过渡金属催化硝基芳烃与末端炔烃交叉偶联构筑C(sp2)-C(sp)键的研究

Construction of C(sp2)-C(sp), one of efficient methods for preparation of aromatic alkynes, 1,3-conjugated eneynes and so on, is important in organic synthesis. When we constructed C(sp2)-C(sp) by traditional Sonogashira coupling, we frequently experienced some inconvenience such as difficult to obtain expensive halohydrocarbon electrophilic synthon, difficult to separate multi-site coupling products and difficult to prepare cyclic phenyl polyynes efficiently. In order to solve the above inconvenience and to construct C(sp2)-C(sp) more efficiently, this project focuses on using nitroarenes as electrophiles, constructing C(sp2)-C(sp) through transition metal catalyed cross coupling with terminal acetylenes. The main contents of this project are designing, building and screening out Pd(II)/bulky dialkyl(diaryl) phosphine ligands and Cu(I)/amine homogeneous catalytic system, building structure-activity relationship of catalysts, studying the action mechanism and effect between ligands and Pd, revealing the reaction mechanism, recognizing the nature and law of this reaction, synthesizing cyclic phenyl polyynes by this coupling reaction to improve the present synthetic route. The implementation of this project will construct C(sp2)-C(sp) economically and efficiently using easy available and polar nitroarenes as electrophiles, and will provide new method and thought for preparation of acetylene derivatives.

构筑C(sp2)-C(sp)键是合成芳香炔烃及1,3-共轭烯炔等的最有效途径之一，在有机合成中占有重要地位。传统Sonogashira偶联构筑C(sp2)-C(sp)键时常存在卤代烃亲电试剂难制备较昂贵、多位点反应时偶联产物难分离、无法简捷高效制备环苯基多炔烃等缺陷。针对上述不足，本项目拟以硝基芳烃为亲电试剂，通过过渡金属催化其与末端炔烃交叉偶联来构筑C(sp2)-C(sp)键。拟设计建立和筛选Pd(II)/大位阻双烷基(双芳基)膦配体及Cu(I)/胺均相催化体系，建立催化剂结构与催化性能的构效关系，探索配体对Pd催化性能的作用机制及影响规律，揭示反应机理，认识反应的本质和规律，运用本交叉偶联反应合成环苯基多炔烃，改进其现有合成路线。本项目利用易制备且极性的硝基芳烃为亲电试剂将有望更简单经济有效地构筑C(sp2)-C(sp)键，并为炔烃衍生物的合成提供新方法和思路。

构筑C(sp2)-C(sp)键是合成芳香炔烃及1,3-共轭烯炔等的最有效途径之一，在有机合成中占有重要地位。传统Sonogashira偶联构筑C(sp2)-C(sp)键时常存在卤代烃亲电试剂难制备较昂贵、多位点反应时偶联产物难分离、无法简捷高效制备环苯基多炔烃等缺陷。针对上述不足，本项目以硝基芳烃为亲电试剂，通过过渡金属催化其与末端炔烃交叉偶联来构筑C(sp2)-C(sp)键。此外，通过萘醌的膦化反应/铜催化的缩合反应，以及甲基化和还原反应制备了膦噁唑配体。膦噁唑配体在过渡金属催化的C-N及C-C键形成反应中展示了优越的催化性能。发展了脱Ph2P(O)保护基/CuAAC一锅反应，将Ph2P(O)保护硫炔烃转化为硫1,2,3-三氮唑。不脱Ph2P(O)保护基，Ph2P(O)保护硫炔烃与叠氮化合物的直接CuAAC反应可制备含硫和Ph2P(O)基团的1,2,3-三氮唑。含硫和Ph2P(O)基团的1,2,3-三氮唑的可进行还原和氧化反应。在MeMgBr试剂作用下，其可脱去Ph2P(O)子并转化为1,2,3-三氮唑镁试剂，其与醛类化合物发生加成反应得到含硫和羟基1,2,3-三氮唑。Ph2P(O)保护硫炔烃经过氧化及无铜催化的AAC反应转化为含Ph2P(O)和RS(O)2的1,2,3-三氮唑。具有拮抗孕酮生物活性的化合物LC-58和LC-59也通过本方法成功合成。