Study on Electron Transfer Reaction on Electrode aimed at Nitrogen Atomcontaining Pharmaceuticals

为了将电化学反应有效地应用于含氮药物的精细有机合成，我们对氨基甲酸酯类化合物与电极之间的电子转移反应进行了详细的研究。研究结果如下：1)电化学氧化与不对称合成：研究了N-甲氧基甲酰化的脯氨酸酯在甲醇中的电化学氧化反应的区域选择性，即α和α‘位氧化的选择性，并利用氧化产物制备了光学活性的α-烷基脯氨酸。2)β-取代基对电子转移反应的影响：为了阐明电子转移反应中的取代基对电子转移反应的影响，研究了β-位含卤素原子或甲氧基的氨基甲酸酯类化合物的电化学氧化。3)在哌啶环的伽马位引入取代基：利用N-甲氧羰基哌啶的电化学氧化产物实现了在哌啶环的伽马位不对称引入烷基。4)在精细有机合成中的应用：1)利用电化学氧化产物非对映选择性地合成3-氨基-2-羟基烷基甲酸；2)伯胺合成具有多种官能团的烯胺；3)伯胺制备光学活性的β-羟基胺。

We have studied in detail on the electron transfer reactions from carbamates to electrode in order to efficiently apply the electochemical reactions to fine organic synthesis which involves nitrogenatom containing pharmaceuticals. The following results were obtained.1) Electorhchemical oxidation of proline ester and asymmetric synthesis : Electrochemical oxidation of N-methoxycarbonylated proline ester in methanol was carried out to see the regioselectivity, that is, selectivity of the oxidation at alpha-and alpha'-positions, and optically active alpha-alkylprolines were prepared by use of the oxidation products.2) beta-Substituent effect on electron transfer reaction : Electrochemical oxidation of carbamates possessing a halogen atom or a methoxycarbonyl group at the beta-position was investigated in order to clarify the substituent effect on the electron transfer reaction, and it was found that such electron-withdrawing substituents did not give much effect on the electron transfer type oxidation. As the results, a-substituted aziridines could be synthesized utilizing the oxidation products.3) Introduction of substituent on gamma-position of piperidine ring : Asymmetric introduction of an alkyl group into the gamma-position of piperidine ring was achieved by use of the electrochemical oxidation products of N-methoxycarbonylpiperidine.4) Application to fine organic synthesis : The following three projects, i) diastereoselective synthesis of 3-amino-2-hydroxyalkanecarboxylic acids using electrochemical oxidation products, ii) synthesis of enamines possessing a variety of functional groups from primary amines, and iii) preparation of optically active beta-hydroxyamines from primary amines, were achieved.