Enantioselective Dearomative [4+2] Cycloaddition Reaction of 1-Naphthols with In-Situ Generated ortho-Quinone Methides.

Abstract

We disclose a catalytic, enantioselective dearomative reaction of non-functionalized 1-naphthols, which poses a synthetic challenge to organic chemists because of the relative ease of rearomatization via the elimination of a proton. In this work, the direct dearomatization of non-functionalized 1-naphthols was achieved through a chiral phosphoric acid (CPA) catalyzed enantioselective dearomative [4+2] cycloaddition reaction with in-situ generated ortho-quinone methides (o-QMs). The reported convergent method allows the use of readily available simple 1-naphthols without pre-functionalization, furnishing a variety of naphthopyran derivatives in good yields (up to 96 %) and moderate to excellent enantioselectivities (up to >99 % ee) under mild reaction conditions. The observed regio-, diastereo-, and enantioselectivities are the keys to the success of the current strategy utilizing o-QM as a diene surrogates, in combination with CPA catalysis.