Palladium-Catalyzed C-H Bond Arylation

Palladium-catalyzed C-H arylation is perhaps the most rigorously studied C-H bond functionahzation reaction up to now [4, 8a, 11]. A broad set of benzofused oxacydes have been synthesized by this approach. Both aromatic hahdes and arenes with the innate hydrogen remaining could be used as the couphng partners to arylate the inert C-H bond. 

Subsequently, Doucet and coworkers reported a palladium-catalyzed intramolecular direct arylation of 2-bromobenzenesulfonic acid derivatives 

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As an example, Schiff base 1, with its bidentate chelation separated by a three-carbon fragment (the correct distance for formation of a six-membered metalla-cycle) from the C-H bond, can undergo palladium-catalyzed C-H bond arylation... 

Wang X, Gribkov DV, Sames D (2007) Phosphine-free palladium-catalyzed C-H bond arylation of free (N-H) -indoles and pyrroles. J Org Chem 72 1476-1479... 

The pioneering studies by Moritani and co-workers set the stage for further applications of palladium-catalyzed C—H bond functionalizations to oxidative C (sp2)-C(sp2) bond-forming processes. Thus, catalyzed oxidative arylations for biaryl syntheses could be accomplished with either stoichiometric [120] or catalytic [121] amounts of palladium complexes. 

The last decade has seen an explosive growth in the development of palladium catalyzed C—H bond activation reactions [81]. These have provided intriguing methods to couple the C—H bond of simple arenes with activated aryl halides, and... 

The functionalization of iV-iminopyridium ylides with various aryl and heteroarylbromides using a palladium-catalyzed C-H bond activation strategy has been reported (eq 27). This... 

A wide range of sulfoxides 78, except for the one with a 2-substituted phenyl group, were converted to the corresponding dibenzothiophenes 80 in moderate to high yields. The authors proposed that sulfoxides 78 are first transformed to 2 -mercaptobiphenyl-2-ylcarbaldehydes 79 by a palladium catalyst. Then the palladium-catalyzed C—H bond activation/intramolecular S-arylation of aldehydes 79 affords dibenzothiophene 80. Indeed, they confirmed that biphenyl-2-ylthiol (81) was converted to dibenzothiophene (82) under the palladium catalysts (Scheme 23.31). 

Palladium and copper-catalyzed arylation of C-H bonds by aryl halide reagents is reviewed. The emphasis of the review is on directing-group-containing arene and alkane arylation catalyzed by palladium and on sp2 C-H bond arylation catalyzed by copper. Literature up to early 2009 is covered. 

This review will cover recent advances in the palladium-catalyzed C-H activation of the indole and pyrrole nucleus, specifically for the formation of new C-C bonds via arylation and alkenylation. Most commonly, activation is achieved through... 

Lane BS, Sames D (2004) Direct C-H bond arylation selective palladium-catalyzed C2-arylation of iV-substituted indoles. Org Lett 6 2897-2900... 

C—H bond arylations of electron-deficient heteroarenes, such as azines, remain highly challenging. An elegant and versatile solution was recently elaborated, however, through a redistribution of electron density in the starting pyridine by chemical modification [77, 78]. It was found that pyridine N-oxides smoothly underwent regioselectively palladium-catalyzed direct arylations with a variety of aryl bromides (Scheme 9.36) [77a]. 

Although palladium-catalyzed cross-coupling reactions provide an efficient entry to C-arylated indoles, these reactions require the preparation of functionalized hetero-arenes such as boronates and halides. Therefore, C-arylation reactions of azole and related heteroarenes via direct C-H bond functionalization of the parent heteroar-enes would be much more favorable. In 2004, Sames reported a selective palladium-catalyzed C2-arylation of W-substituted indoles via direct C—H bond arylation [199]. Use CsOAc as the base and low concentration of the substrates proved to be critical for the success of this methodology. 

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... 

A chelation-assisted mthenium-catalyzed arylation of aldehyde 99 was accomplished in combination with a palladium complex [47]. This cooperative catalysis [48] proved applicable to organostannanes and aryl iodides as arylating reagents (Scheme 9.35). The direct arylation proceeded most likely through ruthenium-catalyzed C—H bond activation, subsequent transmetallation to palladium, and reductive elimination from a palladium intermediate. 

Scheme 3.13 Palladium-catalyzed decarboxylative C-H bond arylation of thiophenes, as described by Su and coworkers [26].

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). 

Palladium-catalyzed directed intramolecular activations of aryl C-H bonds have been reported, as in the phenyla-tion of heterocycle analogs. Palladacycles are proposed intermediates, acting as effective catalysts, and the mechanism is likely to proceed via oxidation of Pd(ll) to Pd(iv) by the iodonium salt, as for the Equation (57), which described the activation of benzylic i/-CH bonds (Equations (121)—(123).109... 

The palladium-catalyzed arylation of 2-phenylphenols and naphthols shows an interesting feature of arylation of C-H bonds, leading to the formation of an (aryl)(aryloxy)palladium(n) intermediate.65,65a,65b The phenolates are suitable as precoordinating groups. The reaction of 2-hydroxybiphenyl with an excess of iodobenzene occurs regioselectively at the two ortho-positions of phenyl group under palladium catalysis (Equation (57)). In the case of 1-naphthol, the peri-position is phenylated (Equation (58)). 

Palladium-catalyzed reaction of 2-hydroxy-2-methylpropiophenone with aryl bromides shows a unique multiple arylation via successive C-C and C-H bond cleavages, giving tetraarylethanes.96 For example, the reaction of 2-hydroxy-2-methylpropiophenone with bromobenzene in the presence of Pd(OAc)2, P(/-Bu)3, and CS2CO3 gives 1,1,2,2-tetraphenylethane quantitatively, together with l,4,4-triphenyl-7-methylisochroman-3-one (13% yield) (Equation (74)). 

Palladium(0)-catalyzed cross-coupling of aryl halides and alkenes (i.e., the Heck reaction) is widely used in organic chemistry. Oxidative Heck reactions can be achieved by forming the Pd -aryl intermediate via direct palladation of an arene C - H bond. Intramolecular reactions of this type were described in Sect. 4.1.2, but considerable effort has also been directed toward the development of intermolecular reactions. Early examples by Fu-jiwara and others used organic peroxides and related oxidants to promote catalytic turnover [182-184]. This section will highlight several recent examples that use BQ or dioxygen as the stoichiometric oxidant. 

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