(5R,8R,8aS)-(-)-5-cyano-8-methylindolizidine | 134457-78-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚里西啶
• 英文名称: (5R,8R,8aS)-(-)-5-cyano-8-methylindolizidine
• 英文别名: (5R,8R,8aS)-8-methyl-1,2,3,5,6,7,8,8a-octahydroindolizine-5-carbonitrile
• CAS: 134457-78-6
• 化学式: C₁₀H₁₆N₂
• 分子量: 164.25
• InChiKey: SXXCUMGHSJKFMZ-BBBLOLIVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  12
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  27
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (5R,8R,8aS)-(-)-5-cyano-8-methylindolizidine 在 lithium diisopropyl amide 作用下， 反应 1.0h， 生成 (5R,8R,8aS)-(-)-5-cyano-(7-hept-3-enyl)-8-methylindolizidine
  参考文献：
  名称：

  Enantioselective total syntheses of indolizidine alkaloids (-)-205A and (-)-235B

  摘要：

  Enantioselective total syntheses of indolizidine alkaloids (-)-205A and (-)-235B are described. The syntheses proceed via a common late-stage intermediate, alpha-aminonitrile 1. Absolute stereochemical control over the C8 and C8a stereocenters in these materials was achieved by a stereoselective crotylation reaction between chiral acyliminium ion (R)-3b and crotylmagnesium chloride. The selectivity of this reaction, which produced the (future)-8R,8aS configuration was complementary to the result obtained by crotylation of acyliminium ion (S)-3a with trans-crotyltrimethylsilane, which produced predominantly an adduct with the (future)-8S,8aS configuration. This latter crotyl lactam was converted to two additional diastereomers of alkaloid 205A. Comparison of the H-1 and C-13 NMR and optical rotation values of the four synthetic diastereomers of 205A with literature values supported the proposed assignment of the absolute and relative configuration of (-)-205A. The C-13 spectrum of synthetic (5R,8R,8aS)-235B was identical with that of natural 235B and supported the proposed assignment of relative configuration of the alkaloid. The optical rotation differed in sign and magnitude from the published value. Revised values of the optical rotations of (-)-205A and (-)-235B are suggested. This work constitutes the first enantioselective syntheses of 205A and 235B, which were prepared in 15 and 14 steps, respectively, from succinic anhydride, in an average overall yield of 17%.

  DOI：

  10.1021/jo00016a013
• 作为产物：
  描述：

  (2S)-1-benzyloxycarbonyl-2-[(2R)-5,5-dimethoxypent-2-yl]pyrrolidine 在 palladium on activated charcoal 盐酸 、 氢气 作用下， 以 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 11.5h， 生成 (5R,8R,8aS)-(-)-5-cyano-8-methylindolizidine
  参考文献：
  名称：

  通过N-酰氧基亚胺鎓离子向硝酮加成手性烯醇化物不对称合成β-氨基酸

  摘要：

  N-Acyloxyiminium 离子是由硝酮与酰卤反应生成的，是高活性物质，可与多种亲核试剂发生轻松反应，如烯酮甲硅烷基缩醛、钛 (IV) 和硼烯醇化物、氢化和烯丙基锡 (IV) ) 试剂和炔基钛 (IV) 试剂，得到 α-取代的胺衍生物。光学活性 β-氨基酸可以通过 N-酰氧基亚胺鎓离子与带有手性助剂的硼和钛 (IV) 烯醇反应制备。通过硼和钛 (IV) 烯醇化物的反应观察到非对映选择性的逆转。例如，使用这些反应，可以高度非对映选择性地制备 α-甲基-β-苯丙氨酸的所有四种立体异构体。环状 N-酰氧基亚胺离子可用于吡咯烷和哌啶生物碱的不对称合成；

  DOI：

  10.1246/bcsj.73.2423

文献信息

• Asymmetric Synthesis of<b><i>β</i></b>-Amino Acids by Addition of Chiral Enolates to Nitrones via<b><i>N</i></b>-Acyloxyiminium Ions
  作者：Toru Kawakami、Hiroaki Ohtake、Hiroaki Arakawa、Takahiro Okachi、Yasushi Imada、Shun-Ichi Murahashi

  DOI：10.1246/bcsj.73.2423

  日期：2000.11

  both boron and titanium(IV) enolates bearing chiral auxiliaries. Reversal of diastereoselectivity was observed by the reactions of the boron and titanium(IV) enolates. Using these reactions, all of the four stereoisomers of α-methyl-β-phenylalanines, for example, can be prepared highly diastereoselectively. Cyclic N-acyloxyiminium ions are useful for the asymmetric synthesis of pyrrolidine and piperidine

  N-Acyloxyiminium 离子是由硝酮与酰卤反应生成的，是高活性物质，可与多种亲核试剂发生轻松反应，如烯酮甲硅烷基缩醛、钛 (IV) 和硼烯醇化物、氢化和烯丙基锡 (IV) ) 试剂和炔基钛 (IV) 试剂，得到 α-取代的胺衍生物。光学活性 β-氨基酸可以通过 N-酰氧基亚胺鎓离子与带有手性助剂的硼和钛 (IV) 烯醇反应制备。通过硼和钛 (IV) 烯醇化物的反应观察到非对映选择性的逆转。例如，使用这些反应，可以高度非对映选择性地制备 α-甲基-β-苯丙氨酸的所有四种立体异构体。环状 N-酰氧基亚胺离子可用于吡咯烷和哌啶生物碱的不对称合成；
• Enantioselective total syntheses of indolizidine alkaloids (-)-205A and (-)-235B
  作者：Richard P. Polniaszek、Stephen E. Belmont

  DOI：10.1021/jo00016a013

  日期：1991.8

  Enantioselective total syntheses of indolizidine alkaloids (-)-205A and (-)-235B are described. The syntheses proceed via a common late-stage intermediate, alpha-aminonitrile 1. Absolute stereochemical control over the C8 and C8a stereocenters in these materials was achieved by a stereoselective crotylation reaction between chiral acyliminium ion (R)-3b and crotylmagnesium chloride. The selectivity of this reaction, which produced the (future)-8R,8aS configuration was complementary to the result obtained by crotylation of acyliminium ion (S)-3a with trans-crotyltrimethylsilane, which produced predominantly an adduct with the (future)-8S,8aS configuration. This latter crotyl lactam was converted to two additional diastereomers of alkaloid 205A. Comparison of the H-1 and C-13 NMR and optical rotation values of the four synthetic diastereomers of 205A with literature values supported the proposed assignment of the absolute and relative configuration of (-)-205A. The C-13 spectrum of synthetic (5R,8R,8aS)-235B was identical with that of natural 235B and supported the proposed assignment of relative configuration of the alkaloid. The optical rotation differed in sign and magnitude from the published value. Revised values of the optical rotations of (-)-205A and (-)-235B are suggested. This work constitutes the first enantioselective syntheses of 205A and 235B, which were prepared in 15 and 14 steps, respectively, from succinic anhydride, in an average overall yield of 17%.