Catalytic C—H Activation and Functionalization

The real challenge in organometaUic chemistry is the integration of the C—H activation processes described previously into catalytic transformations. Such reactions are very promising and powerful for the construction of C—C bond frameworks. A wide variety of methodologies have been developed on the basis of the understanding of the mechanism. Combination of experimental and computational chemistry has aimed to the development of new catalysts. The following will describe the study of the C—H activation of arenes into successful catalytic cycles. 

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Abstract The Shilov system, a mixture of di- and tetravalent chloroplatinate salts in aqueous solution, provided the first indication of the potential of organotransition metal complexes for activating and functionalizing alkanes under mild conditions the participation of higher-valent species plays a crucial role. In this chapter, we discuss the experimental and computational studies that have led to detailed mechanistic understanding of C-H activation and functionalization by both the original Shilov system and the many subsequent modifications that have been developed, and assess the prospects for practical, selective catalytic oxidation of alkanes using this chemistry. 

Methodologies for the selective arylation of indoles at the C3 position are largely limited to couplings of free indole with bromoarenes. Larrosa et al. employed a decarboxylative functionalization approach to selectively C3-arylate Af-pivaloylindole (94) with electron-poor benzoic acids to afford 95A-C in good yields one of the reasons that this method is attractive is because CO2 is the sole waste by-product (Scheme 10.32). The authors proposed a mechanism based on two catalytic cycles linked by the transmetallation of an arylsilver species to palladium in which the metal catalyst is responsible for the C—H activation and reductive elimination steps and the silver salts perform the decarboxylative activation step. 

After two years, Inamoto developed an approach to the synthesis of 3-aryl/ alkylindazoles [20], by means of a Pd(OAc)2-catalyzed C-H amination reactions of hydrazine compounds. This method features the use of novel combinations of such Pd(OAc)2/Cu(OAc)2/AgOCOCF3, which successfully effect catalytic C-H activation followed by amination to give the cyclized products. The cyclization proceeded in milder reaction conditions (50 °C) and hence tolerated various functional groups such as alkoxycarbonyl and cyano groups and halogen atoms (Scheme 2.20). The data showed that the cyclization may be controlled by both steric and electronic factors on the arene. 

A Pd-catalysed method for C-H activation/C-C bond formation, with iodine(III) reagent, [Ph2I]BF4, has been reported. The reaction showed a high functional group tolerance, regioselectivity, and scope under relatively mild conditions. Preliminary mechanistic experiments have provided evidence in support of a Pd(II)/(IV) catalytic cycle for this transformation.42... 

Recently, Sames and co-workers showed an interesting application, in which it was demonstrated that the Shilov chemistry permits heteroatom-directed functionalization of polyfunctional molecules [16]. The amino acid valine (10) was allowed to react in an aqueous solution of the oxidation catalyst PtCU and Cu(ii) chloride as stoichiometric oxidant (Scheme 3). At temperatures >130 °C a catalytic reaction was observed, and a regioselective C-H functionalization delivered the hydroxyvaline lactone 11 as a 3 1 mixture of anti/syn isomers. It was noted that the hydroxylation of amino acid substrates occurred with a regioselectivity different from those for simple aliphatic amines and carboxylic acids. The authors therefore proposed that the amino acid functionalization proceeded through a chelate-directed C-H activation. 

Considering the mechanistic rationales of the transition metal-catalyzed enyne cycloisomerization, different catalytic pathways have been proposed, depending on the reaction conditions and the choice of metal catalyst [3-5, 45], Complexation of the transition metal to alkene or alkyne moieties can activate one or both of them. Depending on the manner of formation of the intermediates, three major mechanisms have been proposed. The simultaneous coordination of both unsaturated bonds to the transition metal led to the formation of metallacydes, which is the most common pathway in transition metal-catalyzed cycloisomerization reactions. Hydrometalation of the alkyne led to the corresponding vinylmetal species, which reacts in turn with olefins via carbometalation. The last possible pathway involves the formation of a Jt-allyl complex which could further react with the alkyne moiety. The Jt-allyl complex could be formed either with a functional group at the allylic position or via direct C-H activation. Here the three major pathways will be discussed in a generalized form to illustrate the mechanisms (Scheme 8). 

H2PtIV(OH)6 as a stoichiometric oxidant to the catalytic reaction system at 150 °C. In this case, in addition to deuterated methane, methanol is also formed in quantitative yield relative to the added Pt(IV). This suggests that the functionalization step is faster than the oxidation step and leads to the proposal that (above 90 % sulfuric acid) the latter is the rate-limiting step. Below this concentration of acid solvent, studies suggest that the C-H activation step is the rate-limiting step. 

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