DS0304 - Chimie Durable, produits, procédés associés

Chiral Bifunctional N-Heterocyclic-Carbene (NHC) Ligands in Metal-Catalyzed Asymmetric C-H Bond Functionalization – CHADOC

Firstly, the efficient and modulable synthesis of the chiral NHC ligands developed within the laboratory allows rapid access to a variety of organometallic complexes having a wide structural variety.
Thus, following a methodical approach, the difficulty is gradually increased, initially carrying out studies concerning the activation of sp2 C-H bonds, and then turning to the functionalization of sp3 C-H bonds. Initially carried out with Pd(II) complexes, these studies are then transposed to the Ruthenium(II), Rhodium(I), Rhodium(III) Iridium(I) and Iridium(III) complexes. The ultimate goal is to develop enantioselective cross-dehydrogenative-couplings.
The possible demonstration of a non-innocent character of the basic fragment of the ligand NHC and of its involvement in the key step of activation of the CH bond will allow us to acquire a better understanding of the mechanism involved in this type of process and adapt if necessary.

1) The strategy initially considered for the preparation of chiral metal complexes provides simple and efficient access to a variety of unpublished complexes of Palladium (II), Ruthenium (II), Rhodium (I) and (III) Iridium (I) and (III). Using this method, a Palladium (II) complex, equivalent to PEPPSI, could be prepared on a gram scale.
2) The study for the preparation of more congested chiral NHCs ligands incorporating the diisopropylphenyl (DiPP) fragment was published (J. Org. Chem 2016, 82, 1880).

Task 2.
1) The mechanistic study showed that the NHC/Pd(II) complexes are not able to perform CH activation, but that this activation took place in contact with a Pd (IV) metal center with a high degree of oxidation ( Publication under consideration).

Task 3.
1) NHC/Ruthenium-arene complexes, catalysts for the regioselective arylation of Csp2-H bonds (publication in preparation).
2) NHC/Rh complexes, catalysts for regioselective borylation of nitrogen-containing heterocycles by C-H functionalization (publication in preparation).

After 18 months, the progress of the project remains in line with the milestones and deliverables. Some of the results obtained from this project have already been published in a high-impact journal (J. Org. Chem 2016, 82, 1880). Some objectives have had to be revised in order to be more in line with the timetable of the deliverables, in particular with regard to the reactivity of the synthesized metal complexes and their future applications in asymmetric catalysis. Indeed, the studies carried out have been able to demonstrate unexpected and particular reactivities to the metal complexes of newly synthesized transitions. These results open new perspectives in terms of catalytic applications. Thus, the NHC-Pd and NHC-Ru complexes demonstrate new behaviors in C-H functionalization model reactions (publications in preparation). In addition, two NHC-Rh complexes have provided excellent selectivities in regioselective borylation reactions of nitrogen heterocyclic substrates (publications in preparation).

It is also important to note that during this project new luminescent chiral organometallic complexes have been synthesized and that the study of these latter has led to a new partnership between our research group and that of Dr. Jeanne Crassous and Dr. Ludovic Favereau at the institut des sciences chimiques de Rennes

In order to extend the synthesis process to a wider variety of metal complexes and to extend the structural diversity of the latter, we have undertaken a study for the preparation of more congested chiral NHCs incorporating the diisopropylphenyl (DiPP) fragment. The introduction of sterically hindered groups constituted a major limitation of our previous multicomponent synthetic method of unsymmetrical imidazolium salts. Optimization of this synthetic methodology by adding ZnCl2 as an additive has enabled efficient access to the precursors of the desired NHCs ligands (work published in J. Org. Chem 2016, 82, 1880). It is important to note that these novel chiral ligands have shown interesting properties in asymmetric catalysis other than C-H activation.

Submission summary

Innovative methods to rapidly and efficiently construct valuable natural products and pharmaceuticals are in popular demand in the field of organic chemistry. In this concern, metal-catalyzed direct selective functionalization of C-H bonds has recently became an attractive alternative to traditional cross-coupling reactions by avoiding the prefunctionalization of the corresponding substrates. Interestingly, such reactions also offer unprecedented strategic disconnections to be applied in more efficient retrosynthetic analyses. The enthusiasm for the C-H bond functionalization strategy is spreading among research fields and is today opening new routes with potential application in areas ranging from pharmaceutical industry to material science and polymers. Nevertheless, and despite the recent achievements, the asymmetric C-H bond functionnalization remains today a formidable challenge. The aim of the “ CHADOC ” project is to explore one of the most promising potential applications of new chiral bifunctional N-heterocyclic carbene (NHC)-carboxylate ligands and to contribute to sustainable chemistry by developing robust and efficient metal-based catalysts for the direct and selective functionalization of C-H bonds. Through mechanistic investigations and theoretical calculations a large effort will be devoted to understanding the factors governing the reaction and its selectivity.

Project coordinator

Monsieur Olivier BASLE (CNRS / Laboratoire de Chimie de Coordination)

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.


CNRS/LCC CNRS / Laboratoire de Chimie de Coordination

Help of the ANR 199,159 euros
Beginning and duration of the scientific project: February 2016 - 42 Months

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