Boronate esters palladium-catalyzed cross-coupling

Suzuki couphng, the palladium-catalyzed cross-coupling of aryl or vinyl hahdes with organoboronates, is employed widely in organic synthesis. The reaction is most often carried out in an organic solvent (benzene) in the presence of a base [228]. Because of the reasonable stabihty of boronic acids and esters towards hydrolysis, Suzuki couphng can also be carried out in aqueous media. An extensive study of the reaction has shown that similar results are obtained in aqueous and non-aqueous systems [229]. 

The second synthesis of fascaplysin (44), from labs at the CNRS, is also very high in overall yield (157). Palladium-catalyzed cross-coupling of the boronic ester 189 with the halogenated pyridine 190 lead to intermediate 191 (Scheme 20). Metalation of 191 with n-BuLi was regioselective, due in part to the inductive effects of nearby electronegative groups. The double cyclization of 192 to fascaplysin provides the natural product in 76% overall yield. 

The coupling of stable organosulfur compounds with boronic acids is of great synthetic importance, since both reaction partners are readily available, low toxicity, and are stable toward many reagents. 4-Halo-n-butyl and normal thio esters (Fig. 2) were prepared and investigated as substrates for palladium-catalyzed cross-coupling with boronic acids. 

Suzuki-Miyaura reactions are perhaps the most widely employed palladium catalyzed cross-couplings in the realm of thiazole medicinal chemistry. They typically take place only when the thiazole is an electrophile in the transformation. The nucleophilic thiazole boronic acid or ester, especially at the 2-position, is relatively unstable and therefore difficult to prepare. The electrophiles namely the 2-, 4-, or 5-substituted halothiazoles are often readily accessible in terms of their synthetic ease or commercial availability. A remarkable application has been described by Jang et al. in the discovery... 

Functionalized alkenyl diamino- and dialkoxyboranes have been produced regio-and stereoselectively through addition of carbon- or heteroatomgenerated from bromotrichloromethane, thiols, phosphines and tributyltin hydride) to ethynylbis(diisopropylamino)boranes. The synthetic utility of these reactions was illustrated by the preparation of stereodefmed (Z)- or ( )-alkenylboronic esters via palladium-catalyzed crossStille reaction and a Suzuki coupling under basic conditions can be further conducted (Scheme 9.14) [33]. 

One of the most reliable methods for the construction of an oligoheteroarene structure is the transition-metal-catalyzed cross-coupling reaction [26]. However, a problem to be overcome remains in the cross-coupling. The installation of a metal group into heteroaromatic compounds is often dififlcult because of problems with the stability of the resulting heteroaromatic metal reagent [27]. For example, 2-pyridyl boronic acid and its esters are easily decomposed by proton [28]. In addition to this problem with stability, the transmetallation of an electron-deficient heteroaromatic boron reagent to palladium is relatively slow [29]. 

Suzuki Coupling Reaction Suzuki reaction is palladium-catalyzed cross-couphng between organoboronic acid and halides. Recently, newly developed catalysts and methods have broadened possible applications enormously, so that the scope of the reaction partners is not restricted to aryls but includes alkyls, alkenyls, and alkynyls. Potassium trifluoroborates and organoboranes or boronate esters may be used instead of boronic acids. Some pseudohaUdes (e.g., triflates) may also be used as coupling partners. 

Various carbon-carbon cross-coupling reactions are employed to arrive at oligomers from fluorene monomers, including nickel-cataylzed Yamamoto coupling between aryl halides [48], palladium(0)-catalyzed Suzuki coupling between boronic acids/esters and halides [49], and ferric-chloride-catalyzed Scholl reaction, also called Friedel-Crafts arylation, of bare fluorenes [50,51]. 

Evans and co-workers developed rhodium catalyzed hydroboration reactions, which enable the use of catechol borane and other boronate esters as hydroborating agents to afford organoboronic esters as products.9 These products have increased stability and can be used directly in palladium cross-coupling applications. However, the rhodium-catalyzed method is most effective for the hydroboration of monosubstitued olefins (i.e., 16), as lower reactivity is observed with more substituted alkenes. 

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