Rh(I)-bisphosphine-catalyzed asymmetric, intermolecular hydroheteroarylation of α-substituted acrylate derivatives
Asymmetric hydroheteroarylation of alkenes represents a convenient entry to elaborated heterocyclic motifs. While chiral acids are known to mediate asymmetric addition of electron-rich heteroarenes to Michael acceptors, very few methods exploit transition metals to catalyze alkylation of heterocycles with olefins via a C-H activation, migratory insertion sequence. Herein, we describe the development of an asymmetric, intermolecular hydroheteroarylation reaction of α-substituted acrylates with benzoxazoles. The reaction provides 2-substitued benzoxazoles in moderate to excellent yields and good to excellent enantioselectivities. Notably, a series of mechanistic studies appears to contradict a pathway involving enantioselective protonation of a Rh(I)-enolate, despite the fact that such a mechanism is invoked almost unanimously in the related addition of aryl boronic acids to methacrylate derivatives. Evidence suggests instead that migratory insertion or beta-hydride elimination is enantiodetermining and that isomerization of a Rh(I)-enolate to a Rh(I)-heterobenzyl species insulates the resultant α-stereocenter from epimerization. A bulky ligand, CTH-(R)-Xylyl-P-Phos, is crucial for reactivity and enantioselectivity, as it likely discourages undesired ligation of benzoxazole substrates or intermediates to on- or off-cycle rhodium complexes and attenuates coordination-promoted product epimerization.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2015 |
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| Erschienen: |
2015 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:137 |
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| Enthalten in: |
Journal of the American Chemical Society - 137(2015), 1 vom: 14. Jan., Seite 508-17 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Filloux, Claire M [VerfasserIn] |
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| Links: |
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| Themen: |
Acrylates |
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| Anmerkungen: |
Date Completed 01.03.2016 Date Revised 10.11.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1021/ja511445x |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM244935963 |
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| 245 | 1 | 0 | |a Rh(I)-bisphosphine-catalyzed asymmetric, intermolecular hydroheteroarylation of α-substituted acrylate derivatives |
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| 500 | |a Date Revised 10.11.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Asymmetric hydroheteroarylation of alkenes represents a convenient entry to elaborated heterocyclic motifs. While chiral acids are known to mediate asymmetric addition of electron-rich heteroarenes to Michael acceptors, very few methods exploit transition metals to catalyze alkylation of heterocycles with olefins via a C-H activation, migratory insertion sequence. Herein, we describe the development of an asymmetric, intermolecular hydroheteroarylation reaction of α-substituted acrylates with benzoxazoles. The reaction provides 2-substitued benzoxazoles in moderate to excellent yields and good to excellent enantioselectivities. Notably, a series of mechanistic studies appears to contradict a pathway involving enantioselective protonation of a Rh(I)-enolate, despite the fact that such a mechanism is invoked almost unanimously in the related addition of aryl boronic acids to methacrylate derivatives. Evidence suggests instead that migratory insertion or beta-hydride elimination is enantiodetermining and that isomerization of a Rh(I)-enolate to a Rh(I)-heterobenzyl species insulates the resultant α-stereocenter from epimerization. A bulky ligand, CTH-(R)-Xylyl-P-Phos, is crucial for reactivity and enantioselectivity, as it likely discourages undesired ligation of benzoxazole substrates or intermediates to on- or off-cycle rhodium complexes and attenuates coordination-promoted product epimerization | ||
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| 650 | 7 | |a Benzoxazoles |2 NLM | |
| 650 | 7 | |a Organometallic Compounds |2 NLM | |
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