Reaction C-H activation

Similarly, when both the Cp and arene ligands are permethylated, the reaction of 02 with the Fe1 complex leads to C-H activation of the more acidic benzyl bond [57]. When no benzylic hydrogen is present, superoxide reacts as a nucleophile and adds onto the benzene ligand of the FeCp(arene)+ cation to give a peroxocyclohexadienyl radical which couples with a Fe Cp(arene) radical. A symmetrical bridging peroxo complex [(Fe"Cp)2(r 5-C6H60)2] is obtained. The C-H activation reactions of the 19e Fe1 radicals BH can be summarized as follows... 

Activation of a C-H bond requires a metallocarbenoid of suitable reactivity and electrophilicity.105-115 Most of the early literature on metal-catalyzed carbenoid reactions used copper complexes as the catalysts.46,116 Several chiral complexes with Ce-symmetric ligands have been explored for selective C-H insertion in the last decade.117-127 However, only a few isolated cases have been reported of impressive asymmetric induction in copper-catalyzed C-H insertion reactions.118,124 The scope of carbenoid-induced C-H insertion expanded greatly with the introduction of dirhodium complexes as catalysts. Building on initial findings from achiral catalysts, four types of chiral rhodium(n) complexes have been developed for enantioselective catalysis in C-H activation reactions. They are rhodium(n) carboxylates, rhodium(n) carboxamidates, rhodium(n) phosphates, and < // < -metallated arylphosphine rhodium(n) complexes. 

In an attempt to improve the enantioselectivity, following the precedent from Ponsford and Southgate,188 Hashimoto demonstrated that the tetrahydro-l,3-oxazine system gave great selectivity in the C-H activation reaction. Indeed, highly selective formation of the / -lactam 60 was accomplished in up to 94% yield and 96% ee using Rh2(V-PTA)4 (Equation (51)).189 This strategy was applied in a novel approach to a key intermediate 61 in the synthesis of trinem 62 (Equation (52)).190,191... 

Rhodium(n) carboxamidates are clearly superior to all other types of catalysts in effecting highly chemo-, regio-, diastereo-, and enantioselective intramolecular C-H activation reactions of carbenoids derived from diazoacetates. Specifically, Rh2(4Y-MPPIM)4 is the catalyst of choice for C-H activation reactions of simple primary and secondary alkyl diazoacetates. Likewise, Rh2(4Y-MACIM)4 thus far has been the most successful catalyst with tertiary alkyl diazoacetates, whereas for primary acceptor-substituted diazoacetates with a pendant olefin side chain, Rh2(4A-MEOX)4 has proved to be highly selective. 

The intramolecular G-H insertion of aryldiazoacetates is a very powerful strategy for synthesizing heterocyclic rings such as dihydrobenzofurans and dihydrobenzopyrans. The first effective asymmetric copper-catalyzed C-H activation reaction was reported by the group of Sulikowski in the synthesis of the anti-tumor antibiotic FR-66979 93 (Scheme 7)123 219 The G-H insertion of the aryldiazoacetate 90 formed four diastereomeric products 91a, 91b, 92a,... 

All these examples support the concept that hydrocarbon may need to bind directly to the Pt(II) center as shown in Scheme 9 in order to facilitate the C-H activation reaction. The product of the reaction... 

Electron-rich iridium(l) complexes can perform C—H activation reactions under mild conditions [13]. In this line, acetone-dis solutions of the [(ri -l,3,5-C 5H3Me3)) lr(Ti -C2H4)(P Pr3)]BF4 complex, at room temperature, show deuterium incorporation to the ethane ligand, most likely due to the participation of hydrido vinyl iridium(lll) species, formed by the C—H activation of ethane, according to Scheme 2.25 [21]. 

Bedford ef al. reported the total synthesis of glycozolidine (40) and clausine P (46) using the palladium(0)-catalyzed sequential amination and C-H activation reactions... 

Such C—H activation reactions were extended to the related Sn systems. The rates of addition for this chemistry were 4 to 6 times slower for the latter compared with the Ge reactions, in order to avoid the competing formation of Sn(I)[N(SiMe3)2]2Ph. Thus, similar... 

Basuli, F., Bailey, B.C., Huffman, J.C. and Mindiola, D.J., (2005) Intramolecular C-H activation reactions derived from a terminal titanium neopentylidene functionality. Redox-controlled 1,2-addition and a-hydrogen abstraction reactions. Organometallics 24, 3321. 

Scheme 1. C-H activation reactions proceed by transfer of one or two electrons.

The development of catalytic C-H activation reactions is one of the most challenging enterprises in organic chemistry. The only complexes able to activate C-H bonds by oxidative addition are coordinatively unsaturated at the metal center. The lifetimes of these highly reactive metal species, however, are usually very short. A key issue is therefore the development of stabilizing metal ligands. In addition, it is desirable that the ligands should confer a selectivity to the functionalization reaction, such that repeated functionalization can be prevented. 

The first activation of an alkane C-H bond was described in 1969 [29]. Three decades were to pass until the development of the current catalytic procedures for dehydrogenation and C-O, C-C, and C-B bond-forming reactions. Progress has been slow. Nevertheless, significant advances in catalyst research were achieved in the 1990s, aided by the development of improved metal ligands and the increased understanding of the mechanism of transition metal-catalyzed C-H activation reactions. Further improvements of catalytic cycles are nec-... 

The directing group promoted C-H activation reaction is applicable to sp C-H bonds adjacent to the nitrogen in alkylamines, as shown in Scheme 5. Alkylation occurred when reaction of 25 with CO and ethylene was conducted in the presence of Ru3(CO)12 as catalyst [11], On the other hand, the use of a rhodium complex as catalyst resulted in C-H carbonylation [12],... 

Figure 1. Catalytic scheme for alkane oxy-functionalization based on the C-H activation reaction.

In this review homogeneous complexes that catalyze the oxidative conversion of alkanes to products containing C-O bonds and which may operate via the C-H activation reaction are discussed, with emphasis on our own research. Some notable systems that catalyze this transformation are shown in Fig. 2. 

During the 1970s Shilov published extensively on the reactions of alkanes in aqueous solutions of platinum(II) complexes [3]. The reactions are typically carried out in aqueous hydrochloric acid as solvent at <100°C with chloride salts of Pt(II) as catalyst and the chloride salts of Pt(IV) as the stoichiometric oxidant. Typical reaction yields, based on added methane, are less than 3% with >75% selectivity to methanol and methyl chloride. It was proposed the reaction proceeded via C-H activation to generate alkyl platinum intermediates in reactions with alkanes and later results are consistent with this proposal [4]. This system is one of the first systems proposed to operate via the C-H activation reaction and to generate potentially useful functionalized products. The key disadvantages of the Shilov system were the low rates (catalyst tum-over-frequency, TOF, <10 s ), short catalyst life (turnover-number, TON, <20), and the use of Pt (IV) as a stoichiometric oxidant. 

Another strategy for developing active and stable oxidation catalysts that operate via the alkane C-H activation reaction is to use metals that can be readily dis-... 

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