Abstract
Chiral cage architectures have been of long-standing interest for synthetic chemists as mimics of Nature’s inherent asymmetry. The high yield and feasible reaction conditions of dynamic covalent and coordination bond-derived chiral cage architectures have placed these methods as the most common approach. However, the lack of stability under harsh conditions is often overlooked, limiting application. Covalent (non-dynamic linkages) are preferred but suffer from low efficiency cage synthesis due to lack of self-correction. To date, there are only a handful of examples of stable covalent bond-derived chiral cages, but with low yields. Furthermore, self-sorting of chiral precursors has played no role for existing chiral covalent cages. In this thesis, the synthesis and characterisation of novel chiral covalent cages derived from chiral resorcin[4]arenes, with or without templation, are described.
Chapter 1 introduces existing cage types, from dynamic and non-dynamic covalent bonds to coordination bonds, particularly cages from resorcin[4]arene-derived cavitands as precursors.
Chapter 2 presents a cation template-directed approach to the formation of encapsulated helical chiral ether cages from a racemic derivative of resorcin[4]arene. The generality of the reaction was established using different linker lengths to connect the two capping ends. Narcissistic self-sorting on pre-organization of precursor around the template is a driving force in forming exclusive homochiral (PP and MM) specific ether cages. For cages from longer linkers, heating drives out the encapsulated cation to give the cage without the template. All cages are extensively characterized with 1D, 2D NMR, and X-ray crystallography.
Chapter 3 extends the synthesis to encapsulated enantiopure ether cages, also employing an alkylammonium template, and subsequent decomplexation to afford enantiopure ether cages without a guest. A facile, high-yielding chiral resolution of ethyl footed-resorcin[4]arene using (S)-(+)-10-camphorsulfonyl chiral auxiliary is described. All diastereomers and chiral cages are extensively characterized with 1D, 2D NMR experiments, and X-ray crystallography.
Chapter 4 explores the synthesis of ether cages from an extended cyclophane core. Two individual approaches to synthesizing chiral ether cages with an extended cavity were investigated: heterogeneous and homogeneous. The synthesis of heterogeneous ether cage was unsuccessful. However, the success of homogenous ether cage synthesis was revealed by only on ESI-MS and X-ray crystallography, a meso arrangement confirmed in the solid state.
Chapter 5 investigates a click chemistry approach to synthesize chiral covalent cages. Like the previous chapter, two methods, heterogeneous and homogeneous, are investigated. Four novel precursors (tetraazide and tetraalkyne derivatives) were prepared, and their click adduct were prepared by reacting with complementary counterparts. Although the cages were not isolated in pure form, cage formations is supported by ESI-MS.
A novel class of chiral tetradentate mono-ligand coordination cage synthesis is reported in Chapter 6. Two regioisomeric chiral ligands were obtained by increasing the depth of the cavity of a chiral resorcin[4]arene derivative, and 1,2,3-triazole donors were constructed employing a click reaction. The obtained cage was ultimately assigned using 1D and 2D NMR experiments.