Coupling with chlorobenzene

Chloroarenes are rarely employed as coupling partners because the C —Cl bond is reluctant to undergo oxidative addition compared with C—Br or C—l bonds. However, chlorobenzene could also be used when a palladium catalyst having a triisopropylphosphine or l,2-bis(dicyclohexylphosphino)ethane (dcpe) ligand was employed [Eq.(19)] [18]. 

For the coupling reaction of less-reactive heteroaromatic halides, diaryldichlorosilanes are conveniently employed to give heterobiaryls in high yields [Eq.(20)] [19]. 

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A 3-branched, optically active primary alkyl Grignard reagent has been shown to undergo coupling with chlorobenzene without loss of optical activity in the presence of NiCbCDPPP), while about 10% racemization is induced when NiCh(PPh3)2 or NiCh(DMPE) are used as catalysts, possibly due to 3-H elimination-addition sequences (equation 94). ... 

The Suzuki-Miyaura cross-coupling reaction is a standard method for carbon-carbon bond formation between an aryl halide or triflate and a boronic acid derivative, catalyzed by a palladium-metal complex. As with the Mizoroki-Heck reaction, this cross-coupling reaction has been developed in ionic liquids in order to recycle and reuse the catalyst. In 2000, the first cross-coupling of a halide derivative with phenylboronic acid in [bmim] [BF4] was described. As expected, the reaction proceeded much faster with bromobenzene and iodobenzene, whereas almost no biphenyl 91 was obtained using the chloride derivative (Scheme 36). The ionic liquid allowed the reactivity to be increased, with a turnover number between 72 and 78. Furthermore, the catalyst could be reused repeatedly without loss of activity, even when the reaction was performed under air. Cross-coupling with chlorobenzene was later achieved - although with only a moderate yield (42%) - using ultrasound activation. 

Various other substituted azoles such as pyrazoles, benzimidazoles, and primary and secondary aliphatic cyclic amines were also successfully coupled with chlorobenzenes to afford (V-arylated products in fair yields (Scheme 9, entries 1-10). 

Chlorides are inert. However, the reaction ofp-chlorobenzophenone (9) with a styrene derivative proceeds satisfactorily at 150 C by u.sing dippb [l,4-bis(-diisopropylphosphino)butane] as a ligand to give the stilbene derivative 10. However, dippp [l,3-bis(diisopropylphosphino)propane] is an ineffective ligand[13]. On the other hand, the coupling of chlorobenzene with styrene proceeds in the presence of Zn under base-free conditions to afford the cis-stilbene 11 as a main product with evolution of H . As the ligand, dippp is... 

Chlorobenzenes activated by coordination of Cr(CO)3 react with terminal alkynes[253). The 1-bromo-1,2-alkadiene 346 reacts with a terminal alkyne to afford the alka-l,2-dien-4-yne 347[254], Enol tritlates are used for the coupling with terminal alkynes. Formation of 348 in the syntheses of ginkgolide[255] and of vitamin D are examples[256] Aryl and alkenyl fluorides are inert. Only bromide or iodide is attacked when the fluoroiodoalkene 349 or fluoroiodoar-ene is subjected to the Pd-catalyzed coupling with alkynes[257-259]. 

Pd/P(t-Bu)., in the presence of Cy2NMe, is an unusually mild and versatile catalyst for Heck reactions of aryl chlorides (Tables 1 and 2) (as well as for room-temperature reactions of aryl bromides).21 22 23 Example A, the coupling of chlorobenzene with butyl methacrylate, illustrates the application of this method to the stereoselective synthesis of a trisubstituted olefin a-methylcinnamic acid derivatives are an important family of compounds that possess biological activity (e.g., hypolipidemic24 and antibiotic25) and serve as intermediates in the synthesis of pharmaceuticals (e.g., Sulindac, a non-steroidal anti-inflammatory drug26). Example B, the coupling of 4-chlorobenzonitrile with styrene, demonstrates that Pd/P(t-Bu). can catalyze the Heck reaction of activated aryl chlorides at room temperature. 

E)-stilbene was the exclusive product of the Pd colloid-catalyzed Heck arylation of styrene with chlorobenzene. Recently, a polymer-mediated self-assembly of functionalized Pd and Si02 nanoparticles have been found to be highly active catalysts for hydrogenation and Heck coupling... 

The Gomberg coupling reaction of aryl diazonium salts with arenes is catalysed by quaternary ammonium salts [49], Although yields are variable, they are generally >50% [49, 50]. When aromatic solvents other than benzene are used, the appropriate biaryls are produced, e.g. 4-chlorobenzenediazonium tetrafluoroborate reacts with chlorobenzene to produce the 2,4 -, 3,4 - and 4,4 -dichlorobiphenyls in a ca. 67 18 15 ratio. 

A limitation of both methods is that the second component must be liquid at the temperature of-the reaction, which is 5-10° for the diazohydroxide reaction and room temperature or slightly higher for the nitrosoacetylamine reaction. Experiments with solid reactants in solution have not been very successful, because of the difficulty of finding a suitable solvent. The solvent should be neutral and immiscible with water, have a high solvent action and reasonably low boiling point, and be inert to the free radicals which result from the diazo compound. The last qualification is the most difficult one to satisfy. Of the solvents which have been tried, carbon tetrachloride and chloroform appear to be the most suitable.18 From diazotized aniline and biphenyl in these solvents, some p-terphenyl is obtained, and from diazotized p-nitroaniline and biphenyl a small amount of 4-nitro-4 -phenylbiphenyl is formed. In these reactions an appreciable amount of tfie aryl halide (chlorobenzene and p-nitrochlorobenzene) is produced as a by-product. In general, the yields of products obtained by coupling with reactants in solution are extremely low. 

C4)4N][OAc] [(C4)4N]Br and others Large variety NaOAc, [(C4)4N]OAc and others 120-160 °C. Successful coupling or chlorobenzene with styrene using NaOAc as base more active than the corresponding reactions in DMF very high recyclability of the phospha-palladacyle catalyst in [(C4)4N]Br with product isolated by distillation. [61] [62]... 

Figure 6.1 Carbene and phosphapalladacyle complexes evaluated for the coupling of styrene with chlorobenzene in [(C NJBr...

A charged support, double layered hydroxide, that can be described by the general formula, Mgi xAlx(OH)2Cl zH20, was used to immobilise [PdCl4]2-/811 While results with this catalyst were only poor in A-methyl pyrrolidinone, good conversion and selectivity was obtained in [(C4)4N]Br with arylchlorides as substrates. By employing microwave irradiation coupling between chlorobenzene and styrene afforded the desired product in 95% yield within 30 minutes. The products were isolated by distillation and the catalytic activity remained essentially stable for at least 5 runs. 

Carbon—carbon coupling reactions of aryl halides are commonly catalyzed by palladium triarylphosphine complexes and proceed well for aryl bromides and iodides while aryl chlorides are generally unreactive. More basic chelating trialkylphosphines, however, render palladium sufficiently electrophilic to undergo rapid oxidative addition with chlorobenzene ... 

The less reactive chlorobenzene and arene sulfonates coupled with phenylindole in the presence of a palladium catalyst generated from X-phos (31, Figure 8). For example, 4-tezt-butylphenyl tosylate reacted to give quantitative yields of ZV-(4-tezt-butylphenyl)indole in the presence of 2 mol% Pd, 5 mol% X-phos and K3PO4 as the base98. 

Milstein and co-workers were the first to introduce catalysts capable of activating various aryl chlorides in 1992 [175]. By using palladium complexes of highly basic and sterically demanding chelating bisphosphines, for example, dippb [l,4-bis(di-isopropylphosphinyl) butane], even chlorobenzene was coupled with alkenes in high yields (Table 1, 70-95% yield TON = 70-95) [175]. However, these catalysts are extremely sensitive to air. Herrmann, Beller, and co-workers introduced more robust palladacycles [cyclopalladated... 

A communication and full paper tell of the efficient photoreduction of 4-chlorobiphenyl to biphenyl by excitation of 9,10-dihydro-lO-methylacridine (163) or acriflavine (164) in aqueous acetonitrile containing sodium borohydride. A variety of alkyl halides, benzyl halides and chlorobenzenes were also reduced. The reaction proceeds by electron transfer from the excited state of the dihydroacridine to the chloroarene, chloride loss and hydrogen atom donation to the arene radical. Thus photoreduction of the arene is coupled with oxidation of the dihydroacridine to the acridinium salt the latter is reduced back to the dihydroacridine by the borohydride. 

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