Diastereoselective synthesis of tetrahydroisoquinolines through the Pd-catalyzed post-Ugi transformations

We present a diastereoselective approach to sp³-enriched tetrahydroisoquinolines from Ugi-derived propargylamides through a sequence combining Pd-catalyzed reductive Heck cyclization with heterogeneous double-bond hydrogenation. Although the initial reductive Heck annulation generally proceeded with weak stereocontrol over the exocyclic alkene geometry, the subsequent Pd-catalyzed hydrogenation proved highly diastereoselective, predominantly affording tetrahydroisoquinolines with a cis relative configuration. The hydrogenation was largely stereoconvergent, delivering the same major cis diastereomer irrespective of the E/Z geometry of the intermediate isoquinolines.