Aryl-heteroaryl compounds, Suzuki

Scheme 41 Aryl-heteroaryl compounds via Suzuki coupling...

The imidoyl chloride moiety of 5-chloro-l-alkyl-1,4-benzodiazepin-2-ones participates in Pd-catalyzed, Suzuki crosscoupling reactions, reacting with a range of functionalized aromatic boronic acids to provide an efficient and versatile approach to 5-aryl and 5-heteroaryl compounds (Scheme 19) <2003JOC2844>. This chemistry readily extends to 3-amino-substituted compounds that are orally bioavailable inhibitors of the aspartyl protease 7-secretase <2003BML4143>. 

A major advantage of this MCR is that organoboronic acids are readily available in a large variety of structural configurations and they can be formed in isomeri-cally pure forms. As a result of their widespread utility in Suzuki-Miyaura coupling [27, 28] and other reactions [29, 30], a variety of aryl and heteroaryl [31] boronic adds are now commercially available and can be employed in this MCR process. Most of these compounds are also air and water stable as well as non-toxic and environmentally friendly. They also tolerate many functional groups, thereby... 

NMR experiments on the reactions of halophosphates esters with pyridine showed that equilibria involving the formation of pyridinium salts in these reactions are almost entirely shifted to the left for chloro- and bromo-phosphates and to the right for the corresponding iodophosphates. This explains dramatic differences in chemical reactivity between these compounds. Substituted medium-sized and large N-heterocycles (117) have been prepared via an extension of the Suzuki reaction involving the palladium-catalysed coupling of vinyl-phosphates (118) with aryl or heteroaryl boronic acids (Scheme 27). ... 

Suzuki methodology, with a 3-halotriazolopyridine and an aryl or heteroaryl boronic acid, sodium carbonate and tetrakistriphenylphosphine as catalyst, the synthesis of 3-aryl derivatives 6b-g, i, j, ha ve been described (Figure 2). In these reactions a secondary compound was also formed, the 33 -bitriazolopyridine 37 (Figure 10), as a consequence of a homocoupling Ullman reaction. From 7-bromo-3-methyl-triazolopyridine, the synthesis of some 7-aryl derivatives 7a-g in very good yields (60-90%) was also reported (Figure 2) (06TL8101). 

The Suzuki reaction is a powerful carbon-carbon bond-forming reaction method for the rapid introduction of diverse substituent onto an aromatic ring. Substituted arylacetic acids represent an important class of cyclooxygenase inhibitors. These inhibitors that are built on the phenylacetic acid core, typically incorporating three elements of variability an a-alkyl group, R alkyl, aryl or heteroaryl substitution on the phenyl ring, R and acid or amide functionality (Scheme 31.5). To synthesize this variety of molecules requires successful construction of a combinatorial library of a class of compounds and that depends... 

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