Cross-dehydrogenative coupling for the intermolecular C–O bond formation

The present review summarizes primary publications on the cross-dehydrogenative C–O coupling, with special emphasis on the studies published after 2000. The starting compound, which donates a carbon atom for the formation of a new C–O bond, is called the CH-reagent or the C-reagent, and the compound, an oxygen atom of which is involved in the new bond, is called the OH-reagent or the O-reagent. Alcohols and carboxylic acids are most commonly used as O-reagents; hydroxylamine derivatives, hydroperoxides, and sulfonic acids are employed less often. The cross-dehydrogenative C–O coupling reactions are carried out using different C-reagents, such as compounds containing directing functional groups (amide, heteroaromatic, oxime, and so on) and compounds with activated C–H bonds (aldehydes, alcohols, ketones, ethers, amines, amides, compounds containing the benzyl, allyl, or propargyl moiety). An analysis of the published data showed that the principles at the basis of a particular cross-dehydrogenative C–O coupling reaction are dictated mainly by the nature of the C-reagent. Hence, in the present review the data are classified according to the structures of C-reagents, and, in the second place, according to the type of oxidative systems. Besides the typical cross-dehydrogenative coupling reactions of CH- and OH-reagents, closely related C–H activation processes involving intermolecular C–O bond formation are discussed: acyloxylation reactions with ArI(O2CR)2 reagents and generation of O-reagents in situ from C-reagents (methylarenes, aldehydes, etc.).


Introduction
The development of methods for the cross-dehydrogenative coupling (CDC; or oxidative cross coupling) is an important field of modern organic chemistry. These terms commonly refer to reactions, in which two different molecules are linked by a new bond accompanied by the elimination of a hydrogen atom from each molecule (Scheme 1) [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15]; however, these terms are also applied to a large number of various reactions with oxidants, which involve the intermolecular formation of new bonds between the starting molecules. For instance, such reactions involve the oxidation of several C-H bonds, the elimination not only of hydrogen atoms but also of other moieties from the starting molecules, the addition at C-C multiple bonds, and so on. The cross-dehydrogenative coupling can be employed to form a new bond with high atomic efficiency and does not require additional synthetic steps for the introduction of functional groups (for example, such as -Hal, -OTf, -BR 2 , -SnR 3 , -SiR 3 , -ZnHal, -MgHal) into molecules necessary in other cross-coupling reactions. Therefore, the cross-dehydrogenative coupling is a promising approach to the minimization of byproduct formation and the reduction of the number of steps of the organic synthesis [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15].
Studies of the cross-dehydrogenative coupling are not only of practical but also of fundamental interest because new aspects of the reactivity of organic compounds have to be found for the performance of these reactions. The prediction of the conditions necessary for the efficient cross-dehydrogenative coupling is an important problem that requires an understanding of the mechanisms of these processes.
Among cross-dehydrogenative coupling reactions, C-C coupling reactions have been studied in most detail [1][2][3][4][5][6][7][8][9][10][11][12][13][14], whereas the C-O coupling is less well-known (Scheme 2). We present the first systematic review of the main approaches to the cross-dehydrogenative C-O coupling. The starting compound, which donates a carbon atom for the formation of a new C-O bond, is called the CH-reagent or the C-reagent, and the compound, an oxygen atom of which is involved in the new bond, is called the OH-reagent or the O-reagent. Alcohols and carboxylic acids are most commonly used as O-reagents; hydroxylamine derivatives, hydroperoxides, and sulfonic acids are employed less frequently. In the case of O-reagent PhI(O 2 CR) 2 , dehydrogenated carboxylic acid RCO 2 H is preliminary included in the oxidant, so C-H acyloxylation with PhI(O 2 CR) 2 can be considered as the second stage in a two-step cross-dehydrogenative C-O coupling. The formation of a new C-O bond generally takes place with the involvement of an O-nucleophile, an O-radical, or an O-electrophile. In the oxidative coupling with O-reagents as nucleophiles, electrophilic intermediates that are generated from C-reagents are prone to side transformations. Therefore, O-reagents are often used in excess amounts. The C-O coupling reactions involving O-centered radicals are generally performed under severe conditions. In addition, O-radicals are highly reactive and unstable, and the reactions with these radicals are often nonselective and are accompanied by the formation of alcohols, carbonyl compounds, and fragmentation products. The examples of the C-O bond formation between two molecules using O-electrophiles are rare; electron-deficient peroxides with a specific structure can act as O-electrophiles [16][17][18]. These processes are not consistent with general Scheme 2 of the crossdehydrogenative C-O coupling and are not considered in the present review.
The cross-dehydrogenative C-O coupling reactions are carried out using different C-reagents, such as compounds containing directing functional groups (amide, heteroaromatic, oxime, and so on) and compounds with activated C-H bonds (aldehydes, alcohols, ketones, ethers, amines, amides, compounds containing a benzyl, allyl, or propargyl moiety). An analysis of the published data showed that the principles at the basis of a particular cross-dehydrogenative C-O coupling reaction are dictated mainly by the nature of the C-reagent. Hence, in the present review the data are classified according to the structures of C-reagents, and, in the second place, according to the type of oxidative systems. Since structurally different OH-reagents are often involved in C-O coupling reactions of the same type, the classification according to the structures of O-reagents is inconvenient and was not applied.
Some cross-dehydrogenative C-O coupling reactions are cursorily described in reviews on the oxidative C-heteroatom bond formation without the use of metal compounds [15], the Pd(II)catalyzed oxidative C-C, C-O, and C-N bond formation [3], the transition metal-catalyzed etherification of unactivated C-H bonds [19], the Pd(II)-catalyzed oxidative functionalization at the allylic position of alkenes [20,21], the oxidative functionalization catalyzed by copper compounds to form C-C, C-N, C-O, C-Hal, C-P, and N-N bonds [10], the Bu 4 NI/t-BuOOH oxidative system [22], selective functionalization of molecules [23], the oxidative esterification and oxidative amidation of aldehydes [24], and the transition metal-catalyzed radical oxidative cross-couplings [13]. The present review summarizes primary publications on the cross-dehydrogenative C-O coupling, with special emphasis on the studies published after 2000. The focus is on the reactions described by general Scheme 2.

Review 1 C-Reagents containing directing groups in cross-dehydrogenative C-O coupling
Nitrogen-containing moieties (amide, pyridine, oxime, etc.) are most commonly used as directing groups, which are responsible for the regioselectivity of the C-O coupling. Most transformations of this type are catalyzed by Pd(II) compounds. Examples of the use of copper and ruthenium compounds as catalysts were also reported. It is commonly assumed that the reaction proceeds via the C-metal bond formation accompanied by the C-H bond cleavage assisted by the directing group of the substrate, which forms a complex with the metal ion. The mechanism of this type of reactions was considered in detail in the publications [25][26][27][28][29][30][31][32].

Reactions involving C(sp 2 )-H bonds of aromatic C-reagents
In one of the first publications on the preparative introduction of the -OR group into CH-reagents containing directing groups, 8-methylquinoline, 2-arylpyridines, N-phenylpyrazole, azobenzene, and benzylideneaniline were subjected to the acetoxylation using the Pd(OAc) 2 /PhI(OAc) 2 system [33]. More recently, reactions involving the same and some other directing groups were studied in more detail. In most of the studies, Pd(OAc) 2 was used as the catalyst, and PhI(OAc) 2 or peroxides served as the oxidants.
The regioselectivity of the ortho-acetoxylation of meta-substituted arylpyridines and N-arylamides 1 was studied [34]. The acetoxylation occurs mainly at the sterically more accessible para-position relative to the substituent R to form product 2.
The pyridine moiety served as the directing group in many works to accomplish the ortho-acyloxylation of arenes 4 giving products 5 ( Table 1). The reactions were catalyzed by copper, palladium, or rhodium salts. Carboxylic acids or their salts, as well as aldehydes, methylarenes, arylethylenes, and arylacetylenes were used as precursors of the acyloxy fragment.
The cross-dehydrogenative C-O coupling with 2-arylpyridines 4 proceeds also in the presence of the Cu(OAc) 2 /O 2 system [40] and under electrochemical oxidation in the presence of Pd(II) salts [41]. dehydrogenative C-O coupling products 24-30 (Scheme 6). The alkoxylation of 1-naphthonitrile 20 occurs not at the orthoposition but at the 8-position of the aromatic system to give product 26. The acetoxylation takes place under more severe conditions compared with the alkoxylation. The acetoxylation employing the S-methyl-S-2-pyridylsulfoximine moiety as the bidentate directing group can be performed at lower temperature (50 °C instead of 100 °C, as in the case of CH-reagents 22 and 23) [53].
The ruthenium-catalyzed ortho-acyloxylation of acetanilides 39 with carboxylic acids in the presence of AgSbF 6 and ammonium persulfate afforded products 40 (Scheme 8) [57]. This method can be used for the selective replacement of one of the two hydrogen atoms in the ortho-position of acetanilide; the molar ratio of the C-and O-reagents is close to stoichiometric.
The acetoxylation (product 42) and methoxylation (product 43) of N-(2-benzoylphenyl)benzamides 41 at the ortho-position of the benzamide moiety of the substrate were performed using Pd(OAc) 2 combined with PhI(OAc) 2 as the oxidant (Scheme 9) [58]. The alkoxylation of N-tosylbenzamides 44 in the presence of the same oxidative system takes place at room temperature and gives products 45 [59]. The reactions of benzamides containing the nitro group at the ortho-position are most difficult to perform [58,59].
The quinoline-8-amine directing moiety was used for coppercatalyzed aerobic ortho-aryloxylation and alkoxylation of arenes 59 with electron donating or electron withdrawing substituents to afford products 60 [66] (Scheme 12). The method is applicable to a wide range of OH-reagents; the molar ratio OH-reagent/CH-reagent was 1:1 for aromatic OH-reagents and 5:1 for aliphatic alcohols. Different organic and inorganic bases were used depending on the structures of substrates.
form coupling products with one (product 62) or two (product 63) equivalents of phenol (Scheme 13) [67]. The same directing group was used for aerobic ortho-alkoxylation of arenes 64 in the presence of CuCl and K 2 CO 3 to afford monoalkoxylated products 65 [68].
The 2-aminopyridine-1-oxide directing group was used in a rare example of a cobalt-catalyzed oxidative alkoxylation of arenes 66 and alkenes 67 to afford products 68 and 69 under mild contitions [69] (Scheme 14). The directing group can be removed to obtain the corresponding benzoic acid 71 from the cross-dehydrogenative coupling product 70 [69].
The majority of above mentioned directing groups cannot be easily removed or modified, thus limiting the scope of possible target products. To overcome these limitations, 2-pyridyldiisopropylsilyl (PyDipSi) [70,71] and 2-pyrimidyldiisopropylsilyl (PyrDipSi) [72,73] directing groups were proposed by the research group of Prof. V. Gevorgyan. The PyDipSi group was used for selective monoacetoxylation or pivaloyloxylation of the arene ortho-position [70,71], whereas the PyDipSi group allowed to achieve one-pot sequential acyloxylation of both ortho-positions affording, in particular, orthogonally protected resorcinol derivatives 73 in one step starting from PyrDipSi arenes 72 [72] (Scheme 15).
Pd(OAc) 2 was used as catalyst with addition of AgOAc or LiOAc; PhI(OAc) 2 or PhI(OPiv) 2 were used as oxidants and sources of OAc and OPiv fragments, respectively, the syntheses were performed in dichloroethane at 80 °C for 1-168 h. After ortho-acyloxylation step silyl directing group can be removed or substituted by a desirable moiety (-Aryl, -OH, -B(pin), -I, etc.).
Another example of an easily modifiable directing group is an N-nitroso moiety that can be easily reduced to amine employing Fe/NH 4 Cl [74]. N-Nitroso directed C-H alkoxylation of arenes 74 was realized using the Pd(MeCN) 2 Cl 2 /PhI(OAc) 2 oxidative system to obtain products 75 [74] (Scheme 16).

Reactions involving C(sp 3 )-H bonds of C-reagents with alkyl groups
In some studies, directing groups were used to accomplish the C-O coupling involving sp 3 -carbon atoms of C-reagents. Scheme 17 presents the alkoxylation of CH-reagents 76, 77 and the acetoxylation of CH-reagents 78.

Scheme 14:
Cobalt-catalyzed aerobic alkoxylation of arenes and alkenes containing pyridine N-oxide moiety.  reaction occurs at the methylene group of the molecule (with the sp 3 -carbon atom) rather than at the ortho-position of the aromatic system, which is also adjacent to the directing group. The Pd(OAc) 2 /PhI(OAc) 2 oxidative system was employed in the methoxylation of dimethylcarbamoyltetrahydrocarbazoles 76 [75] and the acetoxylation of compounds containing the picolinamide directing group 78 [76,77]; the butoxylation of the methylene group of 2-benzylpyridine 77 took place in the presence of the Cu(OAc) 2 /AgOTf/O 2 system [47]. Cross-dehydrogenative C-O coupling products 79-81 were obtained, despite the potential possibility of the more profound oxidation of the methylene group to the keto group.
The benzylic position of 2-alkylpyridines and related compounds 82 was acetoxylated using the Pd(OAc) 2 /CuI catalytic system in acetic acid under an oxygen pressure of 8 atm to prepare products 83 (Scheme 18) [78].

Scheme 19:
Acyloxylation and alkoxylation of alkyl fragments of substrates containing amide or sulfoximine directing groups.
In the above considered examples, the oxidative C-O coupling occurs with the involvement of methyl or methylene groups directly bonded to the aromatic ring. The C-O coupling reactions involving unactivated alkyl groups of C-reagents are considered below.
The amide moiety was most commonly employed as the directing group. The alkoxylation of alkyl groups of N-(quinolin-8-yl)amides 84 [81], picolinamides 85 [62], and N-(2-pyridin-2-yl)propan-2-yl)amides 86 [63], the trifluoroacetoxylation of amides 87 [82], and the acyloxylation of compounds containing the S-methyl-S-pyridylsulfoximine moiety 88 [83] were accomplished to prepare coupling products 90-95 (Scheme 19). In some cases, the latter reaction proceeds efficiently even at room temperature. Iodine(III) compounds 89, (diacetoxyiodo)benzene, or potassium persulfate served as oxidants. The former three reactions are applicable to a broad range of substrates and alcohols. The drawback is that a large excess of alcohols is required. Unlike the alkoxylation of 84-86, the trifluoroacetoxylation of 87 was performed with structurally simple amides. This method is applicable only to α-disubstituted amides. The reactions with amides containing hydrogen in the α-position give coupling products 93 in substantially lower yields [82]. Similar limitations are encountered when performing the acyloxylation of S-methyl-S-pyridylsulfoximines 88.
Using the N-(quinolin-8-yl)amide directing group Pd(OAc) 2 catalyzed the double sp 3 C-H alkoxylation of 96 for the synthesis of symmetric acetals 97 and unsymmetric acetals [84] (Scheme 20). The method demonstrates good functional group tolerance and the applicability in the synthesis of products containing α-hydrogen next to an amide moiety.  [56]. The acylation of oxime 101 and the C-H acetoxylation of 102 are performed as a one-pot operation. In the acetoxylation of alkyl groups, the methyl group is more reactive than the methylene one.
The O-methyl oxime [54,86] or pyridine moieties [86] were employed as directing groups in the acetoxylation of alkyl groups using the Pd(OAc) 2 /PhI(OAc) 2 system. The synthesis was carried out at 80-100 °C during a period of time from 5 min to 12 h in acetic acid, a 1:1 AcOH/Ac 2 O mixture, or dichloromethane. More recently, a Pd(OAc) 2 /NaNO 3 /O 2 catalytic system was developed for acetoxylation of unactivated sp 3 -C-H bonds using the same directing groups [87]. Air or oxygen (1 atm) played a role of terminal oxidant and sodium nitrate was a redox co-catalyst; the reactions were performed in a AcOH/Ac 2 O solvent mixture at 100-110 °C for 18 h.
The oxazole moiety also acts as the directing group in the acetoxylation of alkyl groups with Pd(OAc) 2 /AcOOt-Bu or Pd(OAc) 2 /lauroyl peroxide oxidative systems; in these reactions acetic anhydride served as the source of the acetoxy  groups [88]. Recently, Cu(OAc) 2 -mediated аcetoxylation of unactivated methyl fragments using the N-(quinolin-8-yl)amide directing group and AgOAc as oxidant was achieved without a Pd catalyst [89].

Aldehydes and alcohols as C-reagents in cross-dehydrogenative C-O coupling
There are numerous reactions, in which aldehydes are involved in the oxidative C-O coupling with alcohols under the action of oxidizing agents to form esters. In some cases, primary alcohols are used instead of aldehydes. It is commonly assumed that, under these reaction conditions, primary alcohols are oxidized to aldehydes followed by cross-dehydrogenative C-O coupling. These processes with aldehydes or primary alcohols as C-reagents giving esters are often referred to as oxidative esterification.

Transition metal salt-catalyzed reactions using compounds with C=C, C=O, and C-Hal bonds as oxidants
One of the types of the oxidative esterification is based on the hydrogen transfer catalyzed by transition metal complexes. In these reactions, compounds with a double bond or a C-Hal bond act as oxidants (hydrogen acceptors). Examples of these reactions with aldehydes or primary alcohols as C-H reagents are given in Table 2.
Scheme 23: Possible mechanism of oxidative esterification catalyzed by N-heterocyclic nucleophilic carbene.
Crotononitrile, acetone, and benzyl halides were used as oxidants. Ruthenium, iridium, and palladium complexes acted as catalysts. In most cases, structurally simple alcohols, which are taken in a large excess relative to the CH-reagent, served as OH-reagents. The exception is a study [95], in which the coupling was accomplished using an equivalent amount of alcohol.

Oxidative systems based on noble metals and oxygen
The oxidative coupling of benzyl alcohols with aliphatic alcohols in the presence of Pd(II) salt/Ag(I) salt/base/oxygen system was proposed [96,97]. In the study [97], phosphine ligands were additionally employed. It is suggested that the coupling occurs through oxidation of benzyl alcohol to benzaldehyde. Alcohols (OH-reagents) are taken in a twofold molar excess [96] or are used as solvents [96,97]; the reaction time is 20-40 h at 45-80 °C. The aerobic oxidative coupling of aldehydes or primary alcohols as CH-reagents with low-molecular-weight alcohols was performed in the presence of heterogeneous catalysts, such as Au/TiO 2 [98][99][100], Au/β-Ga 2 O 3 [101], Au/polymer [102], and AuNiO x /SiO 2 -Al 2 O 3 -MgO [103]. In all the abovementioned processes in the presence of heterogeneous catalysts, low-molecular-weight alcohols are used as the solvents or are taken in a large excess relative to the CH-reagent.

Reactions catalyzed by N-heterocyclic carbenes
N-heterocyclic nucleophilic carbenes 105 have found use for the oxidative esterification. Scheme 23 shows, in a simplified way, the proposed mechanism of this type of cross-dehydrogenative C-O coupling [104][105][106][107][108][109][110][111][112][113]. The aldehyde is subjected to the attack of N-heterocyclic nucleophilic carbene 105, which can be generated from the corresponding azolium salt 104. The resulting intermediate 106 is oxidized to 107 followed by the nucleophilic attack by the alcohol to form ester 108.
The mechanism of the aerobic oxidative coupling of benzaldehyde with methanol in the presence of the 4-ethyl-1-methyl-1H-1,2,4-triazolium iodide/DBU system was studied in detail [114]. It was shown that the reaction proceeds via another mechanism, involving the formation of 2-hydroxy-1,2-diphenylethanone from benzaldehyde followed by the oxidation of this intermediate to 1,2-diphenylethanedione.
Scheme 24 shows an example of the oxidative coupling of aldehydes and alcohols, in which CH-and OH-reagents are taken in equivalent amounts [104]. Thiazolium salt 109 combined with triethylamine acted as the catalyst, and azobenzene 110 served as the oxidizing agent. Esters 111 were prepared in 16-97% yield.
The selective oxidative coupling of aldehydes 112 and alcohols 113 in the presence of amines 114 using 1,4-dimethyltriazolium iodide (115), DBU and quinone 116 afforded esters 117. This method was also applied to the synthesis of esters 117a-c from amino alcohols (Scheme 25) [115,116].
Different conditions were proposed for the cross-dehydrogenative C-O coupling of aldehydes with alcohols and phenols catalyzed by N-heterocyclic carbenes (118,129) or their precursors, azolium salts (119-128), combined with bases (Table 3; the publications are summarized in chronological order). In most cases, alcohols were taken in an excess.
The oxidative esterification in the presence of azolium salts 119, 121, and 125 was performed with primary alcohols instead of aldehydes (Table 4). It is supposed that under the reaction conditions primary alcohol is initially oxidized to aldehyde without the participation of N-heterocyclic carbene [106,113,123,124].
The oxidative esterification of aldehydes with racemic mixtures of alcohols catalyzed by chiral N-heterocyclic carbenes was used for the kinetic separation of enantiomers of alcohols [125,126].

Reactions using halogen-containing oxidative systems
This section considers cross-dehydrogenative C-O coupling reactions with aldehydes and primary alcohols as C-reagents in  which halogens and their compounds, for example, molecular iodine, the Bu 4 NI/t-BuOOH system, organic iodine(III or V) compounds, bromides combined with oxidants, hypochlorite, and so on, acted as oxidants.
The oxidative coupling of primary alcohols 130 with methanol or trifluoroethanol and the oxidative coupling of aldehydes 132 with structurally diverse alcohols 133 were performed using molecular iodine in the presence of potassium carbonate (Scheme 26) [127]. In the former case, methanol or trifluoroethanol served as the solvent. In the latter case, the reaction was carried out in tert-butanol; the amount alcohol was nearly equivalent relative to aldehyde. It is suggested that the reaction proceeds through the formation of hemiacetal from alcohol and aldehyde, which is oxidized by iodine to ester 131 or 134. In the coupling of two alcohols, one of them is initially oxidized to aldehyde by iodine.
The oxidative C-O coupling of benzyl alcohols 135 with alkylarenes 136 took place under the action of the Bu 4 NI/t-BuOOH system in the presence of NaH 2 PO 4 [140]. It was proposed that under the reaction conditions benzyl alcohol 135 is oxidized to carboxylic acid 138, while alkylarene gives iodide 139; the nucleophilic substitution between the carboxylate anion and benzyl iodide affords coupling product 137 [140] (Scheme 27).
This mechanism differs from that proposed in the study [141]. According to the latter mechanism, the benzylic carbocation rather than benzyl iodide is generated and this carbocation undergoes nucleophilic attack by carboxylic acid. This mecha-nism is confirmed by the fact that iodide is inert under the reaction conditions. The conditions of the oxidative coupling used in the study [140] differ from the conditions described in the work [141]. However, it should be noted that the formation of benzyl iodide was not experimentally confirmed in the study [140], and the presence of this species was proposed based on the literature data.
The coupling of methyl-and ethylarenes 141 with aromatic aldehydes 140 was performed with the Bu 4 NI/t-BuOOH system in the presence of an excess of either alkylarene 141 or aldehyde 140 [142]. It was supposed that the coupling occurs through the generation of tert-butoxyl radicals, which abstract a hydrogen atom from the benzylic position of the C-reagent to form the C-radical, which is oxidized to the carbocation; in turn, the aldehyde is oxidized to acid, which reacts with the carbocation to give the target coupling product 142 (Scheme 28).
It was shown that under the reaction conditions, tert-butyl perester is generated as an important intermediate from aldehyde and t-BuOOH, and this intermediate can serve as the source of acid and tert-butoxyl radicals [142]. tert-Butyl peresters 144 were synthesized on a preparative scale by the cross-dehydrogenative C-O coupling of aldehydes 143 with t-BuOOH in the presence of Bu 4 NI [143]. It is proposed that tert-butyl peresters 144 are produced as a result of the recombination of acyl radicals 145 and tert-butyl peroxide radicals. The radical reaction mechanism was confirmed by the experiment, in which acyl radicals generated from aldehyde 146 were trapped by the stable radical TEMPO, and trapping product 147 was obtained in an almost quantitative yield (Scheme 29).
The reaction of aldehydes 148a with ethers 149 in the presence of Bu 4 NI and t-BuOOH generated corresponding α-acyloxy ethers 150. Reactions between (hetero)aromatic aldehydes or cyclohexanecarbaldehyde 148b with arylalkyl ketones 151 under similar conditions resulted in α-acyloxy ketones 152 [144] (Scheme 30). The plausible mechanism includes the formation of tert-butyl peresters from the aldehydes.
N-Hydroxyimides 154 are efficient OH-reagents in the coupling with aldehydes and primary alcohols. Their oxidative coupling products, so-called activated esters 155, readily react with nucleophiles, alcohols or amines, due to which they are employed for the preparation of esters and amides. This type of coupling was accomplished using iodine-containing oxidants. The proposed reaction mechanism involves the nucleophilic addition of N-hydroxyimides to aldehydes followed by the oxidation of the resulting adduct to form the activated ester. For example, the C-O coupling of aldehydes 153 with N-hydroxyimides 154 was carried out in the presence of the Bu 4 NHal/t-BuOOH system (Hal = I or Br) [145]. This method is applicable to the oxidative coupling of aldehydes 156 with hexafluoroisopropanol giving esters 157. One of the coupling components is added in a twofold excess (Scheme 31).
A similar oxidative coupling reaction was performed with primary alcohols 158 as CH-reagents and N-hydroxyimides 154a,b [146]. The coupling reaction with N-hydroxyphthalimide (154b) was carried out using the NaI/aqueous t-BuOOH/KOH system instead of Bu 4 NI/t-BuOOH in decane [146]. The resulting activated esters 159 and 160 were isolated or used in the one-pot reaction with amines to prepare amides (Scheme 32).
The oxidative C-O coupling of alcohols and aldehydes 161-164 with N-hydroxysuccinimide (154a) was performed in the pres- ence of (diacetoxyiodo)benzene [147] or iodoxybenzoic acid (IBX) [148] as the oxidant. The authors hypothesized that the reaction proceeds via the nucleophilic addition of N-hydroxysuccinimide (154a) to aldehyde followed by the oxidation of the adduct that formed with iodine(III) [147] or iodine(V) [148] compounds to form products 165, 166 (Scheme 33).
In the study [149], activated esters were synthesized by the oxidative coupling of aldehydes and N-hydroxysuccinimide in the presence of (diacetoxyiodo)benzene, and these compounds were subjected, without isolation, in the reaction with amines to prepare amides. The reaction was performed at room tempera-ture with N-hydroxysuccinimide (154a) taken in an equivalent amount or a small excess relative to aldehyde. Iodoxybenzoic acid (IBX) or the Co(OAc) 2 ·4H 2 O/O 2 system proved to be less efficient in the coupling reactions compared with (diacetoxyiodo)benzene. According to the proposed radical mechanism, N-hydroxysuccinimide (154a) adds to aldehyde to form intermediate 167 followed by the hydrogen atom abstraction from 167 by succinimide-N-oxyl radical 168 to give radical 169 and the oxidation of the latter resulted in the formation of coupling product 170 (Scheme 34). Radical intermediates 168 and 169 were detected by ESR spectroscopy [149].
The oxidative coupling of aldehydes 171 with pivalic acid (172) was performed using the TEMPO cat /t-BuOCl system; the coupling products, unsymmetrical anhydrides 173, were employed in the synthesis of esters and amides 174 (Scheme 35) [150].

Scheme 34:
Proposed mechanism of the oxidative coupling of aldehydes and N-hydroxysuccinimide under action of (diacetoxyiodo)benzene.

Scheme 37:
Copper-catalyzed acyloxylation of C(sp 3 )-H bond adjacent to oxygen in ethers using benzyl alcohols. In a series of works, the oxidative coupling of alcohols, aldehydes, or formamides with 1,3-dicarbonyl compounds or phenols was accomplished in the presence of tert-butyl hydroperoxide and copper salts (Table 5). In most cases, the range of phenols applicable to the coupling is limited to 2-acylphenols. However, 2-(benzothiazol-2-yl)phenol was used along with 2-acylphenols as the OH-reagent in the study [153].
In the coupling with aldehydes, the components are taken in a nearly stoichiometric molar ratio. In the coupling with formamides, the latter served as the solvent. In the studies [155,156], 1,3-cyclohexanedione was used as the OH-reagent along with 1,3-ketoesters. However, the reaction with 1,3cyclohexanedione gave products in low yields (19-26%). The coupling of a number of substituted salicylaldehydes with formamides was performed; the aldehyde group, which is prone to oxidation, remaining intact [157].
The oxidative C-O coupling of aromatic aldehydes 181 with cycloalkanes 182 was accomplished in the presence of the Cu(OAc) 2 /t-BuOOH system to prepare products 183. This reaction is unusual in that it involves the cleavage of four C-H bonds, including unactivated C-H bonds of cycloalkane, and the formation of two C-O bonds and one C=C double bond [169]. The yields of products 183 were not higher than 53%. However, the transformation is a rare example of the oxidative coupling with the participation of inert CH-reagents, cycloalkanes, to form a product, which can be subjected to higher oxidation under the conditions of oxidative coupling (Scheme 38). Related oxidative C-O coupling reactions of alkanes with methylarenes and carboxylic acids are discussed in sections 4.1 and 6, respectively. Different radical mechanisms were proposed, the common feature is the generation of alkene via the radical dehydrogenation of alkane.

Other oxidative systems
Esters were synthesized from aldehydes and methanol (6 equiv excess relative to aldehyde) using pyridinium dichromate in DMF [170]. Methyl esters were synthesized also from aromatic aldehydes, α,β-unsaturated aldehydes, or allylic alcohols in the presence of the DDQ (2,3-dichloro-5,6-dicyanobenzoquinone)/ amberlyst-15 system in a methanol/toluene mixture under microwave irradiation [171]. Methyl, ethyl, and isopropyl benzoates were prepared from benzaldehyde under irradiation of its alcoholic solutions with a mercury lamp in an oxygen Scheme 39: Ruthenium catalyzed cross-dehydrogenative coupling of primary and secondary alcohols.
atmosphere; esters were obtained in higher yields in the presence of catalytic amounts of HCl [172]. The formation of primary and secondary alcohol esters was observed after the ozonolysis of a mixture of aldehyde and alcohol in a basic medium [173]. The oxidative esterification of aldehydes was performed using peroxides in the presence of Lewis acids or in the absence of the latter; for example, using oxone in the presence of In(OTf) 3 [174,175], oxone [174,176], Caro's acid [177], H 2 O 2aq (30%) in the presence of CaCl 2 or MgCl 2 [178], H 2 O 2aq (50%) [179].
An efficient aerobic cross-dehydrogenative coupling of alcohols and α-carbonyl aldehydes was achieved employing a CuBr/pyridine catalytic system in toluene, only 1.5-fold excess of alcohols over aldehydes was used [181]. The reaction time is 18 h at 90 °C, the yields of α-ketoesters vary from 42 to 88%.
The unusual C-O cross-coupling of primary alcohols 184 with secondary alcohols 185 in the absence of oxidants was performed in the presence of ruthenium complex 186 as the catalyst; the reaction afforded molecular hydrogen and unsymmetrical ester 187 (Scheme 39) [182].
Cross-coupling products 187 were obtained in high yields; the expected homocoupling of primary alcohols giving symmetrical esters and the dehydrogenation of secondary alcohols yielding ketones were avoided.

Ketones and 1,3-dicarbonyl compounds as C-reagents in cross-dehydrogenative C-O coupling
Most of cross-dehydrogenative C-O coupling reactions involving the α-position of carbonyl compounds (acetoxylation, alkoxylation, sulfonyloxylation) are based on the use of iodinecontaining oxidizing agents. Transition metal salts, such as copper and manganese salts, were less often employed for this purpose.

Oxidative systems based on iodine compounds
Iodine(III) organic compounds, including those generated in situ from aryl iodides and peracids (for example, m-chloroperbenzoic acid (MCPBA) and peracetic acid) are most commonly employed in the oxidative coupling of OH-reagents with carbonyl compounds. Methods were developed for the sulfonyloxylation of ketones, in which iodoarene is generated in situ by the iodination of arene with molecular iodine [183] or NH 4 I [184] in the presence of m-chloroperbenzoic acid.
In the presence of p-(difluoroiodo)toluene (188) Table 6 presents other examples of C-O coupling reactions at the α-position of carbonyl compounds based on the oxidation Scheme 40: Cross-dehydrogenative C-O coupling reactions of β-dicarbonyl compounds with sulfonic acids, acetic acid, diphenyl phosphate, and alcohols using p-(difluoroiodo)toluene.  with iodine(III) compounds or iodoarenes in the presence of peroxides. Chiral iodoarenes, such as 197, served as the catalysts in the asymmetric C-O coupling of sulfonic acids with ketones. The enantiomeric excess of the product was not higher than 58% due, in particular, to instability of the configuration of the products, α-sulfonyloxy ketones, under the reaction conditions, resulting in the partial racemization [186].
Good results were achieved in the oxidative C-O coupling of ketones, aldehydes and β-dicarbonyl compounds 198 with carboxylic acids 199 in the presence of the Bu 4 NI/t-BuOOH system [194]  The authors hypothesized that the reaction proceeds through a radical mechanism [194].
The authors proposed two radical reaction pathways, including the formation of C-radicals from ketones. One of these pathways involves the formation of tert-butyl peresters from alcohols. This pathway is confirmed by the fact that, in the presence of Bu 4 NI, tert-butyl per(1-naphthylate) gives products 203 in the reaction with propiophenone.

Oxidative systems based on transition metal compounds
In addition to iodine compounds, transition metal salts, such as copper and manganese salts, were used for the oxidative functionalization at the α-position of carbonyl compounds.
N-Hydroxyimides and N-hydroxyamides 204 are involved in the oxidative C-O coupling with 1,3-dicarbonyl compounds and their hetero analogues, such as 2-substituted malononitriles and cyanoacetic esters, 205 in the presence of oxidants based on manganese, cobalt, and cerium [197]. The best results were achieved with the use of Mn(OAc) 3 and the Co(OAc) 2(cat) / KMnO 4 system (Scheme 43). The yields of products 206 were as high as 94%. It is supposed that the oxidant serves two functions: the generation of N-oxyl radicals 207 from N-hydroxyimides or N-hydroxyamides 204 and the one-electron oxidation of 1,3-dicarbonyl compounds via the formation of complex 208.
The oxidative coupling of 1,3-dicarbonyl compounds [199] and their hetero analogues [200] 213 with tert-butyl hydroperoxides catalyzed by transition metal salts (Cu, Fe, Co, Mn) was achieved. tert-Butyl hydroperoxide acts both as the oxidizing agent and the O-component in the coupling. The best results were obtained in the reaction catalyzed by Cu(ClO 4 ) 2 ·6H 2 O. It was hypothesized that copper serves for the formation of the reactive complex with 1,3-dicarbonyl compounds or their hetero analogues, as well as for the generation of tert-butyl peroxide radicals, which react with this complex to give coupling products 214 (Scheme 44).
The improved version of that oxidative coupling method is based on CuCl/Cu(OAc) 2 /ligand/air catalytic system; different β-keto esters and hydroxamic acid derivatives can be used [203].
The acetoxylation at the α'-position of α,β-unsaturated ketones with Mn(OAc) 3 was studied in detail. It is suggested that manganese(III) acetate causes the generation of C-radicals from ketones followed by the acetoxylation of these radicals. In this reaction, Mn(OAc) 3 [204][205][206][207][208][209][210] or acetic acid [209,210], which was used as the co-solvent, can serve as the source of the acetoxy group. The synthesis is usually performed in benzene. In some cases, the α'-phenylation-α'-acetoxylation was observed due, apparently, to the addition of the C-radical generated from ketone to benzene [204]. It was shown [209] that the α'-acetoxylation of enones occurs with good selectivity in other solvents, such as cyclohexane and acetonitrile, as well.
The acyloxylation of enones and aryl ketones 220 with carboxylic acids occurs in benzene in the presence of KMnO 4 to form coupling products 221 (Scheme 46) [211]. Acids were present in a large excess relative to ketones.
The synthesis was successfully accomplished, in particular, with readily oxidizable formic acid; the corresponding formates (for example, 221b) were obtained in 61-85% yield [211]. This method was modified by using not carboxylic acids but their mixtures with the corresponding anhydrides and was applied to the α'-acyloxylation of α,β-unsaturated ketones with complex structures with the aim of preparing analogues of natural compounds [212].
4 Compounds with an allyl, propargyl, or benzyl group as C-reagents in cross-dehydrogenative C-O coupling 4

.1 Palladium-and copper-based oxidative systems
Studies on the acyloxylation at the allylic position of alkenes with palladium(II) complexes started in the 1960s [213]. This type of reactions was considered in more detail in reviews on the palladium complex-catalyzed functionalization of allylcontaining compounds [20,21].
It is suggested that the reaction proceeds through the cleavage of the allylic C-H bond in 222 to form π-allyl-palladium complex 223 followed by the nucleophilic attack of acetate to give C-O coupling product 224a (Scheme 47) [214][215][216][217]. lowed by the elimination of HPdOAc to give product 224b [213]. The first mechanism of the acetoxylation was confirmed by the data on the acetoxylation of 1,2-dideuteriocyclohexene [215], as well as by the detection of the π-allyl-palladium intermediate [217]. However, it cannot be ruled out that the acetoxylation can occur via the second mechanism under certain conditions (Scheme 47) [21,213]. It was found that the selectivity of the reaction can be controlled by changing the polarity of the solvent. The reactions of terminal alkens with the Pd(OAc) 2 /benzoquinone system in a mixture of DMSO and AcOH as the solvent selectively produced linear E-allyl acetates in 50-65% yield [218]. The reaction in acetic acid affords methyl ketone and vinyl acetate; branched allyl ether is formed as the major product in the CH 2 Cl 2 /AcOH system using the 1,2-bis (benzylsulfinyl)ethane ligand [218].
The acyloxylation of terminal alkenes 232 with carboxylic acids 233 in the presence of 1,4-benzoquinone (BQ) as the oxidant, vinyl phenyl sulfoxide ligand 234, and Pd(OAc) 2 resulted in the selective formation of branched allyl esters 235 [217]. This reaction afforded linear esters 236 as byproducts. Apparently, ligand 234 serves for the formation of the π-allyl-palladium intermediate, and benzoquinone mediates the subsequent reductive elimination to give product 235 (Scheme 49) [217].
The Pd(OAc) 2 -catalyzed acetoxylation of terminal alkenes employing 4,5-diazafluorenone as the ligand can be performed in the presence of oxygen as the oxidizing agent (1 atm). The reaction gave linear allyl esters. The authors reported that this ligand facilitates the reductive elimination of the allyl ester from the π-allyl-palladium intermediate [220]. Linear E-allyl acetates were synthesized also by the acetoxylation of terminal alkenes with the PdCl 2 /NaOAc/AcOH/O 2 system (5 atm) in N,Ndimethylacetamide [221]. The Wacker reaction giving methyl ketones occurs when using water instead of sodium acetate and acetic acid, all other conditions being the same [221].
The coupling of terminal alkenes 237 with carboxylic acids having complex structures 238 resulted in the selective formation of linear E-allyl esters 239 (Scheme 50) [222]. These reactions afford a Z isomer of linear ester and branched allyl ester as byproducts.
Similar results were obtained in the coupling of terminal alkenes in the presence of lithium hydroxide as the base in carboxylic acid acting as the OH-reagent or in a carboxylic acid/acetonitrile mixture; the coupling was performed with acetic, propionic, isobutyric, and pivalic acids [223]. It was shown that the stereoselectivity of the Pd(OAc) 2catalyzed acetoxylation of Z-vinyl(triethylsilanes) 240 can be controlled using benzoquinone or (diacetoxyiodo)benzene as the oxidant [224]. The reaction with benzoquinone affords the E isomer of C-O coupling product 241, whereas Z isomer 242 is formed as the major product in the case of (diacetoxyiodo)benzene (Scheme 51).
The oxidative acyloxylation at the allylic position of alkenes and at the benzylic position of some alkylarenes 245 with carboxylic acids 246 was accomplished in the presence of tertbutyl hydroperoxide and mixed copper aluminum oxide as the heterogeneous catalyst (Scheme 53) [226]. The catalyst was prepared from CuCl 2 and AlCl 3 ·6H 2 O by the co-precipitation from an aqueous solution in the presence of NaOH and Na 2 CO 3 . Allyl esters 247 with various structures were synthesized. The reactions were carried out taking alkene and carboxylic acid in a ratio of 1:1 or in the presence of an excess of alkene.
Methylarenes 252 were introduced into the oxidative C-O coupling with β-dicarbonyl compounds 253 and phenols 254 [228]. The coupling afforded structures 255 and 256. The method is applicable to phenols containing an aldehyde group, which was not oxidized in the course of the reaction (Scheme 55).

Scheme 53:
Oxidative acyloxylation at the allylic position of alkenes and at the benzylic position of alkylarenes with carboxylic acids.
The proposed mechanism includes the copper-mediated generation of tert-butyl peresters from t-BuOOH and methylarenes and the formation of final products via intermolecular coupling of O-centered and C-centered radicals. Related oxidative C-O coupling reactions of alkanes with aromatic aldehydes [169] and carboxylic acids are discussed in sections 2.5 and 6, respectively. The 4-methyl group of 2,4,6-trimethylphenol was selectively methoxylated in methanol in the presence of a copper(II) complex and hydrogen peroxide [230]; the similar alkoxylation reaction was performed with a stoichiometric amount of copper(II) chloride [231].
The benzylation of aryl-, alkyl-, and cycloalkylcarboxylic acids 262 in toluene was accomplished in the presence of the Pd(OAc) 2 /CF 3 SO 3 H/dimethylacetamide/O 2 system (Scheme 57) [232]. Apparently, the reaction proceeds through an ionic mechanism involving the cleavage of the C-H bond of toluene with Pd(II). The product is formed either via the nucleophilic attack of carboxylic acid on Pd(II) complex 264 or as a result of the reductive elimination of product 263 from complex 265. It is supposed that dimethylacetamide promotes the reoxidation of Pd(0) to Pd(II) with oxygen and suppresses the aggregation of Pd(0), while trifluoromethanesulfonic acid facilitates the cleavage of the C-H bond of toluene through the formation of cationic Pd(II) compounds [232].

Reactions catalyzed by tetrabutylammonium iodide
The oxidative acyloxylation at the allylic position of alkenes 266 with carboxylic acids 267 was performed using the Bu 4 NI/ t-BuOOH system to prepare esters 268 [237]. Apparently, the reaction proceeds through a radical mechanism, involving the hydrogen atom abstraction from the allylic position of alkene 266 with the tert-butyl peroxyl or tert-butoxyl radical; the authors suggested that the new C-O bond is formed as a result of the cross-recombination of the allyl and carboxyl radicals (Scheme 58) [237].

Scheme 59:
Cross-dehydrogenative C-O coupling of carboxylic acids with alkylarenes using the Bu 4 NI/t-BuOOH system. generated in the Bu 4 NI/t-BuOOH system act as active oxidizing agents; the fact that the reaction proceeds via the hydrogen atom abstraction from the benzylic position to form the benzyl radical is confirmed by a number of experiments, including the trapping of the benzyl radical by the TEMPO radical [141]. The authors hypothesized that the benzyl radical is oxidized to the benzyl cation, which undergoes nucleophilic attack by the carboxylate anion to give cross-dehydrogenative C-O coupling product 271. It was shown that 1-iodo-1-phenylethane does not react with carboxylic acid under these reaction conditions [141].
The oxidative C-O coupling of alkylarenes with aromatic benzyl alcohols [140] and aldehydes [142] in the presence of the Bu 4 NI/t-BuOOH system is considered in section 2.4 (Scheme 27 and Scheme 28).
The synthesis of symmetrical esters from methylarenes and of unsymmetrical esters 274 from methylarenes 272 and ethylarenes 273 in the presence of the Bu 4 NI/t-BuOOH system was documented (Scheme 60). The reaction was accomplished at low conversions of alkylarenes [238]. It was suggested that methylarene is oxidized to carboxylic acid and reacts with the benzylic carbocation generated from the second methylarene molecule or from ethylarene through the hydrogen atom abstraction followed by the oxidation.
The achievement of the cited study is that the authors succeeded in performing the selective oxidative C-O cross-coupling of methylarenes 272 with ethylarenes 273 and excluded side processes, in which symmetrical esters could be generated from methylarenes 272 (the formation of only small amounts of symmetrical esters was observed; 2-5% yield), as well as the oxidation of ethylarene 273 to aryl methyl ketone.
Phosphorylation of benzyl C-H bonds of alkylarenes 275 using the Bu 4 NI/t-BuOOH oxidative system was documented to afford products 277 (Scheme 61) [239]. In this process two The authors supposed that indoles undergo iodination (as exemplified by indoles 278a,b) with AcOI, which is generated from PhI(OAc) 2 and the iodide anion, through the formation of intermediates 281a,b to give one of the two allyl iodides (282a or 282b); the nucleophilic attack of acetic acid or the acetate anion (S N ' nucleophilic substitution) affords products 280a or 279a.

Reactions using 2,3-dichloro-5,6-dicyano-1,4benzoquinone (DDQ)
The common feature of the cross-dehydrogenative C-O coupling reactions that take place in the presence of DDQ is that C-reagents should contain conjugated systems without strong electron-withdrawing groups.
The ultrasound irradiation results in a considerable increase in the selectivity of the reaction. The proposed mechanism involves the generation of acetoxyl radicals and DDQ-H radicals in the reaction of DDQ with acetic acid, and the latter radicals abstract a hydrogen atom from the benzylic position of alkylarene. The target product is formed as a result of the recombination of benzyl and acetoxyl radicals. The reactions with methylarenes were not performed; alkylarenes containing electron-withdrawing substituents (Br, NO 2 ) were not involved in the oxidative coupling.
The oxidative coupling of diarylmethanes 285 with carboxylic acids 286 takes place in the presence of the DDQ cat /MnO 2 system (Scheme 64) [242]. It is suggested that DDQ oxidizes diarylmethanes to diarylmethyl cations, which react with carboxylic acids to form esters 287. Manganese dioxide serves for the oxidation of the reduced form of the catalyst DDQH 2 to DDQ. The drawback of this method is that the reaction center of the C-component should contain two aryl groups and that a fourfold excess of carboxylic acids (O-components) is required.
In the cited study, it was also reported that the coupling of carboxylic acids 289 with 3-phenyl-2-propen-1-yl acetate (288) in the presence of DDQ gives allyl esters 290. DDQ was used also for the acyloxylation at the benzylic position of dimethoxyarene 291 with carboxylic acids 292 to prepare esters 293 (Scheme 64) [243].
The benzylic position of β-phenylethylbenzamides was acetoxylated with DDQ in acetic acid at 80 °C; the reaction readily proceeds if the phenyl ring contains activating methoxy groups; in the case of unsubstituted β-phenylethylbenzamide, the conversion was incomplete [244]. (p-Isopropoxyphenyl)acetic acid esters were stereoselectively acetoxylated with DDQ despite the presence of an electron-withdrawing ester group in the vicinity of the reaction center [245].
The oxidative C-O coupling of 1,3-diarylpropylenes 294 with alcohols 295 was accomplished in the presence of DDQ [246]; the reaction was completed at room temperature in a period of time shorter than one hour; a mixture of two isomeric coupling products 296 was obtained in the case of different substituents R 1 and R 2 . Under similar conditions, the oxidative coupling of 1,3-diarylpropynes 297 with alcohols, phenols, and carboxylic acids 298 afforded coupling products 299 (Scheme 65) [247]. A method was developed for the one-pot synthesis of 3-acyloxy-3-azido-1-aryl-1-propynes 302 from 3-chloro-1-arylpropynes 300 involving the acyloxylation of the methylene group with carboxylic acids 301 under the action of the FeCl 2 / DDQ system (Scheme 66) [248]. In the absence of iron salts, the reaction is less efficient. products 305, 308, and 311 [249,250]. N-Hydroxyphthalimide was also employed as the O-reagent, the yield of the coupling product with isochromane was 62% [250]. DDQ was also used in the acetoxylation at the benzylic position of p-alkoxyalkylarenes and p-alkylphenols in acetic acid [251].

Reactions with N-hydroxyphthalimide
The oxidative C-O coupling of alkylarenes and related compounds 312 with N-hydroxyphthalimide (154b) was performed using CuCl/PhI(OAc) 2 [252] or (NH 4 ) 2 Ce(NO 3 ) 6 [253] as the oxidizing agent (Scheme 68). The reaction in the presence of the CuCl/PhI(OAc) 2 system gives somewhat higher yields of coupling products 313 compared with (NH 4 ) 2 Ce(NO 3 ) 6 , but it requires higher temperature, a longer reaction time, and relatively larger excesses of alkylarene. Apparently, the C-O bond is formed as a result of the recombination of benzyl and phthalimide-N-oxyl radicals. Alkylarenes should be taken in an excess amount to achieve high yields. The coupling of N-hydroxyphthalimide with ethers and alkenes proceeds in a similar fashion [252].
It was reported that such oxidative coupling reactions with NHPI and alkylarenes can proceed through the generation of phthalimide-N-oxyl radicals from NHPI in the presence of Pb(OAc) 4 ; however, the yields of the products were not published [254]. Later on, it was shown that cross-dehydrogena-  4 , or Co(OAc) 2 /O 2 to afford N-benzyloxyphthalimide in yields of 11-75% [255]. The oxidative coupling of NHPI with cyclohexene and cyclooctene using NaIO 4 in the CH 2 Cl 2 /H 2 O mixture in the presence of silica gel was documented [256]; the coupling products were only partially characterized (the NMR spectra of the crude compounds were reported). In another study, the oxidative coupling of NHPI with cyclic and acyclic alkenes was performed in the presence of (NH 4 ) 2 Ce(NO 3 ) 6 , Pb(OAc) 4 , or anthraquinone; in the case of metal-containing oxidizing agents, the radical reaction mechanism is suggested along with the competitive ionic mechanism; the reaction products and procedures for their synthesis were not completely characterized [257].
The acetoxylation at the benzylic position of alkylarenes 314 in acetic acid was performed using the N-hydroxyphthalimide/ iodine/nitric acid system; in some experiments, Co(OAc) 2 was employed as the cocatalyst (Scheme 69) [258]. Oxygen or nitric acid acts as the oxidant.
In the presence of oxidizing agents, phthalimide-N-oxyl radicals are generated from NHPI, and these radicals abstract a hydrogen atom from the benzylic position of alkylarene 314; the resulting benzyl radical is trapped by iodine to form iodide followed by the replacement of iodine by acetic acid to give product 315. The proposed mechanism is confirmed by the fact that the reactions of alkylarenes containing electron-withdrawing substituents in the benzene ring afford benzyl iodides rather than the corresponding acetates.

Other reactions
The C-O coupling of methylarenes 316 with aromatic carboxylic acids 317 in the presence of the NaBrO 3 /NaHSO 3 system was described [259]. The synthesis was performed at room temperature with aromatic carboxylic acids 317 containing both electron-donating and -withdrawing groups; methylarene 316 (toluene or 3-ethoxytoluene), and carboxylic acid 317 were taken in a ratio of 1:1. It was suggested that benzyl bromides are formed in situ followed by the generation of products 318 through the nucleophilic attack by carboxylic acid (Scheme 70).
The tert-butyl peroxide group was introduced into allyl, propargyl and benzyl ethers 319 in the presence of the Fe(acac) 3 /t-BuOOH system [260]. It was suggested that a hydrogen atom is abstracted from the CH-reagent by tert-butylperoxyl and tert-butoxyl radicals generated from tert-butyl hydroperoxide in the presence of Fe(acac) 3 ; the resulting C-radical is oxidized with Fe(III) to the carbocation, and the latter is subjected to nucleophilic attack by tert-butyl hydroperoxide to give product 320 (Scheme 71).
The tert-butyl peroxidation at the allylic and benzylic positions of cyclohexene and ethylbenzene with tert-butyl hydroperoxide catalyzed by nanosized CeO 2 proceeds with low yields [261].
The alkoxylation [267,268] or acyloxylation [267,269]  or SeO 2 [269]. It is suggested that the reactions proceed through electrophilic attack of selenium on the C=C double bond [268,269].
5 Ethers, amines, and amides as C-reagents in cross-dehydrogenative C-O coupling

Reactions catalyzed by tetrabutylammonium iodide
The Bu 4 NI/t-BuOOH system proved to be efficient in the oxidative C-O coupling of ethers 322 with carboxylic acids 321 (Scheme 72) [270]. The coupling was performed with ethers taken in a 20-fold excess relative to carboxylic acids. It is supposed that the tert-butoxyl radical, which is generated in the Bu 4 NI/t-BuOOH system, abstracts a hydrogen atom from the α-position of the ether, and the resulting C-radical is oxidized to the carbocation, which reacts with the carboxylate anion to form coupling product 323.
The Bu 4 NI/t-BuOOH system was applied to perform the oxidative acyloxylation of dimethylamides 325 and dioxane with 2-aryl-2-oxoacetic acids 324 accompanied by the decarboxylation [271]. It was shown that, in the presence of the Bu 4 NI/t-BuOOH system, 2-oxo-2-phenylacetic acid (324a) is transformed into benzoic acid (328) followed by the coupling of the latter with dimethylformamide to give product 326a. Hence, it is supposed that arylcarboxylic acids are intermediates in the synthesis of compounds 326 and 327 (Scheme 73).
The peroxidation of N-benzylamides and N-allylbenzamide 329 with the Bu 4 NI/t-BuOOH system (Scheme 74) was documented [272]. The tert-butyl peroxide group in products 330 can be replaced with an aryl, benzyl, or alkyl group by the reaction with the corresponding Grignard reagent to afford products 331.

Scheme 75:
Cross-dehydrogenative C-O coupling of aromatic carboxylic acids with ethers using Fe(acac) 3 as catalyst and di-tert-butyl peroxide as oxidant.

Scheme 76:
Cross-dehydrogenative C-O coupling of cyclic ethers with 2-hydroxybenzaldehydes using iron carbonyl as catalyst and tert-butyl hydroperoxide as oxidant.
In addition to aromatic carboxylic acids 332, the coupling was performed with phenylacetic acid. The reaction takes place both with ethers and cyclohexene. In almost all syntheses, one of the following two C-reagents was used: 1,4-dioxane or 1,3-dioxo-lane. It is interesting that the oxidative coupling of carboxylic acids with 1,3-dioxolane occurs at the 4-poisition of dioxolane (with one adjacent oxygen atom) rather than at the 2-position (with two adjacent oxygen atoms), which is usually considered to be more activated for the hydrogen atom abstraction. product 349 and the reactivity of related CH-and OH-reagents under these reaction conditions were not discussed.
The ruthenium chloride-catalyzed acyloxylation of β-lactams 350 with an excess of acids as O-reagents was accomplished using oxygen in the presence of acetaldehyde (Scheme 79). It was hypothesized that the reaction proceeds through the generation of the Ru(V) oxo intermediate, which oxidizes the β-lactam to the carbocation, and the latter is subjected to nucleophilic attack by carboxylic acid to form substituted β-lactam 351 [277].
The tert-butyl peroxidation (product 354) or acetoxylation (product 355) of the methylene groups of amides 352 and 353 adjacent to the nitrogen atom was performed in the presence of a ruthenium-based catalyst using tert-butyl hydroperoxide or peracetic acid, respectively [278] (Scheme 80).
Examples of the alkoxylation of tertiary amines 358 and 359 by their electrooxidation in alcohols were reported in the literature, examples are given in Scheme 82 [280] (the ratio of products 360-363 was determined by gas chromatography). The coupling of N-hydroxyphthalimide with tetrahydrofuran (70% yield) and isochromane (71% yield) takes place in the presence of the CuCl/PhI(OAc) 2 system; CH-reagents are taken in a 10-fold excess (see section 4.4, Scheme 68) [252].

Other cross-dehydrogenative C-O coupling reactions
Ketene dithioacetals 364 were subjected to acyloxylation in the presence of the Pd(OAc) 2 /PhI(OAc) 2 system and an excess of carboxylic acids that served as the co-solvents to prepare products 365 (Scheme 83) [281]. The range of carboxylic acids used in this reaction is limited to lower members of the series.
The following mechanism was proposed. Anilide 373 is subjected to electrophilic attack by (di(trifluoroacetoxy)iodo)benzene to form intermediate 374 followed by the elimination of phenyl iodide from 374 to give cation 375, which is subjected to nucleophilic attack (ROH, AcOH, or TsOH) affording coupling product 376 (Scheme 86).
In the presence of PhI(OAc) 2 , aldehydes 377, anilines 378 and alcohols undergo three-component coupling to produce alkoxyl- substituted N-arylimines 379 (Scheme 87). The preliminary mechanism investigations revealed that the transformation proceeds via imines as intermediates. Reactions were performed in the medium of alcohol (OH-reagent) at room temperature [285].
Scheme 89: 2-Acyloxylation of quinoline N-oxides with arylaldehydes in the presence of the CuOTf/t-BuOOH system.

Scheme 90:
Cross-dehydrogenative C-O coupling of azoles with primary alcohols.

Scheme 91:
Oxidation of dipyrroles to dipyrrins and subsequent oxidative alkoxylation in the presence of Na 3 Co(NO 2 ) 6 .

Scheme 88:
Oxidative coupling of phenols with alcohols.
The 2-acyloxylation of quinoline N-oxides 383 with arylaldehydes 384 in the presence of the CuOTf/t-BuOOH system afforded products 385 (Scheme 89) [290]. Benzaldehyde and aromatic aldehydes containing electron-donating groups were employed in the coupling. In addition to aromatic aldehydes, the coupling was performed with cyclohexanecarbaldehyde. It is suggested that the reaction proceeds through a radical mechanism.
The oxidative coupling of primary alcohols 387 with azoles 386 was performed in the presence of the CuCl/(t-BuO) 2 system (Scheme 90) to prepare products 388 in 16-57% yield [291]. It was hypothesized that the C-O bond is formed as a result of the reductive elimination of coupling product 388 from the copper(III) complex.
Alkoxylated heterocycles 391 were obtained in an excess of alcohol in the presence of Na 3 Co(NO 2 ) 6 from dipyrrins 390, which were generated from dipyrroles 389 (Scheme 91) [292].
Alkanes are rarely used in the cross-dehydrogenative C-O coupling because of low reactivity of C-H bonds. An example is the trifluoroacetoxylation of cyclohexane, cycloheptane, cyclooctane, and adamantane in trifluoroacetic acid in the presence of peracetic acid [296] or hydrogen peroxide [297][298][299] with the addition of transition metal salts (Rh, Ru, Pd, Pt, Fe) [296,297] or in the absence of metal compounds [298,299]; the reactions were usually accomplished at room temperature for a few hours.
Copper-catalyzed oxidative dehydrogenative carboxylation of unactivated alkanes 393 with various aromatic acids 392 to produce the corresponding allylic esters 394 was reported recently [300] (Scheme 92). Mechanistic studies allowed proposing a mechanism involving the generation of an allyl radical via the formation of alkene from the starting alkane. Related oxidative C-O coupling of aromatic aldehydes [169] and methylarenes [229] with cycloalkanes using a Cu(OAc) 2 /t-BuOOH system were considered in sections 2.5 (Scheme 38) and 4.1 (Scheme 56), respectively.
Acetoxylation of benzene was achieved employing Pd(OAc) 2 / K 2 S 2 O 8 oxidative system in AcOH/Ac 2 O mixture in the presence of a pyridinium-substituted pyridine ligand [301] (Scheme 93). It was proposed that a key role for this cationic ligand is to serve as a phase transfer catalyst to bring poorly soluble S 2 O 8 2− into contact with the Pd catalyst.
The electrochemical cross-dehydrogenative C-O coupling, in which the O-reagent serves as the solvent, was described in the literature. For example, the methoxylation of methylarenes, amides, phenols, and other compounds was performed in methanol using bases immobilized on a solid support [302].

Conclusion
The analysis of the published data shows that oxidative C-O coupling reactions attract an increasing interest of organic chemists in recent years. In the past two decades, a considerable body of experimental data has been accumulated. Compared with other types of coupling, the oxidative C-O coupling is less well-studied despite the fact that the C-O-R group is rather commonly present in various classes of organic compounds, and a large number of diverse O-reagents are available for the coupling.
The drawback of the majority of the available methods for the cross-dehydrogenative C-O coupling, which limits their application to the coupling of two expensive complex compounds, is the use of an excess of one of the starting components, the C-or O-reagent. Besides, the synthesis often requires high temperature and long time to be completed.
The main goals in the development of the cross-dehydrogenative C-O coupling are as follows: (1) a search for new reactions involving various oxidative systems, C-and O-reagents; (2) the development of methods, which do not require an excess of the C-or O-reagent; (3) the development of methods based on available, convenient, and safe oxidants; (4) a decrease in the reaction temperature and time; (5) investigations of the mechanisms of the oxidative coupling with the aim of predicting conditions necessary for the efficient synthesis.