Cross coupling reactions heteroaryl acid chloride

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]. 

Scheme 21 Cross-coupling reaction of Ar3Bi with heteroaryl acid chlorides...

Most recently, Botella and Najera have reported that oxime-derived palladacycles such as 51 are air- and water-stable catalysts that are suitable for cross-coupling reactions of different aryl and heteroaryl chlorides with boronic acids in neat water (Equation 84) [123],... 

There were some literature reports on the reactions of T2,4-triazoles. 3-Bromo- and 3-iodo-N,S-dibenzyl-5-mercapto-l,2,4-triazoles 140 participated in Suzuki—Miyaura cross-coupling reactions with aryl, heteroaryl, and vinyl boronic acid derivatives to give 141, followed by deprotection with aluminum chloride to give 5-hetero(aryl)-3-mercapto-l,2,4-triazoles 142 (13TL4524). Multiple regioisomers of arylated 1,2,4-triazoles via C-H arylation could be obtained from judicious reactions of SEM- and THP-protected 1,2,4-triazoles (13JOC738). 

Nucleophilic displacement of chlorine, in a stepwise manner, from cyanuric chloride leads to triazines with heteroatom substituents (see Section 6.12.5.2.4) in symmetrical or unsymmetrical substitution patterns. New reactions for introduction of carbon nucleophiles are useful for the preparation of unsymmetrical 2,4,6-trisubstituted 1,3,5-triazines. The reaction of silyl enol ethers with cyanuric chloride replaces only one of the chlorine atoms and the remaining chlorines can be subjected to further nucleophilic substitution, but the ketone produced from the silyl enol ether reaction may need protection or transformation first. Palladium-catalyzed cross-coupling of 2-substituted 4,6-dichloro-l,3,5-triazine with phenylboronic acid gives 2,4-diaryl-6-substituted 1,3,5-triazines <93S33>. Cyanuric fluoride can be used in a similar manner to cyanuric chloride but has the added advantage of the reactions with aromatic amines, which react as carbon nucleophiles. New 2,4,6-trisubstituted 1,3,5-triazines are therefore available with aryl or heteroaryl and fluoro substituents (see Section 6.12.5.2.4). 

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