Enantioselective Hydrogenation of Prochiral Olefins

Homochiral syntheses is one of the main objectives of production of biologically active substances such as Pharmaceuticals, agrochemicals, etc. 

In many cases only one of the enantiomers displays the desired biological effect, the other is ineffective or even harmful. The development of enantioselective catalysis in non-aqueous solvents has been closely followed by the studies of similar aqueous systems - logically, attempts were made in order to solubilize the ligands and catalysts in aqueous media. Using aqueous/organic biphasic systems (often water/ethyl acetate) one may have a possibility of recovery and recycle of the often elaborate and expensive catalysts. However, with a few exceptions, up till now catalyst recovery has been rather a desire than a subject of intensive studies, obviously because of the lack of large-scale synthetic processes. 

Product isolation and recovery of the catalyst is relatively easy in aqueous/organic biphasic systems and in several cases the aqueous solution of the catalyst was reused with only negligible loss of the reaction rate or of theenantioselectivity [105,112], 

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Effect of amphiphiles on the enantioselective hydrogenation of prochiral olefins in water... 

These heterogeneous catalysts have shown excellent reactivity in the enantioselective hydrogenation of prochiral olefins with enantiomeric excess (ee s) > 92% and regioselectivities (>99%) with quantitative conversion. 

Enantioselective Hydrogenation of Prochiral Olefins - The presence of SDS increased both the rate and the enantioselectivity of hydrogenation of prochiral dehydroaminoacid derivatives using rhodium catalysts modified with the diphosphine 75a (Table 4) in aqueous media.500 For example, addition of 0.13 mmol of SDS to the Rh/75a catalyst shortened the reaction half time (tj/2) from... 

In the pioneering studies of Homer et al. [57] and Knowles and Sabacky [58], chirally modified Wilkinson catalysts were introduced in the homogeneous enantioselective hydrogenation of prochiral olefins. To this end, in Wilkinson-type catalysts the triphenylphosphine ligand was replaced by the optically active phosphine ligands (-i-)-PMePr"Ph and H-PMePfPh, chiral at the phosphoms atom. 

Table 3.5, Enantioselective hydrogenation of prochiral olefins in aqueous solutions...

Enantioselective hydrogenation of prochiral olefins such as conjugated acids or enamides (also asymmetric hydroboration) with chiral Rh phosphine catalysts (also Ti-catalysts)9 (see 1st edition). 

Several S/N ligands have also been investigated for the asymmetric hydrogenation of prochiral olefins. Thus, asymmetric enamide hydrogenations have been performed in the presence of S/N ligands and rhodium or ruthenium catalysts by Lemaire et al., giving enantioselectivities of up to 70% ee. Two... 

In recent years, the asymmetric hydrogenation of prochiral olefins have been developed in the presence of various chiral sulfur-containing ligands combined with rhodium, iridium or more rarely ruthenium catalysts. The best results have been obtained by using S/P ligands, with enantioselectivities of up to 99% ee in... 

The tetradentate ligands (340) and (341) form 1 1 metakligand complexes with [IrCl(cod)]2.548 The complexes were tested in the asymmetric hydrogenation of prochiral olefins, providing enantioselectivities up to 36%. The multitopic ligands L, (342) and (343), bind to Ir1 to form [IrL] species which have been characterized by elemental analysis, mass spectrometry, IR and NMR spectroscopy.549 The complexes show enantioselectivities of up to 30% for the hydrogenation of prochiral olefins under mild reaction conditions. 

The maximum enantioselectivity of 18 % achieved so far in aqueous hydroformylations may not seem very promising. However, the history of asymmetric hydrogenation of prochiral olefins and ketones demonstrates that such a situation may change fast if there is a strong drive behind the case. 

Enantioselective hydrogenation of prochiral carbonyl compounds with Wilkinson-type catalysts is less successful than the hydrogenation of prochiral olefins. Both rates and enantioselectivities are greatly diminished in the hydrogenation of ketones, compared with olefins. Enantioselectivities only occasionally reach 80% ee, e. g., in the hydrogenation of acetophenone with the in-situ catalyst [Rh(nbd)Cl]2/DIOP, where nbd = norbomadiene [71]. The Ru-based BINAP catalysts improved this situation, by allowing the hydrogenation of a variety of functionalized ketones in enantioselectivities close to 100% ee [72]. 

It should be finally noted that hydroxyphosphines can be converted under very smooth conditions into sulfonated phosphines by acylation with o-sulfobenzoic anhydride, as shown by Borner et al. (Eq. 5) [26]. With this methodology in hand the severe conditions commonly used for the incorporation of sulphonate groups in phosphines can be avoided. Acid-labile functional groups like acetals survive under these conditions. In comparison to the parent hydroxyphosphines the water solubility of the relevant Rh catalysts was strongly enhanced [27]. In the asymmetric hydrogenation of prochiral olefins, moderate enantioselectivities were achieved. 

In comparison to the parent hydroxyphosphines the water solubility of the relevant Rh catalysts was strongly enhanced [23]. In the asymmetric hydrogenation of prochiral olefins, moderate enantioselectivities were achieved. 

Efficient enantioselective asymmetric hydrogenation of prochiral ketones and olefins has been accompHshed under mild reaction conditions at low (0.01— 0.001 mol %) catalyst concentrations using rhodium catalysts containing chiral ligands (140,141). Practical synthesis of several optically active natural... 

In this chapter, we review the growing family of phospholane-based chiral ligands, and specifically examine their applications in the field of enantioselective hydrogenation. In general, this ligand class has found its broadest applicability in the reduction of prochiral olefins and, to a significantly lesser extent, ketones and imines this is reflected in the composition of the chapter. Several analogous phosphacycle systems have also been included, where appropriate. 

An excellent review of the problems of the enantioselective heterocatalytic hydrogenation of prochiral double bonds, covering the literature up to 1970, has been compiled by Izumi57). Raney nickel catalysts modified with chiral amino acids or dipeptides gave only very moderate enantiomeric excesses of between 0 and 10% in the hydrogenation of olefins, carbonyl compounds or oximes 57). Only Raney nickel modified with (S)-tyrosine furnished a higher enantiomeric excess in the products58). 

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