Total Synthesis of (−)-Calycanthine via Iron-Catalyzed Stereoselective Oxidative Dimerization

Abstract

Dimeric cyclotryptamine alkaloids typically feature vicinal all-carbon quaternary stereocenters and four nitrogen atoms. In comparison with the actual biosynthetic tryptophan derivatives, we designed the 2<i>N</i>-featured monomer <b>7</b>, aiming to construct vicinal all-carbon quaternary stereocenters via a one-step dimerization process to access the 4<i>N</i>-featured isomeric members of this family. In this work, we disclose the first synthetic route to access the skeleton of (-)-isocalycanthine, featuring an iron-catalyzed oxidative dimerization reaction in a catalytic single-step operation with an overwhelming control of the absolute and relative stereochemistry. This strategy has been successfully applied to the total synthesis of (-)-calycanthine and 16 isocalycanthine derivatives, which demonstrates a new synthetic pathway for dimeric cyclotryptamine alkaloids.