New Catalytic Enantioselective Approach to 1,4-Diamines

The Malcolmson Lab has developed an enantio- and diastereoselective copper-catalyzed method for assembling chiral 1,4-diamines, nitrogen-containing molecules with broad applications in pharmaceuticals and ligand design for which there are few direct synthetic approaches. A research team led by former postdoc, Pengfei Zhou (now an assistant professor at Chongqing Medical University) and graduate student, Jiaqi Zhu, discovered the novel carbon–carbon bond-forming strategy that proceeds through reductive coupling of 2-azatrienes and N-phosphinoyl imines.

Compared to related previously reported methods from the Malcolmson group, where the same two reaction components led to 1,2-diamines, Zhou, Zhu and co-workers found that a copper catalyst bearing Josiphos SL-J001-1 as the chiral supporting ligand allowed for a different reaction site for uniting the azatriene and imine. A combination of experiments and computational modeling provided insight into the reaction mechanism and the key non-covalent interactions between the ligand and reactants that is responsible for the observed selectivities. This work provides a versatile and precise new tool for constructing complex nitrogen-containing molecules in a streamlined manner. Learn more about these recent findings in Journal of the American Chemical Society, available here.