Wilkinson type catalysts

Asymmetric hydrogenation has been achieved with dissolved Wilkinson type catalysts (A. J. Birch, 1976 D. Valentine, Jr., 1978 H.B. Kagan, 1978). The (R)- and (S)-[l,l -binaph-thalene]-2,2 -diylblsCdiphenylphosphine] (= binap ) complexes of ruthenium (A. Miyashita, 1980) and rhodium (A. Miyashita, 1984 R. Noyori, 1987) have been prepared as pure atrop-isomers and used for the stereoselective Noyori hydrogenation of a-(acylamino) acrylic acids and, more significantly, -keto carboxylic esters. In the latter reaction enantiomeric excesses of more than 99% are often achieved (see also M. Nakatsuka, 1990, p. 5586). 

Another possibility for asymmetric reduction is the use of chiral complex hydrides derived from LiAlH. and chiral alcohols, e.g. N-methylephedrine (I. Jacquet, 1974), or 1,4-bis(dimethylamino)butanediol (D. Seebach, 1974). But stereoselectivities are mostly below 50%. At the present time attempts to form chiral alcohols from ketones are less successful than the asymmetric reduction of C = C double bonds via hydroboration or hydrogenation with Wilkinson type catalysts (G. Zweifel, 1963 H.B. Kagan, 1978 see p. 102f.). 

The modifier in these cases seems to generate enantioselective sites at the metal surface and helps the molecule to adsorb in a preferred fashion so that the formation of only one stereo- product is possible. There are several milestones that have contributed to this state-of-the-art technology. Discovery of Wilkinson s catalyst led to the feasibility of asymmetric hydrogen transfer with the aid of an optically active Wilkinson-type catalyst for L-DOPA (Monsanto s anti-Parkinson disease drug) synthesis (Eqn. (21)). 

A simple method for the in-situ preparation of Wilkinson-type catalysts consists of the addition of the appropriate amount of the triarylphosphine to the rhodium dimers, [Rh(/<-Cl)(diene) 2 or Rh(//-Cl)(cyclooctene)2]2, according to Eqs. (4) and (5). The best results are usually obtained for a rhodium/phosphine ratio of 1 2. 

In transfer hydrogenation with 2-propanol, the chloride ion in a Wilkinson-type catalyst (18) is rapidly replaced by an alkoxide (Scheme 20.9). / -Elimination then yields the reactive 16-electron metal monohydride species (20). The ketone substrate (10) substitutes one of the ligands and coordinates to the catalytic center to give complex 21 upon which an insertion into the metal hydride bond takes place. The formed metal alkoxide (22) can undergo a ligand exchange with the hydride donor present in the reaction mixture, liberating the product (15). 

The first step consists of the substitution of one of the ligands (L) of 18 by dioxane (39) in an oxidative addition (a) (Scheme 20.16). / -Elimination of 40 releases 2,3-dihydro-dioxine (41) and the 16-electron dihydrogen rhodium complex (42) (b). Alkene 43 coordinates to the vacant site of 42 (c) to give complex 44. A hydride insertion then takes place (d), affording complex 45. After a reductive elimination (e) of the product 46, the coordination of a ligand reconstitutes the Wilkinson-type catalyst (18). 

Scheme 20.16 Alkene reduction with dioxane (39) as hydride donor and a Wilkinson-type catalyst (18).

During the late 1960s, Homer et al. [13] and Knowles and Sabacky [14] independently found that a chiral monodentate tertiary phosphine, in the presence of a rhodium complex, could provide enantioselective induction for a hydrogenation, although the amount of induction was small [15-20]. The chiral phosphine ligand replaced the triphenylphosphine in a Wilkinson-type catalyst [10, 21, 22]. At about this time, it was also found that [Rh(COD)2]+ or [Rh(NBD)2]+ could be used as catalyst precursors, without the need to perform ligand exchange reactions [23]. 

A classical example is the development of soluble chiral catalysts for homogenous asymmetric hydrogenation. The story began with the discovery of Wilkinson s catalyst [4]. In 1968, Horner [5] and Knowles [6], independently, reported the feasibility of asymmetric hydrogenations in the presence of optically active Wilkinson-type catalyst. Although the optical yields were rather low, further studies in this direction were the basis of the success of Monsanto s asymmetric synthesis of the anti-Parkinson s drug L-DOPA. The key steps of the synthesis are outlined in Scheme 11.1. 

In principle, the mechanism of homogeneous hydrogenation, in the chiral as well as in the achiral case, can follow two pathways (Figure 9.5). These involve either dihydrogen addition, followed by olefin association ( hydride route , as described in detail for Wilkinson s catalyst, vide supra) or initial association of the olefin to the rhodium center, which is then followed by dihydrogen addition ( unsaturate route ). As a rule of thumb, the hydride route is typical for neutral, Wilkinson-type catalysts whereas the catalytic mechanism for cationic complexes containing diphosphine chelate ligands seems to be dominated by the unsaturate route [1]. 

New Chiral Phosphinite Ligands Used For Asymmetric Homogeneous Hydrogenation in the Wilkinson-Type Catalyst System... 

The water-soluble Wilkinson-type catalyst chlorotris(diphenylphosphinoben-zene-m-sulfonate)rhodium(I), RhQfdpm) (19), acts as catalyst for H2-evolution [158], hydrogenation and hydroformylation [159]. In a photosystem composed of Ru(bpy)i+ as photosensitizer, ascorbic acid, HA, as electron donor and RhCl(dpm)3, hydrogen evolution proceeds with a quantum efficiency corresponding to (p = 0.033. In the presence of ethylene or acetylene, hydrogen evolution is blocked and hydrogenation of the unsaturated organic substrates predominates. Table 6 summarizes the quantum yields for H2-evolution and... 

FIG. 4. Early examples of asymmetric homogeneous hydrogenation with a Wilkinson-type catalyst. 1,5-HD = 1,5-hexadiene. 

FIG. 6. Asymmetric homogeneous hydrogenation of a-substituted acrylic acids with a Wilkinson-type catalyst under extended conditions (higher temperature and pressure than usual). 

The extended reaction conditions involve higher pressure and temperature than are normally used for Wilkinson-type catalysts and unhindered substrates. 

The catalyst [CoH(CN)5] is soluble in water. It is selective for the reduction of olefinic double bonds in a,y9-unsaturated systems. Reduction of NO2 groups only occurs at elevated pressures. Hydrogenolysis of C-Hal bonds is observed [20]. Progress as far as water-soluble hydrogenation catalysts is concerned has also been made with Wilkinson-type catalysts by using phosphine ligands with sulfonic acid substituents [44]. 

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. 

In the 1970s and early 1980s the development of new catalysts was mainly based on new optically active chelating phosphines used in Wilkinson-type catalysts. This era of design and synthesis of optically active bidentate phosphines started in 1971 with Kagan s tartaric acid derived ligand DIOP [59, 60]. Successful and well-known examples followed, namely DIPAMP [62], prophos [63], chiraphos [64], BPPM [65], BPPFA [66], norphos [67], and BINAP [68]. A selection is depicted in Figure 3. 

Up to the mid-1980s the field of enantioselective hydrogenation had been dominated by the Rh-based Wilkinson-type catalysts. Then, Noyori et al. introduced a new family of Ru-based catalysts, which showed a wider applicability than the Rh catalysts. a, ff-Unsaturated acids other than dehydroamino acids became substrates which could be hydrogenated with high enantioselectivity... 

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]. 

Usually, a catalyst has to be synthesized or conditioned prior to its use in a catalytic reaction. However, there is an alternative to such an isolated or preformed catalyst, the so-called in-situ catalyst. The in-situ catalyst is prepared by mixing the transition metal compound (the procatalyst) and the ligand (the cocatalyst) in the solvent in which the reaction is to be carried out [79]. The use of in-situ catalysts is most appropriate in enantioselective hydrogenation reactions with Wilkinson-type catalysts. The optically active phosphines needed for optical induction have to be synthesized in multi-step syntheses [80, 81]. It is most convenient to combine them directly with the Rh-containing procatalysts. 

Scheme 2. Mechanism of the hydrogenation of methyl (Z)-a-acetamidocinnamate with Wilkinson-type catalysts.

Another application of the Wilkinson-type catalyst 18 is the rhodium catalyzed hydroboration of olefins [19]. Various alkenes 20 (internal, terminal, styrenes, etc.) have been successfully hydroborated with catecholborane (21) providing the corresponding boronic esters 22 in nearly quantitative yield. Oxidative work-up (Na0H/H202) led to the corresponding alcohols 23 in 76-90% yield Eq. (11). 

In contrast to unfunctionalized ketones, Wilkinson-type catalysts are quite effective in the hydrogenation of 2-oxo esters. With in situ catalysts consisting of [Rh(cod)Cl]2 2 and a proline derived chelate phosphane BPPM 3l4, quantitative hydrogenation of 2-oxo esters to (7 )-2-hydroxy esters was achieved. Dry benzene or dry tetrahydrofuran as solvent were superior to alcohols usually used in hydrogenation reactions with Wilkinson-type catalysts. While methyl 2-oxopropanoate was reduced to methyl (R)-2-hydroxypropanoate in only 66% eel5, propyl and 2-methylpropyl 2-oxopropanoate gave the (R)-alcohols with 76% and 71 % ee, respectively (Table 2)15,10. 

Hydrogenation of olefins, enols, or enamines with chiral Wilkinson type catalysts, e.g., Noyorl hydrogenation. Hydroboration of olefins with chiral boranes. Sharpless epoxi-dation of allylic alcohols. 

Neutral Wilkinson type catalysts with chiral ligands are quite effective for the hydrogenation of C=0 bonds in prochiral 2-oxocarbo Q lic acids or their esters and are applied to the as5mimetric S5mthesis of 2-hydroxyesters with rather high ee s of up to 80-95%. The reduction of alpha- iQ o esters, such as alkyl-pymvates into alkyl-lactates (Scheme 7.18.) on chiral complexes is one of the most important methods of the synthesis of chiral synthones for practical use. 

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