Institut de Chimie Moléculaire et des Matériaux d'Orsay

The main part of our research activities is based on the valorization of easily accessible and inexpensive biomass compounds (isosorbide, isomannide, natural amino acids such as L-proline, (S)-pyroglutamic acid, ...). The transformation of these compounds under 'Green Chemistry' conditions, namely, solvent-free synthesis under microwaves activation method, allowed us to prepare (reversible) functionalized chiral ionic liquids, multi-dentate ligands (amino-alcohols, diamines, phosphines,...), chiral N-heterocyclic carbenes and functionalized chiral organocatalysts. These compounds have shown excellent activities in asymmetric metal or organic catalysis. Part of the group's research activities concerns the synthesis of therapeutic products (natural or unnatural) and their derivatives for QSAR studies. Some application examples are presented below. It should be noted that during this five-year period, many international and national collaborations have been established.

Asymmetric organocatalysis

Having previously reported the synthesis of new bifunctional chiral phosphine-thiourea organocatalysts AB and C, derived from L-proline, and their applications in asymmetric [3+2] cyclisation between ethyl-butan-2,3-dienoate and N-benzylidene-p-toluenesulfonamide; we have demonstrated, in this project, that these compounds catalyzed efficiently asymmetric allylic substitution of tert-butoxycarbonyloxy-MBH adduct with phthalimide. Good yields and enantioselectivities were observed.

 

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We have also described the first example of phosphine-thiourea organocatalyzed C–S bond formation affording enantioenrichied α-methylene-β-mercapto esters in good yields and with enantiomeric excess up to 93%. In collaboration with the Prof. Sasai’s group (Osaka University), and supported by Sakura and Core-to-Core Programs (Japan-European Program), we have reported the first [4+2] annulation of allenoate and all-carbon tetrasubstituted alkenes catalyzed by an amine catalyst for the synthesis of highly functionalized 2H-and 4H-pyran derivatives. These results will open opportunities in synthesis of bioactive heterocyclic products and other pharmaceutical products.

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Chiral ligands and NHCs: Design, synthesis and applications in asymmetric catalysis

During the past five years, some new families of ligands (amino alcohols, diamines, phosphines, ...) were designed and synthesized from isosorbide and isomannide as optically pure, inexpensive biomass starting materials. The transition metal complexes formed with these ligands are evaluated for catalytic activity in asymmetric carbon-carbon, carbon-heteroatom bond formation reactions. An example of β-amino alcohol ligand in ethylation of benzaldehyde is presented. 

NHCOrganocatalysis.png In continuation of our research on the design and synthesis of new chiral ligands for asymmetric catalysis, a new and flexible procedure for the preparation of cis- and trans-bicyclic functionalized chiral azolinium salts, precursors toN-heterocyclic carbenes, derived from L-proline and (S)-pyroglutamic acid has been developed. The efficiency of these NHC ligands has been evaluatedin asymmetric allylic substitution and in conjugate addition of Grignard reagent to α,β-unsaturated ketones. This work is currently underway in our group

 

 

 

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Reversible (chiral) ionic liquids: Design, synthesis and applications in (asymmetric) organic synthesis

In continuation of our research on the synthesis and applications of chiral ionic liquids as new chiral reaction media for asymmetric synthesis and catalysis, of which G. Vo-Thanh is one of the pioneers in this research field,we have managed to synthesize and formulate, in collaboration with Dr. F.-D. Boyer (ICSN-Gif sur Yvette), a novel class of reversible chiral ammonium carbamate-based ionic liquids derived from natural amino acids. Silylamines reacted reversibly with CO2 to form ammonium carbamates referring to as RevCILs. Some physical properties of these chiral ammonium carbamate salts were measured, especially their reversibility temperature and their stability which were determined thanks to DSC and TGA analyses. The properties of reversibility, chirality, and ease of preparation should make these silylamine-ionic liquid phases as promising solvents and/or catalysts for several applications, especially in asymmetric catalysis fields. It should be noted that for the first time, single-component RevCILS derived from natural amino acids have been reported. This work is currently underway in our group.

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Fluorinated compounds chemistry

This work focuses on the preparation of a new family of (chiral) perfluorinated sulfoximines and sulfinimines. Different transformations and functionalizations of fluorinated sulfoximines have been developed in collaboration with Dr. E. Magnier’s group in Versailles. These new compounds are used as organocatalysts or (chiral) ligands for transition metal catalyzed reactions. This methodology is applied to the synthesis of therapeutic products, eg Prazosin analogues. 

 

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Synthesis of Bio-based polymers for antibacterial surface applications. Structure-Antibacterial Activity Relationships (SAAR) studies

As part of an agreement signed between Paris-Sud University and VAST (Vietnam Academy of Science and Technology), G. Vo-Thanh, in collaboration with researchers at the Institute of Chemistry of Natural Substances in Hanoi, has developed the synthesis of Febrifugine and GA derivatives. Thus, 10 Febrigugine and 25 GA derivatives were synthesized. In vitro, antimalarial activity evaluation, for Febrifugine derivatives, indicated that all synthesized compounds had strong antimalarial activity against both chloroquine-sensitive and -resistant strains of P. falciparum. The cytotoxicity of GA derivatives was tested on the cancerous cell lines Lu1, HepG2, RD and showed very promising results. SAR studies are currently underway on new synthesized analogs. 

 

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Structure-Activity Relationship studies of Febrifugine, antimalarial activity, and Gambogic Acid (GA), antitumor activity

Preparation of new polymers and polymeric surfaces with antibacterial properties would be of great interest in different areas such as household, industry, hospital. These polymers could be used respectively as disinfection solution or to manufacture sheets and clothes for protection against nosocomial infections. They could be obtained by a polymerization process using monomers which are obtained in some steps starting from isosorbide. This project, in collaboration with Prof. P. Roger (ICMMO), is funded by the Roquette Company and will not be detailed for confidentiality reasons

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Enzymatic promiscuity

Recently, M. Toffano, in collaboration with Prof. L. Zouioueche (Annaba University), have developed a simple and eco-friendly preparation of α-aminophosphonates and Bis(α-aminophosphonates) viaa multicomponent Kabachnik-Fields reaction in the presence of an immobilized Candida Antarctica lipase as catalyst under solvent-free conditions

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Recent publications:

An efficient and recyclable ionic diphosphine-based Ir-catalyst for hydroaminomethylation of olefins with H2O as hydrogen source. H. Liu, D. Yang, D.-L. Wang, P. Wang, Y. Lu, G. Vo-Thanh, Y. Liu, Chemical Communications, 2018, 54, 7979-7982

Facile Preparation of Vinyl S-Trifluoromethyl NH Aryl Sulfoximines. A.-L. Barthelemy, A. Prieto, P. Diter, J. Hannedouche, M. Toffano, E. Anselmi, E. Magnier, Eur. J. Org. Chem., 2018, 3764-3770

Novel Class of Reversible Chiral Ionic Liquids Derived from Natural Amino Acids: Synthesis and Characterization. L. Bouchardy, V. Rodriguez-Ruiz, F.-D. Boyer, C. Bournaud, M. Toffano, P. Judeinstein, G. Vo-Thanh, ChemistrySelect, 2018, 3, 958-962

Amphiphilic Zwitterionic phosphine based Au(I)-complex as efficient and recyclable catalyst for hydration of alkynes free of additional additives. X. Chen, X. Ye, W.-Y. Liang, Q. Zhou, G. Vo-Thanh, Y. Liu, Molecular Catalysis, 2018, 448, 171-176

Imidazolium based Ionic liquids as efficient reagents for lignin C-O bond cleavage. M. Thierry, A. Majira, B. Pégot, L. Cezard, F. Bourdreux, G. Clément, F. Perreau, S. Boutet-Mercey, P. Diter, G. Vo-Thanh, C. Lapierre, P.-H. Ducrot, E. Magnier, S. Baumberger, B. Cottyn, ChemSusChem, 2018, 11, 439-448

Promiscuous lipase catalyzed a new P–C bond formation: Green and efficient protocol for one‐pot synthesis of α‐aminophosphonates. S. Guezane‐lakoud, M. Toffano, L. Aribi‐zouioueche, Heteroatom Chemistry, 2017, 28, e21408

Fast and Efficient Hantzsch Synthesis using Acid-activated and Cation-exchanged Montmorillonite Catalysts under Solvent-free Microwave Irradiation Conditions. D. D. Pham, N. T. Le, G. Vo-Thanh, ChemistrySelect, 2017, 2, 12041-12045

Chiral Organocatalyzed Intermolecular Rauhut–Currier Reaction of Nitroalkenes with Ethyl Allenoate. S. Takizawa, M. Sako, K. Kishi, M. Shigenobu, G. Vo-Thanh, H. Sasai, Chemical and Pharmaceutical Bulletin, 2017, 65, 997-999

Efficient and Green Synthesis of 4H-pyran derivatives under Ultrasound Irradiation in the presence of K2CO3 supported on Acidic Montmorillonite. D. D. Pham, G. Vo-Thanh, N. T. Le, Synthetic Communications, 2017, 47, 1684-1691

S-Trifluoromethyl Sulfoximine as a Directing Group in Ortho-Lithiation Reaction toward Structural Complexity. T.-N. Le, P. Diter, B. Pégot, C. Bournaud, M. Toffano, R. Guillot, G. Vo-Thanh, E. Magnier, Org. Lett., 2016, 18, 5102-5105

Organocatalyzed [4+2] Annulation of All-Carbon Tetrasubstituted Alkenes with Allenoates: Synthesis of Highly Functionalized 2H- and 4H-Pyran Derivatives. T.-T.-D. Ngo, K. Kishi, M. Sako, M. Shigenobu, C. Bournaud, M. Toffano, R. Guillot, J.-P. Baltaze, S. Takizawa, H. Sasai, G. Vo-Thanh, ChemistrySelect, 2016, 1, 5414-5420

Biosourced Ligands from Isosorbide for the Ethylation of Aldehydes or Alkynylation of Imines. K.-D. Huynh, H. Ibrahim, L. Bouchardy, C. Bournaud, E. Kolodziej, M. Toffano, G. Vo-Thanh, Asian Journal of Organic Chemistry, 2016, 1242-1246

Phosphine–Thiourea-Organocatalyzed Asymmetric C−N and C−S Bond Formation Reactions. T.-T.-D. Ngo, T.-H. Nguyen, C. Bournaud, R. Guillot, M. Toffano, G. Vo-Thanh, Asian Journal of Organic Chemistry, 2016, Volume 5, Issue 7, 895–899

Synthesis of Novel Triazolo Cyclobutane Nucleoside Analogues. T.-T.-T. Tran, N.-T. Ngo, T.-H. Dinh, G. Vo-Thanh, S. Legoupy, Bull. Korean Chem. Soc, 2015, 36, 1390-1395

Functionalized S-perfluorinated sulfoximines: preparation and evaluation in catalytic process. T.-N. Le, P. Diter, B. Pégot, C. Bournaud, M. Toffano, R. Guillot, G. Vo-Thanh, Y. Yagupolskii, E. Magnier, Journal of Florine Chemistry, 2015, 179, 179-187

P-Aryl-Diphenylphospholanes and their Phospholanium Salts as Efficient Monodentate Ligands for Asymmetric Rhodium-Catalyzed Hydrogenation. C. Dobrota, J.-C. Fiaud, M. Toffano, ChemCatChem, 2015, 7, 144-148