Lusby, Paul

Schneider, Uwe

Wang, Jianzhu

2021-12-08T12:04:09Z

2021-12-08T12:04:09Z

2021-11-27

Synthetic supramolecular host molecules are able to mimic enzymes by using their cavities as an artificial active site. Previous research has shown that synthetic hosts are able to accelerate chemical transformations using mechanisms such as constrictive binding or enclosed proximity of reactants. These methods have generally led to modest activity and poor turnover. This thesis will describe a different approach to coordination cage catalysis, one that utilises electrostatic effects to leverage activity. In Chapter 2 it will be shown that such mechanisms can be exploited to promote Michael addition, using a simple cationic Pd2L4 cage to stabilise anionic intermediates. These electrostatic effects dramatically increase the acidity of several pro-nucleophiles, such that catalysis spontaneously occurs through the release of hydronium ions. Reactivity can be further enhanced using 18-crown-6, which stabilises this conjugate acid. The cage also promotes high levels of diastereoselectivity for reactions that generate multiple stereoisomers. Counterintuitively, catalysis only occurs with weakly binding reactants, which also leads to broad substrate scope. In Chapter 3, the broad substrate scope has also been extended to Diels-Alder catalysis using similar Pd2L4 cages. In this study, transition state stabilisation was found to play an essential role in the rate enhancement and the enhanced diastereoselectivity that is observed for several Diels-Alder reactions. Chapter 4 will describe the synthesis, characterisation, host-guest studies, and catalytic studies using several new Pd2L4 cages. These cages were designed to explore factors such as flexibility, cavity dimensions and an alternative palladium coordination site. Catalytic studies of the new Pd2L4 cages was investigated using the Diels-Alder and Michael addition reactions. It was found that the new cages exhibited lower activity than the Pd2L4 catalysts investigated in chapter 2 and 3. The influence that these structural modifications have on the catalysis is discussed.

https://hdl.handle.net/1842/38328

http://dx.doi.org/10.7488/era/1593

en

The University of Edinburgh

Harnessing coordination cage electrostatics to unlock bio-inspired catalysis

Thesis or Dissertation

Doctoral

PhD Doctor of Philosophy