Atropisomeric palladium-NHC complexes : esign,synthesis and applications in asymmetric catalysis

Les performances des catalyseurs à base de palladium dans diverses réactions de couplage croisé ont suscité un intérêt croissant depuis les années soixante-dix et le développement de versions énantiosélectives a fait l’objet de recherches intensives. Dans ce domaine, les ligands auxiliaires N-hétérocycliques carbènes (NHCs) monodentates possédant de bonnes propriétés σ donneur et π-accepteur confèrent au métal d’excellentes réactivités. Les ligands NHCs sont appelés ligands intelligents, car leurs propriétés électroniques et stériques peuvent être finement ajustées à des transformations catalytiques spécifiques. Par conséquent, les complexes chiraux NHC-Pd sont une classe de catalyseurs chiraux qui se sont développés rapidement au cours des dernières décennies. Néanmoins, de nouveaux catalyseurs avec une réactivité et une énantiosélectivité améliorées sont nécessaires car seules quelques applications sont réellement développées dans l’industrie. L’objectif de mon doctorat était d’étudier un nouveau concept de complexes chiraux NHC-Pd et leurs applications pour explorer de nouvelles transformations catalytiques. Le premier chapitre expose la chimie du carbène en tant que ligands des métaux de transition avec les principales réalisations décrites dans la littérature. Les propriétés chimiques des NHCs sont également brièvement présentées. Dans ce chapitre, les différents designs de ligands chiraux NHC pour la catalyse à base de palladium sont résumés ainsi que les applications dans la catalyse énantiosélective. Enfin, des études antérieures sur les complexes chiraux NHC-palladium réalisées dans notre laboratoire sont présentées afin de définir les objectifs et les enjeux de mon travail de doctorat. Dans le deuxième chapitre de ce manuscrit, nous analysons les avantages et les inconvénients des catalyseurs développés dans notre groupe, afin de simplifier les étapes de synthèse et d’améliorer l’activité catalytique. En conséquence, certains nouveaux complexes NHC-avec chiralité axiale ont été conçus et synthétisés par des méthodologies de synthèse décrites dans la littérature. Les complexes chiraux de palladium possédants un NHC de symétrie C2 ont été d’abord préparés puis les diastéréoisomères ont été purifiés par chromatographie sur colonne de gel de silice pour éliminer les composés méso. Par la suite, les complexes hétérochiraux ont été résolus par HPLC chirale à l’échelle préparative pour les obtenir sous forme énantiomériquement pure. Enfin, la réactivité catalytique et l’induction énantiomérique que permet d’atteindre ces catalyseurs Pd-NHC-chiraux ont été évaluées dans une réaction modèle : l’α-amide arylation d’amides. De très bonnes inductions chirales ont été atteintes.Dans le troisième chapitre, de nouvelles transformations catalysées par le palladium ont été conçues et étudiées avec les nouveaux complexes chiraux-NHC précédemment établis en laboratoire. Après une étape d’optimisation des conditions de réaction et le criblage de plusieurs catalyseurs, nous avons constaté que ces nouveaux catalyseurs permettent d’obtenir une bonne induction chirale dans l’α-arylation de cétones. Nous avons également essayé l’hydrogénation catalysée par des complexes Pd-NHC cependant cette réaction n’a pas conduit à des résultats notables. Les réactions de couplage de Kumada ont également été étudiées pour synthétiser des métacyclophanes possédant une chiralité planaire. Divers métacyclophanes chiraux ont été préparés et leurs stabilités de configuration ont été étudiées. Des conditions de réaction optimales ont été identifiées afin de réaliser cette réaction asymétrique avec de bons résultats en termes de réactivité et d’énantiosélectivité.The performances of palladium-based catalysts in various cross-coupling reactions have attracted an ever-growing attention since the seventies and the development of enantioselective versions was the subject of intensive research. In this field, monodentate auxiliary N-heterocyclic carbene (NHCs) ligands possessing robust σ-donating and adaptable π-accepting properties confer to the metal excellent reactivities. NHCs ligands are referred as smart ligands, because their electronic and steric properties can be finely tuned to specific catalytic transformations. Therefore, chiral NHC-Pd complexes are a class of chiral catalysts that have developed rapidly in the recent decades. Nevertheless, new catalysts with enhanced reactivity and enantioselectivities are required as only few applications are actually developed in the industry. The goal of my Ph.D. was the investigated of a new design of chiral NHC-Pd complexes and their application to explore new catalytic transformations. The first chapter is focused on carbene chemistry as ligands of transition metals with main achievements reported in the literature. Chemical properties of NHCs have been also reviewed. In this chapter, the different designs of chiral NHC ligands for palladium-based catalysis reported in the literature as well as their applications in enantioselective catalysis have been also surveyed. Finally, previous studies on chiral NHC-palladium complexes in our laboratory are presented in order to define the objectives and issues of my Ph.D. work. In the second chapter of this manuscript, we analyze the advantages and disadvantages of the catalysts developed in our group, with the goal of simplifying the synthesis steps and improving the catalytic activity. As a result, some novel NHC-Pd complexes with axial chirality were designed and synthesized by known synthetic methods. The synthesized C2-symmetric NHC-Pd complexes were first attempted to separate diastereomers by silica gel column chromatography to remove meso compounds. Subsequently, heterochiral complexes were resolved in enantiomerically pure form by preparative-scale chiral HPLC. Finally, the catalytic reactivity and enantiomeric inductions of these highly enantiomerically pure chiral NHC-Pd catalysts were evaluated in the benchmark reaction: α-amide arylation of amides. Up to good chiral inductions were reached.In the third chapter, novel palladium-catalyzed transformations were investigated and developed with the new chiral Pd-NHC complexes previously established in the laboratory. After the optimization of reaction conditions and the screening of several catalysts, we found that these new catalysts can achieve good chiral induction in the α-arylation of ketones. We also tried NHC-Pd catalyzed hydrogenation, although the reaction did not lead to noticeable results. Kumada coupling reactions were also studied to synthesize planar-chiral metacyclophanes. Various chiral metacyclophanes have been prepared and their configurational stabilities have been investigated. Finally, optimal reaction conditions have been identified allowing to carry this asymmetric reaction with good results in terms of both reactivity and enantioselectivity

Research progress of chiral rare earth complexes in asymmetric catalysis

With the increasing demand of the optical compounds,asymmetric catalysis becomes a hot research area.The rare earth elements are defined as the elements of lanthanide from La to Lu,together with Sc and Y.Compared to the orbital interaction between the other transition metals and ligands,the one between rare earth metals and ligands is unique.Therefore,the application of chiral rare earth complexes in asymmetric catalysis has also attracted much attention.This paper reviewed research progress of chiral rare earth complexes in asymmetric catalysis

C1 ‐Symmetric Atropisomeric NHC Palladium(II) Complexes: Synthesis, Resolution and Characterization

International audienceSeries of chiral palladium(II) allyl and cinnamyl complexes bearing a C1-symmetric N-heterocyclic carbenes were synthesized from achiral precursors. The chirality of theses complexes results from the formation of the carbene-palladium bond which restricts the rotation of dissymmetric N-aryl substituents of the NHC and thus creates an axis of chirality. Chiral HPLC at preparative scale enabled the resolution of racemic complexes and provided a straightforward access to complexes with excellent enantiopurities (>99.5% ee). Enantiopure complexes were studied by crystal X-ray diffraction and electronic circular dichroism (ECD). Their configuration stabilities were investigated both experimentally and theoretically through the determination of the rotational barrier values. These complexes were tested for the intramolecular α-arylation of amides, with a moderate chiral induction (up to 54% ee)

C 1 ‐Symmetric Atropisomeric NHC Palladium(II) Complexes: Synthesis, Resolution and Characterization

International audienceSeries of chiral palladium(II) allyl and cinnamyl complexes bearing a C1-symmetric N-heterocyclic carbenes were synthesized from achiral precursors. The chirality of theses complexes results from the formation of the carbene-palladium bond which restricts the rotation of dissymmetric N-aryl substituents of the NHC and thus creates an axis of chirality. Chiral HPLC at preparative scale enabled the resolution of racemic complexes and provided a straightforward access to complexes with excellent enantiopurities (>99.5% ee). Enantiopure complexes were studied by crystal X-ray diffraction and electronic circular dichroism (ECD). Their configuration stabilities were investigated both experimentally and theoretically through the determination of the rotational barrier values. These complexes were tested for the intramolecular α-arylation of amides, with a moderate chiral induction (up to 54% ee)

C2 -Symmetric atropisomeric N-heterocyclic carbene–palladium( ii ) complexes: synthesis, chiral resolution, and application in the enantioselective α-arylation of amides

This picture illustrates the following publication: C2-Symmetric Atropisomeric N-Heterocyclic Carbene-Palladium(II) Complexes: Synthesis, Chiral Resolution and Application in enantioselective α-Arylation of Amides” L. Kong, Y. Chou, M. Albalat, M. Jean, N. Vanthuyne, S. Humbel, P. Nava, H. Clavier, Dalton Trans. 2023, 52, 8728-8736.DOI: 10.1039/d3dt01182hIt has been produced using the software ChemDraw.Cette image est l'illustration de la publication suivante : C2-Symmetric Atropisomeric N-Heterocyclic Carbene-Palladium(II) Complexes: Synthesis, Chiral Resolution and Application in enantioselective α-Arylation of Amides” L. Kong, Y. Chou, M. Albalat, M. Jean, N. Vanthuyne, S. Humbel, P. Nava, H. Clavier, Dalton Trans. 2023, 52, 8728-8736.DOI: 10.1039/d3dt01182hElle a été réalisée en utilisant le logiciel ChemDraw

C2 -Symmetric atropisomeric N-heterocyclic carbene–palladium( ii ) complexes: synthesis, chiral resolution, and application in the enantioselective α-arylation of amides

International audienceThe concept of atropisomeric N-heterocyclic carbene (NHC)–metal complexes was extended to NHCs possessing a C2-symmetry and implemented to prepare palladium-based complexes. An in-depth study of the NHC precursors and the screening of various NHC ligands enabled us to circumvent the issue associated with the formation of meso complexes. A set of 8 atropisomeric NHC–palladium complexes were prepared and then obtained with high enantiopurities, thanks to an efficient resolution by chiral HPLC at the preparative scale. These complexes displayed good activity in the intramolecular α-arylation of amides and various cyclic products were isolated with excellent enantioselectivities (up to 98% ee)

Chiral Atropisomeric‐NHC Catechodithiolate Ruthenium Complexes for Z ‐Selective Asymmetric Ring‐Opening Cross Metathesis of Exo ‐Norbornenes

This image illustrates the article "Chiral Atropisomeric-NHC Catechodithiolate Ruthenium Complexes for Z-Selective Asymmetric Ring-Opening Cross Metathesis of Exo-Norbornenes" Chem. Eur. J. 2023, 29, e202300341 (doi 10.1002/chem.202300341

Chiral Atropisomeric-NHC Catechodithiolate Ruthenium Complexes for Z-Selective Asymmetric Ring-Opening Cross Metathesis of Exo-Norbornenes

International audienceA set of 16 chiral ruthenium complexes containing atropisomerically stable N-Heterocyclic Carbene (NHC) ligands was synthesized from prochiral NHC precursors. After a rapid screening in asymmetric ring-opening-cross metathesis (AROCM), the most effective chiral atrop BIAN-NHC Ru-catalyst (up to 97:3 er) was then converted to a Z-selective catechodithiolate complex. The latter proved to be highly efficient in Z-selective AROCM of exo-norbornenes affording valuable trans-cyclopentanes with excellent Z-selectivity (>98%) and high enantioselectivity (up to 96.5:3.5 er)

Expedient Access to Optically Pure Atropisomeric-NHC Ruthenium Complexes for (Z)-Selective Asymmetric Ring- Opening Cross Metathesis

Optically pure ruthenium complexes containing atropisomerically stable N-Heterocyclic Carbene (NHC) ligands are described. Isolated in excellent optical purities (up >99.5% ee) by a successful preparative HPLC resolution on a chiral stationary phase, these catalysts demonstrate excellent enantioselectivities in asymmetric ring-opening-cross metathesis (AROCM) (up to 97:3 er). Additionally, an optically pure Z-stereoselective catechodithiolated complex was also synthesized in nearly quantitative yield (or in-situ generated), furnishing enantioenriched Z-AROCM products in excellent 99/1 Z/E ratio and high enantioselectivity (up to 96.5:3.5 er)

Chiral Atropisomeric‐NHC Catechodithiolate Ruthenium Complexes for Z ‐Selective Asymmetric Ring‐Opening Cross Metathesis of Exo ‐Norbornenes

This image illustrates the article "Chiral Atropisomeric-NHC Catechodithiolate Ruthenium Complexes for Z-Selective Asymmetric Ring-Opening Cross Metathesis of Exo-Norbornenes" Chem. Eur. J. 2023, 29, e202300341 (doi 10.1002/chem.202300341