Chemoselective Amide Ligations by Decarboxylative Condensations of <i>N</i>‐Alkylhydroxylamines and α‐Ketoacids

Bode, Jeffrey W.; Fox, Ryan M.; Baucom, Kyle D.

doi:10.1002/ange.200503991

Cited by 100 publications

(28 citation statements)

References 30 publications

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“…The synthesis of a-oligopeptides hinges upon decarboxylative condensation of a-ketoacids and N-alkyl hydroxyamines. [125] This powerful transformation does not involve added reagents and produces no by-products. For the b-oligopeptide synthesis, isoxazolidine acetals, which are available in enantiomerically pure form by using Vasellas method, can be coupled with a-ketoacids.…”

Section: Decarboxylative Amide Ligationmentioning

confidence: 99%

Chemoselectivity and the Curious Reactivity Preferences of Functional Groups

2009

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Achieving high levels of chemoselectivity has been the Achilles' heel of chemical synthesis. The excitement generated by the successful realization of chemoselective strategies underscores the painstaking efforts to define a set of conditions conducive to selection among the available reaction pathways. We discuss in this Review various aspects of chemoselectivity that have been addressed in a range of synthetic methods over the past decade. We have focused on the proposed mechanistic basis of the reactions under consideration in an attempt to categorize them and highlight the key concepts that have been emerging on the basis of these studies. Our overview of recent advances in chemoselective processes suggests that significant progress has been made, but a lot of challenges lie ahead.

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Section: Decarboxylative Amide Ligationmentioning

confidence: 99%

Chemoselectivity and the Curious Reactivity Preferences of Functional Groups

2009

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“…[2] The activated derivatives may also be generated in situ by employing stoichiometric coupling reagents, such as carbodiimides, uronium, and phosphonium salts, [5] for which the latter two are the methods of choice in peptide synthesis. Other general procedures for amide synthesis include the Beckman rearrangement, [6] Staudinger ligations, [7] oxidative amidation of aldehydes, [8] coupling of aketoacids and hydroxylamines, [9] and amidation of ketones and thioacids with azides. [10] More recently, a number catalytic procedures have been developed including amidationhydrolysis of gem-dihaloolefins, [11] redox rearrangement of a-functionalized aldehydes, [12] and aminocarbonylation of aryl halides and terminal alkynes.…”

Section: Introductionmentioning

confidence: 99%

Amide Synthesis from Alcohols and Amines Catalyzed by Ruthenium N‐Heterocyclic Carbene Complexes

Dam

Osztrovszky

Nordstrøm

et al. 2010

Chemistry A European J

176

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The direct synthesis of amides from alcohols and amines is described with the simultaneous liberation of dihydrogen. The reaction does not require any stoichiometric additives or hydrogen acceptors and is catalyzed by ruthenium N-heterocyclic carbene complexes. Three different catalyst systems are presented that all employ 1,3-diisopropylimidazol-2-ylidene (IiPr) as the carbene ligand. In addition, potassium tert-butoxide and a tricycloalkylphosphine are required for the amidation to proceed. In the first system, the active catalyst is generated in situ from [RuCl(2)(cod)] (cod=1,5-cyclooctadiene), 1,3-diisopropylimidazolium chloride, tricyclopentylphosphonium tetrafluoroborate, and base. The second system uses the complex [RuCl(2)(IiPr)(p-cymene)] together with tricyclohexylphosphine and base, whereas the third system employs the Hoveyda-Grubbs 1st-generation metathesis catalyst together with 1,3-diisopropylimidazolium chloride and base. A range of different primary alcohols and amines have been coupled in the presence of the three catalyst systems to afford the corresponding amides in moderate to excellent yields. The best results are obtained with sterically unhindered alcohols and amines. The three catalyst systems do not show any significant differences in reactivity, which indicates that the same catalytically active species is operating. The reaction is believed to proceed by initial dehydrogenation of the primary alcohol to the aldehyde that stays coordinated to ruthenium and is not released into the reaction mixture. Addition of the amine forms the hemiaminal that undergoes dehydrogenation to the amide. A catalytic cycle is proposed with the {(IiPr)Ru(II)} species as the catalytically active components.

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“…[176] rung der a-Ketosäuren auftritt. Entscheidend an dieser Reaktion ist aber, dass ungeschützte Peptide mit Lys-und Asp- [176] sowie Trp-, Tyr-und Arg-Bausteinen [177] verknüpft werden können, wie mit der Synthese des Hexapeptids 135 demonstriert wurde (Schema 24 B). Mögliche Ligationsstellen schließen dabei Phe-Ala, Pro-Ala, Val-Gly und Ala-Ala ein.…”

Section: Spurlose Staudinger-ligationunclassified

Chemoselektive Ligations‐ und Modifikationsstrategien für Peptide und Proteine

2008

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Die Untersuchung biologischer Fragestellungen mit chemischen Methoden wird meist als “Chemische Biologie” bezeichnet und setzt voraus, dass biologisch relevante Makromoleküle, wie Peptide und Proteine, chemisch zugänglich sind. Auf der Festphasensynthese von Peptiden aufbauend wurden viele chemoselektive Ligations‐ und Modifikationstechniken zur Verknüpfung synthetischer Peptide oder funktionaler Einheiten zu größeren synthetischen, biologisch relevanten Makromolekülen entwickelt. Dieser Aufsatz fasst die aktuellen Entwicklungen auf dem Gebiet der chemoselektiven Ligations‐ und Modifikationsstrategien zusammen und illustriert ihre Anwendbarkeit an Beispielen aus der chemischen Totalsynthese von Proteinen bis hin zur Semisynthese natürlicher modifizierter Proteine.

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Chemoselective Amide Ligations by Decarboxylative Condensations of N‐Alkylhydroxylamines and α‐Ketoacids

Cited by 100 publications

References 30 publications

Chemoselectivity and the Curious Reactivity Preferences of Functional Groups

Chemoselectivity and the Curious Reactivity Preferences of Functional Groups

Amide Synthesis from Alcohols and Amines Catalyzed by Ruthenium N‐Heterocyclic Carbene Complexes

Chemoselektive Ligations‐ und Modifikationsstrategien für Peptide und Proteine

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