Radical di- and multi-functionalization of alkenes: recent advances in diverse reaction modes utilizing TBHP as reactants

Abstract

In recent years, radical-mediated functionalization of olefins has gradually become a research hotspot in the field of organic synthesis due to its high reactivity, excellent regioselectivity, and wide substrate applicability. Compared to traditional ionic pathways, radical strategies effectively avoid compatibility issues with some functional groups through modes, such as photocatalysis, electrocatalysis, or chemical initiation, and provide new pathways for the diversified conversion of olefins, such as bifunctional, hydrogen functionalization, and cyclization reactions. Among them, tert-butyl hydroperoxide (TBHP) plays multiple roles in synthetic chemistry as an efficient and inexpensive oxidant and radical precursor: it is not only a classic initiator of radical chain reactions but also a source of tert-butyl peroxide, tert-butyl oxygen, methyl, oxygen, hydrogen, or hydroxyl groups. The unique capacity to generate controllable radical species establishes TBHP as an indispensable platform for advancing green synthetic methodologies, empowering pharmaceutical innovation and deciphering fundamental reaction mechanisms. In this review, we summarize the recent progress in TBHP-enabled transformations of alkenes, which are categorized as peroxidation, carbonylation, epoxidation, etherification, hydrogenation, and hydroxylation. Within each category, representative studies are presented and discussed in terms of mechanistic insights and substrate scope expansion.

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Jiantao Zhang

Jiantao Zhang received his Ph.D. degree in organic chemistry from the South China University of Technology in 2019 under the supervision of Prof. Shifa Zhu. In July 2019, he joined the College of Chemistry at the Guangdong University of Petrochemical Technology. His current research interests involve the functionalization of alkenes/alkynes and radical cascade reactions.

Renhua Su

Renhua Su was born in Guangdong, China, in 1995. He obtained his undergraduate degree from the Guangdong University of Petrochemical Technology in 2019. Currently, under the guidance of Professor Weibing Liu and Dr Jiantao Zhang, he is pursuing his master's degree at the same university. His research interests focus on the field of organic chemistry.

Weibing Liu

Weibing Liu received his Ph.D. degree from the South China University of Technology in 2010 under the supervision of Prof. Huangfeng Jiang. In July 2010, he joined the Guangdong University of Petrochemical Technology. He was a postdoctoral fellow at the King Abdullah University of Science & Technology in Saudi Arabia. His research interests focus on green organic synthesis and formula design for industrial cleaning agents.

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1. Introduction

tert-Butyl hydroperoxide (TBHP) stands out as a privileged reagent in modern organic synthesis, distinguished by its dual functionality as a radical initiator and a versatile group-transfer agent. Unlike conventional peroxides (e.g., hydrogen peroxide), TBHP exhibits superior thermal stability and tunable reactivity, enabling efficient execution of diverse transformations under mild conditions (room temperature to moderate heating) while suppressing undesired side pathways.¹ Its reactivity originates from peroxide bond cleavage and dissociation of the tert-butyl moiety. Specifically: (1) radical initiation occurs via thermal or photochemical activation, generating tert-butoxy radicals (^tBuO˙) that drive radical addition/cyclization pathways of alkenes under metal-catalyzed conditions.² (2) As a dual donor of methyl (CH₃), tert-butoxy (^tBuO), tert-butyl peroxide (^tBuOO), hydroxyl (OH), and hydrogen (H), TBHP enables selective functionalization of alkenes including methylation,³ peroxidation,⁴ etherification, hydroxylation, and hydrofunctionalization (Scheme 1). In addition, TBHP has important applications in radical polymerization, drug intermediate synthesis, and polymer material modification, especially in constructing complex molecular frameworks and chiral centers, demonstrating unique advantages.

Scheme 1 Reactive intermediates generated during the decomposition of TBHP.

On the other hand, multicomponent radical-mediated transformations of alkenes have emerged as a paradigm-shifting strategy in contemporary synthetic chemistry, offering unparalleled efficiency in assembling complex molecular architectures from simple feedstocks.⁵ By harnessing the transient and highly reactive nature of radicals, these reactions enable simultaneous activation and coupling of diverse components under mild conditions, circumventing traditional stepwise methodologies.

This review systematically summarizes recent advances (2010–2025) in TBHP-enabled transformations of alkenes, which are categorized as peroxidation, carbonylation, epoxidation, etherification, hydrogenation, and hydroxylation (Scheme 2). Within each category, representative studies are presented and discussed in terms of mechanistic insights and substrate scope expansion. By critically analysing current challenges in selectivity control and energy efficiency, this work aims to provide a roadmap for developing methods for the stable and controllable decomposition of TBHP that harness the full potential of TBHP in synthetic organic chemistry.

Scheme 2 Application of TBHP as a multifunctional reagent in the radical reactions of alkenes.

2. Peroxidation

Peroxygenated compounds are present in many important natural products and biologically active drugs. They are widely used in the fields of chemistry, pesticides and pharmaceutical chemistry. Thus, a number of peroxidation reactions have been developed.⁶

Recently, difunctionalization of alkenes with a peroxy and another functional group has become an attractive strategy for the preparation of organic peroxides (Scheme 3). Furthermore, peroxides have been recognized as efficient synthetic intermediates, which can be converted into ketones, alcohols, phenols and epoxy compounds under mild conditions.^7,8

Scheme 3 Peroxidation of alkenes with TBHP.

2.1 Carbo-peroxidation

2.1.1 Carbonylation–peroxidation. In 2011, Li⁹ demonstrated a practical protocol for FeCl₂-catalyzed carbonylation–peroxidation of alkenes with aldehydes and TBHP (Scheme 4). A variety of β-peroxy ketones were selectively and efficiently constructed by the three-component reaction. Aliphatic aldehydes with butyl or cyclopropyl groups were successfully applied to this transformation under standard conditions. It was noted that a decarbonylation product instead of the desired carbonylation–peroxidation product was obtained quantitatively when pivaldehyde was applied.

Scheme 4 Fe-catalyzed carbonylation–peroxidation of alkenes with aldehydes and TBHP.

A possible reaction mechanism was proposed: TBHP generates ^tBuOO˙ and ^tBuO˙ radicals in the presence of an Fe(II) catalyst and then ^tBuO˙ radicals help aldehydes generate acyl radicals via hydrogen abstraction. Subsequently, the radical addition of acyl radicals with alkenes occurs to give a benzylic radical, which undergoes a radical–radical coupling reaction with ^tBuOO˙ radicals to furnish the final product. In addition, these products could be transformed into epoxides.^8a,d

These preliminary results prompt them to further investigate Fe-catalyzed three-component reactions of α,β-unsaturated compounds with TBHP. In 2012, Li¹⁰ developed a method for the synthesis of multifunctional peroxides by Fe-catalyzed three-component reactions of α,β-unsaturated esters, aromatic/aliphatic aldehydes, and TBHP (Scheme 5). The densely functionalized peroxides, 2-peroxy-1,4-dicarbonyls, were efficiently and selectively synthesized with a broad scope of substrates. Besides the terminal alkenes, the implementation of this synthetic strategy to tri-/tetra-substituted acrylates could also give the desired carbonylation–peroxidation products.

Scheme 5 Fe-catalyzed carbonylation–peroxidation of α,β-unsaturated esters with aldehydes and TBHP.

Conversely, moisture tolerant VOCl₂ serves as an alternative catalytic system for FeCl₂ and provides an additional advantage for aliphatic aldehydes bearing 2° alkyl groups. In 2015, Weng¹¹ developed a tandem and complementary β-peroxidation–carbonylation of styrenes with TBHP by using VOCl₂ as the catalyst (Scheme 6). Most aromatic aldehydes led to the products in moderate yields which were comparable to or slightly higher than those catalyzed by FeCl₂. In the cases of hetero-aromatic and aliphatic aldehydes, which were less studied before, the peroxides were furnished in 72–78% yields.

Scheme 6 V-catalyzed complementary β-oxidative carbonylation of styrene derivatives with aldehydes and TBHP.

Despite these advances, most transformations require metal catalysts, such as Fe, Co, Cu, Ru, and V. Metal-free cases are rare. It has been known that a halogen anion X⁻ (especially I⁻ and Br⁻) also enables the efficient decomposition of peroxides, just as a metal initiator does.¹² In 2018, Wang¹³ developed a TBAB-initiated carbonylation–peroxidation of styrene derivatives for the synthesis of β-peroxy ketones using aldehydes and TBHP (Scheme 7). The present three-component reaction is characterized by its environmentally benign catalyst, operational simplicity, and mild reaction conditions. Analysis of the mechanism revealed that bromide acted as an efficient radical initiator for the difunctionalization of styrene derivatives. Compared to the previous methods, the present bromine initiated version is a valuable complementary approach.

Scheme 7 TBAB-initiated carbonylation–peroxidation of styrene derivatives with aldehydes and TBHP.

A plausible mechanism for this bromine-catalyzed carbonylation–peroxidation of alkenes is depicted. First, radicals ^tBuO˙ and ^tBuOO˙ were generated through the redox reaction of bromine. The radical ^tBuO˙ is more reactive and less stable than ^tBuOO˙. The subsequent process is similar to what was previously reported.

In contrast to the thermal reaction process using expensive metals as the catalysts or under harsh reaction conditions mentioned above, visible-light driven hydrogen atom transfer from aldehydes for acyl-radical generation enables the organic transformation to proceed under mild and operationally simple conditions. In 2021, Zhu¹⁴ developed a three-component radical acylation–peroxidation reaction under visible-light photocatalysis conditions by using indole derivatives, which provides tremendous opportunities to discover novel drugs with different modes of action (Scheme 8). The overall reaction yield is not high, and when unactivated alkenes (such as allylbenzene) and aliphatic aldehydes (such as propionaldehyde and heptanal) were tested under the reaction conditions, no target products were observed.

Scheme 8 Visible-light driven acylation–peroxidation of alkenes with indole-3-carbaldehydes and TBHP.

In 2015, Li¹⁵ developed a high yielding alkoxycarbonylation–peroxidation of alkenes through Fe-catalysis (Scheme 9). The reaction provides practical and selective access to β-ester peroxides in a single step from readily available starting materials. Both styrenes and acrylates as alkenes smoothly reacted with methyl carbazate and TBHP to give the corresponding alkoxycarbonylation–peroxidation products in good isolated yields. Importantly, a variety of functional groups were quite compatible with this transformation. During the reaction process, ^tBuO radicals assist in the production of alkoxycarbonyl radicals from carbazates.

Scheme 9 Fe-catalyzed alkoxycarbonylation–peroxidation of alkenes with carbazates and TBHP.

In 2017, Hu and Loh¹⁶ established an Fe-catalyzed three-component radical coupling reaction which assembled β-peroxy amides with TBHP and formamide derivatives through difunctionalization of styrenes as well as 1,3-enynes under mild conditions (Scheme 10). Other metal salts (Cu, Co) showed inferior effectiveness for this reaction. In addition, the resulting β-peroxy amides serve as versatile synthetic precursors, which could be transformed into β-hydroxy amide, β-keto amide and β-lactam. Intriguingly, the addition of benzoic acid markedly enhanced reaction yields for specific enyne substrates, yet the underlying mechanistic basis of this effect remains unresolved with current experimental evidence.

Scheme 10 Fe-catalyzed carbamoylation–peroxidation of alkenes with formamides and TBHP.

2.1.2 Alkylation–peroxidation. In 2014, Klussmann¹⁷ developed a multicomponent alkylation–peroxidation reaction of styrene derivatives with ketones by Brønsted acid catalysis (Scheme 11). Going from primary over secondary to tertiary ketones, a major drop in reactivity is observed (20a–20c), which could be attributed to steric effects. In addition, the γ-peroxy ketone products obtained could be further converted into synthetically useful 1,4-diketones, homoaldol products, and alkyl ketones. The low yield of alkyl alkene suggests that a resonance-stabilizing group on the olefin is beneficial.

Scheme 11 Acid-catalyzed oxidative radical addition of olefins with ketones and TBHP.

In 2017, Li¹⁸ developed a CoCl₂-catalyzed alkylation–peroxidation reaction of alkenes to access γ-carbonyl peroxides in a single step with 1,3-dicarbonyl compounds and TBHP (Scheme 12). In addition, gram-scale syntheses demonstrated that the protocol is practical and useful in organic synthesis. Compared to Klussmann's¹⁷ work, pTsOH·H₂O completely shut down the desired reaction, while HOAc could increase the yield of the target product. The results indicated that suitable acidic conditions favor the desired transformation.

Scheme 12 Co-catalyzed alkylation–peroxidation of alkenes with 1,3-dicarbonyl compounds and TBHP.

In 2022, Li¹⁹ reported the concomitant functionalization of two distinct α-C–H bonds of carbonyls integrated with unactivated olefins and TBHP selectively and efficiently in one pot by merging Brønsted acid catalysis and radical relay coupling, which delivers an array of structurally valuable unsymmetrical peroxy 1,9-diketones in moderate to good yields (Scheme 13). The reaction efficiency for alkenyl aryl ketones exhibited negligible dependence on the electronic or steric characteristics of the aryl substituents. Notably, even aliphatic ketones appended with alkenyl groups could be effectively processed under the optimized protocol to yield the target products.

Scheme 13 Brønsted acid-catalyzed remote alkacylation–peroxidation of unactivated alkenes.

The direct engagement of sp³ α-C–H bonds in alcohols through activation–functionalization sequences offers a streamlined approach for synthesizing multifunctional alcohol architectures.²⁰

In 2015, Loh²¹ developed a copper- and cobalt-catalyzed three-component oxidative coupling of 1,3-enynes with alcohols and TBHP, which involved the α-C–H activation of alcohols (Scheme 14). A broad substrate scope encompassing aliphatic, silylated, and aryl-substituted 1,3-enynes, as well as vinylarenes, was successfully engaged in alkylation–peroxidation sequences to construct β-peroxy alcohols. These intermediates proved convertible to β-hydroxy ketones and 1,3-diols through subsequent transformations. Notably, aryl alkenes diverged from this pathway, exclusively delivering oxyalkylation products under standard conditions.

Scheme 14 Cu- or Co-catalyzed direct coupling of sp³ α-carbon of alcohols with alkenes and TBHP.

In the past few decades, transition-metal-based carbene complexes have proven to be highly efficient intermediates in various organic syntheses.²² Among them, copper carbene complexes, which are mainly generated from copper-induced decomposition of diazo compounds, have been extensively employed in transformations such as X–H insertion, cross-coupling, cyclization and ylide reactions.^23–26 Nevertheless, their engagement in radical-involved coupling regimes persists as a conspicuous blind spot—a consequence of kinetic incompatibility between electrophilic carbene centers and transient radical species, where mutual quenching pathways dominate under conventional stoichiometric control paradigms.

In 2015, Bao and Wan²⁷ developed a crossover reaction that combined Cu carbene and radical intermediates in a single catalytic cycle, allowing for the synthesis of various γ-peroxy esters and 1,4-dicarbonyl compounds (Scheme 15). This would broaden the utility of the Cu carbene transfer reaction and represents a significant technological advancement in the fields of both copper carbene and radical chemistry. Unfortunately, aliphatic alkenes proved incompatible as coupling partners in this transformation, and no desired product was detected in the crude reaction mixture.

Scheme 15 Cu-based crossover reaction of alkenes with diazo compounds and TBHP.

Current radical-mediated alkylation systems remain constrained by a narrow substrate scope, predominantly restricted to prefunctionalized alkenes bearing carbonyl, hydroxyl, or ester moieties.²⁸ This limitation underscores the critical need for developing alkylperoxidation protocols capable of installing non-functionalized linear/branched alkyl chains onto electronically unactivated alkenes—a transformative yet underexplored frontier in radical chemistry. Similarly, these radical type decarbonylative alkylations of aldehydes with C≡C and C=C bonds were further updated by Z.-P. Li,^29a J.-H. Li^29b and Pan^29c groups.

In 2019, Yang³⁰ developed an Fe-catalyzed three-component decarbonylative alkylation–peroxidation of styrene derivatives with aliphatic aldehydes and TBHP to provide chain elongated benzyl peroxides and alkylated ketones via a one-pot procedure (Scheme 16). Aliphatic aldehydes were decarbonylated into 1°, 2° and 3° alkyl radicals at low temperature, which subsequently allows the cascade construction of C(sp³)–C(sp³) and C(sp³)–O bonds via radical insertion and radical–radical coupling. This methodology demonstrated broad functional group tolerance across structurally diverse alkenes, including mono-/terminal di-/internal di-substituted styrenes, as well as electron-deficient acrylates. TBHP played a triple role of a radical initiator, terminal oxidant and radical coupling partner.

Scheme 16 Fe-catalyzed decarbonylative alkylation–peroxidation of alkenes with aliphatic aldehydes and TBHP.

The photocatalytic decarboxylation of carboxylic acids has emerged as a robust platform for generating alkyl radical intermediates, enabling efficient interception by alkenes through radical addition or cross-coupling pathways.³¹ In 2024, Li³² presented a photoinduced, CeCl₃-catalyzed three-component decarboxylative reaction that couples carboxylic acids, alkenes and TBHP for the formation of various organic peroxides (Scheme 17). The ligand-to-metal charge transfer (LMCT) excitation mode allows the decarboxylative alkylation–peroxidation reaction to occur under mild conditions. The decarboxylative alkylation–peroxidation cascade exhibited an exceptional substrate scope, seamlessly integrating 1°, 2° and 3° alkyl carboxylic acids with electronically varied styrenes to deliver well-defined peroxides bearing orthogonal functional groups.

Scheme 17 Visible-light-induced synthesis of organic peroxides from alkenes, carboxylic acids, and TBHP.

Over the past decades, cyclopropanol and its derivatives have evolved into privileged three-carbon synthons, demonstrating exceptional adaptability in ring-opening cascade reactions, stereoselective rearrangements, and transition-metal-catalyzed coupling protocols.³³

In 2021, Li³⁴ developed an iron-catalyzed radical ring-opening reaction of cyclopropanols with alkenes and TBHP (Scheme 18a). This three-component protocol enabled the incorporation of both the β-carbonyl fragment and a peroxy entity across the C=C double bonds regioselectively, which provided facile and efficient access to structurally diverse 5-oxo peroxides including the modification of biologically active molecules. The resulting 5-oxo peroxides were demonstrated as versatile building blocks for the synthesis of important derivatives such as aldehydes, alcohols, diketone heterocycles, and carbocycles.

Scheme 18 Fe-catalyzed ring-opening reactions of cyclopropanols and their derivatives with alkenes and TBHP.

In 2022, Li³⁵ developed an efficient protocol for the synthesis of 4-ester peroxides via ring-opening coupling of siloxy cyclopropanes with alkenes and TBHP in the presence of an iron catalyst (Scheme 18b). The reaction involves a TBAF-mediated radical relay process and exhibits good functional group compatibility. This cascade radical alkene difunctionalization reaction successfully delivers a series of 4-ester peroxides and enables the late-stage functionalization of biologically active molecules and streamlined diversification of peroxide pharmacophores.

Direct functionalization of inert aliphatic C(sp³)–H bonds represents a paradigm shift in sustainable synthesis, enabling atom- and step-economical construction of C–C/C–X bonds without prefunctionalized substrates.³⁶ This strategy capitalizes on alkanes as ideal coupling partners – inherently benign, operationally robust, and commercially abundant alternatives to traditional electrophilic alkylating reagents requiring multistep preparation.³⁷

In 2015, Patel³⁸ demonstrated regioselective cycloalkylation–peroxidation of 3-substituted coumarins (Scheme 19). In this three-component Cu(I)-promoted process, the components are coumarin, TBHP and cycloalkane as reactants, where C–O and C–C bonds are installed via C(sp³)–H functionalization with concurrent generation of two stereocentres. A significant electronic effect was observed in this radical addition reaction. Notably, the regioselective dual functionalization observed in the coumarin system displays a pattern diametrically opposed to that of styrene derivatives. This method, however, which was only useful for a specific natural compound, 3-acetylcoumarin, significantly limited its use in practice. Even worse, a large amount of catalyst was used.

Scheme 19 Cu-promoted cycloalkylation–peroxidation of alkenes with cycloalkanes and TBHP.

Considering the shortage of previous work and the difficulties of direct coupling of alkanes with simple α,β-unsaturated carbonyl compounds and peroxides to yield alkyl α-peroxy ketones, Loh³⁹ and co-workers explored the direct coupling of alkanes with more common α,β-unsaturated ketones and esters in 2017 (Scheme 20). They developed a copper-initiated oxidative coupling of unsaturated carbonyl compounds with TBHP and alkanes, which involved the C(sp³)–H activation of alkanes. Various aliphatic and aryl vinyl ketones and esters underwent alkylation–peroxidation to assemble α-peroxy carbonyl compounds.

Scheme 20 Cu-initiated oxidative coupling of unsaturated carbonyl compounds with alkanes and TBHP.

2.1.3 Haloalkylation–peroxidation. Perfluorinated compounds, which can be prepared via a variety of methods, exhibit enhanced stability, lipophilicity, bioavailability, and biopotency over their nonfluorinated counterparts.^40,41

In 2016, Bao and Wan⁴² developed a difunctionalization reaction that combined styrene with an electrophilic perfluoroalkyl radical and a ^tBuOO˙ radical in a one-pot synthesis method to produce (1-(tert-butylperoxy)-2-perfluoroalkyl)-ethylbenzene with chemo- and regioselectivity at room temperature (Scheme 21). In contrast, no desired products were generated when aliphatic alkenes were employed as substrates. In addition, the products were amenable to further chemical modifications, which allowed the preparation of a variety of synthetically valuable molecules.

Scheme 21 Co-catalyzed perfluoroalkylation–peroxidation of alkenes with perfluoroalkyl iodide and TBHP.

As a privileged fluorine-containing pharmacophore, the –CF₃ substituent strategically enhances drug-like character through synergistic C–F bond polarization effects.⁴³ Therefore, many efficient methods for trifluoromethylation have been developed.⁴⁴

In 2017, Zhang⁴⁵ developed the cobalt-catalyzed trifluoromethyl–peroxide difunctionalization of alkenes (Scheme 22). This radical-mediated process demonstrates exceptional substrate generality including allyl, vinyl, chain terminal, and internal alkenes with different functional groups. The cheap and bench-stable CF₃SO₂Na serves as the CF₃ source in this reaction. This transformation provides a convenient and economic method for the construction of vicinal trifluoromethyl–peroxide derivatives, which are useful in organic synthesis.

Scheme 22 Co-catalyzed trifluoromethylation−peroxidation of unactivated alkenes with CF₃SO₂Na and TBHP.

In 2017, Duan⁴⁶ achieved the trifluoromethylation–peroxidation of styrenes in a heterogeneous mode (Scheme 23a). The rigid 3D framework of Cu₃(BTC)₂ is necessary to maintain the structural integrity of the binuclear paddle-wheel Cu(II) catalytic center for the effective electrophilic activation of Togni's reagent 52 and TBHP with a low loading amount of catalyst, and the bowl-bottom like confined environment around the copper node is vital for the discrimination of reaction sites with different steric demands. In contrast to the homogeneous copper salts, the heterogeneous Cu₃(BTC)₂ showed superior catalytic activity and intrinsic shape- and regioselectivity for this transformation. Due to the bioactivities of molecules containing α-CF₃ acetophenone/benzylic alcohol scaffolds, it will be attractive to apply this heterogeneous MOF catalysis and the two successive protocols in the pharmaceutical industry. Notably, aliphatic alkenes (terminal and internal derivatives) exhibited negligible reactivity in this catalytic system, with conversions remaining below 10% even under optimized reaction conditions.

Scheme 23 Trifluoromethylation–peroxidation of alkenes with Togni's reagent/trifluoroacetic acid and TBHP.

Compared to Duan's work,⁴⁶ Li's group has effectively solved the problem of alkyl olefins not participating in the reaction. In 2024, Li⁴⁷ developed a photocatalytic trifluoromethylation–peroxidation of alkenes utilizing an iron-LMCT strategy (Scheme 23b). A diverse array of fluoroalkylated organic peroxides were synthesized in moderate to good yields. This synergistic catalytic system efficiently mediates a three-component coupling of fluoroalkyl carboxylic acids, alkenes, and tert-butyl TBHP through a proposed radical–polar crossover mechanism. Particularly noteworthy is its capability for direct late-stage functionalization of bioactive molecules, thus offering new avenues for prodrug development.

Halodifluoromethylated compounds are promising building blocks for the preparation of valuable fluorinated compounds as well as candidates for investigating halogen bonding.⁴⁸

In 2022, Li⁴⁹ demonstrated a cobalt–tertiary amine mediated trifluoromethylation–peroxidation and halodifluoromethylation–peroxidation of alkenes with CF₂XBr (X = F, Cl, Br) to afford various α,β-peroxyl trifluoromethyl and halodifluoromethyl derivatives (Scheme 24). Mono-, di-, and trisubstituted alkenes with both electron-donating and electron-withdrawing groups could be tolerated well. Further transformation of this type of compounds into other useful molecules, such as a ketene aminal, an α-trifluoromethyl ketone, and a gem-difluoroalkene, demonstrated the utility of this methodology.

Scheme 24 Co-tertiary amine-mediated halodifluoromethylation–peroxidation of alkenes with CF₂XBr and TBHP.

In 2021, Li⁵⁰ developed a manganese-catalyzed remote peroxidation of C(sp³)–H bonds by a 1,5-HAT mediated radical relay strategy (Scheme 25). This protocol allows the convenient incorporation of both the –CF₃ group and the peroxy functionality into the C=C bond, and thus, a series of valuable 1,6-difunctionalized products were achieved with good to excellent regioselectivity and functional group compatibility under mild conditions. TBHP plays a dual role as both the oxidant and the peroxy precursor.

Scheme 25 Mn-catalyzed remote trifluoromethylation–peroxidation of unactivated alkenes.

Unlike trifluoromethyl (–CF₃) and perfluoroalkyl (–R_f) groups, the difluoromethyl (–CF₂H) moiety possesses a strongly polarized C–H bond that enables it to function as an effective hydrogen-bond donor. This unique characteristic enhances cellular membrane permeability in bioactive molecules.⁵¹ Importantly, the –CF₂H group demonstrates dual pharmaceutical advantages: it serves as a bioisosteric replacement for polar functional groups (–OH, –NH, –SH) while exhibiting higher lipophilicity compared to these conventional hydrogen-bond donating groups. This combination of hydrogen-bonding capacity and enhanced lipid solubility has established –CF₂H as a valuable structural motif in bioisosteric replacement strategies for optimizing drug-like properties. Therefore, new methodologies for the efficient incorporation of –CF₂H into diverse organic skeletons have received increasing attention.⁵²

In 2022, Li⁵³ developed a copper-catalyzed difluoromethylation–peroxidation reaction of alkenes with CF₂HSO₂Na and TBHP (Scheme 26). This three-component cascade difunctionalization strategy facilitates efficient access to diverse β-difluoromethyl peroxides with moderately high yields. The synthetic utility of these peroxides was further demonstrated through their successful transformation into structurally diverse heterocyclic systems, including β-enaminones, isoxazoles, and diazepine derivatives, highlighting the method's versatility in constructing medicinally relevant scaffolds. Notably, internal and aliphatic alkenes exhibited complete inertness under the optimized conditions, probably due to the steric hindrance or diminished electrophilicity of the CF₂H radical.

Scheme 26 Cu-catalyzed radical difluoromethylation–peroxidation of alkenes and TBHP.

In 2019, Li⁵⁴ demonstrated a Co(acac)₂-catalyzed three-component difluoroalkylation–peroxidation of alkenes with difluorohaloacetates and TBHP (Scheme 27). Remarkably, the developed protocol demonstrated extensibility to unactivated alkenes, with systematic evaluation confirming their successful participation in the transformation under the optimized reaction conditions, albeit with significantly lower yields. This methodology enables efficient and regioselective synthesis of diverse β-peroxyl-difluoroalkyl compounds, which serve as versatile intermediates for constructing α-amino acid derivatives and pyrimidine scaffolds via nucleophilic reactions with amines and amidines. Remarkably, the strategy demonstrates broad applicability to various halide precursors, delivering structurally diverse alkylation–peroxidation hybrids through this modular platform.

Scheme 27 Co-catalyzed difluoroalkylation–peroxidation of alkenes with difluorohaloacetates and TBHP.

Chloroform (CHCl₃) is commonly used as a reaction medium and is an easily obtainable chemical resource. In addition, it can also serve as a flexible precursor for various halogenated groups in organic synthesis.⁵⁵

In 2018, our group⁵⁶ developed a protocol for the construction of various α-tert-butylperoxy-β-dichloromethyl alkanes via the TBHP-mediated alkylation–peroxidation of alkenes using CHCl₃ (Scheme 28). Compared to traditional transition metal-catalyzed atom transfer radical addition (ATRA) reactions, this approach utilizes CHCl₃ as an alkylating reagent, offering a unique and innovative method for generating –CHCl₂ groups.

Scheme 28 TBHP-mediated alkylation–peroxidation of alkenes with CHCl₃ and TBHP.

In 2019, Doyle⁵⁷ reported a copper-catalyzed dichloromethylation–peroxidation reaction involving olefins, CHCl₃, and TBHP (Scheme 29). The authors believe that diisopropylethylamine plays a crucial role in the reaction process. The α-amino radicals hinder the preferential transfer of hydrogen atoms and facilitate the transfer of halogen atoms, thereby releasing halogenated methyl radicals for the addition to olefins. Through computational analysis, the authors determined that the oxidation addition/reduction elimination pathway is the lowest energy pathway for the reaction and clearly explained the differences between CHCl₃ and traditional hydrogen atom transfer (HAT) processes.

Scheme 29 Cu-catalyzed dichloromethylation–peroxidation of alkenes with CHCl₃ and TBHP.

2.2 Heteroatomic peroxidation

2.2.1 Silylation/germanium peroxidation. Emerging evidence highlights silicon-substituted drug analogues as privileged pharmacophores, where silicon's unique physicochemical properties—enhanced lipophilicity, distinct bond polarization, and tetrahedral distortion—enable superior bioactivity profiles.⁵⁸ Notably, functionalized alkylsilanes serve as versatile building blocks in polymer engineering and industrial catalysis. These dual advantages position strategic isosteric replacement of carbon with silicon as a powerful paradigm for developing innovative therapeutic candidates.⁵⁹

In 2017, Loh and Xu⁶⁰ developed a copper-catalyzed difunctionalization of C=C double bonds of α,β-unsaturated ketones, esters, amides, and conjugated enynes (Scheme 30). This silylperoxidation reaction allows for the synthesis of silicon-containing peroxy products with high efficiency.

Scheme 30 Cu-catalyzed silylperoxidation reaction of α,β-unsaturated compounds with HSiEt₃ and TBHP.

A plausible mechanistic pathway of copper-catalyzed silylperoxidation transformation of α,β-unsaturated systems was proposed. First, the ^tBuO˙ radical species was generated from TBHP in the presence of a copper catalyst. Then, abstracting an H atom of the ^tBuO˙ radical from triethylsilane gives an Si-centered radical, which would react with an α,β-unsaturated carbonyl compound to form an α-carbonyl radical intermediate. Subsequently, this intermediate would be reduced via a single electron transfer (SET) process to form an alkylcopper intermediate. After reductive elimination, the desired silylperoxidation product would be afforded with the release of catalytically active Cu(I) species.

In 2018, Li⁶¹ developed an Fe-catalyzed silylation–peroxidation of alkenes with hydrosilanes and TBHP (Scheme 31). A variety of acrylates were used for this three-component reaction. It is noteworthy that excellent diastereoselectivity of the silylation–peroxidation of alkenes was achieved when dimethyl fumarate and dimethyl maleate were used. Styrene derivatives, which were not used in Loh and Xu's⁶⁰ works, were also applicable for the silylation–peroxidation reaction to give the desired products in the presence of CoCl₂. In addition, epoxidation and reduction of the obtained β-silyl peroxides were also studied.

Scheme 31 Fe-catalyzed silylation–peroxidation of alkenes with hydrosilanes and TBHP.

Organogermanium compounds are gaining significant interest across multiple disciplines due to their distinctive properties.⁶² However, achieving simultaneous installation of germyl and functional groups across C=C bonds remains challenging: germanium hydrides’ strong hydrogen-donating capacity promotes radical chain transfer processes that predominantly yield hydrogermylation products, while competing oxidative self-coupling pathways require stringent control. Therefore, a new strategy for the construction of vicinally functionalized germanium-containing molecules via the selective 1,2-germylfunctionalization of alkenes is greatly desirable and fascinating.⁶³

In 2022, Li⁶⁴ established a copper-catalyzed germyl-peroxidation of electron-deficient alkenes with germanium hydrides and TBHP (Scheme 32). This three-component radical relay strategy provided straightforward access to a variety of highly functionalized germanium-containing peroxy products in good to excellent yields. Styrene and alkyl olefins failed to engage in the reaction manifold; however, interestingly, electron-poor styrene exhibited exceptional compatibility, delivering the desired germanium-containing peroxides in synthetically useful yields. Remarkably, this strategy enabled late-stage functionalization of sterically demanding bioactive scaffolds including diacetone glucose, α-tocopherol, and estrone.

Scheme 32 Cu-catalyzed germylperoxidation of electron-deficient alkenes with germanium hydrides and TBHP.

2.2.2 Azidation/nitration/amination–peroxidation. Organic azides have emerged as pivotal components across chemical biology and materials engineering, particularly valued as multifunctional synthons in medicinal scaffolds and supramolecular architectures.⁶⁵ Their synthetic versatility stems from dual reactivity profiles: serving as programmable amine precursors, nitrene reservoirs, 1,3-dipolar partners, and click chemistry substrates.⁶⁶ This broad utility has driven substantial methodological innovations in azide synthesis protocols.⁶⁷

In 2019, Li⁶⁸ demonstrated an azidation–peroxidation of alkenes with TMSN₃ and TBHP (Scheme 33). This methodology enables efficient construction of diverse β-azido peroxides. Notably, styrenes bearing both electron-donating and withdrawing groups demonstrated broad substrate generality, affording target compounds in moderate to good yields. Furthermore, the obtained peroxides underwent chemoselective transformations to α-azido carbonyl derivatives (aldehydes/ketones) and triazole architectures under operationally simple protocols. The use of other metal catalysts (e.g. CuBr, CoCl₂, FeCl₃) also has good effects.

Scheme 33 Mn-catalyzed azidation–peroxidation of alkenes with TMSN₃ and TBHP.

The radical-mediated addition of ˙NO₂ to C=C bonds has recently emerged as an efficient protocol for constructing nitroalkenes and cyclic nitroalkanes.⁶⁹ However, implementing alkene difunctionalization strategies that simultaneously install nitro groups alongside orthogonal functionalities remains nontrivial, primarily stemming from inherent challenges in controlling reaction chemo- and regioselectivity.

In 2019, Li⁷⁰ demonstrated the nitration–peroxidation of alkenes. This protocol provides facile access to a variety of β-peroxyl nitroalkanes by using readily available reagents (^tBuONO and TBHP) under mild conditions (Scheme 34). Substituent electronic effects at the para-position of styrenes showed minimal influence on reaction efficiency, enabling effective product formation. Conversely, cyclic alkenes and acrylates demonstrated compromised reactivity in analogous nitration–peroxidation cascades, yielding targets with moderate efficiency. Mechanistic investigations combining experimental evidence and computational validation support a radical-mediated pathway with controlled selectivity.

Scheme 34 Mn-catalyzed nitration–peroxidation of alkenes with tert-butyl nitrite and TBHP.

In 2017, our group⁷¹ described a practical method for the synthesis of 1,2-oxazetidine derivatives via a [2 + 1 + 1] cycloaddition from styrenes, arylamines and TBHP (Scheme 35). TBHP employed in this conversion not only acted as the oxidant but also as the source of “O” for the products. This work represented the first regioselective approach for accessing diverse functionalized 1,2-oxazetidines with excellent substrate generality, filling a significant synthetic gap in this important heterocyclic system. Nevertheless, the detailed reaction mechanism requires further elucidation.

Scheme 35 [2 + 1 + 1] cycloaddition from styrenes, arylamines and TBHP.

2.2.3 Phosphorylation–peroxidation. Organophosphorus scaffolds have a ubiquitous presence across bioactive pharmaceuticals, optoelectronic devices, and advanced synthetic methodologies.⁷² This functional versatility has driven intensive research on developing operationally simple C–P bond-forming strategies.⁷³ Particularly, the engagement of P-centered radicals with olefinic substrates has emerged as a robust platform for installing structurally diverse C–P linkages in contemporary organic synthesis.⁷⁴

In 2018, Li⁷⁵ developed a copper-catalyzed phosphorylation–peroxidation of alkenes (Scheme 36). This three-component protocol provides practical access to multisubstituted β-phosphoryl peroxides by the reactions of P(O)–H compounds, alkenes and TBHP. Alkyl/aryl H-phosphonates proved competent for phosphorylative–peroxidative dual functionalization, whereas diphenylphosphine oxide exhibited complete reactivity suppression under optimized conditions. Significantly, LiHMDS-mediated chemoselective transformation of β-phosphoryl peroxides to the corresponding epoxides was achieved, establishing a versatile protocol for architecting multifunctional organophosphorus architectures.

Scheme 36 Cu-catalyzed phosphorylation–peroxidation of alkenes with P(O)–H compounds and TBHP.

In 2019, Yang⁷⁶ developed the cobalt(II)-catalyzed bisfunctionalization of styrenes with aryl phosphorus reagents and TBHP (Scheme 37). This reaction proceeds efficiently to furnish various phosphonation–peroxidation compounds in a one-pot manner. A P(O)-radical-mediated pathway is proposed following the computational and preliminary mechanistic studies (Scheme 38). It should be noted that alkylalkenes afforded hydrophosphination byproducts rather than the desired products. Heteroatom-conjugated alkenes (e.g., sulfides, pyridines, enones) also failed to produce phosphonation–peroxidation adducts.

Scheme 37 Co-catalyzed phosphorylation–peroxidation of alkenes with diarylphosphine oxide and TBHP.

Scheme 38 Mechanism of the metal-catalyzed phosphorylation–peroxidation of alkenes with diarylphosphine oxide and TBHP.

In 2024, Li⁷⁷ developed a visible-light promoted transition-metal-free chemodivergent phosphorylation–peroxidation and oxyphosphorylation of alkenes using Eosin Y as a SET photocatalyst at room temperature (Scheme 39). With this strategy, a variety of β-phosphoryl peroxides were selectively obtained with a catalytic amount of base, while the addition of acid led to the formation of β-keto-phosphine oxides. This methodology features operationally simple conditions, excellent functional group compatibility, and switchable access to phosphorus-containing architectures through bench-stable additives.

Scheme 39 Photoinduced chemodivergent phosphorylation–peroxidation and oxyphosphorylation of alkenes with diarylphosphine oxide and TBHP.

2.2.4 Oxylation–peroxidation. Vicinal bisperoxides have emerged as privileged pharmacophores in drug discovery, demonstrating tripartite bioactivity against malaria parasites, helminthic infections, and neoplastic proliferation.⁷⁸

In 2010, Han and Pan⁷⁹ developed a palladium-catalyzed tandem process, including diperoxidation of olefins and C–H activation (Scheme 40). The current system provides a new pathway for the synthesis of biologically active diperoxides, as well as oxindole functionalities. However, this reaction requires the use of excess HOAc (used as the solvent) and TBHP (10.0 equiv.), which limits its application in organic synthesis.

Scheme 40 Pd-catalyzed tandem diperoxidation/C–H activation of N-arylacrylamides.

Manganese(III) acetate functions as a high-potential oxidant, demonstrating exceptional efficacy in mediating both electron-transfer processes and radical-mediated transformations that enable selective construction of C–C, C–O, and C–N bonds in synthetic methodologies.^80–82

In 2015, Terent'ev⁸³ developed a method for the bisperoxidation of styrenes with TBHP in the presence of Mn(OAc)₃ (Scheme 41). The combination of two oxidizing agents, Mn(OAc)₃ and TBHP, imparts new properties to the system. The synthesized compounds and the method for their preparation may be applied for the production of radical polymerization initiators of unsaturated monomers. However, the overall yield of the product is moderate, and the authors only conducted reactions on nine aromatic olefins, which is insufficient to demonstrate the superiority of this strategy.

Scheme 41 Mn-catalyzed bisperoxidation of styrenes.

In 2020, Gnanaprakasam⁸⁴ reported a mild and efficient protocol for Mn-2,2′-bipyridine-catalyzed vicinal bisperoxidation of arylidene-9H-fluorene derivatives at room temperature (Scheme 42). This approach features the use of Earth-abundant manganese catalysts and readily available 2,2′-bipyridine ligands, rapid and room-temperature reaction conditions and a wide substrate scope. Likewise, the bisperoxidation of arylidene-indolin-2-one derivatives also proceeded smoothly in the presence of an Mn catalyst.

Scheme 42 Mn-catalyzed bisperoxidation of alkenes.

The reported methods for the synthesis of vicinal bisperoxides from styrenes and TBHP are catalyzed by metal catalysts. However, metal-free catalyzed bisperoxidation of alkenes is less known.

In 2021, Xu and Liu⁸⁵ developed a metal-free and efficient bisperoxidation approach for alkenes by iodine, employing TBHP as the oxidant (Scheme 43). By varying the employed solvent systems and additives, the reaction conditions can be fine-tuned to selectively synthesize biperoxidates. Importantly, the use of an additional base significantly accelerated the process, reducing the duration to 4 h.

Scheme 43 Iodine-initiated bisperoxidation of aryl alkenes.

It was known that the catalytically active species, the phthalimide N-oxyl (PINO) radical derived from N-hydroxyphthalimide (NHPI), mediates C–O bond formation via radical-mediated alkene addition pathways.^86,87

In 2015, Xia⁸⁸ developed a copper-catalyzed dioxygenation of olefins for the direct synthesis of substituted peroxides under mild reaction conditions (Scheme 44). A radical addition process was involved in this reaction, as evidenced by the successful trapping of a transient radical intermediate by TEMPO.

Scheme 44 Cu-catalyzed dioxygenation of olefins.

While α-carbon peroxidation of alkenes has been predominantly realized, the corresponding β-carbon peroxidation still presents an underexplored synthetic challenge in this transformation.^89,90

In 2022, He and Gao⁸⁹ described regioselective, environment-friendly, and efficient oxy-peroxidation of alkenes mediated by NH₄I using TBHP and oxygen sources (Scheme 45). Mechanistic investigations revealed that products are governed by regioselective radical addition coupled with S_N2 substitution, alongside conventional S_N2 pathways. Compared to the traditional pathway of the S_N2 reaction, an unusual transition configuration with the H₂O molecule attacking the α-C atom at the front side was obtained.

Scheme 45 NH₄I-promoted oxyperoxidation of alkenes.

In 2023, Fernandes⁹⁰ demonstrated a highly efficient regioselective, orthogonal direct difunctionalization of 1,3-dienes with TBHP under metal-free conditions for the synthesis of hydroxylperoxidates in good yields (Scheme 46). This approach represents a promising strategy for constructing valuable hydroxyperoxidates, stemming from its operationally mild conditions, cost-effective reagents, excellent functional group compatibility, and facile derivatization of products into valuable derivatives.

Scheme 46 TBAI-catalyzed regioselective hydroxyperoxidation of 1-aryl/alkyl-1,3-dienes.

2.2.5 Thiolation–peroxidation. The sulfonyl group serves as a key functional group in medicinal chemistry, materials science, and synthetic methodologies.^91,92 Within sulfonylation chemistry, alkene oxysulfonylation—enabling concurrent installation of sulfonyl and oxygen-containing moieties—has emerged as a powerful strategy for accessing structurally diverse sulfonyl-containing compounds with tailored functionalities.⁹³

In 2018, Li⁹⁴ developed a silver-catalyzed sulfonylation–peroxidation of alkenes with sulfonyl hydrazides and TBHP (Scheme 47). The Ag-catalyzed three-component peroxidation provides a method for the synthesis of a variety of β-sulfonyl peroxides, which could be converted into various sulfone derivatives.

Scheme 47 Ag-catalyzed sulfonylation–peroxidation of alkenes with sulfonyl hydrazides and TBHP.

Sulfonyl azides constitute fundamental organic reagents that have been widely recognized as pivotal amination agents, diazo precursors, and 1,3-dipolar components for constructing 1,2,3-triazole scaffolds in synthetic chemistry.⁹⁵ However, sulfonyl azides have rarely been converted into sulfonyl radicals in chemical transformations.⁹⁶

In 2023, Ding and Liu⁹⁷ showed a cobalt-catalyzed oxysulfonylation of alkenes to afford β-sulfonyl peroxides in moderate to good yields under mild conditions (Scheme 48). Mechanistic studies show that this protocol enables sulfonyl azides to be a new sulfonyl radical source. However, when allyl benzene was inspected, no expected product 99f was observed.

Scheme 48 Co-catalyzed sulfonylation–peroxidation of alkenes with sulfonylazides and TBHP.

Photocatalytic radical strategies employing N-sulfonyl imines have evolved into complementary platforms for installing sulfonyl motifs into alkene substrates through synergistic radical-involved processes.⁹⁸

In 2024, Li⁹⁹ demonstrated a photocatalytic three-component sulfonyl peroxidation of alkenes with N-sulfonyl ketimines and TBHP via an energy transfer process (Scheme 49). A variety of β-peroxyl sulfone derivatives were synthesized under mild reaction conditions without a transition metal catalyst. This methodology's synthetic value was further illustrated through the preparation of 11β-HSD1 inhibitors and the therapeutic agent bicalutamide. Nevertheless, the reaction system exhibited substrate specificity restricted to arylsulfonyl peroxide formation.

Scheme 49 Photocatalytic sulfonylation–peroxidation of alkenes with N-sulfonyl ketimines and TBHP.

In 2024, Li¹⁰⁰ reported their progress on the alkyl sulfonylation–peroxidation of alkenes with N-alkyl sulfonyl ketimines and TBHP (Scheme 50). What's more, when N-trifluoromethyl sulfonyl imine was applied, the trifluoromethylation–peroxidation of alkenes was achieved by a release of SO₂ from the trifluoromethane sulfonyl radical. These established approaches share a fundamental constraint: while successfully addressing aryl olefins, they remain inapplicable to alkyl olefin systems.

Scheme 50 Photo-induced alkyl sulfonylation/trifluoromethylation–peroxidation of alkenes with N-sulfonyl ketimines and TBHP.

In the past few years, the trifluoromethylthio (–SCF₃) moiety has garnered continuous attention owing to its unique physicochemical characteristics, notably its pronounced electron-withdrawing nature and exceptional lipophilicity.¹⁰¹ This functional group has been strategically incorporated into multiple pharmaceuticals and agrochemical agents.¹⁰²

In 2020, Li¹⁰³ presented the trifluoromethylthiolation–peroxidation of alkenes by reactions with AgSCF₃ and TBHP (Scheme 51). This method gives access to new structural motifs with excellent regio- and chemoselectivities. This reaction follows a stepwise radical-based difunctionalization mechanism at C=C bonds. This protocol demonstrates broad substrate compatibility encompassing acrylates and diverse aliphatic alkenes, efficiently delivering trifluoromethylthiolation–peroxidation adducts. Electron-rich aromatic alkenes exhibited diminished catalytic efficiency relative to electron-deficient analogs, whereas alkyl-substituted olefins and acrylic esters showed further reduced yields compared to their aromatic counterparts.

Scheme 51 Cu-catalyzed trifluoromethylthiolation–peroxidation of alkenes with AgSCF₃ and TBHP.

In 2022, Li¹⁰⁴ realized trifluoromethylthiolation–peroxidation of unactivated alkenes by using readily-available AgSCF₃ and TBHP in the presence of a copper catalyst (Scheme 52). The radical trifluoromethylthiolation of alkenes triggers a 1,5-HAT process and further remote α-C–H bond peroxidation to afford a series of distal trifluoromethylthiolated organic peroxides in moderate to good yields with excellent regioselectivity under mild conditions.

Scheme 52 Cu-catalyzed remote trifluoromethylthiolation–peroxidation of unactivated alkenes.

2.2.6 Iodization–peroxidation. Iodinated derivatives have been established as crucial multifunctional synthons in organic transformations, serving as powerful reagents for preparative SN reactions that preserve the peroxide functionality.¹⁰⁵ Consequently, the concurrent formation of iodide and peroxide groups within a single molecular framework could enable the straightforward development of pharmacologically relevant compounds.

In 2017, Zhu¹⁰⁶ established a metal-free process for the direct vicinal difunctionalization of alkenes with iodine and TBHP to synthesize 1-(tert-butylperoxy)-2-iodoethanes (Scheme 53). This simple and high-yielding method with excellent regioselectivity for the iodination and peroxidation of the C=C double bond of alkenes shows good functional group compatibility.

Scheme 53 Difunctionalization of alkenes with iodine and TBHP.

In 2018, Gao and Wang¹⁰⁷ developed a highly atom-economical, environment-friendly, and efficient method for the synthesis of α- and β-iodoperoxidates with TBHP and iodide/NH₄I under solvent-free reaction conditions (Scheme 54). By varying the iodide reagents, the reaction conditions could be fine-tuned for the regioselective synthesis of α-iodoperoxidates and β-iodoperoxidates. The excellent regioselectivity for the anti-Markovnikov type iodoperoxidates (α-iodoperoxidates) depended on the persistent radical effect, while the exclusive formation of Markovnikov type iodoperoxidates (β-iodoperoxidates) was attributed to the formation of a more stable carbocation intermediate.

Scheme 54 Iodide reagent-controlled highly regioselective synthesis of α- and β-iodoperoxidates.

In 2024, Abdukader¹⁰⁸ explored a method to selectively synthesize α/β-aromatic peroxy thiols in one pot and two steps under mild conditions (Scheme 55). This methodology enables metal-free C–S bond formation under ambient conditions. Upon employing thiophenols as model substrates, the system demonstrated a broad substrate scope encompassing diverse thiophenols and heterocyclic variants, effectively affording the desired products with structural fidelity.

Scheme 55 Regioselective synthesis of α/β-aromatic peroxy thiols mediated by an iodine source.

3. Carbonylation

Multicomponent reactions (MCRs) enable the simultaneous formation of multiple bonds in a one-step process using easily accessible starting materials.¹⁰⁹ These reactions offer an efficient pathway to synthesize compounds with high structural complexity and functional diversity, making them a focus of significant interest in both academic research and industrial applications.¹¹⁰

The Kornblum–DeLaMare rearrangement is a base-catalyzed transformation that converts peroxides into carbonyl compounds, widely recognized as a fundamental ionic reaction mechanism (Scheme 56).^111,112

Scheme 56 Multicomponent reactions for the synthesis of carbonyl compounds.

In 2014, Wan¹¹³ developed a Co-catalyzed reaction involving the sequential addition of 1,3-dioxolanes to electron-deficient alkenes and vinylarenes with a high degree of selectivity using TBHP as an oxidant (Scheme 57). A radical–polar crossover mechanism has been proposed to account for this reaction, where a benzyl radical selectively couples with ^tBuOO˙ to give a peroxide intermediate, which undergoes a subsequent Kornblum–DeLaMare reaction.

Scheme 57 Co-catalyzed four-component radical–polar crossover reaction.

In 2019, Yang¹¹⁴ developed a convenient Fe-catalyzed four-component radical dual difunctionalization of two different alkenes with aldehydes and TBHP to provide β,δ-functionalized ketones via a one-pot procedure (Scheme 58). This radical-mediated dual difunctionalization strategy achieves simultaneous functionalization and sequential assembly of two distinct alkenes in a one-pot process, effectively incorporating three functional groups while extending the carbon chain, where TBHP serves as a multifunctional reagent acting as a radical initiator, terminal oxidant, and radical coupling partner.

Scheme 58 Fe-catalyzed radical dual difunctionalization of two different alkenes with aldehydes and TBHP.

In 2016, Wan¹¹⁵ developed a tandem process that features a cobalt-based carbene radical and involves radical and ionic reactions (Scheme 59). The interception of the cobalt-based carbene radical with the α-aminoalkyl radical, followed by the Kornblum–DeLaMare reaction, enables the streamlined preparation of diverse, highly functionalized β-ester-γ-amino ketones. This one-pot transformation simultaneously establishes two C–C bonds and one carbonyl (C=O) bond.

Scheme 59 Co/Cu-catalyzed cascade reaction to construct β-ester-γ-amino ketones.

In 2016, a variety of highly functionalized β-ester-γ-amino ketones were efficiently synthesized by Wan's¹¹⁶ group via the interception of electrophilic Cu-based carbene with nucleophilic α-aminoalkyl radicals, which was different from previous reports that provided proton sources.²⁷

In 2022, Koenigs¹¹⁷ developed the photocatalytic 1,2-difunctionalization reaction of styrenes with acceptor-only diazoalkanes (Scheme 60). This method demonstrates excellent functional group compatibility and provides an efficient route to access valuable 1,4-dicarbonyl scaffolds. Unlike traditional photochemical or transition-metal-catalyzed processes, the photocatalytic strategy enables innovative reaction manifolds for diazoalkanes that bypass conventional carbene-involved pathways.

Scheme 60 Photocatalytic 1,2-oxo-alkylation reaction of styrenes with diazoacetates and TBHP.

The isoxazole scaffold represents a privileged structural motif widely employed in both synthetic and medicinal chemistry.¹¹⁸ Significant research endeavors have been devoted to developing efficient methodologies for the preparation of isoxazole derivatives.¹¹⁹

In 2019, Li¹²⁰ developed a four-component strategy for the synthesis of the isoxazole skeleton (Scheme 61). This approach achieves the synthesis of perfluoroalkyl isoxazoles by using simple perfluoroalkyl reagents. This method presents a practical, atom-economic, one-pot procedure that delivers functional isoxazoles without intermediate workup or solvent change. In addition, this work pioneers the strategic deployment of Togni's reagent as a versatile C1 synthon, evidenced by its successful integration into the isoxazole scaffold to generate previously unreported 3-azido-5-aryl derivatives. Mechanistic studies support that the transformation includes a tandem process of perfluoroalkylation–peroxidation/Kornblum–DeLaMare rearrangement/elimination/substitution/N–O bond formation to give the isoxazoles.

Scheme 61 Four-component reactions for the synthesis of perfluoroalkyl isoxazoles.

In 2015, Wan¹²¹ demonstrated a cobalt-catalyzed procedure for the synthesis of (Z)-β-perfluoroalkyl enaminones via a multicomponent radical process involving sequential fluoroalkylation–peroxidation and a Kornblum–DeLaMare reaction (Scheme 62). This oxidative transformation demonstrates remarkable efficiency and selectivity through the simultaneous cleavage of three distinct bonds (two C–F and one C–X [X = Br/I]) while concurrently forming three new bonds (one carbonyl C=O bond, one C=C bond, and one C–N bond).

Scheme 62 Synthesis of (Z)-β-perfluoroalkyl enaminones from alkenes with perfluoroalkyl halides and TBHP.

In 2021, our group¹²² developed a four-component tandem reaction without a catalyst, utilizing TBHP, CHCl₃, and triethylamine to construct multiple chemical bonds in a one-pot manner, thereby efficiently producing enamine derivatives (Scheme 63). The simultaneous bond cleavage and formation were achieved under identical reaction conditions without requiring additional modifications or supplementary reagents. Mechanistic investigations revealed that this transformation occurs through a cascade involving radical addition, nucleophilic substitution, and elimination steps. Notably, the resulting products serve as versatile intermediates for the synthesis of thiadiazole derivatives. Such multi-step transformations demonstrate considerable potential for applications in heterocyclic synthesis and pharmaceutical development.

Scheme 63 Metal-free sequential reactions for the synthesis of enaminones.

Dichloro ketones have emerged as highly valuable synthetic building blocks in organic chemistry, serving as key intermediates for the assembly of natural products and pharmacologically active molecules.¹²³ Considerable attention has been focused on developing diverse synthetic methods to access both 1,1-dichloro and 1,2-dichloro ketone derivatives.^124,125 However, the construction of 1,3-dicholoro ketones is rarely investigated.

In 2024, Liu¹²⁶ developed a convenient one-pot method for the construction of 1,3-dichloro-1,5-diarylpentan-5-ones via the cascade oxidative addition of styrenes with TBHP and CHCl₃ (Scheme 64). This method successfully generated a ketone group through a Kornblum–DeLaMare rearrangement. From a mechanistic perspective, the reaction undergoes dichloromethylation–peroxidation of olefins, followed by a chlorine atom transfer process involving the participation of a second molecule of olefins.

Scheme 64 Cascade oxidative radical addition of styrenes for the synthesis of 1,3-dichloro-1,5-diarylpentan-5-ones.

In 2014, Wan¹²⁷ reported a Co-catalyzed reaction for the construction of 1,4-dicarbonyls, which involves cascade organocobalt addition/trapping/Kornblum–DeLaMare rearrangement (Scheme 65). Bromoalkylketones, bromoalkylesters, and bromoalkylnitriles could be used as reactants to generate the corresponding products. This method utilizes easily available starting materials, offers operational simplicity, and exhibits a broad substrate scope as well as functionality tolerance.

Scheme 65 Co-catalyzed synthesis of 1,4-dicarbonyl compounds from alkenes, α-bromoamides and TBHP.

In 2015, Wang¹²⁸ reported a Cu/Mn co-catalyzed direct oxidative coupling of terminal vinylarenes with ketones via C(sp³)–H bond functionalization following C–C bond formation to generate 1,4-dicarbonyls (Scheme 66). This strategy offers an alternative method to synthesize useful functionalized complex molecules directly using simple and inexpensive reactants. Experimental observations indicate that the reaction system exhibits moderate yields overall, with both steric constraints and electronic characteristics of the aromatic substituents playing crucial roles in determining the final product yields.

Scheme 66 Cu/Mn cocatalyzed oxidative coupling of vinylarenes with ketones and TBHP.

γ-Keto diesters serve as versatile building blocks in synthetic chemistry, playing crucial roles in the construction of complex molecular architectures.^129,130 These bifunctional compounds find wide applications across biochemical research and advanced material development due to their unique reactivity and structural features. In 2018, Maity¹³¹ developed a simple and efficient approach for the synthesis of γ-keto diesters via oxidative coupling of styrenes with malonic esters (Scheme 67). A catalytic amount of cost-effective TBAI in combination with TBHP efficiently coupled a variety of malonic esters with styrenes in moderate to good yields. The radical clock experiment reveals strong support for the participation of the manonyl radical in this transformation. The present coupling was characterized by the use of a metal-free catalyst with excellent levels of regioselectivity, particularly for internal and conjugated styrenes.

Scheme 67 TBAI/TBHP-promoted oxidative coupling of styrenes with malonic esters and TBHP.

In 2020, Patel¹³² achieved a carbonylation–peroxidation of vinyl arenes in the absence of any carbonyl source (Scheme 68). Vinyl arenes underwent decarbonylative C–C bond formation followed by a concurrent carbonylation–peroxidation catalyzed by Cu(I) and TBHP but α-methyl styrenes yielded aryl methyl ketones as the only product. In contrast to conventional approaches,^9–11,13 this study employs alkenes as the acyl sources without the requirement for supplementary aldehyde reagents.

Scheme 68 Cu-catalyzed differential peroxidation of alkenes with TBHP.

Ethers, particularly thioethers, have gained significant research interest owing to their vital roles in bioactive compounds and drug development. Consequently, various synthetic strategies have been established to access structurally diverse derivatives of these valuable functional groups.¹³³

In 2022, Wang¹³⁴ developed a metal-free, TBHP and DBU mediated C(sp³)–H bond functionalization of thioethers with styrenes (Scheme 69). A radical relay process was first proposed and confirmed. Extended experiments on reaction mechanisms further revealed the necessity for the reactions under conjugated systems. The crucial and successful employment of DBU contributed to the unique benzoyl group formation in the products. This transformation is constrained by a suboptimal reaction yield and marked solvent dependency (6 mL solvent consumption per 0.2 mmol substrate), coupled with the requirement for a substantial TBHP loading (40 equiv.).

Scheme 69 DBU-mediated C(sp³)–H bond functionalization of thioethers with styrenes.

In 2016, Wang¹³⁵ described a metal-free unactivated C(sp³)–H bond functionalization of alkyl nitriles with terminal vinylarenes to provide γ-ketonitrile derivatives. In 2024, Singh and coworkers¹³⁶ reported a decarboxylative cyanomethylation of β-aryl/heteroaryl substituted α,β-unsaturated carboxylic acids accomplished via C(sp³)–H activation of alkyl nitriles to afford diverse γ-ketonitriles (Scheme 70). Notably, employing aliphatic cinnamic acid derivatives (specifically trans-but-2-enoic acid) with acetonitrile offered the corresponding product only in a trace quantity.

Scheme 70 Decarboxylative cyanomethylation of β-aryl/heteroaryl substituted α,β-unsaturated carboxylic acids.

In 2019, She¹³⁷ described a copper-catalyzed oxidative phosphonation of α-tert-hydroxylalkenes (Scheme 71). This protocol displays a broad scope with good functional group compatibility and gives efficient access to diverse β-oxophosphine oxides from simple allylic alcohols and H-phosphine oxides. A plausible reaction mechanism was proposed (Scheme 72), and they held the opinion that an unprecedented fragmentation process was involved in this transformation.

Scheme 71 Cu-catalyzed oxidative phosphonation of α-tert-hydroxylalkenes with P(O)–H compounds and TBHP.

Scheme 72 Possible mechanism of Cu-catalyzed oxidative phosphonation of α-tert-hydroxylalkenes.

4. Epoxidation

α,β-Epoxy ketones serve as crucial building blocks in contemporary organic synthesis, attracting considerable research focus due to their synthetic utility. Significant efforts have been devoted to developing efficient methodologies for constructing these valuable intermediates.¹³⁸

In 2015, Li¹³⁹ developed an oxidative coupling of unactivated terminal alkenes with aldehydes and TBHP using base catalysis for the selective synthesis of 2,3-epoxy ketones (Scheme 73A). This method proceeds via a transition metal-free tandem C–H/alkene functionalization step that occurs through an oxidative radical pathway. The ^tBuOK/TBHP-mediated oxidative coupling of alkyl aldehydes with alkenes proceeded via an epoxidation pathway, delivering 2,3-epoxy ketones with synthetically serviceable yields. Remarkably, alkylalkene reacted with aldehyde, TBHP and ^tBuOK to afford 1-para-tolylnonan-1-one (146c), not the 2,3-epoxy ketone.

Scheme 73 Oxidative coupling of alkenes with aldehydes and TBHP.

In 2015, Wang¹⁴⁰ established a visible-light-promoted photoredox synthesis method for α,β-epoxy ketones that directly employed abundantly available styrenes and benzaldehydes as substrates and operated under very mild conditions (Scheme 73B). Although this photocatalytic method is more in line with the theme of green chemistry than Li's method, in terms of the use of base, the reaction requires an excess of base, while Li only needs a catalytic amount of base.¹³⁹

In 2024, Thakur¹⁴¹ developed the first Co-based homogeneous photocatalytic route, which provides a straightforward and convenient yet powerful method for the synthesis of α,β-epoxy ketones in water (Scheme 74). The reaction demonstrated a broad substrate scope, successfully accommodating various aromatic, heteroaromatic and aliphatic aldehydes, electron-rich and electron-deficient styrenes, α-substituted styrenes, stilbene derivatives, acrylates, and the particularly challenging unactivated aliphatic alkenes. Mechanistic studies, Hammett analysis, and DFT studies have revealed that photoexcitation of Co is necessary for the inclusion of a wide substrate scope in good yields. The α,β-epoxy ketones were obtained via acylation–peroxidation products in the presence of a base (Scheme 75).

Scheme 74 Visible light-mediated Co(II) catalyzed synthesis of α,β-epoxy ketones.

Scheme 75 Possible mechanism of oxidative coupling of alkenes with aldehydes and TBHP.

5. Etherification

Under the influence of heat, transition metal catalysts, or radiation, the relatively weak O–O bond of TBHP is cleaved, allowing further synthesis of tert-butyl etherification substances.

In 2015, Li¹⁴² developed the copper-catalyzed oxidative difunctionalization of enol ethers with α-amino carbonyl compounds and TBHP (Scheme 76). This approach features operational simplicity and enables the regioselective synthesis of 2-amino-3,4-dioxy carbonyl derivatives in satisfactory yields. Notably, it constitutes the pioneering demonstration of alkene oxyalkylation via direct C(sp³)–H bond functionalization.

Scheme 76 Cu-catalyzed oxyalkylation of enol ethers with TBHP.

In 2020, our group¹⁴³ developed an efficient and general method for the highly selective construction of 2-tert-1-butoxyarylethanone frameworks via a Cu(I)-catalyzed oxidation/tert-butoxylation reaction (Scheme 77). In this method, TBHP acts not only as the oxidant but also as the tert-butoxy and carbonyl oxygen sources for this oxidation–tert-butoxylation transformation.

Scheme 77 Cu-catalyzed oxidation–tert-butoxylation of alkenes with TBHP.

6. Hydrogenation

In 2019, based on our previous work,⁵⁶ we utilized alkyl olefins as the reaction substrate and CHCl₃ as the chloromethylation reagent. By adjusting the reaction temperature to 70 °C, we successfully obtained the hydrogen dichloromethylation product of olefins (Scheme 78).¹⁴⁴ Additionally, when replacing the chlorine reagent with 1,1,2-trichloroethane or CCl₄, the reaction proceeded smoothly. Preliminary mechanistic studies reveal that this reaction involves oxidative radical processes. Specifically, triethylamine functions as a base, effectively inhibiting atom transfer radical addition (ATRA) and facilitating proton transfer to complete the reaction. This unique transformation holds significant potential in novel organic reactions.

Scheme 78 Oxidative radical addition–chlorination of alkenes.

7. Hydroxylation

Alcohol derivatives exhibit versatile utility across pharmaceutical, biological, and materials science domains.¹⁴⁵ Notably, certain bioactive alcohol compounds serve as therapeutic agents or key pharmaceutical intermediates for disease treatment, demonstrating significant value in clinical applications, biomedical research, and drug development.¹⁴⁶

Due to the low dissociation energy of the O–O bond (≈43.6 kcal mol⁻¹), TBHP preferentially undergoes O–O homo cleavage, and the given ^tBuO˙ radical generates new radicals through hydrogen capture in most reactions, which are then converted into tert-butanol.¹⁴⁷ However, ˙OH radicals are difficult to control due to their high activity and are usually reduced to HO⁻ (ultimately converted to H₂O), which has received little attention from researchers (Scheme 79).

Scheme 79 Multicomponent reactions for the synthesis of alcohol compounds.

In 2023, our group¹⁴⁸ developed a catalyst-free 1,2-difunctionalization of 1,3-dienes with CHCl₃ and TBHP in the presence of NEt₃ to give dichloromethylation–hydroxylation products (Scheme 80). This reaction showed good compatibility with diverse substituents on the diene aryl rings, affording the desired products in moderate to excellent yields. However, when Na₂CO₃ was used as the base, the formation of the crucial α-amino radical intermediate was inhibited, leading to the exclusive formation of 1,2-peroxyhydroxylation products. This protocol provides an effective and functional group tolerant strategy for diene 1,2-difunctionalization, thus providing great potential for further functionalization and modification of synthetic molecules.

Scheme 80 Base-tuned selective 1,2-dichloromethylhydroxylation and 1,2-peroxyhydroxylation of 1,3-dienes.

In 2024, our group¹⁴⁹ achieved a TMSCN-promoted difunctionalization of styrenes with CHCl₃ and TBHP via the radical addition/cross-coupling process (Scheme 81). A series of dichloromethylated alcohol derivatives were successfully prepared through a transition-metal-free protocol. Notably, this strategy demonstrates broad applicability even to unreactive alkenes. The critical factor involves TMSCN as an effective inhibitor against the dichloromethylation–peroxylation pathway. This methodology provides a practical alternative for constructing structurally diverse alcohol derivatives from easily accessible starting materials, offering considerable potential for pharmaceutical development and natural product synthesis.

Scheme 81 TMSCN-promoted difunctionalization of styrenes with CHCl₃ and TBHP.

In recent decades, fluorinated compounds have gained growing attention across pharmaceutical, agricultural, and materials research fields.¹⁵⁰ The establishment of novel synthetic strategies for introducing perfluoroalkyl moieties (–R_f) into various functional frameworks would significantly expand chemists’ capability to create compounds with enhanced biological activities and advanced material properties.¹⁵¹

In 2024, our group¹⁵² developed a TBHP-mediated three-component hydroxylation–perfluoroalkylation of 1,3-dienes with perfluoroalkyl iodides at ambient temperature, streamlining the access to a diverse range of synthetic valuable β-perfluoroalkyl allyl alcohols under mild conditions (Scheme 82). Furthermore, this methodology demonstrates broad applicability to both mono-olefins and 1,3-enyne substrates. Detailed mechanistic studies indicate that TBHP serves as the hydroxyl group donor in this transformation.

Scheme 82 TBHP-mediated hydroxyperfluoroalkylation of alkenes with perfluoroalkyl iodides.

In 2024, our group¹⁵³ developed an amine-promoted three-component radical selenofunctionalization reaction of alkenes with the simultaneous construction of C–Se and C–O bonds for the synthesis of oxyselenation products (Scheme 83). This approach efficiently provides diverse β-hydroxy selenide compounds with varied structural features in yields ranging from moderate to excellent, demonstrating potential utility for both synthetic and pharmaceutical research. Initial mechanistic investigations suggest that the reaction likely occurs through a radical-mediated process.

Scheme 83 Amine-promoted radical selenofunctionalization of alkenes with diselenides and TBHP.

8 Conclusion

Although some progress has been made in the study of TBHP's participation in the functionalization reaction of olefins, there are still the following problems that need to be solved urgently: (1) insufficient selectivity control: radical pathways can easily lead to side reactions (such as peroxidation and polymerization), and regioselectivity and stereoselectivity still need to be optimized, especially in complex molecular systems; (2) catalyst compatibility challenge: the strong oxidizing nature of TBHP may lead to deactivation or structural damage of metal catalysts (such as manganese and cobalt), affecting the stability of reaction cycles; (3) due to limitations in reaction conditions, the demand for high temperature, high pressure, or high concentration TBHP may increase energy consumption and operational risks, limiting the potential for industrial applications; (4) currently, reactions are mostly limited to aromatic olefins or terminal olefin substrates. The compatibility of non-activated olefins (such as alkyl substituted olefins) still needs to be improved; especially the reactivity and regioselectivity/stereoselectivity of internal olefins have not been effectively addressed. (5) Achieving precise enantioselective control continues to pose a significant challenge, whereas metal–ligand cooperative catalysis systems or advanced chiral ligand architectures (particularly those with stereodirecting auxiliaries) represent promising avenues for breakthroughs.

Perhaps the following aspects could further address the current issues. (1) New catalyst design: developing oxidation resistant and highly stable non-precious metal catalysts (such as improved cobalt based materials), combined with ligand engineering to optimize catalytic active centers; (2) deepening research on the reaction mechanism: analysing the interaction mechanism between TBHP and the catalyst through in situ characterization techniques, revealing the micro-dynamic processes of radical generation and functional group migration; (3) green process development: exploring reaction systems driven by light/electrocatalytic isothermal and condition-driven TBHP participation, reducing energy consumption and minimizing byproduct generation; (4) multifunctional expansion: based on the synthesis needs of bioactive molecules, TBHP-mediated cascade reactions should be developed to achieve efficient functionalization of olefins and the construction of complex skeletons.

Author contributions

J. Zhang conceived the review framework and drafted the manuscript; R. Su performed systematic literature retrieval and critical analysis; W. Liu provided expert supervision and substantive revisions. All authors contributed to intellectual content development and approved the final version of the 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 are grateful to the National Natural Science Foundation of China (22401052), the Guangdong Provincial Junior Innovative Talents Project for Ordinary Universities (2023KQNCX043), the Sailing Plan of Maoming Green Chemical Industry Research Institute (MMGCIRI-2022YFJH-Y-037), and the Special Projects in Key Fields of Ordinary Universities of Guangdong Province (2020ZDZX2054).

References

1. A. Rezaeifard, F. Doraghi, F. Akbari, B. Bari, E. Kianmehr, A. Ramazani, M. Khoobi and A. Foroumadi, Organic Peroxides in Transition-Metal-Free Cyclization and Coupling Reactions (C−C) via Oxidative Transformation, ACS Omega, 2025, 10, 15852–15907.
2. (a) W. Hu, S. Sun and J. Cheng, Formal [3+2] Reaction of α,α-Diaryl Allylic Alcohols with sec-Alcohols: Proceeding with Sequential Radical Addition/Migration toward 2,3-Dihydrofurans Bearing Quaternary Carbon Centers, J. Org. Chem., 2016, 81, 4399–4405; (b) W. Shao, M. Lux, M. Breugst and M. Klussmann, Radical addition of ketones and cyanide to olefins via acid catalyzed formation of intermediate alkenyl peroxides, Org. Chem. Front., 2019, 6, 1796–1800; (c) C.-W. Chuang, G.-R. Huang, S.-F. Hung, C.-W. Hsu, Y.-H. Liu, C.-H. Hwang and C.-T. Chen, Enantioselective Radical-Type 1,2-Alkoxy-Phosphinoylation to Styrenes Catalyzed by Chiral Vanadyl Complexes, Angew. Chem., Int. Ed., 2023, 62, e202300654; (d) Y.-H. Liu, H.-Y. Tsui, P.-H. Chien and C.-T. Chen, Asymmetric Radical-Type 1,2-Alkoxy-Sulfenylation of Benzoxazole-2-Thiols to Vinylarenes Catalyzed by Chiral Vanadyl Complexes, ACS Catal., 2024, 14, 10549–10560.
3. (a) Y. Zhu, H. Yan, L. Lu, D. Liu, G. Rong and J. Mao, Copper-Catalyzed Methyl Esterification Reactions via C–C Bond Cleavage, J. Org. Chem., 2013, 78, 9898–9905; (b) P. Li, J. Zhao, R. Lang, C. Xia and F. Li, Copper-catalyzed methyl esterification of aromatic aldehydes and benzoic alcohols by TBHP as both oxidant and methyl source, Tetrahedron Lett., 2014, 55, 390–393; (c) Y. Yang, Y. Bao, Q. Guan, Q. Sun, Z. Zha and Z. Wang, Copper-catalyzed S-methylation of sulfonyl hydrazides with TBHP for the synthesis of methyl sulfones in water, Green Chem., 2017, 19, 112–116; (d) O. P. S. Patel, N. K. Nandwana, A. K. Sah and A. Kumar, Metal-free synthesis of aminomethylated imidazoheterocycles: dual role of tert-butyl hydroperoxide as both an oxidant and a methylene source, Org. Biomol. Chem., 2018, 16, 8620–8628; (e) S. Rajamanickam, C. Sah, B. A. Mir, S. Ghosh, G. Sethi, V. Yadav, S. Venkataramani and B. K. Patel, Bu₄NI-Catalyzed, Radical-Induced Regioselective N-Alkylations and Arylations of Tetrazoles Using Organic Peroxides/Peresters, J. Org. Chem., 2020, 85, 2118–2141; (f) S. Jin, H. Yao, S. Lin, X. You, Y. Yang and Z. Yan, Peroxide-mediated site-specific C–H methylation of imidazo[1,2-a]pyridines and quinoxalin-2(1H)-ones under metal-free conditions, Org. Biomol. Chem., 2020, 18, 205–210; (g) X. Rong, L. Jin, Y. Gu, G. Liang and Q. Xia, Transition-Metal-Free Radical C−H Methylation of Quinoxalinones with TBHP, Asian J. Org. Chem., 2020, 9, 185–188; (h) P. Macías-Benítez, A. Sierra-Padilla, M. J. Tenorio, F. J. Moreno-Dorado and F. M. Guerra, Copper-Catalyzed Microwave-Expedited Oxyphosphorylation of Alkynes with Diethyl Phosphite and t-Butyl Hydroperoxide Synthesis of Densely Functionalized Phosphonylated Indenones, J. Org. Chem., 2021, 86, 16409–16424.
4. (a) T. J. Fisher and A. E. Mattson, Synthesis of α-Peroxyesters via Organocatalyzed O−H Insertion of Hydroperoxides and Aryl Diazoesters, Org. Lett., 2014, 16, 5316–5319; (b) D.-L. Kong, L. Cheng, T. Yue, H.-R. Wu, W.-C. Feng, D. Wang and L. Liu, Cobalt-Catalyzed Peroxidation of 2-Oxindoles with Hydroperoxides, J. Org. Chem., 2016, 81, 5337–5344; (c) C. Lou, L. Lv and Z. Li, Mn-Catalyzed Ring-Opening Peroxidation of Cyclobutanols: A Method for the Synthesis of 4-Oxo Peroxides, Adv. Synth. Catal., 2022, 364, 3743–3748; (d) D. I. Fomenkov, R. A. Budekhin, V. A. Vil’ and A. O. Terent'ev, The Ozone and Hydroperoxide Teamwork: Synthesis of Unsymmetrical Geminal Bisperoxides from Alkenes, Org. Lett., 2023, 25, 4672–4676; (e) O. V. Bityukov, K. V. Skokova, V. A. Vil’, G. I. Nikishin and A. O. Terent'ev, Electrochemical Generation of Peroxy Radicals and Subsequent Peroxidation of 1,3-Dicarbonyls in an Undivided Cell, Org. Lett., 2024, 26, 166–171.
5. (a) J. Sun, L. Wang, G. Zheng and Q. Zhang, Recent advances in three-component radical acylative difunctionalization of unsaturated carbon–carbon bonds, Org. Chem. Front., 2023, 10, 4488–4515; (b) X.-B. Zhu, Y. Yu, Y. Yuan and K.-Y. Ye, Electrochemical multicomponent reaction toward vicinal sulfenyltetrazolation of unactivated alkenes, Org. Chem. Front., 2023, 10, 5064–5069; (c) J. Liu, J.-P. Wan and Y. Liu, Electrochemical difunctionalization of alkenes and alkynes for the synthesis of organochalcogens involving C–S/Se bond formation, Org. Chem. Front., 2024, 11, 597–630; (d) M. Liu, X. Ouyang, C. Xuan and C. Shu, Advances in photoinduced radical–polar crossover cyclization (RPCC) of bifunctional alkenes, Org. Chem. Front., 2024, 11, 895–915.
6. X.-W. Lan, N.-X. Wang and Y. Xing, Recent Advances in Radical Difunctionalization of Simple Alkenes, Eur. J. Org. Chem., 2017, 5821–5851.
7. (a) X. Zheng, L. Lv, S. Lu, W. Wang and Z. Li, Benzannulation of Indoles to Carbazoles and Its Applications for Syntheses of Carbazole Alkaloids, Org. Lett., 2014, 16, 5156–5159; (b) Y. Ma, Y. Chen, C. Lou and Z. Li, DABCO-mediated [4+1] cycloaddition of β,β-dihalo peroxides with sodium azide toward isoxazoles, Asian J. Org. Chem., 2020, 9, 1018–1023; (c) Y. Ma, Y. Chen, L. Lv and Z. Li, Regioselective Synthesis of Emission Color-Tunable Pyrazolo[1,5-a]pyrimidines with β,β-Difluoro Peroxides as 1,3-Bis-Electrophiles, Adv. Synth. Catal., 2021, 363, 3233–3239; (d) Y. Ma, L. Lv and Z. Li, β-Perfluoroalkyl Peroxides as Fluorinated C3-Building Blocks for the Construction of Benzo[4,5]imidazo[1,2-a]pyridines, J. Org. Chem., 2022, 87, 1564–1573; (e) S.-Z. Cai, D. Ge, L.-W. Sun, W. Rao, X. Wang, Z.-L. Shen and X.-Q. Chu, Three-Component Heteroannulation for Tetrasubstituted Furan Construction Enabled by Successive Defluorination and Dual Sulfonylation Relay, Green Chem., 2021, 23, 935–941; (f) X.-Q. Chu, S.-Z. Cai, J.-W. Chen, Z.-L. Yu, M. Ma, P. J. Walsh and Z.-L. Shen, Defluorophosphorylation of fluoroalkyl peroxides for the synthesis of highly substituted furans, Green Chem., 2023, 25, 2000–2010; (g) Y.-Y. Ren, W.-J. Ji, C. Zhang, D. Ge, M. Ma, Z.-L. Shen and X.-Q. Chu, 1,2-Dichloroethane-Assisted Defluorinative Ring-Opening Reaction of DABCO and Polyfluoroalkyl Peroxides: Synthesis of Fluorinated N-Ethyl Piperazines, Chin. J. Chem., 2025, 43, 378–384.
8. (a) K. Liu, Y. Li, W. Liu, X. Zheng, Z. Zong and Z. Li, Efficient and Selective Synthesis of α,β-Epoxy-γ-Butyrolactones from 2-Peroxy-1,4-Dicarbonyl Compounds, Chem. – Asian J., 2013, 8, 359–363; (b) X. Zheng, S. Lu and Z. Li, The Rearrangement of tert-Butylperoxides for the Construction of Polysubstituted Furans, Org. Lett., 2013, 15, 5432–5435; (c) L. Lv, B. Shen and Z. Li, Total Synthesis of (±)-Clavilactones A, B, and Proposed D through Iron-Catalyzed Carbonylation–Peroxidation of Olefin, Angew. Chem., Int. Ed., 2014, 53, 4164–4167; (d) Z. Zong, X. Bai, S. Lu and Z. Li, A general method for synthesis of cis-dicarbonyl epoxides through DBU/LiBr-cocatalyzed cyclization of α,β-dicarbonyl peroxides, Tetrahedron Lett., 2016, 57, 3827–3831; (e) L. Lv, B. B. Snider and Z. Li, Total Synthesis and Structure Revision of (±)-Clavilactone D Through Selective Cyclization of an α,β-Dicarbonyl Peroxide, J. Org. Chem., 2017, 82, 5487–5491; (f) C. Lou, Y. Feng, Q. Huang, L. Lv and Z. Li, Visible Light-Induced Decarboxylative Peroxidation of Carboxylic Acids: Metal-Free Synthesis of Benzyl Peroxides, Asian J. Org. Chem., 2023, 12, e202300408; (g) C. Lou, Q. Huang, L. Lv and Z. Li, Formal Transformation of Benzylic Carboxylic Acids to Phenols, Chem. – Eur. J., 2024, 30, e202403301.
9. W. Liu, Y. Li, K. Liu and Z. Li, Iron-Catalyzed Carbonylation–Peroxidation of Alkenes with Aldehydes and Hydroperoxides, J. Am. Chem. Soc., 2011, 133, 10756–10759.
10. K. Liu, Y. Li, X. Zheng, W. Liu and Z. Li, Synthesis of α-ester-β-keto peroxides via iron-catalyzed carbonylation–peroxidation of α,β-unsaturated esters, Tetrahedron, 2012, 68, 10333–10337.
11. W.-C. Yang, S.-S. Weng, A. Ramasamy, G. Rajeshwaren, Y.-Y. Liao and C.-T. Chen, Vanadyl species-catalyzed complementary β-oxidative carbonylation of styrene derivatives with aldehydes, Org. Biomol. Chem., 2015, 13, 2385–2392.
12. (a) X.-F. Wu, J.-L. Gong and X. Qi, A powerful combination: recent achievements on using TBAI and TBHP as oxidation system, Org. Biomol. Chem., 2014, 12, 5807–5817; (b) P. Ghosh, B. Ganguly and S. Das, NaI/KI/NH₄I and TBHP as powerful oxidation systems: use in the formation of various chemical bonds, Org. Biomol. Chem., 2021, 19, 2146–2167.
13. Y. Yao, Z. Wang and B. Wang, Tetra-n-Butylammonium Bromide (TBAB)-Initiated Carbonylation–Peroxidation of Styrene Derivatives with Aldehydes and Hydroperoxides, Org. Chem. Front., 2018, 5, 2501–2504.
14. D. Zhao, Y. Pan, X. Chen, Y. Han, C. Yan, Y. Shi, H. Hou and S. Zhu, Three-Component Acylation/Peroxidation of Alkenes through Visible-Light Photocatalysis, ChemistrySelect, 2021, 6, 10834–10838.
15. Z. Zong, S. Lu, W. Wang and Z. Li, Iron-catalyzed alkoxycarbonylation–peroxidation of alkenes with carbazates and T-Hydro, Tetrahedron Lett., 2015, 56, 6719–6721.
16. J.-K. Cheng, L. Shen, L.-H. Wu, X.-H. Hu and T.-P. Loh, Iron-Catalyzed Peroxidation–Carbamoylation of Alkenes with Hydroperoxides and Formamides via Formyl C(sp²)–H Functionalization, Chem. Commun., 2017, 53, 12830–12833.
17. B. Schweitzer-Chaput, J. Demaerel, H. Engler and M. Klussmann, Acid-Catalyzed Oxidative Radical Addition of Ketones to Olefins, Angew. Chem., Int. Ed., 2014, 53, 8737–8740.
18. S. Lu, L. Qi and Z. Li, Cobalt-catalyzed alkylation–peroxidation of alkenes with 1,3-dicarbonyl compounds and T-hydro, Asian J. Org. Chem., 2017, 6, 313–321.
19. L. Wang, L. Lv and Z. Li, Concomitant functionalization of two different ketones by merging Brønsted acid catalysis and radical relay coupling, Org. Chem. Front., 2022, 9, 1561–1566.
20. (a) S.-Y. Zhang, F.-M. Zhang and Y.-Q. Tu, Direct Sp³ α-C–H activation and functionalization of alcohol and ether, Chem. Soc. Rev., 2011, 40, 1937–1949; (b) W. Zhou, P. Qian, J. Zhao, H. Fang, J. Han and Y. Pan, Metal-Free Oxidative Functionalization of C(sp³)–H Bond Adjacent to Oxygen and Radical Addition to Olefins, Org. Lett., 2015, 17, 1160–1163.
21. J. Cheng and T.-P. Loh, Copper- and Cobalt-Catalyzed Direct Coupling of sp³ α-Carbon of Alcohols with Alkenes and Hydroperoxides, J. Am. Chem. Soc., 2015, 137, 42–45.
22. (a) Y. Xia, D. Qiu and J. Wang, Transition-Metal-Catalyzed Cross-Couplings through Carbene Migratory Insertion, Chem. Rev., 2017, 117, 13810–13889; (b) Y. He, Z. Huang, K. Wu, J. Ma, Y.-G. Zhou and Z. Yu, Recent advances in transition-metal-catalyzed carbene insertion to C–H bonds, Chem. Soc. Rev., 2022, 51, 2759–2852; (c) X. Zhang, P. Sivaguru, Y. Pan, N. Wang, W. Zhang and X. Bi, The Carbene Chemistry of N-Sulfonyl Hydrazones: The Past, Present, and Future, Chem. Rev., 2025, 125, 1049–1190.
23. H. Yuan, T. Nuligonda, H. Gao, C.-H. Tung and Z. Xu, Copper-catalyzed carbene insertion into the sulfur–sulfur bond of benzenesulfonothioate, Org. Chem. Front., 2018, 5, 1371–1374.
24. A. A. Danopoulos, T. Simler and P. Braunstein, N-Heterocyclic, Carbene Complexes of Copper, Nickel, and Cobalt, Chem. Rev., 2019, 119, 3730–3961.
25. F.-L. Hong, Y.-B. Chen, S.-H. Ye, G.-Y. Zhu, X.-Q. Zhu, X. Lu, R.-S. Liu and L.-W. Ye, Copper-Catalyzed Asymmetric Reaction of Alkenyl Diynes with Styrenes by Formal [3+2] Cycloaddition via Cu-Containing All-Carbon 1,3-Dipoles: Access to Chiral Pyrrole-Fused Bridged [2.2.1] Skeletons, J. Am. Chem. Soc., 2020, 142, 7618–7626.
26. P. Yang, T. Brockmann and X.-F. Wu, Copper-catalyzed strain-enabled reaction of bicyclobutanes with diazo compounds to synthesize penta-1,4-dienes, Chem. Commun., 2024, 60, 13048–13050.
27. J. Jiang, J. Liu, L. Yang, Y. Shao, J. Cheng, X. Bao and X. Wan, Cu-Based Carbene Involved in a Radical Process: A New Crossover Reaction to Construct γ-Peroxy Ester and 1,4-Dicarbonyl Compounds, Chem. Commun., 2015, 51, 14728–14731.
28. (a) J. Fang, W.-L. Dong, G.-Q. Xu and P.-F. Xu, Photocatalyzed Metal-Free Alkylheteroarylation of UnactivatedOlefins via Direct Acidic C(sp³)−H Bond Activation, Org. Lett., 2019, 21, 4480–4485; (b) F.-S. He, S. Ye and J. Wu, Recent Advances in Pyridinium Salts as Radical Reservoirs inOrganic Synthesis, ACS Catal., 2019, 9, 8943–8960; (c) Y. Xu, H. Luo, D. Hu, L. Gao, F. Yu, S. Li, C.-Y. Li, Y.-L. Li, M. Gao and L. Lin, Photoinduced Copper-Catalyzed Radical Mizoroki–Heck Reaction with Unactivated Alkyl Iodide, Org. Lett., 2025, 27, 3566–3570.
29. (a) Z. Zong, W. Wang, X. Bai, H. Xi and Z. P. Li, Manganese-Catalyzed Alkyl-Heck-Type Reaction via Oxidative Decarbonylation of Aldehydes, Asian J. Org. Chem., 2015, 4, 622–625; (b) X.-H. Ouyang, R.-J. Song, B. Liu and J.-H. Li, Metal-Free Oxidative Decarbonylative Hydroalkylation of Alkynes with Secondary and Tertiary Alkyl Aldehydes, Adv. Synth. Catal., 2016, 358, 1903–1909; (c) C. Pan, Y. Chen, S. Song, L. Li and J.-T. Yu, Metal-Free Cascade Oxidative Decarbonylative Alkylation/Arylation of Alkynoates with Alphatic Aldehydes, J. Org. Chem., 2016, 81, 12065–12069.
30. C.-S. Wu, R. Li, Q.-Q. Wang and L. Yang, Fe-Catalyzed decarbonylative alkylation–peroxidation of alkenes with aliphatic aldehydes and hydroperoxide under mild conditions, Green Chem., 2019, 21, 269–274.
31. (a) H. T. Dang, G. C. Haug, V. T. Nguyen, N. T. H. Vuong, V. D. Nguyen, H. D. Arman and O. V. Larionov, Acridine Photocatalysis: Insights into the Mechanism and Development of a Dual-Catalytic Direct Decarboxylative Conjugate Addition, ACS Catal., 2020, 10, 11448–11457; (b) D. M. Kitcatt, S. Nicolle and A.-L. Lee, Direct decarboxylative Giese reactions, Chem. Soc. Rev., 2022, 51, 1415–1453; (c) A. Rahaman, S. S. Chauhan and S. Bhadra, Recent advances in catalytic decarboxylative transformations of carboxylic acid groups attached to a non-aromatic sp² or sp carbon, Org. Biomol. Chem., 2023, 21, 5691–5724.
32. Q. Huang, C. Lou, L. Lv and Z. Li, Visible-light-induced synthesis of organic peroxides via decarboxylative couplings of carboxylic acids, alkenes and tert-butyl hydroperoxide, Chem. Res. Chin. Univ., 2024, 40, 863–873.
33. (a) T. R. McDonald, L. R. Mills, M. S. West and S. A. L. Rousseaux, Selective Carbon–Carbon Bond Cleavage of Cyclopropanols, Chem. Rev., 2021, 121, 3–79; (b) N. Jha, P. Mishra and M. Kapur, Strained cycloalkanols in C–C bond formation reactions: a boon in disguise, Org. Chem. Front., 2023, 10, 4941–4971.
34. C. Lou, X. Wang, L. Lv and Z. Li, Iron-Catalyzed Ring-Opening Reactions of Cyclopropanols with Alkenes and TBHP: Synthesis of 5-Oxo Peroxides, Org. Lett., 2021, 23, 7608–7612.
35. C. Lou, L. Lv and Z. Li, Fe-catalyzed ring-opening reactions of siloxy cyclopropanes with alkenes and TBHP: Synthesis of 4-ester peroxides, J. Organomet. Chem., 2022, 977, 122467.
36. (a) S. Biswas, D. Das, K. Pal, P. Chandu and D. Sureshkumar, Photocatalyzed Direct C(sp³)–H Alkenylation of Unactivated Alkanes via Tandem C–C Activation of Cyclopropenes, J. Org. Chem., 2024, 89, 12421–12431; (b) J.-L. Tu, Y. Zhu, P. Li and B. Huang, Visible-light induced direct C(sp³)–H functionalization: recent advances and future prospects, Org. Chem. Front., 2024, 11, 5278–5305.
37. A. Banerjee, S. K. Santra, N. Khatun, W. Ali and B. K. Patel, Oxidant controlled regioselective mono- and difunctionalizations of coumarins, Chem. Commun., 2015, 51, 15422–15425.
38. A. Banerjee, S. K. Santra, A. Mishra, N. Khatun and B. K. Patel, Copper(I) Promoted Cycloalkylation–Peroxidation of Unactivated Alkenes via sp³ C−H Functionalisation, Org. Biomol. Chem., 2015, 13, 1307–1312.
39. Y. Lan, C. Yang, Y.-H. Xu and T.-P. Loh, Direct coupling of sp³ carbon of alkanes with α,β-unsaturated carbonyl compounds using a copper/hydroperoxide system, Org. Chem. Front., 2017, 4, 1411–1415.
40. (a) X. Ma and Q. Song, Recent progress on selective deconstructive modes of halodifluoromethyl and trifluoromethyl-containing reagents, Chem. Soc. Rev., 2020, 49, 9197–9219; (b) Y. Zhu, J. Han, J. Wang, N. Shibata, M. Sodeoka, V. A. Soloshonok, J. A. S. Coelho and F. D. Toste, Modern Approaches for Asymmetric Construction of Carbon–Fluorine Quaternary Stereogenic Centers: Synthetic Challenges and Pharmaceutical Needs, Chem. Rev., 2018, 118, 3887–3964.
41. (a) A. Adachi, T. Hashimoto, K. Aikawa, K. Nozaki and T. Okazoe, Difluorination of heterobenzylic C–H bonds with N-fluoro-N-(fluorosulfonyl)carbamate (NFC), Org. Chem. Front., 2023, 10, 5362–5368; (b) X. Chen, J. Jiang, X.-J. Huang and W.-M. He, Electrochemical oxidative radical cascade reactions for the synthesis of difluoromethylated benzoxazines, Org. Chem. Front., 2023, 10, 3898–3902.
42. E. Shi, J. Liu, C. Liu, Y. Shao, H. Wang, Y. Lv, M. Ji, X. Bao and X. Wan, Difunctionalization of Styrenes with Perfluoroalkyl and tert-Butylperoxy Radicals: Room Temperature Synthesis of (1-(tert-Butylperoxy)-2-perfluoroalkyl)-ethylbenzene, J. Org. Chem., 2016, 81, 5878–5885.
43. Z. Wang, J.-H. Lin and J.-C. Xiao, Photocatalytic Keto- and Amino-Trifluoromethylation of Alkenes, Org. Lett., 2024, 26, 1980–1984.
44. (a) H. Xiao, Z. Zhang, Y. Fang, L. Zhu and C. Li, Radical trifluoromethylation, Chem. Soc. Rev., 2021, 50, 6308–6319; (b) R. Shaw, N. Sihag, H. Bhartiya and M. R. Yadav, Harnessing photocatalytic and electrochemical approaches for C–H bond trifluoromethylation and fluoroalkylation, Org. Chem. Front., 2024, 11, 954–1014.
45. H.-Y. Zhang, C. Ge, J. Zhao and Y. Zhang, Cobalt-Catalyzed Trifluoromethylation−Peroxidation of Unactivated Alkenes with Sodium Trifluoromethanesulfinate and Hydroperoxide, Org. Lett., 2017, 19, 5260–5263.
46. B. Qi, T. Zhang, M. Li, C. He and C. Duan, Highly Shape- and Regio-selective Peroxy–trifluoromethylation of Styrene by Metal-Organic Framework Cu₃(BTC)₂, Catal. Sci. Technol., 2017, 7, 5872–5881.
47. Q. Huang, C. Lou, L. Lv and Z. Li, Photoinduced fluoroalkylation–peroxidation of alkenes enabled by ligand-to-iron charge transfer mediated decarboxylation, Chem. Commun., 2024, 60, 12389–12392.
48. Q. Jiang, Y. Liang, Y. Zhang and X. Zhao, Chalcogenide-Catalyzed Intermolecular Electrophilic Thio- and Halofunctionalization of gem-Difluoroalkenes: Construction of Diverse Difluoroalkyl Sulfides and Halides, Org. Lett., 2020, 22, 7581–7587.
49. L. Pang, Q. Sun, Z. Huang, S. Li and Q. Li, Cobalt-Tertiary Amine Mediated Peroxy-trifluoromethylation and -halodifluoromethylation of Alkenes with CF₂XBr (X = F, Cl, Br) and tert-Butyl Hydroperoxide, Synthesis, 2022, 2193–2204.
50. L. Wang, Y. Ma, Y. Jiang, L. Lv and Z. Li, A Mn-catalyzed remote C(sp³)–H bond peroxidation triggered by radical trifluoromethylation of unactivated alkenes, Chem. Commun., 2021, 57, 7846–7849.
51. W. Zhang, P. Guo, Y. Zhang, Q. Zhou, Y. Sun and H. Xu, Application of Difluoromethyl Isosteres in the Design of Pesticide Active Molecules, J. Agric. Food Chem., 2024, 72, 21344–21363.
52. J. B. I. Sap, C. F. Meyer, N. J. W. Straathof, N. Iwumene, C. W. am Ende, A. A. Trabanco and V. Gouverneur, Late-stage difluoromethylation: concepts, developments and perspective, Chem. Soc. Rev., 2021, 50, 8214–8247.
53. F. Liu, L. Lv, Y. Ma and Z. Li, Copper-Catalyzed Radical Difluoromethylation–Peroxidation of Alkenes: Synthesis of β-Difluoromethyl Peroxides, Asian J. Org. Chem., 2022, 11, e202200393.
54. Y. Chen, L. Li, Y. Ma and Z. Li, Cobalt-Catalyzed Three-Component Difluoroalkylation−Peroxidation of Alkenes, J. Org. Chem., 2019, 84, 5328–5338.
55. G. Huang, J.-T. Yu and C. Pan, Recent Advances in Polychloromethylation Reactions, Adv. Synth. Catal., 2021, 363, 305–327.
56. C. Chen, H. Tan, B. Liu, C. Yue and W. Liu, ATRA-like alkylation–peroxidation of alkenes with trichloromethyl derivatives by the combination of ^tBuOOH and NEt₃, Org. Chem. Front., 2018, 5, 3143–3147.
57. R. K. Neff, Y.-L. Su, S. Liu, M. Rosado, X. Zhang and M. P. Doyle, Generation of Halomethyl Radicals by Halogen Atom Abstraction and Their Addition Reactions with Alkenes, J. Am. Chem. Soc., 2019, 141, 16643–16650.
58. J.-L. Panayides, D. L. Riley, F. Hasenmaile and W. A. L. van Otterlo, The role of silicon in drug discovery: a review, RSC Med. Chem., 2024, 15, 3286–3344.
59. L. Chen, S. Zhang, Y. Duan, X. Song, M. Chang, W. Feng and Y. Chen, Chem. Soc. Rev., 2024, 53, 1167–1315.
60. Y. Lan, X.-H. Chang, P. Fan, C.-C. Shan, Z.-B. Liu, T.-P. Loh and Y.-H. Xu, Copper-Catalyzed Silylperoxidation Reaction of α,β-Unsaturated Ketones, Esters, Amides, and Conjugated Enynes, ACS Catal., 2017, 7, 7120–7125.
61. S. Lu, T. Tian, R. Xu and Z. Li, Fe- or Co-catalyzed Silylation–Peroxidation of Alkenes with Hydrosilanes and T-Hydro, Tetrahedron Lett., 2018, 59, 2604–2606.
62. (a) Q.-H. Xu and B. Xiao, Organogermanium(IV) compounds in photo-induced radical reactions, Org. Chem. Front., 2022, 9, 7016–7027; (b) J. Ke, C. D. Chen, L.-Q. Ren, B. Zu, B. Li and C. He, Transition-metal-catalyzed C–Ge coupling reactions, Org. Chem. Front., 2024, 11, 6558–6572.
63. J. Cao, Y. Liu, Z. Wang and L. Liu, Arylgermylation of alkenes by a cooperative photoactivation and hydrogen atom transfer strategy, Org. Chem. Front., 2024, 11, 7098–7106.
64. Y. Luo, B. Xu, L. Lv and Z. Li, Copper-Catalyzed Three-Component Germyl Peroxidation of Alkenes, Org. Lett., 2022, 24, 2425–2430.
65. J. Kaur, M. Saxena and N. Rishi, An Overview of Recent Advances in Biomedical Applications of Click Chemistry, Bioconjugate Chem., 2021, 32, 1455–1471.
66. (a) A. K. Agrahari, P. Bose, M. K. Jaiswal, S. Rajkhowa, A. S. Singh, S. Hotha, N. Mishra and V. K. Tiwari, Cu(I)-Catalyzed Click Chemistry in Glycoscience and Their Diverse Applications, Chem. Rev., 2021, 121, 7638–7956; (b) L. Zhu and R. Kinjo, Reactions of main group compounds with azides forming organic nitrogen-containing species, Chem. Soc. Rev., 2023, 52, 5563–5606; (c) H. Tanimoto and T. Tomohiro, Spot the difference in reactivity: a comprehensive review of site-selective multicomponent conjugation exploiting multi-azide compounds, Chem. Commun., 2024, 60, 12062–12100.
67. P. Sivaguru, Y. Ning and X. Bi, New Strategies for the Synthesis of Aliphatic Azides, Chem. Rev., 2021, 121, 4253–4307.
68. Y. Chen, T. Tian and Z. Li, Mn-Catalyzed Azidation–Peroxidation of Alkenes, Org. Chem. Front., 2019, 6, 632–636.
69. J. Huang, F. Ding, P. Rojsitthisak, F.-S. He and J. Wu, Recent advances in nitro-involved radical reactions, Org. Chem. Front., 2020, 7, 2873–2898.
70. Y. Chen, Y. Ma, L. Li, H. Jiang and Z. Li, Nitration−Peroxidation of Alkenes: A Selective Approach to β-Peroxyl Nitroalkanes, Org. Lett., 2019, 21, 1480–1483.
71. W. Liu, C. Chen, P. Zhou and H. Tan, Preparation of 1,2-Oxazetidines from Styrenes and Arylamines via a Peroxide-Mediated [2+1+1] Cycloaddition Reaction, Org. Lett., 2017, 19, 5830–5832.
72. (a) S. Mitra, S. Mukherjee, S. K. Sen and A. Hajra, Environmentally benign synthesis and antimicrobial study of novel chalcogenophosphates, Bioorg. Med. Chem. Lett., 2014, 24, 2198–2201; (b) S. Shi, J. Chen, S. Zhuo, Z. Wu, M. Fang, G. Tang and Y. Zhao, Iodide-Catalyzed Phosphorothiolation of Heteroarenes Using P(O)H Compounds and Elemental Sulfur, Adv. Synth. Catal., 2019, 361, 3210–3216.
73. (a) W. Deng, Y. Hu, J. Hu, X. Li, Y. Li and Y. Huang, Electrochemically induced Markovnikov-type selective hydro/deuterophosphonylation of electron-rich alkenes, Chem. Commun., 2022, 58, 12094–12097; (b) X.-H. Yu, L.-Q. Lu, Z.-H. Zhang, D.-Q. Shi and W.-J. Xiao, Cobalt-catalyzed asymmetric phospha-Michael reaction of diarylphosphine oxides for the synthesis of chiral organophosphorus compounds, Org. Chem. Front., 2023, 10, 133–139.
74. A. K. Ghosh, S. Neogi, P. Ghosh and A. Hajra, Synergistic Photoredox and Iron(II) Catalyzed Carbophosphorothiolation of Vinyl Arenes, Adv. Synth. Catal., 2023, 365, 2271–2278.
75. Y. Chen, Y. Chen, S. Lu and Z. Li, Copper-catalyzed three-component phosphorylation–peroxidation of alkenes, Org. Chem. Front., 2018, 5, 972–976.
76. J. Shen, B. Xiao, Y. Hou, X. Wang, G.-Z. Li, J.-C. Chen, W.-L. Wang, J.-B. Cheng, B. Yang and S.-D. Yang, Cobalt(II)-Catalyzed Bisfunctionalization of Alkenes with Diarylphosphine Oxide and Peroxide, Adv. Synth. Catal., 2019, 361, 5198–5209.
77. J. Pan, Y. Feng, L. Lv and Z. Li, Photoinduced transition-metal-free chemodivergent phosphorylation–peroxidation and oxyphosphorylation of alkenes, Adv. Synth. Catal., 2024, 366, 3860–3867.
78. (a) V. A. Vil’, G. dos Passos Gomes, M. V. Ekimova, K. A. Lyssenko, M. A. Syroeshkin, G. I. Nikishin, I. V. Alabugin and A. O. Terent'ev, Five Roads That Converge at the Cyclic Peroxy-Criegee Intermediates: BF₃-Catalyzed Synthesis of β-Hydroperoxy-β-peroxylactones, J. Org. Chem., 2018, 83, 13427–13445; (b) V. A. Vil’, Y. A. Barsegyan, L. Kuhn, M. V. Ekimova, E. A. Semenov, A. A. Korlyukov, A. O. Terent'ev and I. V. Alabugin, Chem. Sci., 2020, 11, 5313–5322.
79. G. An, W. Zhou, G. Zhang, H. Sun, J. Han and Y. Pan, Palladium-Catalyzed Tandem Diperoxidation/C–H Activation Resulting in Diperoxy-oxindole in Air, Org. Lett., 2010, 12, 4482–4485.
80. M. Mondal and U. Bora, Recent advances in manganese(III) acetate mediated organic synthesis, RSC Adv., 2013, 3, 18716–18754.
81. X.-M. Xu, S. Chen, Q. Liu, X. Cao, Z. Zhao, J. Chen, Y. Yao, C. Yang and K. Sun, Manganese(III)-Mediated Selective Cascade Phosphorylation-Cyclization of Tertiary Enamides for the Synthesis of Multi-Substituted 3-Phosphorylpyridines, J. Org. Chem., 2025, 90, 1434–1446.
82. J. Wang, Y. Zhang, Y. Zhou, X. Gu, B. Han, X. Ding and S. Liang, Manganese(III) acetate in organic synthesis: a review of the past decade, Org. Chem. Front., 2024, 11, 6850–6917.
83. A. O. Terent'ev, M. Y. Sharipov, I. B. Krylov, D. V. Gaidarenko and G. I. Nikishin, Manganese triacetate as an efficient catalyst for bisperoxidation of Styrenes, Org. Biomol. Chem., 2015, 13, 1439–1445.
84. A. S. Ubale, M. B. Chaudhari, M. A. Shaikh and B. Gnanaprakasam, Manganese-Catalyzed Synthesis of Quaternary Peroxides: Application in Catalytic Deperoxidation and Rearrangement Reactions, J. Org. Chem., 2020, 85, 10488–10503.
85. X. Gao, J. Lin, L. Zhang, X. Lou, G. Guo, N. Peng, H. Xu and Y. Liu, Iodine-Initiated Dioxygenation of Aryl Alkenes Using tert-Butylhydroperoxides and Water: A Route to Vicinal Diols and Bisperoxides, J. Org. Chem., 2021, 86, 15469–15480.
86. I. B. Krylov, S. A. Paveliev, B. N. Shelimov, B. V. Lokshin, I. A. Garbuzova, V. A. Tafeenko, V. V. Chernyshev, A. S. Budnikov, G. I. Nikishin and A. O. Terent'ev, Selective cross-dehydrogenative C–O coupling of N-hydroxy compounds with pyrazolones. Introduction of the diacetyliminoxyl radical into the practice of organic synthesis, Org. Chem. Front., 2017, 4, 1947–1957.
87. S. A. Paveliev, O. O. Segida, A. Dvoretskiy, M. M. Dzyunov, U. V. Fedorova and A. O. Terent'ev, Electrifying Phthalimide-N-Oxyl (PINO) Radical Chemistry: Anodically Induced Dioxygenation of Vinyl Arenes with N-Hydroxyphthalimide, J. Org. Chem., 2021, 86, 18107–18116.
88. X.-F. Xia, S.-L. Zhu, Z. Gu, H. Wang, W. Li, X. Liu and Y.-M. Liang, Catalyst-Controlled Dioxygenation of Olefins: An Approach to Peroxides, Alcohols, and Ketones, J. Org. Chem., 2015, 80, 5572–5580.
89. H. Xu, X. Lou, J. Xie, Z. Qin, H. He and X. Gao, Regioselective Approach to β-Peroxyl Alcohols and Ethers from Alkenes, J. Org. Chem., 2022, 87, 9957–9968.
90. A. Kumar, G. N. Khatun and R. A. Fernandes, TBAI-Catalyzed Regioselective Hydroxyperoxidation of 1-Aryl/Alkyl-1,3-dienes, Org. Lett., 2023, 25, 4313–4317.
91. A. García-Domínguez, S. Müller and C. Nevado, Nickel-Catalyzed Intermolecular Carbosulfonylation of Alkynes via Sulfonyl Radicals, Angew. Chem., Int. Ed., 2017, 56, 9949–9952.
92. B.-C. Qian, C.-Z. Zhu and G.-B. Shen, The Application of Sulfonyl Hydrazides in Electrosynthesis: A Review of Recent Studies, ACS Omega, 2022, 7, 39531–39561.
93. R. Yi, L.-T. Wang, J. Chen, W.-T. Wei and K.-W. Lei, Applications of sulfonyl hydrazides in radical cyclization of alkenes, Org. Biomol. Chem., 2023, 21, 5906–5918.
94. R. Xu and Z. Li, Ag-catalyzed Sulfonylation–Peroxidation of Alkenes with Sulfonyl hydrazides and T-Hydro, Tetrahedron Lett., 2018, 59, 3942–3945.
95. (a) M. V. K. Rao, S. Kareem, S. R. Vali and B. V. S. Reddy, Recent advances in metal directed C–H amidation/amination using sulfonyl azides and phosphoryl azides, Org. Biomol. Chem., 2023, 21, 8426–8462; (b) D. Dam, J. Schoenmakers, E. Bouwman and J. D. C. Codée, Photocatalytic Nitrene Radical Anion Generation from Sulfonyl Azides for Intermolecular Aziridination of Unactivated Alkenes, J. Org. Chem., 2025, 90, 6577–6583.
96. (a) S. Zhu, A. Pathigoolla, G. Lowe, D. A. Walsh, M. Cooper, W. Lewis and H. W. Lam, Sulfonylative and Azidosulfonylative Cyclizations by Visible-Light-Photosensitization of Sulfonyl Azides in THF, Chem. – Eur. J., 2017, 23, 17598–17604; (b) F. Chen, Y. Shao, M. Li, C. Yang, S.-J. Su, H. Jiang, Z. Ke and W. Zeng, Photocatalyzed Cycloaromatization of Vinylsilanes with Arylsulfonylazides, Nat. Commun., 2021, 12, 3304.
97. R. Chen, Y. Tang, X. He, K.-K. Wang, L. Ding and L. Liu, Catalyst-Controlled Direct Oxysulfonylation of Alkenes by Using Sulfonylazides as the Sulfonyl Radical, Org. Lett., 2023, 25, 5454–5458.
98. (a) X. Du, J.-S. Zhen, X.-H. Xu, H. Yuan, Y.-H. Li, Y. Zheng, C. Xue and Y. Luo, Hydrosulfonylation of Alkenes with Sulfonyl Imines via Ir/Cu Dual Photoredox Catalysis, Org. Lett., 2022, 24, 3944–3949; (b) J. E. Erchinger, R. Hoogesteger, R. Laskar, S. Dutta, C. Hümpel, D. Rana, C. G. Daniliuc and F. Glorius, EnT-Mediated N−S Bond Homolysis of a Bifunctional Reagent Leading to Aliphatic Sulfonyl Fluorides, J. Am. Chem. Soc., 2023, 145, 2364–2374.
99. Y. Feng, S. Chen, L. Lv, I. A. Yaremenko, A. O. Terent'ev and Z. Li, Photocatalytic Sulfonyl Peroxidation of Alkenes via Deamination of N-Sulfonyl Ketimines, Org. Lett., 2024, 26, 1920–1925.
100. Y. Feng, L. Lv and Z. Li, Photo-Induced Sulfonylation/Trifluoromethylation-Peroxidation of Alkenes via EnT-Mediated N-S Bond Homolysis of N-Sulfonyl Ketimines, Asian J. Org. Chem., 2024, 13, e202400384.
101. (a) S. Barata-Vallejo, S. Bonesi and A. Postigo, Late stage trifluoromethylthiolation strategies for organic compounds, Org. Biomol. Chem., 2016, 14, 7150–7182; (b) Y. Li, J. Fu, L. He, W. Li and V. Esmail, Recent advances in intermolecular 1,2-difunctionalization of alkenes involving trifluoromethylthiolation, RSC Adv., 2021, 11, 24474–24486.
102. A. Li, X. Wang, Y. Liu, D. Hao, X. Zhao and K. Lu, Copper-catalyzed ring-opening trifluoromethylthiolation/trifluoromethylselenolation of cyclopropanols with TsSCF₃ or Se-(trifluoromethyl) 4-methoxybenzenesulfonoselenoate, Org. Biomol. Chem., 2023, 21, 3675–3683.
103. Y. Chen, Y. Ma, L. Li, M. Cui and Z. Li, Copper-Catalyzed Trifluoromethylthiolation–Peroxidation of Alkenes and Allenes, Org. Chem. Front., 2020, 7, 1837–1844.
104. L. Wang, S. Shu, L. Lv and Z. Li, Copper-catalyzed remote trifluoromethylthiolation–peroxidation of unactivated alkenes via 1,5-hydrogen atom transfer, Tetrahedron Lett., 2022, 104, 154029.
105. (a) B. M. Monks and S. P. Cook, Palladium-Catalyzed Alkyne Insertion/Suzuki Reaction of Alkyl Iodides, J. Am. Chem. Soc., 2012, 134, 15297–15300; (b) I. Scheipers, E. Koch and A. Studer, Stereoselective Palladium-Catalyzed Decarboxylative γ-Arylation of Acyclic β,γ-Unsaturated Carboxylic Acids, Org. Lett., 2017, 19, 1741–1743.
106. H. Wang, C. Chen, W. Liu and Z. Zhu, Difunctionalization of alkenes with iodine and tert-butyl hydroperoxide (TBHP) at room temperature for the synthesis of 1-(tert-butylperoxy)-2-iodoethanes, Beilstein J. Org. Chem., 2017, 13, 2023–2027.
107. X. Gao, H. Yang, C. Cheng, Q. Jia, F. Gao, H. Chen, Q. Cai and C. Wang, Iodide Reagents Controlled the Reaction Pathway of Iodoperoxidation of alkenes: A High Regioselectivity Synthesis of α- and β-iodoperoxidates under Solvent-free Conditions, Green Chem., 2018, 20, 2225–2230.
108. K. Zhang, C. Liu, D. Abdukerem, Z. Mao, W. Zhu, K. Xia and A. Abdukader, Synthesis of α/β-Aromatic Peroxy Thiols Mediated by Iodine Source, J. Org. Chem., 2024, 89, 3049–3057.
109. G. A. Coppola, S. Pillitteri, E. V. Van der Eycken, S.-L. You and U. K. Sharma, Multicomponent reactions and photo/electrochemistry join forces: atom economy meets energy efficiency, Chem. Soc. Rev., 2022, 51, 2313–2382.
110. (a) S. Garbarino, D. Ravelli, S. Protti and A. Basso, Photoinduced Multicomponent Reactions, Angew. Chem., Int. Ed., 2016, 55, 15476–15484; (b) J. Li, J. Cui, H. Guo, J. Yang and W. Huan, The road to green efficiency: exploration of multicomponent reactions from transition metal catalysis to no catalyst conditions, React. Chem. Eng., 2025, 10, 500–510.
111. (a) S.-Z. Cai, D. Ge, L.-W. Sun, W. Rao, X. Wang, Z.-L. Shen and X.-Q. Chu, Three-Component Heteroannulation for Tetrasubstituted Furan Construction Enabled by Successive Defluorination and Dual Sulfonylation Relay, Green Chem., 2021, 23, 935–941; (b) X.-Q. Chu, S.-Z. Cai, J.-W. Chen, Z.-L. Yu, M. Ma, P. J. Walsh and Z.-L. Shen, Defluorophosphorylation of fluoroalkyl peroxides for the synthesis of highly substituted furans, Green Chem., 2023, 25, 2000–2010.
112. Y.-Y. Ren, W.-J. Ji, C. Zhang, D. Ge, M. Ma, Z.-L. Shen and X.-Q. Chu, 1,2-Dichloroethane-Assisted Defluorinative Ring-Opening Reaction of DABCO and Polyfluoroalkyl Peroxides: Synthesis of Fluorinated N-Ethyl Piperazines, Chin. J. Chem., 2025, 43, 378–384.
113. P. Du, H. Li, Y. Wang, J. Cheng and X. Wan, Radical−Polar Crossover Reactions: Oxidative Coupling of 1,3-Dioxolanes with Electron-Deficient Alkenes and Vinylarenes Based on a Radical Addition and Kornblum−DeLaMare Rearrangement, Org. Lett., 2014, 16, 6350–6353.
114. C.-S. Wu, R.-X. Liu, D.-Y. Ma, C.-P. Luo and L. Yang, Four-Component Radical Dual Difunctionalization (RDD) of Two Different Alkenes with Aldehydes and tert-Butyl Hydroperoxide (TBHP): An Easy Access to β,δ-Functionalized Ketones, Org. Lett., 2019, 21, 6117–6121.
115. J. Zhang, J. Jiang, D. Xu, Q. Luo, H. Wang, J. Chen, H. Li, Y. Wang and X. Wan, Interception of Cobalt-Based Carbene Radicals with α-Aminoalkyl Radicals: ATandem Reaction for the Construction of b-Ester-g-amino Ketones, Angew. Chem., Int. Ed., 2015, 54, 1231–1235.
116. J. Ling, J. Zhang, Y. Zhao, Y. Xu, H. Wang, Y. Lv, M. Ji, L. Ma, M. Ma and X. Wan, A Cu-Catalyzed Four-Component Cascade Reaction to Construct β-Ester-γ-Amino Ketones, Org. Biomol. Chem., 2016, 14, 5310–5316.
117. F. Li, S. Zhu and R. M. Koenigs, Photocatalytic 1,2-oxo-alkylation reaction of styrenes with diazoacetates, Chem. Commun., 2022, 58, 7526–7529.
118. G. J. Martis and S. L. Gaonkar, Advances in isoxazole chemistry and their role in drug discovery, RSC Adv., 2025, 15, 8213–8243.
119. (a) S. Das and K. Chanda, An overview of metal-free synthetic routes to isoxazoles: the privileged scaffold, RSC Adv., 2021, 11, 32680–32705; (b) S. D. L. Holman, A. G. Wills, N. J. Fazakerley, D. L. Poole, D. M. Coe, L. A. Berlouis and M. Reid, Electrochemical Synthesis of Isoxazolines: Method and Mechanism, Chem. – Eur. J., 2022, 28, e202103728; (c) Y. Li, Y. Zhang, J. Wang, D. Xia, M. Zhuo, L. Zhu, D. Li, S.-F. Ni, Y. Zhu and W.-D. Zhang, Visible-Light-Mediated Three-Component Strategy for the Synthesis of Isoxazolines and Isoxazoles, Org. Lett., 2024, 26, 3130–3134.
120. Y. Chen, L. Li, X. He and Z. Li, Four-Component Reactions for the Synthesis of Perfluoroalkyl Isoxazoles, ACS Catal., 2019, 9, 9098–9102.
121. C. Liu, E. Shi, F. Xu, Q. Luo, H. Wang, J. Chen and X. Wan, Combination of Fluoroalkylation and Kornblum–DeLaMare Reaction: A New Strategy for the Construction of (Z)-β-Perfluoroalkyl Enaminones, Chem. Commun., 2015, 51, 1214–1217.
122. J. Zhang, P. Zhou, A. Yin, S. Zhang and W. Liu, Synthetic Route to Enaminones via Metal-Free Four-Component Sequential Reactions of Aryl Olefins with CHCl₃, Et₃N, and TBHP, J. Org. Chem., 2021, 86, 8980–8986.
123. D. Canestrari, S. Lancianesi, E. Badiola, C. Strinna, H. Ibrahim and M. F. A. Adamo, Desulfurative Chlorination of Alkyl Phenyl Sulfides, Org. Lett., 2017, 19, 918–921.
124. Z. Chen, B. Zhou, H. Cai, W. Zhu and X. Zou, Simple and efficient methods for selective preparation of α-mono or α,α-dichloro ketones and β-ketoesters by using DCDMH, Green Chem., 2009, 11, 275–278.
125. J.-C. Xiang, J.-W. Wang, P. Yuan, J.-T. Ma, A.-X. Wu and Z.-X. Liao, Switching Over of the Chemoselectivity: I₂-DMSO-Enabled α,α-Dichlorination of Functionalized Methyl Ketones, J. Org. Chem., 2022, 87, 15101–15113.
126. M. Liu, B. Liu, Q. Wang, K. Feng, Y. Li, L. Liu and J. Tong, Metal-free synthesis of 1,3-dichloro-1,5-diarylpentan-5-ones via cascade oxidative radical addition of styrenes with CHCl₃, Org. Biomol. Chem., 2024, 22, 699–702.
127. F. Zhang, P. Du, J. Chen, H. Wang, Q. Luo and X. Wan, Co-Catalyzed Synthesis of 1,4-Dicarbonyl Compounds Using TBHP Oxidant, Org. Lett., 2014, 16, 1932–1935.
128. X.-W. Lan, N.-X. Wang, W. Zhang, J.-L. Wen, C.-B. Bai, Y. Xing and Y.-H. Li, Copper/Manganese Cocatalyzed Oxidative Coupling of Vinylarenes with Ketones, Org. Lett., 2015, 17, 4460–4463.
129. N. G. Turrini, R. C. Cioc, D. J. H. van der Niet, E. Ruijter, R. V. A. Orru, M. Hall and K. Faber, Biocatalytic access to nonracemic γ-oxo esters via stereoselective reduction using ene-reductases, Green Chem., 2017, 19, 511–518.
130. N. Kunitomo and T. Kano, Cu-Catalyzed Asymmetric Arylation of Enone Diesters with Arylboronic Acids, J. Org. Chem., 2024, 89, 11048–11052.
131. S. R. Chowdhury, I. U. Hoque and S. Maity, TBAI/TBHP-Promoted Generation of Malonyl Radicals: Oxidative Coupling with Styrenes Leads to γ-Keto Diesters, Chem. – Asian J., 2018, 13, 2824–2828.
132. B. A. Mir, S. Rajamanickam, P. Begum and B. K. Patel, Copper(I) Catalyzed Differential Peroxidation of Terminal and Internal Alkenes Using TBHP, Eur. J. Org. Chem., 2020, 252–261.
133. B. Kang, W. Li, H. Jiang and C. Qi, Metal-free four-component coupling of cyclic diarylchloronium salts, tetrahydrothiophene, amines and carbon dioxide, Chem. Commun., 2025, 61, 3395–3398.
134. Z. Yan, N.-X. Wang, L.-Y. Zhang, Y.-H. Wu, J.-L. Li, M.-Y. She, X.-W. Gao, K. Feng and Y. Xing, The C(sp³)–H bond functionalization of thioethers with styrenes with insight into the mechanism, Org. Biomol. Chem., 2022, 20, 5845–5851.
135. X.-W. Lan, N.-X. Wang, C.-B. Bai, C.-L. Lan, T. Zhang, S.-L. Chen and Y. Xing, Unactivated C(sp³)−H Bond Functionalization of Alkyl Nitriles with Vinylarenes and Mechanistic Studies, Org. Lett., 2016, 18, 5986–5989.
136. S. Chand, S. Kumar, A. K. Sharma and K. N. Singh, Metal-Free Decarboxylative Cyanomethylation of β-Aryl/Heteroaryl Substituted α,β-Unsaturated Carboxylic Acids to γ-Ketonitriles, Org. Lett., 2024, 26, 10051–10055.
137. S. Feng, J. Li, F. He, T. Li, H. Li, X. Wang, X. Xie and X. She, Copper-Catalyzed Radical Coupling/Fragmentation Reaction: Efficient Access to, β-Oxophosphine Oxides, Org. Chem. Front., 2019, 6, 946–951.
138. (a) Q. P. Ke, B. Y. Zhang, B. L. Hu, Y. X. Jin and G. Z. Lu, A Transition-Metal-Free, One-Pot Procedure for the Synthesis of α,β-Epoxy Ketones by Oxidative Coupling of Alkenes and Aldehydes by Base Catalysis, Chem. Commun., 2015, 51, 1012–1015; (b) V. Ashokkumar and A. Siva, One-pot synthesis of α,β-epoxy ketones through domino reaction between alkenes and aldehydes catalyzed by proline based chiral organocatalysts, Org. Biomol. Chem., 2017, 15, 2551–2561; (c) J. Hu, F. F. Xia, F. L. Yang, J. S. Weng, P. F. Yao, C. Z. Zheng, C. J. Zhu, T. D. Tang and W. Q. Fu, Design and synthesis of bi-functional Cocontaining zeolite ETS-10 catalyst with high activity in the oxidative coupling of alkenes with aldehydes for preparing α,β-epoxy ketones, RSC Adv., 2017, 7, 41204–41209.
139. W.-T. Wei, X.-H. Yang, H.-B. Li and J.-H. Li, Oxidative Coupling of Alkenes with Aldehydes and Hydroperoxides: One-Pot Synthesis of 2,3-Epoxy Ketones, Adv. Synth. Catal., 2015, 357, 59–63.
140. J. Li and D. Z. Wang, Visible-Light-Promoted Photoredox Syntheses of α,β-Epoxy Ketones from Styrenes and Benzaldehydes under Alkaline Conditions, Org. Lett., 2015, 19, 5260–5263.
141. A. Pal, B. Mondal, S. Sau, S. De and A. Thakur, Visible Light-Mediated Co(II) Catalyzed Synthesis of α,β-Epoxy Ketones by Oxidative Coupling of Alkenes and Aldehydes in Water, Org. Lett., 2024, 26, 8183–8187.
142. W.-T. Wei, H.-B. Li, R.-J. Song and J.-H. Li, Copper-Catalyzed Oxidative Oxyalkylation of Enol Ethers with α-Amino Carbonyl Compounds and Hydroperoxides, Chem. Commun., 2015, 51, 11325–11328.
143. J. Zhang, D. Xiao, H. Tan and W. Liu, Highly Selective Synthesis of 2-tert-Butoxy-1-Arylethanones via Copper(I)-Catalyzed Oxidation/tert-Butoxylation of Aryl Olefins with TBHP, J. Org. Chem., 2020, 85, 3929–3935.
144. C. Chen, Y. Li, Y. Pan, L. Duan and W. Liu, Oxidative radical addition–chlorination of alkenes to access 1,1-dichloroalkanes from simple reagents, Org. Chem. Front., 2019, 6, 2032–2036.
145. Y. Xiong, Y.-H. Chen, T. Li, J.-H. Xie and Q.-L. Zhou, Enantioselective Total Synthesis of (−)-Hamigeran F and Its Rearrangement Product, Org. Lett., 2022, 24, 5161–5165.
146. Y. Tanabe, E. Sato, N. Nakajima, A. Ohkubo, O. Ohno and K. Suenaga, Total Synthesis of Biselyngbyolide A, Org. Lett., 2014, 16, 2858–2861.
147. (a) Y. Jiao, M.-F. Chiou, Y. Li and H. Bao, Copper-Catalyzed Radical Acyl-Cyanation of Alkenes with Mechanistic Studies on the tert-Butoxy Radical, ACS Catal., 2019, 9, 5191–5197; (b) L. Ge, Y. Li and H. Bao, Iron-Catalyzed Radical Acyl-Azidation of Alkenes with Aldehydes: Synthesis of Unsymmetrical β-Azido Ketones, Org. Lett., 2019, 21, 256–260; (c) G. Zhang, L. Fu, P. Chen, J. Zou and G. Liu, Proton-Coupled Electron Transfer Enables Tandem Radical Relay for Asymmetric Copper-Catalyzed Phosphinoylcyanation of Styrenes, Org. Lett., 2019, 21, 5015–5020.
148. J. Zhang, W. Zhu, P. Zhou, C. Chen and W. Liu, Base-tuned selective 1,2-dichloromethylhydroxylation and 1,2-peroxyhydroxylation of 1,3-dienes via a tandem radical process, Chem. Commun., 2023, 59, 9481–9484.
149. J. Zhang, R. Su, W. Zhu, D. Xiao, P. Zhou, C. Chen and W. Liu, TMSCN-Promoted Difunctionalization of Alkenes for the Synthesis of Alcohol Derivatives, J. Org. Chem., 2024, 89, 12062–12070.
150. (a) O. A. Tomashenko and V. V. Grushin, Aromatic Trifluoromethylation with Metal Complexes, Chem. Rev., 2011, 111, 4475–4521; (b) C. Zhang, K. Yan, C. Fu, H. Peng, C. J. Hawker and A. K. Whittaker, Biological Utility of Fluorinated Compounds: from Materials Design to Molecular Imaging, Therapeutics and Environmental Remediation, Chem. Rev., 2022, 122, 167–208.
151. (a) W. K. Hagmann, The Many Roles for Fluorine in Medicinal Chemistry, J. Med. Chem., 2008, 51, 4359–4369; (b) Y. Yu, A. Liu, G. Dhawan, H. Mei, W. Zhang, K. Izawa, V. A. Soloshonoke and J. Han, Fluorine-containing pharmaceuticals approved by the FDA in 2020: Synthesis and biological activity, Chin. Chem. Lett., 2021, 32, 3342–3354.
152. J. Zhang, W. Zhu, R. Su, D. Xiao, P. Zhou, K. Chen, M. Zhang, C. Chen and W. Liu, TBHP-Mediated Hydroxyperfluoroalkylation of Alkenes with Perfluoroalkyl Iodides to Construct β-Perfluoroalkyl Alcohols, Adv. Synth. Catal., 2024, 366, 3572–3577.
153. J. Zhang, R. Su, P. Zhou, C. Chen and W. Liu, Amine-Promoted Three-Component Radical Selenofunctionalization for the Construction of β-Hydroxy Selenide Derivatives, J. Org. Chem., 2025, 90, 217–224.

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