Allenes in Multicomponent Synthesis of Heterocycles

Reißig, Hans‐Ulrich; Zimmer, Reinhold

doi:10.1002/9783527678174.ch11

Cited by 5 publications

(6 citation statements)

References 110 publications

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“…Numerous earlier unknown and inaccessible N -alkyl-, N -cycloalkyl-, N -aryl-, N , N -dialkyl-, N -alkyl- N -cycloalkyl-, and N -alkyl- N -arylthiophen-2-amines have been synthesized using this procedure. Previously, we have also shown that the reaction of 1-lithio-1-alkoxyallenes with isothiocyanates, followed by S-alkylation of the adducts leads to alkyl 2-alkoxybuta-2,3-dienimidothioates (1-aza-1,3,4-trienes), which further undergo thermally induced structural reorganization into azaheterocycles, e.g., pyrroles, quinolines or 2,3-dihydropyridines depending on the nature and structure of the substituent at the nitrogen atom …”

Section: Introductionmentioning

confidence: 99%

A One-Pot Assembly of Fully Substituted Alkyl 5-Aminothiophene-2-carboxylates from Allenes, Isothiocyanates, and Alkyl 2-Bromoacetates

et al. 2017

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A novel simple approach to highly functionalized multisubstituted thiophenes such as alkyl 4-alkoxy-5-amino-3-methylthiophene-2-carboxylates through the one-pot sequential reaction of α-lithiated alkoxyallenes with isothiocyanates and alkyl 2-bromoacetates has been discovered. The process proceeds quickly (30-45 min) via in situ formation and intramolecular cyclization of alkyl 2-[(2-alkoxybuta-2,3-dienimidoyl)sulfanyl]acetates (1-aza-1,3,4-trienes).

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Section: Introductionmentioning

confidence: 99%

A One-Pot Assembly of Fully Substituted Alkyl 5-Aminothiophene-2-carboxylates from Allenes, Isothiocyanates, and Alkyl 2-Bromoacetates

et al. 2017

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“…The chemistry of allenes has captivated the scientific community, over the past few decades, and is now regarded as one of the hot topics in Organic Chemistry . Once regarded as too reactive to bear any synthetic value, allenes have proven to be relatively stable moieties, also found in many natural products . Allenes exhibit unique chemical, conformational, and structural characteristics, as well as important applications in synthetic Organic Chemistry, catalysis, diastereoselective synthesis, and pharmaceuticals. − ,− ,, Their synthetic value is easily realized, considering the plethora of useful organic transformations they can undergo.…”

Section: Introductionmentioning

confidence: 99%

“…Once regarded as too reactive to bear any synthetic value, allenes have proven to be relatively stable moieties, also found in many natural products . Allenes exhibit unique chemical, conformational, and structural characteristics, as well as important applications in synthetic Organic Chemistry, catalysis, diastereoselective synthesis, and pharmaceuticals. − ,− ,, Their synthetic value is easily realized, considering the plethora of useful organic transformations they can undergo. These include cyclization and cycloaddition reactions, ,, hydroarylations, hydroaminations, hydrocyanations, hydroalcoxylations, and hydroborations .…”

Section: Introductionmentioning

confidence: 99%

Zinc Iodide Catalyzed Synthesis of Trisubstituted Allenes from Terminal Alkynes and Ketones

et al. 2021

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A straightforward, user-friendly, efficient protocol for the one pot, ZnI 2 -catalyzed allenylation of terminal alkynes with pyrrolidine and ketones, toward trisubstituted allenes, is described. Trisubstituted allenes can be obtained under either conventional heating or microwave irradiation conditions, which significantly reduces the reaction time. A sustainable, widely available, and low-cost metal salt catalyst is employed, and the reactions are carried out under solvent-free conditions. Among others, synthetically valuable allenes bearing functionalities such as amide, hydroxyl, or phthalimide can be efficiently prepared. Mechanistic experiments, including kinetic isotope effect measurements and density functional theory (DFT) calculations, suggest a rate-determining [1,5]-hydride transfer during the transformation of the intermediate propargylamine to the final allene.

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“…In many cases, compounds bearing functional groups of relatively high energy level with the potential of multiple reactivity are employed, for instance nitriles, isonitriles or alkynes [ 1 – 9 ]. Not surprisingly, simple or functionalized allenes have also been used in multicomponent processes and – dependent on the substitution pattern of the allene – a remarkable variety of reactions and product types are known using the three-carbon backbone of these reactive compounds [ 10 ]. During the exploration of alkoxyallene chemistry [ 11 – 20 ] we accidently discovered a new three-component reaction leading to β-ketoenamides that are uniquely functionalized alkenes and suitable for a variety of subsequent reactions, in particular in heterocyclic synthesis.…”

Section: Introductionmentioning

confidence: 99%

The LANCA three-component reaction to highly substituted β-ketoenamides – versatile intermediates for the synthesis of functionalized pyridine, pyrimidine, oxazole and quinoxaline derivatives

Lechel

Kumar

Bera

et al. 2019

Beilstein J. Org. Chem.

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The LANCA three-component reaction of lithiated alkoxyallenes LA, nitriles N and carboxylic acids CA leads to β-ketoenamides KE in good to excellent yields. The scope of this reaction is very broad and almost all types of nitriles and carboxylic acids have successfully been used. The alkoxy group introduced via the allene component is also variable and hence the subsequent transformation of this substituent into a hydroxy group can be performed under different conditions. Enantiopure nitriles or carboxylic acids can also be employed leading to chiral KE with high enantiopurity and dinitriles or dicarboxylic acids also lead to the expected bis-β-ketoenamides. β-Ketoenamides incorporate a unique combination of functional groups and hence a manifold of subsequent reactions to highly substituted heterocyclic compounds is possible. An intramolecular aldol-type condensation reaction efficiently furnishes pyridin-4-ols PY that can be further modified by palladium-catalyzed reactions, e.g., to specifically substituted furopyridine derivatives. Condensations of β-ketoenamides with ammonium salts or with hydroxylamine hydrochloride afford pyrimidines PM or pyrimidine N-oxides PO with a highly flexible substitution pattern in good yields. The functional groups of these heterocycles also allow a variety of subsequent reactions to various pyrimidine derivatives. On the other hand, acid-labile alkoxy substituents such as a 2-(trimethylsilyl)ethoxy group are required for the conversion of β-ketoenamides into 5-acetyl-substituted oxazoles OX, again compounds with high potential for subsequent functional group transformations. For acid labile β-ketoenamides bearing bulky substituents the acid treatment leads to acylamido-substituted 1,2-diketones DK that could be converted into quinoxalines QU. All classes of heterocycles accessed through the key β-ketoenamides show a unique substitution pattern – not easily accomplishable by alternative methods – and therefore many subsequent reactions are possible.

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Allenes in Multicomponent Synthesis of Heterocycles

Cited by 5 publications

References 110 publications

A One-Pot Assembly of Fully Substituted Alkyl 5-Aminothiophene-2-carboxylates from Allenes, Isothiocyanates, and Alkyl 2-Bromoacetates

A One-Pot Assembly of Fully Substituted Alkyl 5-Aminothiophene-2-carboxylates from Allenes, Isothiocyanates, and Alkyl 2-Bromoacetates

Zinc Iodide Catalyzed Synthesis of Trisubstituted Allenes from Terminal Alkynes and Ketones

The LANCA three-component reaction to highly substituted β-ketoenamides – versatile intermediates for the synthesis of functionalized pyridine, pyrimidine, oxazole and quinoxaline derivatives

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