Brønsted Acid Catalyzed Friedel-Crafts Alkylation of Naphthols with In Situ Generated Naphthol-Derived ortho-Quinone Methides: Synthesis of Chiral and Achiral Xanthene Derivatives.

Abstract

We disclose herein an enantioselective protocol for the Brønsted acid catalyzed addition of naphthols to in situ generated naphthol-derived ortho-quinone methides (o-QMs) followed by intramolecular cyclization, which delivers substituted chiral xanthene derivatives, in a one-pot reaction sequence under mild conditions. This process serves to convert naphthol-derived ortho-hydroxyl benzylic alcohols into reactive naphthol-derived o-QMs using a chiral phosphoric acid (CPA) catalyst. Moreover, it is helpful in controlling the enantioselectivity of the carbon-carbon bond-forming event via hydrogen-bonding followed by intramolecular cyclization. Additionally, for the first time, we observe a Brønsted acid catalyzed C(sp2)-C(sp3) bond cleavage of naphthol-derived ortho-hydroxyl benzylic alcohols for the synthesis of achiral xanthene (sigma plane containing) derivatives in good to excellent yields.