Highly Enantioselective Hydrogenation of Ethyl 5,5‐Dimethoxy‐3‐oxopentanoate and its Application for the Synthesis of a Statin Precursor | Zendy

Korostylev Andrei | Zendy; Andrushko Vasyl | Zendy; Andrushko Natalia | Zendy; Tararov Vitali I. | Zendy; König Gerd | Zendy; Börner Armin | Zendy

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Highly Enantioselective Hydrogenation of Ethyl 5,5‐Dimethoxy‐3‐oxopentanoate and its Application for the Synthesis of a Statin Precursor

Author(s) -

Korostylev Andrei,

Andrushko Vasyl,

Andrushko Natalia,

Tararov Vitali I.,

König Gerd,

Börner Armin

Publication year - 2008

Publication title -

european journal of organic chemistry

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 0.825

H-Index - 155

eISSN - 1099-0690

pISSN - 1434-193X

DOI - 10.1002/ejoc.200701059

Subject(s) - chemistry , enantioselective synthesis , asymmetric hydrogenation , catalysis , rosuvastatin , alcohol , noyori asymmetric hydrogenation , homogeneous , substrate (aquarium) , homogeneous catalysis , combinatorial chemistry , stereochemistry , medicinal chemistry , organic chemistry , medicine , physics , oceanography , geology , thermodynamics

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 Rh I and Ru II 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 Genêt's procedure with a Ru[( R )‐BINAP]Cl 2 pre‐catalyst (substrate/catalyst ratio up to 20 000:1, 50 bar H 2 , 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)

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