N‐Aryl Imidazole Platforms – Synthesis and Structural Investigation

Abstract

Cyclic oligomers of azole peptides were isolated from a multitude of marine organisms and were used for a variety of applications in supramolecular chemistry. Up to now the use of imidazole‐containing platforms based on Lissoclinum cyclopeptides were limited to N‐alkyl imidazole scaffolds. Here we present the synthesis of chiral N‐aryl imidazole amino acids by starting from the corresponding amidoketones and aniline derivatives. By using the optimized reaction conditions even chiral imidazoles with large substituents at the α‐carbon atom and at ortho position of the aryl ring were obtained without racemization at the stereogenic center. Subsequent one‐pot cyclotrimerization of the N‐aryl imidazole amino acids leads to the desired C3‐symmetric platforms in rather good yields. The investigation of the structures of the platforms with bromine atoms in ortho, meta and para position relative to the imidazole unit were conducted by NMR spectroscopy, X‐ray crystallography, and quantum chemical calculations. The experimental data reveals that the ortho isomer is present in a single conformer in which all bromine atoms are oriented in the same direction. The rotation around the aryl‐imidazole axis in this isomer is completely prevented in the measured temperature range.