Unified <i>N</i> -Sulfonylated Urea Catalyzed Enantioselective Dimerization, Arylation, and Amination of Tryptamines: Total Synthesis of Five Pyrroloindoline Alkaloids

Direct oxidative dimerization reactions of tryptamine monomers are biosynthetic pathways that straightforwardly lead to dimeric and oligomeric pyrroloindoline alkaloids that display a diverse range of valuable bioactivities. However, catalytic enantioselective dimerizations have remained a long-standing challenge in asymmetric synthesis due to the difficulties in controlling the radical recombination process of transient single-electron oxidized tryptamines and the formation of a sterically congested all-carbon quaternary stereocenter. Here, we present a strategy that employs catalytic enantioselective dearomative iodocyclization/dimerization cascades to achieve asymmetric oxidative dimerizations of tryptamines. This unified organocatalytic approach enables asymmetric dimerization, arylation, and amination of tryptamines by virtue of a newly developed spiropyrrolidine-derived bifunctional N -sulfonylated urea catalyst, providing efficient and versatile entries to enantioenriched dimeric, arylated, and aminated pyrroloindolines of notable synthetic values. Strategic applications of these methodologies have been showcased in the catalytic asymmetric total syntheses of (−)-folicanthine, (−)-chimonanthine, (+)-calycanthine, (−)-psychotriasine, and (−)-psychotetramine.