The asymmetric synthesis of an acyclic N-stereogenic amine

非环状N-立体异构胺的不对称合成

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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.

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