An Investigation into Organocatalytic and Photoenzymatic Methodologies

Abstract

Design and development of chemical processes in an environmentally friendly manner is a vastly developing area of chemistry. Improving an overall reaction to make it greener can be done in a variety of ways including, reduction of resources used and lowering the overall energetic burden of the reaction. Suppression of resource consumption can be done by minimising synthetic steps, such as by negating pre-activation of starting materials or reducing the overall waste of the reaction itself, for instance by removing purification steps. Another way to reduce the overall resource consumption is to maintain a high atom economy between the starting materials and product, commonly, achieved through intramolecular processes. An alternative strategy to reduce the energy needed to drive a reaction, is the employment of catalysts to lower the activation barrier required for reactivity. This thesis will discuss two green catalytic rearrangement reactions, both of which do not require transition metals, stoichiometric reagents or harsh conditions. Integration of the Smiles rearrangement with modern techniques and knowledge has led to renewed interest in the reaction. The rearrangement is an attractive candidate for exploration due to its ability to interchange easily formed carbon-heteroatom bonds for carbon-carbon bonds without the need for transition metals. As with other rearrangement reactions, the Smiles is highly atom-economical and, due to its intramolecular nature, can be performed under ever increasingly, mild conditions. A new avenue for exploration of the Smiles rearrangement is the integration of both polar and radical manifolds with new catalytic methods. The first part of this thesis details efforts to produce a system which combines organocatalysis and the Truce-Smiles rearrangement in order to synthesise 2-aroylpyrrole/indole derivatives. The second section of this thesis investigates the combination of photocatalysis and biocatalysis as an attractive way to develop novel bond forming reactions in a stereoselective manner. When used in conjunction these methods can drastically reduce waste of organic synthesis, particularly in the pharmaceutical industry. Photoexciting molecules opens up many reaction pathways not available under thermal conditions and can negate the need for pre-functionalisation of stating materials. Herein, is reported the employment of MAO-N as a photoenzyme, under visible light, in a novel 2- electron oxidative cycle. Upon irradiation the flavin adenine dinucleotide (FAD) bound cofactor is able to oxidatively decarboxylate a series of α-hydroxy acids in an enantioselective fashion. The photocatalytic cycle takes advantage of MAO-Ns natural oxidative half cycle by using molecular oxygen to regenerate the photoactive FAD cofactor following its reduction.

Date of Award	1 Aug 2023
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Anthony Green (Supervisor), Sam Hay (Supervisor) & Michael Greaney (Supervisor)