JCJC SIMI 7 - JCJC - SIMI 7 - Chimie moléculaire, organique, de coordination, catalyse et chimie biologique

Chiral zwitterionic aryl-group surrogates for asymmetric catalysis – ChirASCat

A novel approach towards chiral ligands for asymmetric catalysis

Asymmetric catalysis now holds a prominent place in organic synthesis as exemplified by its use as key step in the synthesis of natural and/or biologically active compounds. This project aims at developing a new paradigm for the conversion of efficient, achiral ligands into their chiral version.

Chiral adaptation of achiral, efficient ligands : a new paradigm and concept in asymmetric catalysis

Whereas several privileged, efficient, chiral ligand classes are well established, the conversion of an achiral catalytic system into its chiral version remains not straightforward. Indeed, the structural changes often lead to a strong reorganization of the coordination sphere and thus to a decrease of the catalytic performances of the catalyst compared to the original achiral one. This project introduces a facile method to address this problem, and focuses on two highly efficient ligand classes, namely the N-Heterocyclic Carbenes (NHCs) and the Buchwald-type phosphines.

Starting from the observation that the structures of those two ligand families include aryl groups pointing towards the metal center, our strategy is based on the replacement of the latter by pyrimidinium betaines, which would mimic their geometrical properties. The chirality would be easily brought by enantiopure chiral amines. To our knowledge, this constitutes the first example of the incorporation of mesoionic heterocycles into a ligand architecture for organometallic catalysis.

Two novel phosphine classes, derived from the Buchwald-type phosphines by substitution of the distal aryl group by a pyrimidinium betaine, have been synthesized. The only difference is the position of the connection between the heterocycle and the phosphine part. In both classes, a weak interaction has been observed between the metal center and the ipso carbon atom of the heterocycle, and the latter has been shown to be not as innocent as initially supposed. A third family based on NHCs is still under study in our laboratory. Two families appear particularly well designed for efficient asymmetric gold(I) catalysis.
These results constitute a solid preliminary basis for future developments, currently under progress in our laboratories.

Brought to fruition, this project will :
- show that the interest in designing new, modern approaches and concepts in asymmetric catalysis is still important.
- allow the access to highly enantio-enriched, complexes and highly valuable compounds for industrial and pharmaceutical industries.
- open a vast research area with new chiral, conceptually original ligands.

Three publications have been published on this project: (1) V. César, S. Labat, K. Miqueu, J.-M. Sotiropoulos, R. Brousses, N. Lugan, G. Lavigne, Chem. Eur. J. 2013, 19, 17113-17124 (Publication on the original and unprecedented reactivity of the anionic maloNHC dervide from the pyrimidinium betaines) ; (2) L. Noël-Duchesneau, N. Lugan, G. Lavigne, A. Labande, V. César, Organometallics 2014, 33, 5085-5088 (original disclosure of the achiral representative of the first phosphine family) ; (3) L. Noël-Duchesneau, N. Lugan, G. Lavigne, A. Labande, V. César, manuscrit soumis (original disclosure of the achiral representative of the second phosphine family).

Although numerous efficient chiral ligands are known in asymmetric organometallic catalysis, the implementation of an achiral catalytic system into its chiral version is usually not straightforward, since the structural changes required to obtain chiral induction involve an important reorganization of the metal’s coordination sphere which often reduces the performances of the initial catalyst. This project aims at introducing a simple method to overcome this difficulty. Starting from the observation that the most widely used achiral ligands, like N-heterocyclic carbenes of phosphines, possess aryl groups that will come in close proximity to the metal center, we propose to replace such aryl groups by chiral pyrimidinium betaines, which are currently used in our laboratory as precursors of anionic N-Heterocyclic Carbenes (NHCs). The advantages of these heterocycles include i) a simple and rational synthetic accessibility in few steps from commercial enantiopure amines, ii) a perfect mime of the geometrical properties of the aryl groups, and iii) good chemical and thermal stabilities. More precisely, the study will focus on two classes of highly efficient monodentate ligands: N-Heterocyclic carbenes and biarylphosphines developed by Buchwald. As the aryl substituents of these ligands point towards the metal centre, their formal replacement by chiral pyrimidinium betaines will play a key role in the construction of a well-defined chiral first coordination sphere, thereby resulting in a strong chiral induction. The enantioselective Suzuki-Miyaura cross-coupling reaction is chosen as the model catalysis to evaluate the efficiency of the new chiral ligands. The latter will then be applied in challenging catalytic reactions for which there is no really convincing chiral catalytic system yet. We target the Gold(I)-catalyzed C-C and C-N bond forming reactions, whose enantioselective versions are hampered by the linear coordination geometry of Gold(I) complexes, and the Copper(I) catalysts, whose applications in organic synthesis are dramatically growing these recent years.

Project 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.



Help of the ANR 163,800 euros
Beginning and duration of the scientific project: October 2011 - 36 Months

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