Rearrangements of organic peroxides and related processes

This review is the first to collate and summarize main data on named and unnamed rearrangement reactions of peroxides. It should be noted, that in the chemistry of peroxides two types of processes are considered under the term rearrangements. These are conventional rearrangements occurring with the retention of the molecular weight and transformations of one of the peroxide moieties after O–O-bond cleavage. Detailed information about the Baeyer−Villiger, Criegee, Hock, Kornblum−DeLaMare, Dakin, Elbs, Schenck, Smith, Wieland, and Story reactions is given. Unnamed rearrangements of organic peroxides and related processes are also analyzed. The rearrangements and related processes of important natural and synthetic peroxides are discussed separately.


Introduction
The chemistry of organic peroxides has more than a hundredyear history. Currently, organic peroxides are widely used as oxidizing agents and initiators for free-radical reactions both in industry and in laboratory. These compounds are produced and involved in various natural and biological processes and were explored extensively as antimalarial agents, anthelmintics, and anticancer drugs.
Organic peroxides, their rearrangements and related processes play an important role in the chemistry of oxidation processes. Thus, the key reagent in the Sharpless epoxidation of allylic alcohols [48] and in the manufacture of propylene oxide via the Prilezhaev reaction [49][50][51] is tert-butyl hydroperoxide. In industry, phenol and acetone are mainly produced by the Hock process, which is based on the rearrangement of cumene hydroperoxide. In 2003, phenol was produced to more than 95% by this oxidation process [52][53][54]. Another important application of organic peroxides is the synthesis of lactones from cyclic ketones via the Baeyer−Villiger oxidation and it is one of the methods for the synthesis of commercially important caprolactone from cyclohexanone with peracetic acid [55,56].
Autoxidation processes with formation of hydroperoxides and their subsequent free-radical transformations with generation of carbon-and oxygen-centered radicals are key reactions in the drying process of oil-based and alkyd paints containing double bonds [57][58][59][60][61].
Organic peroxides and their transformation play an important role not only in industrial but also in biological processes. Thus, the firefly luciferase-catalyzed oxidation of luciferin yields the peroxy compound 1,2-dioxetane. This four-membered peroxide cycle is unstable and spontaneously decays to carbon dioxide and excited ketones, which release excess energy through light emission (bioluminescence) [62][63][64][65]. The in vivo oxidation of cholesterol by singlet oxygen produces the hydroperoxide cholesterol-5α-OOH, which undergoes a Hock oxidation to form atheronal A. The latter possesses proatherogenic effects and triggers the development of cardiovascular diseases [66][67][68][69][70][71].
The development of the chemistry of organic peroxides is closely related to the application and preparation of unsaturated compounds, such as epoxides, aldehydes, ketones, carboxylic acids, and their derivatives . Organic peroxides are widely used as oxidants in oxidative coupling processes [114][115][116][117][118][119][120].
Industrial-scale production of readily available and efficient initiators of free radical polymerization and effective biologically active compounds promotes the search for new synthetic methods for peroxides starting from carbonyl compounds, hydrogen peroxide, and hydroperoxides .
In many cases, rearrangements and related reactions of peroxides are key pathways in laboratory, industrial, and biological processes. The rearrangements of organic peroxides are covered in the literature in hundreds of publications and in several specialized and partial reviews [183][184][185][186][187][188]. The present review is the first to combine the key data on both, name rearrangements and less well-known rearrangements and related oxidative processes, and to summarize systematically related and different features of these reactions, compares their mechanisms, and assesses the prospects of their application.
By definition, a rearrangement is a migration of an atom or a group of atoms from one atom to another within the same molecule [189]. In contrast, a rearrangement of organic peroxides means a change in the structure of the starting molecule to form an isomeric compound without a peroxy group [183]. The terminology of rearrangements of organic peroxides and related processes encountered in the literature shows that this definition is not generally applicable as rearrangements of peroxides can give both isomeric and non-isomeric compounds either containing a peroxy group or without the latter. In most cases, a rearrangement involves the migration or cleavage of the peroxide group in an intermediate molecule, and the stability of the latter is responsible for the further pathway of the process.
The review covers main studies published over the last 15-20 years with a brief excursion to the history of the development of various reactions and transformations. The review consists of three parts: the first part considers named transformations of organic peroxides (Figure 1), the second one deals with unnamed reactions, and the third part covers transformations of some important natural and synthetic peroxides. Since the term "rearrangements", as applied to transformations of peroxides, is not clearly defined all parts of the review include processes related to rearrangements. finds application for the synthesis of phenols from arylaldehydes or aryl ketones and the Elbs persulfate oxidation allows the preparation of hydroxyphenols from phenols. Finally, the Schenck and Smith rearrangements are of interest in allyl hydroperoxide transformations.

Baeyer-Villiger oxidation
The BV reaction is the oxidation of ketones or aldehydes A under the action of hydrogen peroxide, hydroperoxides, Caro's acid (H 2 SO 5 ), or organic peracids to yield esters, lactones, or carboxylic acids B (Scheme 1) [190,191].

Scheme 2:
The general mechanism of the peracid-promoted Baeyer-Villiger oxidation. Baeyer and Villiger accomplished the oxidation of ketones to esters for the first time in 1899 while they attempted the reaction of Caro's acid (H 2 SO 5 ) with menthone, tetrahydrocarvone, and camphor to transform these compounds into the corresponding lactones [192][193][194].
Since that time, this reaction has shown to be of general applicability and it has gained wide application for the oxidation of carbonyl compounds of different structures. In this reaction, cyclic ketones are transformed into lactones, acyclic ketones, into esters and aldehydes into carboxylic acids. The BV oxidation is one of the most important reactions in organic chemistry because it produces lactones, which are useful synthetic products in polymer, agrochemical, and pharmaceutical industry. m-Chloroperbenzoic, peracetic, and perfluoroacetic acids, as well as hydrogen peroxide/protic acid, hydrogen peroxide/ Lewis acid, and hydrogen peroxide/base systems are widely employed in the Baeyer-Villiger oxidation [185,194,195].
The general mechanism of the peracid-promoted Baeyer-Villiger oxidation involves two main steps. In the first step, the oxygen atom of the peroxide moiety of the peracid 2 binds to the carbonyl group of ketone 1 to form the tetrahedral intermediate 3 which is referred to as the Criegee intermediate. The next step involves the concerted migration of the R 2 group to the peroxide oxygen atom, resulting in the formation of ester 4 and carboxylic acid 5 (Scheme 2).
The migratory ability of substituents in the Criegee intermediate decreases in the following series: tertiary alkyl > cyclohexyl > secondary alkyl > benzyl > phenyl > primary alkyl > cyclopentyl, cyclopropyl > methyl. In some cases, stereoelectronical effects strongly influence the regioselectivity of the reaction, specifically the ability of the migrating C-C to align with the back of the breaking O-O bond, and the presence or absence of strain in cyclic ketone substrates [197,198]. The strongest electron-donating group migrates in unsymmetrical ketones [199].
There are thousands of publications on the Baeyer-Villiger reaction. In the latest reviews published by Krow [195] in 1993 and by Renz and Meunier [185] in 1999, the field of application, the reactivity of substrates, and the reaction kinetics and mechanisms are considered in detail. In the review by Strukul, special emphasis was placed on metal-catalyzed Baeyer-Villiger oxidations [196]. Green approaches in the Baeyer-Villiger reaction were highlighted by another review [200].
The present review covers a more modern aspect of this reaction, viz., the performance of the process using hydrogen peroxide. Oxidizing systems containing hydrogen peroxide as the oxidizing agent allow the usual and asymmetric oxidation of the substrate to the target product with high conversion and yield. In recent years, the inexpensive, commercially available, and environmentally friendly H 2 O 2 was utilized in the Baeyer-Villiger reaction with increasing frequency. Various catalysts that activate hydrogen peroxide, such as heterogeneous catalysts based on solid acids [201], zeolites [202,203], Se [204], As [205], Co [206], sulfonated organic ion exchange resins [203,207], and homogeneous catalysts based on Pt [208], Zr [209], Re [210,211], Se [212,213], As [205], Mo [214], Co [215], Brønsted [216], and Lewis acids [217] are described in the literature. The general mechanism of a Lewis acid-catalyzed Baeyer-Villiger rearrangement is presented in Scheme 3 [200,218]. Scheme 3: General mechanism of the Lewis acid-catalyzed Baeyer-Villiger rearrangement.

Scheme 4:
The theoretically studied mechanism of the BV oxidation reaction promoted by H 2 O 2 and the Lewis acid BF 3 . Scheme 4 shows the theoretically studied mechanism of the oxidation reaction promoted by H 2 O 2 and the Lewis acid BF 3 [217,219]. In the first step, the hydrogen peroxide-boron trifluoride complex 8 reacts with ketone 9 to form adduct 10. Despite the fact that the Baeyer-Villiger reaction is known since 1899, the mechanism of this reaction is still not fully understood. The nature of the acid catalyst [220] and the type of O-O-bond cleavage in the Criegee intermediate [221] were found to play an important role in this reaction. Probably the hydrogen bonds in Baeyer-Villiger reactions play an important role [222]. The tetramolecular transition states TS1 and TS2 are considered to be the two key steps determining the course of the oxidation: the nucleophilic addition of a peroxy acid molecule to ketone (TS1) and the migration of R and cleavage of O-O bond (TS2). Thus, electrophilic substrates favor TS1 and nucleophilic migrating groups prefer TS2 (Scheme 5).   Table 1) [223].
The oxidation of isophorone oxide (29) is an industrial process for the production of dimethylglutaric acid 30 (Scheme 8) [223].
Acyl phosphate 32 can be synthesized from acyl phosphonate 31 in high yield by oxidation with H 2 O 2 (Scheme 9) [224].
The Baeyer-Villiger oxidation provides a valuable tool for the synthesis of oxygenated natural products [218,225,226] as exemplified by the synthesis of aflatoxin B 2 (36, Scheme 10) [227].
The Baeyer-Villiger reaction is also a key step in the multistep synthesis of cannabinergic lactones from dimethylheptylresorcinol. Two regioisomeric cannabinergic lactones were obtained, one of which possessed pronounced affinity towards the CB1 receptor and lower affinities for mCB2 and hCB2 receptors [228].  45a-c to the corresponding esters 46a-c using the H 2 O 2 /aryl benzyl selenoxide system are collected in Table 2 [232].
The oxidation results of ketones 47a,b and aldehydes 47c-e to lactones 48a,b and carboxylic acids 49a-c promoted by the H 2 O 2 /diaryl diselenide system is presented in Table 3 [212].  [233].
The mechanism of the oxidation of ketones 58a-f by hydrogen peroxide in the presence of arsonated polystyrene 60 as the Scheme 17: The mechanism of oxidation of ketones 58a-f by hydrogen peroxide in the presence of arsonated polystyrene 60. A number of other modern oxidizing systems are based on transition metal-peroxo complexes. The use of transition metal complexes were also used as catalysts for the Baeyer-Villiger reaction and the first example was documented in 1978 [196,214]. For example, Mo(VI) peroxo complexes 64 and 65 were employed as the catalysts and 90% H 2 O 2 served as the oxidizer (Table 5).  [247]. Benzoic acids 71a-d, 74 and phenyl esters 75a-d were reported as oxidation byproducts.
Sn-containing mesoporous silica nanospheres (Sn-MSNSs) with uniform crater-like mesopores exhibited high activities in The Baeyer-Villiger rearrangement of 2-adamantanone (45с) was performed using hydrogen peroxide (H 2 O 2 ) and stannosilicate zeolites with nanosheet morphology and MFI topology (Sn-MFI-ns) as highly efficient catalysts [249]. The Sn-beta zeolites prepared by a steam-assisted conversion method are efficient catalysts for the Baeyer-Villiger reaction of cyclohexanone to ε-caprolactone [250]. A mesoporous Mg-Al-mixed oxide showed good catalytic efficiency in the Baeyer-Villiger oxidation of a series of ketones to the corresponding lactones and esters in the presence of diluted aqueous H 2 O 2 and benzonitrile [251]. Asymmetric oxidation: Asymmetric Baeyer-Villiger oxidation reactions can be performed using chiral acetals, organic hydroperoxides, chiral metal complexes and organocatalysts [262,263]. There are also Green chemistry approaches for Baeyer−Villiger oxidations based on enzyme-mediated processes, which are used for the preparation of chiral lactones. This type of biocatalysis is useful in synthetic chemistry and either isolated enzymes or living whole cells are applied for the oxidative production of valuable intermediates [264][265][266][267][268][269].
The asymmetric oxidation of 3-substituted cyclopentane-1,2diones 87a-f is an efficient tool in organic synthesis for the preparation of unsymmetrical γ-lactone acids 88a-f with high optical purity and good yields ( Table 6). These γ-lactone acids are valuable substrates for the synthesis of compounds with potentially useful pharmacological properties, such as homocitrates, alkyl-and aryl-substituted nucleosides [270][271][272].
The reaction starts with an asymmetric epoxidation of the substituted cyclopentane-1,2-dione 87a to form epoxide 89a. The second step involves the Baeyer-Villiger oxidation of epoxide 89a to peroxide 90a followed by the rearrangement into intermediate 91a. The latter is hydrolyzed by H 2 O to form dicarboxylic acid 92a, which is cyclized under the acidic conditions to γ-lactone acid 88a (Scheme 29) [270].  In most cases, the Baeyer-Villiger oxidation is a stereospecific and regioselective process with retention of the configuration. The oxidation of cis-4-tert-butyl-2-fluorocyclohexanone (93) with m-chloroperbenzoic acid in the presence of NaHCO 3 affords fluorolactones 94 and 95 in 91% and 9% yields, respectively (Scheme 30) [273].
A highly regio-and enantioselective Baeyer-Villiger oxidation of cyclic ketones 101 bearing amido, ureido, or sulfonamido functional groups to lactones 102 and 103 was carried out using the peptide-based catalyst 104. Hydrogen-bonding interactions are responsible for both types of selectivity. Notably, a reversal of the typically seen selectivity was observed with the peptide catalyst (Scheme 33) [285].
Versatility of the Baeyer-Villiger reaction with respect to starting reactants: The Baeyer-Villiger reaction cannot only be performed with ketones but also with acetals and aldimines as the starting substrates. The oxidation of cycloalkanone acetals 105a-g with performic acid generated in situ provides a new route to dicarboxylic acids 106a-g and hydroxycarboxylic acids 107a-g (Table 8) [286].
The proposed mechanism of the oxidation of acetal 105f is shown in Scheme 34.
In the first step of the reaction, the elimination of methanol from 105f and formation of 108 takes place. Probably perester 109 is formed alongside of 108. After formation of 109, the reaction proceeds by two different routes A and B (second stage). The first route A leads to formation of epoxide 110, This method can be applied to the synthesis of dodecanedioic acid, which is used in anticorrosive composites, polyester and polyamide threads, and lubricants, for the synthesis of tridecanedioic acid, and as a component of perfume formulations.
The oxidation of aldimines 118a-f with m-chloroperbenzoic acid in the presence of boron trifluoride etherate produces amides 119a-f in good yields ( Table 9). The products of this transformation are strongly dependent on the electronic properties of the aromatic substituents at the carbon atom of the aldimines [288]. In the case of electron-donating substituents on the aryl fragment (Ar), formamides 119a-c are obtained as the result of imine oxidation and aryl migration. On the other hand, electron-withdrawing substituents on the aryl group (Ar) promote the formation of amides 119d-f as result of hydride migration.

Criegee rearrangement
The Criegee rearrangement involves the transformation of a peroxide, mainly peroxyesters B, into carbonates, esters, or ketones C and alcohols D through an oxygen insertion or consecutive oxygen insertions. The peroxyester B is initially prepared from a tertiary alcohol A and a peracid. In addition, the peroxy ester can also be prepared via the reaction of a ketone and a peracid (i.e., through a Baeyer-Villiger oxidation); the additional product of peracid to ketone is often referred to as the Criegee intermediate. The mechanism of the Criegee rearrangement was studied using 2-alkoxy-2-propyl per-4-nitrobenzoates [292]. It was shown that the ionic cleavage of 2-methoxy-2-propyl perester 129 to p-nitrobenzoic acid (132), methyl acetate (133)  The Criegee rearrangement of 1-hydroperoxy-2-oxabicycloalkanes 147a-d in formic or acetic acid containing catalytic amounts of sulfuric acid affords ω-alkoxy-(ω-3)-hydroxyalkanoic acid lactones 148a-d and 149a-d (Table 10) [297]. This method for the insertion of an oxygen atom was applied to the oxidation of triarylmethanols 159a-d [299]. The successive insertion of oxygen atoms gave rise to diaryl carbonates 160a-d in good yields (Scheme 47).
A method for the large-scale synthesis of a trans-hydrindan derivatives 164, 165 related to vitamin D, based on the Criegee rearrangement of alkene 163 was realized (Scheme 49) [308].

Hock rearrangement
The Hock rearrangement is a protic or Lewis acid-promoted rearrangement of hydroperoxides A resulting in a C-C bond The Hock rearrangement is a key step in the cumene process, which is used for the industrial production of phenol (170) and acetone (171) from benzene (166) and propylene (167) in the presence of air and radical initiators. The cumene process was described by Udris and Sergeev in 1947 [314,315] and independently by Hock in 1944 [316,317]. The general scheme of the cumene process, involving the formation of cumene hydroperoxide is shown in Scheme 51.
The cumene process involves the acid-catalyzed rearrangement of cumene hydroperoxide (168) as a key step. The reaction starts with the protonation of the terminal oxygen atom of cumene hydroperoxide (168) followed by the migration of the phenyl group from the benzylic carbon atom to the peroxide oxygen atom and the elimination of a water molecule to form carbocation 169. The carbocation 169 is attacked by a water molecule, a proton is transferred to the oxygen atom attached to the phenyl group, and finally the cleavage of the adduct yields phenol (170) and acetone (171).
The Hock rearrangement of aliphatic hydroperoxides proceeds quite readily in concentrated H 2 SO 4 [318] or superacids [319] (Scheme 52). This is associated with higher resistance of these compounds toward acid-catalyzed rearrangements compared with benzylic or allylic hydroperoxides. For example, aliphatic hydroperoxides are not cleaved in 5-50% aqueous H 2 SO 4 but on the contrary, these compounds are produced under these conditions. More efficient catalysts are the compounds Sn(OTf) 2 and La(OTf) 3 which can be used for the transformation of 2-hydroperoxy-2,4,4-trimethylpentane (172) into neopentyl alcohol (173) and acetone (171). The Sn(OTf) 2 and La(OTf) 3 -catalyzed reaction afforded neopentyl alcohol (173) in 62 and 70% yield, respectively [320]. The hydrogen peroxide promoted ring expansion for the synthesis of oxabicycles 176a-c was described for the first time in 1985 [321]. The reaction involved the solvolysis of homoallylic brosylates 174a-c or spiro cyclopropyl carbinols 175a-c in the THF/H 2 O 2 system, resulting in the increase in the ring size by two atoms and the formation of hydroperoxy oxabicyclo derivatives 176a-c (Table 11).
The mechanism of the solvolysis of 174 or 175 in the THF/ H 2 O 2 system involves the formation of solvolytically generated cyclobutyl hydroperoxides 177 followed by the rearrangement of the latter into oxa-bridged, hydroperoxyhemiketals 176 (Scheme 53).
The fragmentation of hydroperoxy acetals 178a-e in the presence of Ca(OCl) 2 or t-BuOCl as the catalysts in CH 3 CN generating esters 179a-e proceeds through the Hock-like rearrangement mechanism (Table 12) [322].
The fragmentation of hydroperoxy acetals 178 to esters 179 involves the formation and heterolytic fragmentation of intermediate secondary chloroperoxides 180. The possible mechanism of the process is presented in Scheme 54.
The acid-catalyzed rearrangement of phenylcyclopentyl hydroperoxide 181, involving the Hock reaction, is accompanied by the formation of a series of products: 1-phenylcyclopentene  An attempt was made [324] to synthesize hydroperoxides through the peroxidation of tertiary alcohols in the presence of a catalytic amount of acid. The treatment of 185 with H 2 O 2 in the presence of a catalytic amount of H 2 SO 4 for 72 hours did not lead to the formation of products via the Hock rearrangement of hydroperoxides, bicyclic hydroperoxides and о-hydroxyphenyl alkyl ketones. Instead, cyclic 2-methylchroman-2-yl hydroper- oxide 188, geminal bishydroperoxides 190, and condensation products of peroxides such as 191 were isolated (Scheme 56).
The reaction mechanism presumably involves the following steps: the replacement of the hydroxy group by hydrogen peroxide to form tertiary hydroperoxides 186, the acid-catalyzed rearrangement of compounds 186 into cyclic phenoxycarbenium ions 187, and the addition of the second hydrogen peroxide molecule to 187 resulting in the formation of cyclic phenoxy hydroperoxide 188. The latter was isolated as the Scheme 56: The peroxidation of tertiary alcohols in the presence of a catalytic amount of acid. 3 4 Me 3 c (1:10) d (12) major product in the case of the six-membered ring (n = 1). In the case of the seven-membered ring (n = 2), geminal dihydroperoxide 190 and bridged bis(hydroxy)dialkyl peroxide 191 were obtained instead of 188. In case of the eight-membered ring (n = 3) an exclusive transformation into geminal dihydroperoxide 190 was observed (  [330]. The benzannulation of indoles 211 can be performed with γ-carbonyl tert-butyl peroxides 212 catalyzed by trifluoromethanesulfonic acid to give carbazoles 213. The key step of this approach is based on the acid-catalyzed rearrangement of tertbutyl peroxides (Scheme 61) [331].
The direct dehydrogenative construction of C-N bonds between unprotected phenols 215 and a series of 10H-phenox-azines and 10H-phenothiazines 214 with formation of 216 was carried out using a Hock-like activation with O 2 followed by amine oxidation (Scheme 62) [332].
The Hock rearrangement plays an important role not only in fine organic synthesis but also in biological processes. Scheme 63 shows the proposed mechanism for the biosynthetic conversion of 217 to 218, which is an important component of the structural skeleton of the antitumor-antibiotic CC-1065 [333].
The synthetic model of the in vivo oxidation of cholesterol (219) by singlet oxygen produces cholesterol-5α-OOH 220, which is subjected to a Hock reaction to form the aldolization product 221 and keto aldehyde (atheronal A, 222) (Scheme 64) [67].
Keto aldehyde (atheronal A, 222) exhibits proatherogenic activity and plays a causal role in the development of cardiovascular diseases [66]. The proposed mechanism of the rearrangement of cholesterol-5α-OOH 220 is presented in Scheme 65.

Kornblum−DeLaMare rearrangement
The Kornblum−DeLaMare rearrangement (KDLM) is a rearrangement of organic peroxides A containing a primary or secondary carbon atom into ketones B and alcohols C mainly under base-catalyzed reaction conditions (Scheme 67) [335].
The Kornblum-DeLaMare rearrangement is a convenient tool in organic chemistry for the conversion of monocyclic endoperoxides. These compounds are discussed in this review in the order of increasing ring size and the number of the starting substrates.
The treatment of unsubstituted bicyclic endoperoxides 229 by bases affords 4-hydroxyenones 230 [344] which are useful precursors in asymmetric organic syntheses. Alternative synthetic methods towards this class of compounds normally require a metal-catalyzed or biocatalyzed oxidation of diols 231 in an additional reaction step [345] (Scheme 69). It is interesting to note, that a reduction of the bicyclic endoperoxide 234 with thiourea in methanol at 10 °C produces similar to KDLM product tropolone 235 in 94% yield (Scheme 71) [347]. Tropolones exhibit a broad spectrum of biological activities, including antibacterial, antiviral, antifungal, anti-allergic, antioxidant, and anti-inflammatory [348,349].
The reaction of endoperoxide 242a containing an electron-donating substituent at the double bond with bases results in the rearrangement product diketone 243. Under the same conditions, the base-catalyzed rearrangement of endoperoxide 242b containing an electron-withdrawing substituent leads to a product mixture of hydroxy ketone 244, and diketones 245 and 246 (Scheme 75) [353]. A further study [352] on the base-catalyzed rearrangements of substituted bicyclic endoperoxides showed that the pathway of the rearrangement is largely determined by the position of the substituent. The rearrangement of endoperoxides 247a,b containing an electron-withdrawing substituent in the seven-membered ring occurs mainly via a retro-aldol cleavage giving rise to formyl benzoates 248a,b (Scheme 76).
The Kornblum-DeLaMare reaction of endoperoxide 251a containing an electron-withdrawing substituent at the bridge head One approach to the enantioselective synthesis of 4-hydroxyenones 262 is based on the Kornblum-DeLaMare rearrange- ment of meso-endoperoxides 261 catalyzed by a chiral base [345] ( Table 14). The base-catalyzed isomerization of bicyclic saturated fulvene endoperoxides 275 is employed as one approach to the preparation of 2-alkenylcyclopentanones 276 and cyclopentenones 277 [358]. Thus, the treatment of a solution of endoperoxides 275 in CH 2 Cl 2 with triethylamine while increasing the temperature from 0 °C to room temperature affords hydroxyketone 276. The use of the stronger base DBU results in the formation of 2-vinyl-2-cyclopentenones 277 in high yield (Table 15).
The reaction of unsymmetrical epoxy dioxanes 290a-d with triethylamine is accompanied by the 1,2-dioxane-ring opening to form 4-hydroxy-2,3-epoxy ketones 291a-d in high yields. The  In another study [369], the transformation of peroxide 302, produced from 301, was applied to prepare compounds such as 3H-quinazolin-4-one 303, which is a core subunit of some important quinazolinone-based drugs (Scheme 90).
The Kornblum-DeLaMare rearrangement is one of the steps in the synthesis of the natural compound angelone from Nauclea, a plant species widely acclaimed for its anti-inflammatory and antibacterial utilities in traditional Chinese herbal medical formulations [370]. A Kornblum-DeLaMare enantiomeric resolution was also used to obtain both fragments of the polypropionate metabolite dolabriferol from a common precursor. The endoperoxide 304 was converted into ketone 305 with the help of the pseudo-enantiomeric quinine-derived catalyst (deMeQ-Ac) in toluene with moderate 47% yield. The peroxide 306 was transformed into ketone 307 with good 92% yield by using Et 3 N (Scheme 91) [371]. cleanly produced 344 (85% yield). The latter compound represents the base-promoted Kornblum-DeLaMare rearrangement product of endoperoxide 342 (Scheme 100) [380].
It is worth mentioning that the synthesis of 4-hydroxycyclopentenone 343 and litsaverticillols was achieved in a similar way in other works [381][382][383][384]. The nucleophilic addition of the hydroperoxide to the carbon atom of a carbonyl group and the [1,2]-aryl migration are the two rate-determining reaction steps in the Dakin oxidation process [387]. The total rate of the Dakin oxidation depends on the nucleophilicity of the hydroperoxide, the electrophilicity of the carbonyl carbon atom, the nature of alkyl substituents in the proximity of the carbonyl group, the existence of other functional groups in the aromatic ring, and the alkalinity of the reaction mixture. Generally, hydroxybenzaldehydes are more reactive in the Dakin oxidation than hydroxyacetophenones. This is due to the fact, that the carbonyl carbon atom of ketones is less electrophilic than the carbonyl carbon atom of an aldehyde. Under weakly basic conditions, о-hydroxybenzaldehydes and о-hydroxyacetophenones are oxidized more rapidly than p-hydroxybenzaldehydes and p-hydroxyacetophenones, whereas m-hydroxybenzaldehydes and m-hydroxyacetophenones are unreactive [387]. Electron-donating substituents in the ortho and para positions of the aromatic ring enhance the electron density on the migrating carbon atom thus promoting the [1,2]aryl migration and accelerating the oxidation. Electron-donating substituents in the meta position have little effect on the electron density on the migrating carbon atom. Electron-with-drawing substituents in the ortho and para positions of the aromatic ring reduce the electron density on the migrating carbon atom, interfering with the [1,2]-aryl migration. The hydroperoxide anion is a more reactive nucleophile than neutral hydrogen peroxide. The reaction rate of the oxidation of hydroxyphenylaldehydes or ketones increases with increasing pH value, however, at pH higher than 13.5 the oxidation does not take place [387].
The efficient oxidation of hydroxylated aldehydes and ketones to hydroquinones and catechols was performed using a complex of urea with hydrogen peroxide as an oxidant [388]. The main advantage of this method is, that the reaction is performed under solvent-free conditions and provides the products in high yields. ated from o-alkoxybenzaldehydes is employed as the starting reagent in the synthesis of catecholamine derivatives [394]. Catechols, for example are substrates in the manufacture of synthetic adhesives and coatings. Their multifaceted reactions with both, organic and inorganic reagents, make catechols widely applied compounds for surface modifications [395].
Vanillin was oxidized under Dakin conditions under formation of 2-methoxyhydroquinone with 97% yield. This vanillin-derivative was used as a building block in the synthesis of bio-based compounds applicable in polymer field [396].
The Dakin oxidation of mixtures of lignin depolymerization products is an important process for increasing the number of hydroxy groups in arene cycles. Then, these byproducts are glycidylated with mixtures of epoxy monomers. The obtained products are interesting compounds for the synthesis of biobased epoxy thermosets with outstanding thermomechanical indexes [397].

Acid-catalyzed Dakin oxidation:
The mechanism of Dakin oxidation under mild acidic conditions is similar to the base-catalyzed mechanism. A 30-35% aqueous H 2 O 2 /acid system can be employed as the oxidizing agent to synthesize phenols 367a-c from benzaldehydes 366a-c. The oxidation of 366a using traditional peracids produces a mixture of aryl formate 368 and epoxides 369 and 370 (Scheme 108) and cannot be applied to substrates containing peracid-labile functional groups [398].
The addition of boric acid to the H 2 O 2 /acid system leads to an increase in the yield of phenols 372a-f even in the case of benzaldehydes 371a-c or acetophenones 371d-f containing electron-donating groups in the meta position or electron-withdrawing groups in the ortho or para positions with respect to the carbonyl group (Table 16) [399].
Presumably, the coordination of the H 2 O 2 -aldehyde adduct 373 by the highly polarized boric acid is responsible for the increased yields of phenols 372. The adduct 373 easily eliminates a borate ion with concerted migration of the aryl group giving phenols 372. The migrating rate of the aryl group is higher in comparison with hydride migration and formation of 374 (Scheme 109).

Elbs persulfate oxidation of phenols
The Elbs oxidation is the oxidation of phenols 375 with potassium persulfate in the presence of alkali hydroxides to form p-hydroquinones 376 (Scheme 110) [400,401].
The Elbs oxidation is a multistep process, which commences by the formation of the phenolate anion 377. This is followed by the nucleophilic substitution of peroxide oxygen in the peroxydisulfate ion 378 [402] and the resulting sulfoxy group positioned in the para position (compound 379) is hydrolyzed the with formation of p-hydroquinone 376 (Scheme 111). The oxidation of phenols containing electron-donating substituents to dihydroxybenzenes gives products in higher yields compared with phenols containing electron-withdrawing substituents (Table 17) [403][404][405].

Schenck and Smith rearrangements
In 1958, Schenck observed that the storage of 5α-hydroperoxide 385 in chloroform for 3 days results in the shift of the OOH group from the 5α to 7α position and a double-bond migration with formation of 386. This reaction is nowadays known as the Schenck rearrangement (Scheme 114) [409][410][411].
In 1973, Smith discovered another type of rearrangement of allylic hydroperoxides [412]. The 7α-hydroperoxide 386 under- The mechanisms of these, at first glance simple, reactions were systematically investigated 40 years after their discovery.
Three main pathways for the Schenck rearrangement have been proposed (Scheme 116). Path A involves the cyclization resulting in the formation of a carbon-centered radical. Path B comprises the formation of a transition state with the electron density distributed over a cyclic system. Path C proceeds through a dissociation to form an allylic radical and triplet oxygen (Scheme 116) [186,413].
Path A, the initially considered most favorable pathway, was excluded because the isomerization of hydroperoxides 388 and 389 following this route would lead to a β-scission ring opening of 390 (Scheme 117).
However, this process was not observed and none of the possible carbon-centered radicals 390 was trapped by molecular oxygen [414]. Meanwhile, it is known that the dioxacyclopentyl radical 392 formed from 391 is trapped by oxygen to form hydroperoxide 393 (Scheme 118) [415].
It was hypothesized that the Schenck rearrangement of peroxide 394 proceeds through a cyclic structure 395 according to the pathway shown in Scheme 119 [414]. However, this hypothesis was also rejected because the ESR spectra recorded after the photolysis of 5α-and 7α-hydroperoxides 385 and 386 showed that the tertiary allylperoxyl radical and secondary allylperoxyl radical are separate and distinct species, and that they do not have the common cyclic structure 395 [416].
In a study using labeled isotope 18  acid (397) underwent the Schenck rearrangement without incorporating dioxygen from the atmosphere (Scheme 120) [417,418]. Later on, Beckwith and Davies confirmed this fact for cholesterol hydroperoxide [416] and the hydroperoxide generated from valencene [419].
Based on these results, no formation of triplet oxygen occurs in the reaction, thus excluding path C in Scheme 116. Instead, a cyclic transition state (path B, Scheme 116) became more likely, which was confirmed by the stereoselective rearrangement of optically pure olefinic hydroperoxides [420].
However, the study on the rearrangement of hydroperoxides 398, 399 obtained from oleic acid (397) using stereochemical, oxygen-isotopic labeling and solvent viscosity analyses demonstrated that, in hexane, a small amount of atmospheric oxygen is incorporated into the product. The replacement of the solvent by more viscous dodecane and then by octadecane led to a decreased content of atmospheric oxygen in the final product [421,422]. These results provided evidence that the Schenck rearrangement proceeds also through path C in Scheme 116.
Besides, path C was also confirmed by the rearrangement of 18  Examples of the Schenck rearrangement are given in Table 18.
The Schenck rearrangement takes also place with allylic hydroperoxides derived from lipids. The rearrangement of the oleatederived allylic hydroperoxides (S)-421, and (R)-425 involved free radicals includes the oxygen-centered radicals 422, 423,  [426] In CCl 4 at 40 °C for 141 h, the rearrangement proceeds by 80% 5 408a 408b [427] In CDCl 3 , the rearrangement of A into B is completed in 24 h 6 409a 409b [428] In CDCl 3 , the rearrangement is completed in 72 h 7 410a 410b [429] In C 6 H 6 in presence of 10 equiv TBHP and 20 mol % DTBN at 40 °C for 16 h, isomers A and B are formed in equal amounts
The Smith rearrangement is a free-radical chain reaction in which atmospheric oxygen may play a greater role than in the Schenck rearrangement. Apparently, the Smith rearrangement proceeds through a dissociation to the allylic radical and 3 O 2 .
Presumably, the distance between these active species is large enough to allow an exchange with atmospheric oxygen (Scheme 123). The Schenck and Smith rearrangements are both  [430] In CDCl 3 the rearrangement is completed in 48 h 9 412a 412b [431] In CHCl 3 for 5 d at room temperature, only partial conversion 10 413a 413b [432] In CDCl 3 the rearrangement is completed after 3-4 weeks; R: CO 2 H, CO 2 Me, CH 2 OH, CH 3 11
a consequence of the reversibility of the reaction of allyl radicals with triplet dioxygen and differ mechanistically in the degree of separation of these two components [186]. There are only a few examples of the Smith rearrangement known and some of them are collected in Table 19.

Wieland rearrangement
In 1911 Wieland performed the decomposition of bis(triphenylmethyl)peroxide (437) under an atmosphere of CO 2 in boiling xylene for 10 min and obtained the crystalline product 438 in 70% yield (Scheme 125) [441].
The mechanism of the Wieland rearrangement involves the following three steps: Initial formation of O-centered radical A, the rearrangement of radical A into diphenylphen- 2 Unnamed rearrangements of organic peroxides and related processes

Protic acid-catalyzed rearrangements of organic peroxides and related processes
The oxidative transformation of cyclic ketones 58d and 443a-d in the reaction with hydrogen peroxide in alcohols in the presence of sulfuric acid proceeds through the formation of geminal dihydroperoxides 444a-e. The latter compounds are oxidized to dicarboxylic acids 445a-e followed by their transformation into the corresponding dicarboxylates 446a-e, rather than formation of lactones via the Baeyer-Villiger reaction (Scheme 127) [446].
This transformation requires the following key conditions to proceed: a reaction temperature higher than 80 °C, the H 2 SO 4 concentration in the range of 0.2-1.0 mol/L, and a molar ratio of hydrogen peroxide/ketone in the range of 5-10. The corresponding dibutyl esters were prepared in 53−70% yields by oxidation in butanol, which keeps the temperature in the range of 98−106 °C (Table 20).
In a study on the hydroxylation of compounds containing a double bond to the corresponding α-glycols, the tungstic acidcatalyzed reaction of cyclohexene (447) with 90% hydrogen peroxide in methanol, ethanol, or isopropanol afforded the cor- A detailed study on the hydroxylation of cyclohexene (447) in tert-butanol using 30% hydrogen peroxide showed that in this reaction the formation and rearrangements of 2-hydroperoxyalkanols 451 is involved. The treatment of 2-hydroperoxycyclohexanol (451) with acetone afforded the cyclic peroxide 452.
The acid-catalyzed rearrangement of the peroxide 452 gave dialdehyde 453, which further transformed into aldehyde 454.
The isolation and characterization of the latter compound was crucial to an understanding of the oxidation of olefins to aldehydes under the action of hydrogen peroxide (Scheme 129).
The study of the reactions of various unsaturated molecules with hydrogen peroxide demonstrated that the reaction of butenylacetylacetone 455 with H 2 O 2 at pH 5-6 at 38-40 °C produces 2-methyl-3-hexenoic acid (457). Other possible products 456 resulting from a double-bond oxidation reaction were not observed. Apparently, the formation of carbanion A is the driving force of this reaction. Carbanion A transforms into the symmetrical dihydroxyperoxide B, which subsequently rearranges through a deacetoxylation to finally afford 2-methyl-3-hexenoic acid (457) (Scheme 130) [448].
The oxidation of bridged 1,2,4,5-tetraoxanes 458 upon heating in an acidic medium in the presence of H 2 O 2 is leading to esters 459 (Scheme 131) [449]. It is assumed that the reaction of tetraoxanes 458a-f proceeds as an acid-catalyzed oxidative transformation, similar to the Baeyer-Villiger and Hock rearrangements, to yield intermediate A. This is further transformed into esters 459a-f through the oxidation of the CH group and esterification (Scheme 132).
In another study [450], the rearrangement of isomeric ozonides was described. Here, the ozonides 460a,b were interconverted and rearranged into the tricyclic monoperoxide 461 under the action of phosphomolybdic acid (PMA). This result is attributable to the protic acid nature of PMA as well as its ability to form peroxo compounds containing M-O-O groups that influence the direction of the reaction (Scheme 133).
The observed interconversion of ozonides may be useful for the interpretation of the data on the ozonolysis of unsymmetrical unsaturated compounds.

Lewis acid-catalyzed cleavage of peroxides
The The TiCl 4 -promoted rearrangement of (tert-butyldioxy)cyclohexanedienones 472a-d, which are generated by the rutheniumcatalyzed oxidation of phenols with tert-butyl hydroperoxide, provides an efficient route to 2-substituted quinones 473a-d (Table 21) [453,454]. The mechanism of this transformation is depicted in Scheme 136.
In the first step, the coordination of dienone 472 to the Lewis acid gives rise to cation 474. The second step involves a 1,2- alkyl migration to form cation 475. The subsequent deprotonation of the latter affords aromatic intermediate 476.

Scheme 137:
The synthesis of Vitamin K 3 from 472a.
The use of SnCl 4 or TMSOTf as the catalyst made it possible to prepare trimethylsilyl-substituted cyclic peroxides 479a-d and 480a,b in a cis configuration starting from allyltrimethylsilane and bicyclic [2.2.n]endoperoxides 478a-d (Table 22) [457].
The mechanism of this reaction implies that TMSOTf or SnCl 4 promote the heterolytic cleavage of the C-O bond in 478d to form carbocation 481d, which is then attacked by allyltrimethylsilane through a chair-like transition state 482d. The subsequent cyclization of 482d through the stabilized carbocation 483d affords silyl-substituted peroxide, 1,2-dioxane 479d, containing the substituent (-CH 2 SiMe 3 ) in the equatorial position (Scheme 138).
The employment of BF 3 ·Et 2 O as the catalyst for the rearrangement of hydroperoxide 485, which is generated by the oxidation of steroid 484, enables the opening of the D ring between C-14 and C-16 to form diketone 486 (Scheme 139) [458].

Rearrangements and related processes of organic peroxides in the presence of bases
The base-catalyzed rearrangement of cyclic peroxides 488a-g, which are prepared by the manganese-catalyzed oxidation of 1and 1,2-disubstituted cyclopropanols 487a-g, provides a convenient approach to the synthesis of aliphatic and arylaliphatic α,β-epoxy ketones 489a-g. The latter compounds are attractive substrates for the synthesis of for example natural compounds (Scheme 140) [459]. A 1:1 mixture of the diastereomeric hydroperoxides 495a-e was synthesized by ozonolysis of (R)-carvone (494) and in situ trapping with primary alcohols ROH (R = Me, Et, Bu, Pent, Oct). Further cyclization of these hydroperoxides 495a-e using the sodium methanolate/MeOH system results in endoperoxides 496a-e exhibiting antimalarial activity (Scheme 142) [461].
Catalytic amounts of a sodium bicarbonate are sufficient to induce the decomposition of anthracene endoperoxide 499 to anthraquinone (500) (Scheme 143) [478].
There could be two possible paths for base-promoted decomposition of α-azidoperoxides 502 (Scheme 145). The abstraction of the α-hydrogen in the azidoperoxide leads to the direct de-Scheme 142: The multistep transformation of (R)-carvone (494) to endoperoxides 496a-e.

Thermal and photochemical transformations of organic peroxides
Story and co-workers discovered that the thermal and photochemical decomposition of cyclic ketone peroxides 506 produces cycloalkanes 507 and cyclic lactones 508 (Scheme 146 and Scheme 147) [480][481][482][483]. This transformation is a general method for the synthesis of macrocyclic compounds from readily available starting materials.
Examples of the thermal decomposition and photolysis of diperoxide 506a and triperoxide 506b are given in Table 24.
Unsaturated endoperoxides are convenient starting compounds for thermal and photochemical rearrangements. The thermal rearrangement of endoperoxides A into diepoxides B (Scheme 148) is one of the commonly used transformations [353,484,485].  The transformation of peroxide 510 is a key step in the synthesis of the cytotoxic agent stemolide (511) from methyl dehydroabietate (509) (Scheme 149) [486].
The possible mechanism of the rearrangement of endoperoxide 261g is shown in Scheme 150. It is supposed that diepoxide 513a and keto epoxide 514a are generated from diradical 516 via cyclization of the diradical or a 1,2-hydride shift, respectively. Since 1,4-cyclohexanedione is not generated from endoperoxide, it can be concluded that the first cyclization of 515 to 1,3-biradical 516 occurs rapidly and the formation of epoxide rings takes place successively rather than simultaneously.
The photooxidation of indene 517 without a sensitizer provides dioxetane 518, in the presence of Rose Bengal, the diepoxyendoperoxide 521 is obtained. Product 521 originates probably from a [2 + 4] addition of singlet oxygen to give 519, followed by rearrangement to diepoxydiene 520, which is capable of adding a second mole of oxygen. The use of meso-tetraphenylporphyrin instead of Rose Bengal leads to the formation of diendiperoxide 522 (Scheme 151) [484].  [490]. Thermal and photochemical isomerization of related endoperoxides have been applied to the syntheses of other ascaridole analogs [491].
The diepoxide 526 was obtained in 67% yield by photolysis of 525 with a medium-pressure Hg vapor lamp (Scheme 153) [492].
The thermal transformation of endoperoxides produces mainly bis-epoxides, but can also provide unexpected products such as epoxy ketals. The heating of endoperoxide 236 to 160 °C in tol-uene affords epoxy ketal 528 in 53% yield through the formation of biradical 527 (Scheme 154) [347].
The extensive development of methods for the synthesis of cyclopentenones lies in the fact that this structural unit is present in some natural compounds, such as dihydrojasmone, prostaglandins, and rethrolones. The mechanism of thermal decomposition of saturated fulvene endoperoxides 533a-d involves the formation of one of the three intermediates A, B, C, which are precursors to cyclopentenones 534a-d (Table 26) [493].
The replacement of the vinyl group at the exocyclic double bond in the fulvene precursor by a 3-butenyl group and the thermal decomposition of the resulting endoperoxides 535 at 80 °C lead to a [3,4]-sigmatropic shift of the 3-butenyl group and for- mation of the 5-oxo-6-heptenal derivatives 536. The mechanism of this process involves the formation of epoxide A, which undergoes a [3,4]-shift through the intermediate B [494] ( Table 27).
The methylene blue-sensitized photooxidation of arabinofuranosyl furan 537a as an 1:6 α,β-anomeric mixture at −20 °C followed by warming of the reaction mixture to room temperature produced furanoside 539a as an anomeric mixture in the same molar ratio. The photooxidation of pure β-arabinofuranosyl furan 537a produced exclusively β-furanoside 539a. Based on these data, the intermediate endoperoxide 538a originates from the cycloaddition of 1 O 2 to the furanosyl furan. The selective The thermally unstable endoperoxides 541a-d generated from 2-alkoxyfurans 540a-d rearrange through several pathways depending upon the nature of the substituent at the carbon atom C5 in 541 with formation of 542 or 543 (Table 28) [496].
The rearrangement of endoperoxides 541a-c containing a substituent with a tertiary hydroxy group in the 5 position results in the formation of hydroperoxyoxetanes 542a-c and trace amounts of Z-ketoesters 543a-c. Under the same conditions, the rearrangement of endoperoxide 541d containing a substituent with a secondary hydroxy group in the 5 position produces exclusively the Z-keto ester 543d [497].
This difference is apparently attributable to the following two factors: (1) the lower nucleophilicity of the secondary hydroxy group compared to the tertiary hydroxy group; (2) the conformer, which would be suitably orientated towards the nucleophilic attack, is sterically unfavored in the case of R 2 = H. At −20 °C, the transformation of 541d into a conformational isomer occurs more slowly than the thermal decomposition giving 543d (Scheme 157). Thermal rearrangements of strained cyclic peroxides 544a-d and 546a-e provide a versatile tool for the synthesis of carbonyl compounds 545a-d and 547a-e and heterocyclic systems 548 and 549 (Scheme 158) [498,499].

Metal-catalyzed transformations of peroxides
This section focuses on transformations of peroxides under the action of the most representative metals used for these types of reactions: Fe(II), Co(II), Ru(II), and Pd(II).
The Fe(II)-promoted activation of peroxides is believed to be involved in the antimalarial activity of a number of peroxides, including the natural product artemisinin. The understanding of the underlying mechanism of the Fe(II)-promoted cleavage of bicyclic peroxides is critical to the design and preparation of more efficient antimalarial peroxides. From this perspective, metal-catalyzed transformations of peroxides are of special interest. It was shown [502] that the reaction of fluorinated cyclic peroxide 557a with FeBr 2 in THF proceeds through an intermediate O-centered radical to form epoxy ketone 558a and 1,4-diol 559a. The reaction of 557b with FeCl 2 (PPh 3 ) 2 in CH 2 Cl 2 proceeds in a different manner through an intermediate O-centered radical to yield diepoxide 560b (Scheme 161) [503].
In a related study investigating the reaction of 557а-с with FeBr 2 , bis-epoxides 560а-с and epoxy ketones 561а-с were obtained as the major products (Table 29) [504] and the proposed mechanism of the rearrangement of 557a-c is presented in Scheme 162.

Scheme 161:
The Fe(II)-promoted cleavage of aryl-substituted bicyclic peroxides.  formation of a 1:1 mixture of products 566 and 567. This is attributed to the fact that the reaction proceeds through 1,5-hydrogen transfer, while β-scission does not occur (Scheme 164) [505].

Both in THF and CH 3 CN, the intermediate O-centered radical
The reaction of Fe(II) cysteinate with dioxolane 568 produced compounds 569 and 570, which were isolated from the reaction mixture. The formation of methyl acetate 571 was confirmed by GC analysis of the reaction mixture before work-up (Scheme 165) [506].
The reaction of 1,2-dioxanes 572a-c with FeCl 2 is accompanied by the formation of lactones 573a,b, which were isolated in the individual state (Scheme 166) [507].
The reaction of synthetic tetraoxane 574 with Fe(II) cysteinate affords a complex mixture of products. Only one product, 575, could be isolated from the mixture and identified. This was the first work, where the Fe(II)-promoted cleavage of 1,2,4,5tetraoxane was investigated (Scheme 167) [508].
The study of the CoTPP-catalyzed transformation of bicyclic endoperoxides containing non-strained diene moieties demonstrated that the formation of epoxides can be accomplished in yields up to 90-100%, while the side reaction giving epoxy ketones is suppressed. A detailed study on the CoTPP-catalyzed reaction of 600a showed that this reaction affords, in addition to the expected diepoxide 601a, two isomeric epoxy aldehydes 602a and 603a. The reaction of bicyclic endoperoxides 600b,c gives, instead of the expected epoxides 601b,c, exclusively epoxy aldehydes 602b, 603b and the reaction of endoperoxide 600d produces solely the diepoxide 601d (Scheme 168) [519].
The reaction of epoxy-1,2-dioxanes 604a-d and 606 with Co(II) complexes affords 4-hydroxy-2,3-epoxy ketones 605a-d and 607 in good yields (Scheme 169) [364]. Possibly the selectivity towards the hydroxyketones formation is provided by means of cobalt ions interaction. The obtained compounds are useful synthons in organic synthesis.    Transformations of endoperoxides catalyzed by variablevalence metals are well studied for metals such as Cu(II), Fe(II), or Co(II), which can initiate the reaction through a one-electron oxidation-reduction mechanism. The decomposition of endoperoxides catalyzed by Ru(II)phosphine complexes also belongs to this type of reaction and the decomposition produces diepoxides as the major products.
The reactivity of bicyclic substrates depends on the carbon-ring size. Strained 1,4-endoperoxide derivatives are readily decomposed under the action of Pd(PPh 3 ) 4 at room or elevated tem-peratures, whereas substrates containing larger rings require more severe conditions. Monocyclic substrates are less reactive than bicyclic endoperoxides and require even more harsh conditions.
3 Rearrangements and related processes of important natural and synthetic peroxides 3.1 Antimalarial, antiparasitic, and antitumor peroxides The extensive development of the chemistry of organic peroxides has been stimulated largely by the isolation of the antimalarial agent artemisinin from leaves of the annual wormwood Artemisia annua in 1972. The structural identification showed that artemisinin contains a cyclic endoperoxide moiety (1,2,4trioxane ring), which plays a key role in its antimalarial activity [526,527]. The highly reactive and unusual chemical structure, in addition to low yields isolated from natural sources gave impetus to the development of total synthesis methods of artemisinin. Several routes towards the total synthesis of this compound were elaborated and several semisynthetic derivatives were prepared [12,16,[528][529][530][531][532][533]. The high costs of these products stimulated the search for alternative peroxides, which are synthetically easier accessible and less expensive compared with the natural and semisynthetic structures. It was shown that 1,2-dioxolanes [35], 1,2-dioxanes [40], 1,2,4-trioxolanes [534][535][536], 1,2,4-trioxanes [44], and 1,2,4,5-tetraoxanes [537] exhibit antimalarial activity, which was sometimes higher than that of the parent artemisinin (Scheme 172). As a milestone of this research, arterolane, a fully synthetic 1,2,4-trioxolane was discovered and in 2012, the arterolane-based drug synriam was approved to the market.  Although artemisinin has been used in medicine for about three decades, the mechanism of its action remains unclear [538,539]. Two main theories of its antiparasitic action are assumed. In accordance with one theory, the endoperoxide bond is reduced by means of iron ions leading to the formation of oxygen-centered radicals, which are responsible for the initiation of oxidative stress in infected erythrocytes. An alternative theory proposes that specific parasites' proteins or heme are alkylated by carbon-centered radicals derived from the peroxide [540,541]. In infected human erythrocytes, malaria parasites digest more than 70% of the hemoglobin with formation of globin and heme. After the hydrolysis of globin, the resulting amino acids are used by the parasites for protein synthesis. Malaria parasites detoxify the toxic heme via a heme polymerization process with preparation of hemozoin, which exists in the crystalline form. Parasite metalloproteins, superoxide dismutase and ferredoxin, use a small part of the host's iron for their construction. In such a manner parasite cells always contain heme iron and non-heme iron, allows for the interaction with artemisinin or other peroxides [542]. In the reaction with Fe(II), the natural antimalarial terpene cardamom peroxide 639 isolated from Amomum krervanh Pierre (Siam cardamom) is transformed into acids 640, 641, and 642 (Scheme 177) [164].
However, the cleavage of tetraoxane 643 gives two major products, namely 644 and 645, in yields of 44% and 51%, respec-tively. The reaction mechanism based on the results of this study is shown in Scheme 178 [556].
Presumably, in accordance with the direction from Fe(II) to O2, tetraoxane 646 interacts with iron(II) heme 647. Starting heme 647 reacts within 30 min with formation of three products. The LC-MS study proved the formation of the covalent coupling product 648 formed from heme (mass 616) and the tetroxanederived secondary C-centered radical. The molecular ion [M] + of coupling product 648 was observed at m/z 782.3, which is consistent with the prediction (Scheme 179) [537,556].
Under similar conditions, the same alkylated heme adduct was obtained with trioxolanes [557]. Four peaks at m/z 782.3 were detected which were assigned to the four possible regioisomers of alkylated heme adduct 648 as reported for heme-artemisinin adducts [558]. Later, in an initial study dealing with monoclonal antibodies that recognize the alkylation signature (sum of heme and protein alkylation) of synthetic peroxides it was shown that the artemisinins alkylate proteins in P. falciparum [559].
All the above-mentioned transformations involve the homolytic O-O-bond cleavage resulting in the formation of an O-centered radical, which is followed by the rearrangement into a C-centered radical, as a key step. The subsequent transformation of the C-centered radical determines the structure of the final product.

Rearrangement of lipid peroxides
Lipids contained in cell membranes maintain the structure and control of the vital functions of cells. Lipids are the targets of the reactions with reactive oxygen species (ROS) such as various oxygen-centered radicals, which play a key role in several pathological states [561]. Compounds containing double bonds, polyunsaturated fatty acids and esters, cholesterol and its derivatives easily undergo oxidation by action of oxygencentered radicals (Scheme 181) [562,563]. transformations mediated by a series of specific isomerases and synthases with production of PGE 2 , PGI 2 , PGD 2 , PGF 2 , and T X A 2 (Scheme 182) [564][565][566][567].
The formation of the metabolites isoprostanes, neuroprostanes, phytoprostanes, and isofurans 655-657 from fatty acids under autoxidative conditions in vivo involves both the reduction of peroxides and their rearrangements (Scheme 183). These compounds proved to be widespread in nature. Compounds 655-657 display significant biological activities, and the isoprostanes are currently the most reliable indicators of oxidative stress [568][569][570].

Scheme 183:
The reduction and rearrangements of isoprostanes.
One of the essential fatty acids, linoleic acid, contains a homoconjugated diene fragment, which is responsible for a specific peroxidation mechanism without the formation of cyclic peroxides. In addition to linoleic acid, its esters are present in the human circulating low-density lipoprotein (LDL). For this reason, the oxidation of linoleic acid esters is of special biomedical interest [566]. A mechanism for linoleate (658) oxidation, which involves hydroperoxyoctadecadienoates (HPODE, 660-662) preparation, is presented in Scheme 184. The first step of the oxidation process is the formation of the carboncentered pentadienyl radical 659. The reaction of 659 with O 2 produces three peroxyl radicals, one of them having a nonconjugated diene part with the oxygen at C-11 position. The two other radicals have Z,Eand E,E-conjugated diene parts with oxygen substituents at the C-9 and C-13 positions. These peroxyl radical intermediates after abstracting hydrogen atoms transform to the hydroperoxyoctadecadienoates (HPODE, 660-662) [570].
The Hock cleavage mechanism is a possible route to transform lipid hydroperoxide 663 into smaller carbonyl compounds 664-666, although this transformation seems to occur only in the presence of photosensitizers (Scheme 185) [571]. In mammalian tissues and cells, cholesterol is found to a large extent. One of the main cholesterol functions represents to maintaining the stability of plasma membranes. The oxidation Scheme 186: The acid-catalyzed cleavage of the product from free-radical oxidation of cholesterol (667).
of cholesterol by means of free radical particles is responsible for the initiation of a range of pathological conditions [572,573]. Many processes including the rearrangement of intermediately formed peroxides accompany the oxidation of cholesterol. The major product of 1 O 2 oxidation of cholesterol (667), cholesterol 5α-hydroperoxide (668), readily forms 5,6secosterol ketoaldehyde 669 and the product of its intramolecular aldolization 670 through an acid-catalyzed (Hock) cleavage of the C5-C6 bond in 668 (Scheme 186) [67].

Rearrangement of dioxygenase enzyme-substrate systems
A useful chemical property of most soil bacteria concludes in their capability to oxidize aromatic compounds. This multistep process depends on the structure of dioxygenase enzymes, which utilize molecular oxygen for oxidation [574]. This oxidation has attracted much attention as a green chemistry approach for the conversion of aromatic compounds to water-soluble products and for degradation of lignin [575,576]. The ring cleavage of 1,2-dihydroxybenzene (catechol) is likely the most thoroughly studied reaction which is catalyzed by iron-dependent catechol dioxygenase enzymes [577][578][579]. The oxidation of catechols 671 and 673 by two types of enzymes -intradiol dioxygenase and extradiol dioxygenase -affords 3-carboxyhexa-2,4-dienedioic acid (672) and 2-hydroxy-6-ketonona-2,4dienoic acid (674) (Scheme 187) [580,581].
A key step in the cleavage of the aromatic ring is the oxygenatom insertion into the C-C-double bond as the result of a Criegee-like or Hock-like intermediate rearrangement [582,583]. It was demonstrated that, despite the different mechanisms of the initial step of the substrate/molecular oxygen activation, both reactions produce hydroperoxide 675 as the intermediate.  [585,586].
In this section, we considered rearrangements of the most important natural and synthetic peroxides, which proceed or can take place in biological systems. Apparently, there are is a much larger number of biological processes, involving rearrangements of peroxides, which has to be discovered and studied in the future.

Conclusion
The rearrangements of organic peroxides and related processes are covered in the literature in hundreds of publications and several specialized reviews. However, these reviews are limited in scope, narrow in their approach, and do not provide an overall picture of this field of chemistry. The present review is the first to offer a complex analysis of the available data on re- arrangements of peroxides published in the last 15−20 years with an excursion to the history of the discovery of particular reactions and transformations. The rearrangements and related processes are classified according to the type of the catalysts used: acid-and base-catalyzed processes, reactions catalyzed by variable-valence metals, photochemical and thermal action. Special emphasis is drawn to current trends in the performance and application of rearrangements of organic peroxides, such as asymmetric synthesis, organocatalysis, and the use of transition metal-peroxo complexes for the preparation of compounds interesting for pharmacological applications. The published data summarized in the review provide, for the first time, an insight into the common and different features of the reaction mechanisms and allow predicting experimental and structural requirements for performing rearrangements with specified results. An analysis of the published data shows that there are numerous new and unnamed processes related to name reactions. The development and investigation of these processes are apparently the future of peroxide chemistry.
Rearrangements of organic peroxides are the key steps in processes such as the Baeyer−Villiger, the Criegee and Hock reactions, the Kornblum−DeLaMare rearrangement, and Dakin and Elbs oxidation reactions. These reactions are widely used in chemistry: The Baeyer−Villiger oxidation is widely used for the synthesis of esters and lactones. The Criegee reaction is employed to transform tertiary alcohols into ketones and aldehydes. The Kornblum−DeLaMare rearrangement is an important tool in the synthesis of γ-hydroxy enones. The Dakin oxidation is applied in the synthesis of phenols from arylaldehydes or aryl ketones and the Elbs persulfate oxidation is used to prepare hydroxyphenols from phenols.
The comprehensive analysis of the published data makes the knotty term "peroxide rearrangement" more exact. Two types of processes are actually included under the term "peroxide rearrangement": processes that fall under the definition of a classical rearrangement, resulting in the formation of a compound of isomeric structure, and processes, in which the O-O-bond cleavage is followed by the rearrangement of one of the resulting fragments.
The pathways of peroxide rearrangements mainly depend on the type of the catalysts used, the reaction conditions, and the structure of the starting peroxide. Rearrangements can be accompanied by a homolytic or heterolytic O-O-bond cleavage, through the formation of a carbocation (e.g., the Criegee rearrangement), a carbanion (e.g., the Kornblum−DeLaMare rearrangement), or an O-centered radical (e.g., the Wieland rearrangement or rearrangements promoted by variable-valence metals).
In recent years, there has been a growing interest in organic peroxides as a base for the design of antiparasitic and antitumor agents, which led to an extensive search for new classes of peroxides. New compounds and new structural classes play a key role in the development of the chemistry of rearrangements and the performance of related useful transformations of peroxides.