Direct arylation of aromatic C-H bonds

Iridium-Catalyzed Direct 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... 

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

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... 

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],... 

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. 

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 " . 

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... 

Under similar oxidative conditions, with activation of the aromatic C-H bond, some arenes could be used directly as aryl sources [41]. Unfortunately, by analogy with the Friedel-Crafts acylation, this reaction is regioselective for very few substrates only. High regioselectivity was, however, obtained if coordinating substituents on the arenes facilitate an orthopalladation reaction by a Pd(II) species [42]. After carbometallation and reductive elimination, Pd(0) is released, which has to be converted into the initial Pd(II) species in an extra oxidation step. Usually, quinines are used for this purpose, but in combination with certain heteropolyacids as cocatalysts even molecular oxygen can be employed as the oxidant. 

Since aryl halides are fairly cheap reagents, there has been less recent emphasis (see Section 3 below) on the development of aryl relative to that of alkyl C-H bond activation [13-17]. However, the manufacture of aryl halides is not an environmentally friendly process and thus the future of bulk aromatic synthesis may he in the direct activation of C-H bonds. For example, the formation of ben-zaldehyde from the insertion of CO into a C-H bond of benzene is a recent development in this area [17]. 

Direct formation of isolable cr-aryl complexes by intermolecular oxidative addition of an aromatic C—H bond to a transition-metal complex was first observed in an alkyl phosphine complex of Ru and has now been extended to most of the transition metals. The relevant literature is summarized in Table 1. There are reviews of C—H activation by homogeneous metal complexes and its relevance to homogeneous and heterogeneous catalysis s " . 

Aromatic compounds can react with Pd(II) species, typically Pd(OAc)2, via cleavage of their C-H bonds to give arylpalladium(II) species (Scheme 1, mechanism D). Therefore, the arylation of alkenes can be performed directly using arenes and aromatic heterocycles [10, 11]. In this arylation, halogenation of arenes can be omitted, but an oxidizing reagent for the reoxidation of Pd(0) to Pd(II) should be added to make the reaction catalytic. 

In one of the earliest reports about the catalytic functionalization of inactivated aromatic C—H bonds, Murai and co-workers demonstrated that a pendent heteroatom could act as a directing group to achieve selective ort/ o-alkylation of aryl ketones. Ever since this work, transition metal catalyzed C—H bond... 

The arguments for replacing through substitution an aromatic C-H bond rather than an aryl C-halide bond are convincing, and hence, a tremendous amount of attention has rightly been directed to such transformations involving catalysis. By far. 

A variety of methods for the catalytic direct arylation of aromatic and heteroaromatic compounds via the cleavage of C—H bonds has been developed during recent years. As complementary synthetic tools for conventional cross-couplings in the preparation of biaryls and arylated heteroarenes that require neither stoichiometric metallation nor halogenation, these reactions may be both useful and economical in a variety of situations. Consequently, it is highly likely that a major effort will be made in the near future to enhance the catalytic efficiency and regioselectivity of these reactions. 

In 1993, Murai reported the reactions of aryl ketones witti ethylene and vinylsilanes to form the product from the addition of the C-H bond ortho to the carbonyl group to the olefin (Equation 18.49). This finding led to subsequent work on the addition of the C-H bonds of a variety of aromatic groups to a series of olefins. Catalysts that react under milder conditions than the original ones and extensions of the C-H activation to intramolecular cyclizations to form heterocyclic structures have made this reaction capable of being used in the synthesis of complex molecules. For example, alkylated diterpe-noids and (+)-lithospermic acid (Equations.18.50 and 18.51) have been synthesized using directed hydroarylation. ... 

Following this study, Fagnou et al. [34] reported the direct arylation of different aromatic substrates promoted by [Pd(OAe)J. This process followed a CMD mechanism, which describes simultaneous making-breaking bonds. A closer look to the transition state highlights that the elongation of the C—H bond is not in relation with the acidity of the arene as electron-rich and electron-deficient arenes promote the C—H activation by similar activation barriers (see numbers in bold in Fig. 25.23). This observation highhghts that the metal and the base are key to promote the arylation reaction with no dependency on the nature of the substrate. 

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