Unsaturated carboxylic acids asymmetric hydrogenation

Prochiral organic acids were hydrogenated on clay-supported Rh-chiral phosphine complexes.205,206 Hectorite-supported chiral Rh(I)-phosphine complexes were used for the asymmetric hydrogenation of a,P-unsaturated carboxylic acids.207 It was found that the interaction between the a-ester group of itaconates and phenyl groups of phosphine can play an important role in the determination of the configuration of products. 

In the early 1990s, Burk introduced a new series of efficient chiral bisphospholane ligands BPE and DuPhos.55,55a-55c The invention of these ligands has expanded the scope of substrates in Rh-catalyzed enantioselective hydrogenation. For example, with Rh-DuPhos or Rh-BPE as catalysts, extremely high efficiencies have been observed in the asymmetric hydrogenation of a-(acylamino)acrylic acids, enamides, enol acetates, /3-keto esters, unsaturated carboxylic acids, and itaconic acids. 

Table 2.1.5.3 Asymmetric hydrogenation of a, P-unsaturated carboxylic acid derivatives.

This ligand, MeO-BIPHEP (96a), has shown similar reactivities and enantioselectivities to catalysts that contain BINAP.117 Ruthenium catalysts that contain MeO-BIPHEP have been used in several asymmetric hydrogenations from bench scale to multi-ton scale, which include the large-scale preparation of a P-keto ester, an aryl ketone, allylic alcohol, and several oc,P-unsaturated carboxylic acid substrates, which are shown in Figure 12.5. 

Ruthenium and rhodium complexes that contain TMBTP have shown utility in the asymmetric hydrogenation of allylic alcohols,155,156 P-keto esters,155,157 and a,P-unsaturated carboxylic acids.155... 

The NMDPP, MDPP, and CAMPHOS Catalysts Reaction Conditions for Asymmetric Hydrogenations of a,(1- Unsaturated Carboxylic Acids... 

Asymmetric Homogeneous Hydrogenation of a, p-Unsaturated Carboxylic Acids with the Rhodium(I)-(+)-CAMPHOS Catalysta... 

Asymmetric Homogeneous Hydrogenation of a,(i-Unsaturated Carboxylic Acids with [Rh (COD) (ACMP)ij BFa a,b... 

Asymmetric Hydrogenation of a, p- Unsaturated Carboxylic Acids A Comparison of Product Percent Enantiomeric Excess Values for Several Ligandsa c... 

The asymmetric transfer hydrogenation of the unsaturated carboxylic acids using formic acid or alcohols as the hydrogen source is catalyzed by Ru(acac-F6)( / -C3H5)(BINAP) or [RuH(BINAP)2]PFe to produce the saturated acids in up to 97% ee (eq 15). ... 

A considerable success has been realized for asymmetric hydrogenation of functionalized alkenes since the discovery of BINAP-Ru complexes in the mid-1980s [5]. The details are described in each of the following substrates, enamides, alkenyl esters and ethers, a,/3- and /3,y-unsaturated carboxylic acids, a,/3-unsaturated esters and ketones, and allylic and homoallylic alcohols. 

The asymmetric hydrogenation of a,fi- or )0,g-unsaturated carboxylic acids has been applied successfully to the preparation of some key intermediates for pharmaceuticals. For example, a Rh complex with (5,5)-CHIRAPHOS catalyzes hydrogenation of the sodium salt of unsaturated carboxylic acids, intermediates for the non-peptide endothelin antagonists SB209670 and SB217242, in 90% yield and 94% ee [29]. 

Noyori asymmetric hydrogenation Formation of enantio-enriched carboxylic acids, alcohols and amino acids from unsaturated carboxylic acids, allylic alcohols and enamides, respectively. 316... 

Xiao, J., Nefkens, S. C. A., Jessop, P. G., Ikariya, T., Noyori, R. Asymmetric hydrogenation of a,P-unsaturated carboxylic acids in supercritical carbon dioxide. Tetrahedron Lett. 1996, 37, 2813-2816. 

Ohta, T., Takaya, H., Kitamura, M., Nagai, K., Noyori, R. Asymmetric hydrogenation of unsaturated carboxylic acids catalyzed by BINAP-ruthenium(ll) complexes. J. Org. Chem. 1987, 52, 3174-3176. 

Ashby, M. T., Halpern, J. Kinetics and mechanism of catalysis of the asymmetric hydrogenation of a,P-unsaturated carboxylic acids by bis(carboxylato) 2,2 -bis(diphenylphosphino)-1,1 -binaphthyl ruthenium(ll), [Rull(BINAP) (02CR)2]. J. Am. Chem. Soc. 1991,113, 589-594. 

Yoshikawa, K., Murata, M., Yamamoto, N., Inoguchi, K., Achiwa, K. Asymmetric reactions catalyzed by chiral metal complexes. III. The origin of the enantioselection in the ruthenium(ll)-catalyzed asymmetric hydrogenation of a,P-unsaturated carboxylic acid. Chem. Pharm. Bull. 1992, 40, 1072-1074. 

Application of subcritical gaseous CO2 to an organic liquid causes the liquid phase to expand noticeably, due to extensive dissolution of the CO2 into the liquid phase (131). This expansion is accompanied by a reduction in the liquid phase viscosity, an increase in the solubility of H2 in the liquid, and an increase in the mass transfer rates from the gas to liquid phase. There is evidence that this can affect the enantioselectivity of reactions in viscous liquids. The enantioselectivity of asymmetric hydrogenation of unsaturated carboxylic acids in a viscous ionic liquid was shown to be strongly affected by CO2 expansion of the liquid, the enantioselectively being improved for one substrate (atropic acid) and decreased for another (tiglic acid). The results were explained in terms of the solubility and rate of transfer of H2 gas into the expanded ionic liquid (23). The same effect was not observed in expanded methanol. 

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