N. Andrushko, V. Andrushko, Thomas Thyrann
Oct 6, 2008
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0
Influential Citations
11
Citations
Journal
Tetrahedron Letters
Abstract
Abstract The enantioselective hydrogenation of ( E )-2-(4-methoxy-3-(3-methoxypropoxy)-benzylidene)-3-methylbutanoic acid ( 1 ) to ( R )-2-(4-methoxy-3-(3-methoxypropoxy)-benzyl)-3-methylbutanoic acid ( 2 )—a key intermediate in the synthesis of the pharmacologically important renin inhibitor Aliskiren—is described. The stereochemistry of the catalytic transformation has been studied using a number of homogeneous chiral Rh(I) and Ru(II) complexes bearing ferrocene-based phosphine ligands. The highest enantioselectivity for the homogeneous hydrogenation of 1 (up to 95% ee) was achieved with a [Rh(NBD) 2 ]BF 4 pre-catalyst (substrate/catalyst ratio 100:1, 10 bar H 2 , 40 °C, in MeOH). To bring the enantioselectivity to perfection an effective method for the isolation of the enantiopure carboxylic acid is suggested likewise.