Ag(I)/PPh3-Catalyzed Diastereoselective Syntheses of the Spiro[indole-3,4'-piperidine] Scaffold and Its Derivatives via Chelation-Controlled Cycloisomerizations of Tryptamine-Ynamides

A Ag(I)/PPh3-catalyzed chelation-controlled cycloisomerization of tryptamine-ynamide was developed to access the spiro[indole-3,4'-piperidine] scaffold. The asymmetric products with this scaffold were obtained through a diastereoselective synthesis via a chiral pool approach. Such a synthesis could be realized on a gram scale and derivatization of this scaffold afforded various derivatives. DFT calculations indicated that strong non-covalent effects between the substrate and catalyst/ligand complex stabilized the spiroindoleninium intermediate via cation-π-π interactions, leading to the diastereoselective syntheses of spiro[indole-3,4'-piperidine derivatives.