Construction of Indole Skeletons through Direct Catalytic Three-Component Domino Reactions of Vinylarenes, Aldehydes, and Pronucleophiles

A synthesis of 3-alkyl-2-arylindoles was performed by sequential oxidation and reduction of 2-(2-nitrophenyl)ethanols that were prepared by base-catalyzed three-component reactions of vinylarenes, aldehydes, and various pronucleophiles, including nitroalkanes, thiols, and malonates. In addition to indoles, a selective synthesis of an N-hydroxyindole was accomplished. The highly nucleophilic character of transient benzylic anions in DMSO was also clarified for the three-cornponent reactions.

Automated summary

A novel method for the synthesis of 3-alkyl-2-arylindoles was developed through sequential oxidation and reduction reactions. Starting from 2-(2-nitrophenyl)ethanols prepared by a base-catalyzed three-component reaction, the desired products were obtained by oxidation and reduction steps. Notably, a selective synthesis of N-hydroxyindole was also achieved. Furthermore, the highly nucleophilic nature of transient benzylic anions in DMSO was demonstrated for the three-component reactions.