Generation of Chiral Acvliminium Ions

开发合成光学活性氮杂环，特别是α-取代哌啶和吡咯烷的有效方法是很重要的，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-酰化的环状a-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a-取代吡咯烷和吡咯烷的过程中，我们已经找到了手性记忆的条件，在这种条件下，即使亚胺离子可能作为转化的中间产物，起始的a-氨基酸的手性也被保留在产物中。然而，手性记忆的效率还不高。因此，我们仔细研究了在手性酰亚胺离子产生过程中影响手性记忆的各种因素。(1)结构效应对手性记忆的影响：在N-保护基和α-氨基酸结构都较大的情况下，可以观察到较高的手性记忆(83~91%ee)，在非大体积的α-氨基酸具有较大的N-保护基的情况下，可以观察到中等的ee(例如46%ee)的手性记忆，在非大的N-保护基的α-氨基酸的情况下不能观察到任何手性记忆。(2)手性Lewis酸催化的N-苯甲酰亚胺离子与活性亚甲基化合物之间的C-C成键反应：铜(II)与光学活性双恶唑啉的反应得到了动态手性铜离子催化剂，该催化剂能够促进N-酰基哌啶离子与丙二酸二甲酯之间的不对称C-C成键反应，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.