Studies on Practical Synthetic Methods of Pyrrolidine and Piperidine Alkaloids Utilizing Electrochemical Reactions

本研究的主要结果如下：i）阳极法制备的N-甲氧羰基-N-甲氧甲基氨基丙二酸二甲酯与芳基烯烃经刘易斯酸处理得到β-芳基吡咯烷衍生物，其中一种产物成功地转化为介晶。ii）通过对吡咯烷环上的α ′-取代基或氮原子上的官能团进行修饰，在α-取代吡咯烷的α ′-位引入烷基，具有高的非对映选择性。iii）通过哌啶衍生物的阳极β-乙酰氧基化反应合成了光学活性的N-甲基假盐酸麻黄碱。iv）以N-烷氧基羰基哌啶为原料，通过阳极氧化的关键步骤制备了β，γ-不饱和的N-烷氧基羰基哌啶，实现了哌啶环上的区域选择性烷基化反应，并将该反应应用于meroquinene等的合成。v）通过α，α ' -二价阳离子或α，γ-二价阳离子当量与二价阴离子当量。vi）找到了有效电还原脱氰的条件，并将其应用于α-取代的吡咯烷和哌啶衍生物的合成。vii）开发了用于生成α-氨基碳负离子的新途径。

The main results obtained in the research were as follow ; i) Lewis acid treatment of anodically prepared dimethyl N-methoxycarbonyl-N-methoxymethylaminomalonate with aryl olefins afforded beta -aryl- pyrrolidine derivatives, and one of the products was successfully converted to mesembrine. ii) An alkyl group was introduced to the alpha' position of alpha-substituted pyrrolidines with high diastereoselectivities by modifying the alpha'-substituents or the functional groups located at the nitrogen atom of pyrrolidine ring. iii) Optically active N-methylpsuedconhidrine was synthesized by anodic beta -acetoxylation of piperidine derivatives. iv) Regioselective alkylation on a piperidine ring was achieved by using beta, gamma-unsatureated N-alkoxycarbonylpiperidines which were prepared from N-alkoxycarbonylpiperidinesby utilizing anodic oxidation in a key step, and this reaction was applied to the synthesis of meroquinene, etc. v) Nitrogen-containing bicyclic compounds were synthesized by the reaction of alpha, alpha' -di- cation or alpha, gamma- dication equivalents with dianion equivalents. vi) Conditions for the efficient electroreductive decyanation were found and they were applied to the synthesis of alpha-substituted pyrrolidine and piperidine derivatives. vii) A new route for the generation of alpha -amino carbanions was exploited.