Synthesis of Versatile Building Blocks through Asymmetric Hydrogenation of Functionalized Itaconic Acid Mono-Esters

• Published in: Advanced synthesis & catalysis 2008-01, Vol.350 (1), p.85-94
• Main Authors: Hekking, Koen F. W., Lefort, Laurent, de Vries, André H. M., van Delft, Floris L., Schoemaker, Hans E., de Vries, Johannes G., Rutjes, Floris P. J. T.
• Format: Article
• Language: English
• Subjects: asymmetric catalysis; asymmetric hydrogenation; itaconic acid; monodentate phosphoramidite ligands; rhodium; succinic acid
• ISSN: 1615-4150; 1615-4169
• DOI: 10.1002/adsc.200700307

The rhodium‐catalyzed asymmetric hydrogenation of several β‐substituted itaconic acid monoesters, using a library of monodentate phosphoramidite and phosphite ligands is described. Two β‐alkyl‐substituted substrates were readily hydrogenated by the rhodium complex Rh(COD)2BF4 in combination with (S)‐PipPhos as a ligand resulting in ees of 99 %. In contrast, the corresponding more hindered β‐aryl‐substituted substrates did not exhibit acceptable enantioselectivities under these conditions. However, the use of a 48‐membered ligand library led to the identification of several suitable ligands for these substrates, resulting in ees of 89–99 %. The resulting optically active succinic acid derivatives are potentially useful building blocks for more elaborate compounds, because of the ability to differentiate between the carboxylic acid and the ester groups on either side of the molecule.