Synthesis of new heterocycles

Keywords :
methyl coumalate ; renewable feedstock ; aromatic heterocycles

2023

3-Hydroxypyridinyl-Substituted-1,2,4-Triazoles as New ESIPT Based Fluorescent Dyes: Synthesis and Structure–Fluorescence Properties Correlations. A. Nina-Diogo, B. Bertrand, S. Thorimbert, G. Gontard, S. Nassem-Kahn, A. Echeverri, J. Contreras-García, C. Allain, G. Lemercier, E. Luppi, C. Botuha. Advanced Optical Materials 2023, 11, 2300336. http://doi.org/10.1002/adom.202300336

This report presents the design, synthesis, and photophysical study of two new series of promising fluorescent trisubstituted triazoles, 3-hydroxypyridinyl substituted-1,2,4-triazoles (PyOHTr) and 2-pyridonyl substituted-1,2,4-triazoles (PyCOTr). An excited state intramolecular proton transfer (ESIPT) fluorescence mechanism is evidenced for PyOHTr molecules by ab initio theoretical calculations. These fluorescent dyes possess unique optical properties such as large Stokes shifts, dual emission, solvatochromism, solid-state emission and, for one of them, a white light emission, rendering them particularly attractive for future applications in both medicinal chemistry and materials science.


1,6-Naphthyridin-7(6H)-ones: synthesis and optical properties. A. Beghennou, G. Gontard, H. Dossmann, K. Passador, S. Thorimbert, V. Corcé, C. Botuha. Organic & Biomolecular Chemistry 2023, 21, 2976-2982. http://doi.org/10.1039/d3ob00081h

Efficient synthesis of original 1,6-naphthyridin-7(6H)-ones and their optical properties are described. Their powerful fluorescence properties including dual fluorescence, solvatochromism, acidochromism, large Stokes shifts and high quantum yields, suitable for biological applications or as luminescent devices in materials science, are evidenced.


Iron Catalyzed Dearomatization of Pyridines into Annelated Azepine Derivatives in a One-Step, Three-Component Reaction. Mamontov, A. ; Chang, L. ; Dossmann, H. ; Bertrand, B. ; Dechoux, L. ; Thorimbert, S. Org. Lett. 2023 ; http://dx.doi.org/10.1021/acs.orglett.2c04088

“Commercially available Fe(TTP)Cl catalyzes three-component dearomative formal cycloaddition reactions between pyridines, diazo compounds, and coumalates. Diversely substituted annelated seven-membered N-heterocycles could be generated in less than 10 min in one step at room temperature. The reaction is compatible to gram scale. The extension to benzimidazoles in place of pyridines has been successfully demonstrated. The mechanism of this reaction has been carefully examined by computational studies that corroborate the observed regioselectivities.”

2021

A Solvent-Free, Catalyst-Free Formal [3+3] Cycloaddition Dearomatization Strategy : Towards New Fluorophores for Biomolecules Labelling. Chang, L. ; Fischer-Durand, N. ; Gontard, G. ; Bertrand, B. ; Thorimbert, S. ; Dechoux, L.ChemSusChem 2021, 14, 1821–1824 ; http://dx.doi.org/10.1002/cssc.202100301.

No solvent, no catalyst : A single solvent-free step starting from the biobased methyl coumalate enables the dearomatization of a broad range of heterocycles affording in high yields luminescent polycyclic compounds bearing a carboxylic acid function for later grafting onto biomolecules.”

2020

Synthetic Strategy Studies for a Concise Access to Functionalized Pyrano[4,3-b]Pyridin-7-Ones : An Entry to Semi-Rigid Analogs of Antihistamines. Beghennou, A. ; Passador, K. ; Passador, A. ; Corcé, V. ; Thorimbert, S. ; Botuha, C. Eur. J. Org. Chem. 2020, 5880–5889 ; http://dx.doi.org/10.1002/ejoc.202001016.

“Original pyranopyridinones containing polyfunctionalized delta-lactones ring have been synthesized using three concise and efficient synthetic methodologies. Potential semi-rigid analogs of antihistamines containing a pyranopyridinone scaffold have also been prepared using the outlined synthetic methodologies.”

2019

The Bio-Based Methyl Coumalate Involved Morita–Baylis–Hillman Reaction. Chang, L. ; Thorimbert, S. ; Dechoux, L. Org. Biomol. Chem. 2019, 17, 2784–2791 ; http://dx.doi.org/10.1039/C9OB00328B.

“We report the first use of renewable, bio-based, non-hazardous feedstock methyl coumalate (MC) in organocatalyzed Morita–Baylis–Hillman (MBH) reactions. This atom-economical pathway employs inexpensive Et3N as a catalyst in ethanol. Synthon MC efficiently constructs C–C bonds with various imines and aldehydes in moderate to good yields. This catalytic process is triggered via an unprecedented 1,6-conjugated addition, as opposed to the classical MBH reaction. Moreover, this methodology expands Morita–Baylis–Hillman donor capabilities to a 2-pyrone derivative for the first time. MBH adducts described herein could be applied to the synthesis of fine chemicals with biologically active structural cores, such as diphenylmethanol, hydroisobenzofurans, and hydroisoindoles.”

2018

Heteroaromatic Rings of the Future’ : Exploration of Unconquered Chemical Space. Passador, K. ; Thorimbert, S. ; Botuha, C. Synthesis 2018, 51, 384–398 ; http://dx.doi.org/10.1055/s-0037-1611279.

“William Pitt and co-workers have created a virtual exploratory heterocyclic library ‘VEHICLe’ containing over 200 unconquered bicyclic heteroaromatic rings, synthetically feasible with potential medicinal interest. Since the publication of the 22 ‘heteroaromatic rings of the future’ by Pitt in 2009, 15 of them have been successfully synthesized as bicyclic or polycyclic forms and evaluated for applications in both biology and material science. This short review presents the critical synthesis associated with innovative synthetic methodologies of the synthetically conquered ring scaffolds from the list of 22 with a spotlight on the scientific contribution of this fascinating article for the expansion of the chemical diversity.”

2017

Chemoselective Access to π-Conjugated Heterocycles by Stille and Sonogashira Reactions on 2-Substituted 4H-Pyrido[e][1,3]Oxazin-4-Ones. Le Falher, L. ; Mumtaz, A. ; Nina Diogo, A. ; Thorimbert, S. ; Botuha, C. Eur. J. Org. Chem. 2017, 2017, 827–832 ; http://dx.doi.org/10.1002/ejoc.201601338.

“Efficient site-selective Pd-catalyzed cross-coupling reactions of 2-substituted-4H-pyrido[e][1,3]oxazin-4-ones are reported that allow rapid access to polyfunctionalized precursors with extended π-conjugation for further application as fluorescent materials.”


Chang, L. ; Plevová, K. ; Thorimbert, S. ; Dechoux, L. Preparation of Substituted 2H-Pyrans via a Cascade Reaction from Methyl Coumalate and Activated Methylene Nucleophiles. J. Org. Chem. 2017, 82, 5499–5505 ; http://dx.doi.org/10.1021/acs.joc.7b00761.

“The reaction of methyl coumalate with a wide range of methylene active compounds, such as keto-esters or keto-sulfones and cyclic or acyclic diketones, afforded more than 30 2,3,5,6-tetrasubstituted 2H-pyrans. The reaction proceeds via a cascade reaction involving a Michael addition-6π-electrocyclic ring opening-proton transfer and 6π electrocyclization, in which a variety of functional groups were tolerated.”