论文总字数：20485字

摘 要

钯催化不对称烯丙基取代反应是过渡金属催化反应中利用不对称催化反应构建碳碳键及碳杂键的最重要反应之一。Tsuji-Trost烯丙基取代反应提供了一种高效的方法来构建sp³杂化碳之间的C-C键。利用该反应不仅能在外消旋的烯丙位上形成手性中心，而且也能在潜手性亲核试剂上形成手性中心。在Tsuji-Trost反应中亲核试剂对钯π-烯丙基中间体的进攻模式是不同的，“软”亲核体直接攻击π-烯丙基部分，而“硬”亲核体在与烯丙基形成键之前首先攻击金属中心（通过金属转移）。通过筛选手性配体和优化反应条件可得到高对映选择性和高非对映选择性的烯丙基取代产物，所合成的高烯丙基胺结构单元是一些天然产物及药物分子的重要合成片段或中间体。我们合成出氮杂芳甲基胺类底物，之后用2-环己烯酮通过Luche还原反应得到烯丙基取代物2-环己烯-1-醇并引入Boc基团，两者反应得到所要研究的氮杂芳甲基胺类化合物烯丙基取代的含有两个手性中心的产物，进行HPLC分析得到ee值和dr值。筛选40多种手性配体后，我发现Taniaphos这种手性催化剂对两组对映体都可得到66%的ee值，此外Segphos这种骨架的手性配体可得到较高的ee值，尝试了在Segphos的苯环上引入叔丁基和甲基等基团加大空间位阻效应后得到63% ee，并且也能得到较好的收率。通过比较分析得出手性配体BINAP比Segphos更具有提升ee值的潜力。

关键词：钯催化 烯丙基取代 亲核试剂 手性配体 ee值

Study on Asymmetric Allyl Substituted Reaction of Palladium-catalyzed Aza-Aminomethylamine Compounds

ABSTRACT

Palladium catalyzed asymmetric allylic substitution is one of the most important reactions in the transition metal catalyzed reaction using asymmetric catalytic reactions to construct carbon and carbon bonds. The Tsuji-Trost allylic substitution reaction provides an efficient way to construct the C-C bond between sp³ hybrid carbon. The reaction can not only form a chiral center on the racemic allylic position, but also form a chiral center on a latent nucleophile. In the Tsuji-Trost reaction, the nucleophile is different from the palladium π-allyl intermediate attack mode, and the "soft" nucleophile directly attacks the π-allylic moiety, while the "hard" nucleophile is Before the propyl formation bond first attacks the metal center (via metal transfer). The high allylamine structural units synthesized by screening chiral ligands and optimizing the reaction conditions are highly enantioselective and highly diastereomeric allyl substituents. The synthetic allylamine structural units are important for some natural products and drug molecules Synthetic fragments or intermediates. We synthesized the aza-arylmethylamine-based substrate, followed by 2-cyclohexenone by Luche reduction reaction to obtain allyl-substituted 2-cyclohexen-1-ol and the introduction of Boc groups, both reaction The allylmethylamine compounds to be studied are allyl-substituted products containing two chiral centers, and the ee and dr values are obtained by HPLC analysis. After screening more than 40 chiral ligands, I found that Taniaphos, a chiral catalyst, had a 66% ee value for both sets of enantiomers, and that the chiral ligand of Segphos had a higher ee value, Try to introduce a tert-butyl group and a methyl group on the benzene ring of Segphos to increase the steric hindrance effect to obtain 63% ee, and also get a better yield. The comparative analysis shows that the chiral ligand BINAP has the potential to enhance the ee value more than Segphos.

Key words: Palladium-catalyzed; Allyl substitution; Nucleophile; Chiral ligand; Enantiomeric excess

目 录

摘要 Ⅰ

ABSTRACT Ⅱ

第一章 绪论 1

1.1 背景 1

1.1.1 手性合成发展历程及其常用方法 1

1.1.2 不对称烯丙基取代反应的发展 2

1.1.3 钯催化的不对称烯丙基取代反应的研究历程 2

1.1.4 用二芳基甲烷的钯催化烯丙基取代的开发和优化 3

1.2 Tsuji-Trost反应机理 6

1.3 手性配体在钯催化不对称反应中的应用 7

第二章 实验部分 9

2.1 实验药品与仪器 9

2.2 实验总路线 10

2.3 实验内容 11

2.3.1 A-1的制备 11

2.3.2 B-1的制备 11

2.3.3 B-2的制备 11

2.3.4 AB的制备 12

2.3.5 手性配体的筛选 12

第三章 结果与讨论 14

3.1 实验结果及表征 14

3.1.1 物质A-1的表征 14

3.1.2 物质B-2的表征 14

3.1.3 物质AB的表征 15

3.2 手性配体ee值的讨论 16

第四章 结论与展望 18

4.1 结论 18

4.2 展望 18

参考文献 20

致 谢 23

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