Chiral Phosphoric-Acid-Catalyzed Asymmetric Dearomatization [4 + 3] Annulation for de Novo Construction of Cyclohepta[ de ]naphthalenones

Abstract

The cyclohepta[de]naphthalenone skeleton constitutes an important privileged structural motif found in numerous natural products. However, the asymmetric catalytic synthesis of this skeleton has not yet been reported. Herein, we disclose the first chiral phosphoric acid (CPA)-catalyzed asymmetric [4 + 3] annulation between 2-naphthol-derived benzyl alcohols and 2-indolylmethanols. This transformation enables the facile assembly of enantioenriched cyclohepta[de]naphthalenone derivatives in good to excellent yields (up to 98%) with outstanding stereoselectivities (up to 98% ee and >20:1 dr). Mechanistic investigations reveal that intermolecular hydrogen bonding between the chiral catalyst and the substrates governs both reaction reactivity and stereoselectivity.