Ruthenium acid hydrogenation

An example of a stereoselective hydrogenation in ionic liquids was recently successfully demonstrated by Drie en-H6lscher et al. On the basis of investigations into the biphasic water/n-heptane system [51], the ruthenium-catalyzed hydrogenation of sorbic acid to cis-3-hexenoic acid in the [BMIM][PFg]/MTBE system was studied [52], as shown in Scheme 5.2-8. 

A very interesting result on ruthenocene showed that when fission product ruthenium was projected into dimeric cyclopentadiene, the yield of ruthenocene was quite low, while when monomeric cyclopentadiene was used, the yield was close to 100%. This was interpreted as involving a thermal reaction between the ruthenium atom and a cyclopentadiene monomer molecule, likely the simple displacement of an acid hydrogen. 

These transition-metal catalysts contain electronically coupled hydridic and acidic hydrogen atoms that are transferred to a polar unsaturated species under mild conditions. The first such catalyst was Shvo s diruthenium hydride complex reported in the mid 1980s [41 14], Noyori and Ikatiya developed chiral ruthenium catalysts showing excellent enantioselectivity in the hydrogenation of ketones [45,46]. 

In addition, several S/S ligands were also investigated for the asymmetric hydrogenation of olefins. In 1977, James and McMillan reported the synthesis of various disulfoxide ligands, which were applied to the asymmetric ruthenium-catalysed hydrogenation of prochiral olefinic acid derivatives, such as itaconic acid. These ligands, depicted in Scheme 8.16, were active to provide... 

A special example for a regioselective hydrogenation in ionic liquids was reported by our group and by DrieRen-Holscher [96, 97]. Based on investigations in the biphasic system water/n-heptane, the ruthenium-catalyzed hydrogenation of sorbic acid to ds-3-hexenoic acid according to Scheme 41.3 in the system [BMIM][PF6]/MTBE was studied [98],... 

ENANTIOSELECTIVE RUTHENIUM-CATALYZED HYDROGENATION OF VINYLPHOSPHONIC ACIDS... 

More recently, the ruthenium-catalyzed hydrogenation of sorbic acid to cis-hex-3-enoic acid. Scheme 16, was achieved in a biphasic bmim-PF6-methyl tert- miy ether (MTBE) system. The ruthenium cluster [H4Ru(q -C6H6)4] [Bp4]4, in [bmim][BF4], was shown to be an effective catalyst for the hydrogenation of arenes to the corresponding cycloalkanes at 90 °C and 60 bar. The cycloalkane product formed a separate phase, which was decanted and the IL phase, containing the catalyst, could be repeatedly recycled. 

Molybdenum-based catalysts are highly active initiators, however, monomers with functionalities with acid hydrogen, such as alcohols, acids, or thiols jeopardize the activity. In contrast, ruthenium-based systems exhibit a higher stability towards these functionalities (19). An example for a molybdenum-based catalyst is (20) MoOCl2(t-BuO)2, where t-BuO is the tert-butyl oxide radical. The complex can be prepared by reacting M0OCI4 with potassium tert-butoxide, i.e., the potassium salt of terf-butanol. 

The ruthenium cluster [Ru2(i76-C6H6)H6]C12 is a catalyst for fumaric acid hydrogenation in aqueous solutions, with a turnover frequency of 35 h 1 at 50°C (86). 

Benzylidene anilines formed from benzaldehydes and anilines have been found to undergo ortho arylation effectively when a ruthenium catalyst such as [RuC12(/ 6-C6H6)]2 is used in the presence of K2C03 as base (Eqs. 11 and 12) [17]. A polar solvent such as NMP is used. In this reaction the substrates have no acidic hydrogen and thus ortho metalation seems to occur via coordination of the neutral nitrogen to the metal center, as in the reaction of phosphinite (Scheme 3). Similarly, 2-phenylpyridine [18] (Eq. 13) and 2-phenyl-lH-imidazole (Eq. 14) [19] are arylated. 

Reduced ruthenium catalysts stored in air are usually oxidized on the surface and must be activated by prereduction with hydrogen for 1-2 h before use for hydrogenations at a low temperature and pressure. In contrast for platinum and palladium catalysts, organic as well as inorganic acids strongly poison the ruthenium catalyzed hydrogenation. Thus acetic acid should not be added or used as solvent for the hydrogenations over ruthenium, particularly under mild conditions. 

With hydrochloric acid hydrogen cyanide is evolved on warming, and after a time a deep violet-blue precipitate of ruthenium cyanide with a little potassium cyanide is obtained. Chlorine colours the solution brownish yellow, possibly in consequence of the formation of a ruthenicyanide, although no crystalline salt can be isolated from it. 

The ruthenium-catalyzed hydrogenation of sorbic acid to c/r-hexenoic acid is achieved in a bipha-sic [bmim][PF( ]-methyl-ferf-butyl ether (MTBE) system (see Steines, 2000) ... 

Kitamura, M., Tokunaga, M., Pham, T., Lubell, W.D. and Noyori, R., Asymmetric synthesis of a-amino P-hydroxy phosphonic acids via BINAP-ruthenium catalyzed hydrogenation. Tetrahedron Lett., 36, 5769, 1995. 

If this compound were needed on the tonne scale then auxihary chemistry is no good, however efficient recychng may be. A good alternative for the synthesis of compounds with unfunctionalized chiral centres adjacent to carboxylic acids or alcohols is the use of ruthenium-catalysed hydrogenation. 

Reduction of unsaturated carboxylic adds gives products that you might alternatively think of making by auxiliary-controlled alkylation methods. When the NutraSweet company needed this chiral branched carboxylic acid as a single enantiomer, they initially used the auxiliary methods of p. 1110 to make a small amount, but they found that ruthenium-catalysed hydrogenation was greatly to be preferred on a large scale just 22 g of the ruthenium-(5)-BINAP complex is needed to produce SO kg of product with 90% ee. 

In the last 20 years, the variety of ligands available for rhodium and ruthenium-catalysed hydrogenations has increased to the point where the right combination of metal and ligand will reduce almost any unsaturated carboxylic acid derivative in high enantiomeric excess. Details are beyond the scope of this book, but we leave you with four examples, all from industrial drug syntheses, to illustrate how versatile the method can be. 

A widely-reported method for the DKR of secondary alcohols and a- and p-hydroxy acid esters involves ruthenium catalysed hydrogenation. No additional base is required as a cocatalyst (and consequently base-catalysed transesterification can be avoided) because one of the ligand s oxygen atoms can act as a basic centre. A robust ruthenium complex (named Shvo s catalyst) along with a p-chlorophenylacetate was developed by the BackvaU group. The metal catalyst must be used in combination with thermostable enzymes because it is activated by heat (Scheme 4.26). This system (with CALB) has been successfully used for the DKR of many secondary alcohols and diols (Scheme 4.27) [52, 63, 64]. 

---