Catalyse au fer des réactions de couplage croisé : mécanismes, identification et spéciation des intermédiaires réactionnels

For a few years iron catalysis has been considered as a cheap and environmentally benign alternative for traditional noble metal catalysts. Still, because of its hardly controlled access to a large scope of oxidation and spin states, iron’s reactivity as a catalyst has not been fully understood yet. This work first investigates the question of iron’s catalytically active oxidation states in cross-coupling reactions, through an experimental and computational study. The second part of the manuscript deals with the comprehension of some Fe-catalyzed cross-coupling reactions. The detrimental homocoupling pathway of an aryl-aryl Kumada reaction is elucidated, and the mechanism of the reaction between organomanganese nucleophiles and alkenyl electrophiles is investigated. Finally, the modification of the metal’s coordination sphere thanks to the addition of σ-donating ligands helps to understand the matter of the transmetallation degree control during the cross-coupling process. This work uses classic inorganic chemistry techniques, along with several spectroscopies (NMR, EPR, Mössbauer) and theoretical DFT calculations.Depuis quelques années, le fer s’est imposé comme une alternative pertinente, peu toxique et peu coûteuse, aux catalyseurs à base de métaux nobles classiquement développés. Par les larges gammes de degrés d’oxydation et d’états de spin auxquelles il a accès, le fer présente pourtant une réactivité peu comprise et donc délicate à orienter. Ces travaux de thèse s’intéressent d’abord à l’identification des degrés d’oxydation du fer actifs en catalyse des réactions de couplage croisé, via une étude bibliographique et une étude expérimentale et théorique qui relie les degrés d’oxydation +II, +I et 0 du fer. La deuxième partie du manuscrit vise à la compréhension des mécanismes de réactions de couplage ferrocatalysées et des réactions secondaires concurrentielles. Elle décrit en particulier l’élucidation du mécanisme d’une réaction indésirable d’homocouplage concurrentielle au couplage de Kumada aryle-aryle, et la détermination de l’espèce active au cours d’un couplage de nucléophiles organomanganeux et d’électrophiles alcényle. Enfin, la modification de la sphère de coordination du fer via l’ajout de ligands σ-donneurs permet d’appréhender la question du contrôle du degré de transmétallation du catalyseur. Ces travaux utilisent des techniques classiques de chimie inorganique, ainsi que les spectroscopies RMN, RPE ou Mössbauer. Ces techniques expérimentales sont complétées par des modélisations théoriques par calculs DFT

Fe-catalyzed cross-coupling reactions : mechanisms, identification and speciation

Depuis quelques années, le fer s’est imposé comme une alternative pertinente, peu toxique et peu coûteuse, aux catalyseurs à base de métaux nobles classiquement développés. Par les larges gammes de degrés d’oxydation et d’états de spin auxquelles il a accès, le fer présente pourtant une réactivité peu comprise et donc délicate à orienter. Ces travaux de thèse s’intéressent d’abord à l’identification des degrés d’oxydation du fer actifs en catalyse des réactions de couplage croisé, via une étude bibliographique et une étude expérimentale et théorique qui relie les degrés d’oxydation +II, +I et 0 du fer. La deuxième partie du manuscrit vise à la compréhension des mécanismes de réactions de couplage ferrocatalysées et des réactions secondaires concurrentielles. Elle décrit en particulier l’élucidation du mécanisme d’une réaction indésirable d’homocouplage concurrentielle au couplage de Kumada aryle-aryle, et la détermination de l’espèce active au cours d’un couplage de nucléophiles organomanganeux et d’électrophiles alcényle. Enfin, la modification de la sphère de coordination du fer via l’ajout de ligands σ-donneurs permet d’appréhender la question du contrôle du degré de transmétallation du catalyseur. Ces travaux utilisent des techniques classiques de chimie inorganique, ainsi que les spectroscopies RMN, RPE ou Mössbauer. Ces techniques expérimentales sont complétées par des modélisations théoriques par calculs DFT.For a few years iron catalysis has been considered as a cheap and environmentally benign alternative for traditional noble metal catalysts. Still, because of its hardly controlled access to a large scope of oxidation and spin states, iron’s reactivity as a catalyst has not been fully understood yet. This work first investigates the question of iron’s catalytically active oxidation states in cross-coupling reactions, through an experimental and computational study. The second part of the manuscript deals with the comprehension of some Fe-catalyzed cross-coupling reactions. The detrimental homocoupling pathway of an aryl-aryl Kumada reaction is elucidated, and the mechanism of the reaction between organomanganese nucleophiles and alkenyl electrophiles is investigated. Finally, the modification of the metal’s coordination sphere thanks to the addition of σ-donating ligands helps to understand the matter of the transmetallation degree control during the cross-coupling process. This work uses classic inorganic chemistry techniques, along with several spectroscopies (NMR, EPR, Mössbauer) and theoretical DFT calculations

Aryl-Alkyl Cross-coupling versusversus Homo-coupling: A Mechanistic Study On The Catalytic Performance Of A Bulky Silylamide Iron(II) Complex

International audienceIron catalysis has raised a great interest in the organometallic field since the 1970s and the first successful Fe-catalyzed cross-coupling reactions developed by Kochi, as it is a cheaper, more earth-abundant and less toxic alternative to many other transition metals. Kumada-type reactions between aryl Grignard reagents and organic electrophiles are of high importance, but a significant issue remains in the competition between effective cross-coupling, and homocoupling of the Grignard reagent affording unwanted symmetrical biaryl byproducts. Nakamura proposed an explanation for the large presence of this byproduct in the presence of several aryl groups on the iron center resulting from multiple Mg-to-Fe transmetallations, and proposed the addition of a source of fluoride anions to block this possibility. However, our study of the catalytic behavior of the bulky silylamide iron(II) complex [Fe(N(SiMe$_2$Ph)$_2$)$_2$] in an aryl-alkyl cross-coupling reaction refutes the hypothesis that the multi-transmetallations are the only cause of homocoupling. The steric hindrance of the ligands effectively prevents more than one transmetallation on the iron atom, affording a stable Ar-Fe bond, but it does not quite impede the homocoupling. Stoichiometric and catalytic tests involving 1H paramagnetic NMR, EPR spectroscopy and cyclic voltammetry were lead in order to discuss the mechanism of the reaction, evidencing transient Fe III species responsible for the formation of the homocoupling product

Importance of two-electron processes in Fe-catalyzed aryl-(hetero)aryl cross-couplings: evidence of Fe0 / FeII couple implication.

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Assessment of the ground spin state of iron(I) complexes : insights from DFT predictive models

International audienceAn efficient DFT benchmarking method is described for the assessment of the ground spin state of various iron(I) organometallic complexes. Factors determining the spin multiplicity are discussed. A focus is put on the analysis of the electronic structure of bis-ligated X$-$[Fe$^I$]$-$X species

Iron-Catalyzed Cross-Coupling of Bis-(aryl)manganese Nucleophiles with Alkenyl Halides: Optimization and Mechanistic Investigations

International audienceVarious substituted $bis$-(aryl)manganese species were prepared from aryl bromides by one-pot insertion of magnesium turnings in the presence of LiCl and in situ trans-metalation with MnCl$_2$ in THF at −5°C within 2 h. These $bis$-(aryl)manganese reagents undergo smooth iron-catalyzed cross-couplings using 10 mol% Fe(acac)$_3$ with various functionalized alkenyl iodides and bromides in 1 h at 25°C. The aryl-alkenyl cross-coupling reaction mechanism was thoroughly investigated through paramagnetic $^1$H-NMR, which identified the key role of $tris$-coordinated $ate$-iron(II) species in the catalytic process

Iron-Catalyzed Cross-Coupling of Functionalized Benzylmanganese Halides with Alkenyl Iodides, Bromides, and Triflates

International audienceVarious substituted benzylic manganese chlorides were prepared by insertion of magnesium turnings in the presence of MnCl2·2LiCl in THF at −5 °C within 2 h. These benzylic manganese reagents underwent smooth cross-couplings with various functionalized alkenyl iodides, bromides, and triflates or iodoacrylates in the presence of 10 mol % FeCl2 at 25 °C for 1–12 h. Mechanistic studies showed that benzylic manganese halides produced, in the presence of FeCl2, a very reactive iron ate complex

Relevance of Single-Transmetalated Resting States in Iron-Mediated Cross-Couplings: Unexpected Role of σ-Donating Additives

International audienceControl of the transmetalation degree of organoiron(II) species is a critical parameter in numerous Fe-catalyzed cross-couplings to ensure the success of the process. In this report, we however demonstrate that the selective formation of a monotransmetalated FeII species during the catalytic regime counterintuitively does not alone ensure an efficient suppression of the nucleophile homocoupling side reaction. It is conversely shown that a fine control of the transmetalation degree of the transient FeIII intermediates obtained after the activation of alkyl electrophiles by a single-electron transfer (SET), achievable using σ-donating additives, accounts for the selectivity of the cross-coupling pathway. This report shows for the first time that both coordination spheres of FeII resting states and FeIII short-lived intermediates must be efficiently tuned during the catalytic regime to ensure high coupling selectivities

Evolution of Ate- organoiron(II) species towards lower oxidation states: role of the steric and electronic factors

International audienceAte -iron(II) species such as [Ar 3 Fe II ] ─ (Ar = aryl) are key intermediates in Fe-catalyzed couplings between aryl nucleophiles and organic electrophiles. They can be active species in the catalytic cycle, or lead to Fe 0 and Fe I oxidation states, which can themselves be catalytically active or lead to unwished organic byproducts. Analysis of the reactivity of the intermediates obtained by step-by-step displacement of the mesityl groups in high-spin [Mes 3 Fe II ] ─ by less hindered phenyl ligands was performed, and enlightened the crucial role of both steric and electronic parameters in the formation of the Fe 0 and Fe I oxidation states. The formation of quaternized [Ar 4 Fe II MgBr(THF)] ─ intermediates allows to reduce the bielectronic reductive elimination energy required for the formation of Fe 0 . Similarly, a small steric pressure of the aryl groups in [Ar 3 Fe II ] ─ enables the formation of aryl-bridged [{Fe II (Ar) 2 } 2 (µ-Ar) 2 ] 2─ species, which afford the Fe I oxidation state by bimetallic reductive elimination. These results are supported by 1 H NMR, EPR and 57 Fe-Mössbauer spectroscopies, as well as by DFT calculations

Iron-catalyzed C―C cross-coupling in the absence of additional ligands: active species and off-cycle pathways

International audienceIron-catalyzed cross-coupling between a Grignard reagent RMgX and an electrophile R'─X was discovered by Kochi in the 1970s and witnessed recent improvements. This transformation can be carried out using simple iron salts such as FeCl$_2$ , FeCl$_3$ or Fe(acac)$_3$ in the absence of additional ligand. However, these systems lead to short-lived reactive species, making in-situ mechanistic analysis challenging. By means of Mössbauer, cw-and pulse-EPR spectroscopies, we demonstrated that two arene-stabilized Fe$^0$ and Fe$^I$ resting states were obtained by reduction of the precursor in toluene (Fig. 1a). Analysis of the bulk revealed that the ($\eta^4$-C$_6$H$_5$Me)$_2$Fe$^0$ complex catalyzes efficiently aryl-heteroaryl coupling, via a Fe$^0$ /Fe$^{II}$ cycle (Fig. 1b). Preliminary results moreover show that transient tris(aryl) species such as [Ph$_3$ Fe$^{II}$ ]-are key intermediates in the formation of the lower oxidation states. Fe$^0$ and Fe$^I$ are respectively afforded by 2-electron reductive elimination and by redox disproportionation of the +II ox. state