Chemo-, regio- and enantioselective dearomative (3+2) reaction of non-functionalized 1-naphthols

Abstract

The catalytic asymmetric dearomatization reaction of non-functionalized arenes poses a long-standing synthetic challenge to organic chemists because of the relative ease of rearomatization via the departure of a proton. In this work, the direct dearomatization of non-functionalized 1-naphthols was achieved through a phosphoric acid-catalyzed asymmetric (3+2) annulation reaction with azoalkenes. The reported convergent method allows the use of readily available simple 1-naphthols without pre-functionalization under mild conditions, furnishing a variety of tricyclic hexahydrobenz[e]indole derivatives in good yields and excellent enantioselectivities (75%–96% yields and 92%–99% ee). Density functional theory (DFT) calculations were performed to gain insights into the origins of the observed chemo-, regio-, and enantioselectivities. It is noteworthy that using azoalkenes as 1,3-dipole surrogates, in combination with powerful chiral phosphoric acid (CPA) catalysis, was key to the success of current reaction.