Suzuki-Miyaura reaction synthetic application

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... 

Boronic acids and boronate esters serve a myriad of purposes, and the discovery of the Suzuki-Miyaura reaction facilitated the widespread interest and application of organoboron compounds. This palladium-catalyzed C-C bond forming reaction initiated renewed interest in the preparation of diversely functionalized boronic acids that would lead to valuable products. From this synthetic standpoint, Suzuki coupling reactions have been employed in the production of natural products and the preparation of materials of interest. " The search for interesting starting materials for the Suzuki reaction produced a series of methods to prepare boronic acids so these species could be exploited in further applications. These compounds... 

Let us now consider some key synthetic applications of the Suzuki-Miyaura reaction in recent years. In the case of the synthesis of pharmaceuticals, this reaction has played a very prominent role. The excellent review by Magano and Dunetz [12k] describes many interesting examples of the application of this reaction in this industry. In our case, the following examples are particularly interesting and relevant. 

Conveniently prepared from phenols, more readily available than the corresponding aryl halides, and recognized as the most powerful in the hierarchy of DMGs [63], the aryl O-carbamates are primed for synthetic application. One application is their use in the regioselective preparation of polysubstituted aromatics and then involvement as leaving groups in subsequent Suzuki-Miyaura or Kumada-Corriu (Section 14.3.1.2) cross-coupling reactions for the establishment of 1,2-disubstituted aromatics, illustrated by the conceptual 1,2-dipole synthetic equivalent, 35 36 = 37 (Scheme 14.10 and Scheme 14.11) [64]. 

Palladium-catalyzed hydroboration, haloboration, and similar reactions involving addition of organoboron compounds to alkynes have been reviewed.Alkylborane addition to alkynes followed by intra- or intermolecular cross-coupling with a vinyl halide or triflates according to the Suzuki-Miyaura protocol constitutes a very powerful synthetic route for the generation of two carbon-carbon bonds in cascade. This subject and its applications in synthesis have been reviewed. ... 

Synthetic Applications of Suzuki-Miyaura Cross-Coupling Reaction ... 

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