Development of diamidophosphite ligands towards the palladium-catalyzed trimethylenemethane cycloaddition
Abstract/Contents
- Abstract
- The synthesis of complex molecules in an efficient and selective fashion remains to be one of the driving forces in the development of the field of organic chemistry. Towards that end, the study of cycloaddition reactions has garnered much attention due to its ability to form multiple bonds in a single step while accessing complicated ring structures. Since its inception in 1979, the palladium-catalyzed trimethylenemethane (TMM) [3+2] cycloaddition has been heavily studied by the Trost group. It was found that the key zwitterionic palladium-TMM intermediate is capable of performing cycloaddition reactions with various coupling partners, forming cyclopentanes, tetrahydrofurans, and pyrrolidine rings, as well as seven- and nine-membered rings in good yields and selectivities. Additionally, substituents placed on the starting TMM-precursor, also known as the TMM donor, are also directly introduced onto the cycloadduct, allowing for the synthesis of highly-substituted ring systems. In 2006, the Trost group was able to perform the reaction in an enantioselective fashion through the development of BINOL-derived phosphoramidite ligands. While these cycloadducts were generated with high yields and enantioselectivities, the substitution on the TMM precursor was limited, owing to the reactivity of the phosphoramidite ligand employed. Herein, we describe the development of a new class of ligands, diamidophosphites, and their utility in the substituted-TMM cycloaddition. These ligands are easily accessed in a two-step procedure with high levels of modularity, allowing for the fine-tuning of the catalyst system. The effectiveness of these ligands will first be discussed in a vinyl-substituted TMM cycloaddition, where tetrasubstituted cyclopentanes bearing three contiguous stereocenters are synthesized in high yields, diastereo- and enantioselectivities. Additionally, a new disubstituted TMM donor was developed for the synthesis of pyrrolidine ring systems bearing a quaternary stereocenter. Finally, this method is applied towards the total synthesis of jogyamycin, where the core cyclopentane ring is accessed through the TMM cycloaddition.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2014 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Lam, Tom Ming To |
|---|---|
| Associated with | Stanford University, Department of Chemistry. |
| Primary advisor | Trost, Barry M |
| Thesis advisor | Trost, Barry M |
| Thesis advisor | Du Bois, Justin |
| Thesis advisor | Wender, Paul A |
| Advisor | Du Bois, Justin |
| Advisor | Wender, Paul A |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Tom Ming To Lam. |
|---|---|
| Note | Submitted to the Department of Chemistry. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2014. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2014 by Tom Ming To Lam
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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