Flexible Synthesis of Rigid Cyclophanes - Synthesis and derivatisation of 2,7-diaza-1,2,3,6,7,8-hexahydropyrene into chiral macrocycles

Sammanfattning: Rigid, chiral and amphiphilic cyclophanes of potential use as biomimetic host molecules were prepared by cyclic dimerisation of chiral diamino building blocks with amino-reactive cross-linking reagents. A reliable synthesis of the scaffold 2,7-diaza-1,2,3,6,7,8-hexahydropyrene was developed. Chiral bidentate building blocks were formed by acylation of the aromatic diamine 2,7-diaza-1,2,3,6,7,8-hexahydropyrene with L-amino acids. 1,5-Difluoro-2,4-dinitrobenzene was employed as a cross-linking reagent, stepwise nucleophilic aromatic substitution with bidentate building block gave rise to a range of macrocyclic bis-dinitrodianilines. Macrocyclic bis-ureas were formed by using substituted phenyl chloroformates as cross-linking reagents. The substitution pattern of the phenyl chloroformates was optimised the synthesis of macrocycles. This investigation favoured phenyl chloroformates substituted with electron-withdrawing groups of intermediate power. Applying the results from the investigation of phenyl chloroformate substituents, macrocyclic bis-thioureas were prepared by using substituted phenyl chlorothionoformates as cross-linking reagents. The synthesis of chiral macrocycles was further diversified by incorporating other aromatic diamines as scaffolds, namely p-xylylenediamine and bis-2,3:6,7-iminodimethylene-anthracene. Future development and application of the macrocycles was discussed with emphasis on rational design based on conformational analyses.