Transition metal catalysts immobilization

Recyclability requires rates and yields of reactions to be maintained at a reasonable level after repeated reactions. In particular, reactions containing a transition metal catalyst immobilized into the IL of a biphasic reaction system have proved to be recyclable. Generally, recycling is based on the non-volatile nature of ILs and the solubility differences between ILs, organic compounds and water. Products can be extracted from ILs with a nonpolar solvent or they can be separated by distillation. A water-immiscible IL can be washed with water to get a water-soluble product or side products out of the reaction mixture [Karkkainen, 2007]. 

Since no special ligand design is usually required to dissolve transition metal complexes in ionic liquids, the application of ionic ligands can be an extremely useful tool with which to immobilize the catalyst in the ionic medium. In applications in which the ionic catalyst layer is intensively extracted with a non-miscible solvent (i.e., under the conditions of biphasic catalysis or during product recovery by extraction) it is important to ensure that the amount of catalyst washed from the ionic liquid is extremely low. Full immobilization of the (often quite expensive) transition metal catalyst, combined with the possibility of recycling it, is usually a crucial criterion for the large-scale use of homogeneous catalysis (for more details see Section 5.3.5). 

Ambient-temperature ionic liquids have received much attention in both academia and industry, due to their potential as replacements for volatile organic compounds (VOCs) [1-3]. These studies have utilized the ionic liquids as direct replacements for conventional solvents and as a method to immobilize transition metal catalysts in biphasic processes. 

The other direction concerns the use of immobilized transition metal catalysts in the synthesis of libraries of organic compounds of interest in therapeutic drug discovery. One such strategy uses immobilized catalysts (e.g., scandium complexes), leading to efficient library syntheses of quinolines, amino ketones, and amino acid esters.72,73... 

Thus 31P CP/MAS NMR may be used to characterize solid and immobilized transition metal catalyst systems. The results indicate that high yields of single complex may be formed by the correct choice of preparative route, but that the most commonly used procedures are relatively inefficient and that the measured catalytic activities cannot represent the optimal performance of these systems. 

In the search to develop new materials for immobilization of homogeneous transition metal catalyst to facilitate catalyst-product separation and catalyst recychng, the study of dendrimers and hyperbranched polymers for application in catalysis has become a subject of intense research in the last five years [68], because they have excellent solubility and a high number of easily accessible active sites. Moreover, the pseudo-spherical structure with nanometer dimensions opens the possibility of separation and recycling by nanofiltration methods. Although dendrimers allow for controlled incorporation of transition metal catalysts in the core [69] as well as at the surface [70], a serious drawback of this approach is the tedious preparation of functionalized dendrimers by multi-step synthesis. 

Transition metal catalysts and biocatalysts can be combined in tandem in very effective ways as shown by the following example (Scheme 2.21). An immobilized rhodium complex-catalyzed hydrogenahon of 46 was followed by enzymatic hydrolysis of the amide and ester groups of 47 to afford alanine (S)-9 in high conversion and enanhomeric excess. Removal of the hydrogenation catalyst by filtration prior to addition of enzyme led to improved yields when porcine kidney acylase 1 was used, although the acylase from Aspergillus melleus was unaffected by residual catalyst [23]. 

There are reports of numerous examples of dendritic transition metal catalysts incorporating various dendritic backbones functionalized at various locations. Dendritic effects in catalysis include increased or decreased activity, selectivity, and stability. It is clear from the contributions of many research groups that dendrimers are suitable supports for recyclable transition metal catalysts. Separation and/or recycle of the catalysts are possible with these functionalized dendrimers for example, separation results from precipitation of the dendrimer from the product liquid two-phase catalysis allows separation and recycle of the catalyst when the products and catalyst are concentrated in two immiscible liquid phases and immobilization of the dendrimer in an insoluble support (such as crosslinked polystyrene or silica) allows use of a fixed-bed reactor holding the catalyst and excluding it from the product stream. Furthermore, the large size and the globular structure of the dendrimers enable efficient separation by nanofiltration techniques. Nanofiltration can be performed either batch wise or in a continuous-flow membrane reactor (CFMR). 

Aiming at easier workup conditions, immobilization of several transition metal catalysts, which show activity for the epoxidation of allylic alcohols, on polymer support has been investigated. For example, Suzuki and coworkers incorporated an oxo-vanadium ion into cross-linked polystyrene resins functionalized with iminodiacetic acid or diethylenetri-amine derivatives (Scheme 57), which afforded a heterogeneous catalyst that can promote... 

An example where a transition metal catalyst is used in combination with an enzyme has been described (Scheme 19.26).207 The racemic alcohol 50 was converted to the (A1)-acetate 51, using a ruthenium catalyst along with Novozym 435 (immobilized Lipase B from Candida antarctica), 3 equivalents of p-chlorophenylacetate in t-BuOH, and 1 equivalent of 1-indanone. The reaction yield was 81% with an optical purity of >99.5% ee. 

The same CALB preparation was appUed in many dynamic kinetic resolutions combining two types of catalysts with each other. In the presence of homogeneous transition metal catalysts that catalyze the racemization and heterogeneous acids or bases or immobilized transition metals Novozym 435 was not deactivated [1, 26-28]. This is all the more remarkable since the reactions catalyzed by these catalysts include redox reactions at elevated temperatures (>60°C). When Novozym 435 was applied for the enantioselective synthesis of cyanohydrin acetates (10) from aliphatic aldehydes (7), good results were achieved (Scheme 2.2) for this dynamic kinetic resolution (DKR) [29]. Here NaCN is used as the base for the dynamic racemic formation and degradation of the cyanohydrins (6 and 8). 

To apply Reverse Flow Adsorption, a combination of two adsorbents has to be used for the reversible adsorption of a homogeneous transition-metal catalyst. The transition-metal center can be adsorbed by a suitable ligand immobilized onto a solid carrier, while the ligand is adsorbed by an immobilized transition-metal. Two groups of adsorbents have been studied, based on the HSAB predictions ( i the interactions with the Co(ll) transition-metal center or PPhj ligands ... 

In 1972, Parshall used an ionic liquid for the first time for the immobilization of a transition metal catalyst in a biphasic reaction set-up [7]. He described the hydrogenation of CC-double bonds with PtCl2 dissolved in tetraethylammonium chloride associated with tin dichloride ([Et4N][SnCl3], m.p. 78 °C) at temperatures between 60 and 100 °C. A substantial advantage of the molten salt medium [over conventional organic solvents]. .. is that the product may be separated by decantation or simple distillation . The use of ionic liquids as novel media for transition metal catalysis started to receive increasing attention when in 1992 Wilkes reported on the synthesis of... 

Immobilization of otherwise homogeneous transition metal catalysts represents the second broad area in which chemically modi-... 

Most widely used are N,N -dialkyhrnidazohum salts, since they are easily prepared. Ionic liquids have been used as solvents for numerous reactions. Their physical and chemical properties vary with the combination of cation and anion. This allows a degree of tuning of their properties. Since they are highly polar solvents, ionic liquids can dissolve many inorganic salts and transition metal complexes, and often form biphasic mixtures with non-polar organic solvents. Thus, organic products can be extracted from ionic liquids, while ionic transition metal catalysts are immobilized. Volatile products can be easily distilled off from ionic liquids, since the latter show no volatility [17]. 

Structured supported ionic liquid-phase (SSILP) catalysis is a new concept that combines the advantages of ionic liquids (ILs) as solvents for homogeneous catalysts with the benefits of structured solid catalysts. In an attempt to prepare a homogeneous IL film on a microstructured support, SMFs were coated by a layer of carbon nanofibers as described above. An IL thin film was then immobilized on the CNF/SMF support. The high interfacial area of the IL film enabled the efficient use of a transition metal catalyst for the selective gas-phase hydrogenation of acetylenic compounds [267,268]. 

Transition metal loaded organic synthetic resins are employed industrially for numerous synthetic transformations. With increasing cost pressures and environmental restrictions on processes using transition metal catalysts, the need for more recyclable transition metal catalysts intensifies. Organic synthetic resins have been around for more than 60 years and are ideal substrates for transition metal immobilization. They are well poised for chemical modification and the resultant catalysts can be used in either batch or continuous systems. 

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