C-H bond activation processes

The hydroacylation of olefins with aldehydes is one of the most promising transformations using a transition metal-catalyzed C-H bond activation process [1-4]. It is, furthermore, a potentially environmentally-friendly reaction because the resulting ketones are made from the whole atoms of reactants (aldehydes and olefins), i.e. it is atom-economic [5]. A key intermediate in hydroacylation is a acyl metal hydride generated from the oxidative addition of a transition metal into the C-H bond of the aldehyde. This intermediate can undergo the hydrometalation ofthe olefin followed by reductive elimination to give a ketone or the undesired decarbonyla-tion, driven by the stability of a metal carbonyl complex as outlined in Scheme 1. 

To enhance the kinetics of the C—H activation process, Wayland and co-workers prepared homodinuclear complexes consisting of two (porphyrinato)-Rh(II) complexes tethered by different spacers (170-172). This significantly accelerates the C—H bonds activation process by diminishing the unfavorable entropy contribution to the activation barrier [Fig. 59(a)]. Within one dinuclear complex, one Rh-site receives a hydride ligand and the other Rh-site receives an alkyl ligand (Fig. 60). 

The few studies made with catalytic precursors containing phosphine ligands have revealed that the presence of such ligands in the clusters generally results in slower catalytic rates and sometimes in ligand degradation via P-C or C-H bond-activation processes. Current data do not, therefore, warrant recommendation of the use of phosphine-substituted clusters as catalyst precursors for hydrogenation reactions. 

In contrast to cobalt, simple alkene complexes of rhodium and iridium have been the subjects of prolific research, much of it ultimately directed toward the development of catalysts for hydrogenation and C—H bond activation processes. In view of the expansive literature on these materials, it would seem appropriate to consider their synthesis and structural facets separately from their reactivity. 

C-H activation by oxidative addition generally proceeds by generation of an unsaturated metal fragment in the presence of a hydrocarbon solvent. As intermediates in the C-H bond activation process, cr-alkane complexes have widely been proposed as described in the preceding section. Several new metal systems have been found to undergo oxidative addition to hydrocarbon C-H bonds. 

A number of eomputational studies have contributed to our understanding of the XOR and AO reaction coordinate. Figure 2.24 highlights the salient features of the XOR eatal)Tic cycle for the oxidation of xanthine to uric acid that are consistent with experimental data and the results of recent QMMM stud-iesi2.i3.i37 j ye probed the XOR and AO reaction coordinates. The results of these caleulations have converged on a mechanistic sequence whereby catalysis is initiated by nueleophilic attack of metal activated water ie. hydroxide) on the appropriate earbon atom of substrate. This is followed by the net formal transfer of a hydride at the tetrahedral transition state to the terminal sulfido of the [MoOS] eenter to yield bound product as the enolate tautomer and a reduced [MoOSH] site. The nature of the C-H bond activation process was... 

Similar substituent effects have been determined in the reaction of complexes 10 to form palladacycles 11 (Scheme 11.3) [31]. The opposite process-the intramolecular palladium-catalyzed arylation of alkanes to form dihydrobenzofuranes-has also been examined [32]. For this transformation, a mechanism based on a C—H bond-activation process by the aryl-Pd(II) involving a three-center transition state was found to be more consistent with the experimental kinetic isotope effect (3.6 at 115 °C), as well as with density functional theory (DFT) calculations. 

Although the results of these experiments suggest that the palladation proceeds by an electrophilic aromatic substitution, the transformations are probably more complex than the above results suggest. Indeed, the reaction of alkyl palladium complex 6a with KOPh in MeCN was almost completely inhibited by the addition of lequiv. of PPhs [29], which indicates that ligand substitution, presumably by an associative mechanism, occurs during the C—H bond-activation process. Biden-... 

Another important point is that while recently methyl and methylene C-H bond activation processes have undergone significant progress, tertiary C(sp )-H bond functionalizations with Pd catalysis remain largely elusive (discussed in the following section) [94]. This is probably caused by the decreased acidity of the C-H bond, coupled with it being more shielded. 

An example of a C-H bond activation process that employs this strategy is found in the pioneering work by Suggs et al. Specifically, Rh(I)-promoted activation of an a-C-C bond to ketone in 8-quinolinyl ketone 12 takes place via formation of a stable five-membered ring acylrhodium(III) complex (Scheme 3a) [18,19]. Examples of chelation-assisted C-C bond activation processes are foimd in reactions of the bidentate pincer-type compound 13 [20] (Scheme 3b) and ortho-a.cyl 2-phenyloxazole derivative 14 [21] (Scheme 3c). 

The C-H bond activation process by Ru(OAc)2(p-cymene) and Pd(OAc)2 can be compared by kinetic study of their reaction with phenylpyridine leading in both cases to a cyclometallate complex. Although the reaction with Pd(OAc)2 is faster than with the ruthenium(II) catalyst, it is not affected by addition of acetic acid or acetate, thus the reaction with Pd(OAc)2 proceeds - to the difference of Ru(OAc)2L - via an intramolecular non-autocatalysed Concerted Metallation-Deprotonation (CMD) mechanism [91]. 

The C-C bond cross-coupling reaction of sp C-H bond with alkylhalides following the ruthenium(II) catalysed C-H bond activation process has not been well explored in comparison with arylations with arylhalides, especially for the secondary alkylhalides which are more sterically demanding and electron-rich thus leading to the oxidative addition step with difficulty [106]. 

Overall, these early studies of carboxylate-assisted intramolecular C-H activation established the key features of these AML A/CMD processes, where an electron-deficient metal center works in concert with a pendant carboxylate base to promote C-H activation. This is most evident when an agostic intermediate is involved and such species also rationalize how these systems can also perform C(sp )-H bond activation. Whether C-H activation is achieved as a one- or two-step process appears rather system dependent. Alternative mechanisms, for example, proton transfer onto a halide ligand, oxidative addition, or AMLA-4 processes involving proton transfer onto the inner (Pd-bound) oxygen of the carboxylate were all ruled out. Likewise, no evidence for S Ar processes had been reported. Subsequent work was set against this background and considered the various other parameters that may affect the C-H bond activation process. 

Chiba et al. developed an efficient copper -catalyzed synthesis of phenanthridine derivatives from biaryl-2-carbonitriles and Grignard reagents under an O2 atmosphere (Scheme 8.101). This Cu(OAc)2-catalyzed C-N bond formation involves an aromatic C-H bond activation process. This reaction proceeds via N-H imine formation by the nucleophiUc addition of a Grignard reagent to biaryl-2-carbonitrile and intramolecular aryl C(sp )-H functionaUzation with copper catalyst [174]. 

Bp3.0Et2 has also been used in promoting rhodium-catalyzed C-H bond activation processes. Tu and coworkers have recently reported that a combination... 

Scheme 58 Carbazole synthesis via a Pd-catalyzed domino amination/C-H bond activation process...

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