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Contact : Laurent El Kaïm, professor

 

Isocyanide and multicomponent reactions (MCR)

 

MCRs represent an important trend in organic synthesis. These reactions, that assemble more than two components within a same molecular framework, have attracted considerable interest in relation with the structural complexity reached in a reduced number of synthetic steps. Indeed organic chemists, in response to growing environmental concerns, are more and more adapting their synthetic strategies in order to comply with the concepts of step and atom economy. In this context, multicomponent reactions are important tools. When MCRs involving more than three components are considered, isocyanide chemistry is often introduced due to the high efficiency and versatility of the Ugi 4-component reaction. This reaction discovered in 1959 has been extensively used in the last twenty years. Most 4-component synthetic strategies display a Ugi coupling followed by a so-called "post-condensation" step in order to form highly diverse scaffolds in less than three steps. Research on isocyanide based MCR at ENSTA has focused on original Ugi post-condensations involving complex cascades, new organometallic catalyzed process as well as radical couplings.

Scheme 1 presents two examples taken from our research :

Scheme 1 : Ugi post-condensations

 

On other important strategy in our group is to think about original ways of introducing isocyanides in multicomponent couplings. Among various projects involving Nef isocyanide reaction, [4+1] cyclizations, and variations on the Ugi coupling, our Ugi-Smiles extension certainly represent the project with the highest synthetic potential. Taking phenols and hydroxy-heterocycles as acidic partners in Ugi reaction, we were able to disclose a new N-arylative coupling involving as Smiles rearrangement as the key step.This new family of Ugi couplings opens the way to many post-condensation studies involving new cyclocondensations as well as organometallic couplings.

Scheme 2 represent a selection of these studies :

Scheme 2 : Ugi-Smiles post-condensations

 

Organometallic chemistry

 

During our attempts to perform aldol type addition between hydrazone and aldehydes, we discovered that the addition of an aldehyde to the preformed complex of trimethylaluminum and hydrazone lead to an N-alkylated compound with transfer of the methyl group. Apart from the mechanistic interest of this reaction (analogous reaction with secondary amine instead of the hydrazone is not described), this coupling allows the preparation of highly hindered hydrazine derivatives...

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Hydrazone chemistry

 

We have been interested in hydrazone chemistry for a long time, and various axes have been explored. For instance, we have developed a new Mannich-type coupling involving hydrazones as the nucleophilic partner. Based on the former Keil and Reid work (1965), we developed a very effcient thre-component access to a-aminohydrazones which are stable precursor of azoalkenes. The use of N-benzyl piperazine allows efficient couplings whatever the aldehyde used and some mild conditions for the azoalkene generation. These heterodienes could be trapped in various cycloaddition reactions -[4+1] and [4+2]- to form different heterocyclic scaffolds...

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Isocyanide chemistry

 

Nef-type reactions : Trifluoroacetic anhydride

Isocyanides addition to trifluoroacetic anhydride allows a straightforward preparation of trifluoropyruvamides derivatives. These compounds are useful fluorinated synthetic intermediates ; we have demonstrated that various nucleophiles are easily added on these stable hydrates...

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Self-assemblies

 

Nanostructured surfaces for nanophotonics, supra (macro) molecular assemblies (nanotubes, gels, core-shell particles).

In this topic, recently we demonstrated highly ordered 3D nanostructures on highly-oriented pyrolitic graphite (HOPG) at the liquid-solid interface at room temperature. Our strategy followed classical architectural paradigms based on the realization of a well-organized on-plane monolayer paving the HOPG, and the emergence, perpendicular to the substrate, of an array of standing organic nanopillars of tunable height in view of obtaining large atomically-precise alignments both in-plane and vertically controlled. To validate this concept, we chose the multilayered [2.2]paracyclophanyl (PCP) moiety as nanopillars with variable height. More precisely, we designed and synthesized a series of molecules bearing two functional 'clips' end-capping a central either benzene ring, or the lower deck of a two- and three-layered PCP unit...

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Polymers

 

Conjugated liquid crystal polymers for organic electronics, controlled free radical polymerizations for Non Linear Optics (NLO) applications...

The self-organization of p-conjugated organic materials forming highly ordered supramolecular architectures has been extensively investigated in the last two decades in view of optoelectronic applications. Indeed, the control of both the mesoscopic and nanoscale organization within thin semiconducting films is the key issue for the improvement of charge transport properties and achievement of high charge carrier mobilities. These wellordered materials are currently either self-organized semiconducting polymers or liquid crystals. Indeed, on the one hand previous studies have shown that well-defined polymer architectures such as a regioregular poly(3-alkylthiophenes) promote self-organizations in a two-dimensional sheet-like lamellar structures due to the high planarity of the polymer chains...

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