Enantioselective synthesis

Catalysis

Alkylation

Atropisomer

Organic chemistry

Chemistry

Axial chirality

Friedel–Crafts reaction

Combinatorial chemistry

Desymmetrization

Kinetic resolution

Nitrogen

Journal of the American Chemical Society

Nitrogen-nitrogen bonds containing motifs are ubiquitous in natural products and bioactive compounds. However, the atropisomerism arising from a restricted rotation around an N-N bond is largely overlooked. Here, we describe a method to access the first enantioselective synthesis of N-N biaryl atropisomers via a Cu-bisoxazoline-catalyzed Friedel-Crafts alkylation reaction. A wide range of axially chiral N-N bisazaheterocycle compounds were efficiently prepared in high yields with excellent enantioselectivities via desymmetrization and kinetic resolution. Heating experiments showed that the axially chiral bisazaheterocycle products have high rotational barriers.

Enantioselective Synthesis of Nitrogen–Nitrogen Biaryl Atropisomers via Copper-Catalyzed Friedel–Crafts Alkylation Reaction