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| title | chunk | source | category | tags | date_saved | instance |
|---|---|---|---|---|---|---|
| Asymmetric hydrogenation | 4/4 | https://en.wikipedia.org/wiki/Asymmetric_hydrogenation | reference | science, encyclopedia | 2026-05-05T10:46:00.770091+00:00 | kb-cron |
An alternative technique and one that allows more control over the structural and electronic properties of active catalytic sites is the immobilization of catalysts that have been developed for homogeneous catalysis on a heterogeneous support. Covalent bonding of the catalyst to a polymer or other solid support is perhaps most common, although immobilization of the catalyst may also be achieved by adsorption onto a surface, ion exchange, or even physical encapsulation. One drawback of this approach is the potential for the proximity of the support to change the behaviour of the catalyst, lowering the enantioselectivity of the reaction. To avoid this, the catalyst is often bound to the support by a long linker though cases are known where the proximity of the support can actually enhance the performance of the catalyst. The final approach involves the construction of MOFs that incorporate chiral reaction sites from a number of different components, potentially including chiral and achiral organic ligands, structural metal ions, catalytically active metal ions, and/or preassembled catalytically active organometallic cores. One of these involved ruthenium-based catalysts. As little as 0.005 mol% of such catalysts proved sufficient to achieve the asymmetric hydrogenation of aryl ketones, although the usual conditions featured 0.1 mol % of catalyst and resulted in an enantiomeric excess of 90.6–99.2%.
== Industrial applications ==
Asymmetric hydrogenations are used in the production of several drugs, such as the antibacterial levofloxacin, the antibiotic carbapenem, and the antipsychotic agent BMS181100. Knowles' research into asymmetric hydrogenation and its application to the production scale synthesis of L-Dopa gave asymmetric hydrogenation a strong start in the industrial world. A 2001 review indicated that asymmetric hydrogenation accounted for 50% of production scale, 90% of pilot scale, and 74% of bench scale catalytic, enantioselective processes in industry, with the caveat that asymmetric catalytic methods in general were not yet widely used. Asymmetric hydrogenation has replaced kinetic resolution based methods has resulted in substantial improvements in the process's efficiency. can be seen in a number of specific cases where the For example, Roche's Catalysis Group was able to achieve the synthesis of (S,S)-Ro 67-8867 in 53% overall yield, a dramatic increase above the 3.5% that was achieved in the resolution based synthesis. Roche's synthesis of mibefradil was likewise improved by replacing resolution with asymmetric hydrogenation, reducing the step count by three and increasing the yield of a key intermediate to 80% from the original 70%.
Noyori-inspired hydrogenation catalysts have been applied to the commercial synthesis of number of fine chemicals. (R)-1,2-Propandiol, precursor to the antibacterial levofloxacin, can be efficiently synthesized from hydroxyacetone using Noyori asymmetric hydrogenation: Newer routes focus on the hydrogenation of (R)-methyl lactate. An antibiotic carbapenem is also prepared using Noyori asymmetric hydrogenation via (2S,3R)-methyl 2-(benzamidomethyl)-3-hydroxybutanoate, which is synthesized from racemic methyl 2-(benzamidomethyl)-3-oxobutanoate by dynamic kinetic resolution.
An antipsychotic agent BMS-181100 is synthesized using BINAP/diamine-Ru catalyst.
== References ==