A highly enantioselective conjugate reduction of 3-arylinden-1-ones using bakers' yeast for the preparation of (S)-3-arylindan-1-ones.
[formula: see text] The bakers' yeast reduction of 3-(1,3-benzodioxol-5-yl)-6-propoxy-1H-inden-1-one 4 has been shown to give (S)-3-(1,3-benzodioxol-5-yl)-2,3-dihydro-6-propoxy-1H-indan-1-one 6 in 65% yield with high enantioselectivity (> 99.0% ee), a key intermediate for the synthesis of the endothelin receptor antagonist SB 217242. In addition, the substituted 3-arylinden-1-ones 10a-e gave equally high enantioselectivity for the 3-arylindan-1-one products 13a-e. Mechanistic studies of the reaction indicate the operative pathway to be an asymmetric conjugate reduction, wherein the hydride transfer from NAD(P)H occurs from the Re-face of the indenone substrate.
Clark
W M
WM
Synthetic Chemistry Department, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406, USA.
Kassick
A J
AJ
Plotkin
M A
MA
Eldridge
A M
AM
Lantos
I
I
D002264:Carboxylic Acids / Q000138:chemical synthesis; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D065128:Endothelin Receptor Antagonists; D006863:Hydrogen-Ion Concentration; D007189:Indans / Q000138:chemical synthesis*; D009249:NADP; D010084:Oxidation-Reduction; D012441:Saccharomyces cerevisiae; D013237:Stereoisomerism
D002264:Carboxylic Acids; D065128:Endothelin Receptor Antagonists; D007189:Indans; D009249:NADP; C098288:enrasentan