Self-assembled orthoester and trialkoxysilane cryptands : synthesis, scope and kinetic studies

Abstract

The serendipitous discovery of crown ethers by Pedersen and cryptands by Lehn has opened up new avenues in the vibrant field of supramolecular chemistry. Progress in this area was often associated with the discovery of new macro(bi)cyclic compounds, generally synthesised by stepwise procedures. More recently, the development of constitutionally dynamic cage compounds has gained considerable attention because dynamic covalent chemistry (DCvC) is ideal to tackle future challenges of host-guest systems, such as dynamic adaptability and biodegradability. In 2015, the group of Max von Delius has reported on the orthoester exchange reaction as a new tool for DCvC and its application for the synthesis of a new class of macrobicyclic hosts. Unlike conventional cryptands, orthoester cages are adaptive under acidic conditions and can hydrolyse, which makes them interesting candidates for drug delivery. Therefore, the central goal of this thesis was the detailed investigation of the orthoester exchange reaction, the controlled degradation of orthoesters and the scope of the corresponding cryptands (Figure 1). The first chapter of this thesis introduces the fields of supramolecular host-guest chemistry and dynamic covalent cage compounds with a focus on orthoester chemistry. Additionally, the in,out-stereoisomerism of flexible macrobicycles and the chemistry of (tri-)alkoxysilanes are presented. Chapter 2 is a personal account of the aims and achievements of each of the four research projects that have been part of this thesis. The four research articles that we have published recently or that are under peer-review are shown in chapter 3. Project I (Figure 1 and chapter 3.1) describes the detailed investigations on the scope of orthoester cryptands, their post-functionalisation and kinetic locking as well as studies on the kinetics of both orthoester exchange and degradation. Section 3.2 deals with the serendipitous discovery of an orthoformate in,in-cryptand which is formed by self-templation via intramolecular hydrogen bonding. Additionally, we report on its bridgehead inversion by DCvC (Project II, Figure 1). Project III portrays the stereoisomerism of larger orthoformate cryptands that equilibrate between out,out-, in,in- and in,out-configurations (Figure 1 and chapter 3.3). Section 3.4 presents the transfer of the orthoester exchange to another reaction, namely the trialkoxysilane exchange reaction and the self-assembly of cryptands with Si-bridgeheads (Project IV, Figure 1). Chapter 4 summarises this thesis, discusses the significance of the presented work and proposes future investigations to be carried out in the Delius group.