Arylation of aromatic C-H bonds

For the alkylation and alkenylation of C-H bonds, olefins and acetylenes are used as reactants. This type of coupling protocol is not applicable to arylation. Recently, a nitrogen-directed arylation of aromatic C-H bonds, leading to biaryl compounds has been developed. In 2001, Oi demonstrated that ruthenium(II)-phosphine can be used as a catalyst in the regioselective arylation of 2-arylpyridines using aryl halides (Eq. 9.34) [4 ]. The predominant ortho selectivity indicates that the coordination of 

Very recently, Kakiuchi reported on the ruthenium-catalyzed arylation of C-H bonds using organoborane reagents. The reaction of aromatic ketones with arylboro-nates using a ruthenium catalyst resulted in the production of arylated aromatic ketones (Eq. 9.36) [50], This arylation reaction using arylboronates can be applied to a variety of aromatic ketones and arylboronates. The authors proposed that this reaction involves the oxidative addition of a C-H bond to a Ru(0) species. 

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

Fujita K-i, Nonogawa M, Yamaguchi R (2004) Direct arylation of aromatic C-H bonds catalyzed by Cp Ir complexes. Chem Commun 1926-1927... 

A Pd(II)/(0) catalytic cycle is common in Pd catalytic reactions. Sanford s group has demonstrated a Pd(II)/(IV) catalytic cycle for arylation of aromatic C—H bonds (Equation 11.33) [71]. The method demonstrated high functional group tolerance, high regioselectivity, and broad scope under mild conditions. Preliminary mechanistic experiments have provided evidence supporting a Pd(II)/(IV) catalytic cycle for this transformation. 

Copper-catalyzed direct arylation of aromatic C—H bonds 12CJO1041. Copper-catalyzed Ulbnann-type coupling reactions in water 13CJO760. Copper-mediated oxidative direct C—C (hetero)aromatic cross-coupling 12CC10704. 

The direct arylation of aromatic C—H bonds takes place with [Cp IrHCl]2 complexes as catalysts in the presence of KOt-Bu [48]. The regjoselectivity observed in... 

The palladium-catalyzed intramolecular C-H arylation of aromatic C-H bonds with haloarenes (Ar-H/Ar-X coupling, where X is halogen) is effective for the synthesis of carbazole alkaloids with amine linkers, as reported by Bedford and coworkers in 2006 (Scheme 16.16a) [34]. Buchwald-Hartwig coupling of an aryl bromide and an aniline derivative generated aryl chloride 91 in situ, which was easily cyclized under palladium catalysis to give clausine P in 80% yield. They also... 

The catalytic activation of aromatic C-H bonds leading to useful addition with new C-C bond formation is of considerable interest in organic synthesis and industrial processes, because it would provide simple and economical methods for producing aryl-substituted compounds directly from simple arenes, as shown in Scheme 1. 

The reaction sequence in the vinylation of aromatic halides and vinyl halides, i.e. the Heck reaction, is oxidative addition of the alkyl halide to a zerovalent palladium complex, then insertion of an alkene and completed by /3-hydride elimination and HX elimination. Initially though, C-H activation of a C-H alkene bond had also been taken into consideration. Although the Heck reaction reduces the formation of salt by-products by half compared with cross-coupling reactions, salts are still formed in stoichiometric amounts. Further reduction of salt production by a proper choice of aryl precursors has been reported (Chapter III.2.1) [1]. In these examples aromatic carboxylic anhydrides were used instead of halides and the co-produced acid can be recycled and one molecule of carbon monoxide is sacrificed. Catalytic activation of aromatic C-H bonds and subsequent insertion of alkenes leads to new C-C bond formation without production of halide salt byproducts, as shown in Scheme 1. When the hydroarylation reaction is performed with alkynes one obtains arylalkenes, the products of the Heck reaction, which now are synthesized without the co-production of salts. No reoxidation of the metal is required, because palladium(II) is regenerated. 

The catalytic enantioselective addition of aromatic C - H bonds to alkenes would provide a simple and attractive method for the formation of optically active aryl substituted compounds from easily available starting materials. The first catalytic, highly enantioselective Michael addition of indoles was reported by Jorgensen and coworkers. The reactions used a,fl-unsaturated a-ketoesters and alkylidene malonates as Michael acceptors catalyzed by the chiral bisoxazoline (BOX)-metal(II) complexes as described in Scheme 27 [98,99]. 

Additions of aromatic C-H bond to olefins and acetylenes result in the formation of aryl-alkyl and aryl-alkenyl bonds. This type of addition reaction is not applicable to aryl-aryl bond formation. Catellani and Chiusoli [52] reported the first example of this type of arylation in 1985. To date, several arylation reactions of aromatic rings have been developed. In almost all cases, C-H bond cleavage proceeds through electrophilic substitution with transition-metal complexes [53]. 

With the success of transition-metal-catalyzed aryl-aryl cross-coupling reactions through C-H activation of one of the coupling partners, obviously, a more economic and attractive alternative is the coupling reaction via double C-H activation of two arenes, neither of which needs to be preactivated (Scheme 5). However, the development of such a process is very challenging because many difficulties remain to be solved. For instance, the control of selectivity when two coupling partners have more than one type of aromatic C-H bond is a challenge. 

Recently, Heck-type reactions, which proceed through activation of aromatic C—H bonds, have been investigated. Jia et al. reported that the reaction of aryl alkynoates 529 in the presence of Pd (OAc) 2 in TFA gave the corresponding coumarins 530 in high yields (Scheme 157).223 The reaction proceeds through electrophilic attack of Pd(II) to the aromatic C—H... 

One important mechanism for homogeneous catalytic activation of aromatic C—H bonds is electrophilic attack by transition-metal complexes on the aromatic substrates. It is presumed t -aryl complexes are important intermediates in these reactions, but they are rarely isolated. Direct electrophilic metallation of aromatic substrates is closely related to reactions observed with nontransition metals ( 5.6., auration 5.7.2., mercuration and 5.3., thallation - ). References to metal-aryl complexes synthesized by electrophilic attack on arenes by transition metals are sununarized in Table 1. Reviews are available " . 

The hydroarylation of aHc5mes, which has emerged as a powerful alternative to the oxidative arylation of alkene, is not discussed in this chapter as it is not a true Heck alkenylation. Jia, C., Piao, D., Oyamada, J. et al. (2(X)0) Efficient activation of aromatic C—H bonds for addition to C—C multiple bonds. Science, 287,1992-5. 

A variety of catalysts have been used for these hydroary lation reactions of the C-H bonds in aromatic ketones, imines, and 2-arylpyridines. The intermolecular additions of aromatic C-H bonds of aryl ketones to olefins reported by Murai were conducted with RuH fCO) (PPh3)3 as catalyst. [RuH2(H2)(PCy3)2] was shown subsequently to catalyze this process at room temperature and even the much different Rh(I) complex [Cp Rh(C,H3SiMe,),] catalyzes this reaction. Additions of the C-H bonds to N-Bu and N-Bn benzaldimines... 

To overcome the ring closure of intermediate 10 giving rise to by-product 8 that was particularly encountered with secondary alkyl halides. Tautens and coworkers [22] developed conditions that favor the oxidative addition of alkyl hahdes. The methodology was widely applied to the intramolecular (Scheme 19.12) and intermolecular ortho alkylation of aromatic C-H bonds with secondary alkyl iodides and bromides [23]. Depending on the terminating reactions employed (the Heck reaction, direct arylation of heterocycles, and the Buchwald-Hartwig amination), a variety of valuable heterocydes were efficiently prepared. It should be pointed out that the reaction of enantioenriched substrates occurred with... 

Amines are valuable synthetic targets because of their abundance in medicine, agrochemicals, and materials science [47]. Transition metal-catalyzed direct conversions of aromatic C—H bonds to C—N bonds are attractive synthetic routes toward accessing aryl amines [48]. These reactions are more advantageous over the conventional amination methods that either requires harsh conditions (e.g., nitration followed by reduction) [49] or prefunctionalized substrates (amination of aryl halides) [50, 51]. The Hartwig group recently reported the first example of Pd-catalyzed intermo-lecular amination of arenes (Scheme 24.55) [52a],... 

This reaction appears to be more difficult than the insertion into a vinylic C-H bond, which occurs in the synthesis of indoles from 2-nitrostyrenes (see paragraph 5.3.). The known chemical inertness of aromatic C-H bonds towards nitrene insertion [13] and the stabilisation of the intermediate aryl nitrene triply bridged in the ruthenium cluster are probably responsible for the poor yield of the heterocyclic product. 

Efficient proeedures for the cross-dehydrogenative synthesis of aryl ketones have been introduced by complementing the radieal acylation with transition-metal-eatalyzed activation of aromatic C-H bonds. The first eross-dehydrogenative Pd-eatalyzed acylation of 2-phenylpyridines was developed independently by the groups of Chengf and Li. The latter demonstrated that various aliphatie, alicyclic and some aromatie aldehydes are smoothly converted in the presenee of 5 mol% of Pd(OAe)2 in combination with 1.5 equiv. of TBHP at 120 °C under an air atmosphere (Scheme 1.38). 

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). 

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]. 

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