Bronsted\nAcid-Catalyzed Regioselective [5 +\n1] Annulation for the Synthesis of Indole-Fused Dihydrochromanes

A Bro̷nsted acid-catalyzed [5 + 1] annulation of\n2-(1<i>H</i>-indol-2-yl)phenols, a class of indole-based\n1,5-CO-synthons,\nwith aldehydes has been established. By this approach, various indole-fused\ndihydrochromanes were synthesized in moderate to good yields (up to\n99%) with excellent regioselectivities. Control experiments not only\nshowed the H-bonding interaction between the NH group of the substratesand\nthe acid catalyst is vital to realize this transformationbut\nalso indicated that an indolylmethanol-type intermediate was possibly\nformed via the first step of nucleophilic addition of indole C3-position\nto aldehydes during the reaction process. This reaction represents\nthe first Bro̷nsted acid-catalyzed regioselective [5 + 1] annulation\nof 2-(1<i>H</i>-indol-2-yl)phenols and provides a novel\nstrategy for constructing biologically intriguing indole-fused dihydrochromane\nskeletons in a highly regioselective manner.