title: A highly enantioselective conjugate reduction of 3-arylinden-1-ones using bakers' yeast for the preparation of (S)-3-arylindan-1-ones.
abstract: [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.
authors.affiliation: Synthetic Chemistry Department, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406, USA.
authors.forename: W M
authors.initials: WM
authors.lastname: Clark
authors.forename: A J
authors.initials: AJ
authors.lastname: Kassick
authors.forename: M A
authors.initials: MA
authors.lastname: Plotkin
authors.forename: A M
authors.initials: AM
authors.lastname: Eldridge
authors.forename: I
authors.initials: I
authors.lastname: Lantos
mesh_terms: 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
chemical_list: D002264:Carboxylic Acids; D065128:Endothelin Receptor Antagonists; D007189:Indans; D009249:NADP; C098288:enrasentan