Synthesis of Resorcin[4]arenes Derivatives through Selective Functionalization and their Applications

The field of supramolecular chemistry has experienced rapid growth since its foundation more than 50 years ago. Supramolecular systems have contributed a great share of groundbreaking discoveries and first applications to real-life problems have been identified. A particularly important class of molecules that play a key role in supramolecular chemistry are calixarenes. This family of readily accessible, phenolic macrocycles, composed of the key members calix[4]arene, resorcin[4]arene, and pyrogallol[4]arene, has emerged as a versatile platform for supramolecular host systems. Functionalization of these macrocycles has enabled further applications such as chiral sensing, catalysis, and metal-ligand interactions.
In this thesis, multiple novel selective derivatization strategies for resorcin[4]arenes were developed to access highly functionalized macrocycles with targeted applications. Successive tetrafunctionalizations on macrocycle 115a enabled the synthesis of the missing, inherently chiral member of the calix[4]arene family 152, denoted “catechol[4]arene”. This novel phenolic macrocycle outperformed its sister molecules 8 and 9 as a host for ammonium salts. Furthermore, enantiopure forms of 152 showed modest chiral recognition for optically active ammonium species. The synthesis of thiol analogs of 8 and 9 provided answers to important questions addressing the tolerance of thiols in hydrogen bonded self-assemblies, their potential application in dynamic covalent chemistry, and the influence of the thiol on the catalytic activity of supramolecular capsule catalysts. In addition, two novel resorcin[4]arene-based tetraphosphate ligands (156, 157) for nanocrystal surfaces were designed and synthesized. In both cases, these multidentate ligands were able to bind with exceptionally strong affinities in at least tridentate fashion.
Overall, this work contributed significantly to the expansion of the toolbox for selective derivatizations on the resorcin[4]arene scaffold. At the same time, the corresponding methods were employed to generate many highly specialized functional molecules suited for specific tasks such as enantiodiscrimination, disulfide bridging, and nanocrystal stabilization. As a result, the insights gained in these projects will prove useful for future designs and syntheses of novel, functional macrocycles and will enable their targeted application.