Synergistic Lewis and Brønsted acid-mediated annulation of o-alkynylbenzaldehydes with nitriles for amide-substituted benzo[a]fluorenes

Abstract

Herein, we report a Lewis and Brønsted acid-mediated cyclization/amidation reaction of o-alkynylbenzaldehydes with nitriles, constructing a series of amide-substituted benzo[a]fluorene derivatives. The transformation initiated via the acid-mediated 6-endo-dig cyclization of o-alkynylbenzaldehyde generates an isochromenylium intermediate that undergoes [4 + 2] benzannulation with a second substrate's alkyne group, eliminating additional unsaturated hydrocarbons. Nitrile, as a readily available amide source, facilitates direct C–N bond formation. This unified process forges multiple C–C bonds and a C–N bond in a single operation under mild conditions, achieving excellent step economy and chemoselectivity.