Generation of Chiral Acvliminium Ions

开发合成光学活性氮杂环（特别是α-取代的哌啶和吡咯烷）的有效方法很重要，因为这些化合物经常用作手性药物的合成前体。在我们对从N-酰化环状α-氨基酸电化学生成酰亚胺离子，然后用亲核试剂捕获亚胺离子中间体以得到α-取代的哌啶和吡咯烷的继续研究中，我们已经发现了手性记忆的条件，其中起始α-氨基酸的手性保留在产物中，即使亚胺离子可能作为中间体参与转化。然而，手性的存储效率还不高。因此，我们仔细研究了各种因素对手性记忆的影响，在手性酰基离子的产生。今年取得的成果概述如下。（1）对手性记忆的结构效应：在N-protecting.group和α-氨基酸的结构都是庞大的情况下，可以观察到高的手性记忆（83 - 91%ee），在具有庞大N-保护基的非庞大α-氨基酸的情况下，可以获得中等的手性记忆%ee（例如，46%ee），在α-氨基酸的非庞大N-保护基的情况下，不能观察到任何手性记忆。（2）手性刘易斯酸催化的N-苯甲酰亚胺离子与活性亚甲基化合物的C-C键形成反应：Cu（II）与光学活性的双恶唑啉反应得到了动态手性Cu离子催化剂，该催化剂能够促进N-酰基哌啶离子与丙二酸二甲酯的不对称C-C键形成反应，具有中等的对映选择性。

Exploitation, of efficient methods for the synthesis of optically active nitrogen-heterocycles, particularly a-substituted piperidines and pyrrolidines, is important because those compounds are often used as synthetic precursors of chiral drugs. In our continuing study on an electrochemical generation of acyliminium ions from N-acylated cyclic a-amino acids followed by the trapping of the iminium ion intermediates with nucleophiles to afford a-substituted peperidmes and pyrrolidines, we have already found conditions for memory of chirality in which the chirality of starting a-amino acids is preserved in the products even though iminium ions might be involved as the intermediates in the transformation. However, the efficiency of memory of chirality has not yet been high. So, we scrutinized a variety of factors to affect on the memory of chirality in the generation of chiral acyliminium ions. The results obtained this year are summarized as follows.(1)Structural effect on the memory of chirality : High memory of chirality (83〜91%ee) can be observed in a case that both N-protecting.group and the structure of α-amino acids are bulky, Moderate %ee (for example, 46%ee) of memory of chirality is available in a case of non-bulky α-amino acids having bulky N-protecting group, Any memory of chirality can not be observed in a case of non-bulky N-protecting group of α-amino acids. (2)Chiral Lewis acid-catalyzed C-C bond forming reaction between N-benzoylated iminium ions and active methylene compounds : The reaction of Cu(II) with optically active bis-oxazoline gave dynamic chiral Cu ions catalyst which had an ability to promote,an asymmetric C-C bond forming reaction between N-acylpiperidinium ions and dimethyl malonate with a moderate enantioselectivity.