Organocatalytic triazole formation, followed by oxidative aromatization: Regioselective metal-free synthesis of benzotriazoles

Abstract

Herein we report on our studies on the sequential one-pot combinations of amine-catalyzed multicomponent reactions (MCRs). We have developed the copper-free synthesis of functionalized bicyclic N-aryl-1,2,3-triazole and N-arylbenzotriazole products 4 and 5 from the simple unmodified starting materials through [3+2]-cycloaddition ([3+2]-CA) and oxidative aromatization reactions in one pot under amine catalysis. The sequential one-pot reaction proceeds in good yields with high selectivity by using pyrrolidine as the catalyst from the simple unmodified substrates of enones, aryl azides, and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ). Furthermore, we have demonstrated the medicinal applications of products 4 and 5 through simple organic reactions. Organo-click approach to benzotriazoles: A practical synthesis of N-arylbenzotriazoles was achieved through the sequential one-pot combination of [3+2]-cycloaddition followed by 2,3-dichloro-5,6-dicyano-1,4- benzoquinone (DDQ)-mediated oxidative aromatization of unmodified cyclic enones with aryl azides. For the first time, the synthesis of privileged CF3 containing N-arylbenzotriazoles through metal-free catalysis has been discovered (see scheme). Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.