Trifluoroacetylation and Sulfur Oxidation States Modulate Cis-Trans Isomerization and Atropisomerism in N-Aryl Peptoids.

Trifluoroacetylation and varying sulfur oxidation states can modulate the stereodynamic features in N-aryl peptoids. This study elucidates the restricted rotation about both the chiral Caryl-N axis and the N-C(O) amide bond, highlighting the inherently flexible nature of tertiary amide scaffolds. Tertiary amide bond isomerization, axial chirality, and multiple stereochemical forms were investigated utilizing 19F NMR, dynamic HPLC, crystallographic studies, and computational analysis. Notably, the introduction of a sulfoxide moiety as an auxiliary stereogenic element facilitates the formation of multiple and distinct stereochemical forms, as evident from 19F NMR studies and computational modeling. These structural modifications can provide a robust platform to understand stereodynamic features in N-aryl peptoids.