Exploring Nickel Catalysis in Carbonyl and Alcohol Addition Reactions

The nucleophilic addition of organomagnesium/lithium reagents to aldehydes and ketones has long enabled the synthesis of valuable alcohol derivatives; however, these types of transformations are often plagued by poor functional group tolerance and require harsh reaction conditions. The direct coupling of carbonyls and alcohols with aryl halides is an appealing alternative to access secondary alcohol products. However, this necessitates a formal C-H bond activation which is not well established in the literature. Chapter 1 provides a detailed literature background of the transition metal-catalyzed functionalization of carbonyls and alcohols. The work discussed in Chapter 2 of this thesis demonstrates the addition of aryl halides to aryl and aliphatic aldehydes and alcohols providing secondary alcohol products in moderate to high yields. Key to the success of this transformation was the implementation of underexplored and readily synthesized 1,5-diaza-3,7-diphosphacyclooctane (P2N2) ligands. Chapter 3 extends the methodology established in chapter 2 and aims to get a preliminary understanding of the application and mechanism of the reaction described above. For this purpose, pharmaceutically relevant isatin substrates are derivatized, providing access to substitution at the 3-position. Coupling isatins with aryl halides yields 3-aryl-3-hydroxy-2-oxindole products which are scaffolds for many natural product derivatives. Through high-throughput experimentation (HTE), we were able to discover that 1,2-addition at the carbonyl position of isatins is highly compatible with our established system and led us to develop a modest scope as well as gain useful mechanistic insights for this coupling.

Grantor dc:publisher

Université d'Ottawa / University of Ottawa

Year dc:date

2022

Author dc:creator

• Nasim, Amrah

Contributors dc:contributor

• Newman, Stephen

• nickel catalysis
• reductive arylation
• redox-neutral arylation
• secondary alcohol synthesis
• primary alcohol arylation
• cross-coupling
• 1,2-arylation of aldehydes

Statement dc:rights

• Attribution-NonCommercial-NoDerivatives 4.0 International

Licence

• http://creativecommons.org/licenses/by-nc-nd/4.0/

Language dc:language

en

Identifier

http://dx.doi.org/10.20381/ruor-27890

OAI identifier oai:identifier

oai:ruor.uottawa.ca:10393/43676