Public defence in Chemistry: Prakriti Dhillon
Thesis title:
Novel strategies for C-C/X bond formation and application in late-stage functionalization
Third-cycle subject area:
Chemistry
Faculty:
Faculty of Health and Life Sciences
Date:
Friday 9 May 2025 at 13:00
Place for thesis:
Room Lapis, building Vita, Kalmar and via Zoom
External reviewer:
Professor Yannick Landais, University of Bordeaux, France
Examining committee:
Professor Susanne Striegler, University of Arkansas, USA
Professor Panagiotis Manesiotis, Queen’s University Belfast, Great Britain
Docent Sinisa Bjelic, Department of Chemistry and Biomedical Sciences, Linnaeus University
Chairperson:
Docent Björn C G Karlsson, Department of Chemistry and Biomedical Sciences, Linnaeus University
Supervisor:
Professor Ian Nicholls, Department of Chemistry and Biomedical Sciences, Linnaeus University
Assistant supervisor:
PhD Suppan Kathiravan, PhD Jesper Wiklander, PhD Subramanian Suriyanarayanan, Docent Susanne Wikman, Department of Chemistry and Biomedical Sciences, Linnaeus University and PhD Michael Whitcombe, University of Leicester, Great Britain
Examiner:
Professor Kristina Nilsson-Ekdahl, Department of Chemistry and Biomedical Sciences, Linnaeus University
Spikning:
Thursday 17 April 2025 at 10:00 at University Library, Kalmar
In order to receive the Zoom link for the thesis defense, please contact Faculty Administrator Linnéa Larsson: linnea.larsson@lnu.se
Abstract
The development of efficient and selective strategies for C-C/C-X bond formation is of central importance to synthetic organic chemistry, enabling the construction of complex molecules for a broad range of applications in the pharmaceuticals, materials, and agrochemicals sectors. This thesis explores novel methodologies for forging these ubiquitous bonds through both transition-metal catalysis and metal- catalyst-free approaches emphasizing sustainable and atom-economical protocols. New transformations, including cross-coupling reactions, C-H activated catalytic isotope labeling, and hypervalent iodine chemistry, were explored and investigated with respect to reactivity, selectivity, and functional group tolerance. Lastly, the applicability of the developed protocols was tested for the late-stage functionalization (LSF) of commercially available drugs.
In paper I, a diyne-switchable cobalt-catalyzed C-H-activated annulation of benzamides, was studied. The reaction furnished regioselective isoquinolones, where the 3- or 4-substitution was steered by the nature of the diynes. An iridium-catalyzed, pivaloyl group-directed hydrogen isotope exchange (HIE) on indoles and carbazoles was explored in paper II. The key result of the study was a highly regioselective deuteration on carbazoles in contrast to the indoles and the potential for a transient directing-group-based strategy for late- stage functionalization. Paper III, explores a metal-free reaction, where the hypervalent iodine-based reagent phenyliodine(III) diacetate (PIDA) was used as a coupling mediator for the synthesis of unsymmetrical ureas. The study underscores the utility of the reaction system for the late-stage derivatization of different drug molecules integrated with the amine-functionality.
The findings of this thesis expand the synthetic toolbox by offering new strategies for creating C-C/C-X bonds which could potentially enable the precise assembly of intricate molecular frameworks.
Keywords: Catalysis, cobalt, iridium, C-H activation, annulation, late-stage functionalization, isotope labeling, hydrogen isotope exchange, regioselective, hypervalent iodine chemistry, phenyliodine(III) diacetate.