Show simple item record

Files in this item


Item metadata

dc.contributor.advisorO'Hagan, David
dc.contributor.authorClark, Joshua
dc.description.abstractStrategically fluorinated compounds such as the all-cis-pentafluorocyclohexane ‘Janus’ rings, the subject of this research, can have strong molecular dipole moments because the electronegative fluorines polarise the geminal hydrogens rendering them electropositive. In Chapter 1, a general discussion of the dominant interactions associated with organofluorine compounds is given. This is followed by an examination of the variety of fluorination methods available. The role of fluorine in medicinal chemistry is explored including in positron emission tomography (PET). A summary of previous work from the St Andrews group provides the contextual basis on which the following chapters build. Chapter 2 explores a recently reported Rh-catalysed hydrogenation reaction of fluoroarenes to access all-cis-fluorocyclohexanes in excellent diastereoselectivity. The scope of this reaction is expanded to generate novel cyclohexane products such as alcohol 2.47 and methyl ester 2.60. Derivatisation of these products has furnished a library of all-cis-pentafluorocyclohexane building blocks for further study. These include alkyl bromide 2.82, organoazide 2.83 and aldehyde 2.87. In Chapter 3, the elaboration of these building blocks to higher order molecular structures is explored. Ugi 4-component reactions (Ugi-4CR) with aldehyde 2.87 provide combinatorial access to medicinally relevant bis-amides 3.20-3.27. The Ugi-4CR, optimised by microwave assistance, can be completed within 45 mins. Using an HPLC method the Log P of three of these Ugi products (3.23, 3.25 and 3.27) was measured and in each case the Log P value reduced relative to phenyl ring analogues. This finding suggests a potential application of the ‘Janus’ ring as an arene isostere in medicinal chemistry. Other methods of elaboration explored in Chapter 3 include amide coupling, Wittig and CuAAC ‘click’ reactions. Chapter 4 reports the preparation of ‘Janus’ ring bearing novel amphiphiles, the long chain carboxylic acid 4.1 and alcohol 4.2 as well as analogous hydrocarbon reference compounds 4.4 and 4.5. A Langmuir isotherm study examined the influence of the ring system on phase behaviour at the air-water interface. Evidence is presented of molecular self-assembly for the long chain 4.1 and 4.2, unlike the classical behaviour observed for the hydrocarbon counterparts 4.4 and 4.5. This analysis is supported by a thorough examination of X-ray crystal structures and presents a platform for the further development of the ‘Janus’ ring motif for supramolecular chemistry. Finally, Chapter 5 summarises the findings of the previous chapters and explores possible avenues for future work such as the development of a ‘pull-down’ assay using biotinylated affinity probes 5.1 and 5.2 to better understand interactions between the ‘Janus’ ring and proteins of interest.en_US
dc.description.sponsorship"The research underpinning this thesis has received funding from the EPSRC Centre for Doctoral Training in Critical Resource Catalysis (CRITICAT, Grant Number EP/L016419/1)." -- Fundingen
dc.publisherUniversity of St Andrews
dc.relationSynthesis, properties and applications of all-cis-pentafluorocyclohexane ‘Janus’ ring building blocks (thesis data) Clark, J., University of St Andrews. DOI:
dc.relationClark, J., Taylor, A., Geddis, A., Neyyappadath, R. M., Piscelli, B., Yu, C., Cordes, D. B., Slawin, A. M. Z., Cormanich, R., Guldin, S., & O'Hagan, D. (2021). Supramolecular packing of alkyl substituted Janus face all-cis 2,3,4,5,6-pentafluorocyclohexyl motifs. Chemical Science, Advance Article. Advance online publication.
dc.relationClark, J., Neyyappadath, R. M., Yu, C., Slawin, A. M. Z., Cordes, D. B., & O'Hagan, D. (2021). Janus all-cis 2,3,4,5,6-pentafluorocyclohexyl building blocks applied to medicinal chemistry and bioactives discovery chemistry. Chemistry - A European Journal, 27(64), 16000-16005. Article 202102819. Advance online publication.
dc.subject.lcshFluorine compounds--Synthesisen
dc.titleSynthesis, properties and applications of all-cis-pentafluorocyclohexane 'Janus' ring building blocksen_US
dc.contributor.sponsorEngineering and Physical Sciences Research Council (EPSRC)en_US
dc.type.qualificationnamePhD Doctor of Philosophyen_US
dc.publisher.institutionThe University of St Andrewsen_US

This item appears in the following Collection(s)

Show simple item record