含二氟碘烷烃与苯硼酸的偶联反应研究

摘要：由于二氟甲基能够显著影响生物分子活性，含二氟甲基化合物在医药、农药和材料领域应用十分广泛。近年来，对于其合成的研究引起了人们很大的兴趣。其中二氟甲基烯烃类化合物，由于氟原子强的吸电子能力，双键的亲电能力增强，容易受亲核试剂的进攻被认为是酶抑制剂。本实验室已经合成了二氟碘代酮为新的含氟砌块，本文拟研究二氟碘代酮、端位炔烃类和苯硼酸类的三组分反应，一锅法合成一系列二氟亚甲基烯烃类化合物，将含二氟亚甲基砌块引入到化合物中，为结构多样的含氟化合物的合成提供了新的高效途径，为开发更高活性的新药提供方法研究基础。通过对反应条件的优化，最终选用了PdCl2(pph3)2为催化剂、K2CO3为碱、端位炔类、苯硼酸类及二氟碘代酮的投料比（1：1.3：2）以及以DCM/H2O（1：1）为溶剂作为反应的条件，同时进行底物的扩展，共合成了5个目标化合物。所有的化合物均经过核磁谱图进行结构表征。43152

毕业论文关键词：二氟碘代烯酮；苯硼酸；三组分反应；合成

The coupling reaction of iododifluoromethyl ketones and phenylboronic acids

Abstract: Since difluoromethyl can significantly affect the biological activity of the molecule containing difluoromethyl compound，which were widely used in pharmaceuticals, pesticides and materials fields. In recent years, the synthesis of difluoromethyl compounds has aroused great interest. Wherein, difluoromethyl olefin compounds, with strong electron withdrawing ability and high electrophilic ability, are vulnerable to the attack of the nucleophile and are used as inhibitors of variuos esters. The thesis reported a three-component reaction of iododifluoromethyl ketones, alkynes and phenylboronic acids to yield a series of difluoromethylenechrysin olefin compound, which provide a novel synthetic method for the preparation of structurally perse fluorine-containing compounds for the development of new drugs studied more active. The reaction conditions were optimized. Finally, the three-component reaction was performed catalyzed by Pd in the presence of K by using CH3CN/H2O () as solvent. The generality of this reaction was investigated. Five target compounds were synthesized under optimized conditions and their structures were verified by NMR spectra.

Key Words: iododifluoromethyl ketones, phenylboronic acids, three-omponent reaction, synthesis

1 绪论 1

1.1 课题背景与意义 ... 1

1.2 含二氟亚甲基化合物 2

1.3 全氟碘烷 3

1.3.1 简介 . 3

1.3.2 从全氟碘烷烃出发进行的自由基加成反应 .. 3

1.4 含氟碘烷烃参与的自由基加成反应 . 4

1.5 多组分反应 . 7

1.5.1 多组分简介 .... 7

1.5.2 多组分反应的发展 .. 7

1.6 含氟碘烷烃参与的三组分反应 8

1.7 本课题研究内容与基本路线的确定 .. 9

1.7.1 研究内容 .... 9

1.7.2 基本路线的确定 .. 9

2 实验部分 . 10

2.1 主要的实验试剂及仪器 10

2.1.1 实验试剂 .. 10

2.1.2 实验仪器 .. 11

2.2 实验步骤 .... 11

2.2.1 对甲基苯乙炔、苯硼酸及二氟碘代苯乙酮的三组分反应 ... 11

2.2.2 对氯苯乙炔、苯硼酸及二氟碘代苯乙酮的三组分反应 . 13

2.2.3 对甲基苯乙炔、对甲基苯硼酸及二氟碘代苯乙酮的三组分反应 14

2.2.4 对氯苯乙炔、苯硼酸及二氟碘代邻氟苯乙酮的三组分反应 ... 15 含二氟碘烷烃与苯硼酸的偶联反应研究:http://www.751com.cn/huaxue/lunwen_43849.html