硝酸铈铵直接硝化α-取代环状酮构建硝基取代的季碳立体中心骨架及其合成应用

发布时间：2018-04-29 07:55

本文选题：C(sp~3)-H硝基化反应 + 硝酸铈铵(CAN)　；参考：《兰州大学》2017年硕士论文

【摘要】：在现代有机合成中,脂肪族C-H键的硝基化反应是一类具有挑战性的课题,尤其是羰基化合物α-位的C(sp~3)-H键的硝基化反应。我们以廉价易得的铜盐作为添加剂,以硝酸铈铵为硝基化试剂对羰基化合物α-位的C(sp~3)-H键的硝基化反应进行了研究。建立了一种有效直接地构建具有季碳中心的α-硝基,α-取代的骨架的硝基化方法。在此转化过程中,硝酸铈铵可以作为“一石三鸟”试剂,即:硝基化试剂、单电子氧化剂和Lewis acid。同时,运用已发展的硝基化反应作为关键步骤,高效地实现了被广泛应用于临床的药物分子Ketamine的全合成。本论文共分为两章:第一章:主要介绍了硝酸铈铵作为硝基化试剂在有机合成中的应用。第二章:以硝酸铈铵(CAN)为硝基化试剂、单电子氧化剂及Lewis acid,醋酸铜为添加剂,成功实现了2-取代环酮羰基α-位C(sp~3)-H硝基化反应。该反应表现出了如下优点:底物普适性好、官能团容忍度高以及反应条件相对温和。同时,利用发展的硝基化反应高效地完成了临床使用的药物分子Ketamine的全合成。另外,对反应机理进行了详细地研究,提出了可能的反应机理。
[Abstract]:In modern organic synthesis, the nitro reaction of the aliphatic C-H bonds is a challenging topic, especially the nitro reaction of the C (sp~3) -H bond of the carbonyl compounds. We use the cheap and easy copper salts as additives and the nitro - nitro - nitro - Nitro reagent for the nitro reaction of the C (sp~3) -H bond of the carbonyl compounds. In the process of this transformation, ceric nitrate can be used as a "one stone three bird" reagent, namely, nitrochemical reagent, single electron oxidizer and Lewis acid., using the developed nitration reaction as the key step. This paper is divided into two chapters: Chapter 1: Chapter 1: mainly introduce the application of ammonium ceric nitrate as nitration reagent in organic synthesis. The second chapter: using ceric ammonium nitrate (CAN) as nitro reagent, monoelectric oxidant and Lewis acid, copper acetate as additive. The reaction of 2- substituted CYCLOKETONE carbonyl alpha - C (sp~3) -H nitration is presented. The reaction shows the following advantages: good substrate universality, high functional group tolerance and relatively mild reaction conditions. At the same time, the synthesis of clinical drug molecule Ketamine is effectively completed by the nitrogenation of development. In addition, the mechanism of the reaction is detailed. The possible mechanism of the reaction is proposed.

【学位授予单位】：兰州大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：O621.3

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