Solvent‐ and Temperature‐Switched Chemoselectivity: Controlled Synthesis of Diverse Pyrazolo[5,1‐a]isoquinolines

Abstract

Abstract. Divergent synthesis of two types of functionalized pyrazolo[5,1‐a]isoquinolines was established via a one‐pot two‐step protocol involving a tunable dehydrogenation process and deacylative oxidation accompanied by elimination of the HNO2 pathway. Key attributes of the procedure included the initial formation of C,N‐cyclic‐N’‐acyl azomethine imines and subsequent switchable chemoseletivity that either led to aroyl‐ and nitro‐substituted pyrazolo[5,1‐a]isoquinolines or proceeded via deacylative oxidation and elimination of HNO2 pathway to afford solvent and temperature used. The present approach features the use of readily available amines and aldehydes as raw materials, switchable chemoselectivity, wide functional group tolerance such as nitro, halide, aryl, aroyl and sulfonyl group, and easy separation and purification. A combination of control experiments and density functional theory (DFT) calculations provided important insights into the possible mechanism.