemie der freien Radikale, Ber. Dtsch. Chem. Ges., 1911, 44, 2550–2556.
39. J.-L. Shi, Z. Wang, Z. He, B. Dou and J. Wang, Visible Light-Promoted Ring-Opening Alkenylation of Cyclic Hemiacetals through β-Scission of Alkoxy Radicals, Chin. J. Chem., 2023, 41, 259–264.
40. M. Dong, X. Lu, S. Yu, Z. Qi, Y. Yuan, Y. Gong, S. Wei, X. Du and D. Yi, Alkoxy Radical-Triggered 1,1,2-Trifunctionalization of Unactivated Alkenes towards N,O-Spiroaminals, Chin. J. Chem., 2025, 43, 1657–1663.
41. A. Yoshimura and V. V. Zhdankin, Advances in Synthetic Applications of Hypervalent Iodine Compounds, Chem. Rev., 2016, 116, 3328–3435.
42. N. Zhu, H. Yao, X. Zhang and H. Bao, Metal-catalyzed asymmetric reactions enabled by organic peroxides, Chem. Soc. Rev., 2024, 53, 2326–2349.
43. X. Q. Hu, Z. K. Liu, Y. X. Hou and Y. Gao, Single Electron Activation of Aryl Carboxylic Acids, iScience, 2020, 23, 101266.
44. H.-M. Huang, P. Bellotti, J. Ma and F. Glorius, Bifunctional reagents in organic synthesis, Nat. Rev. Chem., 2021, 5, 301–321.
45. J. Chateauneuf, J. Lusztyk and K. U. Ingold, Spectroscopic and kinetic characteristics of aroyloxyl radicals. 2. Benzoyloxyl and ring-substituted aroyloxyl radicals, J. Am. Chem. Soc., 1988, 110, 2886–2893.
46. J. Chateauneuf, J. Lusztyk and K. U. Ingold, Spectroscopic and kinetic characteristics of aroyloxyl radicals. 1. The 4-methoxybenzoyloxyl radical, J. Am. Chem. Soc., 1988, 110, 2877–2885.
47. J. W. Hilborn and J. A. Pincock, Rates of decarboxylation of acyloxy radicals formed in the photocleavage of substituted 1-naphthylmethyl alkanoates, J. Am. Chem. Soc., 1991, 113, 2683–2686.
48. S. Kubosaki, H. Takeuchi, Y. Iwata, Y. Tanaka, K. Osaka, M. Yamawaki, T. Morita and Y. Yoshimi, Visible- and UV-Light-Induced Decarboxylative Radical Reactions of Benzoic Acids Using Organic Photoredox Catalysts, J. Org. Chem., 2020, 85, 5362–5369.
49. S. Xia, K. Hu, C. Lei and J. Jin, Intramolecular Aromatic C–H Acyloxylation Enabled by Iron Photocatalysis, Org. Lett., 2020, 22, 1385–1389.
50. F. Strieth-Kalthoff, M. J. James, M. Teders, L. Pitzer and F. Glorius, Energy transfer catalysis mediated by visible light: principles, applications, directions, Chem. Soc. Rev., 2018, 47, 7190–7202.
51. H. Yao, W. Hu and W. Zhang, Difunctionalization of Alkenes and Alkynes via Intermolecular Radical and Nucleophilic Additions, Molecules, 2020, 26, 105–136.
52. B. N. Hemric, Beyond osmium: progress in 1,2-amino oxygenation of alkenes, 1,3-dienes, alkynes, and allenes, Org. Biomol. Chem., 2021, 19, 46–81.
53. Q. Sun, S.-P. Wang, Y. Xu, A. Yin, L. Yang, J. Zhu, C.-L. Zheng, G. Wang, Z. Fang, S. Sui, D. Wang, Y. Dong, D. Zhang and C.-S. Wang, Visible-Light-Induced Energy-Transfer-Mediated Hydrofunctionalization and Difunctionalization of Unsaturated Compounds via Sigma-Bond Homolysis of Energy-Transfer Acceptors, ACS Catal., 2025, 15, 1854–1941.
54. D. S. Lee, V. K. Soni and E. J. Cho, N–O Bond Activation by Energy Transfer Photocatalysis, Acc. Chem. Res., 2022, 55, 2526–2541.
55. M. Bera, D. S. Lee and E. J. Cho, Advances in N-centered intermediates by energy transfer photocatalysis, Trends Chem., 2021, 3, 877–891.
56. X. L. Luo, D. J. Luo, L. L. Qin, Z. P. Ye and P. J. Xia, Recent Advances in Diphenylmethanone Oxime Reagent Chemistry for Unsaturated Bond Bifunctionalization via Energy Transfer Catalysis, Eur. J. Org. Chem., 2025, e202401186.
57. J. Hartung, Stereoselective Construction of the Tetrahydrofuran Nucleus by Alkoxyl Radical Cyclizations, Eur. J. Org. Chem., 2001, 619–632.
58. I. M. McWhinnie, R. T. Martin, J. Xie, R. Chen, C. N. Prieto Kullmer and D. W. C. MacMillan, Radical Sorting Catalysis via Bimolecular Homolytic Substitution (SH2): Opportunities for C(sp³)–C(sp³) Cross-Coupling Reactions, J. Am. Chem. Soc., 2025, 147, 23351–23366.
59. 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.
60. Z. Zhang and V. Gevorgyan, Visible Light-Induced Reactions of Diazo Compounds and Their Precursors, Chem. Rev., 2024, 124, 7214–7261.
61. N. A. Romero and D. A. Nicewicz, Organic Photoredox Catalysis, Chem. Rev., 2016, 116, 10075–10166.
62. D. S. Lee, V. K. Soni and E. J. Cho, N−O Bond Activation by Energy Transfer Photocatalysis, Acc. Chem. Res., 2022, 55, 2526–2541.
63. S. Dutta, J. E. Erchinger, F. Strieth-Kalthof, R. Kleinmans and F. Glorius, Energy transfer photocatalysis: exciting modes of reactivity, Chem. Soc. Rev., 2024, 53, 1068–1089.
64. Q. Xue, J. Xie, P. Xu, K. Hu, Y. Cheng and C. Zhu, Metal-Free, n-Bu₄NI-Catalyzed Regioselective Difunctionalization of Unactivated Alkenes, ACS Catal., 2013, 3, 1365–1368.
65. A. K. Jones, T. E. Wilson and S. S. Nikam, in Encyclopedia of Reagents for Organic Synthesis, ed. L. A. Paquette, John Wiley & Sons, New York, 1995, p. 880.
66. R. Zhu and S. L. Buchwald, Versatile Enantioselective Synthesis of Functionalized Lactones via Copper-Catalyzed Radical Oxyfunctionalization of Alkenes, J. Am. Chem. Soc., 2015, 137, 8069–8077.
67. Y. Zeng, M. F. Chiou, X. Zhu, J. Cao, D. Lv, W. Jian, Y. Li, X. Zhang and H. Bao, Copper-Catalyzed Enantioselective Radical 1,4-Difunctionalization of 1,3-Enynes, J. Am. Chem. Soc., 2020, 142, 18014–18021.
68. Y. Zeng, Y. Li, D. Lv and H. Bao, Copper-catalyzed three-component oxycyanation of alkenes, Org. Chem. Front., 2021, 8, 908–914.
69. H. Qin, Z. Liu, Y. Zhang and Y. Chen, Photocatalytic Oxyalkynylation of Unactivated Alkenes Enabled by Hypervalent Iodine(III) Reagents, ACS Catal., 2024, 14, 13202–13208.
70. M. Zheng, K. Gao, H. Qin, G. Li and H. Lu, Metal-to-Ligand Ratio-Dependent Chemodivergent Asymmetric Synthesis, Angew. Chem., Int. Ed., 2021, 60, 22892–22899.
71. T. Patra, M. Das, C. G. Daniliuc and F. Glorius, Metal-free photosensitized oxyimination of unactivated alkenes with bifunctional oxime carbonates, Nat. Catal., 2021, 4, 54–61.
72. K. Yang, J. Liu, D. Fu, L. Niu, S.-J. Li and Y. Lan, A theoretical study of selective radical relay and coupling reactions for alkene difunctionalization, Org. Chem. Front., 2023, 10, 4336–4341.
73. S. Q. Lai, B. Y. Wei, J. W. Wang, W. Yu and B. Han, Photocatalytic Anti-Markovnikov Radical Hydro- and Aminooxygenation of Unactivated Alkenes Tuned by Ketoxime Carbonates, Angew. Chem., Int. Ed., 2021, 60, 21997–22003.
74. A. Tagata, M. Sawamura and Y. Shimizu, Oxyamination of alkenes enabled by direct photoexcitation of fluorenone oxime derivatives, Chem. Lett., 2024, 53, 216–221.
75. C. Gao, J. Zeng, X. Zhang, Y. Liu and Z.-P. Zhan, A Photosensitizer for N–O Bond Activation: 2,7-Br-4CzIPN-Catalyzed Difunctionalization of Alkenes with Oxime Esters, Org. Lett., 2023, 25, 3146–3151.
76. J. Li, Y. Yuan, X. Bao, T. Sang and C. Huo, Visible-Light-Induced Intermolecular Oxyimination of Alkenes, Org. Lett., 2021, 23, 3712–3717.
77. X.-K. Qi, M.-J. Zheng, C. Yang, Y. Zhao, L. Guo and W. Xia, Metal-Free Amino(hetero)arylation and Aminosulfonylation of Alkenes Enabled by Photoinduced Energy Transfer, J. Am. Chem. Soc., 2023, 145, 16630–16641.
78. T. Sang, C. Zhou, J. Li, X. Liu, Y. Yuan, X. Bao, X. Zhao and C. Huo, Photosensitized Anti-Markovnikov Hydroesterification of Unactivated Alkenes, Org. Lett., 2023, 25, 4371–4376.
79. G. Tan, F. Paulus, Á. Rentería-Gómez, R. F. Lalisse, C. G. Daniliuc, O. Gutierrez and F. Glorius, Highly Selective Radical Relay 1,4-Oxyimination of Two Electronically Differentiated Olefins, J. Am. Chem. Soc., 2022, 144, 21664–21673.
80. F. Paulus, C. Stein, C. Heusel, T. J. Stoffels, C. G. Daniliuc and F. Glorius, Three-Component Photochemical 1,2,5-Trifunctionalizations of Alkenes toward Densely Functionalized Lynchpins, J. Am. Chem. Soc., 2023, 145, 23814–23823.
81. Y.-S. Jiang, D.-N. Chen, H. Jiang and P.-J. Xia, Photocatalytic selective 1,4-oxyimination/diamination across C=C and N=N bonds to access structurally diverse N-N-N triazane derivatives, Green Synth. Catal., 2024 DOI:10.1016/j.gresc.2024.07.003.
82. S.-S. Li, J. Luo, S.-N. Liang, D.-N. Chen, L.-N. Chen, C.-X. Pan and P.-J. Xia, Efficient and regioselective C=S bond difunctionalization through a three-component radical relay strategy, Chin. Chem. Lett., 2025, 36, 110424–110431.
83. L. Quach, S. Dutta, P. M. Pflüger, F. Sandfort, P. Bellotti and F. Glorius, Visible-Light-Initiated Hydrooxygenation of Unactivated Alkenes—A Strategy for Anti-Markovnikov Hydrofunctionalization, ACS Catal., 2022, 12, 2499–2504.
84. H. Yang, Y. Wang, L.-C. Wang and X.-F. Wu, Visible light-promoted oxycarbonylation of unactivated alkenes, EES Catal., 2024, 2, 1247–1252.

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Footnote

† Equally contributing authors.

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