Enantioselective [4 + 2] Cycloaddition/Cyclization Cascade Reaction and Total Synthesis of <i>cis</i>-Bis(cyclotryptamine) Alkaloids

Abstract

The asymmetric catalytic synthesis of 3-cyclotryptamine substituted oxindoles through formal [4 + 2] cycloaddition/cyclization cascade is described. A wide range of cyclotryptamine derivatives were obtained in enantioenriched form under mild reaction conditions and were found to have potential anticancer activity. The strategy enables ready assembly of cyclotryptamine subunits at the C_3a-C_3a' positions with two quaternary stereogenic centers in <i>cis</i>-selectivity, leading to the concise synthesis of optically active <i>cis</i>-bis(hexahydropyrroloindole) and others of the cyclotryptamine alkaloid family.