Kawabata Takeo, Matsuda Seiji, Kawakami Shimpei, Monguchi Daiki, Moriyama Katsuhiko
Institute for Chemical Research, Kyoto University, Uji, Kyoto 611-0011, Japan.
J Am Chem Soc. 2006 Dec 6;128(48):15394-5. doi: 10.1021/ja0670761.
An enantiodivergent asymmetric cyclization of N-Boc-N-omega-bromoalkyl-alpha-amino acid derivatives has been developed. With potassium amide bases in DMF, cyclization proceeds with retention of configuration, while inversion of configuration was observed with lithium amide bases in THF. Chirality of the parent amino acids was preserved during enolate formation and cyclization to give aza-cyclic amino acids in up to 98% ee with retention of configuration or inversion of configuration, depending on the reaction conditions. Thus, both enantiomers of cyclic amino acids with a tetrasubstituted stereocenter were prepared in high enantiomeric purity from readily available l-alpha-amino acids. This protocol is also applicable to a spirocyclization and an intramolecular conjugate addition of alpha-amino acid derivatives, giving either of the enantiomers of a diazaspiro compound and a tetrahydroisoquinoline derivative, respectively, in up to 99% ee.
已开发出一种N - Boc - N - ω - 溴烷基 - α - 氨基酸衍生物的对映发散性不对称环化反应。在DMF中使用氨基钾碱时，环化反应以构型保持进行，而在THF中使用氨基锂碱时，则观察到构型翻转。在烯醇盐形成和环化过程中，母体氨基酸的手性得以保留，根据反应条件，可得到高达98% ee的构型保持或构型翻转的氮杂环氨基酸。因此，由易得的L - α - 氨基酸以高对映体纯度制备了具有四取代立体中心的环状氨基酸的两种对映体。该方法也适用于α - 氨基酸衍生物的螺环化和分子内共轭加成反应，分别以高达99% ee的产率得到二氮杂螺环化合物和四氢异喹啉衍生物的任一对映体。
