Chirality is central to life, and controlling the formation of one of a pair of mirror-image molecules (enantiomers) is a central tenet of synthetic chemistry. Although controlling stereogenic carbon1–3, silicon4,5, phosphorus6,7 and sulfur8,9 centres is commonplace, nitrogen centres in amines are not typically stable. Limited achievements in the enantioselective construction of nitrogen chirality have primarily been established in quaternary ammonium salts10–12 and bridged bicyclic amines13–17, which have a restricted pyramidal configuration. The asymmetric synthesis of non-bridged pyramidal nitrogen-chirogenic compounds suffers from a super-stoichiometric chiral source and exhibits poor stereoselectivity18–24. Here we present a catalytic enantioselective strategy for construction of acyclic nitrogen stereocentres via a chiral Brønsted acid-catalysed chlorination reaction. We designed a stereospecific intramolecular reaction to overcome the structural and configurational instabilities of nitrogen-chlorinated hydroxylamines. The resulting 2-alkoxy-1,2-oxazolidines showed good enantiopurities, and density functional theory calculations confirmed successful enantiocontrol of nitrogen chirality during the chlorination process. Furthermore, this strategy has been applied successfully to synthesize the enantioselective N-chloroaziridines with a configurationally stable nitrogen stereogenic centre. Control experiments provide evidence for an SN2 pathway for the intramolecular nucleophilic substitution event.
