Stereoselective synthesis of trisubstituted (E,E)-1,3-dienes by the site-selective reductive cross-coupling of internal alkynes with terminal alkynes : a fragment coupling reaction for natural product synthesis
A highly selective convergent coupling reaction is described between alkynes for the synthesis of stereodefined trisubstituted (E,E)-1,3-dienes-structural motifs commonly found embedded in the skeletons of bioactive polyketide-derived natural products. While numerous multistep processes for the synthesis of this stereodefined functional group exist, the current method represents a significant advance as it does not require stereodefined olefinic coupling partners (vinyl halide or vinyl organometallic); it proceeds by a single convergent C-C bond-forming event (avoiding multistep methods based on carbonyl olefination) and is tolerant of a diverse array of functional groups including free hydroxyls. Through a systematic study of titanium-mediated reductive cross-coupling reactions of internal alkynes with terminal alkynes, a fragment coupling reaction of great utility in natural product synthesis has emerged. Here, use of a proximal hydroxy group to control regioselection in the functionalization of a preformed titanacyclopropene has led to the establishment of a highly selective bimolecular coupling process, where C-C bond formation occurs in concert with the establishment of two stereodefined alkenes. Compared to the body of literature known for related metal-mediated coupling reactions, the current work defines a powerful advance, achieving site-selective bimolecular C-C bond formation without the need for using TMS-alkynes or conjugated alkynes. Overall, complex 1,3-dienes relevant for the synthesis of polyketide-derived natural products of varying stereochemistry were prepared with typically >or=20:1 selectivity, defining the important role of an alkoxide directing group located delta to preformed titanacyclopropenes.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2009 |
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| Erschienen: |
2009 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:74 |
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| Enthalten in: |
The Journal of organic chemistry - 74(2009), 19 vom: 02. Okt., Seite 7211-9 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Perez, Lark J [VerfasserIn] |
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| Links: |
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| Themen: |
Alkadienes |
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| Anmerkungen: |
Date Completed 11.12.2009 Date Revised 25.09.2009 published: Print Citation Status MEDLINE |
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| doi: |
10.1021/jo901451c |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM191066427 |
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| 100 | 1 | |a Perez, Lark J |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Stereoselective synthesis of trisubstituted (E,E)-1,3-dienes by the site-selective reductive cross-coupling of internal alkynes with terminal alkynes |b a fragment coupling reaction for natural product synthesis |
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| 500 | |a Date Completed 11.12.2009 | ||
| 500 | |a Date Revised 25.09.2009 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a A highly selective convergent coupling reaction is described between alkynes for the synthesis of stereodefined trisubstituted (E,E)-1,3-dienes-structural motifs commonly found embedded in the skeletons of bioactive polyketide-derived natural products. While numerous multistep processes for the synthesis of this stereodefined functional group exist, the current method represents a significant advance as it does not require stereodefined olefinic coupling partners (vinyl halide or vinyl organometallic); it proceeds by a single convergent C-C bond-forming event (avoiding multistep methods based on carbonyl olefination) and is tolerant of a diverse array of functional groups including free hydroxyls. Through a systematic study of titanium-mediated reductive cross-coupling reactions of internal alkynes with terminal alkynes, a fragment coupling reaction of great utility in natural product synthesis has emerged. Here, use of a proximal hydroxy group to control regioselection in the functionalization of a preformed titanacyclopropene has led to the establishment of a highly selective bimolecular coupling process, where C-C bond formation occurs in concert with the establishment of two stereodefined alkenes. Compared to the body of literature known for related metal-mediated coupling reactions, the current work defines a powerful advance, achieving site-selective bimolecular C-C bond formation without the need for using TMS-alkynes or conjugated alkynes. Overall, complex 1,3-dienes relevant for the synthesis of polyketide-derived natural products of varying stereochemistry were prepared with typically >or=20:1 selectivity, defining the important role of an alkoxide directing group located delta to preformed titanacyclopropenes | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 7 | |a Alkynes |2 NLM | |
| 650 | 7 | |a Biological Factors |2 NLM | |
| 700 | 1 | |a Shimp, Heidi L |e verfasserin |4 aut | |
| 700 | 1 | |a Micalizio, Glenn C |e verfasserin |4 aut | |
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