Anion-Templated Macrocycle Synthesis

Significance

Imine metathesis between diamine 1 and dialdehyde 2 at room temperature in the presence of dianion 3 provided pseudopeptidic macrocycles 4 with over 90% conversion. Such dimeric structure was characterized by ¹H NMR, ESI-TOF mass spectra as well as circular dichroism (CD) spectroscopy. Modeling study revealed that binding with 3 increases the rigidity of the intermediate open-chain precursor and sets up the correct geometry for the nucleophilic attack of the amine on the aldehyde carbonyl group, thus explaining the observed acceleration of the templated cyclization process. Scrambling experiments showed that entitites bearing chains of the same chirality (homochiral macrocycles) were exclusively formed, which indicates that anion templation induces a highly stereoselective molecular self-recognition.