Enantioselectivity homogeneous hydrogenation

In 1968, Knowles et al. [1] and Horner et al. [2] independently reported the use of a chiral, enantiomerically enriched, monodentate phosphine ligand in the rhodium-catalyzed homogeneous hydrogenation of a prochiral alkene (Scheme 28.1). Although enantioselectivities were low, this demonstrated the transformation of Wilkinson s catalyst, Rh(PPh3)3Cl [3] into an enantioselective homogeneous hydrogenation catalyst [4]. 

A wide range of a,fi-unsaturated carboxylic acids, including substituted acrylic acids, undergo enantioselective homogeneous hydrogenation when catalyzed by... 

As recently recognized by the Nobel Chemistry award committee, the conceptualization, development, and commercial application of enantioselective, homogeneous hydrogenation of alkenes represents a landmark achievement in modem chemistry. Further elaboration of asymmetric hydrogenation catalysts by Noyori, Burk, and others has created a robust and technologically important set of catalytic asymmetric synthetic techniques. As frequently occurs in science, these new technologies have spawned new areas of fundamental research. Soon after the development of... 

As an aside, decades of work have gone into the study of enantioselective homogeneous hydrogenation processes in both organic and aqueous systems. There is increasing commercial interest in this field spurred by the spectacular, time-encrusted development of a complex catalyst for the enantioselective hydrogenation of an imine to a chiral amine needed for manufacture of the important herbicide, (,S )-Metolaclor. The technical success of this program (Scheme l)25 owed much to the perserverance... 

SCHEME 1. Enantioselective homogeneous hydrogenation in the manufacture of (S)-metolaclor.25... 

Enantioselective homogeneous hydrogenation catalyzed by chiral transition metal complexes is one of the most well established transformations in asymmetric synthesis [1]. Excellent enantioselectivities have been achieved in the hydrogenation of a wide range of substrates, often with very low catalyst loadings. High reliability, mild reaction conditions, and perfect atom economy are further attractive attributes of this method. In particular complexes based on Ru or Rh have found broad application in industrial processes [1] and the impact of these catalysts has been recognized by the Nobel Prize awarded to Ryoji Noyori and William S. Knowles in 2001 [2]. 

The synthesis of cationic rhodium complexes constitutes another important contribution of the late 1960s. The preparation of cationic complexes of formula [Rh(diene)(PR3)2]+ was reported by several laboratories in the period 1968-1970 [17, 18]. Osborn and coworkers made the important discovery that these complexes, when treated with molecular hydrogen, yield [RhH2(PR3)2(S)2]+ (S = sol-vent). These rhodium(III) complexes function as homogeneous hydrogenation catalysts under mild conditions for the reduction of alkenes, dienes, alkynes, and ketones [17, 19]. Related complexes with chiral diphosphines have been very important in modern enantioselective catalytic hydrogenations (see Section 1.1.6). 

Following Wilkinson s discovery of [RhCl(PPh3)3] as an homogeneous hydrogenation catalyst for unhindered alkenes [14b, 35], and the development of methods to prepare chiral phosphines by Mislow [36] and Horner [37], Knowles [38] and Horner [15, 39] each showed that, with the use of optically active tertiary phosphines as ligands in complexes of rhodium, the enantioselective asymmetric hydrogenation of prochiral C=C double bonds is possible (Scheme 1.8). 

Early transition-metal complexes have been some of the first well-defined catalyst precursors used in the homogeneous hydrogenation of alkenes. Of the various systems developed, the biscyclopentadienyl Group IV metal complexes are probably the most effective, especially those based on Ti. The most recent development in this field has shown that enantiomerically pure ansa zirconene and titanocene derivatives are highly effective enantioselective hydrogenation catalysts for alkenes, imines, and enamines (up to 99% ee in all cases), whilst in some cases TON of up to 1000 have been achieved. 

The use of combinatorial and HTE methods in homogeneous hydrogenation has blossomed over the past five years. This has been fuelled first by the urgent need to identify useful catalysts for the production of fine chemicals, in particular enantiopure pharma intermediates. The second impetus came from academia, where many investigators realized that, with regard to enantioselective cat-... 

As already mentioned, the most important industrial application of homogeneous hydrogenation catalysts is for the enantioselective synthesis of chiral compounds. Today, not only pharmaceuticals and vitamins [3], agrochemicals [4], flavors and fragrances [5] but also functional materials [6, 7] are increasingly produced as enantiomerically pure compounds. The reason for this development is the often superior performance of the pure enantiomers and/or that regulations demand the evaluation of both enantiomers of a biologically active compound before its approval. This trend has made the economical enantioselective synthesis of chiral performance chemicals a very important topic. 

Keywords Asymmetric Hydrogenation m Carbon Dioxide m Carbonylation m Dimethylformamide Enantioselectivity m Formic Acid m Homogeneous Hydrogenation n Palladium Catalysts Radical Reactions m Ruthenium Catalysts m Supercritical Fluids m Solvent Replacement... 

Fig. 17.77. Enantioselective homogeneous catalytic hydrogenations of two stereoiso-meric -(acylamino)acrylic acids to one and the same R-amino acid. - The mechanism of the hydrogenation of these acids is exemplified by their Z-isomer Figure 17.78.

For enantioselectivity to occur with homogeneous hydrogenations, the unsaturated substrate must bind to the catalytic center in such a way that a complex with well-defined stereostructure is formed. Accordingly, a highly enantioselective hydrogenation is assured—at least in most cases—if the substrate forms two bonds to the metal. The substrate is -bonded to the metal via the C=C double bond that is to be hydrogenated. It is also (7-bonded to the metal via a heteroatom that is close enough to this C=C double bond. 

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