Bilan de l'équipe 2005-2009

The organization chart describes the current team with 20 permanent members involved in teaching and research (13 professors and “maître de conference”, 7 CNRS researchers) and 4 permanent members for technical and administrative support. Currently AM 2N hosts 23 PhD students, 8 post-docs and over the last 4 years: 14 PhD thesis were defended, 17 post-docs were received and 10 foreign colleagues visited AM 2N for more than 1 month.

7 Young researchers joined the group since 2005 on academic positions (ENSCM or CNRS). It is worth noting that all of them are coming from different fields of organic chemistry, all did a post-doc abroad and 6 of them got their PhD outside Montpellier. It contributes to the scientific diversity and richness of the team.

All members of the group, including CNRS members, are involved in teaching at ENSCM for different degrees and levels. The group is characterized also by a strong involvement in teaching and scientific responsibilities at ENSCM: J. Moreau (Head of ENSCM, Chairman of section 12 of the Comité National 2004-2008, Chairman of FGL 2008- 2010), J-M. Campagne (Vice chairman of ENSCM scientific council, in charge of doctoral studies), D. Virieux (in charge of students employment and professional insertion); J-L. Pirat (in charge of students training and placement in industry), F. Serein-Spirau (in charge of intranet teaching facilities), C. Carcel, J-N. Volle (in charge of teaching laboratories). In addition J-P Lère-Porte is in charge of the master program for forming future physics and chemistry teachers (CAPES) at the university Montpellier 2 and M. Taillefer is chairing the regional section of the French Chemical Society.

■The scientific positioning of the team: All the permanent members of the team are organic and organometallic chemists who have been involved in developing new selective synthetic methodologies based on Si, P, S or transition elements and their uses for example in the field of catalysis or of materials. Members of the team are recognised for their achievements in organic synthesis and in organic and hybrid materials. The AM 2N team is organised around three main themes: “Synthetic Methodologies and Targeted Molecules”, “Nanostructured Organosilicas” and “π-Conjugated Nanoarchitectures”.

The ‘Synthetic Methodologies and Target Compounds’ theme is mainly aimed toward the development of new metal catalysts, catalytic reactions, phosphorus chemistry and more generally synthetic methods for organic chemistry. Ultimately, we are interested in using these methods to design molecules possessing key structural features or potential biological and physical properties. In the field of molecular chemistry, the group did pioneer work and clearly contribute at the higher level in the international competition: the paper on Cu/Fe catalyzed arylation (Angew. Chem. 2007, 934) has already been cited 60 times and the 2005 paper on Au-catalyzed propargylic substitution (JACS 2005, 14180) more than 100 times. Regarding the materials themes, members of the group were at the origin of the key sol-gel synthesis of bridged silsesquioxanes (Moreau+Corriu co-discovery with Shea+Loy in US) Chem. Mater. 1992, about 200 citations) which attracted important attention as new hybrid organic-inorganic materials based on molecular approach. A second key step forward was achieved by the group who described in two JACS in 2001: the first sol gel transcription of supramolecular assemblies into sol-gel hybrid organosilicas (evidence by use of chiral precursors, 150 citations) and the first synthesis of long range ordered hybrid organosilicas with lamellar structure (by combining weak intermolecular interactions, 140 citations). Citations numbers around 30 are found with the more recent contributions in the field of supramolecular chemistry and of organic π-conjugated and hybrid materials: the synthesis of new bridged of organosilicas by use of molecular recognition properties (NJC 2005, 653 and Chem. Eur. J. 2009, 5002); the sol gel controlled supramolecular aggregation of π-conjugated segments (JACS 2006, 4892) and photo polymerisation of self-assembled di-ynes (JACS 2006, 16213).

The group, as a whole, shares the ability to propose new synthetic route, reagents, and new catalysts to reach designed molecular architectures and to make use of the concept of supramolecular chemistry for controlling intermolecular interactions for the synthesis of materials by design.

The group acquired large competence and good scientific recognition in synthetic organic chemistry, π-conjugated organic materials and in hybrid organosilica materials. Indications of these may be found in its responsibility of the organisation of national and international meetings: MNPC07 (Chairman J-P. Lère-Porte); XIV th Internat. Sol-Gel Conference 2007 (Chairman J. Moreau); GECO 2010 (Chairman J-M. Campagne) and as member of the advisory board of 3 International meetings (M. Wong Chi Man).

The scientific recognition of the team brings national and international collaborations with other groups in Montpellier (ICGM, LCVN, ICSM, INM), in France (Paris, Strasbourg, Bordeaux, Rouen, Caen, Versailles, Toulouse, Gif-sur-Yvette, Limoges, Lille, Grenoble, Pau) in Europe (Barcelona, Aveiro, Vila Real, Liege, Prague, Palermo, Potsdam, Heidelberg, Louvain-La-Neuve, Wroclaw), and outside Europe (Los Angeles, Berkeley in US, Quebec in Canada, Lucas Height, Sidney in Australia, Uberlandia and Belo Horizonte in Brasil, Fes and Taza in Morocco). All collaborations are supported by joined funding (ANR franco-allemande; PICS; PAI: Picasso, Tournesol, Pessoa, Barrande; LUSO, PUF, NSF-CNRS, AUF, Averroes). The NoE FAME "Functional Advanced Materials Engineering/Hybrid and Ceramics" - 6ème PCRD, which became EMMI in 2009, helped greatly for scientific exchanges (local coordination M. Wong Chi Man). The collaborations lead to 26 common ACL with foreign teams and 8 “co-tutelle” PhD.

■The AM 2N scientific production: Over the reference period, the current members of the team have published 163 papers in journals with impact factors > 1. Most contributions appeared in multidisciplinary journals (Angew. Chem. (9); JACS (10); Chem. Eur. J. (13); Chem. Comm. (4) or in the best journals of organic chemistry (Adv. Synt. Cat. (9); JOC (8); Org. Lett. (3); EurJOC (11); Tetrahedron (7) and materials chemistry (Adv. Funct. Mat. (3); J. Mat. Chem. (8); Chem. Mater. (2); Small). The average impact factor is 4.8 with 58 articles in journals with IF>5 and 76 with IF>4. With 20 permanent members currently involved in research, it gives 2.04 articles/member/year. The ERN for the team is 13.5 therefore it raises 3.01 articles/ERN/year.

The research team members as well as PhD and postdocs have been encouraged to present their results in scientific meetings. Noticeably young permanent members got invitations to give lectures in national and international meetings (M. Wong Chi Man, J.-M. Campagne). To a total of 35 INV, must be added 63 seminars given by the AM 2N members in universities and industry, in France and abroad. Collaborations with industry and transfer activities resulted in 8 patents and the creation in June 2008 of Athéor: a start-up in the field of non-visible marking and industrial tracing.

■Distinctions: The achievements of the members were recognised by: Grand Prix de l’Etat, Acad. Sciences 2005 (J. Moreau) Prix ACROS 2006 (J-M. Campagne); Ordre du Mérite 2006 (J. Moreau, Chevalier); Winner of “Concours national d'aide à la création d'entreprises des technologies innovantes 2009” (O. Dautel, J-D. Borras).

■Grants : During the reference period, the team was quite successful with proposals and got (in additions to the 3 ongoing ACI 2004-2007) 10 new ANR funding: 5 of them are coordinated by AM 2N members, and in the 5 others, a strong involvement of the team members corresponding to AM 2N main research projects for which collaboration with French and foreign groups have been developed. It allowed the team to support post-docs and PhD students and to get new specific equipments (vide infra).

There are established collaborations with industry, Rhodia, Bayer Cropscience, Neureva, Idenix, Servier, resulting in 4 PhD and 2 post-doc funding and 8 research collaboration agreements. The team is a member of the Institut Carnot CED2. In general, the success in getting funding and in collaboration with industry resulted in a good number of post-doctoral fellows (currently 8) and PhD students in the team (currently 23).

The mean annual budget of the team is around 450 k€/year including part of the salaries for post-doctoral fellows and PhD (average 60k€) and travels (45 k€). It also includes the annual CNRS (35 k€) and MESR (60 k€) funding. Over the last 4 years new equipment represented about 420 k€.

■The AM 2N life: The team is located at ENSCM (rue de l’Ecole Normale) on 3 distinct floors. Website: http://am2n.enscm.fr . Weekly group seminars are the opportunity for PhD students to present their current work. Visiting scientists also interact with students and post-docs during their stay. The team, with common expertise and interest in organic chemistry, has organised common useful synthetic and characterisation equipments. Much new equipment were purchased: HPLC, fluorescence spectrometer, spincoater, profilometer, dipcoater, µ-waves, H-Cube… they are maintained for the group by P. Guiffrey (AI, ACMO) and C. Béord (T) both in charge of the technical aspects and who also train the members of AM 2N to use the different equipments. This organisation turned out to be quite efficient for every one in the group. Safety is introduced to every new member (welcoming notice and “document unique’).

■Some key results:

Theme: Synthetic methodologies and target compounds

Eco-friendly catalytic reactions: gold, iron or copper catalytic systems:

Copper CatalyzedC‑C, C‑O, C‑N, or C‑S bonds: Development of catalytic systems exhibiting a wide and general scope allowing the formation of C‑C, C‑O, C‑N, or C‑S bonds for applications in the field of life sciences, materials and mechanistic studies (Angew. Chem. 2009, 48, issue 36, Angew. Chem. 2008, 47, 3096).

-First general entry into Cu-catalyzed arylation of phenols from aryl chlorides. PCT 08/0003715

-First example of copper catalyzed arylation of aqueous ammonia in mild conditions. PCT 08/051701, Angew. Chem. 2009, 48, 337 (hot paper).

Iron Catalyzed reactions : The low cost and ample supply of iron salts coupled with their environmentally benign nature and lack of toxicity make them ideal for industrial scale synthesis of fine chemicals.

- First example of a cooperative bimetallic catalysis with Fe and Cu that allows the N-, O, or C-arylation of various nucleophiles: WO 08/004088, Angew. Chem. 2007, 46, 934 (cover page of the issue).

- Fe-catalyzed arylation of phenols from aryl iodides. Chem. Eur. J. 2008, 14, 6037.

- Iron is able to selectively promote a high range of atom-economic reactions such as hydroamination and hydroarylation (EurJOC 2007, 2601; Synlett, 2008, 2033).

Gold (III)-catalyzed direct substitutions of propargylic alcohols (JACS 2005, 14180) by various (C, S, N and O-centered) nucleophiles where water is the only by-product. This reaction could then be extended to the direct substitution of allylic and benzylic alcohols (Adv. Synth. Cat. 2006, 2063).

- This methodology has been then applied to the ring-closing metathesis of 1,5-enynes leading to functionalized cyclobutenes (JACS, 2008, 1562; highlighted in C&EN and Angew. Chem.), demonstrating that strained small cycles such as cyclobutenes can be obtained using RCM methodologies.

Stereoselective catalysis and synthesis:

Catalyticand Asymmetric Vinylogous Mukaiyama Reactions on ketones to obtain α,ß-unsaturated lactones (JACS 2005, 7288; Chem. Eur. J. 2006, 8358). These regio- dia- and enantio-selective reactions have been applied to the formal total synthesis of taurospongin A.

Chiral phosphorus compounds present specific interest either as ligands in enantioselective synthesis or targets molecules. Stereoselective arylation of H-phosphinates was developed as a general way to control asymmetry ( JOC 2005, 70, 7035; Tetrahedron Asym. , 2006, 17, 1402).

Applicative Developments of dedicated phosphorus chemistry

Synthesisof new phosphorus ligand, applications in copper catalyzed arylation reactions, and for mechanistic studies. PCT 08/000984 and PCT 08/051736, Angew. Chem. 2009, 48, 333.

A validated Proof of Concept for Neuroactive or Anticancer Drugs: Based on our expertise in the stereoselective synthesis of complex phosphorus heterocycles, we anticipated that a phosphinolactone moiety could constitute a good bioisostere to lactol groups, due to their structural and polar similarities. Phosphinolactone group was easily introduced in replacement of the lactol group of hydroxybupropion, the active metabolite of Bupropion a marketed drug from GlaxoSmithKline leading to 1,2,4-oxazaphosphinanes series. In parallel, about 70 new phosphinosugars (Phostines) were also obtained where the P=O bond mimicked the anomeric carbon. Phosphinolactone proved to be a remarkable lactol bioisostere and afforded an unprecedented scaffold for the elaboration of new drugs: Direct in vivo testing of oxazaphosphinanes delivered outstanding results showing their ability to diffuse through the blood-brain barrier and then to reproduce the original activity of the marketed drug at lower concentration (4 times more effective than Bupropion). Phostines showed nanomolar activities on glioblastoma, a brain cancer with very bad prognostic. These last results were covered by a patent in 2009 ( WO09004096).

Theme: Nanostructured organosilicas

Solid silsesquioxanes resulting from sol-gel hydrolysis and condensation of bis or tris (triakoxysilylated)-organic molecules are quite different from the classical hybrid or grafted silicas. The hybrid network can be simply described as siloxanes chains with bridging or cross-linking organic substructure. The group did pioneer work in the self-organisation of this solids synthesised from molecular precursors by use of weak intermolecular interaction of the organic substructures. It reported new nanostructuring of organosilicas: JACS 2001, 123, 1509 and 7957; Angew. Chem. 2004, 43, 203. The challenges with these solids characterised by a high organic content are: i) to reach a better understanding of the self organisation processes combining weak H-bonding, hydrophobic or π-π interactions; ii) to generalise this approach and to control the interaction between organics for tuning the solid properties (molecular recognition, catalytic activity, electronic or charge transport, optical response…); iii) to control the pore structure of the hybrid framework; iv) to generate material upon appropriated functionalisation; v) to fabricate them into useful forms and to incorporate them into devices. The key results in these respects can be summarised as follows:

Nanostructuring of hybrid silicas:

Mechanistic insights: Strong collaboration with colleagues from the physics department allowed determining the precise structure and also the mechanism of the self-structuration. Our main contributions in this area are described in the followings

- We demonstrated that the combination of additional cooperative weak interactions (H-bonding and hydrophobic interactions) in the organic fragment favours their self-association during hydrolysis condensation steps. It brings a general method for structuring bridged silsesquioxanes (J. Mater. Chem. 2005, 15, 3929)

- Using in-situ X-Ray experiments performed at ESRF, we determined the structure of a self-organised silsesquioxane (Small 2009, 5, 503) and we showed the formation of nanotubes and thin films (Adv. Funct. Mater. 2007, 17, 3926 and 2007, 17, 2349). This afford a better understanding of the mechanism of formation of these structured materials which can be extended to targeted functional hybrids in order to fine tune their properties.

Combining self-assembly and molecular recognition: We first showed that the combination of hydrophobic interactions and molecular recognition allowed the association of different precursors and their self organisation. The use of complementary partners: adenine-thymine or the use of ureidopyrimidone was shown to afford new type of bridged silsesquioxanes, constituting an interesting breakthrough in this field (New J. Chem. 2005, 29, 653). For the first time solid state 1H NMR was used to study these hybrids and evidences the key role of the H-bonds for structuring these novel hybrids (Chem. Eur. J. 2009, 15, 6279; J. Mat. Chem. 2008, 18, 392).

Following this concept, we exploited the hybrid silicas with molecular recognition properties to create specific interactive sites (Chem. Eur. J. 2009, 15, 6279), and demonstrated the role of the H-bonds to allow the tight introduction and the easy release of the organic template molecule within these solids.

Generating bridged silsesquioxanes with organised pore structure by tuning ionic interactions:

The controlled synthesis of porous polysilsesquioxanes featuring regular pore architectures is still a challenge. Generally, high organic/silica ratio is not favourable to generate strong surfactant-precursors interactions and mostly led to non-structured materials. Our approach was to enhance the interactions between structure directing agent and organic precursor molecules via ionic interactions. We first showed that cationic ammonium precursor in the presence of an anionic structure directing agent lead to polysilsesquioxanes with 2D-hexagonally arranged pore structures. Deprotonation of the ammonium ion gave rise to a periodical mesoporous polysilsesquioxane bearing free amine groups which is not accessible by the conventional routes (submitted).

Organosilica materials for catalysis:

The introduction of functional units in silsesquioxane solids lead to material for a variety of uses.

Immobilised organometallic catalysts:

We first reported the use of silsesquioxanes as catalysts for asymmetric reactions ( J. Mater. Chem . 1997, 7, 2331). The developments mainly contribute in the finding of new eco-compatible and efficient catalysts which are recoverable, easy-handling and reusable. It should be noted that although these silsesquioxanes are mostly non-porous, their efficiency are at least similar and ofter higher than in the case of the analogous homogeneous catalysts. Some examples are given below:

- Ru : Grubbs-Hoveyda catalysts was immobilised and ring closing diene and ene-yne metathesis reactions could be performed in milder conditions and give better results than commonly grafted systems (Adv. Synth. & Catal. 2006, 348, 751 and 2007, 349, 1701).

- Pd : Hybrid catalysts were synthesised and proved to be efficient recyclable catalysts for Heck, Sonogashira and Suzuki (single and tandem) reactions: (Tetrahedron Lett. 2006, 47, 2399, Adv. Synth. & Catal. 2008, 350, 577 and 2008, 350, 2566).

- Cu: Immobilised bipyridyl silsesquioxanes/Cu complexes proved to be a green catalyst for Ulmann O-arylation reaction. Negligible leaching of copper was observed; the catalyst is air-stable and can be easily withdrawn and recovered from the reaction, it was re-used ten times without loss of efficiency and more interestingly for subsequent reactions with several substrates It offers a promising route to contribute to the waste reduction (Adv. Synth. & Catal. 2008, 350, 2205).

Immobilised ionic species : We observed that the use of ionic precursor molecules enhances surfactant-precursor interactions and facilitates the formation of nanostructured phases displaying organised pore arrangements. In this field, we reported regular MCM-41 type silica bearing chiral camphorsulfonamide entities (EurJIC 2006, 3697), nanostructured silicas with covalently bound guanidinium-sulfonimide ion pairs (JACS 2009, 131, 2882). This approach allowed generating nanostructured heterogeneous catalyst via metal coordination (Pd containing nanostructured organosilicas for Heck, Sonogashira and cyanation reactions: Tetrahedron 2007, 63, 6784) or ion exchange (perruthenate immobilised in nanostructured organosilicas for oxidation reactions: Chem. Eur. J. 2006, 12, 5220).

Theme: π-Conjugated Nanoarchitectures

In a bottom-up approach to generate active materials for optics and optoelectronics, the control and tuning of the properties of π-conjugated nanoarchitectures require a control of the interactions between conjugated segments resulting from their organisation and respective orientation. Our approach based on molecular and supramolecular engineering has led us to a better understanding of the involved self organization process and has led us to explore the potential of conjugated nanoarchitectures in the field of optics and optoelectronics.

We have been interested in chiral polymer containing repeating conjugated substructures, with weak interaction owing to the helical arrangement of the units. It was showed to give useful sensitive materials for electroluminescent diodes and for sensors with ultra high sensitivity in the detection of nitroaromatics.

We also develop strategies to control the aggregation of molecular precursors during the formation of a solid π-conjugated material via sol-gel routes. The formation of H or J aggregates plays a determining role in the resulting optical and electro-optical properties of the material.

The design of electroactive nano-objects is of particular interest and can allow generating nanostructured material for example in the field of organic photovoltaic devices. We explored a bottom up approach based on the self organization of molecular precursors to form assemblies, the polymerization of which lead to nano fibers.

π-Conjugated Materials containing isolated chromophors:

Polyimides and polyimines containing alternating π-conjugated units as fluorophors and chiral units with C 2 symmetry were synthesized. The resulting material exhibit high fluorescence since the conjugated substructure behaves as isolated units with well defined optical properties. In addition owing to weak interchain interactions, it form easily form thin films with high homogeneity and which can solubilise molecules, such as nitroaromatics

Main results: i) Monolayered electroluminescent diodes. Good fit of the HOMO-LUMO levels of the new imide type fluorophore with the levels of the electrode material (J. Mat. Chem. 2005, 41, 4446). ii) Ultra sensitive nitroaromatic sensors (as low as 2 ppb; French Patent, 2005, FR045719; J. Polym. Sci. part A: Polym. Chem. 2009, 47, 4141).

Controlled formation of J and H aggregates:

Our sol-gel approach (vide supra) is particularly well adapted to generate π-conjugated materials. The control of the aggregation of the π-conjugated molecular units is determining the optical properties; J-aggregation will lead to high fluorescence while high electron mobility is expected in material with H-aggregation of conjugated units.

We first showed how the use of informed molecular precursors allowed a control of their aggregation in the final material. We designed a new route using a photogenerated acid catalyst for sol-gel hydrolysis-condensation which allowed to couple nanostructuring and micropatterning in a single step. The creation of the start-up “Athéor” results from an innovation based on our results (French patents, 2008, n°08 56179and n°08 56199).

Main results: i) from J to H aggregates upon sol-gel hydrolysis-condensation of silylated π-conjugated precursors. Formation of J aggregates by introduction of bulky groups in the mains chain. Evidence for the appropriated properties of J aggregates for electroluminescent diodes and for the appropriated properties of H aggregates for photovoltaic cells (JACS 2006 , 128, 4892 ).ii) Transcription in the solid state of the organisation of the sol-gel precursor, maintaining J aggregation owing to the presence of non hydrolysable bulky groups. One step generation of nanostructured and micropatterned fluorescent material (Adv. Funct. Mater., 2009, 19, 404 ).

Conjugated nano-objects:

In a bottom-up approach of π-conjugated nano-objects we studied self organisation by use of H-bonding.

Main results: i) We showed using AFM and EFM microscopies that self-organization of π-conjugated molecular architectures generated conducting nanorings and nanorods ( Chem. Eur. J., 2008, 14, 4201). They consist in assemblies of strongly conjugated rigid molecules owing to S•••O interactions (EurJOC 2007, 24, 4019). ii)We designed informed functionalized di-ynes upon forming supramolecular fibres which photopolymerise to polydiacetylene fibres. The structure of the precursor was tuned for positioning the di-ynes in the appropriate topology for easy photo polymerisation. The structure/optical properties relationship of the formed blue polydiacetylene fibres, exhibiting thermochromic and solvatochromic properties was reported ( JACS 2006 , 128 , 16213).