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

Helicenes: From and Towards Asymmetric Organometallic Catalysis – HELCATS

HELCATS

HELicenes: From and Towards Asymmetric Organometallic CATalySis

Helical chirality: from and towards synthesis

Helicenes, aromatic compounds with a helical structure, intrinsically possess interesting chiroptic properties and find applications in various fields. Of particular interest is the preparation of optically enriched helicenes, as the latter are paving the way towards asymmetric catalysis. To date, only a few examples of helicenes used as ligands are reported in the literature. This proposal aims at revealing this under-utilized potential of helical chirality in applied organometallic catalysis, by devising a brand new generation of cyclic helicenes; and developing a new eco-compatible efficient catalytic system to access the desired chiral templates. Both strategies combined will allow access to helically chiral organometallic complexes that will lead to high induction in asymmetric catalysis. DFT calculations, already performed for selected examples, will help validating our structures as well as rationalizing the stereochemical outcomes observed in catalysis.

We studied new cobalt catalytic systems for triynes cycloaddition towards helicenes. Indeed, these systems would open new potentialities in helicenes asymmetric synthesis. Moreover, original cyclic helical targets have been selected to bring the active center closer to the helical cavity, to optimize the chirality induction. The evaluation of these new helical catalytic systems was carried out in asymmetric palladium-catalyzed Tsuji Trost allylation reactions, usually used to evaluate the efficiency of new ligands; and gold-catalyzed cycloisomerization of polyunsaturated systems, powerful synthetic methods for the preparation of 5- and 6-membered carbo- and heterocycles which are frequently encountered in complex molecules such as natural products.

This proposal “HELCATS” lies in the field of asymmetric organometallic catalysis. We pursued this project in two directions: (i) The synthesis of enantioenriched platforms, thanks to efficient metallo-catalyzed [2 + 2 + 2] cycloaddition reactions and to racemates resolution. These chiral platforms were functionalized and used in asymmetric organometallic catalysis; (ii) We studied the double stereodifferentiation by double catalytic contribution. In preliminary work, we focused on axial chirality. We have shown that enantioenriched pyridones could be synthesized by using a chiral ligand and a chiral counterion, acting synergistically.

This results obtained in the field of helicenes thanks to the use of metal complexes derived from HELIXOLs made it possible to launch a new thematic in the laboratory, and to settle in the community and the international competition relating to the use of helical chirality in asymmetric organometallic catalysis.
New collaborations have been created within the team around this project, which will allow to fully express the potential of helical chirality in asymmetric catalysis.

Peer-review internationale publication:
- Double Stereodifferentiation in Rhodium-Catalyzed [2+2+2] Cycloaddition: Chiral Ligand/Chiral Counterion Matched Pair, Augé, M.; Feraldi-Xypolia, A.; Barbazanges, M.; Aubert, C.; Fensterbank, L.; Gandon, V.; Kolodziej, E.; Ollivier, C. Org. Lett., 2015, 17, 3754.
- HELIXOL-derived Bisphosphinite Ligand: Synthesis and Application in Gold-catalyzed Enynes Cycloisomerization, Medena, C.; Calogero, F.; Lemoine, Q.; Aubert, C.; Derat, E.; Fensterbank, L.; Gontard, G.; Khaled, O.; Vanthuyne, N.; Moussa, J.; Ollivier, C.; Petit, M.; Barbazanges, M. Submitted.

Oral ommunication:
- Helicenes: Synthesis and Applications in catalysis, C. Medena, M. Barbazanges Journées Bibliographiques de l’ED406, 2 fév. 2015 (UPMC, Paris)
- Metallohelicenes: Synthesis and Application in cycloisomerization reaction, C. Medena, M. Barbazanges Journées de Chimie Moléculaire 24 mai 2016 (UPMC, Paris)
- Chiral phosphate in Rh-catalyzed [2+2+2] reaction: Ligand, Counterion, or Both?, M. Barbazanges, Groupe d’Etude en Chimie Organique (GECO57), 21-26 août 2016, Ascain (64), France.
- Chiral phosphate in Rh+ - and Ir+ -asymmetric catalysis, M. Barbazanges, Journées de Printemps de la Division de Chimie Organique 2017 (DCO), 28 mars 2017, Paris, France.
- Chiral phosphate in Rh+ - and Ir+ -asymmetric catalysis, M. Barbazanges, séminaire invité, 20 décembre 2018, Nanyang Technological University, Singapour

Helicenes, aromatic compounds with a helical structure, intrinsically possess interesting chiroptic properties and find applications in various fields such as optics, electronics, biology, supramolecular and organic synthesis. Of particular interest is the preparation of optically enriched helicenes, as the latter are paving the way towards asymmetric catalysis. To date, only a few examples of helicenes used as ligands are reported in the literature. This proposal aims at revealing this under-utilized potential of helical chirality in applied organometallic catalysis, by devising a new generation of cyclic helicenes. We based our research project on two hypotheses. Helicenes’ under-utilization in organometallic catalysis could be due to the difficult preparation of optically enriched helical devices. Indeed, enantioselective organometallic synthesis of carbohelicenes struggle to reach 70% enantiomeric excess and most of time, chiral helicenes have to be isolated from the corresponding racemate by chiral preparative HPLC. Moreover, in organometallic catalysis, chiral induction by the existing helical systems is not optimal so far. In this proposal, we thus decide to have it both ways: improving the chiral induction in catalysis by designing new helical catalysts; and developing new efficient metal-catalyzed accesses to the desired chiral helical templates. Both strategies combined will allow access to helically chiral organometallic complexes that will lead to high induction in asymmetric catalysis. In this perspective, synthesis of novel cyclic helical systems will be envisioned. Introduction of an organic or an organometallic linker between the extremities of the helicene will bring closer the reactive site and the helical chiral environment, thus optimizing the chiral induction. A bis-helical strategy, totally embedding the reactive site in the helical cavity, will also be considered. To achieve the preparation of such scaffolds, the synthesis of chiral polysubstituted helical platforms, bearing versatile anchors at the hindered inner positions will be realized. Racemic synthesis coupled to new resolution techniques, as well as enantioselective approaches based on [2+2+2] cycloaddition and using bold and innovative cobalt systems, will be implemented. These new helical complexes will be employed as chiral ligands or counter-ions in metal-catalyzed cycloisomerisation reactions and cycloadditions. DFT calculations, already performed for selected examples, will help validating our structures as well as rationalizing the stereochemical outcomes observed in catalysis.

Project coordinator

Madame Marion BARBAZANGES (Institut Parisien de Chimie Moléculaire) – marion.barbazanges@upmc.fr

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

IPCM Institut Parisien de Chimie Moléculaire

Help of the ANR 168,438 euros
Beginning and duration of the scientific project: March 2014 - 42 Months

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