Mild Chlorotrimethylsilane Promoted Annulation of Indoles and Enones to Synthesize Substituted Pyrroloindoles

ABSTRACT The mild Lewis acid chlorotrimethylsilane (TMSCl) enables the regioselective synthesis of 9H‐pyrrolo[1,2‐ 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 pyrrolo[1,2‐ 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.