Intermolecular Arylations

Over the course of the past decade, the intermolecular Mizoroki-Heck reaction has witnessed tremendous progress [9,10]. As a comprehensive survey of this area is certainly beyond the scope of this chapter, the decision was taken to include a few important developments, namely the activation of less-reactive aryl chlorides, waste-minimized processes, and novel catalyst systems. 

At a relatively high reaction temperature (150°C), Reetz et al. also accomplished the Mizoroki-Heck reaction of chlorobenzene with styrene in the presence of Pd(OAc)2 and phosphonium salt PI14PCI [23aj. Again, the high catalytic activity was ascribed to the presence of nanosized palladium colloids, which are beheved to be stabilized by the phosphonium salt 

51) is necessary to promote the decarbonylation step (51- 52). The extrusion of carbon monoxide produces the CT-arylpalladium(II) complex 52, which, after migratory insertion of alkene 41 (52 53) and fl-hydride elimination/reductive ehmina-tion (53— 1), Uberates the desired arene 48. 

The benchmark was set by Herrmarm s carbene complex 65 which, under optimized reaction conditions, showed a respectable TON of 13000. In a similar study by Baker et al., the Mizoroki-Heck arylation of iodobenzene (60b) with 63 in the presence of catalyst 66 bearing a chelating NHC ligand with a cyclophane backbone showed an outstanding TON of 7100000 [34]. In another study, Buchmeiser et al. introduced a new class of NHC based on 1,3-disubstituted tetrahydropyrimi- 

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This adds to other reports of intra- and intermolecular arylations of phenolic derivatives (Equations (145)-( 147)). 124,124a 124c... 

Hartwig has reported an intramolecular/intermolecular process affording the 3-aryloxindoles 105 (Scheme 32).115 The intermolecular arylation of acetanilide derivative 104 is slower than the intramolecular arylation to form the oxindole. Thus, the overall transformation starts with cyclization followed by intermolecular arylation of indole. In order to slow down the intermolecular process and speed up the intramolecular reaction, chloroarene and bromine-substituted acetanilide precursors are used according to their respective reactivity with palladium(O) in the oxidative addition process. 

In a series of papers, Itahara established the utility of Pd(OAc)2 in the oxidative cyclization of C- and A-benzoylindoles, and two examples are shown [61-63], Itahara also found that the cyclization of 3-benzoyl-1,2-dimethylindole proceeds to the C-4 position (31% yield) [61]. Under similar conditions, both 1-acetylindole and l-acetyl-3-methylindole are surprisingly intermolecularly arylated at the C-2 position by benzene and xylene (22-48% yield) [64,65],... 

Larock, R. C. Yum, E. K. Yang, H. Palladium-catalyzed intermolecular arylation of function-ally-substituted cycloalkenes by aryl iodides. Tetrahedron 1994, 50, 305-321. 

Intermolecular Arylation Reactions of Phenols and Aromatic Carbonyl Compounds... 

Scheme 1. Pd-catalyzed and coordination-assisted intermolecular aryl-aryl coupling via C—H bond cleavage...

Scheme 1. Possible catalytic sequences forthe Pd-catalyzed intermolecular arylation of five-membered heteroaromatic compounds involving one heteroatom.

Scheme 2. Possible catalytic sequences for the Pd-catalyzed intermolecular arylation of azole compounds at the 2-position.

Several reports on the application of the intermolecular arylation of primary alkylamines have appeared. For example, the reaction of primary amines with chloro 1,3 azoles has been used to produce the H-l-antihistaminic norastemizole [153]. As shown in Eq. (32), the palladium chemistry is dictated by the steric properties of the amines. This property creates selectivity that complements the thermal chemistry, which is dictated by amine nucleophilicity. These researchers have also shown that this high selectivity for arylation of primary over secondary amines with catalysts containing BINAP as ligand allows for the rapid assembly of other multiamino-based structures [154]. 

Early investigations dealing with intermolecular arylations of uiisymmetrically donor-substituted alkenes often revealed only poor regioselectivities, especially with acyclic enol ethers. However, suitable conditions have since been developed for both the selective a-... 

Scheme 3-36 Intramolecular tiryl-aryl as well as intra-intermolecular aryl-aryl and aryl-alkene coupling cascades [189].

Scheme 12 Sames strategy towards regioselective intermolecular arylation of indoles...

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. 

Facile intermolecular aryl-F bond cleavage in the presence of aryl C-H bonds Is the r]2-arene intermediate bypassed ... 

Since the pioneering work by Beletskaya and co-workers [8] the intra- and (more commonly) intermolecular arylation of alkenes has been shown to proceed very smoothly in aqueous medium in the presence of palladium acetate. At the beginning, the methodology seemed to be limited to aryl iodides under a strong influence of the base it was shown that the presence of potassium acetate instead of carbonate yielded lower reaction temperatures and higher rates (Eq. 4). 

As described above, appropriately functionalized aromatic substrates such as phenols and aromatic carbonyl compounds undergo intermolecular arylation directly and regioselectively on treatment with aryl halides in the presence of palladium catalysts. As illustrated in Scheme 3, which is a proposed general... 

Studies of intermolecular aryl ligand transfer of nickel complexes [149] started almost at the same time as the first preparation of the arylnickel complexes because they were regarded to be involved in Ni complex promoted intermolecular coupling of aryl halides to give biaryls. Kochi reported the reaction of bromoarene with NiBr(ArXPEt3)2 at elevated temperature in THF to produce biaryl as the... 

It is more facile than the reaction of NiBr(Ar)(bpy), whose disproportionation via intermolecular aryl ligand transfer requires polar solvents to assist Ni-halogeno bond activation as mentioned in a previous section. Methylplatinum complexes with monodentate phosphine, arsine and thioether hgands cause methyl ligand transfer leading to disproportionation and cis-trans isomerization [207] (Eq. 5.63). 

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