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

A Pd/C-catalyzed dehydrogenative [3 + 2] cycloaddition is described for the diastereoswitchable synthesis of hexahydropyrrolo[2,1-<i>a</i>]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.