C-H bonds, oxidation

The oxidation by Cr(VI) of aliphatic hydrocarbons containing a tertiary carbon atom has been studied by several groups of workers. Sager and Bradley showed that oxidation of triethylmethane yields triethylcarbinol as the primary product with a primary kinetic isotope effect of about 1.6 (later corrected by Wiberg and Foster to 3.1) for deuterium substitution at the tertiary C-H bond. Oxidations... 

The oxidation of C-H bonds represents one of the major challenges in organic chemistry. C-H bond oxidations are often performed in strongly acidic media (such as oleum) in order to enhance the electrophilicity of the metal centre. This indeed requires catalysts that are stable under very challenging conditions. 

Many related complexes of iridium and rhodium undergo the oxidative addition reaction of alkanes and arenes [1]. Alkane C-H bond oxidative addition and the reverse reaction is supposed to proceed via the intermediacy of c-alkane metal complexes [4], which might involve several bonding modes, as shown in Figure 19.5 (for an arene the favoured bonding mode is r 2 via the K-electrons). 

Despite the mechanistic obscurity of C-H bond oxidation by chromic acid, regio-selectivity has been discerned in well defined systems [256]. For example, oxidation of enrfo-fenchyl acetate and the bomyl acetates (exo and endo) gives ketones in which the new carbonyl group is derived from a donor carbon. 

The use of Mn-salen catalysts for asymmetric epoxidation has been reviewed.30 Oxo(salen)manganese(V) complexes, generated by the action of PhIO on the corresponding Mn(III) complexes, have been used to oxidize aryl methyl sulfides to sulfoxides.31 The first example of C—H bond oxidation by a (/i-oxo)mangancsc complex has been reported.32 The rate constants for the abstraction of H from dihydroanthracene correlate roughly with O—H bond strengths. 

Dissociation of the carbonyl ligand was initially postulated as the role of the photon (Route A, Scheme 3) [4], Mechanistic investigations by Goldman et al. indicated, however, that C-H bond oxidative addition to the photo-excited sixteen-elec-... 

The [Ruv(N40)(0)]2+ complex is shown to oxidize a variety of organic substrates such as alcohols, alkenes, THF, and saturated hydrocarbons, which follows a second-order kinetics with rate = MRu(V)][substrate] (142). The oxidation reaction is accompanied by a concomitant reduction of [Ruv(N40)(0)]2+ to [RuIII(N40)(0H2)]2+. The mechanism of C—H bond oxidation by this Ru(V) complex has also been investigated. The C—H bond kinetic isotope effects for the oxidation of cyclohexane, tetrahydrofuran, propan-2-ol, and benzyl alcohol are 5.3 0.6, 6.0 0.7, 5.3 0.5, and 5.9 0.5, respectively. A mechanism involving a linear [Ru=0"H"-R] transition state has been suggested for the oxidation of C—H bonds. Since a linear free-energy relationship between log(rate constant) and the ionization potential of alcohols is observed, facilitation by charge transfer from the C—H bond to the Ru=0 moiety is suggested for the oxidation. 

Iron-containing cytochrome P-450 constitutes the most famous example of a selective C-H bond oxidizer. Although the exact nature of the mechanism remains controversial, the reaction most likely proceeds through radical intermediates [2]. The hydroxylation of activated C-H bonds has also been carried out in the presence of synthetic porphyrin complexes. In these biomimetic processes, ruthenium plays a relatively minor role when compared with iron. Zhang et al. [50], however, recently reported the enantioselective hydroxylation of benzylic C-H bonds using ruthenium complexes supported by a D4-sym-metric porphyrin bearing a crafted chiral cavity. Thus, complex 23 reacts in a stoichiometric manner with ethylbenzene to give phenethyl alcohol with a... 

Figure 4.5.6 (A) Structure of sMMO (PDB code 1MTY) and (B) Structure of TauD (PDB code 10S7). The active sites and the key intermediates responsible for C-H bond oxidation are shown at the bottom.

Bergman RG. A physical organic road to organometallic C-H bond oxidative addition reactions. J Organomet Chem 1990 400 273-282. 

Figure 18 The concerted, nonsynchronous concerted, and radical (oxygen) rebound mechanisms of C-H bond oxidation by the P450 Compound I intermediate...

Figure 19 Structureofbicyclo[2,l,0]pentaneanditsuseasaradical clock for C-H bond oxidation catalyzed by P450 enzymes. The radical intermediate can undergo the rebound step with the Fe -OH species before and after ring-opening rearrangement...

Figure 20 (a) An ultrafast radical clock substrate capable of distinguishing between radical and carbocation intermediates (b) The proposed two-oxidant pathway of C-H bond oxidation by P450 enzymes in which Compound 1 follows a concerted mechanism with no intermediate while the ferric-hydroperoxo attacks substrates by insertion of HO+ leading to carbocation intermediates which rearrange to give the alcohol product... 

Manganese(III) acetate is poorly reactive with saturated hydrocarbons.However, oxidation of adamantane by Mn(OAc)3 in trifluoroacetic acid gives relatively high yields of 1-adamantyl trifluoroacetate, showing a preferential attack at tertiary C—H bonds.Oxidation of n-alkanes by air in the presence of manganese catalysts constitutes the basis for an industrial process for the manufacture of synthetic fatty acids from n-alkanes of petroleum origin, which has been commercially developed in the Soviet Union. ... 

A much wider range of organopalladium compounds is available, however, by means of cyclopalladation reactions. Such reactions involve a Pd(II) salt and an N or P ligand capable of undergoing intramolecular C—H bond oxidative addition. HCl is eliminated as a by-product, and the reactions occur most readily when a five-membered chelate ring is formed " ... 

Few reports have appeared addressing the stereochemistry of either C-H bond oxidative addition or reductive elimination. The most convincing paper was an intramolecular activation examined by Flood in which a chiral 8-ethylquinoline derivative underwent benzylic activation by PdCl42-. The reaction proceeds with the net retention of configuration at carbon (Eq. 10) [49]. 

The search for new reactivity and new reactions is an important target in homogeneous catalysis. A declared goal is the selective activation of C-H bonds under mild conditions. Although there are numerous examples of stoichiometric C-H bond oxidative additions to transition metal centers, successful examples regarding catalytic functionalization of C-H bonds have been made only during the last five years. Notable advances have been achieved by Moore and coworkers who described in 1992 the ortAo-acylation of pyridine with olefins and carbon monoxide. The cluster compound triruthenium dodecacarbonyl has been used as catalyst (Scheme 10). 

Scheme 25 Selective C-H bond oxidation using NHPI as catalyst...

J. M. Mayer, Thermodynamic Influences on C-H Bond Oxidation, in Biomimetic Oxidations Catalyzed by Transition Metal Complexes, Imperial College Press, London, 2000, p. 1. 

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