Oxidation by C-H Bond Cleavage

The oxidation of alcohols to aldehydes, ketones or carboxylic acids is one of the commonest reactions in organic chemistry, and is frequently achieved by transition metal complexes or salts. However, in most cases the precise mechanisms are not known, and the intermediates not fully characterised. In general, metal complexes of the alcohols are formed as transient intermediates in these reactions, but we shall not deal with these extremely important reactions in any great detail. The precise mechanisms depend upon the accessibility of the various one- and two-electron reduction products of the particular metal ion which is involved in the reaction. However, we will outline a brief indication of the mechanism. The first step involves the formation of an alcohol complex of the metal ion (Fig. 9-14). This might or might not deprotonate to the alkoxide form, depending upon the pH conditions of the reaction, the pK of the alcohol and the polarising ability of the metal ion. 

A typical example of such a process is shown in Fig. 9-15. In the first step the alcohol ligand 9.8 is co-ordinated to ruthenium(n). The resultant ruthenium(n) complex is then oxidised to give a ruthenium(m) species. Ruthenium(m) is more polarising than ruthenium(n), and the co-ordinated alcohol is deprotonated in the ruthenium(m) complex. 

These same alkoxy compounds are also the primary products in the oxidation of alcohols with high oxidation state metal oxo complexes. In a typical process, the reaction of an alcohol with the chromium(vi) compound [HCr04] is shown in Fig. 9-16. The intermediate is often described as a chromate ester, but it is in all respects identical to the alkoxide complexes that we described earlier. 

The precise sequence of events depends upon the combination of ligands and metal centres involved, but the key step involves a C-H bond-breaking reaction. The reaction may be viewed as a consequence of metal ion polarisation of the ligand increasing the acidity of the relevant C-H bond. Loss of a proton yields a carbanion, which undergoes an electron transfer reaction with the metal centre to yield a radical and lower oxidation state metal ion (free or co-ordinated). It must be emphasised that this is purely a formal view of the reactions. 

In the case of the ruthenium-mediated oxidation of the alcohol 9.8 the overall process is as shown in Fig. 9-18. We have already noted that the deprotonation of the alco- 

---

In aromatic combustion flames, cyclopentadienyl radicals (c-CgHj ) can be precursors for PAH formation. " At high temperatures, benzene is oxidized by reaction with an oxygen molecule to yield phenylperoxy (C6H5O2 ) radical, via the initial formation of the phenyl radical (by C-H bond cleavage) and then the rapid addition of O2 (reaction 6.16). After expulsion of CO from phenylperoxy radical, a resonance-stabilized cyclopentadienyl radical (c-CgHg ) is formed (reaction 6.16). 

A series of arylations of olefins by C-H bond cleavage without direction by an ortho functional group has also been reported, and these reactions can be divided into two sets. In one case, the C-H bond of an arene adds across an olefin to form an alkylarene product. This reaction has been called hydroarylation. In a second case, oxidative coupling of an arene with an olefin has been reported. This reaction forms an aryl-substituted olefin as product, and has been called an oxidative arylation of olefins. The first reaction forms the same t)q)es of products that are formed from Friedel-Crafts reactions, but with selectivity controlled by the irietal catalyst. For example, the metal-catalyzed process can form products enriched in the isomer resulting from anti-Markovnikov addition, or it could form the products from Markovnikov addition with control of absolute stereochemistry. Examples of hydroarylation and oxidative arylation of olefins are shown in Equations 18.63 - and 18.64. ... 

Alkynes as well as alkenes are also recognized as readily available building blocks for constructing alkenylarenes. The reactions of (hetero)arenes with alkynes can be performed without any oxidant through C-H bond cleavage and alkyne insertion steps. Early examples of such hydroarylation of alkynes were reported by Hong and coworkers [74]. Benzene and furans react with diphenylacetylene in the presence of Rh4(CO)i2 catalyst at 220°C under CO (25kgcm ) to produce trisubstituted ethenes (Scheme 18.74). 

A tentative mechanism for the oxidation of aUylic and benzylic alcohols to aldehydes with molecular oxygen, in the presence of the novel bifunctional osmium-copper catalyst 0s04-CuCl, has been proposed. Osmate esters are thought to form, followed by C-H bond cleavage in the initial steps. The exact role of copper in the reaction is unclear however, it is possible that copper(II) generated by oxidation of copper(I) by molecular oxygen could (at least partially) reoxidize osmium that is reduced in the reaction. ... 

Recently, we have demonstrated another sort of homogeneous sonocatalysis in the sonochemical oxidation of alkenes by O2. Upon sonication of alkenes under O2 in the presence of Mo(C0) , 1-enols and epoxides are formed in one to one ratios. Radical trapping and kinetic studies suggest a mechanism involving initial allylic C-H bond cleavage (caused by the cavitational collapse), and subsequent well-known autoxidation and epoxidation steps. The following scheme is consistent with our observations. In the case of alkene isomerization, it is the catalyst which is being sonochemical activated. In the case of alkene oxidation, however, it is the substrate which is activated. 

Kinetics of naphthalene and substituted naphthalenes oxidation by stoich. RuOy CCl to phthalic acids suggest an initial second-order reaction giving a complex with a naphthalene-0-Ru(Vl) bond, followed by a slower decomposition of this intermediate involving C-H bond cleavage [371]. 

Abstract This chapter covers oxidation of C-H and C-C bonds in alkanes. Section 4.1 concerns oxidation of C-H bonds aldehydes and other CH species (4.1.1), methylene (-CH groups) (4.1.2) and methyl (-CH ) groups (4.1.3). This is followed by the oxidation of cyclic alkanes (4.1.4) and large-scale alkane oxidations (4.1.5). Alkane oxidations not considered here but covered in Chapter 1 are hsted in Section 4.1.6. The final section (4.2) concerns oxidative cleavage of C-C bonds. 

Palladium-catalyzed allylic oxidations, in contrast, are synthetically useful reactions. Palladium compounds are known to give rise to carbonyl compounds or products of vinylic oxidation via nucleophilic attack on a palladium alkene complex followed by p-hydride elimination (Scheme 9.16, path a see also Section 9.2.4). Allylic oxidation, however, can be expected if C—H bond cleavage precedes nucleophilic attack 694 A poorly coordinating weak base, for instance, may remove a proton, allowing the formation of a palladium rr-allyl complex intermediate (89, path by694-696 Under such conditions, oxidative allylic substitution can compete... 

C kinetic isotope effects (KIEs) of four cinnamyl alcohol oxidations have been determined by 13C NMR spectroscopy using competition reactions with reactants at natural 13C abundance. Primary 13C KIEs of the Pd(II)-catalysed oxidation and of the MnC>2 oxidation are similar ( 1.02) and indicate the C—H bond cleavages to be the irreversible and rate-limiting steps in the respective reactions. Low primary 13C KIEs in Swern and Dess-Martin oxidations, however, indicate that the initial C—H bond breakings and proton transfers are not the irreversible steps in these mechanisms, which control the rate.284... 

Some 2-alkoxytetrahydropyrans show a reactivity toward oxidants which parallels the reactivity of polycyclic amines discussed above, and which is in line with the hypothesis that weakening of C-H bonds by hyperconjugation should also increase the rate of C-H bond cleavage. For instance, of the two epimeric pyrans sketched in Scheme 2.15 only that with an axial 2-H is oxidized by ozone [51]. The same selectivity has been observed in the oxidation of methyl a- and /3-glucopyranoside with ozone [52], and in homolytic C-H bond cleavage in cyclic ethers [53],... 

Together with the findings of EPR spectroscopy (Fig. 15), these results show clearly that in the presence of non-redox main-group oxide catalysts such as Bi203, hydrocarbons are activated by homolytic C—H bond cleavage leading to radicals that form stable products by subsequent C—C coupling in the gas phase. Lunsford et al were the first to have directly detected the radical intermediates in these reactions by their MIESR technique. 

This complex then undergoes reaction with benzene and a second elimination of methane in a reaction where C-H bond cleavage is rate determining (/Th/ d = 4.1) and which is inhibited by water. The final products are biphenyl and a bis-aquo complex presumably formed by a redistribution reaction of an aquo-phenyl complex followed by reductive elimination of biphenyl and by oxidation by O2 of the resulting Pd° complex (equation 20). 

Actually, BHT (2,6-di-tert-butyl-4-methylphenol), carbon tetrachloride, chloroform and dichloromethane neither affected the hydroxylation rate nor produced chlorinated derivatives, thus excluding a free radical mechanism and the presence of long-lived alkyl radicals, both in the pores of the catalyst and in the external solution. The primary isotopic effect in methanol and t-butanol was 4.1 and 4.7, respectively. A kn/feu of this magnitude is not compatible with a radical chain oxidation initiated by hydroxyl radicals ku/ko = 1-2), while it is fully consistent with substantial C—H bond cleavage in the transition state by a Ti-centered radical. 

---