Palladium‐Catalyzed Direct Arylations of 1,2‐Azolo[1,5‐ a ]pyridines using Copper(I) Chloride as a Lewis Acid Activator and the Synthesis of 2,6‐Disubstituted Pyridines

A direct method for the arylation of 1,2‐azolo[1,5‐ a ]pyridines has been developed. In the process, the fused pyridines react with aryl halides in the presence of the palladium complex Pd(OAc) 2 (Phen) as a catalyst and copper(I) chloride (CuCl) as a Lewis acid to form arylated derivatives. While pyrazolo[1,5‐ a ]pyridines and [1,2,4]triazolo[1,5‐ a ]pyridines are arylated at ortho ‐positions of their pyridine rings using this method, in situ ring‐opening of the formed C‐7 arylated [1,5‐ a ]pyridine takes place to generate the 2,6‐disubstituted pyridine. Also, upon treatment with lithium diisopropylamide (LDA), C‐7 arylated pyrazolo[1,5‐ a ]pyridine‐3‐carboxylates react to produce diversely substituted 2,6‐disubstituted pyridines. Finally, a sequential C‐3 arylation was accomplished through a two‐step sequence involving hydrolysis of pyrazolo[1,5‐ a ]pyridine‐3‐carboxylates followed by the bimetallic Pd/Cu‐catalyzed decarboxylative coupling reaction with aryl bromide.