Organocatalytic enantioselective synthesis of Csp2–N atropisomers via formal Csp2–O bond amination

Abstract

Compared with well-developed construction of C_sp2–C_sp2 atropisomers, the synthesis of C_sp2–N atropisomers remains in its infancy, which is recognized as both appealing and challenging. Herein, we achieved the first organocatalyzed asymmetric synthesis of C_sp2–N atropisomers by formal C_sp2–O amination. With the aid of a suitable acid, 3-alkynyl-3-hydroxyisoindolinones reacted smoothly with 1-methylnaphthalen-2-ols to afford a wide range of atropisomers by selective formation of the C_sp2–N axis. Particularly, both the kinetic (Z)-products and the thermodynamic (E)-products could be selectively formed. Furthermore, the rarely used combination of two chiral Brønsted acid catalysts achieved excellent enantiocontrol, which is intriguing and unusual in organocatalysis. Based on control experiments and DFT calculations, a cascade dehydration/addition/rearrangement process was proposed. More importantly, this work provided a new plat-form for direct atroposelective construction of the chiral C_sp2–N axis.