CE07 - Chimie moléculaire

Straightforward access to enantiopure NHC-Transition Metal Complexes: New opportunities for asymmetric catalysis – cResolu

cRésolu

From achiral NHC ligands to enantiopure NHC-Transition Metal Complexes: New opportunities for asymmetric catalysis

Straightforward access to enantiopure NHC-Transition Metal Complexes

The goals of this project are the development of an original design of chiral carbene ligands. In sharp contrast with the literature, the concept which will be developed does not lie neither on the introduction of chiral moieties as N-substituents nor on the use of stereogenic center(s) on cylic carbenes. Thus, the chiral in this new design come from a restricted rotation of the N-aryl substituent about the C-N bond. Given that the restriction of the rotation is taking place at the final stage of the synthesis, the metalation step, complexes will be obtained as racemic mixture and a resolution step is required. However, this design possesses several advantages: i) no need of precursors coming from the chiral pool which can be expensive and the availability and the price might fluctuate along the time; ii) access to both enantiomers with excellent optical purities and in a control and reproducible way; iii) a simplified synthesis since the resolution take place at the final step avoiding the loss of enantiopure material; iv) the use of well-defined complexes which are usually more efficient in (asymmetric) catalysis.

A part of the structures design will be done at an early stage of the project thanks to theoretical calculations in order to identify the structures that will exhibit a configurational stability allowing their access as an enantiopure form and thus make easier the time-consuming synthesis step. Owing the good stability of NHC-TM complexes, a chiral HPLC resolution at preparative scale will allow to obtain NHC-TM complexes with high optical purities. In a first time, the new chiral NHC-TM complexes will be tested in enantioselective benchmark reactions before to use them to the development of new asymmetric transformations.

The proof of concept was demonstrated before the beginning of the project and preliminary results with palladium- and copper-based complexes were used to build the proposal. Since, new carbene precursors have been prepared and used to synthetize carbene-metal complexes. All of these chiral complexes were successfully resolved by chiral HPLC at preparative scale (on almost gram scale). Moreover, whereas initial results were limited to palladium- and copper-based complexes, it has demonstrated that the concept was extended to gold-, ruthenium- and rhodium-based complexes. Some of these complexes exhibited excellent catalytic performances in the model reactions in terms of both activity and enantioselectivity.

Since we succeeded to identify and prepare several structures of enantiopure complexes bearing carbenes ligands based on palladium, copper and more recently ruthenium and gold, the project will move to a second phase with the applications of these catalysts to develop new enantioselective transformations. This will include the synthesis of original substrates to investigate but also the preparation of new carbene structures in order to optimize chiral inductions. Another perspective that will be scrutinized is the application of this concept to other transition metals. We whish also to investigate reaction mechanism in general and more precisely the one of carbene transfer form one metal to another that could be bring new ideas for the extension of the concept to other transition metals.

3 publications and 1 patent
1. L. Kong, Y. Chou, M. Jean, M. Albalat, N. Vanthuyne, P. Nava, S. Humbel, H. Clavier, Adv. Synth. Catal. 2021, 363, 4229-4238 (hal-03338494v1).
2. M. Savchuk, L. Bocquin, M. Albalat, M. Jean, N. Vanthuyne, P. Nava, S. Humbel, D. Hérault, H. Clavier, Chirality 2022, 33, 13-26 (hal-03500191v1).
3. F. Vermersch, L. Oliveira, J. Hunter, M. Soleilhavoup, R. Jazzar, G. Bertrand, J. Org. Chem. 2022, 87, 3511-3518.
4. M. Mauduit, R. Jazzar, G. Bertrand, J. Morvan, N. Vanthuyne, J. Lorkowksi – Synthesis of optically pure AminoAlkyles Cyclic Carbenes – EP 21306194.8 (2021)

In this project, we will develop new chiral transition metal catalysts bearing N-heterocyclic carbene (NHC), cyclic alkyl amino carbenes (CAACs) ligands and other carbene ligands containing a sole axial chirality. In an original and unique manner, the complexes will be prepared from readily available achiral NHC precursors. Thus, the enantiopure complexes will be obtained by preparative chiral HPLC resolution which will provide access to both enantiomers with high optical purity (>99%). The design of the atropisomeric carbenes structures will be supported by DFT calculations which will be performed at an early stage. This project will tackle some fundamental aspects related to chirality including mechanistic aspects of carbene transmetalation, looking to understand the fate of the chiral information during this process. Beyond these fundamental studies, the aim is to create new series of efficient and inexpensive chiral catalysts in order to perform original enantioselective transformations.

Project coordination

Hervé Clavier (Institut des Sciences Moléculaires de Marseille)

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.

Partner

ISCR INSTITUT DES SCIENCES CHIMIQUES DE RENNES
ISM2 Institut des Sciences Moléculaires de Marseille
UCSD-CNRS Joint Research Chemistry Laboratory

Help of the ANR 481,040 euros
Beginning and duration of the scientific project: December 2020 - 48 Months

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