Rational design and atroposelective synthesis of N-N axially chiral compounds

The first catalytic asymmetric synthesis of N-N axially chiral compounds has been accomplished via a quinidine catalyzed N-allylic alkylation reaction. These N-N axially chiral frameworks are a new addition to the families of axially chiral molecules and to the atropisomerism involving heteroatom(s), e.g., N, O, and S. The reaction takes place smoothly under mild conditions and displays excellent functional group tolerance, allowing facile access to a variety of N-N axially chiral 1-aminopyrroles and 3-aminoquinazolinones in high yields and excellent enantioselectivities. DFT calculations have been applied to understand the origin of enantioselectivity and provide guidance for the design of additional molecules of this type. The investigation of N-N axis atropisomerism holds promise for new discoveries in medicinal chemistry and asymmetric catalysis.