Folding‐Induced Folding: The Assembly of Aromatic Amide and 1,2,3‐Triazole Hybrid Helices

Folding-induced folding for the construction of ar- tificial hybrid helices from two different kinds of aromatic se- quences is described. Linear compounds 1a , 1b , and 2, con- taining one aromatic amide trimer or pentamer and one or two aromatic 1,2,3-triazole tetramers, have been designed and synthesized. The trimeric and pentameric amide seg- ments are driven by intramolecluar NH···F hydrogen bond- ing to adopt a folded or helical conformation, whereas the triazole segment is intrinsically disordered. In organic sol- vents of low polarity, the amide foldamer segment induces the attached triazole segment(s) to fold through intramolec- ular stacking, leading to the formation of hybrid helices. The helical conformation of these hybrid sequences has been confirmed by 1 H and 19 F NMR spectroscopy, UV/Vis spectros- copy, circular dichroism (CD) experiments, and theoretical calculations. It was found that the amide pentamer exhibits a stronger ability to induce the folding of the attached tria- zole segment(s) compared with that of the shorter trimer. Enantiomers (R)-3 and (S)-3, which contain an R -o r S-(1-naphthyl)ethylamino group at the end of a tetraamide segment, have also been synthesized. CD experiments showed that introduction of a chiral group caused the whole framework to produce a strong helicity bias. Density- functional-theory calculations on (S)-3 suggested that this compound exists as a right-handed (P) helix.