Kotha–Schollkopf氨基酸合成反应

异氰基乙酸乙酯（EICA）在碱性条件下 (e.g. NaH, t-BuOK, n-BuLi, DBU and Et3N)与C-亲电试剂反应生成二烷基异氰基乙酸乙酯，接着水解得到α-氨基酸衍生物的反应，被称为Kotha–Schollkopf氨基酸合成反应。异氰基乙酸乙酯（EICA）相当于甘氨酸等价物。二卤代烷烃作为底物可以用于合成环状氨基酸衍生物。此反应的一个改进法是利用碳酸钾作为碱，并加入相转移催化剂（四丁基硫酸氢铵），在加热条件下反应进行烷基化，操作更加简便。

反应机理

反应实例

【Tet. Lett., 1998, 39, 4095】

Amino acid (7). To 1 (0.5 mmol) in 20 mL MeCN were added finely powdered K2CO3 (3 mmol), TBAHS (0.1 mmol), and α,α-dibromo-o-xylene 5 (0.5 mmol). The mixture was heated at 70–80℃，until 5 was consumed (TLC). Filtration, washing of the solid with MeCN, filtrate evaporation and chromatography afforded isocyanoester 6 (93%). To the latter (0.16 mmol) in 5 mL abs EtOH at r.t. wasadded a few drops of conc HCl and after a few hours stirring the solution was evaporated. The resultingHCl salt in H2O was washed with ether and NH4OH was added to the aq layer to pH 9–10. Extractionwith EA and workup gave 7 (90%).

【J. Org. Chem., 2000, 65, 1359】

相关文献

1 Scho¨llkopf U， Chem Ber， 1975 108 1580

2 Woodward R， Syn Comm， 1985 15 267

3 Kotha S， Bioorg Med Chem Lett， 1998 8 257

4 Kotha S， Tet Lett， 1998 39 4095

5 Kotha S， J Org Chem， 2000 65 1359

6R Kotha S， Acc Chem Res， 2003 36 342

7 Kobayashi Y， Chem Eur J， 2004 10 617

8 Tanaka M， J Am Chem Soc， 2005 127 11570

9 Cativiela C， Tetrahedron， 2007 63 5056

10R Kotha S， Synlett， 2010 337

编译自：Organic Syntheses Based On Name Reactions, 3RdEd, A. Hassner, Page 269-270.

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