Mild, Modular, and Convergent Synthesis of Helical Naphtho[2,1-c]chromenes via a Multistep Cyclization/Aromatization Cascade Sequence.

Tetracyclic 6H-naphtho[2,1-c]chromenes are expeditiously synthesized through a BF3·OEt2-mediated, three-step cascade reaction, creating new central pyran and aromatic rings. The cascade involves the addition of phenol-derived alkynyl substrates to BF3-activated aldehydes followed by alkyne-Prins cyclization, Friedel-Crafts reaction, and final elimination. Aliphatic and electron-deficient aromatic aldehydes afford the products in 50-74% isolated yields, but benzaldehyde and tolualdehyde resulted in lower yields. X-ray analysis of a p-bromophenyl derivative (5aA) shows the two aromatic moieties are twisted by 28° to create a helical backbone.