Enantioselectivities immobilised catalysts

Covalent attachment chiral Co(salen) complexes to polystyrene and silica gave efficient and highly enantioselective catalysts for the hydrolytic kinetic resolution (HKR) of terminal epoxides, including epichlorohydrin. These systems provide practical solutions to difficulties with the isolation of reaction products from the HKR. Removal of the supported catalyst by filtration and repeated recycling was demonstrated with no loss of reactivity or enantioselectivity. The immobilised catalysts have been adapted to a... 

Some degree of success in supported enantioselective catalysis was accomplished by using functionalisation of mineral support. Due to their unique textural and surface properties, mesoporous micelle-templated silicas are able to bring new interesting properties for the preparation of optically active solids. Many successfully examples have been reported for enantioselective hydrogenation, epoxidation and alkylation. However, the stability of the immobilised catalysts still deserves efforts to allow industrial development of such attractive materials. 

Chiral rhodium-DuPHOS complexes are highly efficient catalyst for the enantioselective hydrogenation of enamides. One drawback of these catalysts is that they are easily oxidised and inert conditions are required for optimal results. The methyl- and ethyl substituted Rh-DuPHOS compounds, 3a and 3b, have been successfully applied in the reduction of a-acetamidocinnamic acids in [C4Ciim][PF6], Scheme 3.7.[7,39] While activities and selectivities are slightly lower compared to the homogeneous reaction in 2-propanol, the ionic liquid-immobilised catalyst is less prone to oxidation and recycling is feasible at least three times. 

Development of molecularly imprinted enantioselective hydrogenation catalysts based on immobilised rhodium complexes was reported by Gamez et al. [29]. The imprinted catalysts were prepared by polymerising Rh(I)-(A,A -dimethyl-l,2-diphe-nylethanediamine) with di- and tri-isocyanates, using a chiral alkoxide as the template (9). The imprinted polymer, after removal of the template, was tested for the reduction of ketones to alcohols. An enhanced enantioselectivity was observed in the presence of the imprinted polymeric catalyst, in comparison to the control polymer. 

Although Cinchona alkaloids are easily separated from products by acid-base extractions and recycled, immobilisation of the catalyst on polymers was investigated by Oda. In parallel with new catalyst synthesis, their immobilisation to various solid supports was also studied. Immobilised catalysts are easily isolated by filtration and reused several times, although their initial enantioselectivity is slightly lower compared with homogeneous catalysis. 

In 2012, the first polymer supported bifunctional primaiy amine-ureas were developed by Portnoy and coworkers. This heterogeneous catalytic system was tested in the Michael addition of acetone, cyclic ketones and aldehydes to aromatic nitro-olefins leading to activities and selectivities unprecedented for immobilised catalysts. Catalyst 41 based on (ll ,2f )-diphenylethylene-1,2-diamine and a L-valine spacer provided the Michael products in yields ranging from 23 to 99% and in high enantioselectivity (up to 99% enantiomeric excess) (Scheme 19.43). Unfortunately, recovery of the polymer-catalyst and reuse was only tested for 3 cycles, maintaining the high levels of enantioselectivity, but with a significant loss in the yield. 

Subsequently, the Sasai group described the immobilisation of the chiral Al-Li-bis(binaphthoxide) catalyst, and applied the immobilised catalyst 20 in an enantioselective Michael addition (Scheme 19.17). After eompletion of the reaction, the insoluble catalyst was recovered by simple filtration in air and exhibited activity even after being used five times. 

One of the most attractive features of the IL/CO2 approach to homogeneous catalysis is the development of continuous processes [7]. Consequently it needs to be demonstrated that the combination of a suitable IL and compressed CO2 can offer more potential for process optimisation than just a simple protocol for batch-wise catalyst recycling. As an example we were able to activate, tune and immobilise Ni catalyst 13 in a continuous-flow system for the hydroviny-lation of styrene (Scheme 3). Styrene is co-dimerised with ethene yielding 3-substituted 1-butenes [26,27]. We could show that this powerful carbon-carbon bond-forming reaction can be achieved with high enantioselectivity in batch-wise operation and in continuous-flow systems. 

Jacobs et al has also reported immobilisation of Jacobsen s catalyst in a polydimethylsiloxane (PDMS) membrane for the epoxidation of terminal alkene (Scheme 6b).53 In the case of styrene epoxidation using NaOCl, styrene oxide was obtained with nearly the same activity and enantioselectivity (52 %) than in homogeneous conditions. Interestingly, the catalytic membranes are easily regenerable. 

The heterogeneised catalyst exhibits significantly higher enantioselectivity than the same free complex. The increase in the chiral recognition could arise from the enhanced stability of the chromium complex upon immobilisation and from the unique spatial environment as previously suggested by Thomas et al26... 

Immobilised Rh Diphosphine Complexes as catalysts for Enantioselective Hydrogenations... 

Several diphosphine ligands have been tested for the immobilisation and as catalysts in the enantioselective hydrogenation (Figure 8). 

As a test reaction for the catalytic activity the hydrogenation of dimethylitaconate was employed. No reaction takes place in the blank test, when the carrier Al-MCM-41 itself is used as catalyst. The immobilised rhodium complexes give enantioselectivities up to 92 % ee of dimethyl-(R)-methylsuccinate with a turn over number of 4000 for the S,S-Me-Duphos ligand. The corresponding supported catalysts with R,R-Diop and S,S-Chiraphos ligands lead to enantioselectivities of 34 % ee and 47 % ee with lower activities. With the (+)-Norphos ligand the favoured enantiomer is dimethyl-(S)-succinate which is formed with 47 % ee. 

The widespread application of enantioselective catalysis, be it with chiral metal complexes or enzymes, raises another issue. These catalysts are often very expensive. Chiral metal complexes generally comprise expensive noble metals in combination with even more expensive chiral ligands. A key issue is, therefore, to minimise the cost contribution of the catalyst to the total cost price of the product a rule of thumb is that it should not be more than ca. 5%. This can be achieved either by developing an extremely productive catalyst, as in the metachlor example, or by efficient recovery and recycling of the catalyst. Hence, much attention has been devoted in recent years to the development of effective methods for the immobilisation of metal complexes [130, 131] and enzymes [132]. This is discussed in more detail in Chapter 9. 

Good to excellent enantioselectivity was achieved in the epoxidation of mainly cyclic olefins with the chiral salen-catalyst 52 immobilised in [C4Ciim][PF6], but selectivity deteriorated upon catalyst recycling, see Scheme 5.6.[48] Relative to molecular solvents, higher reaction rates were observed even under biphasic conditions when the epoxidation reaction was carried out in the presence of an ionic liquid. UV-VIS spectroscopic1341 and cyclovoltammetric[49] studies suggest that the commonly observed superior reaction rates are a reflection of the solvent s ability to stabilise the active metalla-oxo intermediate. 

McMom P, Hutchings GJ (2004) Heterogeneous enantioselective catalysts strategies for the immobilisation of homogeneous catalysts. Chem Soc Rev 33 108... 

In this study chiral dirhodium catalysts (Rh2(MEPY)4) and Rh2(BNOX)4), developed by Doyle [10] (see Scheme 1) were immobilised. It can be anticipated that the spatial constraints induced by the carrier (MCM-41 or silica), and especially by the pores of MCM-41, are able to increase the influence of the chiral ligands. Earlier research [11,12] showed that enantioselective reduction catalysed by a palladium complex immobilised inside the pores of MCM-41 resulted in a threefold increase in enantioselectivity compared to the homogeneous palladium complex. In order to immobilise the homogeneous catalysts on the surface, an organic linker group was... 

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