Diversity-Oriented Synthesis of Polycyclic Indoles: Bronsted or Lewis Acid Catalyzed Three-Component Reaction for the Synthesis of α-Carbolines and Pyrimidoindoles

We report the diversity-oriented synthesis of pyrido- and pyrimido-indoles from an acid-catalyzed three component (3C) reaction involving ethyl 2-amino-1H-indole-3-carboxylates, arylaldehydes, and terminal alkynes. In the presence of a BrOnsted acid such as trifluoroacetic acid (TFA), the 3C reaction furnished a mixture of pyrido- and pyrimido-indoles, whereas when catalyzed by Yb(OTf)(3) as a Lewis acid, pyrimidoindoles were obtained as the single product. The findings demonstrate the ability to control reaction products through change in the acid catalyst. The salient feature during TFA-catalyzed 3C reaction is that two different pathways are followed in one pot after propargylamine formation. The two cascade cyclizations comprise in situ decarboxylation-carbocyclization and an intramolecular hydroamination to afford products with different connectivity.