(R)-(+)-Methyl 2-hydroxy-5,8-dimethoxy-1-oxo-1,2,3,4-tetrahydro-2-naphthoate | 133361-49-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: (R)-(+)-Methyl 2-hydroxy-5,8-dimethoxy-1-oxo-1,2,3,4-tetrahydro-2-naphthoate
• 英文别名: (R)-methyl 2-hydroxy-5,8-dimethoxy-1-oxo-1,2,3,4-tetrahydronaphthalene-2-carboxylate；methyl (2R)-2-hydroxy-5,8-dimethoxy-1-oxo-3,4-dihydronaphthalene-2-carboxylate
• CAS: 133361-49-6
• 化学式: C₁₄H₁₆O₆
• 分子量: 280.277
• InChiKey: BOWOBDURYCPXQU-CQSZACIVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  82.1
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (R)-(+)-Methyl 2-hydroxy-5,8-dimethoxy-1-oxo-1,2,3,4-tetrahydro-2-naphthoate 在 三乙基硅烷 、 aluminum amalgam 、 水 、 三溴化硼 、 sodium hydride 、 二甲基亚砜 作用下， 以 二氯甲烷 、 三氟乙酸 为溶剂， 反应 36.0h， 生成 (R)-(-)-2-Acetyl-8-hydroxy-5-methoxy-1,2,3,4-tetrahydro-2-naphthalenol
  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：

  Methyl 5,8-dimethoxy-1,2,3,4-tetrahydro-2-naphthoate 在 (-)-<(8,8-dimethoxycamphoryl)sulfonyl>oxaziridine 、 双(三甲基硅烷基)氨基钾 作用下， 生成 (R)-(+)-Methyl 2-hydroxy-5,8-dimethoxy-1-oxo-1,2,3,4-tetrahydro-2-naphthoate
  参考文献：
  名称：

  （R）-（-）-2-乙酰基-5,8-二甲氧基-1,2,3,4-四氢-2-萘酚的高度对映选择性合成。蒽环素合成中的关键中间体

  摘要：

  AB-Synthon（R）-（-）- 5是蒽环素3和4的不对称合成中的关键中间体，其总产率为35％，ee≥95 ％。关键步骤涉及使用N-磺酰基恶唑烷（-）- 6c对7的烯醇钾进行羟化反应。

  DOI：

  10.1016/s0040-4039(00)92107-5

文献信息

• A highly enantioselective synthesis of (R)-(-)-2-acetyl-5,8-dimethoxy-1,2,3,4-tetrahydro-2-naphthol. A key intermediate in the synthesis of anthracyclinones
  作者：Franklin A. Davis、Anil Kumar、Bang-Chi Chen

  DOI：10.1016/s0040-4039(00)92107-5

  日期：1991.2

  AB-Synthon (R)-(−)-5, a key intermediate in the asymmetric synthesis of anthracyclinones 3 and 4 is prepared in 35% overall yield and > 95% ee. The key step involves hydroxylation of the potassium enolate of 7 using N-sulfonyloxaziridine (−)-6c.

  AB-Synthon（R）-（-）- 5是蒽环素3和4的不对称合成中的关键中间体，其总产率为35％，ee≥95 ％。关键步骤涉及使用N-磺酰基恶唑烷（-）- 6c对7的烯醇钾进行羟化反应。
• Asymmetric Synthesis of the AB Ring Segments of Daunomycin and 4-Demethoxydaunomycin
  作者：Franklin A. Davis、Charles Clark、Anil Kumar、Bang-Chi Chen

  DOI：10.1021/jo00084a042

  日期：1994.3

  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.
• <i>N,N′</i>-Dioxide-Magnesium Ditriflate Complex-Catalyzed Asymmetric α-Hydroxylation of β-Keto Esters and β-Keto Amides
  作者：Chengkai Yin、Weidi Cao、Lili Lin、Xiaohua Liu、Xiaoming Feng

  DOI：10.1002/adsc.201300335

  日期：2013.7.8

  The highly catalytic asymmetric α‐hydroxylation of 1‐tetralone‐derived β‐keto esters and β‐keto amides using tert‐butyl hydroperoxide (TBHP) as the oxidant was realized by a chiral N,N′‐dioxide‐magnesium ditriflate [Mg(OTf)2] complex. A series of corresponding chiral α‐hydroxy dicarbonyl compounds was obtained in excellent yields (up to 99%) with excellent enantioselectivities (up to 98% ee). The products

  使用叔丁基氢过氧化物（TBHP）作为氧化剂，对1-四氢萘酮衍生的β-酮酯和β-酮酰胺进行高度催化的不对称α-羟基化反应，是通过手性N，N'-二氧化物-三氟甲磺酸镁[Mg（ OTf）2 ]复杂。以优异的收率（最高99％）和优异的对映选择性（最高98％ee）获得了一系列相应的手性α-羟基二羰基化合物。产物易于转化为有用的结构单元，并且首次以不对称催化方式获得了道诺霉素的前体。