Enantioselective Catalytic Aldol Reactions in the Presence of Knoevenagel Nucleophiles: A Chemoselective Switch Optimized in Deep Eutectic Solvents Using Mechanochemistry
In the presence of different nucleophilic Knoevenagel competitors, cyclic and acyclic ketones have been shown to undergo highly chemoselective aldol reactions with aldehydes. In doing so, the substrate breadth for this emerging methodology has been significantly broadened. The method is also no long...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-12-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/29/1/4 |
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| author | Hanaa Al Beiruty Sofiia-Stefaniia Zhylinska Nino Kutateladze Hayley Kay Tinn Cheong José A. Ñíguez Sarah J. Burlingham Xavier Marset Gabriela Guillena Rafael Chinchilla Diego A. Alonso Thomas C. Nugent |
| author_facet | Hanaa Al Beiruty Sofiia-Stefaniia Zhylinska Nino Kutateladze Hayley Kay Tinn Cheong José A. Ñíguez Sarah J. Burlingham Xavier Marset Gabriela Guillena Rafael Chinchilla Diego A. Alonso Thomas C. Nugent |
| author_sort | Hanaa Al Beiruty |
| collection | DOAJ |
| description | In the presence of different nucleophilic Knoevenagel competitors, cyclic and acyclic ketones have been shown to undergo highly chemoselective aldol reactions with aldehydes. In doing so, the substrate breadth for this emerging methodology has been significantly broadened. The method is also no longer beholden to proline-based catalyst templates, <i>e.g.</i>, commercially available O-<i>t</i>-Bu-L-threonine is advantageous for acyclic ketones. The key insight was to exploit water-based mediums under conventional (in-water) and non-conventional (deep eutectic solvents) conditions. With few exceptions, high aldol-to-Knoevenagel chemoselectivity (>10:1) and good product profiles (yield, <i>dr</i>, and <i>ee</i>) were observed, but only in DESs (deep eutectic solvents) in conjunction with ball milling did short reaction times occur. |
| first_indexed | 2024-03-08T15:01:29Z |
| format | Article |
| id | doaj.art-8e4bd45f9a3543d4bf46e9d3e79454b6 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-08T15:01:29Z |
| publishDate | 2023-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-8e4bd45f9a3543d4bf46e9d3e79454b62024-01-10T15:03:50ZengMDPI AGMolecules1420-30492023-12-01291410.3390/molecules29010004Enantioselective Catalytic Aldol Reactions in the Presence of Knoevenagel Nucleophiles: A Chemoselective Switch Optimized in Deep Eutectic Solvents Using MechanochemistryHanaa Al Beiruty0Sofiia-Stefaniia Zhylinska1Nino Kutateladze2Hayley Kay Tinn Cheong3José A. Ñíguez4Sarah J. Burlingham5Xavier Marset6Gabriela Guillena7Rafael Chinchilla8Diego A. Alonso9Thomas C. Nugent10School of Science, Constructor University, Campus Ring 1, 28759 Bremen, GermanySchool of Science, Constructor University, Campus Ring 1, 28759 Bremen, GermanySchool of Science, Constructor University, Campus Ring 1, 28759 Bremen, GermanySchool of Science, Constructor University, Campus Ring 1, 28759 Bremen, GermanyDepartment of Organic Chemistry, Institute of Organic Synthesis (ISO), University of Alicante, P.O. Box 99, 03080 Alicante, SpainDepartment of Organic Chemistry, Institute of Organic Synthesis (ISO), University of Alicante, P.O. Box 99, 03080 Alicante, SpainDepartment of Organic Chemistry, Institute of Organic Synthesis (ISO), University of Alicante, P.O. Box 99, 03080 Alicante, SpainDepartment of Organic Chemistry, Institute of Organic Synthesis (ISO), University of Alicante, P.O. Box 99, 03080 Alicante, SpainDepartment of Organic Chemistry, Institute of Organic Synthesis (ISO), University of Alicante, P.O. Box 99, 03080 Alicante, SpainDepartment of Organic Chemistry, Institute of Organic Synthesis (ISO), University of Alicante, P.O. Box 99, 03080 Alicante, SpainSchool of Science, Constructor University, Campus Ring 1, 28759 Bremen, GermanyIn the presence of different nucleophilic Knoevenagel competitors, cyclic and acyclic ketones have been shown to undergo highly chemoselective aldol reactions with aldehydes. In doing so, the substrate breadth for this emerging methodology has been significantly broadened. The method is also no longer beholden to proline-based catalyst templates, <i>e.g.</i>, commercially available O-<i>t</i>-Bu-L-threonine is advantageous for acyclic ketones. The key insight was to exploit water-based mediums under conventional (in-water) and non-conventional (deep eutectic solvents) conditions. With few exceptions, high aldol-to-Knoevenagel chemoselectivity (>10:1) and good product profiles (yield, <i>dr</i>, and <i>ee</i>) were observed, but only in DESs (deep eutectic solvents) in conjunction with ball milling did short reaction times occur.https://www.mdpi.com/1420-3049/29/1/4organic synthesisgreen chemistryorganocatalysisin-water conditionsdeep eutectic solventsaldol reaction |
| spellingShingle | Hanaa Al Beiruty Sofiia-Stefaniia Zhylinska Nino Kutateladze Hayley Kay Tinn Cheong José A. Ñíguez Sarah J. Burlingham Xavier Marset Gabriela Guillena Rafael Chinchilla Diego A. Alonso Thomas C. Nugent Enantioselective Catalytic Aldol Reactions in the Presence of Knoevenagel Nucleophiles: A Chemoselective Switch Optimized in Deep Eutectic Solvents Using Mechanochemistry Molecules organic synthesis green chemistry organocatalysis in-water conditions deep eutectic solvents aldol reaction |
| title | Enantioselective Catalytic Aldol Reactions in the Presence of Knoevenagel Nucleophiles: A Chemoselective Switch Optimized in Deep Eutectic Solvents Using Mechanochemistry |
| title_full | Enantioselective Catalytic Aldol Reactions in the Presence of Knoevenagel Nucleophiles: A Chemoselective Switch Optimized in Deep Eutectic Solvents Using Mechanochemistry |
| title_fullStr | Enantioselective Catalytic Aldol Reactions in the Presence of Knoevenagel Nucleophiles: A Chemoselective Switch Optimized in Deep Eutectic Solvents Using Mechanochemistry |
| title_full_unstemmed | Enantioselective Catalytic Aldol Reactions in the Presence of Knoevenagel Nucleophiles: A Chemoselective Switch Optimized in Deep Eutectic Solvents Using Mechanochemistry |
| title_short | Enantioselective Catalytic Aldol Reactions in the Presence of Knoevenagel Nucleophiles: A Chemoselective Switch Optimized in Deep Eutectic Solvents Using Mechanochemistry |
| title_sort | enantioselective catalytic aldol reactions in the presence of knoevenagel nucleophiles a chemoselective switch optimized in deep eutectic solvents using mechanochemistry |
| topic | organic synthesis green chemistry organocatalysis in-water conditions deep eutectic solvents aldol reaction |
| url | https://www.mdpi.com/1420-3049/29/1/4 |
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