Preparation of 2,5-Disubstituted Tetrazoles using a Copper-Catalysed Regioselective Direct Coupling of Tetrazoles with Free NH Groups and Boronic Acid Derivatives

The development of a mild and efficient protocol that allows the direct C-N coupling of N-H free tetrazole and low toxic boronic acid was presented. A careful optimization of the reaction conditions revealed that reaction proceeded smoothly in presence of a 10 mol % copper complex catalytic system without the need of any additives. Thus, the results presented herein represents a reliable and efficient protocol for the synthesis of regioselective 2,5-disubstituted tetrazoles. A mild and efficient regioselective synthesis of 2,5-disubstituted tetrazoles has been achieved via direct C-N coupling of N-H free tetrazoles and low toxic boronic acid with 10 mol % Cu(II) catalytic complex system. The developed protocol was found to be applicable for a wide range of electronically diversified phenylboronic acids and phenyl tetrazoles with good yields of the isolated product.image