Chiral Cyclic Alkyl Amino Carbenes in Asymmetric Catalysis – ChiCAAC

The aim of this project is to prepare chiral CAAC ligands with a strong emphasis towards the development of enantioselective transformations of industrial interest. The proposed work has been divided in two different tasks, each capitalizing on the specific expertise of the three partners involved in the project. Task one focuses on the preparation of chiral CAACs and their respectives transition metal catalysts (Ru, Pd, Ni, Cu, Au...). Whereas in Task 2, explores asymmetric transformations catalysed by chiral catalysts obtained in Task 1. Amongst the transformations of interests a particular emphasis has been put towards asymmetric olefin metathesis.

We already demonstrated that chiral CAAC ligands are readily accessible in high enantiopurity (up to 99% ee). Capitalising on these results we have prepared novel chiral ruthenium complexes with full retention of the enantiopurity. We further demonstrated that these chiral ruthenium complexes are also accessible by separation of their racemic form by preparative HPLC (PCT / IB2020 / 000920; PCT / EP2021 / 069049), and exemplified their reactivity in asymmetric olefin metathesis (JACS, 2020, 19895).

A number of applications are possible for the application of CAACs in asymmetric catalysis, in particular industrially with respect to asymmetric metathesis. We are also focusing our efforts in better understanding the asymmetric induction provided by this class of ligands. These results will provide a strong impetus to further development this seminal topic.

Publications:
1. Morvan, J., Mauduit, Bertrand, G., Jazzar, ACS Catal. 2021, 11, 1714. (https://doi.org/10.1021/acscatal.0c05508)
2. Morvan, J., Vermersch, F., Zhang, Z., Falivene, L., Vives, T., Dorcet, V., Roisnel, T., Crévisy, C., Cavallo, L., Vanthuyne, N., Bertrand, G., Jazzar,
R., Mauduit, M. J. Am. Chem. Soc. 2020, 142, 19895. (https://doi.org/10.1021/jacs.0c10705)
3. A. Nouaille, J. Lorkowski, X. Pannecoucke, M. Mauduit, T. Poisson, S. Couve-Bonnaire, ACS Catal. 2021, 11, 12307-12323. (https://pubs.acs.org/doi/10.1021/acscatal.1c03414)
4. Gao, Y.; Yazdani, S.; Kendrick, A.; Junor, G.; Kang, T.; Grotjahn, D.; Bertrand, G.; Jazzar, R.; Engle, K. Angew. Chem. Int. Ed. 2021, 60, 19871. (https://doi.org/10.1002/anie.202106107)


Patents:
1. R. Jazzar, M. Mauduit, G. Bertrand, J. Morvan, F. Vermersch, N. Vanthuyne – Optically pure enantiomers of ruthenium complexes and uses thereof US PCT/IB2020/000920 (2020)
2. R. Jazzar, M. Mauduit, G. Bertrand, J. Morvan, F. Vermersch, N. Vanthuyne – Ruthenium complexes, their optically pure enantiomers and uses thereof – EP 20305787.2 (2020)

Following pioneering work by Bertrand in 1988, and the isolation of the first N-heterocyclic carbene (NHC) by Arduengo, the field of stable carbenes has witnessed outstanding breakthroughs and considerable developments. Due to their strong sigma-donating and pi-accepting character, and their simple, yet versatile synthesis, carbenes have successfully challenged the stronghold of phosphines in transition metal catalysis. In recent years, the success of achiral N-heterocyclic carbenes (NHCs) as stable electron-rich neutral ligands has triggered the development of a diversity of chiral NHCs as stereodirecting ancillary ligands for enantioselective transformations. Today, thanks to their modular design and the ease of accessing azolium salt precursors, tailor-made chiral NHCs have proven to be significant tools in asymmetric transformations. Despite these advances, the toolbox of available chiral carbenes still lags behind more classical chiral phosphine ligands. In part, this situation might originate from the seeming inability to capitalise on the rich structural and electronic diversity of stable singlet carbenes. The goal of this project is therefore to prepare new chiral carbene ligands (other than NHCs), in order to extend the still developing family of stable chiral carbenes.