Biaryls palladium-catalyzed coupling

AN IMPROVED SYNTHESIS OF BIARYL DERIVATIVES VIA THE PALLADIUM CATALYZED COUPLING OF ARYL BROMIDES... 

In terms of methodologies for the preparation of A-arylindoles 140, Buchwald reported improved conditions for the palladium-catalyzed coupling of aryl chlorides, bromides, iodides and triflates 138 with a variety of 2-, 7- and polysubstituted indoles 139 utilizing novel electron-rich biaryl(dialkyl)phosphine ligands in combination with Pd2(dba)3 <00OL1403>. Alternatively, Watanabe reports similar A-arylations of pyrrole, indole and carbazoles with aryl bromides and chlorides using Pd(OAc)2/P(f-Bu)3 in xylene at 120°C <00TL481>. 

Palladium chemistry, despite its immaturity, has rapidly become an indispensable tool for synthetic organic chemists. Today, palladium-catalyzed coupling is the method of choice for the synthesis of a wide range of biaryls and heterobiaryls. The number of applications of palladium chemistry to the syntheses of heterocycles has grown exponentially. 

R = alkenyl, aryl, allyl, benzyl, propargyl R = alkenyl, aryl, alkynyl, alkyl, benzyl, allyl The Negishi Coupling was the first reaction that allowed the preparation of unsymmetrical biaryls in good yields. The versatile nickel- or palladium-catalyzed coupling of organozinc compounds... 

Transition metal-catalyzed cross-coupling is now recognized to be one of the most powerful carbon-carbon bond-formation reactions [1], The palladium-catalyzed coupling of aryl halides or their synthetic equivalents, for example aryl triflates, with arylmetals is very often employed in the synthesis of biaryl molecules, whose skeletons are found in a wide range of important compounds including natural products and organic functional materials [1-3]. 

Aryl(chloro) silanes, upon pretreatment with KF, smoothly undergo the palladium-catalyzed coupling with aryl bromides and iodides to give various biaryls. For this procedure, Pd(OAc)2 (0.5 mol%)/P(o-tol)3 (0.5 mol%) is convenient (Eq. 20). 

The reaction was exploited very recently in a solid phase synthesis of biaryls. Aryl zinc bromides undergo palladium catalyzed coupling reactions with aryl bromides bound to a polystyrene resin. The product can be released from the resin by transesterification [44]. Ni(0) catalysed homocoupling of arylzinc reagents could also be realised using aryl triflates [45], as well as aryl tosylates and mesylates [46]. 

Biaryl structures are found in a wide range of important compounds, including natural products and organic functional materials [8,80,81]. One of the most common and useful methods for preparing biaryls is the palladium-catalyzed coupling of aryl halides with arylmetals (Scheme 1, mechanism A). On the other hand, aryl halides have been known to couple directly with aromatic compounds as formal nucleophiles under palladium catalysis. While the intramolecular cases are particularly effective, certain functionalized aromatic compounds such as phenols and aromatic carbonyl compounds, as well as... 

Cross-coupling reactions have also been examined in water using amphiphilic PS-PEG resin-supported palladium complexes. Palladium-catalyzed coupling of aryl halides with aryl(or alkenyl)boronic acids (the so-called Suzuki-Miyaura coupling) took place in aqueous alkaline solution in the presence of polymeric catalyst 59 at 25 °C to give the biaryls in excellent yields [90,... 

Aldous and co-workers also reported extensive results on palladium-catalyzed coupling reactions. They introduced the utility of electron-deficient pyridazinyl triflate 136 in Stille and Suzuki biaryl cross-couplings with electron rich aryl stannanes and aryl boronales 137 <01SL150>. Electron deficient aryl stannanes resulted in more sluggish reactions and poor yields. In general, Suzuki reactions were found to be better than the corresponding Stille couplings. 

Palladium catalyzed coupling reactions have been applied intensively in research for many years. As a ccmsequence more and more chemical products cmitaining the biaryl substructure are discovered and must be produced on larger scale [5]. 

Ligands 5 and 6 are particularly efficacious for the borylation of aryl chlorides to pinacol boronate esters, thus allowing the direct one-pof synthesis of unsymmetrical biaryls from two aryl chlorides (Equation 2.23) [41]. Due to the wide breadth and scope that this family of biaryldialkylphosphine Hgands offers for palladium-catalyzed couplings of aryl chlorides, many are commercially available and aU are highly crystalline, air-stable solids, and hence easy to use. 

Shimizu M, Mochida K, Hiyama T (2008) Modular approach to silicon-bridged biaryls palladium-catalyzed intramolecular coupling of 2-(arylsilyl)aryl triflates. Angew Chem Int Ed 47 9760-9764... 

Traditionally, the synthesis of symmetrical biaryls was routinely accomplished using the Ullmann reaction. Recently, palladium-catalyzed homocoupling of aryl halides has also been demonstrated to rival the utility of the Ullmann coupling. As illustrated in Scheme 21, using Pd(OAc)2 as the... 

Several microwave-assisted protocols for soluble polymer-supported syntheses have been described. Among the first examples of so-called liquid-phase synthesis were aqueous Suzuki couplings. Schotten and coworkers presented the use of polyethylene glycol (PEG)-bound aryl halides and sulfonates in these palladium-catalyzed cross-couplings [70]. The authors demonstrated that no additional phase-transfer catalyst (PTC) is needed when the PEG-bound electrophiles are coupled with appropriate aryl boronic acids. The polymer-bound substrates were coupled with 1.2 equivalents of the boronic acids in water under short-term microwave irradiation in sealed vessels in a domestic microwave oven (Scheme 7.62). Work-up involved precipitation of the polymer-bound biaryl from a suitable organic solvent with diethyl ether. Water and insoluble impurities need to be removed prior to precipitation in order to achieve high recoveries of the products. 

For purposes of completeness, palladium-catalyzed reactions for the synthesis of biaryls using zincates and arylhalides (Negishi Couplings) [254] or using sihcon compounds [255, 256] need to be mentioned. 

SYNTHESIS OF BIARYLS VIA PALLADIUM-CATALYZED CROSS COUPLING 2-NETHYL-4 -NITROBIPHENYL (l.l -Biphenyl, 2-methyl-4 -nitro-)... 

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