ABSTRACT The mild Lewis acid chlorotrimethylsilane (TMSCl) enables the regioselective synthesis of 9H‐pyrrolo1,2‐ a indoles at room temperature. The annulation proceeds via a cascade sequence consisting of first a Friedel–Crafts 1,4‐addition of an indole to an enone, followed by a second nucleophilic attack and isomerization to a pyrrole. This process afforded many diversely functionalized pyrrolo1,2‐ a indoles in a modular fashion from easily accessed indoles and α,β‐unsaturated ketones in moderate to good yields. Previous approaches to pyrroloindoles required elevated temperatures (70°C–100°C) and strong Brønsted acids or Lewis acidic metals. This protocol employs mild conditions at room temperature (25°C), excludes the use of metals, and allows operation open to the ambient atmosphere. Regioselectivity control experiments showed that the pyrrole substitution pattern is dictated by the enone substitution. Acid/base control experiments showed Brønsted acid formation may be occurring during the course of the reaction, but is not necessary for successful product formation.
Gopavaram et al. (Sun,) studied this question.