Highly Enantioselective Catalytic Asymmetric Synthesis of a (R)-Sibutramin Precursor
DOI:
https://doi.org/10.2533/chimia.2010.59Keywords:
Catalytic asymmetric hydrogenation, Enantioselective synthesis, SibutramineAbstract
The first highly enantioselective, catalytic asymmetric synthesis of di-des-methylsibutramine 3 is described. Dienamide 10, prepared by acetic acid anhydride quenching of the condensation product of nitrile 4 with a methallyl magnesium chloride, proved to be an excellent substrate for ruthenium-catalyzed asymmetric hydrogenation with atropisomeric diphosphine ligands. Hydrogenation with a ruthenium/(R)- MeOBiPheP catalyst at S/C = 500, gave the chiral amide (R)-9 in 98.5% ee in almost quantitative yield. After acidic amide hydrolysis the desired amine (R)-3 was obtained without erosion of enantioselectivity. It is anticipated that the overall process will be amenable to large-scale production.Downloads
Published
2010-02-26
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Copyright (c) 2010 Swiss Chemical Society
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
How to Cite
[1]
Chimia 2010, 64, 59, DOI: 10.2533/chimia.2010.59.