过渡金属催化合成具有潜在生物活性的含氟杂环化合物研究

含氟杂环芳烃被广泛认为是许多现代药物和农药的活性成分。特别是三氟甲基由于其强烈的吸电子性和疏水性，更能显著的修饰靶标分子的生物药效率和稳定性。目前，大量氟化的具有生物活性的药物已经被鉴定，市场上大约有20%左右的药物含有氟元素。因此，将氟原子通过简单的实验方法引入到杂环分子中，是目前合成化学的主要目标之一。尽管在这方面做了很大的努力，但目前的方法常存在需要高温、高催化剂用量；昂贵的试剂、催化剂、配体；以及反应活性低等缺点。因此，我们在本项目中准备研究过渡金属催化合成具有潜在生物活性的含氟杂环化合物。研究内容包括以下三个部分：(1) 含亲核性官能团的非末端炔烃的环化/三氟甲基化反应；(2) 深入拓展利用C-H键活化策略对非苄基Csp3进行氟化或三氟甲基化；(3) 基于联烯和邻炔基苯甲醛肟而发展的串联环化和氟化反应。

Fluorine-containing heteroarenes are widely used as active ingredients of numerous modern pharmaceuricals and agrochemicals. In particular, trifluoromethyl group can dramatically modify the bioavailability and stability of target molecules because of the strong electron-withdrawing nature and large hydrophobic domain of CF3. A myriad of fluorinated biologically active pharmaceutical compounds have been identified, with an estimated 20% of drugs on the market containing fluorine. For this reason, the introduction of fluorine into heterocycles by simple laboratory procedures is a major synthetic goal. Despite much effort to develop the reactions, current methods are limited by some combination of high temperatures, high catalyst loadings, and expensive reagents, catalysts, ligands, and low reactivity. Herein, we will research the transition-metal-catalyzed synthesis of promising biologically active fluorine-containing heterocyclic compounds. Our study includes three parts: (1) cyclization-trifluoromethylation of internal alkyne containing nucleophilic functional group; (2) Ligand-directed Csp3-H fluorination and trifluoromethylation; (3) Synthesis of fluorine-containing heterocyclic compounds from allene and 2-(arylethynyl)benzaldehyde oxime.