Ring-closing metathesis for the synthesis of heteroaromatics: evaluating routes to pyridines and pyridazines

Donohoe, Timothy J.; Bower, John F.; Basutto, José A.; Fishlock, Lisa P.; Procopiou, Panayiotis A.; Callens, Cedric K. A.

doi:10.1016/j.tet.2009.07.076

Cited by 60 publications

(29 citation statements)

References 80 publications

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“…[21] This technology has been used by Donohoe et al for the multistep synthesis of 2,6-di-and 2,3,6-trisubstituted pyridines with alkyl, aryl, and alkoxy substituents (Scheme 11). [22] The Hoveyda-Grubbs second generation ruthenium catalyst was optimal for the conversion of amide precursors to the corresponding a,b-unsaturated lactams. [23] Interestingly, the mode of cyclization was found to be temperature dependent and provided two distinct classes of pyridine derivative (Schemes 12 and 13).…”

Section: Wwwchemeurjorg Recent Advances In Pyridine Synthesismentioning

confidence: 99%

Recent Strategies for the Synthesis of Pyridine Derivatives

Hill

2010

Chemistry A European J

456

130

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Recent advances in pyridine synthesis are described. Modification of traditional condensation strategies continues to be a recurrent theme in contemporary literature. Advancements in transition-metal-catalyzed cyclization and cross-coupling procedures offer new routes to functionalized pyridine derivatives. These recently developed methodologies are a valuable addition to azaheterocycle synthesis.

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Section: Wwwchemeurjorg Recent Advances In Pyridine Synthesismentioning

confidence: 99%

Recent Strategies for the Synthesis of Pyridine Derivatives

Hill

2010

Chemistry A European J

456

130

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“…Generation ist. Ein Jahr später wurde in einer weiteren Publikation [28] angegeben, dass fälschlicherweise das isomere Methyl-1-(benzyloxy)-6-oxo-1,6-dihydropyridin-2-carboxylat als 11 präsentiert worden war. Dies steht in Einklang mit unseren Ergebnissen beim Versuch, die Darstellung von 11 nachzuvollziehen.…”

Section: Synthesewegeüber Ester Von 25-dioxoadipinsäure Und 25-dihyunclassified

“…Dies steht in Einklang mit unseren Ergebnissen beim Versuch, die Darstellung von 11 nachzuvollziehen. In der zweiten Veröffentlichung [28] wurde auch ein veränderter Syntheseweg vorgestellt (Schema 5), auf dem zunächst 2-(Benzyloxy)acetaldehyd zu 2-(Ben- zyloxy)acrylaldehyd (12) olefiniert und dieser zu 2-(Benzyloxy)acrylsäure (13) …”

Section: Synthesewegeüber Ester Von 25-dioxoadipinsäure Und 25-dihyunclassified

“…In unseren Händen hat die Oxidation von 12 unter den in der Publikation angegebenen Bedingungen (Natriumchlorit in einer Mischung aus wässrigem Phosphatpuffer und tert-Butanol mit 2-Methyl-2-buten als Hypochlorit-Fänger [28]) nicht zum gewünschten Produkt 13 geführt. Stattdessen haben wir mehrfach größere Mengen an Benzoesäure isoliert, die auf eine oxidative Spaltung des Benzylethers hinweisen.…”

Section: Synthesewegeüber Ester Von 25-dioxoadipinsäure Und 25-dihyunclassified

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,, ... und ehrt mir ihre Kunst!“ – Evaluierung historischer und neuer Synthesewege zu 1,5-Dihydroxy-6-oxo-1,6-dihydropyridin-2-carbonsäure und 1,3-Dihydroxy-2-oxo-3-pyrrolin-4-carbonsäure / “. . . and honour their art!” – Evaluation of Historical and New Routes to 1,5-Dihydroxy-6-oxo-1,6- dihydropyridine-2-carboxylic Acid and 1,3-Dihydroxy-2-oxo-3-pyrroline-4-carboxylic Acid

Wiedemann

Grohmann

2009

Zeitschrift Für Naturforschung B

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Gewidmet Professor Hubert Schmidbaur anlässlich seines 75. GeburtstagsThe historical and recent literature describing synthetical pathways to the title compounds is comprehensively summarized and evaluated. Routes via 2,5-dioxoadipic acid or 2,5-dihydroxymuconic acid as intermediates could not be followed reproducibly. 3-Hydroxy-2-oxo-2H-pyran-6-carboxylic acid and ethyl 3-hydroxy-2-oxo-3-pyrroline-4-carboxylate were fully characterized by spectroscopic methods and single-crystal X-ray diffraction. Both compounds have an enolic structure in solution as well as in the solid state. A recently published ring-closing metathesis (RCM) protocol to a derivative of the first title compound was unproductive in our hands. We present a new two-step synthesis of the similarly substituted 5-hydroxy-6-oxo-1,6-dihydropyridine-2-carboxamide using succinyl cyanide. The product was indentified and characterized by spectroscopic methods and X-ray crystallography.

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“…In recent years, the potential of ring-closing olefin metathesis (RCM) as a key step for the preparation of aromatic and heteroaromatic compounds has begun to be realized (6)(7)(8). Studies from our own laboratory have delineated versatile RCM-based protocols for the regiodefined synthesis of pyridines, pyridazines, furans, and pyrroles (9)(10)(11)(12)(13)(14)(15). Despite the evident potential of these methods it is notable that any RCM-based approach is reliant upon the a priori construction of a suitable precursor, which necessarily detracts from synthetic convergency and flexibility.…”

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confidence: 99%

An expedient route to substituted furans via olefin cross-metathesis

Donohoe

Bower

2010

Proc. Natl. Acad. Sci. U.S.A.

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The olefin cross-metathesis (CM) reaction is used extensively in organic chemistry and represents a powerful method for the selective synthesis of differentially substituted alkene products. Surprisingly, efforts to integrate this remarkable process into strategies for aromatic and heteroaromatic construction have not been reported. Such structures represent key elements of the majority of small molecule drug compounds; methods for the controlled preparation of highly substituted derivatives are essential to medicinal chemistry. Here we show that the olefin CM reaction, in combination with an acid cocatalyst or subsequent Heck arylation, provides a concise and flexible entry to 2,5-di-or 2,3,5-tri-substituted furans. These cascade processes portend further opportunities for the regiocontrolled preparation of other highly substituted aromatic and heteroaromatic classes.catalysis | cembranolide | Heck reaction R uthenium catalyzed olefin metathesis has become a remarkably powerful tool for organic chemistry (1-5). In recent years, the potential of ring-closing olefin metathesis (RCM) as a key step for the preparation of aromatic and heteroaromatic compounds has begun to be realized (6-8). Studies from our own laboratory have delineated versatile RCM-based protocols for the regiodefined synthesis of pyridines, pyridazines, furans, and pyrroles (9-15). Despite the evident potential of these methods it is notable that any RCM-based approach is reliant upon the a priori construction of a suitable precursor, which necessarily detracts from synthetic convergency and flexibility. A related approach involves the use of olefin cross-metathesis (CM) as a key step. Here both fragment coupling and strategic C=C bond formation are unified and, as such, potentially greater efficiencies are afforded. Despite this potential, and presumably due to perceived problems associated with double bond geometry, olefin CM-based methodologies for aromatic and heteroaromatic construction have not, to the best of our knowledge, been disclosed. Herein we report the successful implementation of this concept in terms of a versatile and direct entry to disubstituted and trisubstituted furans. It is likely that these studies will set the stage for the development of general olefin CM-based entries to other aromatic and heteroaromatic classes of varying ring sizes (Scheme 1, top).Substituted furans are prevalent in natural products and pharmaceuticals and also represent useful intermediates in synthesis. Convergent de novo approaches to furans that embody high levels of flexibility and predictable regiocontrol are of particular value yet are relatively uncommon (16)(17)(18)(19)(20)(21)(22). Specifically, methods that employ simple starting materials, enable facile substituent introduction, and are concise are likely to be of significance to both medicinal chemistry and total synthesis. Our approach to furans relies upon the intermediacy of trans-γ-hydroxyenones 3 that are accessible via the established olefin CM of readily available allylic alcohol...

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Ring-closing metathesis for the synthesis of heteroaromatics: evaluating routes to pyridines and pyridazines

Cited by 60 publications

References 80 publications

Recent Strategies for the Synthesis of Pyridine Derivatives

Recent Strategies for the Synthesis of Pyridine Derivatives

An expedient route to substituted furans via olefin cross-metathesis

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