C-H, oxidation

The oxidative addition of alkane C-H bonds to Pt(II) has also been observed in these TpRa -based platinum systems. As shown in Scheme 19, methide abstraction from the anionic Pt(II) complex (K2-TpMe2)PtMe2 by the Lewis acid B(C6F5)3 resulted in C-H oxidative addition of the hydrocarbon solvent (88). When this was done in pentane solution, the pentyl(hydrido)platinum(IV) complex E (R = pentyl) was observed as a... 

The authors point out that the dependence of the site of electrophilic attack on the ligand trans to the hydride in the model systems may be important with respect to alkane activation. If the information is transferable to Pt-alkyls, protonation at the metal rather than the alkyl should be favored with weak (and hard ) a-donor ligands like Cl- and H20. These are the ligands involved in Shilov chemistry and so by the principle of microscopic reversibility, C-H oxidative addition may be favored over electrophilic activation for these related complexes. 

Miyafuji and Katsuki95 reported the desymmetrization of meso-tetrahydrofuran derivatives via highly enantioselective C-H oxidation using Mn-salen catalysts. The optically active product lactols (up to 90% ee) are useful chiral building blocks for organic synthesis (Scheme 8-48). 

The first reports on c-alkane metal complexes date back to the 1970s, the work of Perutz and Turner on photochemically generated unsaturated metal carbonyls of Group 6 [4], which is well before the C-H oxidative addition studies of alkanes. The enthalpy gain of formation of c-alkane metal complexes... 

Koontz, C. H. Oxidant air pollution and athletic performance A study in Seattle. Submitted to Department of Preventive Medicine, University of Washington, September 26, 1968. 

Pyridine-functionalized N-heterocyclic carbene Rh and Ir complexes have also been described as active precatalysts for C=0 bond TH. For example, Peris and coworkers observed the formation of metal hydrides by C—H oxidative addition of a pyridine-N-substituted imidazolium salt such as N-"Bu-N -(2-pyridylmethyl-imidazolium) hexafluorophosphate in the reaction leading to M-pyNHC complexes, that is [lr(cod)H(pyNHC)Cl] (58) [54]. Transmetallation from silver carbene... 

Katsuki and coworkers have developed a family of salen-metal complexes capable of effecting a C—H oxidation at activated positions. meso-Tetrahydrofurans may be oxidized to the lactol in good yield and excellent enantioselectivity using iodosylbenzene as the stoichiometric oxidant and a Mn-salen complex as catalyst [Eq. (10.45)]. " Meso acylpyrrolidines behave similarly, providing slightly lower enantioselectivities using a similar catalyst [Eq. (10.46)]d ... 

Scheme 17.38 Stereospecific C-H oxidation affords L-vancosamine equivalent.

A subsequent study using neopentane as the alkane substrate gave evidence in support of the same mechanism, and also allowed resolution of near-coincident y(CO) absorptions due to [Cp Rh(CO)Kr] (1946 cm ) and [Cp Rh(CO)(di2-neopen-tane)] (1947 cm ) [18]. Further studies were able to quantify the reactivity of [Cp Rh(CO)Kr] towards a range of alkanes [20]. It was found that binding of the alkane to Rh becomes more favorable, thermodynamically, as the alkane size is increased, but that the rate of the C-H oxidative addition step shows less variation with linear alkane chain length. No reaction with methane was observed, which was explained by the ineffective binding of methane (relative to excess Kr) to Rh. 

The need for a base additive in this reaction implies the intermediacy of acetylide complexes (Scheme 9.10). As in the Rh(III)-catalyzed reaction, vinylidene acetylide S4 undergoes a-insertion to give the vinyl-iridium intermediate 55. A [l,3]-propargyl/ allenyl metallatropic shift can give rise to the cumulene intermediate 56. The individual steps of Miyaura s proposed mechanism have been established in stoichiometric experiments. In the case of ( )-selective head-to-head dimerization, vinylidene intermediates are not invoked. The authors argue that electron-rich phosphine ligands affect stereoselectivity by favoring alkyne C—H oxidative addition, a step often involved in vinylidene formation. 

In 2003, Velusamy and Punniyamurthy reported on a copper(II)-catalyzed C—H oxidation of alkylbenzenes and cyclohexane to the corresponding ketones with 30% hydrogen peroxide (Scheme 131). The reaction was catalyzed by the copper complex 192a depicted in Scheme 131 and yields were high in the case of alkylbenzenes (82-89%) whereas cyclohexanone was obtained with a low yield of 18%. Chemoselectivity was very high in every case neither aromatic oxidation nor oxidation at another position of the alkyl chain was observed. 

Unlike epoxidations, the enantioselective CH oxidation is still a virgin field in dioxirane chemistry. The first (and to date only ) enantioselective C—H oxidation has been reported for vic-diols. Thus, the oxidation with the fructose-derived dioxirane of ketone 7 (Shi s ketone) yields the optically active a-hydroxy ketones in ee values of up to 75% °. A typical example of this asymmetric CH oxidation is shown in equation 32 °. 

The mechanism involving simple nitrogen-coordinated complexes also accounts for reactivities of certain sterically constrained systems. For instance, 3-(diethyamino)cyclohexene undergoes facile isomerization by the action of the BINAP-Rh catalyst (Scheme 18). The atomic arrangement of the substrate is ideal for the mechanism to involve a three-centered transition state for the C—H oxidative addition to produce the cyclometalated intermediate. The high reactivity of this cyclic substrate does not permit any other mechanisms that start from Rh-allylamine chelate complexes in which both the nitrogen and olefinic bond interact with the metallic center. On the other hand, fro/tt-3-(diethylamino)-4-isopropyl-l-methylcyclohexene is inert to the catalysis, because substantial I strain develops during the transition state of the C—H oxidative addition to Rh. 

Figure 12.20 A designer C H oxidation catalyst the positions the reactive CH-bond over the catalyst active site using molecular recognition. The ibuprofen substrate is oxidised to the 2-(4-Isobutyryl-phenyl) -propionic acid product in > 98 % selectivity (reproduced by permission of The Royal Society of Chemistry).

Fig. 38 Examples of molecules prepared following new concepts in total synthesis (a) intricarene (220) generated by protective group-free synthesis and (b) late-stage site-selective C-H oxidations to generate eudesmane-type terpenes like 222 or (c) to prepare the hydroxylated artemisinin derivative 223...

The use of photochemical dinitrogen loss has been selectively employed in similar reactions with some notably enlightening results [124,125]. An early study shows that Cp Re(CO)(L)(N2) (L is P(OEt)3, P(OMe)3, PMe2Ph) photochemically produces frans-Cp Re(CO)(L)(Ph)Cl under UV irradiation in chlorobenzene, similar to the reports above [124]. However, the analogous reaction of Cp Re(CO)2(N2) with 1,4-difluorobenzene, produces both the C-H oxidative addition product Cp/Re(CO)2(Ar)H (Ar is 2,5-C6F2H3) and the coordinated benzene product, Cp Re(CO)2( 2-l,4-C6F2H4) [125]. The two isomers interconvert around 213 K. 

Jacobsen epoxidation of cyclohexa-1,4-dienes allowed a direct comparison of Mn (in)salen-catalysed epoxidation and C-H oxidation within the same molecule... 

Palladium-catalysed directed C-H oxidation with (diacetoxy)iodobenzene of a series of meta -substituted aryl pyridine and aryl amide derivatives resulted in the formation of the corresponding acetoxy compounds. The reactions generally proceed with high levels of regioselectivity for functionalization of the less sterically hindered ortho-C-H bond.144 The mechanism shown in Scheme 4 has been proposed for the oxidation of 2,6-dimethylphenol with (diacetoxyiodo)benzene for the formation of 3,5,3, 5 -tetramethyl-biphenyl-4,4 -diol, via C-C coupling.145... 

A related topic that was already discussed in these first DFT/MM works is that of branching. The scheme shown in Fig. 1 would always produce always a linear polymer if ethylene was used as olefin. But a simple process of / C-H oxidative addition/reductive elimination, coupled with olefin rotation, can produce a branched polymer, as shown in Fig. 4. Calculations on the branching process for cationic diimine Ni(II) complexes [36, 37] indicated a small increase between 0.9 and 2.5 kcal/mol in the barrier for this process, associated with the introduction of the bulky substituents in the catalysts. 

The C-H oxidation of unactivated alkanes is the most direct method of introducing oxygen functional groups in alkanes. Such oxyfunctionalization, especially... 

A concerted, spiro-structured, oxenoid-type transition state has been proposed for C-H oxidation by dioxiranes (Scheme 5). This mechanism is based mainly on the stereoselective retention of configuration at the oxidized C-H bond [20-22], but also kinetic studies [29], kinetic isotopic effects [24], and high-level computational work support the spiro-configured transition structure [30-32], The originally proposed oxygen-rebound mechanism [24, 33] was recently revived in the form of so-called molecule-induced homolysis [34, 35] however, such a radical-type process has been experimentally [36] and theoretically [30] rigorously discounted. 

Scheme 5. The concerted oxenoid versus the stepwise oxygen-rebound mechanism for the C-H oxidation by dioxi ranes.

Acetonitrile is the solvent of choice for in-situ C-H oxidation. Although ethereal solvents, for example dimethoxymethane, 1,2-dimethoxyethane, 1,4-dioxane, and mixtures thereof, have been successfully used for dioxirane-mediated catalytic asymmetric epoxidations, their application in in-situ C-H oxidation has not been vigorously established. 

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