C H activation cross-coupling

Keywords Biaryls Catalysis C-H activation Cross-coupling Rhodium... 

General procedure for C-H activation cross-coupling reactionP ... 

Scheme 7.23 C-H activation/cross-coupling reactions of aryl- and alkenylsilanols.

The progress on S-C bond activation, which covers the reduction of a C-S bond to a C-H bond, cross coupling reaction of sulfides with main group organometaUic nucleophiles, ring opening reactions of thietanes and thiiranes, and desulfurization of thiols, sulfides, and thiophenes has already been reviewed elsewhere [6-10], and... 

Cross-coupling via C-H activation Cross Dehydrogenative Coupling... 

Copper-catalyzed C—H and C—X bond activations have attracted much attention because they can convert a C—H bond directly into a C—C or C—FG bond. These transformations meet the basic requirements of green chemistry [82], One elegant example of a cascade reaction related with the copper-catalyzed C—H bond activation is the copper-catalyzed C—H oxidation/cross-coupling of indole with a-amino carbonyl compounds (Scheme 5.80). 

Palladium salts will attack C-H bonds in functionalised aromatics such as acetoaniline to form palladium-carbon bonds that subsequently undergo insertion of alkenes [31], (3-Hydride elimination gave styryl derivatives and palladium hydride, which requires re-oxidation of palladium by benzoquinone. The reaction can be regarded as a combined Murai reaction (C-H activation, if electrophilic) and a Heck reaction (arylalkene formation), notably without the production of salts as the cross-coupling reactions do. An example is shown in Figure 19.15. 

For a recent review on coupling reactions proceeding via C-H activation see Miura, M. Nomura, M. in Cross-coupling reactions, Topics in Chemistry Vol. 219., Miyaura, N. Ed., Springer Verlag, Berein, Heidelberg, 2002, pp 211-241. 

Making use of an earlier finding that Sn compounds containing Sn—CH2R bonds were suitable for Stille cross-coupling reactions,one-pot C—H activation and cross-coupling products were isolated in modest yields (21 % from MeOBu and 5 % from n-CsH 12 based on Sn amide) as shown in Equation (9.13) (R CH2OBU or n-CsHn). ... 

Cross-coupling reactions 5-alkenylboron boron compounds, 9, 208 with alkenylpalladium(II) complexes, 8, 280 5-alkylboron boron, 9, 206 in alkyne C-H activations, 10, 157 5-alkynylboron compounds, 9, 212 5-allylboron compounds, 9, 212 allystannanes, 3, 840 for aryl and alkenyl ethers via copper catalysts, 10, 650 via palladium catalysts, 10, 654 5-arylboron boron compounds, 9, 208 with bis(alkoxide)titanium alkyne complexes, 4, 276 carbonyls and imines, 11, 66 in catalytic C-F activation, 1, 737, 1, 748 for C-C bond formation Cadiot-Chodkiewicz reaction, 11, 19 Hiyama reaction, 11, 23 Kumada-Tamao-Corriu reaction, 11, 20 via Migita-Kosugi-Stille reaction, 11, 12 Negishi coupling, 11, 27 overview, 11, 1-37 via Suzuki-Miyaura reaction, 11, 2 terminal alkyne reactions, 11, 15 for C-H activation, 10, 116-117 for C-N bonds via amination, 10, 706 diborons, 9, 167... 

Dyker, G. Palladium-catalyzed C-H activation at methoxy groups for cross-coupling reactions a new approach to substituted benzo[h]-furans./. Org. Chem. 1993, 58, 6426-6428. 

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 cyclization of a-chloroacetanilides reported by Buchwald may also involve C-H activation (also Scheme 5). As mentioned above, acetanilides are among the most reactive substrates in this reaction. The presence of a base (Et3N), and 2-PhC6H4PBu2 as the ligand, are conditions more typical of cross-coupling of halides and therefore the sequence may start this way, followed by intramolecular... 

More recently, a protocol was elucidated by Malezcka and Smith to produce aryl borate esters directly without first producing aryl halides.144 The reaction involves an Ir-catalyzed C-H activation (Section 7-2-1) to yield the aryl borate, which can then be used directly in Suzuki cross-coupling (equation 12.71). This new development adds another green aspect to Suzuki cross-coupling, which is already a relatively green synthesis tool. 

The most common means of activating aromatic C-H bonds via palladium catalysis is by electrophilic C-H activation. This proceeds more like a Freidel-Craft type metahation mechanism, followed by rearomatization to form versatile aryl-metal intermediates (Scheme 5) [19]. It can occur with electrophilic palladium(II) catalysts such as Pd(OAc)2, PdCl2, Pd(TFA)2 (Scheme 5a) or on electrophilic aryl-pahadium(II) complexes, that result from oxidative addition of palladium(O) into an aryl halide (Scheme 5b). The resultant aryl-palladium(H) complexes are analogous to those observed in conventional cross-coupling reactions and as such are versatile intermediates in the formation of new C-C bonds. 

Scheme 30 Lu s intermolecular cross-coupling of simple arenes by double C-H activation...

In 2007, the Fagnou group achieved a much more practical and selective Ar-H/ Ar-H cross-coupling [50]. Electron deficient palladium(II) complexes can react via an electrophilic C-H activation mechanism with good selectivity for electron rich arenes. In contrast, Fagnou [51] recently showed that complimentary reactivity to this is displayed by some ArPd(II) complexes that react through a proton-transfer-palladation mechanism, and that they depend on arene C-H acidity rather than arene nucleophilicity (Scheme 31). 

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. 

In 2006, the synthesis of unsymmetrical biaryls from simple arenes was achieved successfully in a catalytic system of Pd(OAc)2/TFA/K2S2Og by tuning the concentrations of arenes and TFA, reported by Lu and coworkers (Scheme 15) [61]. Although the yield of cross-coupling reaction is not practical (11-50% based on the limiting arene), it provides valuable information on the Pd-catalyzed crosscoupling reaction via double aromatic C-H activation. 

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