Hydroxylation of unactivated tertiary carbon-hydrogen bonds using high-valent ruthenium catalysts
Abstract/Contents
- Abstract
- The prevalence of the hydroxyl group in organic molecules of synthetic and biological interest makes direct, selective hydroxylation of unactivated carbon-hydrogen (C—H) bonds in complex molecules a desirable goal. This approach to oxygen incorporation is further inspired by Nature, where enzymes mediate hydroxylation of complex substrates with exquisite selectivity. Chemists have designed catalysts for C—H hydroxylation, but further improvements in chemoselectivity, positional selectivity and turnover numbers are needed for C—H hydroxylation to become a widely-used tool for fine chemicals synthesis. Our approach to the problem of C—H hydroxylation involves the use of high-valent ruthenium oxo complexes. We have found that addition of pyridine to ruthenium tetroxide (RuO¬4, generated using ruthenium trichloride and potassium bromate) results in a notable improvement in the ability of RuO4 to catalyze C—H hydroxylation of functionalized substrates. This reaction proceeds with predictable selectivity in substrates with more than one tertiary C—H center. Incorporation of isotopically labeled oxygen into a substrate is possible using this methodology. However, the highly-oxidizing nature of RuO4 places some limits on the types of functionality that may be present in substrate molecules. Limitations of the ruthenium tetroxide/pyridine catalyst system have led us to examine ruthenium complexes with tunable ligands. The complex (Me3tacn)RuCl3 (Me3tacn = 1,4,7-trimethyl-1,4,7-triazacyclononane), in combination with silver perchlorate and ceric ammonium nitrate, catalyzes tertiary and benzylic C—H hydroxylation at room temperature with up to 80 turnovers. This catalyst system displays functional group compatibility and turnover numbers comparable with or superior to known catalysts for C—H hydroxylation. Mechanistic studies suggest that the reaction proceeds via hydrogen atom abstraction followed by fast, solvent-caged radical rebound. Efforts to tune the ligand to further increase turnover numbers and catalyst selectivity are described.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2012 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | McNeill, Eric Andrew |
|---|---|
| Associated with | Stanford University, Department of Chemistry |
| Primary advisor | Du Bois, Justin |
| Thesis advisor | Du Bois, Justin |
| Thesis advisor | Stack, T. (T. Daniel P.), 1959- |
| Thesis advisor | Waymouth, Robert M |
| Advisor | Stack, T. (T. Daniel P.), 1959- |
| Advisor | Waymouth, Robert M |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Eric McNeill. |
|---|---|
| Note | Submitted to the Department of Chemistry. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2012. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2012 by Eric Andrew McNeill
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