(2S)-tert-Butyl 6,6-dimethyl-5-oxo-2-amino>heptanone | 152381-75-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: (2S)-tert-Butyl 6,6-dimethyl-5-oxo-2-amino>heptanone
• 英文别名: tert-butyl (2S)-6,6-dimethyl-5-oxo-2-[(9-phenylfluoren-9-yl)amino]heptanoate
• CAS: 152381-75-4
• 化学式: C₃₂H₃₇NO₃
• 分子量: 483.651
• InChiKey: GMHDNFRBSUWDDW-MHZLTWQESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.5
• 重原子数：
  36
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (2S)-tert-Butyl 6,6-dimethyl-5-oxo-2-amino>heptanone 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 、 溶剂黄146 为溶剂， 反应 24.0h， 生成 (2S,5R)-5-tert-butylproline tert-butyl ester
  参考文献：
  名称：

  5-tert-Butylproline

  摘要：

  Steric effects on the isomer equilibrium of amides N-terminal to proline can be explored with 5-alkylprolines having bulky 5-position substituents. Enantiopure 5-tert-butylprolines were thus synthesized from glutamic acid via an acylation/diastereoselective reductive amination sequence. Double deprotonation of gamma-methyl N-(PhF)glutamate (2) with LiN(SiMe(3))(2) and C-acylation with pivaloyl chloride provided beta-keto ester 3, which upon gamma-ester hydrolysis and decarboxylation gave delta-oxo-alpha-[N-(PhF)amino]heptanoic acid (4). Syntheses of (2S,5R)- and (2R, 5S)-N-(BOC)-5-tert-butylprolines ((2S,5R)-1 and (2R,5S)-1) were accomplished by catalytic hydrogenation of their respective (2S)- and (2R)-methyl delta-ore-alpha-[N-(PhF)amino]heptanoates ((2S)-5a and (2R)-5a) in methanol with di-tert-butyl dicarbonate followed by chromatography and ester hydrolysis with potassium trimethylsilanolate. The 5-tert-butylproline cis-diastereomers were proven to be of >99% enantiomeric purity after their conversion to diastereomeric alpha-methylbenzylamides 10. Good diastereoselectivity in favor of the trans-diastereomer was observed when (2S,5S)-5-tert-butylproline was synthesized from (2S)-delta-oxo-alpha-[N-(PkF)amino]heptanoate ((2S)-4) by solvolysis of the PhF group in trifluoroacetic acid and subsequent reduction of 5-tert-butyl-Delta 5-dehydroproline (11) with tetramethylammonium triacetoxyborohydride; however, imino acid 11 was shown to be configurationally labile and racemized under acidic conditions. 5-tert-Butyl-Delta 5-dehydroproline N'-methylamide 15 was configurationally stable in acid, yet preliminary attempts to reduce 15 favored cis-diastereomer 16. Alternatively, enantiopure trans-diastereomer, (2R,5R)-methyl N-(BOC)-5-tert-butylprolinate (9) was prepared by epimerization of(2S,5R)-9. In summary, this synthetic methodology now provides access to all four enantiopure 5-tert-butylproline isomers from inexpensive L- and D-glutamate as chiral educts.

  DOI：

  10.1021/jo9618738
• 作为产物：
  描述：

  (S)-2-(2,2-Dimethyl-propionyl)-4-(9-phenyl-9H-fluoren-9-ylamino)-pentanedioic acid 5-tert-butyl ester 1-methyl ester 在 lithium hydroxide 作用下， 以 四氢呋喃 为溶剂， 以63%的产率得到(2S)-tert-Butyl 6,6-dimethyl-5-oxo-2-amino>heptanone
  参考文献：
  名称：

  Synthesis of enantiopure .delta.-oxo .alpha.-amino esters and prolines via acylation of N-(phenylfluorenyl)glutamate enolates

  摘要：

  Acylation of the lithium gamma-enolate of alpha-tert-butyl gamma-methyl N-[9-(9-phenylfluorenyl)]glutamate (1) with different acid chlorides provides beta-keto esters 2. Selective gamma-ester hydrolysis and decarboxylation furnishes good yields of enantiomerically pure delta-oxo alpha-amino esters 3 possessing primary, secondary, and tertiary alkyl, as well as aromatic delta-substituents. Acylation of 1 with methyl oxalyl chloride is followed by condensation of the ketone and amine of 2 to give N-(PhF1)-DELTA2-pyrroline triester 4 in 75% yield. Palladium-catalyzed hydrogenation of (2S)-tert-butyl 4-oxo-2-(N-(PhFl)amino)nonanoate (3f) yields >99.5% enantiopure (2S,5S)-5-butylproline tert-butyl ester (5), an intermediate in the synthesis of 2,5-dialkylpyrrolidine alkaloids.

  DOI：

  10.1021/jo00075a046