基于钯催化的烯烃C-H键直接官能团化反应研究

Palladium catalyzed alkene C-H bonds functionalization reactions have been extensively applied in organic synthesis as atom- and step-economic manners to construct C-C bonds. Recent studies have mainly focused on the manipulation of C-H bonds on alkenes, which are either bearing proper directing groups or pre-activated by strong electronically biased functional groups. However, for the substrates without directing group and electronically nonbiased simple olefins, the direct C-H functionalization reactions have been less studied. In this project, we would investigate palladium catalyzed electronically nonbiased simple olefins C-H bond functionalization reactions, including: (1) selective functionalization of terminal olefin C-H bonds of diene derivatives; (2) palladium-catalyzed reactions of simple alkenes with carbene precursors to give multi-substituted diene derivatives that are difficult to be prepared by the traditional alkene-alkene cross-coupling reactions; (3) palladium-catalyzed reactions of simple alkenes with cyclohexenones to prepare multi-substituted cyclohexanone derivatives. As compared to the reported methods, this proposal would expand the substrate scope and study more distinctive transformative pathways. More importantly, these designed reactions would lead to more diverse products that would be used as valuable building blocks in organic synthesis. Furthermore, these proposed reactions would provide new synthetic routes to access structurally complex natural products tethering an alkene moiety.

钯催化的烯烃C-H键官能团化反应构筑C-C键的方法因其可以简化反应步骤、提高合成效率、实现原子经济性等优点已经被广泛地应用于有机合成中。但由于烯烃C-H键惰性较大、能垒较高，目前的研究主要集中在含有氧、氮等导向基团或电子偏向明显的烯烃底物。对于无导向基团或电子偏向不明显的简单烯烃的研究则相对较少。本项目中，我们将研究钯催化的无电子偏向的简单烯烃C-H键直接官能团化反应：（1）简单共轭二烯类化合物的末端双键C-H键的选择性官能团化反应;（2）末端烯烃与卡宾前体制备传统烯烃-烯烃交叉偶联难以实现的含有多个取代基共轭二烯型化合物;（3）末端烯烃与环己烯酮制备多取代环己酮衍生物。本项目所设计的反应和已报道的相关反应相比，研究的底物范围更加广阔，设计的转化途径更加多样化，所预计的产物具有更广泛的应用价值。此外，我们预计本项目所设计的方法将为快速高效合成含有碳-碳双键的复杂天然产物提供新的途径。

本项目利用钯催化下C-H键活化策略，针对如何实现无导向基团或电子偏向不明显的简单烯烃C-H键官能团化反应为科学问题，开展了各种类型的烯烃（包括环烯酮、1,1-二取代烯烃、1,2-二取代的烯烃、单取代烯烃）在钯催化下的C-H键官能团化反应研究。解决这一科学问题的关键技术是通过构建新型的钯催化体系，实现不活泼烯烃的C-H键官能团化。主要的研究内容为1）钯催化C-H键活化策略下，环己烯酮与噻吩类化合物的交叉偶联反应；2）钯和酸接力催化下，电子偏向不明显的各种烯烃与邻碘苯甲酸酯的Heck偶联/六元内型环化串联反应；3）二甲基亚砜作为硫源高效构筑官能团化烯丙基硫醚和烯丙基砜类化合物。研究结果发表SCI科技论文3篇，正在审查3项发明专利，培养研究生5名。研究的科学价值和贡献在于1）克服了电子偏向不明显的烯烃参与偶联反应时区域选择性较差及环烯酮在偶联反应中应用局限性的难题，为3-位被噻吩取代的环烯酮、间苯酚、异色满酮以及有机硫化合物的快速制备开辟了一条全新的路径，丰富和完善了钯催化C-H键官能团化理论体系；2）相比之前3-位官能团化的环烯酮、异色满酮的合成，上述研究内容所涉及的合成方法具有初始原料廉价易得、反应步骤简捷、合成效率高等优点，为复杂化合物的逆合成分析提供了更多可供选择的路径。