| Author: | Peng, Zifang |
| Title: | Exploration of alkyl-based phosphine ligands for palladium-catalyzed chemoselective cross-coupling of polyhalogenated aryl triflates for construction of C(sp2)‒C(sp2) bond |
| Advisors: | So, Chau Ming (ABCT) Mok, Kam Wah (ABCT) |
| Degree: | M.Phil. |
| Year: | 2023 |
| Subject: | Organic compounds -- Synthesis Palladium catalysts Metal catalysts Hong Kong Polytechnic University -- Dissertations |
| Department: | Department of Applied Biology and Chemical Technology |
| Pages: | xiii, 512 pages : color illustrations |
| Language: | English |
| Abstract: | Palladium-catalyzed cross-coupling reaction has emerged as a powerful and straightforward synthetic tool in organic synthesis. Researchers have recently focused on exploring more effective approaches to access high-value and structural-diverse products. The chemoselective cross-coupling strategy exhibits great potential in iterative or sequential synthesis, as it might shorten the whole synthetic routes to construct the complex molecules. However, the presence of two or more (pseudo)halides on the substrates introduce selectivity as a critical challenge. In general, the selectivity outcomes are influenced by several components, such as the palladium catalyst system, the electrophiles, the nucleophiles, solvents, and additives. Among these factors, the catalyst system is considered as the primary factor since it is controllable and provides predictable results. This thesis focuses on (1) the exploration of new catalyst systems based on known ligands and investigation of the origin of chemoselectivity; and (2) the ligand-controlled chemoselective cross-coupling of polyhalogenated aryl triflates with different coupling partners to achieve new transformations. In chapter 1, a brief introduction is organized in the following manner. The first part provides a brief background of transition metal-catalyzed reactions and the significant advances in cross-coupling chemistry over the past 50 years. These mainly include the development of palladium-catalyzed cross-coupling reactions, the expansion of organometallic coupling partners, and the extension of reaction types via ligand variation. The second to the fourth part discuss the development of the palladium-catalyzed Suzuki-Miyaura cross-coupling reaction, carbonylation reaction via CO-free strategy, and direct arylation of polyfluorobenzene. The fifth part is the development and significance of chemoselective cross-coupling reactions concerning the selective functionalization between the C(sp2)‒Cl and C(sp2)‒OTf bond. Our studies on the exploration of alkyl-based phosphine ligand for palladium-catalyzed chemoselective coupling of halogenated aryl triflates are described in the following Chapters of this thesis. In Chapter 2, di-adamantyl skeleton ligands Ad2PR (R = Me, Et, nPr, and nBu) were used to investigate the reactivity and selectivity of chloroaryl triflates in chemodivergent Suzuki-Miyaura cross-coupling reaction. Three oxidative addition complexes were synthesized and characterized. Further mechanistic studies were undertaken via NMR and HRMS analysis to investigate the possible reaction pathways between C(sp2)‒Cl and C(sp2)‒OTf bond. The reaction conditions exhibited good functional group tolerance toward a wide range of chloro(hetero)aryl triflates and aryl(hetero)boronic acids. In Chapter 3, a successful transformation of palladium-catalyzed chemoselective carbonylation of bromoaryl triflates or chloroaryl triflates with a series of phenyl formates as CO alternatives was achieved using PAd3/Pd or MePAd2/Pd catalyst system. The developed reaction conditions accommodated general substrate scopes. The gram-scale reaction and a two-step strategy to an antidepressant (Moclobemide) were also demonstrated. Chapter 4 developed the first palladium-catalyzed chemoselective direct arylation of polyfluoroarenes with extensive and inexpensive (pseudo)aryl halides. A novel pyrazole scaffold ligand established an effective and direct approach toward C−Cl bond (over C−OTf) activation to biaryls containing polyfluoroarenes moiety under milder conditions. |
| Rights: | All rights reserved |
| Access: | open access |
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