1-[(R)-2,8-Bis-(tert-butyl-dimethyl-silanyloxy)-5-methoxy-1,2,3,4-tetrahydro-naphthalen-2-yl]-ethanone | 155193-39-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: 1-[(R)-2,8-Bis-(tert-butyl-dimethyl-silanyloxy)-5-methoxy-1,2,3,4-tetrahydro-naphthalen-2-yl]-ethanone
• CAS: 155193-39-8
• 化学式: C₂₅H₄₄O₄Si₂
• 分子量: 464.793
• InChiKey: VXYWZCJISLOTTR-RUZDIDTESA-N

物化性质

• 沸点：
  496.4±45.0 °C(predicted)
• 密度：
  0.99±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.92
• 重原子数：
  31.0
• 可旋转键数：
  6.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.72
• 拓扑面积：
  44.76
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  1-[(R)-2,8-Bis-(tert-butyl-dimethyl-silanyloxy)-5-methoxy-1,2,3,4-tetrahydro-naphthalen-2-yl]-ethanone 在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 反应 0.58h， 生成 (-)-(R)-2-Acetyl-2-(tert-butyldimethylsiloxy)-5-methoxy-8-hydroxy-1,2,3,4-tetrahydronaphthalene
  参考文献：
  名称：

  Asymmetric Synthesis of the AB Ring Segments of Daunomycin and 4-Demethoxydaunomycin

  摘要：

  Asymmetric hydroxylation of the potassium enolate of beta-keto ester 14, with (camphorsulfonyl)-oxaziridine (-)-7c [tetrahydro-9,9-dimethyl-8,8-dimethorry-4H-4a,7-methanooxazirino[3,2-i][2,1]-benzisothiazole 3,3-dioxide] affords alpha-hydroxy beta-keto ester (R)-(+)-15 in >95% ee. The high ee's are attributed to the fact that this enolate probably exists in one geometric form as a consequence of intramolecular chelation. Reduction of the ketone in 15 with triethylsilane and conversion of the ester group into the methyl ketone results in a highly efficient synthesis of the AB ring building block (R)-(-)-2-acetyl-5,8-dimethoxy-1,2,3,4-tetrahydro-2-napthol (3b), a key intermediate in the asymmetric synthesis of the antitumor agent 4-demethoxydaunomycin (1c). Selective deprotection of the 8-methoxy group in 3b with BBr3 gives 3a, important in the enantioselective synthesis of the clinically useful antitumor agent adriamycin (1b). Attempts to prepare 3a and 3b more directly by asymmetric hydroxylation of the enolates of methyl 5,8-dimethoxy-1,2,3,4-tetrahydro-2-naphthoate (9) or the 8-benzyloxy derivative of 16 resulted in low ee's, attributable to the formation of E/Z enolate mixtures and increased steric congestion in the transition state for hydroxylation.

  DOI：

  10.1021/jo00084a042
• 作为产物：
  描述：

  (R)-(-)-Methyl 2,8-dihydroxy-5-methoxy-1,2,3,4-tetrahydro-2-naphthoate 在 2,6-二甲基吡啶 、 aluminum amalgam 、 水 、 sodium hydride 、 二甲基亚砜 作用下， 以 二氯甲烷 为溶剂， 反应 19.0h， 生成 1-[(R)-2,8-Bis-(tert-butyl-dimethyl-silanyloxy)-5-methoxy-1,2,3,4-tetrahydro-naphthalen-2-yl]-ethanone
  参考文献：
  名称：

  Asymmetric Synthesis of the AB Ring Segments of Daunomycin and 4-Demethoxydaunomycin

  摘要：

  Asymmetric hydroxylation of the potassium enolate of beta-keto ester 14, with (camphorsulfonyl)-oxaziridine (-)-7c [tetrahydro-9,9-dimethyl-8,8-dimethorry-4H-4a,7-methanooxazirino[3,2-i][2,1]-benzisothiazole 3,3-dioxide] affords alpha-hydroxy beta-keto ester (R)-(+)-15 in >95% ee. The high ee's are attributed to the fact that this enolate probably exists in one geometric form as a consequence of intramolecular chelation. Reduction of the ketone in 15 with triethylsilane and conversion of the ester group into the methyl ketone results in a highly efficient synthesis of the AB ring building block (R)-(-)-2-acetyl-5,8-dimethoxy-1,2,3,4-tetrahydro-2-napthol (3b), a key intermediate in the asymmetric synthesis of the antitumor agent 4-demethoxydaunomycin (1c). Selective deprotection of the 8-methoxy group in 3b with BBr3 gives 3a, important in the enantioselective synthesis of the clinically useful antitumor agent adriamycin (1b). Attempts to prepare 3a and 3b more directly by asymmetric hydroxylation of the enolates of methyl 5,8-dimethoxy-1,2,3,4-tetrahydro-2-naphthoate (9) or the 8-benzyloxy derivative of 16 resulted in low ee's, attributable to the formation of E/Z enolate mixtures and increased steric congestion in the transition state for hydroxylation.

  DOI：

  10.1021/jo00084a042