The Asymmetric Synthesis of an Acyclic N-Stereogenic Amine

"However, while the selective chemical synthesis of molecules where 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 elusive, due to their rapid pyramidal inversion. We describe here 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 critical stereogenicity creating step challenges previously established stereochemical descriptors of enantiodifferentiation. Computational studies provide additional 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."

Stable, enantiopure acyclic N-stereogenic amines are synthesized catalytically by adding enol silanes to nitronium ions that form ion pairs with a confined chiral anion. The products are anomeric amines whose rapid pyramidal inversion is slowed by two N-oxy substituents that hinder nitrogen inversion, producing configurationally stable nitrogen stereocenters. The stereogenicity-creating step challenges previously established stereochemical descriptors of enantiodifferentiation. Computational studies provide mechanistic insight into the origin of the observed stereocontrol. The method enables exploration of enantiopure anomeric amine chemistry and access to otherwise elusive acyclic N-stereogenic compounds.

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