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Mechanism of hydrogenation and transfer hydrogenation of polar unsaturations catalyzed by non N-H systems

Periodic Reporting for period 1 - NONNH (Mechanism of hydrogenation and transfer hydrogenation of polar unsaturations catalyzed by non N-H systems)

Reporting period: 2015-07-12 to 2017-07-11

The project addresses the reduction of compounds containing polar unsaturations, catalyzed by metal complexes under strongly basic conditions. This is an important reaction that enters the manufacture of many high added value fine chemicals. The role of the strong base for catalysts that do not contain active protons in the ligand donor functions is unclear, as well as the relationship between the mechanisms of hydrogenation by H2 and transfer hydrogenation, for instance by alcohols or formic acid. The sought mechanistic understanding can lead to the design of improved catalysts and operating conditions. The project is being implemented by a multifaceted approach that includes synthesis, characterization, catalysis, kinetics, and computations and is further enriched by parahydrogen NMR studies through a 3-month secondment at the University of York. This multisectorial training puts the ER on an excellent basis to further develop his professional career in research. The ER has an excellent basic training from one of the premier institutions in his Country and an outstanding publication record. The ER is also depeloping transferrable skills by assisting the permanent staff with mentoring undergraduate students in the group. He has delivered presentations at internal group meetings and oral/poster presentations at two international conferences. He has also contributed to drafting his research publications.
The ER has started his project by synthesizing rhodium and iridium complexes previously used in the group as pre-catalysts in ketone hydrogenation. These complexes contain a bidentate phosphine-thioether ligand (PS ligand) based on the ferrocene scaffold with planar chirality. He has tested these complexes as catalysts in transfer hydrogenation of the same substrates where the source of hydrogen is now isopropanol rather than gaseous H2. He has also used the same compounds in the catalytic redox isomerization of allylic alcohols. A striking results of this work is that, although the precatalysts need hydrogen from H2 or from isopropanol for activation and these conditions ultimately lead to hydrogenation of the isomerized ketone product, the allylic alcohol isomerization occurs much more rapidly than the subsequent reduction, allowing the ketone intermediates to be obtained in good selectivities, especially under transfer hydrogenation conditions (absence of gaseous H2). The Rh precatalysts were more active than the Ir analogues. All these processes need a strong base for activity.
According to previous work in the group, the active form of the catalyst for the iridium system in ketone hydrogenation seems to be an anionic hydride, [IrH4(L)2]- (L = ligand) involving a cooperative effect of the counter-cation for the ketone activation. The role of the strong base seems that of allowing deprotonation of intermediate alcohol complexes, followed by beta-H elimination and stabilization of the anionic hydride systems. Therefore, a considerable effort has been made in synthesizing, isolating and characterizing models of this anionic complex and in studying the stoichiometric steps leading to these species from the pre-catalyst. Using PPh3 as ligand L, only neutral hydride systems could be obtained starting from the common precatalyst [Ir(COD)Cl]2 (COD = 1,5-cyclooctadiene). This is perhaps related to the monodentate nature of the ligand, allowing stabilization as neuitral [IrH3(L)3]. This work has nevertheless allowed to confirm that the pre-catalyst can be activated under transfer hydrogenation conditions by the strong base, i.d. H2 is not necessary, and that the cyclooctadiene ligand is lost during the process. This point was previously controversial. This work is now published (J. Organometal. Chem. 2017, 829, 14-21).
Using diphenylphosphinoethane (dppe) as a bidentate ligand (L2), the ER has indeed been able to obtain evidence that an anionic hydride is formed. However, this compound is too insoluble and air sensitive for a spectroscopic characterization and decomposes in strongly coordinating solvents (a crystal of [IrH4(dppe)(DMSO)] has been obtained from a crystallization from dimethylsulfoxide). Its catalytic activity in ketone transfer hydrogenation has been demonstrated. It has also been shown that the nature of the cation (Na vs. K) and the presence of chelators for the cation (e.g. crown ethers) affect the catalytic performance, demonstrating the importance of the Ir-cation cooperativity.
During the secondment period at the University of York, the ER has investigated the mechanism of the H2 addition to the Ir complex [Ir(COD)(L2)]+, with L2 = ferrocene PS ligand, by using the NME technique with para-hydrogen at various temperatures. The study has revealed an extremely complex mechanism, with many intermediates. The study is now being continued on a collaborative basis by the York group, after the return of the ER to the main host institution in Toulouse, using simpler ligands (e.g. dppe).
The investigation of the mechanism of action of the strong base on the hydrogenation and hydrogen transfer catalyst is important for the design of improved catalysts and operating conditions. Indeed, these chemical transformations are key steps in a myriad of industrial processes in the fine chemical industry leading to cosmetics, pharmaceutical and agrochemical products. Once the mechanism is fully elucidated, it will be possible to find ways to develop new catalysts with increased efficiency. Most notably, it would be of great impact if it will be possible to anchor the catalyst to a solid support or develop biphasic protocols where the base remains confined together with the catalyst, leading to efficient catalyst recovery and recycling and simplifying the product separation and purification steps. This would lead to economical and environmental advantages.
The progress made so far on the basis of this research activity concerns the fundamental understanding of the reaction and the role of the base. Notably, the nature of the active species, previously only hypothesized on the basis of theoretical calculations, is now more convincingly suggested by the isolation of related species and by the demonstration of their catalytic activity.
Proposed structure of the catalyst active site