Asymmetric Synthesis of 2-Arylindolines and 2,2-Disubstituted Indolines by Kinetic Resolution
© 2021 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:27 |
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| Enthalten in: |
Chemistry (Weinheim an der Bergstrasse, Germany) - 27(2021), 45 vom: 11. Aug., Seite 11670-11675 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Choi, Anthony [VerfasserIn] |
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| Links: |
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| Themen: |
298897D62S |
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| Anmerkungen: |
Date Completed 17.08.2021 Date Revised 03.04.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1002/chem.202101248 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM326586466 |
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2021 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a asymmetric synthesis | |
| 650 | 4 | |a enantioselectivity | |
| 650 | 4 | |a heterocycles | |
| 650 | 4 | |a kinetic resolution | |
| 650 | 4 | |a lithiation | |
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| 700 | 1 | |a El-Tunsi, Ashraf |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Yuhang |e verfasserin |4 aut | |
| 700 | 1 | |a Meijer, Anthony J H M |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Jia |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Xiabing |e verfasserin |4 aut | |
| 700 | 1 | |a Proietti Silvestri, Ilaria |e verfasserin |4 aut | |
| 700 | 1 | |a Coldham, Iain |e verfasserin |4 aut | |
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