Asymmetric hydrogenation pressure effects

In this work, various Ru-BINAP catalysts immobilized on the phosphotungstic acid(PTA) modified alumina were prepared and the effects of the reaction variables (temperature, H2 pressure, solvent and content of triethylamine) on the catalytic performance of the prepared catalysts were investigated in the asymmetric hydrogenation of dimethyl itaconate (DMIT). 

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]. 

In asymmetric hydrogenation, the pressure of hydrogen may have a substantial impact on both the rates and the stereoselectivities of the reaction. These effects may be attributed either to the formation of different catalytically competing species in solution or to the operation of kinetically distinct catalytic cycles at different pressures. 

Asymmetric hydrogenation. Procbiral u,/ -unsaturated acids and their derivatives can be hydrogenated with high stereoselectivity by rhodium complexes with 1, such as (BPPM)Rh(COD)Cl and (BPPM)Rh(COD)+ClCV, in which COD = 1,5-eyclooctadiene. The stereoselectivity is dependent in part on the hydrogen pressure, ami the effect can be attenuated by addition of triethylamine, which also increases Ihc optical yield. The stereoselectivity is markedly controlled by the stereochemistry of the double bond.1... 

The homogeneous catalytic asymmetric hydrogenations of 2-arylacrylic acids have been studied. Both rhodium and ruthenium catalysts have been examined. The reaction temperatures and hydrogen pressures have profound effects on the optical yields of the the products. The presence of a tertiary amine such as triethylamine also significantly increases the product enantiomer excess. Commercially feasible processes for the production of naproxen and S-ibuprofen have been developed based on these reactions. 

Table 3. The Temperature and Pressure Effects of the Asymmetric Hydrogenation of 1 >b...

The catalytic asymmetric hydrosilation of a prochiral ketone to the corresponding chiral silyl ether followed by a mild hydrolysis is in principle an attractive route for the preparation of chiral alcohols that has die advantage that it would not require high hydrogen pressure to effect the reduction (1-6). Despite the synthetic potential only limited application of this technique to the synthesis of complex organic molecules has been made (7-9). This is in part due to the relatively low optical... 

Redaction of Imines. This catalyst system is very effective for the asymmetric hydrogenation of imines. For example, AL(1-cyclohexyl)ethylidenebenzylamine (as a mixture of anti and syn isomers) can be reduced in excellent yield and good enantiomeric excess (eq 3). The reaction must be conducted at high pressures in order to achieve maximum enantioselecdvity. This effect was found for several acyclic imines. 

A novel class of complexes, Ir-(5 )-26a, with chiral spiro aminophosphine ligands was found to be effective catalyst for the asymmetric hydrogenation of a-substituted acrylic acids (Scheme 11) [62]. Under mild reaction conditions and at ambient pressure, various a-aryl and alkyl propionic acids were produced with extremely high efficiency (TONS up to 10 000 TOFs up to 6000h ) and excellent enantioselectivity (up to 99% ee). This reaction provides a practically useful method for the preparation of a-aryl propionic acids, a popular class of non-steroid anti-inflammtory reagents. 

Optimization of the enantioselective catalytic key steps calls for careful experimental investigation of many reaction parameters. Besides temperature, concentration of substrate, solvent effects, pressure, and conversion rate, a defined robustness of the process towards impurities, for example contained in reagents, as well as its sensitivity towards air (oxygen) or moisture at various temperatures are important aspects. In particular, the purity of prochiral substrates is of utmost importance for the success of asymmetric hydrogenation experiments. As a consequence, considerable attention had to be paid to even the smallest differences in the impurity profile of substrates, which may be due to different preparation and/or purification procedures at lab, pilot, or production scale. 

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