Copper-Catalyzed Enantioselective Skeletal Editing through a Formal Nitrogen Insertion into Indoles to Synthesize Atropisomeric Aminoaryl Quinoxalines.

Skeletal editing represents an attractive strategy for adding complexity to a given molecular scaffold in chemical synthesis. Isodesmic reactions provide a complementary skeletal editing approach for the redistribution of chemical bonds in chemical synthesis. However, catalytic enantioselective isodesmic reaction is extremely scarce and enantioselective isodesmic reaction to synthesize atropisomeric compounds is unknown. Herein, we report a facile method to synthesize axially chiral aminoaryl quinoxalines through Cu(I)-catalyzed dearomatization and sequential chiral phosphoric acid (CPA) catalyzed enantioselective isodesmic C-N bond formation and cleavage from indoles and 1,2-diaminoarenes under mild reaction conditions. In this process, the five-membered ring of the indole scaffold was broken and a novel quinoxaline skeleton was constructed. This method allows the practical and atom-economical synthesis of valuable axially chiral aminoaryl quinoxalines in high yields (up to 95 %) and generally excellent enantioselectivities (up to 99 % ee). Notably, this novel type of quinoxaline atropisomers has promising applications in developing axially chiral ligand in asymmetric catalysis. This strategy represents the first example of CPA-catalyzed enantioselective isodesmic reaction to form axially chiral compounds.