A new strategy for the synthesis of pyridines from N-propargylic β-enaminothiones.

A new method for the synthesis of 2,4,5-trisubstituted pyridines from N-propargylic β-enaminothiones is reported. β-Enaminothiones were prepared by thionation of the corresponding β-enaminones with Lawesson's reagent. When treated with diisopropylamine in DMF at room temperature, N-propargylic β-enaminothiones yielded 2,4,5-trisubstituted pyridines in moderate to high yields, along with small amounts of 2-methylene-2,3-dihydro-1,4-thiazepines. The reaction was found to be general for a broad range of N-propargylic β-enaminothiones and tolerated the presence of aromatic, heteroaromatic and aliphatic groups with electron-withdrawing and electron-donating substituents. The method could be widened to the internal alkyne-tethered N-propargylic β-enaminothiones. This operationally simple method may provide rapid access to a library of functionalized pyridines of pharmacological interest.

• Publication year

  2019

• Venue

  Organic and biomolecular chemistry

• Publication date

  2019-02-27

• Fields of study

  Medicine, Chemistry

• Identifiers
  DOI 10.1039/c8ob03180kPMID 30758002
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Synthesis of 1,4-Thiazepines.

  2018cited by this paper
• One-pot synthesis of iodine-substituted 1,4-oxazepines

  2018cited by this paper
• Transition-Metal-Free Cascade Approach toward 2-Alkoxy/2-Sulfenylpyridines and Dihydrofuro[2,3-b]pyridines by Trapping In Situ Generated 1,4-Oxazepine.

  2017cited by this paper
• Silver-catalyzed chemoselective annulation of propargyl amines with alkynes for access to pyridines and pyrroles

  2017cited by this paper
• Zinc Chloride Mediated Synthesis of 1,4‐Oxazepines from N‐Propargylic β‐Enaminones

  2017cited by this paper
• N -Propargylic β -enaminocarbonyls: powerful and versatile building blocks in organic synthesis

  2017cited by this paper
• Base-catalyzed cascade synthesis of 2,3-dihydrofuro[2,3-b]pyridines and 2,3-dihydro-1H-pyrrolo[2,3-b]pyridines from N-propargylic β-enaminones.

  2017cited by this paper
• New page to access pyridine derivatives: synthesis from N-propargylamines

  2016cited by this paper
• Selective synthesis of functionalized pyrroles from 3-aza-1,5-enynes.

  2016cited by this paper
• Base-mediated regiospecific cascade synthesis of N-(2-pyridyl)pyrroles from N-propargylic β-enaminones

  2016cited by this paper
• Base-promoted intramolecular cyclization of N-alkyl, N-propargylic β-enaminones for the synthesis of polysubstituted pyrroles

  2016cited by this paper
• Modular Synthesis of Highly Substituted Pyridines via Enolate α-Alkenylation.

  2015cited by this paper
• Gold-Catalyzed Intramolecular Cyclization of N-Propargylic β-Enaminones for the Synthesis of 1,4-Oxazepine Derivatives.

  2015cited by this paper
• Base-Catalyzed Selective Synthesis of 2-Azabicyclo[3.2.0]hept-2-enes and Sulfonyl Vinyl-Substituted Pyrroles from 3-Aza-1,5-enynes.

  2015cited by this paper
• Base-Promoted β-C(sp(3))-H Functionalization of Enaminones: An Approach to Polysubstituted Pyridines.

  2015cited by this paper
• Thiophene-Based Conjugated Polymers with Photolabile Solubilizing Side Chains

  2015cited by this paper
• Synthesis of Polysubstituted Pyrroles from Activated Alkynes and N-Propargylamines through Base-Catalyzed Cascade Reaction

  2015cited by this paper
• Facile synthesis of iodopyridines from N-propargylic β-enaminones via iodine-mediated electrophilic cyclization

  2015cited by this paper
• Fundamentals of heterocyclic chemistry

  2015cited by this paper
• Base-Promoted N-Pyridylation of Heteroarenes Using N-Propargyl Enaminones as Equivalents of Pyridine Scaffolds.

  2015cited by this paper
• Bioactivation potential of thiophene-containing drugs.

  2014cited by this paper
• Rh(III)-Catalyzed Decarboxylative Coupling of Acrylic Acids with Unsaturated Oxime Esters: Carboxylic Acids Serve as Traceless Activators

  2014cited by this paper
• Fused-thiophene based materials for organic photovoltaics and dye-sensitized solar cells

  2014cited by this paper
• Fully regiocontrolled polyarylation of pyridine.

  2014cited by this paper
• Fluorine in pharmaceutical industry: fluorine-containing drugs introduced to the market in the last decade (2001-2011).

  2014cited by this paper
• [5C + 1N] Annulation of 2,4-pentadienenitriles with hydroxylamine: a synthetic route to multi-substituted 2-aminopyridines.

  2013cited by this paper
• Intramolecular cyclization of N-propargylic β-enaminones catalyzed by silver

  2013cited by this paper
• Synthesis of substituted pyridines from cascade [1 + 5] cycloaddition of isonitriles to N-formylmethyl-substituted enamides, aerobic oxidative aromatization, and acyl transfer reaction.

  2013cited by this paper
• Synthesis of multisubstituted pyridines.

  2013cited by this paper
• Rh(III)-catalyzed regioselective synthesis of pyridines from alkenes and α,β-unsaturated oxime esters.

  2013cited by this paper
• Introduction of fluorine and fluorine-containing functional groups.

  2013cited by this paper
• Design and synthesis of pyrrolotriazepine derivatives: an experimental and computational study.

  2013cited by this paper
• Recent developments in the synthesis of five- and six-membered heterocycles using molecular iodine.

  2012cited by this paper
• Rhenium-catalyzed regioselective synthesis of multisubstituted pyridines from β-enamino ketones and alkynes via C-C bond cleavage.

  2012cited by this paper
• Synthesis of pyridines from ketoximes and terminal alkynes via C-H bond functionalization.

  2012cited by this paper
• Pioglitazone

  2012cited by this paper
• Ni-catalyzed alkenylation of triazolopyridines: synthesis of 2,6-disubstituted pyridines.

  2012cited by this paper
• Chemo- and regioselective assembly of polysubstituted pyridines and isoquinolines from isocyanides, arynes, and terminal alkynes.

  2012cited by this paper
• Synthesis of Thiophene-Based π-Conjugated Polymers Containing Oxadiazole or Thiadiazole Moieties and Their Application to Organic Photovoltaics

  2012cited by this paper
• Atazanavir

  2012cited by this paper
• Synthesis of pyridine and dihydropyridine derivatives by regio- and stereoselective addition to N-activated pyridines.

  2012cited by this paper
• Highly regioselective migration of the sulfonyl group: easy access to functionalized pyrroles.

  2012cited by this paper
• Dual Heterogeneous Catalysis for a Regioselective Three‐ Component Synthesis of Bi‐ and Tri(hetero)arylpyridines

  2012cited by this paper
• Rabeprazole

  2012cited by this paper
• Bone turnover markers and bone mineral density response with risedronate therapy: Relationship with fracture risk and patient adherence

  2011cited by this paper
• Pyridines from azabicyclo[3.2.0]hept-2-en-4-ones through a proposed azacyclopentadienone.

  2011cited by this paper
• Tandem one-pot synthesis of polysubstituted pyridines using the Blaise reaction intermediate and 1,3-enynes.

  2011cited by this paper
• Synthesis of heterocycles via electrophilic cyclization of alkynes containing heteroatom.

  2011cited by this paper
• A simple and highly efficient iron catalyst for a [2+2+2] cycloaddition to form pyridines.

  2011cited by this paper
• Thiophene-based conjugated oligomers for organic solar cells

  2011cited by this paper
• Halogen atoms in the modern medicinal chemistry: hints for the drug design.

  2010cited by this paper
• A New Modification of the Bohlmann-Rahtz Pyridine Synthesis

  2010cited by this paper
• Synthesis of pyrroles by gold(I)-catalyzed amino-claisen rearrangement of N-propargyl enaminone derivatives.

  2010cited by this paper
• Bohlmann-Rahtz Cyclodehydration of Aminodienones to Pyridines Using N-Iodosuccinimide

  2010cited by this paper
• Recent strategies for the synthesis of pyridine derivatives.

  2010cited by this paper
• Novel Approaches to Inhibition of Gastric Acid Secretion

  2010cited by this paper
• A new strategy for the synthesis of poly-substituted 3-H, 3-fluoro, or 3-trifluoromethyl pyridines via the tandem C-F bond cleavage protocol.

  2010cited by this paper
• Targeted Cancer Therapies in the Twenty‐First Century: Lessons From Imatinib

  2010cited by this paper
• Alkyne activation with Brønsted acids, iodine, or gold complexes, and its fate leading to synthetic application.

  2009cited by this paper
• Review article: dual delayed release formulation of dexlansoprazole MR, a novel approach to overcome the limitations of conventional single release proton pump inhibitor therapy

  2009cited by this paper
• Fluorine in medicinal chemistry: a century of progress and a 60-year retrospective of selected highlights.

  2009cited by this paper
• Synthesis of pyridines and pyrazines using an intramolecular hydroamination-based reaction sequence.

  2009cited by this paper
• Of mice and men: blowing away the cobwebs from the mechanism of action of niacin on HDL metabolism.

  2008cited by this paper
• N-propargylic beta-enaminones: common intermediates for the synthesis of polysubstituted pyrroles and pyridines.

  2008cited by this paper
• Regioselective de novo synthesis of cyanohydroxypyridines with a concerted cycloaddition mechanism.

  2008cited by this paper
• Niacin Increases HDL by Reducing Hepatic Expression and Plasma Levels of Cholesteryl Ester Transfer Protein in APOE*3Leiden.CETP Mice

  2008cited by this paper
• Nakinadine A, a Novel Bis-pyridine Alkaloid with a β-Amino Acid Moiety from Sponge Amphimedon sp.

  2007cited by this paper
• Eszopiclone for late-life insomnia

  2007cited by this paper
• The fascinating construction of pyridine ring systems by transition metal-catalysed [2 + 2 + 2] cycloaddition reactions.

  2007cited by this paper
• Use of Lawesson's reagent in organic syntheses.

  2007cited by this paper
• Atazanavir: a review of its use in the management of HIV infection.

  2005cited by this paper
• Sulfone-mediated synthesis of polysubstituted pyridines

  2005cited by this paper
• Synthesis of pyridine and 2,2′-bipyridine derivatives from the aza Diels–Alder reaction of substituted 1,2,4-triazines

  2004cited by this paper
• A new mild method for the one-pot synthesis of pyridines

  2004cited by this paper
• De novo Synthesis of Substituted Pyridines

  2004cited by this paper
• Specific Targeted Therapy of Chronic Myelogenous Leukemia with Imatinib

  2003cited by this paper
• A pyridine ring-containing ecdysteroid from Diploclisia glaucescens

  2003cited by this paper
• Construction of pyridine rings by metal-mediated [2 + 2 + 2] cycloaddition.

  2003cited by this paper
• Acetylene-allene rearrangement of propargyl systems X—CH2—C≡CH (X = H, Me, NMe2, OMe, F, SMe): an ab initio study

  2002cited by this paper
• Synthesis of some unsymmetrical bridged terpyridines.

  2002cited by this paper
• Effect of desloratadine versus placebo on nasal airflow and subjective measures of nasal obstruction in subjects with grass pollen-induced allergic rhinitis in an allergen-exposure unit.

  2002cited by this paper
• A new one-step synthesis of pyridines under microwave-assisted conditions

  2002cited by this paper
• Significant acceleration of 6 pi-azaelectrocyclization resulting from a remarkable substituent effect and formal synthesis of the ocular age pigment A2-E by a new method for substituted pyridine synthesis.

  2001cited by this paper
• Metabolism of fluorine-containing drugs.

  2001cited by this paper
• Pioglitazone: mechanism of action.

  2001cited by this paper
• Effects on 24-hour intragastric pH: a comparison of lansoprazole administered nasogastrically in apple juice and pantoprazole administered intravenously

  2001cited by this paper
• Review article: comparison of the pharmacokinetics, acid suppression and efficacy of proton pump inhibitors

  2000cited by this paper
• Total Synthesis of the Rubrolone Aglycon

  2000cited by this paper
• INTERFACE CONTROL OF LIGHT-EMITTING DEVICES BASED ON PYRIDINE-CONTAINING CONJUGATED POLYMERS

  1999cited by this paper
• Multiple bond migration with participation of a protophilic agent

  1999cited by this paper
• ELECTROPHILE MEDIATED HETEROATOM CYCLIZATIONS ONTO C-C π-BONDS. PART 1: HALOGEN AND CHALCOGEN MEDIATED CYCLIZATION

  1997cited by this paper
• ELECTROPHILE MEDIATED HETEROATOM CYCLIZATIONS ONTO C-C π-BONDS. PART 2: METAL ION MEDIATED CYCLIZATION

  1997cited by this paper
• Medicinal Natural Products

  1997cited by this paper
• A Convenient and Regioselective Synthesis of 4-Trifluoromethylpyridines

  1997cited by this paper
• Poly (p-pyridine) - and poly (p-pyridyl vinylene) -based polymers: their photophysics and application to SCALE devices

  1996cited by this paper
• Ultrasound assisted Diels-Alder reactions of 1-azadienes with “normal” electronic demand.

  1995cited by this paper
• Omeprazole: A Comprehensive Review

  1993cited by this paper
• Synthesis of genotoxic heterocyclic amines Trp-P-1 and Trp-P-2

  1992cited by this paper
• Synthesis of 1-Substituted 2-[(2S)-2-Pyrrolidinyl]pyridine from L-Proline

  1990cited by this paper
• 2-(1-Alkenyl)- and 2-aryl-substituted four-membered cyclic nitrones as precursors for 2,3,4-substituted pyridines and quinolines

  1989cited by this paper

• Facile synthesis of unknown 6,7-dihydrofuro[3,4-c]pyridines and 3,4-diaryloylpyridines from N-homopropargylic β-enaminones.

  2025cites this paper
• One-Pot Sequential Hydroamination Protocol for N-Heterocycle Synthesis: One Method To Access Five Different Classes of Tri-Substituted Pyridines.

  2023cites this paper
• One-Pot Synthesis of 2-Acetyl-1H-pyrroles from N-Propargylic β-Enaminones via Intermediacy of 1,4-Oxazepines.

  2021cites this paper
• Chemoselective synthesis of β-enaminones from ynones and aminoalkyl-, phenol- and thioanilines under metal-free conditions

  2021cites this paper
• Six-membered ring systems: pyridines and benzo derivatives

  2021cites this paper
• 1,4-Oxazepines and 1,4-Thiazepines

  2021cites this paper
• Base‐Promoted Synthesis of 3‐Alkenyl ‐2‐pyridones from N ‐Propargyl ‐β‐enaminones and Aryl Aldehydes

  2021cites this paper
• Indole‐based novel organic anode catalyst for glucose electrooxidation

  2021cites this paper
• Design, Synthesis, andIn vitroEvaluation of Thieno[a]dibenzothiophene Derivatives

  2020cites this paper
• A facile synthesis of 6-chloro-2-methylene-2,3-dihydro-1,4-oxazepines from N-propargylic β-enaminones

  2020cites this paper
• A facile synthesis of 6-[(4-nitrophenyl)thio]-substituted 2-methylene-2,3-dihydro-1,4-oxazepines from N-propargylic β-enaminones

  2020cites this paper
• A facile one-pot synthesis of 2-(prop-2-yn-1-ylidene)-2,3-dihydro-1,4-thiazepines

  2020cites this paper
• Synthesis of 3-[(4-nitrophenyl)thio]-substituted 4-methylene-1-pyrrolines from N-propargylic β-enaminones.

  2020cites this paper
• A New Strategy for the Synthesis of 4‐Propargyl‐Substituted 1 H ‐Pyrroles from N ‐(5‐phenyl‐2,4‐pentadiynyl) β‐Enaminones

  2019cites this paper