Synthesis of indolines and indoles via intramolecular [4 + 2] cycloaddition of ynamides and conjugated enynes ; Synthesis of nitrogen heterocycles in supercritical carbon dioxide
Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2005.
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| Format: | Thesis |
| Language: | eng |
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Massachusetts Institute of Technology
2006
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| Online Access: | http://hdl.handle.net/1721.1/33650 |
| _version_ | 1811083900943859712 |
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| author | Dunetz, Joshua Ross |
| author2 | Rick L. Danheiser. |
| author_facet | Rick L. Danheiser. Dunetz, Joshua Ross |
| author_sort | Dunetz, Joshua Ross |
| collection | MIT |
| description | Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2005. |
| first_indexed | 2024-09-23T12:41:25Z |
| format | Thesis |
| id | mit-1721.1/33650 |
| institution | Massachusetts Institute of Technology |
| language | eng |
| last_indexed | 2024-09-23T12:41:25Z |
| publishDate | 2006 |
| publisher | Massachusetts Institute of Technology |
| record_format | dspace |
| spelling | mit-1721.1/336502019-04-10T12:12:29Z Synthesis of indolines and indoles via intramolecular [4 + 2] cycloaddition of ynamides and conjugated enynes ; Synthesis of nitrogen heterocycles in supercritical carbon dioxide Dunetz, Joshua Ross Rick L. Danheiser. Massachusetts Institute of Technology. Dept. of Chemistry. Massachusetts Institute of Technology. Dept. of Chemistry. Chemistry. Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2005. Vita. Includes bibliographical references. A general amination strategy for the N-alkynylation of carbamates, sulfonamides, and chiral oxazolidinones and imidazolidinones is described. A variety of substituted ynamides are available by deprotonation of amide derivatives with KHMDS followed by reaction with CuI and an alkynyl halide. Ynamides react with conjugated enynes in intramolecular [4 + 2] cycloaddition to afford substituted indolines that undergo oxidation with o-chloranil to furnish the corresponding indoles. The cycloaddition substrates are easily assembled from derivatives of 3-butynylamine by Sonogashira coupling with alkenyl halides followed by copper-catalyzed N-alkynylation with acetylenic bromides. Diynamides participate as particularly reactive 2[pi] components in the cycloaddition, providing access to indolines with carbon substituents at the C-7 position. Enynamides serve as 4[pi] components in a complementary version of the cycloaddition strategy which provides access to indoles and indolines substituted with substituents at C-4. These enyne cycloadditions take place upon heating the substrates at 110-210⁰C in toluene or 2,2,2- trifluoroethanol and in some cases can be achieved at 0⁰C to room temperature in the presence of Lewis acids such as Me₂A1C1. (cont.) We have developed a "green" strategy to effect acyl-Pictet-Spengler reactions in multiphasic scCO₂/CO₂-expanded liquid media. These cyclizations of iminium ions provide tetrahydroisoquinolines and tetrahydro-[beta]-carbolines that have valuable medicinal properties. Critical to the success of these reactions is the in situ conversion of [beta]-arylethylamine reactants to c;arbamate derivatives by reaction with carbon dioxide and dialkyl carbonates. The application of this general strategy for utilizing amines in other carbon-nitrogen bond-forming reactions in environmentally-friendly media is under investigation. by Joshua Ross Dunetz. Ph.D. 2006-07-31T15:20:15Z 2006-07-31T15:20:15Z 2005 2005 Thesis http://hdl.handle.net/1721.1/33650 64549637 eng M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission. http://dspace.mit.edu/handle/1721.1/7582 323 p. 12332395 bytes 12347271 bytes application/pdf application/pdf application/pdf Massachusetts Institute of Technology |
| spellingShingle | Chemistry. Dunetz, Joshua Ross Synthesis of indolines and indoles via intramolecular [4 + 2] cycloaddition of ynamides and conjugated enynes ; Synthesis of nitrogen heterocycles in supercritical carbon dioxide |
| title | Synthesis of indolines and indoles via intramolecular [4 + 2] cycloaddition of ynamides and conjugated enynes ; Synthesis of nitrogen heterocycles in supercritical carbon dioxide |
| title_full | Synthesis of indolines and indoles via intramolecular [4 + 2] cycloaddition of ynamides and conjugated enynes ; Synthesis of nitrogen heterocycles in supercritical carbon dioxide |
| title_fullStr | Synthesis of indolines and indoles via intramolecular [4 + 2] cycloaddition of ynamides and conjugated enynes ; Synthesis of nitrogen heterocycles in supercritical carbon dioxide |
| title_full_unstemmed | Synthesis of indolines and indoles via intramolecular [4 + 2] cycloaddition of ynamides and conjugated enynes ; Synthesis of nitrogen heterocycles in supercritical carbon dioxide |
| title_short | Synthesis of indolines and indoles via intramolecular [4 + 2] cycloaddition of ynamides and conjugated enynes ; Synthesis of nitrogen heterocycles in supercritical carbon dioxide |
| title_sort | synthesis of indolines and indoles via intramolecular 4 2 cycloaddition of ynamides and conjugated enynes synthesis of nitrogen heterocycles in supercritical carbon dioxide |
| topic | Chemistry. |
| url | http://hdl.handle.net/1721.1/33650 |
| work_keys_str_mv | AT dunetzjoshuaross synthesisofindolinesandindolesviaintramolecular42cycloadditionofynamidesandconjugatedenynessynthesisofnitrogenheterocyclesinsupercriticalcarbondioxide |