Aromatic C-H activation

However, the reaction of substrates having a strong electron-withdrawing substituent such as nitro group can occur effectively (e. g., Eq. 43) [91,92]. Thus, another mechanism involving intramolecular aromatic C-H activation would also participate in the reaction. Other possibilities including carbopalladation have also been considered [91]. Therefore, it is likely that the mechanism is not unity and several pathways occur depending on the employed substrates, catalysts, and reaction conditions. 

Although a-elimination is not as common as -elimination, it will typically lead to a metal carbene that is highly reactive (see Chapters 18 and 21) [Eq. (55) 159]. Interestingly, in the same paper, products consistent with aromatic C- H activation, orr/io-metallation, is observed [Eq. (56)] resulting in a low yield of the desired product. 

Cyclopalladations, that is, C-H and C-C activation mediated by Pd(II) species allowing selective functionalizations, are highly important synthetic reactions. In fact, the first examples of aromatic C-H activation were reported by Cope and Siekman in 1965."" " Reacting azobenzenes with PdCb or K2[PtCl4], they observed the formation of dimeric products that were easily transformed into monomeric complexes with a five-membered ring structure [Eq. (6.71)] ... 

Intramolecular aromatic C-H activation was also found with tantalum aryloxy Ugands [Eq. (6.72)] ... 

In 2006, the synthesis of unsymmetrical biaryls from simple arenes was achieved successfully in a catalytic system of Pd(OAc)2/TFA/K2S2Og by tuning the concentrations of arenes and TFA, reported by Lu and coworkers (Scheme 15) [61]. Although the yield of cross-coupling reaction is not practical (11-50% based on the limiting arene), it provides valuable information on the Pd-catalyzed crosscoupling reaction via double aromatic C-H activation. 

Li B-J, Yang S-D, Shi Z-J (2008) Recent advances in direct arylation via Palladium-catalyzed aromatic C-H activation. Synlett 949-957... 

Combined experimental and computational studies on the nature of aromatic C—H activation by octahedral ruthenium(II) complexes Evidence for a-bond metathesis from Hammett studies... 

Four-coordinate Rh(I) hydroxide and related complexes have been demonstrated to initiate aromatic C—H activation (Equation (11.13)).97,100 In contrast to the proposed mechanisms for the Ru(II) and Ir(III) reactions, mechanistic studies for the Rh(I) systems suggest the possibility of an initial exchange between RO (via Rh—OR heterolytic cleavage), coordination of the substrate undergoing C—H activation, and deprotonation by free RO (Scheme 11.47). Alkane C—H activation by late transition metal complexes via 1,2-CH addition across metal-heteroatom bonds has yet to be demonstrated. 

Figure 35. Electron-transfer catalysis in aromatic C—H activation by iridium complexes.

Electrophilic aromatic substitution as a route to differentially substituted products is well established. The often forcing conditions, the incompatibility of this process with acid-sensitive functional groups, and the need for mild and selective syntheses have been the driving forces in the search for new methods of synthesis. A large range of methods has been developed over the past 20 years they include the trimerization of alkynes, the directed orfho-metallation, the benzannellation via metal carbenes, and transition metal-catalyzed carbon-carbon and carbon-heteroatom bond formation. Aromatic C-H activation, while still in its beginning stages, is another area of promise. 

For the aromatic substrates (toluene and mesitylene) competition is observed between benzylic and aromatic C-H activation. Thus, toluene affords the meta-(402) and para (403) tolyl-complexes, alongside the benzyl system 401. Upon heating, the benzyl complex is lost, and a 2 1 thermodynamic mixture of 402 403 obtained. Similarly, mesitylene affords the 3,5-dimethylbenzyl (405) and mesityl (404) complexes (3 1), though comprehensive characterisation of the latter was precluded by its failure to convert cleanly to the corresponding chloride, the dichloride 373 instead being obtained. 

Synthesis of fused heterocycles via Pd-catalyzed multiple aromatic C—H activation reactions 12KGS22. 

In 2003, van der Boom and Milstein [16] reported that the following three mechanistic pathways account for most metal-based aromatic C-H activation processes in a review entitled Cyclometalated Phosphine-Based Pincer Complexes Mechanistic Insight in Catalysis, Coordination, and Bond Activation. ... 

Reaction of mesitylene with 5 gave only the product of benzyUc C-H activation, unlike the reaction with 1 which gave a 3 1 mixture of benzyUc/aromatic C-H activation. The isonitrile ligand appears to induce less crowding at the metal center. As with 1, CF3H proved unreactive. Once again, steric inaccessibility of the C-H bond is believed to be responsible. 

In the course of our study on the interaction of [(NN)PtMc2] (NN = 2,3-bis(2,6-dichlorophenylimino)butane) with copper(I) or silver(I) triflates in benzene [24], we observed a double aromatic C-H activation process yielding moderate yields of [(NN)PtPh2] (Scheme 21). We proposed the mechanism depicted in Scheme 22, which involves the initial one-electron oxidatiOTi of [(NN)PtMe2] by the coinage metal, on the basis of the following considerations ... 

The reaction relies on the fast oxidative addition of the N-O bond onto Pd(0) providing an electrophilic Pd(ll) metal center, which subsequently undergoes aromatic C-H activation. Final reductive ehmination provides the indole derivatives in good yields. 

Catellani and co-workers studied the cyclization of aiylphenols in 2013 (Scheme 2.28). In this system, the formation of a palladacycle with nor-bornene or norbornadiene via aromatic C-H activation was involved. The use of o-bromophenols as partners of iodobenzenes has led to ring formation after norbornene deinsertion, or to arylphenols, containing a pendant norbornenyl or norbornadienyl group or to vinylatylphenols. The availability of a reductive elimination step drives the reaction course toward a preferential product. 

Besides aromatic C-H activation, the high reactivity of [/r-8,8 -I-3,3 -Co(l,2-C2B9Hio)2] results in mild room-temperature C-X activation of halogen alkanes with the formation of the corresponding halogen derivatives [8-X-8 -I-3,3 -Co(l,2-C2B9Hio)2] (X = Cl, Br) (Scheme 6.6) [23]. 

Intramolecular hydroarylation of alkenes through direct aromatic C—H activation was applied to the asymmetric synthesis of the potent protein kinase C inhibitor tricyclic indole (Scheme 18.54) [44]. 

In 2007, the Mlura group reported a Rh(III)-catalyzed oxidative coupling of benzoic acids with internal alkynes to the synthesis of isocoumarins via aromatic C-H activation (Scheme 6.24a) [38]. Importantly, the reaction of benzoic acids with alkynes takes place efficiently even with a reduced amount (5mol%) of Cu(0Ac)2-H20 under air (Scheme 6.24b) [5b]. The same group also developed the rhodium-catalyzed coupling of acrylic acids with alkynes to provide corresponding a-pyrone via vinylic C-H bond cleavage (Scheme 6.24c) [5c]. In 2015, Wen and coworkers described a Rh(III)-catalyzed synthesis of... 

Synthesis by Direct Cross-Coupling Reaction Trauner and co-workers and Bowie and Trauner reported on a concise total synthesis of racemic rhazinilam 122 and rhazinal 123, axially chiral phenylpyrroles having potent antimitotic properties, through an aromatic C—H activation (Scheme 23.24). " To construct the lactam ring of the title compounds, the authors proposed the use of a palladium-catalyzed direct intramolecular cross-coupling reaction. 

The Pd-catalysed addition of aniline to symmetrical acetylene (121) can be controlled by the solvent. Thus, in dioxane and with CuCl as a reoxidant of palladium, the reaction produced pyrrole (122). On the other hand, in DMF and with Cu(OAc)2, the reaction was driven towards indole (123) as a result of the aromatic C-H activation. A mechanism to account for the selectivity has been proposed. ... 

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