Tararov, Vitali I.; Koenig, Gerd; Boerner, Armin published the artcile< Synthesis of statins. I. Synthesis and highly stereoselective hydrogenation of the statin precursor ethyl (5S)-5,6-isopropylidenedioxy-3-oxohexanoate>, Category: esters-buliding-blocks, the main research area is statin intermediate isopropylidenedioxyoxohexanoate preparation stereoselective hydrogenation.
A search for the large-scale preparation of (5S)-5,6-(isopropylidenedioxy)-3-oxohexanoate, a key intermediate in the synthesis of pharmacol. important statins, starting from (S)-malic acid is described. The synthesis of the required intermediate Me (3S)-3,4-(isopropylidenedioxy)butanoate (I) by Moriwake’s reduction of di-Me (S)-malate has been improved. Direct 2-C chain elongation of ester I using the lithium enolate of tert-Bu acetate has been shown to be successful at a 3- to 5-fold excess of the enolate. Unfortunately, the product, tert-Bu (5S)-5,6-(isopropylidenedioxy)-3-oxohexanoate is unstable during distillation Et (5S)-5,6-(isopropylidenedioxy)-3-oxohexanoate (II) was prepared alternatively on a multigram scale from (3S)-3,4-(isopropylidenedioxy)butanoic acid by activation with N,N’-carbonyldiimidazole and subsequent reaction with Mg(O2CCH2CO2Et)2. A convenient pathway for the in situ preparation of the latter is also described. II can be advantageously purified by distillation The stereochem. of the catalytic hydrogenation of II to Et (5S)-5,6-(isopropylidenedioxy)-3-hydrohyhexanoate (III) has been studied using a number of homogeneous achiral and chiral Rh(I) and Ru(II) complexes with phosphine ligands. A comparison of Rh(I) and Ru(II) catalysts with (S)- and (R)-BINAP as chiral ligands revealed opposite activity in dependence on the polarity of the solvent. No influence of the chiral backbone of substrate II on the enantioselectivity was noted. A ratio of syn/anti-III = 2.3 was observed with an achiral (Ph3P)3RuCl2 catalyst. Ru[(R)-Tol-BINAP]Cl2 neutralized with one equivalent of AcONa afforded the most efficient catalytic system for the production of optically pure syn-III at a preparative substrate/catalyst ratio of 1000:1.
Advanced Synthesis & Catalysis published new progress about Hydrogenation catalysts, stereoselective. 617-55-0 belongs to class esters-buliding-blocks, and the molecular formula is C6H10O5, Category: esters-buliding-blocks.
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