Generation of Chiral Acvliminium Ions

开发合成具有光学活性的氮杂环的有效方法，特别是a-取代的哌啶和吡咯烷，是很重要的，因为这些化合物经常被用作手性药物的合成前体。在我们继续研究n -酰化环a-氨基酸的电化学生成酰基离子，然后用亲核试剂捕获亚胺离子中间体以提供-取代的邻苯二甲酸和吡啶时，我们已经发现了手性记忆的条件，在这种条件下，即使亚胺离子可能作为中间体参与转化，起始的a-氨基酸的手性仍保留在产物中。然而，手性记忆的效率还不高。因此，我们考察了影响手性记忆的各种因素在手性铝离子生成过程中的作用。今年取得的成果总结如下：(1)结构对手性记忆的影响：在同时保护n的情况下，可以观察到高的手性记忆（83 ~ 91%ee）。α-氨基酸具有较大n保护基团的非较大α-氨基酸具有中等%ee（例如46%ee）的手性记忆，而α-氨基酸具有较大n保护基团的非较大α-氨基酸则没有手性记忆。(2)手性Lewis酸催化n -苯甲酰化亚胺离子与活性亚甲基化合物的C-C成键反应：Cu（II）与旋光性双恶唑啉反应生成动态手性Cu离子催化剂，具有促进n -酰基哌啶离子与丙二酸二甲酯不对称C-C成键反应的能力，对映选择性中等。

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.