Photochemical Methods for the Construction of C-C and C-X Bonds

This thesis encompasses photochemical methods for the construction of C-C and C-X bonds. Following an introduction on the challenges with photochemistry, early work in photoredox catalysis and the application of continuous processing for photochemical reactions are three research chapters. Chapter 2 discloses the development of a photoredox-catalysed dehydrogenative cross-coupling reaction between aldehydes and alkylarenes in continuous flow. In the process, the reaction was adapted to a flow set-up, further optimised and expanded to prepare a range of α-aryl ketones including drug derivatives. Furthermore, the application of flow reactors towards multi-gram scale-up was investigated and in doing so, a previously unreported method to recycle the iridium photocatalyst was established. Chapter 3 contains a new method to prepare β-spiropyrrolidines using visible-light-driven photocatalysis. By adapting and re-optimising a photocatalytic pyrrolidine ring forming reaction developed within the Ley group, a range of β-spiropyrrolidines were prepared. In addition, the reaction was shown to be well-suited to a flow set-up and was successfully executed on a decagram scale. The products were then derivatised at the halomethyl substituent formed on the pyrrolidine ring. Finally, a brief investigation into the preparation of piperidine rings with this strategy was made. Chapter 4 investigates new methods to access sulfonyl compounds via sulfinate salts. This began with the development of a photoredox-catalysed sulfinate preparation using a previously unexplored piperidine-SO2 surrogate. With this reaction, a variety of alkyl and aryl sulfones were prepared by quenching of the generated sulfinates, including drug derivatives. Following this, a pilot study into a new nitro-sulfinate reductive coupling strategy was conducted to access sulfonamides directly from sulfinates. In doing so, two sets of general conditions were established that enabled access to a selection of N-heteroaryl sulfonamides, that were previously inaccessible with alternative reductive coupling methods.

Name dc:type.qualificationname

Doctor of Philosophy (PhD)

Level dc:type.qualificationlevel

Doctoral

Grantor dc:publisher.institution

University of Cambridge

Year dc:date.issued

2023

Author dc:creator

• Griffiths, Oliver

Advisors dc:contributor.advisor

• Ley, Steven V
• Spring, David

• Cross-coupling
• Flow chemistry
• Photocatalysis
• Photochemistry
• Photoredox catalysis
• Spirocycles
• Sulfonamides
• Sulfones

Licence

• https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/62fd0060-bd61-40fa-aa4e-83981127ba0a/download
• https://www.rioxx.net/licenses/all-rights-reserved/

Language dc:language

eng

Author Identifier

0000-0003-3954-9343

OAI identifier oai:identifier

oai:www.repository.cam.ac.uk:1810/360862