Total Synthesis of (+)-Chimonanthine, (+)-Folicanthine, and (−)-Calycanthine

Abstract

Facile, straightforward, and asymmetric total syntheses of (+)-chimonanthine (<b>1</b>), (+)-folicanthine (<b>2</b>), and (−)-calycanthine (<b>3</b>) were accomplished in four to five steps from commercially available tryptamine. The synthesis features copper-mediated asymmetric cyclodimerization of chiral tryptamine derivative, which established a new entry into constructing the sterically hindered vicinal quaternary stereogenic carbon centers of dimeric hexahydropyrroloindole alkaloids in one procedure. An unprecedented base-induced isomerization from the chimonanthine skeleton to the calycanthine skeleton was observed and facilitated the synthesis of (−)-calycanthine (<b>3</b>)