Stable nitrogen chiral centres are possible – under the right conditions

A straightforward asymmetric strategy has led to the creation of elusive nitrogen stereocentres. The carefully designed intramolecular reaction used substrate engineering to overcome the configurational instability that usually plagues chiral nitrogen structures, opening up a new landscape for enantioselective synthesis.

Despite their pyramidal structure, nitrogen compounds rarely exhibit chirality. The low barrier for pyramidal inversion quickly racemises any component enantiomers and, as a result, students are typically taught that nitrogen is not a stereogenic centre. Chemists have had some success locking a nitrogen atom into a single configuration in a sterically congested bridgehead or trapping the amine as a quaternary ammonium salt, but methods to access more general chiral unbridged amines have remained elusive.