The asymmetric synthesis of acyclic tetrasubstituted stereocenters by palladium-catalyzed allylic alkylation
Abstract/Contents
- Abstract
- Herein are described strategies for the asymmetric synthesis of acyclic tetrasubstituted stereocenters using palladium-catalyzed allylic alkylation. In particular prochiral nucleophiles are exploited for the synthesis of acyclic alpha tertiary hydroxyketones, fully substituted nitroalkanes, and all-carbon quaternary stereocenters. The problem of O-alkylation in benzylic nitronate synthesis was overcome by the use of a decarboxylative asymmetric allylic alkylation of allyl alpha nitroesters. Extensive screening of reaction conditions revealed a unique ligand and solvent combination that proved crucial for achieving high chemo- and enantioselectivity in this challenging reaction. Substrates were readily synthesized via a combinatorial cross-Claisen / alpha arylation protocol, and the method was highlighted by chemoselective functional group interconversions of a highly elaborated substrate. Boronic acids were exploited as templates of ene-diolate systems to solve a longstanding problem of direct asymmetric C-alkylation of alpha hydroxyketones. This process was rendered chemo-, regio-, and enantioselective in allylation reactions, while point and axial chirality were efficiently set in allylic alkylations of racemic allene substrates via a dynamic kinetic asymmetric transformation. This method represents one of the first examples where point and axial chirality are effectively set in allylic alkylation. As a follow-up to this work, enol boranes were found to be effective pronucleophiles in palladium-catalyzed allylic alkylation reactions. A 1,4-hydroboration reaction was exploited for the thermal generation of regio-defined enol boranes, and a unique electron-deficient ligand was found to exhibit differential reactivity in the subsequent alkylation reaction. This chemistry was further extended to provide a room temperature alkylation of ester derived enol boranes, in particular, unactivated esters. A preparative application was demonstrated in the synthesis of acyclic all-carbon quaternary stereocenters, where the stereoselectivity was a function of the identities of a chiral auxiliary, a chiral ligand, and a designer leaving group. It is hoped that this chemistry may spur broader interest in metal-catalyzed reactions of enol boranes.
Description
| Type of resource | text |
|---|---|
| Form | electronic resource; remote; computer; online resource |
| Extent | 1 online resource. |
| Place | California |
| Place | [Stanford, California] |
| Publisher | [Stanford University] |
| Copyright date | 2019; ©2019 |
| Publication date | 2019; 2019 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Schultz, Johnathan Edward |
|---|---|
| Degree supervisor | Trost, Barry M |
| Thesis advisor | Trost, Barry M |
| Thesis advisor | Burns, Noah |
| Thesis advisor | Kanan, Matthew William, 1978- |
| Degree committee member | Burns, Noah |
| Degree committee member | Kanan, Matthew William, 1978- |
| Associated with | Stanford University, Department of Chemistry. |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Johnathan Edward Schultz. |
|---|---|
| Note | Submitted to the Department of Chemistry. |
| Thesis | Thesis Ph.D. Stanford University 2019. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2019 by Johnathan Edward Schultz
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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