Studies in palladium and rhodium catalysis: synthetic strategies for C–C bond formation

This thesis concerns studies in palladium and rhodium catalysis for carbon-carbon bond formation. Chapter 1 involves the synergistic use of tetrabutylammonium acetate (NBu4OAc) with palladium catalysis to expand on the synthesis of dibenzofurans via C-H activation. Dibenzofuran and its derivatives are ubiquitous and important medicinal and natural products. Many contain electron-rich aryl rings. Previously, we found that the wellestablished conditions, which promote C−H functionalisation through Concerted MetalationDeprotonation (CMD), proved unsatisfactory for electron-rich diarylether precursors. Herein, we report a Pd-catalysed C−H functionalisation protocol that works with electron-rich arenes. We suspect that tetrabutylammonium acetate can act as base, ligand and solvent, rendering this protocol a simple and efficient route to electron-rich dibenzofurans. A variety of functionalised dibenzofurans are successfully accessed through this protocol. The methodology can be applied to benzochromenes, with varying degrees of success. However, this protocol can be expanded to enable a robust, one-pot Buchwald-Hartwig, C–H activation sequence to access biologically relevant indoloquinoline scaffolds from simple building blocks. In Chapter 2, rhodium-catalysed asymmetric conjugate additions are performed with indolyl boronic acids. The indole ring system represents one of the most abundant and important heterocycles in natural products, Active Pharmaceutical Ingredients (APIs), drugs and other materials. The prominence of indole compounds makes efficient protocols to derivatise the heterocycle highly desirable. A particular importance is placed on asymmetric protocols and utilising unprotected (NH) variants. Herein, we report a Hayashi-Miyaura-type Rh-catalysed asymmetric conjugate addition using free NH indole boronic acids and enones. Each position on the carbocyclic backbone of indole can be accessed, with a variety of enones. Yield of up to 94%, and e.r. values up to 99:1 can be achieved using mild reaction conditions. Furthermore, a 1,2-addition to benzil can be performed in excellent yield and e.r. Finally, a one-pot conjugate addition and intramolecular cyclisation of 7-indolyl boronic acid allows for the synthesis of a novel tetracyclic indole, similar to that found in natural products.

Grantor dc:publisher

University College Cork

Year dc:date.issued

2024

Author dc:creator

• Power, Mark

Advisor dc:contributor.advisor

• Mcglacken, Gerard P.

• Palladium rhodium catalysis

Statement dc:rights

• © 2024, Mark Power.

Licence dc:rights.uri

• https://creativecommons.org/publicdomain/zero/1.0/

Language dc:language.iso

en

Handle dc:identifier.uri

https://hdl.handle.net/10468/17107

OAI identifier oai:identifier

oai:cora.ucc.ie:10468/17107