IMMOBILIZATION OF CAAC RUTHENIUM CATALYSTS

Over the last decade olefin metathesis1 become a useful tool for carbon-carbon bond forming method2,3. The increased interest for this reaction was attributed to the discovering of ruthenium catalysts4 which combines excellent tolerance to a variety of functional groups and In the mid 1990’s, Grubbs introduced bisphosphane catalyst C55 which presents good activity in ROMP, RCM6. Nevertheless, it shows low efficiency towards substituted olefins and suffers from its thermal instability7. Further studies on improving catalytic activity of the 1st  isopropoxybenzylidene ligands. These systems are remarkably robust; they can be purified by column chromatography. The second generation based Hoveyda catalyst C22 was found to perform well in reaction involving challenging substrates (electron-deficient, substituted olefins) reaction.  One major drawback which limited the industrial application of these catalysts is the formation of deeply colored ruthenium by-products, which are difficult to remove from the reaction products. The presence of catalyst or compounds of catalyst decomposition in the reaction can promote undesired reactions such as carbon double bond isomerization during workup. Removal of metal impurities is crucial in pharmaceutical and fine chemical production. Several methods have been proposed to reduce ruthenium content in final lead tetraacetate15). Chromatographic purification procedures16,17 are generally required to bring the ruthenium content below the 100 ppm level. However, this method is difficult and expensive to implement on an industrial scale. To reduce ruthenium waste levels, the use of tagged catalysts has received a dramatic increased of interest. Numerous studies have been carried out to develop supported or tagged versions of homogeneous catalysts18 on various supports such as solid and soluble polymers19, fluorous phases20, ionic liquids21, and also supercritical carbon dioxide media22. Hoveyda catalysts23 have been specifically modified due to their good stability, as we shown in the bibliographic part (page 29). Some catalytic systems developed by Mauduit, Yao and Grela using ionic liquids were found to lead to low levels of metal leaching (10 ppm) and to be efficient in terms of reusability (10 consecutives runs). However, large amounts of  immobilized catalyst are required (2.5 to 6 mol % Ru) to keep the efficiency of homogeneous analogues. One of the aims of the thesis is to design effective recoverable catalysts for a better use of the catalyst due to its synthetic cost. We choose to modify efficient ruthenium containing cyclic alkyl(amino)carbene complexes with the goal to immobilize them in ionic liquids. Indeed, the  higher molecular weight in ionic liquids. A simple biphasic separation based on the good affinity of the catalyst for the ionic phase allows isolating the final organic products. Thus, we examined the potential structural changing of the CAAC complexes to improve the affinity of the catalyst for the ionic liquid phase.

We focused on tuning the benzylidene moiety. Several groups have reported the modification on the chelating ligand. Blechert has shown that catalysts C2329 and C2530 which contain ortho substituents to the isopropoxy group, show increased initiation rate. These studies suggested that steric parameter is the main factor securing the higher activity of these complexes. On the other hand, Grela has shown that second generation based Hoveyda catalyst can be  isopropoxybenzylidene ring of C22 leads to complex C2431 which is as stable as C22 but more reactive. Then, they observed that the increase of electron density in the benzylidene part of C22 results in an increased stability. Nevertheless, the activity of C86 does not reach the level outlined by C24 and C25. Blechert group prepared a series of catalysts with modified isopropoxybenzylidene ligands32. They confirmed that increasing steric hindrance adjacent to the isopropoxy group enhanced reaction rates. Decreasing electron density at both the chelating oxygen atom and the Ru=C bond accelerated reaction rate in NHC complexes, while higher electron density at oxygen enhanced reaction rates of first generation catalysts. With the aim of decreasing the level of ruthenium by products in pharmaceutical processes, Grela has described a new strategy for the non covalent immobilisation of Ru catalysts that relies on electrostatic binding33. A complex bearing the electron-donating diethylamino group C86 was synthesized and it showed, as expected little or no activity. This catalyst was then immobilized on sulfonated Dowex support and affords good reactivity and recyclability. In fact, the diethylamino group reacts with sulfonic acid leading to the formation of ammonium (EWG). We chose to use the last concept of “electron-donating to electron-withdrawing activity switch” developed by Grela34 to prepare CAAC catalysts which bear a quaternary ammonium group.