Enantioselective Total Syntheses of (−)‐20‐ epi ‐Vincamine and (−)‐20‐ epi ‐Eburnamonine by Ir‐Catalyzed Asymmetric Imine Hydrogenation/Lactamization Cascade

The Eburnamine‐Vincamine alkaloids have been studied intensively over the past six decades for their outstandingly potent vasorelaxation activity. Stereocontrolled assembly of the C20/C21 adjacent chiral centers has been a formidable challenge in the synthesis of this family. Herein, we report a concise stereoselective total synthesis of two trans ‐ring‐fused non‐natural analogues, (−)‐20‐ epi ‐Vincamine and (−)‐20‐ epi ‐Eburnamonine, that features the following key steps: a) a continuous‐flow oxidation/lactam alcoholysis cascade producing the symmetrical dihydro‐β‐carboline diester precursors, and b) a highly stereoselective Ir/f‐Binaphane‐catalyzed hydrogenation/lactamization cascade leading to the privileged trans ‐(20 R , 21 S ) lactam ester scaffold with high‐level enantio‐ and diastereocontrol.