Evaluation of In-Batch and In-Flow Synthetic Strategies towards the Stereoselective Synthesis of a Fluorinated Analogue of Retro-Thiorphan
A stereoselective synthetic strategy for the preparation of trifluoromethylamine mimics of retro-thiorphan, involving a diastereoselective, metal-free catalytic step, has been studied in batch and afforded the target molecule in good yields and high diastereoselectivity. A crucial point of the synth...
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| Format: | Article |
| Language: | English |
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MDPI AG
2019-06-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/24/12/2260 |
| _version_ | 1818872603585019904 |
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| author | Margherita Pirola Alessandra Puglisi Laura Raimondi Alessandra Forni Maurizio Benaglia |
| author_facet | Margherita Pirola Alessandra Puglisi Laura Raimondi Alessandra Forni Maurizio Benaglia |
| author_sort | Margherita Pirola |
| collection | DOAJ |
| description | A stereoselective synthetic strategy for the preparation of trifluoromethylamine mimics of retro-thiorphan, involving a diastereoselective, metal-free catalytic step, has been studied in batch and afforded the target molecule in good yields and high diastereoselectivity. A crucial point of the synthetic sequence was the catalytic reduction of a fluorinated enamine with trichlorosilane as reducing agent in the presence of a chiral Lewis base. The absolute configuration of the key intermediate was unambiguously assigned by X-ray analysis. The synthesis was also investigated exploiting continuous flow reactions; that is, an advanced intermediate of the target molecule was synthesized in only two in-flow synthetic modules, avoiding isolation and purifications of intermediates, leading to the isolation of the target chiral fluorinated amine in up to an 87:13 diastereoisomeric ratio. |
| first_indexed | 2024-12-19T12:41:26Z |
| format | Article |
| id | doaj.art-8822a27dd1514cc399e062b9358cfac2 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-19T12:41:26Z |
| publishDate | 2019-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-8822a27dd1514cc399e062b9358cfac22022-12-21T20:20:57ZengMDPI AGMolecules1420-30492019-06-012412226010.3390/molecules24122260molecules24122260Evaluation of In-Batch and In-Flow Synthetic Strategies towards the Stereoselective Synthesis of a Fluorinated Analogue of Retro-ThiorphanMargherita Pirola0Alessandra Puglisi1Laura Raimondi2Alessandra Forni3Maurizio Benaglia4Dipartimento di Chimica, Università degli Studi di Milano, Via Golgi 19, 20133 Milano, ItalyDipartimento di Chimica, Università degli Studi di Milano, Via Golgi 19, 20133 Milano, ItalyDipartimento di Chimica, Università degli Studi di Milano, Via Golgi 19, 20133 Milano, ItalyIstituto di Scienze e Tecnologie Molecolari–ISTM-CNR, Via Golgi 19, 20133 Milano, ItalyDipartimento di Chimica, Università degli Studi di Milano, Via Golgi 19, 20133 Milano, ItalyA stereoselective synthetic strategy for the preparation of trifluoromethylamine mimics of retro-thiorphan, involving a diastereoselective, metal-free catalytic step, has been studied in batch and afforded the target molecule in good yields and high diastereoselectivity. A crucial point of the synthetic sequence was the catalytic reduction of a fluorinated enamine with trichlorosilane as reducing agent in the presence of a chiral Lewis base. The absolute configuration of the key intermediate was unambiguously assigned by X-ray analysis. The synthesis was also investigated exploiting continuous flow reactions; that is, an advanced intermediate of the target molecule was synthesized in only two in-flow synthetic modules, avoiding isolation and purifications of intermediates, leading to the isolation of the target chiral fluorinated amine in up to an 87:13 diastereoisomeric ratio.https://www.mdpi.com/1420-3049/24/12/2260fluorinated derivativesflow chemistryorganocatalysisstereoselective synthesisreduction |
| spellingShingle | Margherita Pirola Alessandra Puglisi Laura Raimondi Alessandra Forni Maurizio Benaglia Evaluation of In-Batch and In-Flow Synthetic Strategies towards the Stereoselective Synthesis of a Fluorinated Analogue of Retro-Thiorphan Molecules fluorinated derivatives flow chemistry organocatalysis stereoselective synthesis reduction |
| title | Evaluation of In-Batch and In-Flow Synthetic Strategies towards the Stereoselective Synthesis of a Fluorinated Analogue of Retro-Thiorphan |
| title_full | Evaluation of In-Batch and In-Flow Synthetic Strategies towards the Stereoselective Synthesis of a Fluorinated Analogue of Retro-Thiorphan |
| title_fullStr | Evaluation of In-Batch and In-Flow Synthetic Strategies towards the Stereoselective Synthesis of a Fluorinated Analogue of Retro-Thiorphan |
| title_full_unstemmed | Evaluation of In-Batch and In-Flow Synthetic Strategies towards the Stereoselective Synthesis of a Fluorinated Analogue of Retro-Thiorphan |
| title_short | Evaluation of In-Batch and In-Flow Synthetic Strategies towards the Stereoselective Synthesis of a Fluorinated Analogue of Retro-Thiorphan |
| title_sort | evaluation of in batch and in flow synthetic strategies towards the stereoselective synthesis of a fluorinated analogue of retro thiorphan |
| topic | fluorinated derivatives flow chemistry organocatalysis stereoselective synthesis reduction |
| url | https://www.mdpi.com/1420-3049/24/12/2260 |
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