Suzuki Miyaura aryl chlorides

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]. 

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,... 

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... 

An der Heiden, M. and Plenio, H. (2004) Homogeneous catalysts supported on soluble polymers biphasic Suzuki— Miyaura coupling of aryl chlorides using phase-tagged palladium—phosphine catalysts. Chem. Ear. ]., 10, 1789. 

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]. 

Recently, a paper was published describing Suzuki-Miyaura coupling in DMF and water with aryl chlorides using the air- and moisture-stable... 

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

An alternative to solid-supported catalysts are catalysts that are insoluble themselves [136]. A pyridine-aldoxime ligand was presented and evaluated in the Suzuki-Miyaura reaction using water as a solvent. Using an Irori kan to contain the polymeric catalyst, the reaction could be repeated 14 times without any noticeable reduction in efficiency. The optimized reaction conditions were then used to create a small library of approximately 30 biaryl compounds using aryl iodides, bromides, triflates as well as an activated chloride (Scheme 56) [136]. 

When IBioxl2 HOTf was employed as the ligand precursor for the Suzuki-Miyaura coupling of sterically hindered aryl chlorides and aryl boronic acids, excellent to good yields were obtained in refluxing toluene for a variety of starting materials (Table 6). Notably, this work represents the first report of tetra-orf/zo-substitulcd biaryl compounds achieved from aryl chlorides [143]. 

The catalytic activity of benzothiazole-oxime-based Pd (Il)-complexes (xxxv) was evaluated in Suzuki-Miyaura and Heck-Mizoroki C-C cross coupling reactions of aryl bromides and chlorides with aryl boronic acid and olefins under microwave conditions in water was studied by Dawood [55]. 

Dawood KM (2007) Microwave-assisted Suzuki-Miyaura and Heck-Mizoroki crosscoupling reactions of aryl chlorides and bromides in water using stable benzothiazole-based palladium(ll) precatalysts. Tetrahedron 63 9642-9651... 

A convenient and effective palladium-catalysed Suzuki-Miyaura cross coupling reaction of deactivated aryl chlorides with phenylboronic acid utilised the 1,3-diazepinium salts 107 as in situ precursors of the palladium ligands. These salts were prepared from the diamines 106 and cyclocondensation with triethyl orthoformate <05SL2394>. 

Suzuki-Miyaura Cross-Coupling of Aryl Bromides and Chlorides with Boronic Acids at Low Catalyst Loadings... 

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