Applications of Hypervalent Iodine Reagents: From Enantioselective Copper-Catalysed Arylation-Semipinacol Cascade to Methionine Functionalisation for Peptide Macrocyclisation

The unifying theme of this thesis is the exploitation of the reactivity of aryliodonium salts as electrophile transfer reagents. In the first part of the thesis, diaryliodonium salts are employed as arylation reagents for the enantioselective copper-catalysed arylative semipinacol rearrangement (SPR) of various tertiary allylic alcohols. This cascade reaction is a rare example of asymmetrically activating SPR using carbon electrophiles. Different substrate classes – including dihydropyran, indene and dihydronaphthalene moieties – are converted to enantioenriched beta-aryl spirocyclic ketones in excellent yields and enantioselectivities, and often as a single diastereomer. These are in turn useful functional handles for transformations into other moieties, including further rearrangements via Baeyer-Villiger oxidation. In the second part of this thesis, a two-step process for the macrocyclisation of native peptides via a non-natural linkage is developed. This study exploits previous work conducted in the group on the use of aryliodonium salts as methionine-selective diazoacetate transfer reagents. The functionalised methionine is in turn used for an intramolecular rhodium-catalysed insertion into tryptophan. Eventual translation onto solid-phase enables facile access into various macrocyclic peptides.

Name dc:type.qualificationname

Doctor of Philosophy (PhD)

Level dc:type.qualificationlevel

Doctoral

Grantor dc:publisher.institution

University of Cambridge

Year dc:date.issued

2018

Author dc:creator

• Lukamto, Daniel Hartoyo

Advisor dc:contributor.advisor

• Gaunt, Matthew J.

• Iodonium salts
• copper catalysis
• macrocyclic peptides
• methionine conjugation
• Semipinacol rearrangement

Licence

• https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/b45b11de-94bf-46db-a365-681915948caf/download
• https://www.rioxx.net/licenses/all-rights-reserved/

Language dc:language

en

DOI dc:identifier.doi

https://doi.org/10.17863/CAM.30922

OAI identifier oai:identifier

oai:www.repository.cam.ac.uk:1810/283560