Green Synthesis of 1,4-Dihydropyridines through Catalyst-Free Multicomponent Hantzsch Reaction in an Undergraduate Teaching Laboratory

Journal of Chemical Education, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 27, 2025

Multicomponent reactions (MCRs) are fascinating chemical processes where three or more starting materials come together to form a single product. By exploring various MCRs, second-year undergraduate students learn about the synergy between different functional groups and how they influence reactivity, power of streamlined approach compared conventional stepwise reactions, critical thinking MCR mechanisms. Herein, we introduce valuable synthetic method for constructing heterocyclic compounds through multiple-component condensation/cycloaddition process. Specifically, focus on 1,4-dihydropyridine (1,4-DHP), privileged N-heterocyclic scaffold widely used in medicinal chemistry, particularly 4-aryl-3,5-dicarboxylated derivatives. The experiment provides an excellent opportunity explore concept green chemistry while synthesizing structurally interesting useful molecules using readily available materials. achieve this condensation reaction 2-furaldehyde (furfural), acetoacetic acid tert-butyl ester, ammonium acetate. Key features teaching include following. (1) reaction: involves concise, multicomponent with short time. (2) Catalyst-free: Notably, proceeds without need solvents catalysts. (3) Visually striking system: change system is visually evident, enhancing learning experience. (4) Useful methodology drug synthesis: has practical implications synthesis. We successfully implemented proposal across five parallel student groups, involving approximately 150 participants. experimental procedures encompass organic synthesis, thin-layer chromatography (TLC), nuclear magnetic resonance (NMR) analysis.

Language: Английский

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Gold-Catalyzed Regio- and Diastereoselective [3 + 2] Cycloaddition/Unactivated C(sp³)–H Bond Insertion of o-1,6-Enynyl Benzaldehydes to Oxa-Bridged Polycycles

Organic Letters, Journal Year: 2025, Volume and Issue: unknown

Published: April 4, 2025

An efficient and expeditious method to assemble oxa-bridged polycycles bearing up six contiguous stereocenters from a gold(I)-catalyzed [3 + 2] cycloaddition/unactivated C(sp3)-H bond insertion cascade of o-1,6-enynyl benzaldehydes at low catalyst loading 2 mol % is described.

Language: Английский

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Amine-Release Annulation of Enaminones: Bimetallic Co-Catalytic Synthesis of Cyclopentadienes from Alkynes

Organic Letters, Journal Year: 2023, Volume and Issue: 25(25), P. 4688 - 4693

Published: June 20, 2023

An efficient Au(III)/Ag(I) co-catalytic platform has been established for the synthesis of cyclopentadienes through amine-release annulation enaminones with alkynes. Vinylcarbenoids that were generated from 1,2-migration propargyl esters may undergo a tandem process to give aminocyclopentenes as key intermediates. The bimetal catalytic system is compatible broad substrate scope under mild reaction conditions. obtained are allowed late-stage modifications into complex molecules high chemo- and regioselectivities.

Language: Английский

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Desymmetrization of Cyclohexadienones via [3+2]/[2+1] Domino Annulation: Access to Cyclopropane Fused Tricyclic Enones

Advanced Synthesis & Catalysis, Journal Year: 2024, Volume and Issue: 366(13), P. 2939 - 2944

Published: April 26, 2024

Abstract A [3+2]/[2+1] domino annulation reaction of cyclohexadienones and α‐aryl vinylsulfonium salts has been reported. range cyclopropane fused tricyclic enones bearing four contiguous stereocenters were obtained as a single diastereomer in 44–93% yields. The synthetic utility was demonstrated with the gram‐scale reactions further transformations products.

Language: Английский

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Denitrative Formal [5 + 1] Cycloaddition of 1‐(2‐Nitrophenyl)‐2‐yn‐1‐ones with Thioacetamide under Transition Metal‐Free Conditions. Synthesis of Thiochromen‐4‐ones

European Journal of Organic Chemistry, Journal Year: 2024, Volume and Issue: unknown

Published: May 31, 2024

Abstract A new strategy for thiochromen‐4‐one synthesis that relies on the denitrative formal [5+1] cycloaddition of 1‐(2‐nitrophenyl)‐2‐yn‐1‐ones with thioacetamide is described. Achieved under reaction conditions did not require transition metal catalysis, nor exclusion air or moisture, suggested to involve exploiting propensity undergo hydrolysis basic conditions. This follows by addition ensuing sulfide anion 1,3‐alkynone and a nucleophilic aromatic substitution rearomatization cascade give S ‐heterocyclic product in yields 41–99 %.

Language: Английский

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Gold‐Catalyzed Cascade Reaction of Diynamides with Allylic Alcohols: A Versatile Platform to Allenamide, 2‐Aminofuran and Bridged [2.2.2]Octadiene Derivatives

Chemistry - A European Journal, Journal Year: 2023, Volume and Issue: 29(33)

Published: March 28, 2023

Transition metal-catalyzed divergent synthesis through alternation of the catalyst is appealing, as it provides an operationally simple way to access different valuable products, while using same reactants starting materials. Herein, a gold-catalyzed cascade reaction conjugated diynamides with allylic alcohols described. By variation catalysts, substituted allenes and furans could be obtained selectively. Mechanistic studies indicate that, after addition alcohol gold-activated diynamide, [3,3]-sigmatropic rearrangement would take place lead formation common reactive intermediate, which further convert final products Further structure has unveiled additional sequence involving intramolecular Himbert arene/allene Diels-Alder cycloaddition afford series dearomatized bearing bicyclo[2,2,2]octadiene core.

Language: Английский

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Organocatalytic enantio- and diastereoselective assembly of cyclopropane-incorporated polycyclic molecules via isobenzopyrylium ions

Chemical Science, Journal Year: 2024, Volume and Issue: 15(37), P. 15274 - 15279

Published: Jan. 1, 2024

A highly enantio- and diastereoselective organocatalytic formation of cyclopropanes embedded in a complex bridged polycyclic architecture is disclosed. In the presence chiral phosphoric acid catalyst, this reaction generates four new stereogenic centers three C-C bonds efficiently from isochromene acetals vinylboronic acids under mild conditions. Different conventional asymmetric cyclopropanation strategies, process does not involve carbenes or carbenoids. The products can serve as precursors to useful homoenolate equivalents. Mechanistically, DFT studies provided insights into key transition states enantiodetermining [4 + 2] cycloaddition, which enantioselectivity induced by phosphate counter anion isobenzopyrylium intermediate.

Language: Английский

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Direct construction of biaryl-bridged 8–11 membered N-heterocycles via gold(i)-catalyzed intramolecular [4 + 2] benzannulation of N-tethered diynyl benzaldehydes

Organic Chemistry Frontiers, Journal Year: 2023, Volume and Issue: 10(13), P. 3280 - 3287

Published: Jan. 1, 2023

A method for the expeditious assembly of a diverse range biaryl-bridged 8–11 membered N -heterocycles that relies on gold( i )-catalyzed intramolecular [4 + 2] benzannulation -tethered diynyl benzaldehydes is described.

Language: Английский

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Seven-membered rings

Progress in heterocyclic chemistry, Journal Year: 2023, Volume and Issue: unknown, P. 569 - 628

Published: Jan. 1, 2023

Language: Английский

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Theoretical insights into unraveling the mechanism, selectivity patterns, and ligand effects in gold(i)-catalyzed annulations between ynamides and isoxazoles

Organic Chemistry Frontiers, Journal Year: 2023, Volume and Issue: 11(2), P. 489 - 499

Published: Dec. 5, 2023

This cutting-edge research work presents a comprehensive and in-depth theoretical investigation on the mechanism, selectivity patterns, ligand effects in gold( i )-catalyzed annulations between ynamides isoxazoles.

Language: Английский

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