(5S,6R)-5-<(tert-Butyldimethylsilyl)oxy>-6-<(benzyloxy)methyl>-2-piperidinone | 168773-38-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (5S,6R)-5-<(tert-Butyldimethylsilyl)oxy>-6-<(benzyloxy)methyl>-2-piperidinone
• 英文别名: (5S,6R)-6-((benzyloxy)methyl)-5-((tert-butyldimethylsilyl)oxy)piperidin-2-one；(5S,6R)-5-[tert-butyl(dimethyl)silyl]oxy-6-(phenylmethoxymethyl)piperidin-2-one
• CAS: 168773-38-4
• 化学式: C₁₉H₃₁NO₃Si
• 分子量: 349.546
• InChiKey: AYJPJROOMORTNW-SJORKVTESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.87
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  47.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (5S,6R)-5-<(tert-Butyldimethylsilyl)oxy>-6-<(benzyloxy)methyl>-2-piperidinone 在 palladium on activated charcoal 四溴化碳 、 四丁基氟化铵 、 氢气 、 四丁基碘化铵 、 双(三甲基硅烷基)氨基钾 、 sodium hydride 、 三苯基膦 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 为溶剂， 反应 68.5h， 生成 (1R,4S,6S)-6-Hydroxy-2-(p-methoxybenzyl)-2-azabicyclo<2.2.1>-3-heptanone
  参考文献：
  名称：

  Chirospecific Syntheses of Precursors of Cyclopentane and Cyclopentene Carbocyclic Nucleosides by [3 + 3]-Coupling and Transannular Alkylation

  摘要：

  A new method is reported for the preparation of enantiomerically pure (1R,2S,4S)-1-amino-2-hydroxy-4-(hydroxymethyl)cyclopentane, (1R,2R,4S)-1-amino-2-fluoro-4-(hydroxymethyl)cyclopentane, and (1R,4S)-1-amino-4-(hydroxymethyl)-2-cyclopentene, advanced precursors to carbocyclic nucleosides. The method involves initial conversion of D-serine into an aldehyde with 9-phenylfluorenyl protection at nitrogen and O-benzyl protection at oxygen. A [3 + 3]-coupling of this aldehyde with a titanium homoenolate derived from tert-butyl 3-iodopropionate gave the corresponding anti-lactone in high yield. Regioselective hydrogenolysis of the amine protecting group, accompanied by intramolecular O- to N-cyclization formed a lactam. After suitable nitrogen protection and functional group manipulation, transannular alkylation afforded the corresponding 2-benzyl- or 2-(p-methoxybenzyl)-6-hydroxy-2-azabicycclo[2.2.1]-3-heptanone. Functional group modification of the 2-benzyl analogue gave the resulting 6(S)-hydroxy and 6(R)-fluoro N-BOC imides; alternatively, the 2-(p-methoxybenzyl) analogue was converted to an N-BOC imide containing an olefinic Linkage at C-5 and C-6 of the bicycle. Subjecting each of the N-BOC imides to a reduction-deprotection sequence then afforded the desired carbocyclic analogues. The [3 + 3]-coupling method also allowed improved and expedient access to an advanced tribenzylated lactam previously used in the racemic syntheses of the hydroxylated alkaloids D-mannonolactam, deoxymannojirimycin, and prosopinone, providing a formal asymmetric synthesis of these alkaloids.

  DOI：

  10.1021/jo00119a044
• 作为产物：
  描述：

  N-(9-Phenyl-9-fluorenyl)-D-serine isoxazolidide O-benzyl ether 在 palladium on activated charcoal 咪唑 、 lithium aluminium tetrahydride 、 氢气 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 41.67h， 生成 (5S,6R)-5-<(tert-Butyldimethylsilyl)oxy>-6-<(benzyloxy)methyl>-2-piperidinone
  参考文献：
  名称：

  Chirospecific Syntheses of Precursors of Cyclopentane and Cyclopentene Carbocyclic Nucleosides by [3 + 3]-Coupling and Transannular Alkylation

  摘要：

  A new method is reported for the preparation of enantiomerically pure (1R,2S,4S)-1-amino-2-hydroxy-4-(hydroxymethyl)cyclopentane, (1R,2R,4S)-1-amino-2-fluoro-4-(hydroxymethyl)cyclopentane, and (1R,4S)-1-amino-4-(hydroxymethyl)-2-cyclopentene, advanced precursors to carbocyclic nucleosides. The method involves initial conversion of D-serine into an aldehyde with 9-phenylfluorenyl protection at nitrogen and O-benzyl protection at oxygen. A [3 + 3]-coupling of this aldehyde with a titanium homoenolate derived from tert-butyl 3-iodopropionate gave the corresponding anti-lactone in high yield. Regioselective hydrogenolysis of the amine protecting group, accompanied by intramolecular O- to N-cyclization formed a lactam. After suitable nitrogen protection and functional group manipulation, transannular alkylation afforded the corresponding 2-benzyl- or 2-(p-methoxybenzyl)-6-hydroxy-2-azabicycclo[2.2.1]-3-heptanone. Functional group modification of the 2-benzyl analogue gave the resulting 6(S)-hydroxy and 6(R)-fluoro N-BOC imides; alternatively, the 2-(p-methoxybenzyl) analogue was converted to an N-BOC imide containing an olefinic Linkage at C-5 and C-6 of the bicycle. Subjecting each of the N-BOC imides to a reduction-deprotection sequence then afforded the desired carbocyclic analogues. The [3 + 3]-coupling method also allowed improved and expedient access to an advanced tribenzylated lactam previously used in the racemic syntheses of the hydroxylated alkaloids D-mannonolactam, deoxymannojirimycin, and prosopinone, providing a formal asymmetric synthesis of these alkaloids.

  DOI：

  10.1021/jo00119a044

文献信息

• Concise Enantioselective Syntheses of (+)-L-733,060 and (2S,3S)-3-Hydroxypipecolic Acid by Cobalt(III)(salen)-Catalyzed Two-Stereocenter Hydrolytic Kinetic Resolution of Racemic Azido Epoxides
  作者：Arumugam Sudalai、Dattatray Devalankar、Pandurang Chouthaiwale

  DOI：10.1055/s-0033-1340074

  日期：——

  An efficient synthesis of the 2,3-disubstituted piperidines (+)-L-733,060 and (2S,3S)-3-hydroxypipecolic acid (99% ee) in high optical purity from commercially available starting materials is described. The strategy involves a cobalt-catalyzed hydrolytic kinetic resolution of a racemic azido epoxide with two stereocenters and an intramolecular reductive cyclization as key reactions.
• Chirospecific Syntheses of Precursors of Cyclopentane and Cyclopentene Carbocyclic Nucleosides by [3 + 3]-Coupling and Transannular Alkylation
  作者：Jeffrey A. Campbell、Won Koo Lee、Henry Rapoport

  DOI：10.1021/jo00119a044

  日期：1995.7

  A new method is reported for the preparation of enantiomerically pure (1R,2S,4S)-1-amino-2-hydroxy-4-(hydroxymethyl)cyclopentane, (1R,2R,4S)-1-amino-2-fluoro-4-(hydroxymethyl)cyclopentane, and (1R,4S)-1-amino-4-(hydroxymethyl)-2-cyclopentene, advanced precursors to carbocyclic nucleosides. The method involves initial conversion of D-serine into an aldehyde with 9-phenylfluorenyl protection at nitrogen and O-benzyl protection at oxygen. A [3 + 3]-coupling of this aldehyde with a titanium homoenolate derived from tert-butyl 3-iodopropionate gave the corresponding anti-lactone in high yield. Regioselective hydrogenolysis of the amine protecting group, accompanied by intramolecular O- to N-cyclization formed a lactam. After suitable nitrogen protection and functional group manipulation, transannular alkylation afforded the corresponding 2-benzyl- or 2-(p-methoxybenzyl)-6-hydroxy-2-azabicycclo[2.2.1]-3-heptanone. Functional group modification of the 2-benzyl analogue gave the resulting 6(S)-hydroxy and 6(R)-fluoro N-BOC imides; alternatively, the 2-(p-methoxybenzyl) analogue was converted to an N-BOC imide containing an olefinic Linkage at C-5 and C-6 of the bicycle. Subjecting each of the N-BOC imides to a reduction-deprotection sequence then afforded the desired carbocyclic analogues. The [3 + 3]-coupling method also allowed improved and expedient access to an advanced tribenzylated lactam previously used in the racemic syntheses of the hydroxylated alkaloids D-mannonolactam, deoxymannojirimycin, and prosopinone, providing a formal asymmetric synthesis of these alkaloids.