Reactions of Aryl Chlorides

All catalysts presented up to now were strictly limited to aryl bromides. Most of them show lower activity than pure Pd(OAc)2. In the following, heterogeneous 

Entry Catalyst Cat. cone. [mol%] Alkene Solvent Base T rq t[h] Yield [%] Ref. 

In 1997 Ying and coworkers reported that Pd-grafted mesoporous materials are active catalysts for Heck reactions. The Pd-TMSll catalyst (prepared by gas phase reaction of volatile Pd complexes and MCM-41) was one of the very first heterogeneous catalysts that succeeded in the activation of aryl chlorides. With a catalyst amount of 0.1 mol% Pd at least 16% of chlorobenzene could be converted (TON = 64). However, 170 °C and 32 h reaction time were necessary. Only 40% selectivity to the Heck coupling products (= 6% yield) could be achieved [152, 159]. Another catalyst was prepared by Srivastava et al. by ion exchange using SAPO-31 and (NH3)4PdCl2-H20. Up to 70% of chlorobenzene could be converted at 120°C within 70 h (67% yield) [160]. 

A Pd-modified zeolite NaY was utiUzed as a heterogeneous catalyst for Heck reactions of 4-choroacetophenone [161,162]. Entrapped [Pd(NH3)4] gave yields of about 60% of stilbene derivatives with palladium amounts of 0.1mol% (170 °C, 

Addition of NBu4Br had a promoting effect on the reaction. Non- and deactivated aryl chlorides could not be converted under the same reaction conditions. However, under optimized reaction conditions by changing solvent (NMP instead of DMA), base (Ca(OH)2 instead of NaOAc) and atmosphere (O2 instead of argon) 

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Hydrogenolysis of aryl and alkenyl halides and triflates proceeds by the treatment with various hydride sources. The reaction can be explained by the transmetallation with hydride to form palladium hydride, which undergoes reductive elimination. Several boro hydrides are used for this purpose[680], Deuteration of aromatic rings is possible by the reaction of aryl chlorides with NaBD4681]. 

HECK REACTIONS OF ARYL CHLORIDES CATALYZED BY PALLADIUM/TRI-tert-BUTYLPHOSPHINE (E)-2-METHYL-3-PHENYLACRYLIC ACID BUTYL ESTER AND (E)-4-(2-PHENYLETHENYL)BENZONITRILE... 

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. 

FuNn iONAL Group Tolerance of PdildbrO VIMes.HCI Catalyzed Suzuki Cross-Coupling Reactions of Aryl Chlorides with Phenyi.boronic Acid Derivatives... 

We synthesized uniform CU2O coated Cu nanoparticles from the thermal decomposition of copper acetylacetonate, followed by air oxidation. We successfully used these nanoparticles for the catalysts for Ullmann type amination coupling reactions of aryl chlorides. We synthesized core/shell-like Ni/Pd bimetallic nanoparticles from the consecutive thermal decomposition of metal-surfactant complexes. The nanoparticle catalyst was atom-economically applied for various Sonogashira coupling reactions. 

Synthesis of CU2O coated Cu nanoparticles and their successful applications to Ullmann-type amination coupling reactions of aryl chlorides... 

As an example, consider the use of PVPy as a solid poison in the study of poly(noibomene)-supported Pd-NHC complexes in Suzuki reactions of aryl chlorides and phenylboroiuc acid in DMF (23). This polymeric piecatalyst is soluble under some of the reaction conditions employed and thus it presents a different situation from the work using porous, insoluble oxide catalysts (12-13). Like past studies, addition of PVPy resulted in a reduction in reaction yield. However, the reaction solution was observed to become noticeably more viscous, and the cause of the reduced yield - catalyst poisoning vs. transport limitations on reaction kinetics - was not immediately obvious. The authors thus added a non-functionalized poly(styrene), which should only affect the reaction via non-specific physical means (e.g., increase in solution viscosity, etc.), and also observed a decrease in reaction yield. They thus demonstrated a drawback in the use of the potentially swellable PVPy with soluble (23) or swellable (20) catalysts in certain solvents. 

Various PX-ligands showed high efficiency in catalyzing cross-coupling reactions of aryl chlorides. The PO-ligand (L5) is used in the system (1% Pd(dba)2-3L, CsF, toluene, reflux).391... 

Commercially available Pd(PtBu3)2 is a unique, air-stable 14e Pd° complex, an excellent catalyst for cross-coupling reactions of aryl chlorides. The ability of P Bu3 to stabilize such a coordin-atively unsaturated, extremely reactive, and yet easily manageable form of Pd° is one of the most amazing and fruitful recent findings in Pd-based catalysis. The cross-coupling of arylzinc reagents with aryl or vinyl chlorides can be readily accomplished with as little as 0.03% of this catalyst. Both electron-rich and sterically hindered substrates are welcome in this protocol.404... 

Complexes ligated by the unsaturated carbene at the top right of Figure 2, catalyze the reaction of aryl chlorides with a variety of amines, including primary amines at 100°C and the reactions of aryl... 

Scheme 6.2 Heck reactions of aryl chlorides involving air-stable phosphonium salts as ligand precursors.

Scheme 6.61 Buchwald-Hartwig amination reactions of aryl chlorides.

Selected coupling reactions of aryl chlorides in the presence of Pd/1 are shown in Scheme 4. For example, nonactivated and sterically hindered 2,6-dimethylchlorobenzene reacts with bulky, sterically congested anilines smoothly at low catalyst loading (0.5 mol% Pd(OAc)2/l P/Pd = 2 1). 

Mulhaupt et al. synthesized novel soluble copoly-arylenes via a Ni(0)-catalyzed coupling reaction of aryl chlorides. Molar ratios of dichlorodiphenyl sulfone (a) to m-dichlorobenzene (y) were used to vary the amount of m-phenylene in the final copolymer. Then these copolymers were dissolved in chloroform and sulfonated with chlorosulfonic acid. The synthe-... 

Historically, one of the most important limitations of the Suzuki-Miyaura reaction was the poor reactivity of organic chlorides, attributed to the strength of the C-Cl bond. Aryl chlorides are very attractive halides due to their low cost and wider diversity of available compounds. Prior to 1998, reports of effective palladium-catalyzed Suzuki reactions of aryl chlorides were limited to activated substrates, and generally employing very high temperatures. In that year. 

A similar approach was taken for the synthesis of 45 by Miyaura. " Shaughnessy and Booth synthesized the water-soluble alkylphosphine 46, and found it to provide very active palladium catalysts for the reaction of aryl bromides or chlorides with boronic acids. The more sterically demanding ligand 47 was shown to promote the reactions of aryl chlorides with better results than 46. Najera and co-workers recently reported on the synthesis of di(2-pyridyl)-methylamine-palladium dichloride complexes 48a and 48b, and their use in the coupling of a variety of electrophiles (aryl bromides or chlorides, allyl chlorides, acetates or carbonates) with alkyl- or arylboronic acids very low catalyst loadings at Palladium-oxime catalysts 8a and 8b) have also been developed. In conjunction with... 

Littke, A.F. and Fu, G.C., Palladium-catalysed coupling reactions of aryl chlorides, Angew. Chem., Int. Ed. Engl, 2002,41,4176-4211. 

Reactive metal anodes are quite effective in reactions of aryl chlorides in the presence of a large excess of chlorotrimethylsilane in an undivided cell using a sacrificial aluminum anode in THF/HMPA (4 1) which provide the corresponding aryltrimethylsilanes (equations 76 and 77)101402> p is metPod does not require any diaphragms since oxidation of the aluminum anode takes place predominantly as the anodic reaction (equation 76). When excess amount of electricity is passed, traw.s-tris(lriruclhylsilyl)chlorohcxa-1,3-dienes are formed predominantly (equation 78). 

Mukhopadhyay, S., Rothenberg, G., (oshi, A., Baidossi, M. and Sasson, Y. (2002) Heterogeneous palladium-catalyzed Heck reaction of aryl chlorides and styrene in water under mild conditions. Adv. Synth. Gated., 344, 348. 

Littke, A. F. Fu, G. C. A versatile catalyst for Heck reactions of aryl chlorides and aryl bromides under mild conditions./. Am. Chem. Soc. 2001, 123, 6989-7000. 

A series of palladium(O) mono-imidazolylidene complexes have also been prepared and used for the Heck reaction of aryl chlorides in [NBu4]Br.29 The authors report that two of their catalysts, (1,3-dimesi-tylimidazolylidene)(naphthoquinone)palladium(0) and (1,3-dimesitylimida-zolylidene)(benzoquinone)palladium(0) (Fig. 5) remain stable throughout the reaction and will couple even non-activated aryl chlorides in good yields. Clearly, the authors believe that the imidazolylidene complex is responsible for this activity. 

Carbonylation reactions of aryl chlorides may be accomplished by two different approaches. Coordination of the arene ring to a tricarbonylchromium unit facilitates oxidative addition, and carbonylation may consequently be accomplished382. Alternatively, Pd(dippp)2 (47) has proven to be a catalyst capable of converting chloroarenes to aldehydes, amides, esters or acids in good yields. This catalyst may be generated in situ, by the addition of Pd(OAc)2 and dippp. Both electron-withdrawing and electron-donating... 

Pyrrole anion is unreactive in liquid ammonia under irradiation with PhBr or 1-chloro-naphthalene. However, the reactions of aryl chlorides (p-chlorobenzonitrile, 3- and 4-chloropyridines and 4-chlorodiphenyl sulphone) with 2,5-dimethylpyrrole anion under electrochemical inducement in the presence of a redox mediator gave the C3-substituted product in moderate yields (35-40%) (equation 120)225. The rate constant of the coupling reaction between this nucleophile and aryl radicals is about 5-8 x 109 M"1 s 1 determined by electrochemical methods225. 

The electrochemically induced S l reaction of aryl chlorides with redox mediators and pyrrole anion gave mainly 2-aryl pyrroles (52-67%) and, in a lower amount, 3-aryl pyrroles... 

A full account of the scope and limitations of the amination chemistry of these ligands has recently appeared [158]. With ligand 15, a number of aminations were conducted at room temperature. In the absence of an ortho substituent, couplings of primary amines with unactivated aryl chlorides at room temperature required 5 mol % catalyst. However, a variety of secondary amines, both cyclic and acyclic, reacted with activated or deactivated aryl chlorides at room temperature. Thirteen examples were demonstrated. The scope of this process was broader, however, when reactions were conducted at 80 or 110 °C. Under these conditions, unactivated aryl chlorides reacted with a variety of amines in high yields. In favorable cases, such as reactions of aryl chlorides bearing one ortho methyl group, reactions of N-methyl... 

Nolan reported the use of the 2,6-diisopropylphenyl imidazolium carbene precursor, which contains an unsaturated backbone, for the reaction of aryl chlorides with a variety of amines at 100 °C [165, 166]. This temperature is lower than those conventionally used for reactions of aryl chlorides, but is higher than those used with P(tBu)3 or the 2-biphenylyl di-tert-butylphosphines. Reaction yields were high when 2 mol % palladium was used. Reactions of primary amines occurred in good yield, even when unhindered aryl halides were used. The monoarylamine was obtained in 86 % yield, and only a 5 % yield of the diaryl-amine by-product was isolated. Notably, reactions of both aryl bromides and iodides proceeded at room temperature. 

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