Organocatalytic enantioselective cycloaddition of naphthoquinone methides

Abstract Quinone methides and their aza -analogues represent the pivotal intermediates in asymmetric synthesis. However, catalytic enantioselective reactions of extended naphthalene-based analogues including naphthoquinone methides (Nap-QMs) and aza -naphthoquinone methides ( aza -Nap-QMs) remain underdeveloped and are limited to nucleophilic additions. Herein, we report an organocatalytic asymmetric [4 + 2] cycloaddition of enamides with Nap-QMs and aza -Nap-QMs, providing an efficient access to a diverse range of tricyclic phenalene derivatives bearing chiral tertiary amines with excellent remote stereocontrol. Furthermore, a CPA/Ag-catalyzed tandem cycloaddition/cyclization enables an asymmetric relay reaction, affording chiral dihydrobenzo[ e ]indoles and 1,2-dihydronaphtho[2,1- b ]furans with high enantioselectivities. This protocol not only represents the first asymmetric cycloaddition and relay cyclization of ( aza )-Nap-QMs, but also constitutes the first asymmetric synthesis of chiral dihydrophenalenes.