Aromatic C—H bonds

As in the case of 2-substituted pyridine adducts, activation of an aromatic C—H bond is observed when the adducts of 6-thbipy and of 6-Bnbipy are heated under reflux in aqueous media. A cyclic dimer (1) with bridging N,C ligands is obtained in the first case [24], while cyclometallated derivatives [Au(N, N,C)C1] (2) are formed in... 

Wolff rearrangement of a-diazoketones to give ketenes or subsequent products is an often used synthetic procedure the scope and limitations of which are well established 13 390), so that only a few new features of this reaction need to be considered here. Concerning its catalytic version, one knows that copper, rhodium and palladium catalysts tend to suppress the rearrangement390). A recent case to the contrary is provided by the Rh2(OAc)4-catalyzed decomposition of ethyl -2-diazo-3-oxopent-4-enoates 404 from which the p,y-unsaturated esters 405 are ultimately obtained via a Wolff rearrangement 236). The Z-5-aryl-2-diazo-3-oxopent-4-enoates undergo intramolecular insertion into an aromatic C—H bond instead (see Sect. 4.1). 

Cytochrome P-450. Cytochrome P-450 enzymes consist of a large number of haem-containing mono-oxygenases which catalyze aliphatic and aromatic hydroxylations, epoxidations, as well as other oxidation reactions thus, these enzymes are able to cleave aromatic C-H bonds and also... 

Recently, Yu and co-workers developed an operationally simple catalytic system based on [RuCl2(/>-cymene)]2 for stereoselective cyclization of a-diazoacetamides by intramolecular carbenoid C-H insertion.192 /3-Lactams were produced in excellent yields and >99% m-stereoselectivity (Equation (53)). The Ru-catalyzed reactions can be performed without the need for slow addition of diazo compounds and inert atmosphere. With a-diazoanilide as a substrate, the carbenoid insertion was directed selectively to an aromatic C-H bond leading to y-lactam formation (Equation (54)). 

The silylation of benzylic G-H bonds is achieved by using Ru3(GO)12 catalyst in the presence of norbornene as a hydrogen acceptor.145 The reaction of 2-(2,6-dimethylphenyl)pyridine with triethylsilane in the presence of Ru3(CO)i2 catalyst and norbornene affords mono- and disilylation products in 30% and 55% yields, respectively (Equation (106)). The reaction of 2-(2-tolyl)pyridine shows that the silylation of the aromatic C-H bond is more facile than that of the benzylic C-H bond. 

Recently there have been several studies on synthetic reactions via aromatic C-H bond activation. However, there are limitations that still need to be solved. The following points should be considered. 

Infrared methods measure the absorbance of the C-H bond and most methods typically measure the absorbance at a single frequency (usually, 2930 cm Q that corresponds to the stretching of aliphatic methylene (CH2) groups. Some methods use multiple frequencies, including 2960 cm (CH3 groups) and 2900 to 3000 cm (aromatic C-H bonds). 

Fig. 3.37. Insertion of nucleophilic carbene and imido complexes into aliphatic and aromatic C-H bonds [408,683,689,691].

Carbenes and transition metal carbene complexes are among the few reagents available for the direct derivatization of simple, unactivated alkanes. Free carbenes, generated, e.g., by photolysis of diazoalkanes, are poorly selective in inter- or intramolecular C-H insertion reactions. Unlike free carbenes, acceptor-substituted carbene complexes often undergo highly regio- and stereoselective intramolecular C-H insertions into aliphatic and aromatic C-H bonds [995,1072-1074,1076,1085,1086],... 

Fig. 4.6. Possible mechanism of the C-H insertion of electrophilic carbene complexes into aromatic C-H bonds (Z electron-withdrawing group).

Insertion of aUcynes into aromatic C-H bonds has been achieved by iridium complexes. Shibata and coworkers found that the cationic complex [Ir(COD)2]BF4 catalyzes the hydroarylation of internal alkynes with aryl ketones in the presence of BINAP (24) [111]. The reaction selectively produces ort/to-substituted alkenated-aryl products. Styrene and norbomene were also found to undergo hydroarylation under similar condition. [Cp IrCl2]2 catalyzes aromatization of benzoic acid with two equivalents of internal alkyne to form naphthalene derivatives via decarboxylation in the presence of Ag2C03 as an oxidant (25) [112]. 

Recently, Shibita et al. reported catalysis of alkyne insertion into an arylamide sp C-H bond to give allylamides (42) by a cationic iridium complex [118]. An interesting aspect of this work is the unusually selective cleavage of an sp C-H bond over sp aromatic C-H bonds so that the alkenyl arylamide (43) is only a very minor product (30). The carbonyl group is required for the reaction as no coupling... 

Iridium-Catalyzed Direct Arylation of Aromatic C—H Bonds... 

The iridium(III)-complex, [Ir(p-acac-0,0,C )(acac-0,0)(acac-C )]2, mediates the activation of unactivated aromatic C—H bond with unactivated alkenes to form anti-Markovnikov products [57]. The reaction of benzene 131 with propene 132 (0.78 MPa of propylene, 1.96 MPa of N2) leads to the formation of n-propylbenzene 133 in 61% selectivities (turnover number (TON) = 13 turnover frequency (TOE) = 0.0110 s ) (Equation 10.34). The reaction of benzene with ethane at 180 °C for 3h gave ethylbenzene (TON = 455 TOE = 0.0421s ). The anti-Markovnikov selectivity was also proven for the reaction with 1-hexane and isobutene, giving 1-phenyUiexane (69% selectivity) and isobutylbenzene (82% selectivity), respectively. 

Figure 2.4 shows the distributions of anions about cations for [CjCjImJCl as determined from EPSR at two different probabilities. The directionality of the interactions is clear, with the highest probability regions of anions located along the vectors of the aromatic C-H bonds of the ring and... 

Reagents where a carbon-carbon or a carbon-hydrogen bond is broken are classified as neutral (0) and most frequently include carbon-carbon multiple bonds or aromatic C-H bonds. 

Chuan He of the University of Chicago has observed (J. Org. Chem. 2004,69, 3669) that an Au catalyst will rearrange ethyl propiolate 7 to give an intermediate that inserts into aromatic C-H bonds to give the Z-alkene 8. 

Insertion can also be carried out on the C-H bonds of heteroaromatics. Masahiro Murakami of Kyoto University has described (J. Am. Chem. Soc. 2003,125,4720) a Ru catalyst that will effect rearrangement of a silyl alkyne such as 10 into the vinylidene carbene. The intermediate Ru carbene complex is then electrophilic enough to insert into the aromatic C-H bond. The insertion is highly regioselective. The Au and the Ru alkylidene insertions are geometrically complementary, as Ru gives the E-alkcne. 

While this reaction is still balanced, it is less ideal than Eq. (10.38). For instance, on the r.h.s. of Eq. (10.39), there are two aromatic C-H bonds where the carbon atom is bonded to a nitrogen, but on the Lh.s. there is only one. As a result, we might be forced to go to higher levels of theory to ameliorate any error this might introduce. In the extreme, one can imagine balanced reactions like... 

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