The asymmetric synthesis of an acyclic N-stereogenic amine

Abstract

Abstract Most molecules in chemistry and biology are chiral, leading to mirror-image variants, so-called enantiomers. However, although the selective chemical synthesis of molecules in which the stereogenicity arises from a carbon atom is well-established, enantioselective approaches to nitrogen-stereogenic molecules are much less common 1–3 , and in case of acyclic, N -stereogenic amines, even unknown, because of their rapid pyramidal inversion. Here we describe the catalytic asymmetric synthesis of stable, acyclic N -stereogenic amines by the addition of enol silanes to nitronium ions that ion pair to a confined chiral anion. In the produced so-called anomeric amines, the commonly observed isomerization is slowed down by two N -oxy-substituents, which hamper nitrogen inversion. The important stereogenicity-creating step challenges previously established stereochemical descriptors of enantiodifferentiation. Computational studies provide further insight into the origin of the observed stereocontrol. Our work opens up a new avenue to investigate the fascinating and previously underexplored chemistry of enantiopure anomeric amines.