基于含氟稀土Lewis酸催化的氟代芳基碘盐亲电芳基化反应方法学及其应用研究

Aryliodonium salts have been widely used in organic synthesis due to their unique structure features and reactive properties. However, the synthesis and application of fluorinated aryliodonium salts in organic synthesis were scarce. . We plan to synthesize a wide range of fluorinated aryliodonium salts. By use of these salts, this research program aims to develop an electrophilic arylation reaction with nucleophilic substrates such as carbonyl compounds which activated by rare earth catalysts developed by our group. Modify and design novel fluorinated rare earth catalysts based on the reactivity of the reaction for α-arylation were also proposed. This project will focus on: 1) the synthetic methodology of fluorinated aryliodonium salts; 2) "fluorophilic effect" between fluorinated anion of catalyst and fluorinated aryliodonium salts to clarify the mechanism; 3) the enantioselective variant of catalytic fluorinated α-arylation. Apart from the above aspects, further application of this methodology to synthesize some fluorinated drugs, such as diabetic-treatment agents Januvia, will be explored. This methodology is expected to provide an effective way for the synthesis of a variety of fluorine-containing aromatic compounds; it is hoped to open up a new way on the development of the fluorine-containing new drugs.

芳基碘盐由于其独特的结构特点和反应性质被广泛应用于有机合成反应中。然而，氟代芳基碘盐的合成及应用的研究却鲜有报道。本项目将合成各种不同的氟代芳基碘盐，基于本小组前期发展的稀土盐作为Lewis酸催化剂活化羰基化合物等亲核底物，与所合成的氟代芳基碘盐进行反应，探索其反应活性，根据反应反馈的结果修饰和合成新的含氟稀土盐催化剂，发展一种高效的芳基化反应方法学。研究过程中着重考察：1）氟代芳基碘盐的合成方法学；2）催化剂的含氟阴离子与氟代碘盐的"氟效应"，研究催化机理；3）进一步发展不对称含氟芳基化反应；4）将该方法学应用于含氟药物合成中，譬如糖尿病药物西他列汀（Januvia）的合成。该申请可为合成多种含氟芳香化合物提供一种有效的途径，对促进含氟新药的开发具有一定的意义。

二芳基碘盐作为一种温和、无毒、高选择性的芳基化试剂受到了科学家们的广泛关注。本项目基于我们小组之前的工作，合成了一系列含氟二芳基碘盐，并对其性质进行了测定。对含氟芳基碘盐的反应性进行了考察，但是未能将其与羰基化合物反应转移含氟芳基。在研究的过程中，我们首次开发出了一种新型的含氟碘盐抗菌剂，经过测试证明其具有较好的抗菌效果。同时，我们还进一步考察了普通二芳基碘盐与N, O, C等亲核底物反应、多种C-H键活化的反应以及铜、钯、Lewis酸催化的串联反应，合成了一系列具有很高的潜在应用价值的荧光母体分子。此外，我们利用此方法学为更加高效的合成格鲁米特、占吨酮、5-脂氧合酶抑制剂等药物或者关键中间体提供了新的路径。