Synthesis of Indole‐Fused Chromane‐Based Spirooxindoles via Brønsted Acid‐Catalyzed Regioselective [5+1] Annulation

Abstract

A regioselective [5+1] annulation of 2‐(1H‐indol‐2‐yl)phenols with isatins was established by the catalysis of Brønsted acid. Through this strategy, indole‐fused chromane‐based spirooxindoles bearing a quaternary carbon center were synthesized in moderate to good yields (53 % to 99 %) with excellent regioselectivities. Mechanism study demonstrated the importance of hydrogen‐bonding interaction between the N−H group of the substrates and the acid catalyst. Moreover, an indolylmethanol‐type intermediate was possibly generated after the first nucleophilic addition of indole C3‐position to isatins during the reaction process. This transformation not only provided a good example for using 2‐(1H‐indol‐2‐yl)phenols as 1,5‐C/O‐dinucleophiles in [5+1] annulations under acidic environment, but also achieved the first construction of indole‐fused chromane‐based spirooxindole frameworks.