Arylation of heteroarenes

A cobalt-catalyzed method for arylation of heteroarenes including thiazole and benzothiazole was reported in 2003 <030L3607>. According to this report, the direct C-5 arylation of thiazole with iodobenzene was carried out in the presence of cobalt catalyst [Co(OAc)2/IMes] and cesium carbonate, and a complete reversal of arylation from C-5 to C-2 was observed with the bimetallic Co/Cu/IMes system. This report has been retracted as the laboratory of the senior author has not been able to reproduce the key results disclosed in the communication <06OL2899>. 

Palladium-Catalyzed Arylation of Heteroarenes 229 Masahiro Miura and Tetsuya Satoh... 

Ackermann L, Althammer A, Fenner S (2008) Palladium-catalyzed direct arylations of heteroarenes with tosylates and mesylates. Angew Chem Int Ed 48 201-204... 

Join B, Yamamoto T, Itami K (2009) Iridium catalysis for C-H bond arylation of heteroarenes with iodoarenes. Angew Chem Int Ed 48 3644-3647... 

Intermolecular direct arylations of heteroarenes with aryl halides were thus far predominantly accomplished with palladium or rhodium complexes [31, 39,75, 76], Hence rhodium catalysts proved applicable to various electron-rich heteroarenes. In contrast, less expensive and more versatile palladium catalysts allowed for direct arylations of both electron-rich and electron-deficient substrates. Generally, the problem of achieving regioselectivities in direct arylation reactions of heteroarenes is less pronounced than it is for simple arenes, since in many cases the heteroatom can be considered as an endocyclic directing group. 

Several nickel-based catalyst systems have been proven to catalyse C-H arylation of heteroarenes with aryl halides. For example, a combination of Ni(OAc)2 and bipy or dppf catalyses the C-H arylation of azoles including thiazoles, benzothiazoles, oxazoles, benzoxazoles, and benzimidazoles with aryl chlorides, bromides and iodides as well as aryl triflates in the presence of LiOtBu or Mg(OtBu)2. The Ni(OAc)2/dppf/LiOtBu system is more effective for aryl chloride or triflate electrophiles. Nickel-catalysed direct allq ny-lation of azoles with all yl bromides was also carried out. Ni(COD)2/l,2-bis(diphenylphosphino)benzene (dppbz) is an effective catalyst and LiOtBu is a suitable base for this transformation. In some cases, a catalytic amount of Cul additive promotes the coupling. ... 

Direct C—H arylation of heteroarenes catalyzed by palladium/nitrogen-based ligand complexes 13AJ0624. 

Transition-metal-catalyzed direct arylation of heteroarenes 12MR087. 

Intermolecular direct arylations of heteroarenes, such as indoles, pyrroles or (benzo)furans, were, thus far, predominantly achieved with palladium catalysts (see Chapter 10). However, rhodium complexes proved also competent for the direct functionaUzations of various valuable heteroarenes with comparable or, in some cases, improved catalytic performance. Thus, rhodium-catalyzed C—H bond functionalizations of various N-heterocycles, were elegantly developed by Bergman, Ellman and coworkers. Here, the use of a catalytic system comprising [RhCl(coe)2]2 and PCys led to direct arylations of unprotected benzimidazoles with aryl iodides... 

The beneficial effect of copper salts in stoichiometric quantities for palladium-catalyzed direct arylations of N-heterocycles was reported by Miura and coworkers in 1998 [53,54]. However, it was only recently that catalytic amounts of inexpensive Cul were found to enable direct arylations of heteroarenes [55, 56]. Remarkably, a variety of N-heterocycles could be arylated in high yields of isolated products with aryl iodides as electrophiles (Scheme 9.40). Unfortunately, this ligand-free catalytic system required the use of a relatively strong base, thereby limiting its functional group tolerance. 

Catellani [61] reported a palladium/norbomene-catalyzed synthesis of heteroatom-containing o-teraryls from aryl iodides and heteroarenes (including indoles and pyrroles) through double C-H arylation. Fagnou s group [62] applied their own protocol (Pd(II)/Ag(I)/carboxylic acid) to achieve the direct arylation of azaindoles. Itami [63] demonstrated the first iridium-catalyzed C-H arylation of heteroarenes (involving indoles and pyrroles) with aryl halides. 

Daugulis [67] reported a palladium-catalyzed C-H arylation of heteroarenes with aryl chlorides. Although a number of methods of direct arylation of five-membered heteroarenes with aryl halides, including less reactive aryl chlorides, had been reported, thus, the direct arylation of N-substituted indoles, pyrroles, and furans with aryl chloride had been elusive except for Ohta s work [5]. Ohta s group succeeded in the C-H arylation of such heteroarenes with aryl chlorides using a combination of Pd(OAc)2, a bulky Buchwald ligand, and inorganic bases (Scheme 17.14). 

Since a few years, ruthenium- and iridium-based polypyridyl complexes are privileged photocatalysts in visible light photocatalysis. However, organic dyes should constitute a valuable alternative not only due to their relatively lower cost and wider availability but also by giving access to new transformations. The direct arylation of heteroarenes (e.g., furan, thiophene, and pyrrole)... 

This procedure can also be applied to the arylation of heteroarenes (Scheme 4.2). 

Figure 4.10 Direct C-H bond arylation of heteroarenes using Ru catalysis as reported by Ackermann and Lygin [23b].

Electron-deficient SPhos-derived ligands, however, were found to improve yields for the direct arylation of heteroarenes including NMI and by sequestering iodide, cationic Ag allowed for the use of aryl iodides (eq 64). ... 

Changing the heating source to microwave irradiation enhances the reactivity for the direct arylation of heteroarenes. NMI gave the corresponding biheteroaryls in good to excellent yields with fast reaction times (eqs 65-68). ... 

Direct Arylation of Heteroarenes, Aryl silicon reagents were employed to directly arylate heteroarenes via a Pd-catalyzed, ligand-free process. Silver(I) fluoride was the most effective source of fluoride (93%) compared with FeFs, KF, wBu4NF-H20, and CsF, although CuF2 gave a comparable performance (82%). In addition to activating the arylsilanes, silver(I) fluoride acts as a co-oxidant with Cu(0Ac)2-H20 to oxidize Pd° to Pd. The electron-rich and electron-deficient aryl (trimethoxy)silanes could be coupled to access arylated benzothiazoles in excellent yields (83-93%) (eq 19). 

C-H Arylation. Tris(l,l,l,3,3,3-hexafluoro-2-propyl)-phosphite (P[OCH(CF3)2]3) serves as a ligand in C-H activation reactions of aromatic compounds. For exartple, under the catalytic influence of RhCl(CO) P[OCH(CF3)2]3 2 and Ag2C03, the direct arylation of heteroarenes and arenes takes place with iodoarenes to afford a range of biaryls in good yields and with high selectivity. Thiophenes (eq 1), furans, pyrroles, indoles, and alkoxybenzenes are viable in this reaction. Instead of heteroarenes or arenes, allylsilanes also react with iodoarenes in the presence of RhCl(CO) P[OCH(CF3)2]3 2 catalyst to furnish the corresponding arylation product (eq 2) ... 

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