A. Korostylev, V. Andrushko, N. Andrushko
Feb 1, 2008
Citations
0
Influential Citations
15
Citations
Journal
European Journal of Organic Chemistry
Abstract
The highly enantioselective hydrogenation of ethyl 5,5-dimethoxy-3-oxopentanoate (3) to ethyl 3-hydroxy-5,5-dimethoxypentanoate (4) – a key intermediate in the synthesis of pharmacologically important statin drugs – has been investigated. The stereochemistry of the catalytic hydrogenation of the β-keto ester in the presence of a number of homogeneous chiral RhI and RuII complexes with phosphane ligands has been studied. The highest enantioselectivity for the homogeneous hydrogenation of 3 (up to 98.7 % ee) was achieved through an optimized version of Genet's procedure with a Ru[(R)-BINAP]Cl2 pre-catalyst (substrate/catalyst ratio up to 20 000:1, 50 bar H2, 50 °C, in MeOH). The transformation of alcohol R-(4) into ylide R-(6) as an important precursor of the chiral side chain of rosuvastatin is also illustrated. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)