Organocatalytic Pictet-Spengler Reaction in Natural Product Synthesis

Significance

Hiemstra and co-workers disclose a catalytic enantioselective synthesis of (+)-yohimbine (2). The key steps are a H₈-BINOL-derived phosphoric acid catalyzed enantioselective Pictet-Spengler reaction and a diastereoselective Diels-Alder reaction, similar to the one used in the first catalytic enantioselective synthesis of 2 by Jacobsen and co-workers (Org. Lett. 2008, 10, 745). The choice of the phenylselenoaldehyde 1 as substrate in the Pictet-Spengler reaction proved crucial for the success of the following double-bond generation and Diels-Alder reaction. Aldehyde 1 was also employed in a similar sequence to generate a key intermediate of Sato’s synthesis of (-)-corynantheidine (Eur. J. Org. Chem. 2011, 2606) with improved yield and step economy (52% yield over four steps instead of 31% yield over eight steps).