Aryl boronic acids cross coupling

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. 

A rapid MW-assisted palladium-catalyzed coupling of heteroaryl and aryl boronic acids with iodo- and bromo-substituted benzoic acids, anchored on TentaGel has been achieved [174]. An environmentally friendly Suzuki cross-coupling reaction has been developed that uses polyethylene glycol (PEG) as the reaction medium and palladium chloride as a catalyst [175]. A solventless Suzuki coupling has also been reported on palladium-doped alumina in the presence of potassium fluoride as a base [176], This approach has been extended to Sonogashira coupling reaction wherein terminal alkynes couple readily with aryl or alkenyl iodides on palladium-doped alumina in the presence of triphenylphosphine and cuprous iodide (Scheme 6.52) [177]. 

Li and Yue also reported the intermolecular palladium catalyzed cross coupling reactions of bromo quinoxalines 214 and 216 with aryl boronic acids and heterocyclic stannanes, respectively <99TL4507>. The Suzuki couplings (i.e., 214 215) required the use of a... 

In a simple strategy to biaryl formation, Han et al.89 showed that silicon-directed ipso-substitution and concomitant cleavage from supports could be used for formation of functionalized biphenyls. For this they used a tethered silyl aryl bromide in a Suzuki cross-coupling reaction, followed by the ipso-substitution/cleavage step (Scheme 39). A variety of boronic acids were coupled in this manner. The only difficulty occurred with electron-deficient nitrophenylboronic acid where the desired product was formed under anhydrous conditions in only 33% yield (the remainder being starting material). Reversion to the more usual conditions of aqueous base-DME (i.e., those used by Frenette and Friesen)70 improved the yield to 82%. 

Schliiter et al. successfully accomplished generation-specific incorporation of an individual aryl bromide functionality into poly(benzyl ether) dendrimers. Whatever its position in the dendrimer framework, this bromide function could also be utilised for further chemical modification because it can react with aryl-boronic acid via Suzuki cross-coupling [42]. 

Stereospecific cross-couplings of E- and Z-tosylates 5.44 and 5.46 with aryl boronic acids in the presence of PdCl2(PPh3)2 and aqueous Na2C03 in THF gave the corresponding trisubstituted E- and Z-a,(3-unsaturated esters 5.45 and 5.47, respectively. 

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]. 

N-l-Substituted iodoimidazoles behave normally with arylboronic acids to give cross-coupled products <2005T6056>. N-l-Substituted-2-bromoimidazoles also coupled efficiently with aryl boronic acids and alkenyl boronic acids to give cross-coupled products in high yields (Scheme 95) <2004JOC8829>. 

Herradura, P. S., Pendola, K. A., Guy, R. K. Copper-Mediated Cross-Coupling of Aryl Boronic Acids and Alkyl Thiols. Org. Lett. 2000, 2, 2019-2022. 

Since this study, the addition of repeat units capable of a postsynthetic transformation have been investigated. Bo et al. investigated the incorporation of an aryl bromide functionality on the Frechet-type repeat unit, which could be modified by a Suzuki cross-coupling with an aryl boronic acid.521 Freeman et al. explored the attachment of an allyl ether functionality on the same repeat unit,522 while Schultz et al. incorporated an aromatic spacer with two allyl groups to enable internal cross-linking via olefin metathesis.523... 

More recently, Takeda et reported [Pd(SlPr)(cin)Cl)] (39) to be highly efficient in the regioselechve and stereospecific cross-coupling of enantiopure 2-arylaziridines with arylboronic acids. Using 4 mol% of the pre-catalyst, a variety of chiral 2-aryl-phenethylamine derivatives were produced under mild reaction conditions in high yield and with excellent enantioselectivity (up to 99% ee, Scheme 17). Electron neutral and electron deficient aziridines and sterically encumbered and/or funchonalized aryl boronic acids were all well tolerated under the developed conditions. 

Shi described a palladium(II) catalyzed cross-coupling of electron rich (hetero) arenes with aryl boronic acids (Scheme 22) [45]. A major strategic challenge was avoiding homo-coupling of the aryl boronic acids in the presence of palladium(II). 

The reaction is not restricted to forming biaryls. Aryl boronic acids can also react with vinyl halides and vinyl triflates in the presence of palladium (0). Thallium (I) ethoxide is known to promote Suzuki cross coupling reactions for vinyl or arylboronic acids with vinyl and aryl halide partners. 3 synthetic example is... 

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