N-Heterocyclic Carbenes in Pd0-Catalyzed C(sp3)–H Activation

Niggli, Nadja Elena. N-Heterocyclic Carbenes in Pd0-Catalyzed C(sp3)–H Activation. 2022, Doctoral Thesis, University of Basel, Faculty of Science.


Official URL: https://edoc.unibas.ch/88562/

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The direct functionalization of C(sp3)–H bonds by transition metals has emerged as an efficient strategy in the streamlined synthesis of valuable molecules. However, translating this reactivity to an asymmetric transformation has thus far been only moderately successful. A limited array of motifs was accessed in high enantioselectivity by Pd0-catalyzed C(sp3)–H arylation during the course of the last 10 years. In this thesis, we aimed to address this shortcoming with the development of new asymmetric methods for the construction of enantioenriched cyclic products. In the first project, different indanone products were synthesized in excellent yields and moderate enantioselectivity by C(sp3)–H arylation. Strikingly, IBiox-type ligands generally exhibited an exceptional reactivity and product selectivity compared to other classes of ligands. In addition, the IBiox ligands performed best in terms of enantioinduction, but still with limited stereoselectivity. Based on these findings, new IBiox-derived NHC ligands were designed with the intention to improve their stereoinducing properties in the envisioned C(sp3)–H arylation transformation. This plan was pursued in a second project wherein a new IBioxtBuMe4 ligand was synthesized and successfully employed in the challenging desymmetrization of enantiotopic protons in the construction of indanes. In addition to this, the synthetic sequences towards two further ligands were initiated and are now close to completion. In parallel, new carboxylate bearing NHC-complexes were designed, synthesized, and characterized. Careful experimentation and analysis of the data revealed the delicate nature of these complexes which accounts for their unsatisfactory performance in the envisioned reactions. Interestingly, during the course of these investigations, a β-lactam product was identified arising from a new 1,4-Pd shift and subsequent C(sp3)–C(sp3) bond formation. This new reactivity was exemplified in the synthesis of biologically interesting β-lactams. In addition, mechanistic studies were performed to disclose the nature of this transformation. IBiox-type ligands showed a superior product selectivity for this novel reactivity and proved to be key to its success.
Advisors:Baudoin, Olivier and Ward, Thomas R. R. and Albrecht, Martin
Faculties and Departments:05 Faculty of Science > Departement Chemie > Chemie > Synthetische Chemie (Baudoin)
UniBasel Contributors:Baudoin, Olivier
Item Type:Thesis
Thesis Subtype:Doctoral Thesis
Thesis no:14751
Thesis status:Complete
Number of Pages:XIV 380
Identification Number:
  • urn: urn:nbn:ch:bel-bau-diss147510
edoc DOI:
Last Modified:22 Jul 2022 04:30
Deposited On:21 Jul 2022 09:43

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