Catalytic hydrogenation asymmetric

Catalytic asymmetric hydrogenation was one of the first enantioselective synthetic methods used industrially (82). 2,2 -Bis(diarylphosphino)-l,l -binaphthyl (BINAP) is a chiral ligand which possesses a Cg plane of symmetry (Fig. 9). Steric interactions prevent interconversion of the (R)- and (3)-BINAP. Coordination of BINAP with a transition metal such as mthenium or rhodium produces a chiral hydrogenation catalyst capable of inducing a high degree of enantiofacial selectivity (83). Naproxen (41) is produced in 97% ee by... 

Monsanto s commercial route to the Parkinson s drug, L-DOPA (3,4-dihydroxyphenylalanine), utilizes an Erlenmeyer azlactone prepared from vanillin. The pioneering research in catalytic asymmetric hydrogenation by William Knowles as exemplified by his reduction of 24 to 25 in 95% ee with the DiPAMP diphosphine ligand was recognized with a Nobel Prize in Chemistry in 2001. ... 

An early success story in the field of catalytic asymmetric synthesis is the Monsanto Process for the commercial synthesis of l-DOPA (4) (see Scheme 1), a rare amino acid that is effective in the treatment of Parkinson s disease.57 The Monsanto Process, the first commercialized catalytic asymmetric synthesis employing a chiral transition metal complex, was introduced by W. S. Knowles and coworkers and has been in operation since 1974. This large-scale process for the synthesis of l-DOPA (4) is based on catalytic asymmetric hydrogenation, and its development can be... 

Scheme 1 The Monsanto synthesis of l-DOPA (4) using catalytic asymmetric hydrogenation.

In recent years, the catalytic asymmetric hydrogenation of a-acylamino acrylic or cinnamic acid derivatives has been widely investigated as a method for preparing chiral a-amino acids, and considerable efforts have been devoted for developing new chiral ligands and complexes to this end. In this context, simple chiral phosphinous amides as well as chiral bis(aminophosphanes) have found notorious applications as ligands in Rh(I) complexes, which have been used in the asymmetric hydrogenation of a-acylamino acrylic acid derivatives (Scheme 43). 

Catalytic asymmetric hydrogenation is a relatively developed process compared to other asymmetric processes practised today. Efforts in this direction have already been made. The first report in this respect is the use of Pd on natural silk for hydrogenating oximes and oxazolones with optical yields of about 36%. Izumi and Sachtler have shown that a Ni catalyst modified with (i ,.R)-tartaric acid can be used for the hydrogenation of methylacetoacetate to methyl-3-hydroxybutyrate. The group of Orito in Japan (1979) and Blaser and co-workers at Ciba-Geigy (1988) have reported the use of a cinchona alkaloid modified Pt/AlaO.i catalyst for the enantioselective hydrogenation of a-keto-esters such as methylpyruvate and ethylpyruvate to optically active (/f)-methylacetate and (7 )-ethylacetate. 

The bis-DIOP complex HRh[(+)-DIOP]2 has been used under mild conditions for catalytic asymmetric hydrogenation of several prochiral olefinic carboxylic acids (273-275). Optical yields for reduction of N-acetamidoacrylic acid (56% ee) and atropic acid (37% ee) are much lower than those obtained using the mono-DIOP catalysts (10, II, 225). The rates in the bis-DIOP systems, however, are much slower, and the hydrogenations are complicated by slow formation of the cationic complex Rh(DIOP)2+ (271, 273, 274) through reaction of the starting hydride with protons from the substrate under H2 the cationic dihydride is maintained [cf. Eq. (25)] ... 

Asymmetry in metal-alkene coordination plays a critical role in asymmetric catalysis, with implications far beyond the scope of the present treatment. An instructive example is provided by catalytic asymmetric hydrogenation of enamides,... 

For a related complex, see W. V. Konze, B. L. Scott, and G. J. Kubas, J. Am. Chem. Soc. 124 (2002), 12 550 Bill Knowles shared the 2001 Nobel Prize (with Barry Sharpless and Ryoji Noyori) for his development of catalytic asymmetric hydrogenation. 

To date, following significant contributions by Knowles, Kagan, Noyori, and Burk et al., thousands of efficient chiral phosphorus ligands with diverse structures have been developed for asymmetric hydrogenation, and their catalytic asymmetric hydrogenation processes have been extensively utilized in both academic research and industry. 

The catalytic asymmetric hydrogenation with cationic Rh(I)-complexes is one of the best-understood selection processes, the reaction sequence having been elucidated by Halpern, Landis and colleagues [21a, b], as well as by Brown et al. [55]. Diastereomeric substrate complexes are formed in pre-equilibria from the solvent complex, as the active species, and the prochiral olefin. They react in a series of elementary steps - oxidative addition of hydrogen, insertion, and reductive elimination - to yield the enantiomeric products (cf. Scheme 10.2) [56]. 

The effects of added C02 on mass transfer properties and solubility were assessed in some detail for the catalytic asymmetric hydrogenation of 2-(6 -meth-oxy-2 -naphthyl) acrylic acid to (Sj-naproxen using Ru-(S)-BINAP-type catalysts in methanolic solution. The catalytic studies showed that a higher reaction rate was observed under a total C02/H2 pressure of ca. 100 bar (pH2 = 50bar) than under a pressure of 50 bar H2 alone. Upon further increase of the C02 pressure, the catalyst could be precipitated and solvent and product were removed, at least partly by supercritical extraction. Unfortunately, attempts to re-use the catalyst were hampered by its deactivation during the recycling process [11]. 

Figure 6-1. Selected ligands for catalytic asymmetric hydrogenation.

Much effort has been devoted to investigating chiral phosphine ligands for their synthesis and asymmetric catalytic hydrogenation potential, and such chiral phosphine ligands have been extensively used for catalytic asymmetric hydrogenation, both academically and industrially.14... 

Chirality transfer in catalytic asymmetric hydrogenation can be achieved not only by using powerful chiral ligands such as BINAP or DuPhos but also by the formation of a dynamic conformational isomer. The availability of many enantiomerically pure diols allows the production of electron-deficient, bi-dentate phosphate in the form of 27. The backbone O-R -O can define the chirality of the 0-R2-0 in complex 28, hence realizing the chirality transfer.44... 

From a practical point of view, the catalytic asymmetric hydrogenation of the corresponding diones will be the preferred method if high yields and high enantioselectivity can be ensured. Recently, over 98% yield with more than 99% ee has been achieved by optimizing the reaction conditions.64 For example, asymmetric hydrogenation of 2,4-pentanedione catalyzed by Ru-BINAP complex in the presence of hydrochloric acid gave 2,4-pentanediol in more than 95% yield and over 99% ee (Scheme 6-29).64... 

Chiral ligand 78, bearing structural features similar to those of DuPhos, has also been synthesized and gives moderate to high enantioselectivity in the catalytic asymmetric hydrogenation of functionalized carbonyl groups. High levels... 

Preparation of enantiomerically pare secondary amines by catalytic asymmetric hydrogenation or hydrosilylation of imines is as important as the preparation of alcohols from ketones. However, asymmetric hydrogenation of prochiral ON double bonds has received relatively less attention despite the obvious preparative potential of this process.98... 

This section focuses on the preparation of fluorinated compounds through asymmetric hydrogenation/reduction reactions and nucleophilic additions by listing some examples. The first successful example of catalytic asymmetric hydrogenation of a fluoro-compound was reported by Konig et al.81... 

Besides the above-mentioned catalytic asymmetric hydrogenation method for preparing fluorine-containing compounds, other reactions such as asymmetric reduction of achiral fluorine-containing ketones are also feasible methods for preparing chiral fluorinated compounds. For example, the oxazabor-olidine system, which has been discussed in Chapter 6, can also be employed in the catalytic reduction of trifluoromethyl ketones. Scheme 8 40 depicts some examples.85... 

Related catalytic enantioselective processes Although great progress has been achieved in the area of metal-catalyzed hydrogenation reactions [124], examples of catalytic asymmetric hydrogenations of tetrasubstituted alkenes are rare. One other example, reported by Pfaltz and co-workers, is depicted in Eq. 6.26 (81 % ee, absolute stereochemistry of the product not determined) [125],... 

W. S. Knowles, M. J. Sabacky, Catalytic Asymmetric Hydrogenation employing a Soluble, Optically Active, Rhodium Complex, J. Client Soc, Client Commurt 1968, 1445-1446. 

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