(8R,13S,14S)-13-tert-butoxycarbonyl-3-methoxy-7,8,12,13,15,16-hexahydro-6H-cyclopenta[a]phenanthren-17(14H)-one | 1207173-76-9

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: (8R,13S,14S)-13-tert-butoxycarbonyl-3-methoxy-7,8,12,13,15,16-hexahydro-6H-cyclopenta[a]phenanthren-17(14H)-one
• 英文别名: Estrone derivative 11c；tert-butyl (8R,13S,14S)-3-methoxy-17-oxo-7,8,12,14,15,16-hexahydro-6H-cyclopenta[a]phenanthrene-13-carboxylate
• CAS: 1207173-76-9
• 化学式: C₂₃H₂₈O₄
• 分子量: 368.473
• InChiKey: GSKMONXRUVLVEV-YDHSSHFGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (8R,13S,14S)-13-tert-butoxycarbonyl-3-methoxy-7,8,12,13,15,16-hexahydro-6H-cyclopenta[a]phenanthren-17(14H)-one 在 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 生成 tert-butyl (8R,13S,14S,17S)-17-hydroxy-3-methoxy-6,7,8,12,14,15,16,17-octahydro-13H-cyclopenta[a]phenanthrene-13-carboxylate
  参考文献：
  名称：

  Enantioselective Diels-Alder Reactions of Unsaturated ?-Ketoesters Catalyzed by Chiral Ruthenium PNNP Complexes

  摘要：

  We report here dicationic ruthenium PNNP complexes that promote the enantioselective Diels-Alder reaction of alpha-methylene beta-ketoesters with various dienes. Complex [Ru(OEt(2))(2)(PNNP)](PF(6))(2), formed in situ from [RuCl(2)(PNNP)] and (Et(3)O)PF(6)(2 equiv.), catalyzes the Diels-Alder reaction of such unsaturated beta-ketoesters to give novel alkoxycarbonyltetrahydro-1-indanone derivatives (nine examples) with up to 93% ee. The crystal structure of the substrate-catalyst adduct shows that the lower face of the substrate is shielded by a phenyl ring of the PNNP ligand, which accounts for the high enantioselectivity. The attack of the diene from the open re enantioface of the unsaturated beta-ketoester is consistent with the absolute configuration of the product. A useful application of this method is the reaction with Dane's diene to give estrone derivatives with up to 99% ee and an ester-exo:endo ratio of up to 145:1 (after recrystallization). Besides the enantioselective formation of all-carbon quaternary centers, this methodology is notable because unsaturated beta-ketoesters have been rarely used in Diels-Alder reactions. Furthermore, enantiomerically pure estrone derivatives are interesting in view of their potential applications, including the treatment of breast cancer.

  DOI：

  10.2533/chimia.2011.231
• 作为产物：
  描述：

  7-甲氧基-4-乙烯基-1,2-二氢萘 、 2-(methoxycarbonyl)-2-cyclopenten-1-one 在 RuCl2(κ4-N,N'-bis[o-(diphenylphosphino)benzylidene]-(1S,2S)-diiminocyclohexane) 、 triethyloxonium hexaflourophosphate 作用下， 以 二氯甲烷 为溶剂， 以85%的产率得到(8R,13S,14S)-13-tert-butoxycarbonyl-3-methoxy-7,8,12,13,15,16-hexahydro-6H-cyclopenta[a]phenanthren-17(14H)-one
  参考文献：
  名称：

  Enantioselective Diels-Alder Reactions of Unsaturated ?-Ketoesters Catalyzed by Chiral Ruthenium PNNP Complexes

  摘要：

  We report here dicationic ruthenium PNNP complexes that promote the enantioselective Diels-Alder reaction of alpha-methylene beta-ketoesters with various dienes. Complex [Ru(OEt(2))(2)(PNNP)](PF(6))(2), formed in situ from [RuCl(2)(PNNP)] and (Et(3)O)PF(6)(2 equiv.), catalyzes the Diels-Alder reaction of such unsaturated beta-ketoesters to give novel alkoxycarbonyltetrahydro-1-indanone derivatives (nine examples) with up to 93% ee. The crystal structure of the substrate-catalyst adduct shows that the lower face of the substrate is shielded by a phenyl ring of the PNNP ligand, which accounts for the high enantioselectivity. The attack of the diene from the open re enantioface of the unsaturated beta-ketoester is consistent with the absolute configuration of the product. A useful application of this method is the reaction with Dane's diene to give estrone derivatives with up to 99% ee and an ester-exo:endo ratio of up to 145:1 (after recrystallization). Besides the enantioselective formation of all-carbon quaternary centers, this methodology is notable because unsaturated beta-ketoesters have been rarely used in Diels-Alder reactions. Furthermore, enantiomerically pure estrone derivatives are interesting in view of their potential applications, including the treatment of breast cancer.

  DOI：

  10.2533/chimia.2011.231

文献信息

• Asymmetric Diels−Alder Reactions of Unsaturated β-Ketoesters Catalyzed by Chiral Ruthenium PNNP Complexes
  作者：Christoph Schotes、Antonio Mezzetti

  DOI：10.1021/ja910039e

  日期：2010.3.24

  Cyclic alpha-unsaturated beta-ketoesters undergo cycloaddition with di- and trisubstituted butadienes to give tetrahydro-1-indanone derivatives with up to 93% ee in the presence of a ruthenium catalyst formed by activation of [RuCl(2)(PNNP)] with (Et(3)P)PF(6) (2 equiv) (PNNP = (1S,2S)-N,N'-bis[o-(diphenylphosphino)benzylidene]cyclohexane-1,2-diamine). The protocol has been used to prepare the estrone derivative (8R, 13S, 14S)-13-tert-butoxycarbonyl-3-methoxy-7,8,1 2,13,15,16-hexahydro-6H-cyclopenta[a]phenanthren-17(14H)-one as a single diastereoisomer with 85% yield and 99% ee after one crystallization step. Its absolute configuration, which has been determined by X-ray diffraction after reduction to the alcohol and esterification with camphanic chloride, is in agreement with the attack of the diene onto the open enantioface of the beta-keto ester (O-O) in the ruthenium complex [Ru(O-O)(PNNP)](2+), whose X-ray structure has been determined.
• Asymmetric Diels–Alder and Ficini Reactions with Alkylidene β-Ketoesters Catalyzed by Chiral Ruthenium PNNP Complexes: Mechanistic Insight
  作者：Christoph Schotes、Martin Althaus、Raphael Aardoom、Antonio Mezzetti

  DOI：10.1021/ja210372u

  日期：2012.1.18

  Hydride abstraction from the beta-position of the enolato ligand of the previously reported complex [Ru(3a-H)(PNNP)]PF6 (5a; 3a-H is the enolate of 2-tert-butoxy-carbonylcyclopentanone) with (Ph3C)PF6 gives the dicationic complex [Ru(6a)(PNNP)(2+) (7a) as a single diastereoisomer, which contains the unsaturated beta-ketoester 2-tert-butoxycarbonyl-2-cyclopenten-1-one (6a) as a chelating ligand. The methyl analogue 2-methoxycarbonylcyclopentanone (3b) gives [Ru(3b-H)(PNNP)]PF6 as a mixture of noninterconverting diastereoisomers (ester group of 3b trans to P, 5b; or to N, 5c), which were separated by column chromatography. Hydride abstraction from 5b (or 5c) yields diastereomerically pure [Ru(6b)(PNNP)](2+) (7b or 7c). Complexes 7b and 7c do not interconvert at room temperature in CD2CI2 and form opposite enantiomers of the Diets Alder adduct upon reaction with Dane's diene (1 equiv). X-ray studies of 7a, 5b, and 5c give insight into the origin of enantioselection and the sense of asymmetric induction in the previously reported asymmetric Diels-Alder and Ficini cycloaddition reactions with 2,3-disubstituted butadienes and ynamides, respectively. Stoichiometric reactions (substrate coordination, cycloaddition, and product displacement) between [Ru-(OEt2)(2)(PNNP)](2+) (2), 6b (or 6a), and Dane's diene (15, to give estrone derivatives) or N-benzyl-N-(cyclohexylethynyl)-4-methylbenzenesulfonamide (17, to give cyclobutenamides) suggest that product displacement from the catalyst is turnover limiting.