17β-hydroxy-5-aza-4,5-seco-B-homoandrost-3-en-6-one tert-butyldimethylsilyl ether | 142004-81-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 硫杂环戊烷
• 英文名称: 17β-hydroxy-5-aza-4,5-seco-B-homoandrost-3-en-6-one tert-butyldimethylsilyl ether
• CAS: 142004-81-7
• 化学式: C₂₅H₄₅NO₂Si
• 分子量: 419.723
• InChiKey: CWIXYNQPESJGCQ-FDGCDDQTSA-N

物化性质

• 沸点：
  488.8±45.0 °C(predicted)
• 密度：
  0.98±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

反应信息

• 作为反应物：
  描述：

  17β-hydroxy-5-aza-4,5-seco-B-homoandrost-3-en-6-one tert-butyldimethylsilyl ether 在 间氯过氧苯甲酸 作用下， 以 氯仿 为溶剂， 反应 36.0h， 以92%的产率得到3,4-epoxy-17β-hydroxy-5-aza-4,5-seco-B-homoandrostan-6-one tert-butyldimethylsilyl ether
  参考文献：
  名称：

  A novel stereospecific rearrangement of 3-substituted B-homo-5-azasteroids to their A-nor analogs. Preparation, stereochemistry, and conformational studies

  摘要：

  The novel 3-alpha- and 3-beta-hydroxy-B-homo-5-azasteroid lactams 4 and 5 were prepared from testosterone. When the hydroxyl group in these compounds is converted into a leaving group, rearrangement to the corresponding A-nor azasteroids occurs under a variety of conditions, along with competing substitution with inversion of configuration at C-3. The rearrangements proceed with complete stereospecificity and are faster and more efficient in the 3-alpha-series. The observed stereochemistry, as well as the results of molecular modeling, low-temperature NMR, and X-ray crystallographic studies support a mechanism involving neighboring-group participation by the nitrogen atom in the departure of the nucleofuge from C-3 via the formation of aziridinium ion intermediates. Compounds in the 3-alpha-series require prior ring-flipping to the A-boat conformation, while those in the 3-beta-series react through the corresponding A-chairs. The differences in the free energies of the A-boat and A-chair forms are greater in the 3-beta-compounds (1.6-3.4 kcal/mol) than in the corresponding 3-alpha-isomers (0.1-1.3 kcal/mol). The 3-alpha-chloro derivative 19 exists mainly as the A-chair in solution (DELTA-G = 0.3 kcal/mole; DELTA-G* = 12.2 kcal/mol), but crystallizes in the A-boat conformation. Molecular modeling studies of several 3-substituted derivatives and X-ray investigations of 19 and its 3-beta-isomer 20 also reveal separate flip forms of the B-rings associated with the A-chair and A-boat conformations in each case. Relief of steric hindrance between one of the hydrogen atoms at C-19 and the beta-hydrogen at C-7 (this H-H contact is only 1.98 angstrom in the crystal structure of 19) in the A-boat conformations of the 3-alpha-series enhances anchimeric assistance to the departure of the leaving group and facilitates the rearrangements of these compounds relative to their 3-beta-counterparts.

  DOI：

  10.1021/jo00041a013
• 作为产物：
  描述：

  (3S,3aS,5aS,6R,9aR,9bS)-6-But-3-enyl-3-(tert-butyl-dimethyl-silanyloxy)-3a,6-dimethyl-dodecahydro-cyclopenta[a]naphthalen-7-one oxime 在 吡啶 、 4-二甲氨基吡啶 、 对甲苯磺酰氯 作用下， 反应 4.0h， 以53%的产率得到17β-hydroxy-5-aza-4,5-seco-B-homoandrost-3-en-6-one tert-butyldimethylsilyl ether
  参考文献：
  名称：

  A novel stereospecific rearrangement of 3-substituted B-homo-5-azasteroids to their A-nor analogs. Preparation, stereochemistry, and conformational studies

  摘要：

  The novel 3-alpha- and 3-beta-hydroxy-B-homo-5-azasteroid lactams 4 and 5 were prepared from testosterone. When the hydroxyl group in these compounds is converted into a leaving group, rearrangement to the corresponding A-nor azasteroids occurs under a variety of conditions, along with competing substitution with inversion of configuration at C-3. The rearrangements proceed with complete stereospecificity and are faster and more efficient in the 3-alpha-series. The observed stereochemistry, as well as the results of molecular modeling, low-temperature NMR, and X-ray crystallographic studies support a mechanism involving neighboring-group participation by the nitrogen atom in the departure of the nucleofuge from C-3 via the formation of aziridinium ion intermediates. Compounds in the 3-alpha-series require prior ring-flipping to the A-boat conformation, while those in the 3-beta-series react through the corresponding A-chairs. The differences in the free energies of the A-boat and A-chair forms are greater in the 3-beta-compounds (1.6-3.4 kcal/mol) than in the corresponding 3-alpha-isomers (0.1-1.3 kcal/mol). The 3-alpha-chloro derivative 19 exists mainly as the A-chair in solution (DELTA-G = 0.3 kcal/mole; DELTA-G* = 12.2 kcal/mol), but crystallizes in the A-boat conformation. Molecular modeling studies of several 3-substituted derivatives and X-ray investigations of 19 and its 3-beta-isomer 20 also reveal separate flip forms of the B-rings associated with the A-chair and A-boat conformations in each case. Relief of steric hindrance between one of the hydrogen atoms at C-19 and the beta-hydrogen at C-7 (this H-H contact is only 1.98 angstrom in the crystal structure of 19) in the A-boat conformations of the 3-alpha-series enhances anchimeric assistance to the departure of the leaving group and facilitates the rearrangements of these compounds relative to their 3-beta-counterparts.

  DOI：

  10.1021/jo00041a013