C-H activation/direct arylation

Direct arylation of aromatic compounds by C-H activation with aryl halides by transition metal catalysis has become an important synthetic process. However until recently the reported procedures were limited to only electron-rich aromatic rings and heteroaromatic compounds. Biaryl compounds containing pyrazine were isolated in moderate to high yields when potassium... 

Please note that there have been a number of reports in the literature on the direct Suzuki-Miyaura reaction [140] as this is basically a C -H activation process, we have decided to include this in Chapter 4, which deals with C-H activation facilitated arylations. 

Directed Metalating Group (DMG)-Asslsted C(sp )-H Activations Direct Arylation... 

Over the past few decades, substantial research has led to the introduction of efficient procedures that allow for the selective connection of two sp C-H bonds. Direct arylations and oxidative olefinations date back to the pioneering investigations of van Helden and Verberg, ° and Fujiwara and Moritani as well as other contributors who demonstrated that aromatic C-H bonds are efficiently activated for coupling with a second sp C-H bond in the presence of stoichiometric quantities of Pd salts. However the products were usually obtained as isomeric mixtures in moderate yields (Scheme 1.35). 

Cleavage of the C—Si bond is in the direction C SiR3+, in the same sense as aryl-H bonds are broken C H+. Activation to electrophilic attack arises from -stabilization of the carbocation in one of the resonance forms (72) of the intermediate85,86. 

Such an arylation reactioncanneverthelessberendered regioselectiveifcoordinating atoms are present in the starting molecule at the appropriate position, directing the C-H activation at this position. Thus, 2-arylbenzoxazoles have been regioselectively arylated in the presence of palladium acetate and silver acetate (Scheme 10.54).86... 

Various directing groups could be used in such directed arylations even carbox-ylates seemed effective at controlling C-H activation of benzoic acid derivatives (Scheme 10.55).87... 

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. 

In 2006 Fagnou described the direct intermolecular arylation of perfluoro benzene derivatives via the proposed proton-transfer pathway (Scheme 6). The reaction shows complete inversion of reactivity relative to the electrophilic C-H activation pathway and is thought to proceed via a concerted arene-metallation and C-H bond cleaving process, which depends on the acidity of the C-H bond being cleaved. 

Other palladium-catalyzed 1,5-C-H activation processes reported are extensions of known work. In these examples, palladium activates the C-H bond, but whether the migration occurs or not is still debatable. An aryl to imidoyl C-H activation takes place in substrate 28 (7) under the same reaction conditions that promote the 1,4-palladium migration. However, this reaction affords a much lower yield (compare with Scheme 10), which implies a relatively low efficiency for this 1,5-C-H activation. Mechanistically, the reaction can either go through a direct C-H activation to form a six-membered palladacycle, followed by reductive elimination, or a proton channeling-based palladium migration, followed by an arylation with the original aromatic ring. The exact path has not been established experimentally or computationally. 

Over the past decade, significant advances have been made in the transition-metal-catalyzed aryl-aryl bond formation through C-H activation (for reviews see [23-32]). In this direct arylation reaction one of the preactivated reaction partners is replaced by a simple arene. This direct arylation process is not only just of academic interest but also attractive for industrial applications, since only one preactivated reaction partner is needed. Obviously, the cost of the reaction will be reduced by... 

Li B-J, Yang S-D, Shi Z-J (2008) Recent advances in direct arylation via Palladium-catalyzed aromatic C-H activation. Synlett 949-957... 

Oi S, Fukita S, Inoue Y (1998) Rhodium-catalyzed direct ortho arylation of 2-arylpyridines with arylstannanes via C-H activation. Chem Commun 2439-2440... 

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