Lanthanide-mediated organic synthesis : lanthanide(III) compounds as Lewis acid catalysts and cerium(IV) compounds as reagents for reactions in ionic liquids (2007)

In this PhD project, new procedures were investigated for various important organic reactions. Nowadays, organic procedures should not only result in high reaction yields and purity but moreover they should be designed to be environmentally friendly as well. Therefore, a proper choice of catalyst and solvent is an important aspect. In this study, greener solvents such as ionic liquids, water and rather unhazardous organic solvents were used. Moreover, this PhD research was focused on the use of lanthanide complexes in catalysis. The optimal reaction conditions as well as the role of the lanthanide ion in the reaction mechanism were investigated. Besides cerium(IV)-mediated reactions in ionic liquids, the use of lanthanide(III) compounds as strong Lewis acids was examined for the catalysis of various organic reactions. Currently, acid-catalyzed organic synthesis is mostly performed using mineral acids or Lewis acids such as AlCl3, ZnCl2, BF3, TiCl4, SnCl4, BF3·OEt2, … However, these conventional Lewis acids are often required in stoichiometric amounts and are not stable in the presence of water. In addition, large amounts of waste are formed during the work-up procedure as these Lewis acids can not be recovered and reused. Hence, new procedures in which less waste is produced are desired. During the last decade, lanthanide(III) triflates have been widely studied for numerous organic reactions to overcome the drawbacks of conventional Lewis acids. However, the disadvantages of triflate salts include their high cost and the fact that one needs to handle the corrosive triflic acid for their preparation. Based on the work of the groups of Kobayashi and Braddock concerning lanthanide(III) triflates, we investigated the use of lanthanide(III) salts of less corrosive and much cheaper aromatic sulfonic acids, such as p-toluenesulfonic acid and nitrobenzenesulfonic acids, as new Lewis acid catalysts. Lanthanide(III) tosylates and nitrobenzenesulfonates are straightforwardly prepared from the respective lanthanide(III) oxide and sulfonic acid. From the results presented in chapter 3, it can be seen that these complexes efficiently catalyze a variety of reactions like the nitration of aromatic compounds, the acylation of alcohols and the synthesis of calix[4]resorcinarenes. Complete conversion can already be obtained with only a few mol% of catalyst and moreover these catalysts are easily recovered and reused without loss in efficiency and selectivity. The presence of water in the reaction system does not deactivate the catalyst and even hydrated lanthanide(III) salts are effective. Besides trivalent lanthanides, commercially available iron(III) tosylate was also found to be an effective and recyclable catalyst. In addition, we have shown that lanthanide(III) chloride hydrates were also rather efficient catalysts for the acylation of alcohols and the formation of calix[4]resorcinarenes. Although lanthanide(III) chloride hydrates were also reusable and only required in catalytic amounts, their widespread use will probably be limited by solubility problems. Moreover, comparison of ytterbium(III) tosylate and ytterbium(III) chloride showed that ytterbium(III) tosylate is a somewhat superior catalyst. Additionally, hazardous solvents were avoided where possible. The nitration of aromatics for example could be performed in heptane, which is a less hazardous reaction solvent than the 1,2-dichloroethane nowadays used for this reaction. The results presented in chapter 3 demonstrated the efficiency of lanthanide(III) tosylates and nitrobenzenesulfonates as catalysts for various reactions and hence it is worth to extend the use of these catalysts for other Lewis acid-catalyzed reactions. Kobayashi and coworkers also reported that lanthanide(III) triflates can be used to perform reactions in water if a water-soluble organic solvent is added to solubilize the organic reagents. To overcome this solubility problem an anionic surfactant can be added to the Lewis acid. This lead to the development of Lewis acid-surfactant combined catalysts (LASCs). The use of LASCs has extensively been studied for some reactions as for example the aldol reaction but remained largely unexplored for reactions as for example the allylation of aldehydes. Our results in chapter 4 proved that lanthanide(III) and copper(II) surfactant-combined catalysts could efficiently be used in the allylation of benzaldehyde with tetraallyltin in water. Due to the formation of micelles the reaction could be achieved in the absence of organic solvents. Our results indicated that both the cation and the anion have a strong influence on the reactivity of the LASC. Variation of the anion showed that better results were obtained in the order alkylsulfates > arylsulfonates > alkylsulfonates with the highest conversions when using lanthanide(III) or copper(II) dodecylsulfate catalysts. Complete conversion was already obtained at room temperature after a few hours when using a few mol% of copper(II) dodecylsulfate, whereas the use of lanthanide(III) dodecylsulfate required a few hours more. Lewis acid-surfactant-combined catalysts act both as a catalyst activating the substrate molecules and as a surfactant forming micelles. Consequently, they allow the use of water as the reaction medium, which is both economically and environmentally beneficial. In the last decades an enormous interest has arisen in the use of ionic liquids as ‘green solvents’. Based on the research performed in our group by Mehdi, cerium(IV)-mediated reactions in ionic liquids were further explored. The use of CAN, (NH4)2Ce(NO3)6, was studied for the oxidation and nitration of naphthalene and 2-methylnaphthalene in 1-ethyl-3-methylimidazolium triflate, [emim][OTf]. Depending on the reaction conditions, the outcome of these CAN-mediated reactions could be directed towards nitration or oxidation. However, stoichiometric amounts of the cerium salt were required for these oxidation reactions. In order to obtain an attractive procedure, reuse of the cerium-containing ionic liquid is desirable. Our experiments proved that the cerium(III) salt, obtained after the oxidation reaction of benzyl alcohol to benzaldehyde, could to a large extent be reoxidized to cerium(IV) directly in the ionic liquid and this cerium(IV)-containing ionic liquid could then be reused for subsequent oxidation reactions. To the best of our knowledge this is the first proof of principle that a cerium(IV)-containing ionic liquid could be reused for several oxidation reactions by electrochemical reoxidation of the cerium(III) salt.