Asymmetric hydrogenation of unsaturated carboxylic acids

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. 

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. 

Scheme 10 Iridium SIPHOX-based catalysts in the asymmetric hydrogenation of unsaturated carboxylic acids...

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]. 

ASYMMETRIC HYDROGENATION OF 2-OXOCARBOXYLIC ACID ESTERS AND UNSATURATED CARBOXYLIC ACIDS ON MODIFIED PT AND PD CATALYSTS... 

Tellers DM, McWiUiams JC, Humphrey G, Joumet M, DiMichele L, Hinksmon J, McKeown AE, Rosner T, Sun Y, Tillyer RD. On the mechanism of an asymmetric a,P-unsaturated carboxylic acid hydrogenation application to the synthesis of a PGD2 receptor antagonist. J. Am. Chem. Soc. 2006 128(51) 17063 17073. 

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. 

Applications. In the last decade a lot of research has been devoted to the development of catalytic routes to a series of asymmetric carboxylic acids that lack the acetamido ligand as additional functionality. In Figure 4.17 four are listed, which are important as anaesthetics for rheumatic diseases. Their sales in beat many bulk chemicals the turnover of Naproxen (retail) in 1990 was 700 million for 1000 tons. S-Naproxen is now being produced by Syntcx via resolution with a chiral auxiliary. The main patents from Syntex expired in the U.S. in 1993, the reason for a lot of activity to study alternative synthetic routes. Routes leading to an asymmetric centre are o asymmetric hydrogenation of an unsaturated acid, o asymmetric carbohydroxylation of a styrene precursor, o asymmetric hydroformylation of a styrene precursor and oxidation. 

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... 

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