Organocatalytic enantioselective synthesis of C-N atropisomers formal C-O bond amination.

Compared with well-developed construction of C-C atropisomers, the synthesis of C-N atropisomers remains in its infancy, which is recognized as both appealing and challenging. Herein, we achieved the first organocatalyzed asymmetric synthesis of C-N atropisomers by formal C-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-N axis. Particularly, both the kinetic ()-products and the thermodynamic ()-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-N axis.