Suzuki reaction aryl chlorides

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

Cazin and co-workers recently reported on the use of the well-defined dimer complexes [Pd( a-C1)(C1)(NHC)]2 that are commercially available, and perform exceedingly well in the Suzuki-Miyaura reaction involving aryl chlorides [108]. The Cazin group has also recently disclosed well-defined mixed NHC/phosphite palladium systems of the type [PdCl2(NHC) P(OR)3j], enabling the Suzuki-Miyaura of aryl chlorides at 0.1 mol% Pd loading [109]. 

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. 

The pincer-type palladacycle (120) (R = 1Pr), which is actually a derivative of a dialkylphos-phinous acid (themselves excellent ligands see Section 9.6.3.4.6) was shown to allow the crosscoupling of aryl chlorides with terminal acetylenes ((120), ZnCl2, Cs2C03, dioxane, 160 °C). However the high reaction temperature may be prohibitive for the actual application of this catalytic system, as acetylenes are known to be thermally sensitive.433 The same palladacycle (R = Ph) is effective in the Suzuki-Miyaura reaction with aryl bromides and activated aryl chlorides (K2C03, toluene, 130 °C). 

A similarly high performance has been reported for oxime-derived (125) and benzylsulfide-derived (126) palladacycles.438 These precatalysts are effective in the cross-coupling of arylboronic acids,438,439 organotin compounds,440 and terminal acetylenes441 with aryl iodides and bromides, and of activated aryl chlorides. SC-palladacycles can effect the Suzuki-Miyaura reaction even at room temperature. 

A variety of triazole-based monophosphines (ClickPhos) 141 have been prepared via efficient 1,3-dipolar cycloaddition of readily available azides and acetylenes and their palladium complexes provided excellent yields in the amination reactions and Suzuki-Miyaura coupling reactions of unactivated aryl chlorides <06JOC3928>. A novel P,N-type ligand family (ClickPhine) is easily accessible using the Cu(I)-catalyzed azide-alkyne cycloaddition reaction and was tested in palladium-catalyzed allylic alkylation reactions <06OL3227>. Novel chiral ligands, (S)-(+)-l-substituted aryl-4-(l-phenyl) ethylformamido-5-amino-1,2,3-triazoles 142,... 

Buchwald has shown that, in combination with palladium(II) acetate or Pd2(dba)3 [tris(dibenzylideneacetone)dipalladium], the Merrifield resin-bound electron-rich dialkylphosphinobiphenyl ligand (45) (Scheme 4.29) forms the active polymer-supported catalysts for amination and Suzuki reactions [121]. Inactivated aryl iodides, bromides, or even chlorides can be employed as substrates in these reactions. The catalyst derived from ligand (45) and a palladium source can be recycled for both amination and Suzuki reactions without addition of palladium. 

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. 

Heterogeneous Pd catalysts can activate the C-Cl bond in aryl chlorides for the Suzuki-Miyaura reaction, presumably due to a synergistic anchimeric and electronic effect that occurs between the Pd surface and the aryl chlorides. Pd on carbon has been found to be a very effective pre-catalyst for a variety of substrates even under very mild reaction conditions and aqueous solvent mixtures.In 2001, Kabalka and co-workers described that Pd powder and KF as base were useful to couple aryl iodides with arylboronic acids in methanol." At the conclusion of the reaction, Pd metal could be recovered by simple decantation. The use of microwave irradiation accelerates the reaction by... 

Leadbeater and Marco also undertook to optimise the reaction conditions for ligand-free Suzuki reactions in water using both aryl bromides and chlorides. Comparisons between reactions performed under microwave irradiation and oil-bath heating led to the conclusion that the yields were identical or better with oil baths when aryl bromides were used as aryl precursors. However, comparisons between microwave and oil-bath heating with aryl chlorides as starting material clearly favoured the microwave technique38. 

Palladium catalysts have been found which are effective in the Suzuki coupling reaction of arylboronic acids with aryl chlorides carrying electron-withdrawing groups.73 Biaryls may also be synthesized by cross-coupling of arylboronic acids with arenediazonium salts.74,75 There has been a report of the polymer-bound palladium-catalysed Suzuki coupling of aryl triflates with organoboron compounds.76 Arylbor-onates may themselves be synthesized by the palladium-catalysed reactions of... 

In a report by Ozdemir et al. <2005SL2394>, tetrahydrodiazepinium salts 63 (Equation 8) are used as precursors to carbene ligands to be used in Suzuki reactions with aryl chlorides in an aqueous media. In order to prepare these N-heterocyclic carbene ligands, the diamines 62 were reacted with ammonium chloride and triethyl orthoformate. The catalysts prepared from these ligands are stable to air. 

An efficient aqueous phase Suzuki-Miyaura reaction of activated aryl chlorides with aryl boronic acids has been reported. The method uses a new D-glucosamine-based dicyclohexylarylphosphine ligand for the palladium catalyst and works well with nitro-and cyano-activated chlorides.32 The aryl fluoride bond has been considered inert to palladium-catalysed substitution reactions. However, a computational study, backed up by experiment, shows that the presence of a carboxylate group ortho to fluorine will allow reaction both with phenylboronic acids in a Suzuki-type reaction and with organotin reagents in a Stille-type reaction the presence of the adjacent oxyanion stabilizes the transition state.33... 

Efficient Suzuki-Miyaura reactions using electron-rich aryl chlorides were reported with the Pd(OAc)2/PCy3 catalytic combination. The reaction conditions allowed several bases to be used but the authors chose the inexpensive potassium phosphate (Scheme 48) [123]. 

Scheme 48 Suzuki-Miyaura reaction with an aryl chloride...

As Figure 16.7 reveals, an aryl iodide reacts more rapidly with an alkynylcopper compound than an aryl bromide. The palladium-catalyzed C,C coupling reactions, which will be discussed later in the present chapter, also proceed more rapidly with an aryl iodide than with an aryl bromide (example Suzuki coupling in Figure 16.22) or an aryl chloride (example Stille reaction in Figure 16.27). There are still some details that are not fully understood one is inclined to assume that in accordance with the Hammond postulate the weaker C-I bond (dissociation energy DE = 51 keal/mol) breaks more rapidly with the initial oxidative addition... 

The Suzuki reaction of aryl bromides and chlorides is efficiently catalyzed by palladium/ phosphite complexes generated in situ. The influence of the ligand, base, and various additives was examined. The process tolerates various functional groups, and catalyst turnovers of up to 820,000 were obtained, even with deactivated aryl bromides [94]. 

One limitation to the scope of the Suzuki reaction has been its inefficiency when aryl chlorides are employed as substrates. Recently, Buchwald and Fu have discovered the palladium-catalyzed cross-coupling of aryl chlorides with organoboron reagents, employing highly active palladium catalysts mediated by special ligands. These are discussed in Section 3.4. 

One of the challenges in the Suzuki-type cross-coupling is to extend this reaction from electron-rich aryl iodides, bromides, and triflates to less reactive aryl sulfonates and aryl chlorides, which show poor reactivity in terms of oxidative addition in the catalytic cycle. Aryl mesylates, benzenesulfonates, and tosylates are much less expensive than triflates, and are unreactive toward palladium catalysts. The Ni(0)-catalyzed Suzuki-type cross-coupling reaction of aryl sulfonates, including mesylates, with arylboronic acids in the presence of K3P04 has been reported [123]. 

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