(6RS)-6-Methoxy-N-amino>-2-pyrrolidinone

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: (6RS)-6-Methoxy-N-amino>-2-pyrrolidinone
• 英文别名: 6-methoxy-1-[methyl-[(1S)-1-phenylethyl]amino]piperidin-2-one
• 化学式: C₁₅H₂₂N₂O₂
• 分子量: 262.352
• InChiKey: BGMQSLKVGUFOGR-SFVWDYPZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  32.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (6RS)-6-Methoxy-N-amino>-2-pyrrolidinone 、 烯丙基三甲基硅烷 在 三氟化硼乙醚 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 生成 (6S)-N-amino>-6-allyl-2-piperidinone 、 (6R)-N-amino>-6-allyl-2-piperidinone
  参考文献：
  名称：

  Asymmetric Total Synthesis of (R)-(-)-Cryptopleurine and (R)-(-)-Julandine via Highly Enantioselective Amidoalkylations with N-Acylhydrazonium Salts

  摘要：

  The first enantioselective total syntheses of the phenanthroquinolizidine alkaloid(-)-cryptopleurine (1) and its seco base (-)-julandine [(R)-3] are described. The synthesis of(R)-3 allowed the 9aS configuration to be assigned to natural dextrorotatory julandine as shown by structure (S)-3. Both synthetic approaches are based on the high degree of 1,3-asymmetric induction achieved using an N-acylhydrazonium salt, which belongs to a new structural class of activated azomethines. Upon exposure of methoxy lactam 9, with a chiral 2-substituted pyrrolidine auxiliary, to BF3 . Et(2)O and a silyl enol ether the in situ generated N-acylhydrazonium intermediate 10 underwent asymmetric nucleophilic addition to give the (GR)-keto lactams 13 and 14 with complete diastereoselectivity. On the other hand, nucleophilic addition to the N-acylhydrazonium ion 25, with an acyclic chiral auxiliary, showed poor diastereoselectivity. From these results, the high degree of diastereoselection observed for the N-acylhydrazonium ion 10 can be rationalized in terms of the pyramidal stability of the trivalent nitrogen in the chiral pyrrolidine auxiliary. Removal of the chiral auxiliary from 13 and 14 was achieved by reductive N-N bond cleavage using BH3 . THF, affording (BS)-piperidine derivatives 15 and 31, respectively, which were transformed into quinolizidinones 30 and 35, respectively, via intramolecular aldol condensation. Reduction of 30 with alane provided (-)julandine [(R)-3]. In addition, 35 was converted to (-)-cryptopleurine (1) in two steps, by radical cyclization with Bu(3)SnH and AIBN, followed by LiAlH4 reduction.

  DOI：

  10.1021/jo00124a025
• 作为产物：
  描述：

  (S)-(-)-N-甲基-1-苯基乙胺 在 lithium aluminium tetrahydride 、 亚硝酸特丁酯 、 sodium acetate 、 4-甲基苯磺酸吡啶 、 乙酸酐 、 三乙基硼氢化锂 作用下， 以 四氢呋喃 为溶剂， 反应 11.25h， 生成 (6RS)-6-Methoxy-N-amino>-2-pyrrolidinone
  参考文献：
  名称：

  Asymmetric Total Synthesis of (R)-(-)-Cryptopleurine and (R)-(-)-Julandine via Highly Enantioselective Amidoalkylations with N-Acylhydrazonium Salts

  摘要：

  The first enantioselective total syntheses of the phenanthroquinolizidine alkaloid(-)-cryptopleurine (1) and its seco base (-)-julandine [(R)-3] are described. The synthesis of(R)-3 allowed the 9aS configuration to be assigned to natural dextrorotatory julandine as shown by structure (S)-3. Both synthetic approaches are based on the high degree of 1,3-asymmetric induction achieved using an N-acylhydrazonium salt, which belongs to a new structural class of activated azomethines. Upon exposure of methoxy lactam 9, with a chiral 2-substituted pyrrolidine auxiliary, to BF3 . Et(2)O and a silyl enol ether the in situ generated N-acylhydrazonium intermediate 10 underwent asymmetric nucleophilic addition to give the (GR)-keto lactams 13 and 14 with complete diastereoselectivity. On the other hand, nucleophilic addition to the N-acylhydrazonium ion 25, with an acyclic chiral auxiliary, showed poor diastereoselectivity. From these results, the high degree of diastereoselection observed for the N-acylhydrazonium ion 10 can be rationalized in terms of the pyramidal stability of the trivalent nitrogen in the chiral pyrrolidine auxiliary. Removal of the chiral auxiliary from 13 and 14 was achieved by reductive N-N bond cleavage using BH3 . THF, affording (BS)-piperidine derivatives 15 and 31, respectively, which were transformed into quinolizidinones 30 and 35, respectively, via intramolecular aldol condensation. Reduction of 30 with alane provided (-)julandine [(R)-3]. In addition, 35 was converted to (-)-cryptopleurine (1) in two steps, by radical cyclization with Bu(3)SnH and AIBN, followed by LiAlH4 reduction.

  DOI：

  10.1021/jo00124a025

文献信息

• Asymmetric Total Synthesis of (R)-(-)-Cryptopleurine and (R)-(-)-Julandine via Highly Enantioselective Amidoalkylations with N-Acylhydrazonium Salts
  作者：Hideaki Suzuki、Sakae Aoyagi、Chihiro Kibayashi

  DOI：10.1021/jo00124a025

  日期：1995.9

  The first enantioselective total syntheses of the phenanthroquinolizidine alkaloid(-)-cryptopleurine (1) and its seco base (-)-julandine [(R)-3] are described. The synthesis of(R)-3 allowed the 9aS configuration to be assigned to natural dextrorotatory julandine as shown by structure (S)-3. Both synthetic approaches are based on the high degree of 1,3-asymmetric induction achieved using an N-acylhydrazonium salt, which belongs to a new structural class of activated azomethines. Upon exposure of methoxy lactam 9, with a chiral 2-substituted pyrrolidine auxiliary, to BF3 . Et(2)O and a silyl enol ether the in situ generated N-acylhydrazonium intermediate 10 underwent asymmetric nucleophilic addition to give the (GR)-keto lactams 13 and 14 with complete diastereoselectivity. On the other hand, nucleophilic addition to the N-acylhydrazonium ion 25, with an acyclic chiral auxiliary, showed poor diastereoselectivity. From these results, the high degree of diastereoselection observed for the N-acylhydrazonium ion 10 can be rationalized in terms of the pyramidal stability of the trivalent nitrogen in the chiral pyrrolidine auxiliary. Removal of the chiral auxiliary from 13 and 14 was achieved by reductive N-N bond cleavage using BH3 . THF, affording (BS)-piperidine derivatives 15 and 31, respectively, which were transformed into quinolizidinones 30 and 35, respectively, via intramolecular aldol condensation. Reduction of 30 with alane provided (-)julandine [(R)-3]. In addition, 35 was converted to (-)-cryptopleurine (1) in two steps, by radical cyclization with Bu(3)SnH and AIBN, followed by LiAlH4 reduction.