Bronsted Acid-Catalyzed Regioselective [5 + 1] Annulation for the Synthesis of Indole-Fused Dihydrochromanes

A Bro̷nsted acid-catalyzed [5 + 1] annulation of 2-(1<i>H</i>-indol-2-yl)phenols, a class of indole-based 1,5-CO-synthons, with aldehydes has been established. By this approach, various indole-fused dihydrochromanes were synthesized in moderate to good yields (up to 99%) with excellent regioselectivities. Control experiments not only showed the H-bonding interaction between the NH group of the substrates─and the acid catalyst is vital to realize this transformation─but also indicated that an indolylmethanol-type intermediate was possibly formed via the first step of nucleophilic addition of indole C3-position to aldehydes during the reaction process. This reaction represents the first Bro̷nsted acid-catalyzed regioselective [5 + 1] annulation of 2-(1<i>H</i>-indol-2-yl)phenols and provides a novel strategy for constructing biologically intriguing indole-fused dihydrochromane skeletons in a highly regioselective manner.