Chemical Methods for Cobalt-Catalysed C(sp3)–H Activation and Iodonium Salt-Mediated Peptide Functionalisation

The development of a cobalt-catalysed C–H carbonylative cyclisation of aliphatic quinolinamides to furnish the corresponding succinimides in good to excellent yields is reported. The reaction has been applied to a range of substituted analogues, including to the functionalisation of activated methylene bonds. Initial computational interrogation of the reaction suggests a carboxylate-assisted concerted metalation-deprotonation pathway for C–H bond cleavage. Subsequently, the development of a rapid, room-temperature iodonium-salt mediated arylation procedure of hydroxylamines to afford N-oxide products is described. This approach has been applied to the metal-free, room temperature synthesis of substituted anilines. A diverse range of aromatic groups, including aryl halides and heteroaromatic functionality, were successfully transferred by this strategy. Excellent selectivity for the hydroxylamine group was observed in the presence of unprotected nucleophiles. This fast and selective arylation reaction was ulitmately applied to the functionalisation of complex peptide substrates in dilute aqueous solutions, exhibiting high chemoselectivity with respect to peptide sidechains. Excellent conversions were achieved in five minutes at room temperature, demonstrating the potential of this process for bioorthogonal labelling.

Name dc:type.qualificationname

Doctor of Philosophy (PhD)

Level dc:type.qualificationlevel

Doctoral

Grantor dc:publisher.institution

University of Cambridge

Year dc:date.issued

2020

Author dc:creator

• Williamson, Patrick

Advisor dc:contributor.advisor

• Gaunt, Matthew

• Cobalt
• C-H activation
• Bioorthogonal
• Iodonium salt

Licence

• https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/bbc7e242-8278-4bbc-b6dd-3385fe5b7db9/download
• https://www.rioxx.net/licenses/all-rights-reserved/

Language dc:language

en

DOI dc:identifier.doi

https://doi.org/10.17863/CAM.52408

OAI identifier oai:identifier

oai:www.repository.cam.ac.uk:1810/305323