Exchanged Chiral Catalysts

Modification of clays with metal complexes containing chiral ligands can be used for the preparation of catalysts for asymmetric reactions. Since the modified clays have limited interlayer space, the interaction between chiral ligands and substrates can be enforced and this may enhance the selectivity.203,204 

Prochiral organic acids were hydrogenated on clay-supported Rh-chiral phosphine complexes.205,206 Hectorite-supported chiral Rh(I)-phosphine complexes were used for the asymmetric hydrogenation of a,P-unsaturated carboxylic acids.207 It was found that the interaction between the a-ester group of itaconates and phenyl groups of phosphine can play an important role in the determination of the configuration of products. 

BINAP complexes (7 in Fig. 7.7) are among the most efficient chiral catalysts for enantioselective hydrogenations, hydrosilylations, etc. Heterogeniza-tion of this complex is highly desired because of the high price of the complex. 

Ru(II)BINAP was sulfonated and immobilized by the supported-aqueous-phase technique.208-210 Immobilization of Ru(II)BINAP by ion exchange of the sulfonated complex on anionic minerals was also reported.211 The complex is only present at the outer surface and is not intercalated within the interlamel-lar space of the clay. 

---

Silver salts are also employed to create more effective chiral catalysts by exchange of counter anions. For example, in the Mizoroki-Heck reaction of alkenyl or aryl halides, silver salts are employed to form effective chiral Pd intermediates by abstracting a halide group from the Pd11 precursor species (Scheme 53).227,228... 

LA represents Lewis acid in the catalyst, and M represents Bren sled base. In Scheme 8-49, Bronsted base functionality in the hetero-bimetalic chiral catalyst I can deprotonate a ketone to produce the corresponding enolate II, while at the same time the Lewis acid functionality activates an aldehyde to give intermediate III. Intramolecular aldol reaction then proceeds in a chelation-controlled manner to give //-keto metal alkoxide IV. Proton exchange between the metal alkoxide moiety and an aromatic hydroxy proton or an a-proton of a ketone leads to the production of an optically active aldol product and the regeneration of the catalyst I, thus finishing the catalytic cycle. 

In the course of our investigations to develop new chiral catalysts and catalytic asymmetric reactions in water, we focused on several elements whose salts are stable and behave as Lewis acids in water. In addition to the findings of the stability and activity of Lewis adds in water related to hydration constants and exchange rate constants for substitution of inner-sphere water ligands of elements (cations) (see above), it was expected that undesired achiral side reactions would be suppressed in aqueous media and that desired enanti-oselective reactions would be accelerated in the presence of water. Moreover, besides metal chelations, other factors such as hydrogen bonds, specific solvation, and hydrophobic interactions are anticipated to increase enantioselectivities in such media. 

Sharpless et al. coined the word ligand-accelerated catalysis (LAC), which means the construction of an active chiral catalyst from an achiral precatalyst via ligand exchange with a chiral ligand. By contrast, a combinatorial library approach in which an achiral pre-catalyst combined with several chiral ligand components (L, L, —) may selectively assemble in the presence of several chiral activators (A, A, —) into the most catalytically active and enantioselective activated catalyst (ML A" ) (Scheme 8.16). ... 

According to another NMR study, the mechanism of bifunctional activation in the asymmetric aza-Morita-Baylis-Hillman reaction (Scheme 7) involves rate-limiting proton transfer (116) in the absence of added protic species155 (in consonance with the report summarized in Scheme 5144), but exhibits no autocatalysis. Addition of Brpnsted acids led to substantial rate enhancements through acceleration of the elimination step. Furthermore, it was found that phosphine catalysts, either alone or in combination with protic additives, can cause racemization of the reaction product by proton exchange at the stereogenic centre. This behaviour indicates that the spatial arrangement of a bifunctional chiral catalyst for the asymmetric aza-Morita-Baylis-Hillman reaction is crucial not only for the stereodifferentiation within the catalytic cycle but also for the prevention of subsequent racemization.155... 

Leitner and coworkers [27] found that triphenylphosphine either alone or in combination with protonic additives could cause racemization of the aza MBH product by proton exchange at the stereogenic center, but the chiral catalyst 19a developed by Shi s group did not induce any racemization on a similar time scale. 

Zeolites are crystalline but versatile materials. They may be modified in many ways they can be tuned over a wide range of acidity and basicity, and of hydrophylicity and hydrophobicity, many cations can be introduced by ion exchange and isomorphous substitution is possible also allowing build-in of isolated redox centers (e.g. Ti) in the lattice. Moreover metal crystallites and metal complexes can be entrapped within the microporous environment. There is for instance much progress in enantioselective synthesis on chiral catalysts immobilized in microporous or mesoporous materials [16]. 

---