A sonochemical approach to 4-substituted pyrrolo[1,2-a]quinoxalines via Cu-catalyzed N-arylation followed by Wang resin/air promoted oxidative cyclization strategy

Abstract

The 4-substituted pyrrolo[1,2-a]quinoxaline framework was explored for the identification of possible inhibitors of SIRT1. To access the target compounds a general and ultrasound assisted two-step approach was developed for the first time involving the Cu-catalyzed N-arylation followed by Wang resin/air promoted oxidative cyclization strategy. Thus, CN coupling of 2-iodoanilines with pyrrole gave the 1-(2-aminophenyl)pyrrole derivatives in the first step which on CN/CC bond formation with aldehydes afforded the desired products. The second step proceeded in pure water under open air and recovery as well as reuse of the Wang resin catalyst was demonstrated. The methodology offers advantages such as shorter duration, use of eco-friendly energy and wider substrate scope. Further application of this sonochemical method was also demonstrated via Suzuki coupling of a bromo product. Some of the pyrrolo[1,2-a]quinoxalines showed encouraging (52–77 %) inhibition of SIRT1 in vitro (better than nicotinamide) and were identified as initial hits.