Solvent-Controlled Diastereodivergent Synthesis of Hexahydropyrrolo[2,1- a]isoquinolines through Pd/C-Catalyzed Dehydrogenative [3 + 2] Cycloaddition

J Org Chem. 2024 Dec 20;89(24):18723-18728. doi: 10.1021/acs.joc.4c02343. Epub 2024 Dec 10.

Abstract

A Pd/C-catalyzed dehydrogenative [3 + 2] cycloaddition is described for the diastereoswitchable synthesis of hexahydropyrrolo[2,1-a]isoquinolines by altering solvents. The reaction proceeds through a sequential Pd/C-catalyzed dehydrogenative formation of azomethine ylides from tetrahydroisoquinoline acetates and 1,3-dipolar cycloaddition with 2-nitroethenylbenzenes. This method displayed tunable diastereoselectivity, a broad substrate scope and good functional group compatibility. Moreover, a gram-scale synthesis and selective reductive or oxidative transformations of the product further demonstrate the utility of this methodology.