Abstract

Naphthyridine-based macrocycles with urea and formamidine linkages and pyridazine-based macrocyclic ureas with alternating 3,6-pyridazine/2,6-toluene subunits were synthesized in one-step reactions with acceptable to good yields. The non-covalent intramolecular interactions inherent in the designed subunits, particularly, intramolecular hydrogen bonding, play the key role in guiding the cyclization process. Various spectroscopic techniques (NMR, MS, IR, X-ray crystallography, STM) were used to characterize these macrocycles. This self-templated synthesis of macrocycles points to the possibility of preparing folding oligomeric strands with these heterocyclic systems. A crescent trimer and a helical pentamer were obtained with a urea linked 3,6-pyridazine/2,6-toluene system. The trimer exists as a mixture of two helical segments of opposite chirality, and toluene methyl groups and urea carbonyl groups adopt an anti conformation in the crystal structure. The pentamer forms one helical turn with overlapping termini in solution: the s-s stacking of the terminal toluene rings was confirmed by 1 H NMR studies. To our knowledge, this is the first reported synthetic helical architecture that utilizes both hydrogen bonding and steric interactions to drive and stabilize the folded conformation. Attempts were also made to prepare longer strands with a convergent protection/deprotection methodology.