Strained and Twisted Macrocycles via Folding-Assisted Cyclization of Aromatic Ether ε-Amino Acid Oligomers.

Abstract

Twisted and strained macrocycles were synthesized efficiently through condensation of a series of open-chain helical oligo(aromatic ether ε-amino acid) at the sacrifice of the ideal hydrogen bonding pattern present in the linear precursors. Folding-assisted preorganization and the free rotation of terminal aryl groups around the C-O (aromatic ether) axis were identified as key factors enabling such a high cyclization efficiency. X-ray crystallographic analysis revealed the presence of mirror-image conformational enantiomers, the interconversion mechanism of which was further elucidated through DFT calculations.