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Asymmetric Synthesis of 2‐Arylindolines and 2,2‐Disubstituted Indolines by Kinetic Resolution
Kinetic resolution of 2‐arylindolines (2,3‐dihydroindoles) was achieved by treatment of their N‐tert‐butoxycarbonyl (Boc) derivatives with n‐butyllithium and sparteine in toluene at −78 °C followed by electrophilic quench. The unreacted starting materials together with the 2,2‐disubstituted products...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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John Wiley and Sons Inc.
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8456874/ https://www.ncbi.nlm.nih.gov/pubmed/34110662 http://dx.doi.org/10.1002/chem.202101248 |
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author | Choi, Anthony El‐Tunsi, Ashraf Wang, Yuhang Meijer, Anthony J. H. M. Li, Jia Li, Xiabing Proietti Silvestri, Ilaria Coldham, Iain |
author_facet | Choi, Anthony El‐Tunsi, Ashraf Wang, Yuhang Meijer, Anthony J. H. M. Li, Jia Li, Xiabing Proietti Silvestri, Ilaria Coldham, Iain |
author_sort | Choi, Anthony |
collection | PubMed |
description | Kinetic resolution of 2‐arylindolines (2,3‐dihydroindoles) was achieved by treatment of their N‐tert‐butoxycarbonyl (Boc) derivatives with n‐butyllithium and sparteine in toluene at −78 °C followed by electrophilic quench. The unreacted starting materials together with the 2,2‐disubstituted products could be isolated with high enantiomer ratios. Variable temperature NMR spectroscopy showed that the rate of Boc rotation was fast (ΔG (≠)≈57 kJ/mol at 195 K). This was corroborated by DFT studies and by in situ ReactIR spectroscopy. The enantioenriched N‐Boc‐2‐arylindolines were converted to 2,2‐disubstituted products without significant loss in enantiopurity. Hence, either enantiomer of the 2,2‐disubstituted products could be obtained with high selectivity from the same enantiomer of the chiral ligand sparteine (one from the kinetic resolution and the other from subsequent lithiation‐trapping of the recovered starting material). Secondary amine products were prepared by removing the Boc group with acid to provide a way to access highly enantioenriched 2‐aryl and 2,2‐disubstituted indolines. |
format | Online Article Text |
id | pubmed-8456874 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-84568742021-09-27 Asymmetric Synthesis of 2‐Arylindolines and 2,2‐Disubstituted Indolines by Kinetic Resolution Choi, Anthony El‐Tunsi, Ashraf Wang, Yuhang Meijer, Anthony J. H. M. Li, Jia Li, Xiabing Proietti Silvestri, Ilaria Coldham, Iain Chemistry Full Papers Kinetic resolution of 2‐arylindolines (2,3‐dihydroindoles) was achieved by treatment of their N‐tert‐butoxycarbonyl (Boc) derivatives with n‐butyllithium and sparteine in toluene at −78 °C followed by electrophilic quench. The unreacted starting materials together with the 2,2‐disubstituted products could be isolated with high enantiomer ratios. Variable temperature NMR spectroscopy showed that the rate of Boc rotation was fast (ΔG (≠)≈57 kJ/mol at 195 K). This was corroborated by DFT studies and by in situ ReactIR spectroscopy. The enantioenriched N‐Boc‐2‐arylindolines were converted to 2,2‐disubstituted products without significant loss in enantiopurity. Hence, either enantiomer of the 2,2‐disubstituted products could be obtained with high selectivity from the same enantiomer of the chiral ligand sparteine (one from the kinetic resolution and the other from subsequent lithiation‐trapping of the recovered starting material). Secondary amine products were prepared by removing the Boc group with acid to provide a way to access highly enantioenriched 2‐aryl and 2,2‐disubstituted indolines. John Wiley and Sons Inc. 2021-07-08 2021-08-11 /pmc/articles/PMC8456874/ /pubmed/34110662 http://dx.doi.org/10.1002/chem.202101248 Text en © 2021 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Full Papers Choi, Anthony El‐Tunsi, Ashraf Wang, Yuhang Meijer, Anthony J. H. M. Li, Jia Li, Xiabing Proietti Silvestri, Ilaria Coldham, Iain Asymmetric Synthesis of 2‐Arylindolines and 2,2‐Disubstituted Indolines by Kinetic Resolution |
title | Asymmetric Synthesis of 2‐Arylindolines and 2,2‐Disubstituted Indolines by Kinetic Resolution |
title_full | Asymmetric Synthesis of 2‐Arylindolines and 2,2‐Disubstituted Indolines by Kinetic Resolution |
title_fullStr | Asymmetric Synthesis of 2‐Arylindolines and 2,2‐Disubstituted Indolines by Kinetic Resolution |
title_full_unstemmed | Asymmetric Synthesis of 2‐Arylindolines and 2,2‐Disubstituted Indolines by Kinetic Resolution |
title_short | Asymmetric Synthesis of 2‐Arylindolines and 2,2‐Disubstituted Indolines by Kinetic Resolution |
title_sort | asymmetric synthesis of 2‐arylindolines and 2,2‐disubstituted indolines by kinetic resolution |
topic | Full Papers |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8456874/ https://www.ncbi.nlm.nih.gov/pubmed/34110662 http://dx.doi.org/10.1002/chem.202101248 |
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