从共轭二炔合成基础五元杂环的方法研究

Basic Five-membered heterocycles, including furans, thiophenes, pyrroles, etc. are important building blocks in the field of biochemistry, pharmacy, new materials, organocatalyst, etc. Traditional synthetic route towards these structures are mainly based on condensation reactions between carbonyl groups and other nucleophiles. These methods are suffered from the long reaction steps, low atom efficiency , and side reactions together with byproducts. This project could obtain the heterocycles directly from diynes or substitute propynenitriles with nucleophiles such as amines in the presence of transition metal catalyst under mild reaction conditions. Complexes of metals such as Zn, Ti, Cu and Ni would be used to coordinate with alkynes to form the back-donating π bond, which could lower down the electron density of the alkyne and thus accelerate the addition of the nucleophiles. Stoichiometric nucleophiles are used in this system to avoid the waste of the starting materials. Proper Lewis acids or other additives would also be used to make the reaction feasible under mild conditions. The starting materials, diynes, could be easily prepared by Glaser-Hay coupling or from an improved cross coupling developed by the applicant. The reaction could be finished in ONE step with the atom efficiency up to 100% under mild conditions, and no more necessary to use nucleophiles as solvent.

基础五元杂环化合物，包括噻吩、呋喃、吡咯等，是构成生命体、药物、新材料、有机催化剂等的重要基础结构。传统合成方法以羰基等结构和各类小分子的缩合反应为主，反应步骤较长，原子经济性较低，且容易生成副产物和较多废料。本项目从1,3-共轭二炔或氰基炔等原料出发，拟在过渡金属催化剂作用和温和的条件下，通过和胺等小分子亲核试剂一步反应，直接得到各类基础杂环化合物。在催化剂选择上将使用锌、钛、铜、镍等金属的络合物，使之和炔烃配位，形成相应的反馈π键，降低炔烃上电子云密度，有利于各类亲核试剂的加成；使用当量的亲核试剂，避免原料浪费；并加入适量的路易斯酸或其它添加剂，以达到相对温和的反应条件。该项目主要原料1,3-共轭二炔可由Glaser-Hay偶联反应或申请人之前发展的一类方法高效地得到；反应一步进行，原子经济性有望高达100%；反应条件温和，不需以亲核试剂为溶剂，减少浪费。

该项目主要研究共轭二炔及其相关类似结构的衍生化，尤其是进一步生成五元杂环类化合物，如噻吩、吡咯等芳杂环类结构的反应。在整个项目资助期间内，项目负责人围绕着本项目申请时的研究内容，对二炔、炔腈类结构的合成、衍生化等都进行了较为系统的研究，取得了系列的研究成果，包括：发现末端炔烃的炔氢在银催化下的高效氯化方法；发现铁参与的末端炔烃和氰化亚铜氧化偶联得到炔腈类结构的方法；由非对称共轭二炔高效合成双取代噻吩；发现钯催化的氧气条件下由炔腈类物质合成吲哚环的方法等。该项目对炔烃类结构的反应和衍生化有一定的补充和完善。