Introduction

Organic peroxides are used in many different areas of human activities. The traditional and most developed field is the use of peroxides as initiators in the polymerization process for the production of a wide range of polymers . They are also applied as curing, hardening and crosslinking agents . Global demand for organic peroxides is expected to increase as the use of engineered plastics increases and production capacity is expanded. In addition, the need for polymers is expected to increase due to growing urbanization, expanding infrastructure projects and industrialization. A wide range of organic peroxide initiators is now available (Scheme 1) and this is continually being expanded to meet the changing requirements of the polymer industry.

Scheme 1: Organic peroxide initiators in polymer chemistry.

Discovery of artemisinin, which was highlighted with the Nobel Prize, initiated a new era in organic peroxide chemistry. A large number of synthetic antimalarial peroxides have been prepared . Further intensive research indicated that organic peroxides have antihelmintic, antiprotozoal, fungicidal, antiviral and other activities . Therefore, the development of efficient synthetic approaches to implement organic peroxide functionality in various substrates is a timely task.

From the synthetic point of view, organic peroxides are one of the best sources of oxygen atoms for a variety of oxygenation reactions . Hydroperoxides (especially TBHP), acyl peroxides, oxaziridines, and their derived species are often applied as terminal oxidants . The weakness of the O–O bond allows alkoxy radicals to form through homolysis or reduction . The generated alkoxy radicals provide an accessible tool for selective radical cascades, where a variety of functional groups can be functionalized for any synthetic need via HAT or β-scission with subsequent C-centered radical formation . Also, peroxy radicals play a key role in the chemistry of the Earth's lower atmosphere .

The traditional approaches to organic peroxide synthesis mainly include: nucleophilic addition or nucleophilic substitution with H2O2 or ROOH , autoxidation with O2, pericyclic reactions of unsaturated bonds with O3 or O2, and metal-catalyzed peroxidation (Isayama–Mukaiyama hydrosilylperoxidation , for example) . As the topic is broad, the present review mainly focused on radical and metal-catalyzed functionalization of C–H bonds or unsaturated bond with hydroperoxides (Scheme 2). The aim of this review is to cover recent studies in which alkylperoxy radicals have been used for the peroxidation of C(sp3) and C(sp2) sites, either by themselves or with the aid of metal complex catalysis, and to provide an insight into the reactivity of these species. The present work is divided into sections, according to the type of the substrate: C(sp3)–H substrates; aromatic systems; compounds with unsaturated C–C or C–Het bonds.

Scheme 2: Synthesis of organic peroxides.

The pioneer studies devoted to organic peroxide synthesis using radical cascades were reported by Kharasch . In recent decades, there has been an intensive growth of publications in this field due to the integration of traditional peroxide chemistry with modern advances in organo-, metal- and photoredox catalysis . These methods allow selectivity to be controlled despite the presence of the complex cocktail of radical species generated by hydroperoxides under redox or homolysis conditions.

The main challenge in selective radical peroxidation is the wide range of possible pathways involving radical intermediates from hydroperoxides under redox conditions (Scheme 3). The reactivity of O-centered radicals is less predictable and more diverse depending on radical structure and substrate pattern than the chemistry of C-centered radicals . Generally, peroxy radicals have a tendency to recombine with C-centered radicals and add to unsaturated bonds with the formation of new carbon–oxygen bonds. However, alkoxy radicals, which are always present in such systems, are involved not only in the formation of ROO radicals but also in hydrogen atom transfer (HAT) processes and β-scission , which can lead to side reactions.

Scheme 3: Richness of radical cascades with species formed from hydroperoxides in redox conditions.

Some aspects of the rich metal–peroxide redox chemistry have been discussed in previous reviews . Specifically, the radical functionalization of C–C bonds accessed through the transition metal-mediated reduction of organic peroxides has been covered in Kwon’s review . Cu-catalyzed oxygen atom transfer with TBHP were discussed in the review . The review by Xiao considered visible light-driven C–C bond cleavage enabled with organic peroxides . This comprehensive review summarizes all ever published studies on radical peroxidation with ROOH, but most of them were published after 2010.

Review C(sp3)–H peroxidation Allylic C(sp3)–H

The pioneering work on C–H radical peroxidation with hydroperoxides was published by Kharasch in a series of articles entitled "The Chemistry of Hydroperoxides" in the 1950s . Kharasch with colleagues firstly demonstrated that the decomposition of tert-butyl hydroperoxide (TBHP) by Co(II) naphthenate proceeds via a chain mechanism, leading to the formation of tert-butoxy and tert-butylperoxy radicals (Scheme 4) . When cyclohexene (1) and oct-1-ene (3) were added, the corresponding products of allylic peroxidation 2, 4 and 5 were observed (Scheme 4) . Similar transformations were reported later using CuCl as the catalyst . Later, Gade with coauthors demonstrated the allylic peroxidation of cyclohexane with TBHP using the alkylperoxocobalt(III) complexes [Co(BPI)(OAc)(OO-t-Bu)] .

Scheme 4: Co-catalyzed allylic peroxidation of alkenes 1 and 3 by TBHP.

Introduction of the tert-butylperoxy fragment into the allylic position of substituted cyclohexenes 6 was carried out using Pd(OAc)2 in ambient conditions (Scheme 5) . The corresponding allylic peroxy ethers 7 were synthesized in 62–75% yields, the key intermediate was proposed to be L2Pd(OO-t-Bu)2.

Scheme 5: Allylic peroxidation of alkenes 6 by Pd(II)TBHP.

Allylic peroxidation of 3-substituted prop-1-ene-1,3-diyldibenzenes 8 was performed with TBHP as the oxidant/peroxidation agent and with Cu2O as the catalyst (Scheme 6). The proposed mechanism of peroxides 9 formation does not include peroxo–copper complexes and begins with the formation of tert-butoxy and tert-butylperoxy radicals from TBHP as a result of redox reactions with Cu(I)/Cu(II). The tert-butoxy radical abstracts the hydrogen atom from alkene 8 to form the C-centered radical A. The subsequent attack of the tert-butylperoxy radical on intermediate A leads to the formation of peroxide 9.

Scheme 6: Cu(I)-catalyzed allylic peroxidation.

The enantioselective peroxidation of alkenes 10 with TBHP with the formation of the optically active products 11 was carried out in good yields and low ee by the use of in situ-generated chiral bisoxazoline–copper(I) complexes (Scheme 7) .

Scheme 7: Enantioselective peroxidation of alkenes 10 with TBHP in the presence of copper(I) compounds.

Studying the oxidation of α-pinene (12) into verbenol and verbenone , it was found when using the CuI/TBHP system, the major observed products are peroxides 13 and 14 (Scheme 8).

Scheme 8: Oxidation of α-pinene (12) by the Cu(I)/TBHP system.

Carbonyl or cyano-activated C(sp3)–H

In 1959 Kharasch demonstrated the introduction of the tert-butylperoxy fragment into the α-position of cyclohexanone (15) and 2-methylcyclohexanone (17) using the Cu(I)/TBHP system (Scheme 9) . α-Methyl-substituted peroxide 18 was obtained in higher yield (based on consumption of TBHP) than the peroxide from cyclohexanone 16, and was found to be more stable.

Scheme 9: Introduction of the tert-butylperoxy fragment into the α-position of cyclic ketones 15 and 17.

Later, the methods for α-peroxidation of β-dicarbonyl compounds (β-diketones, β-ketoesters, and malonic esters) with TBHP via homogeneous and heterogeneous Cu(II)-catalysis were developed (Scheme 10) . It was assumed that the reaction pathway includes the formation of diketonate complex A from β-dicarbonyl compound 19 and copper(II) salt, which then reacts with tert-butylperoxy radical B to form the target peroxide 20 and Cu(I). Cu(I) is oxidized by TBHP to form Cu(II) and tert-butoxy radical C, which abstracts a hydrogen atom from TBHP to form tert-butylperoxy radical B. Radical B can also be formed via oxidation of TBHP by complex A or the Cu(II) salt.

Scheme 10: α-Peroxidation of β-dicarbonyl compounds 19 using the Cu(II)/TBHP system.

The cobalt-catalyzed peroxidation of cyclic compounds 21 by TBHP has been demonstrated (Scheme 11) . There are three possible reaction pathways: the first starts with the oxidation of cobalt(II) by TBHP to form cobalt(III) and the tert-butoxy radical (step A). Next, the formed Co(III) species react with TBHP, resulting in the formation of a peroxocomplex of TBHP with Co(III) (stage B). The oxidation of 4-hydroxy-2(5H)-furanone 21 by Co(III)OO-t-Bu complex generates the target product 22 (step C). A second reaction pathway is also possible, in which the tert-butoxy radical A abstracts the hydrogen atom from TBHP to form the tert-butylperoxy radical (stage D). Next, tert-butylperoxy radical adds to the enol double bond of 4-hydroxy-2(5H)-furanone 21 (step E). Further oxidation of the resulting C-centered radical I into cation II and the proton transfer results in the target product 22 (steps F, G). The third possible pathway involves the abstraction of a hydrogen atom from 4-hydroxy-2(5H)-furanone 21 by the tert-butoxy radical formed in step A to give the alkoxy radical III (step H). Intermolecular hydrogen atom transfer results in the C-centered radical IV (step I). Further recombination of IV with tert-butylperoxy radical provides the target product 22 (step J).

Scheme 11: Co-catalyzed peroxidation of cyclic compounds 21 with TBHP.

The peroxidation of 2-oxoindoles 23, barbituric acids 25, and 4-hydroxycoumarins 27 by TBHP and α-cumyl hydroperoxide was carried out with the application of catalytic systems based on Co(II) , Mn(III) , and Fe(II) . The corresponding peroxides 30 are enough stable under the reaction conditions and were isolated in high yields (Scheme 12). Flow-modification of the 2-oxoindole peroxidation method using nanoparticles of iron oxide as the catalyst was proposed . The summarized proposed reaction pathway is presented in Scheme 12. The reaction probably begins with the oxidation of M(II) by TBHP into M(III) to form the tert-butoxy radical A, which abstracts a hydrogen atom from the substrate, generating the C-centered radical B. Peroxocomplex C, which can be formed from M(III)OH and TBHP as a result of ligand exchange, acts as a donor of the tert-butylperoxy radical D. The target peroxide 30 is formed by recombination of the C-centered radical B and tert-butylperoxy radical D.

Scheme 12: Co-, Mn- and Fe-catalyzed peroxidation of 2-oxoindoles 23, barbituric acids 25, and 4-hydroxycoumarins 27 by TBHP.

Peroxidation of barbituric acid derivatives 31 by TBHP were further studied in detail . It was demonstrated that the effective peroxidation of 31 with the formation of products 32 can be achieved as both using Cu-catalysis and in metal-free conditions (Scheme 13). The metal-free peroxidation with TBHP was also demonstrated using 3,4-dihydro-1,4-benzoxazin-2-ones 33 as substrates (Scheme 13) . The assumed mechanism of the target product 32 formation is similar to the metal-catalyzed peroxidation described in Scheme 12 in the case of using the Cu(II)/TBHP oxidation system. Under metal-free conditions the tert-butoxy radical A is probably formed via homolytic thermal decomposition of TBHP.

Scheme 13: Cu-catalyzed and metal-free peroxidation of barbituric acid derivatives 31 and 3,4-dihydro-1,4-benzoxazin-2-ones 33 by TBHP.

Recently, the electrochemical generation of a set of tert-butoxy and tert-butylperoxy radicals from TBHP has been demonstrated in an undivided electrochemical cell under constant current conditions (Scheme 14) . Using this approach, the electrochemical peroxidation of cyclic 1,3-dicarbonyl compounds 35 with TBHP was realized to give peroxy derivatives 36 in good yields. Three possible ways were proposed: a) anodic oxidation of TBHP and formation of tert-butylperoxy radical; b) hydrogen reduction of TBHP forming H2O and the tert-butylperoxy radical; c) anodic oxidation of NO3 anion to NO3 radical which act as a mediator to form the tert-butylperoxy radical from TBHP. Intermediate A can be formed by reaction of substrate 35 with the tert-butylperoxy or the NO3 radical, further recombination with the tert-butylperoxy radical leads to the target product 36. Also, peroxidation of barbituric acids was achieved using TBHP/TiO2 photocatalytic system under visible light irradiation (443 nm) .

Scheme 14: Electrochemical peroxidation of 1,3-dicarbonyl compounds 35.

Peroxidation of β-ketoesters, cyanoacetic esters, and malonic esters 37 was performed using the TBAI/TBHP system (Scheme 15) . The highest product yields in the TBAI-catalyzed peroxidation were achieved with malonic acid esters, in contrast to the metal-catalyzed methods . Two possible reaction pathways were proposed (Scheme 15). Pathway I is based on the generation of tert-butoxy A and tert-butylperoxy B radicals in the TBAI/TBHP system, followed by the formation of the C-centered radical C. The recombination of intermediate C with tert-butylperoxy radical B leads to the target product 38. Pathway II involves the oxidation of TBAI with TBHP to form hypervalent iodine compounds D and E. The reaction of species E with substrate 37 leads to the formation of intermediate F, which interacts with TBHP to yield product 38. There is no consensus on the nature of the iodine species formed in reactions when using iodine-containing agents and their role in the mechanism of peroxidation.

Scheme 15: Peroxidation of β-dicarbonyl compounds, cyanoacetic esters and malonic esters 37 by the TBAI/TBHP system.

The selective peroxidation of malonodinitriles and cyanoacetic esters 39 with TBHP under Cu-catalysis without oxidative destruction was presented in 2011 (Scheme 16) . The corresponding peroxides 40 were isolated in good yields. Probably, the interaction of dinitrile 39 with Cu(II) salt leads to complex A, which reacts with the tert-butylperoxy radical B to form the target peroxide 40 and Cu(I). TBHP is reduced with Cu(I) into tert-butoxy radical C, which can abstract the hydrogen atom from TBHP to form tert-butylperoxy radical B. The alternative pathway for the formation of radical B is the oxidation of TBHP with complex A.

Scheme 16: Cu-catalyzed peroxidation of malonodinitriles and cyanoacetic esters 39 with TBHP.

A manganese-catalyzed radical approach for the remote trifluoromethylation–peroxidation of non-activated alkenes 41 was disclosed (Scheme 17) . The target 6-trifluoromethyl peroxides 42 were synthesized in good yields under mild conditions. The electrophilic CF3 radical A, generated from CF3SO2Na through single-electron oxidation by using Mnn/TBHP system, is captured by the carbon–carbon double bond to generate the nucleophilic carbon radical B. The intramolecular 1,5-HAT of B provided the alkyl radical C, which then cross-coupled with the in situ-generated high-valent Mnn+1OO-t-Bu species to form the 1,6-difunctionalized product 42 via peroxy-ligand transfer.

Scheme 17: Mn-catalyzed remote peroxidation via trifluromethylation of double bond.

The remote trifluoromethylthiolation–peroxidation of unsaturated alkenes 43 using AgSCF3 and TBHP was realized in the presence of the copper catalyst (Scheme 18) . The radical trifluoromethylthiolation of alkenes 43 triggers a 1,5-HAT and further recombination of the generated C-centered radical with the tert-butylperoxy radical to afford the trifluoromethylthiolated organic peroxides 44 in good yields.

Scheme 18: Cu-catalyzed remote peroxidation via trifluromethylthiolation of double bond.

Benzyl C(sp3)–H

The direct α-functionalization of alkylaromatic compounds 45 with TBHP with the formation of the mixed peroxides 46 was firstly reported by Minisci using Gif conditions – Fe(NO3)3/HOAc/Py (Scheme 19) . Notably, high yields of peroxides 46 were achieved using 1 equiv TBHP. This can be explained by reoxidation of Fe(II) to Fe(III) by oxygen, which is released during thermal decomposition of pyridinium nitrate presented in the system. Later, Mn-catalyzed peroxidation of alkylarenes 47 and peroxidation of alkylarenes 49 using Ru-exchanged Montmorillonite K10 were presented (Scheme 19). Chemical and kinetic data confirm that the mechanisms of the described processes are probably of a radical nature with the formation of MOO-t-Bu complexes . The proposed pathway of the peroxidation is shown on the example of 9-substituted fluorenes 51 peroxidation (Scheme 19) . Initially, the complex A of 2,2′-bipyridine with manganese(III) acetate is formed. Further oxidation of A by TBHP leads to complex B and tert-butoxy radical C. The later one abstracts an hydrogen atom from fluorene 51 to form C-centered radical F. The reaction of complex B with TBHP gives complex D, which transfers tert-butylperoxy radical E to the C-centered radical F to yield the target peroxide 52 (Scheme 19).

Scheme 19: Fe-, Mn-, and Ru-catalyzed peroxidation of alkylaromatics 45, 47, 49, and 51 with TBHP.

The α-peroxidation of nitriles with hydroperoxides was developed by Kharasch and Sosnovsky in 1958 on the example of the Cu(I)-catalyzed reaction of diphenylacetonitrile (53) with TBHP (Scheme 20) . Peroxide 54 was obtained in a 79% yield using CuBr as the catalyst. The first step of diphenylacetonitrile 53 peroxidation is the oxidation of copper(I) to copper(II) by TBHP, resulting in tert-butoxy radical A, which abstracts the hydrogen atom from substrate 53 to form the C-centered radical B. Copper(II) then oxidizes TBHP to form the tert-butylperoxy radical C and copper(I), closing the catalytic copper cycle. tert-Butylperoxy radical C recombines with radical B to yield the product 54.

Scheme 20: Cu-catalyzed peroxidation of diphenylacetonitrile (53) with TBHP.

The reaction of a mono-substituted nitrile, phenylacetonitrile (55), with TBHP under Cu-catalysis led to a mixture of the oxidation products 56–59 including tert-butyl perbenzoate (57, Scheme 21) . This discovery was later used to develop the synthesis of tert-butyl perbenzoates 61 from phenylacetonitriles 60 and TBHP (Scheme 21) . The process was carried out without solvent and at room temperature, using copper(II) acetate as the catalyst. The reaction pathway of tert-butyl perbenzoate synthesis from benzyl nitriles 60 involves the formation of intermediate D. The Kornblum–DeLaMare rearrangement of peroxide D gives benzoyl cyanide E, which is further attacked by TBHP to give product 61.

Scheme 21: Cu-catalyzed peroxidation of benzyl cyanides 60 with TBHP.

Benzyl alcohols 62 were also converted into tert-butyl perbenzoates 63 under the action of the TBAI/TBHP system (Scheme 22) . During the process, TBHP oxidizes TBAI into iodine, which reacts with the second TBHP to generate tert-butylperoxy radical B. The oxidation of benzyl alcohol 62 with TBHP results in aldehyde C, HAT from which by tert-butoxy radical A leads to the C-centered radical D. Subsequent recombination of radicals D and B provides the target product 63.

Scheme 22: Synthesis of tert-butylperoxy esters 63 from benzyl alcohols 62 using the TBAI/TBHP system.

An enantioselective peroxidation method of alkylaromatics with TBHP using chiral in situ-generated Cu(I) complexes was developed (Scheme 23) . 2-Phenylbutane (64) was converted into peroxide 65 in a 70% yield with 4% ee.

Scheme 23: Enantioselective peroxidation of 2-phenylbutane (64) with TBHP and chiral Cu(I) complex.

A visible light-induced direct decarboxylative peroxidation of carboxylic acids 66 with the formation of peroxides 67 under metal-free conditions using Mes-AcrClO4 as the photocatalyst has been disclosed (Scheme 24) . According to the authors, the irradiation of the photocatalyst (Acr+-Mes) A with a blue LED leads to the excited state (Acr·-Mes·+) B. The aliphatic carboxylic acid 66 is converted by deprotonation to the corresponding carboxylate, which is oxidized by the excited photocatalyst to give the benzyl radical D and CO2. Further, single electron transfer from (Acr·-Mes) C to TBHP results in the ground state photocatalyst (Acr+-Mes) A and tert-butoxy radical E, which abstracts the hydrogen atom from TBHP to yield tert-butylperoxy radical F. The recombination of radicals F and D leads to the product 67.

Scheme 24: Photochemical synthesis of peroxides 67 from carboxylic acids 66.

Photochemical peroxidation of isochromans and other benzylic C(sp3)–H substrates 68 with TBHP was developed using Ir(ppy)3 as the photocatalyst and Bronsted acid as an additive (Scheme 25) . Visible light irradiation of [IrIII(ppy)3] to give the excited state [*IrIII(ppy)3] is likely to initiate a plausible catalytic cycle. Then TBHP is reduced by [*IrIII(ppy)3] through SET, which results in the generation of the tert-butoxy radical. Subsequently, the tert-butoxy radical abstracts a hydrogen atom from substrate 68 to give radical A. Photocatalytic oxidation of radical A with [IrIV(ppy)3] regenerates [IrIII(ppy)3] and completes the photoredox catalytic cycle. The Bronsted acid catalyzes the formation of the isochroman oxocarbenium ion B, which is then nucleophilically attacked by TBHP to produce the target peroxide 69.

Scheme 25: Photochemical peroxidation of benzylic C(sp3)–H.

Heteroatom (N, O)-activated С(sp3)–H

In the pioneering work of Kharasch, N,N-dimethylaniline (70) was peroxidized with TBHP using Cu2Cl2 (Scheme 26) . Later, the peroxidation of N-substituted tetrahydroisoquinolines 72 with TBHP was successfully carried out using a similar oxidation system . The first step in the proposed mechanism of amine 72 peroxidation is the oxidation of Cu(I) with TBHP, resulting in the formation of tert-butoxy radical A, which abstracts the hydrogen atom from substrate 72 to form the C-centered radical B. The generated Cu(II) oxidizes TBHP to form tert-butylperoxy radical C, which recombines with radical B to form product 73. The mechanism of the transition metal-catalyzed oxidation of amines with TBHP was studied in detail in the work of Doyle and Ratnikov . The scope of the amines 74 that can be functionalized by the tert-butylperoxy fragment was significantly broadened by using a catalytic system based on ruthenium salts .

Scheme 26: Cu- and Ru-catalyzed peroxidation of alkylamines with TBHP.

The C(sp3)–H bond at the amides 76 was functionalized with the tert-butylperoxy radical under the action of the TBAI/TBHP system (Scheme 27) . The target amido-peroxides 77 were synthesized in high yields. The authors proposed that the process begins with the formation of tert-butoxy A and tert-butylperoxy B radicals as a result of the iodide/iodine redox cycle. Then the tert-butoxy radical A abstracts a hydrogen atom from the substrate 76 to form the C-centered radical C. The target product 77 is formed via recombination of the radical C and the tert-butylperoxy radical В.

Scheme 27: Peroxidation of amides 76 with the TBAI/TBHP system.

Fe(acac)3-catalyzed oxidation of benzyl, allyl and propargyl ethers 78 with TBHP led to the formation of tert-butylperoxyacetals 79 (Scheme 28) . Probably, in the first step TBHP oxidizes Fe(II) to Fe(III) with the formation of tert-butoxy radical A. Then the second molecule of TBHP is oxidized by Fe(III) into tert-butylperoxy radical B. Radical A abstracts a hydrogen atom from ether 78 to give the C-centered radical C. The authors propose two further pathways for the formation of the target product 79. Pathway I: The C-centered radical C is oxidized to carbocation D, which is captured by TBHP. Pathway II: the recombination of the C-centered radical C and tert-butylperoxy radical B.

Scheme 28: Fe-catalyzed functionalization of ethers 78 with TBHP.

The three-component approach to 4-(tert-butylperoxy)-5-phenyloxazol-2(3H)-ones 82 from benzyl alcohols 80 and isocyanates 81 using the Cu(II)/TBHP system was developed (Scheme 29) . The set of tert-butoxy A and tert-butylperoxy B radicals are formed from TBHP during the Cu(I)/Cu(II) redox cycle. The Cu(II)/TBHP system also provides oxidation of benzyl alcohol 80 to the corresponding aldehyde C. The reaction of isocyanate 81 with aldehyde C generates oxazoline D, HAT from D by the action of radical A leads to intermediate E. The recombination of intermediate E with tert-butylperoxy radical B, following elimination of TsH, and oxidation of oxazole G provides the target peroxide 82 formation.

Scheme 29: Synthesis of 4-(tert-butylperoxy)-5-phenyloxazol-2(3H)-ones 82 from benzyl alcohols 80 and isocyanates 81 under the action of the Cu(II)/TBHP system.

Non-activated С(sp3)–H

A number of studies are devoted to the oxidation of cyclohexane 83 with TBHP using mononuclear and dinuclear non-porphyrin iron complexes (Scheme 30). Besides the oxygen atom transfer products, cyclohexanol (85) and cyclohexanone (15), the formation of peroxide 84 was observed. Oxidation of cyclohexane (83) was also carried out directly by the Co(lll) complexes with TBHP (Scheme 30) . The key step in the Fe-catalyzed peroxidation mechanism is the generation of the set of tert-butoxy and tert-butylperoxy radicals from TBHP via Fe(II)/Fe(III) cycle. HAT from cyclohexane by tert-butoxy radical and the recombination of the resulting C-centered radical A with tert-butylperoxy radical lead to the tert-butylperoxy cyclohexane 84.

Scheme 30: Fe- and Co-catalyzed peroxidation of alkanes with TBHP.

C(sp2)–X peroxidation of arenes

The radical peroxidation of the aromatic core has been realized on the example of the peroxidation of phenols . The first studies were carried out as part of the investigation of the enzymatic function of cytochrome P-450 with low valent ruthenium complex catalysts. Various phenols 86 bearing para-substituents were transformed into the corresponding tert-butyldioxy dienones 87 smoothly using RuCl2(PPh3)3 as the catalyst (Scheme 31) . The authors rationalized that RuCl2(PPh3)3 reacts with TBHP to give the (alkylperoxido)ruthenium(II) complex, which subsequently undergoes heterolytic cleavage of the O–O bond to form the (oxido)ruthenium(IV) species. HAT from the phenols by Ru(IV)=O intermediate leads to the phenoxyl radical–Ru(III)(OH) intermediate, which provides the cationic intermediate from phenol via electron transfer. The reaction of cation D with TBHP results in the mixed peroxide 87 .