自由基加成启动的非末端炔烃远程碳-氢键官能团化反应研究

惰性碳-氢键直接官能团化是合成化学的难点和热点之一。烯基自由基分子内氢迁移是活化惰性碳-氢键的重要方法，但是，产生的烷基自由基往往紧接着发生5-exo环化，局限了烯基自由基介导的惰性碳-氢键官能团化反应的应用。为此，本项目拟用杂原子基团或芳基调控非末端炔烃自由基加成反应的区域选择性，从源头上排除5-exo环化反应可能性，进而发展远程惰性碳-氢键的分子间官能团化反应，如氟化、（杂）芳基化、烷基化、氧化和脱氢成烯等。此外，利用还原自由基-极性交叉策略，发展非末端炔烃的自由基加成/1,5-氢迁移/5-endo还原环化串联反应。在上述反应基础上，还将进行Magnofargesin等生物活性分子的合成研究。拟开展的反应具有高度的区域、立体和位点选择性，可以快速合成热力学相对不稳定的(Z)-烯烃或高度官能团化的五元环，具有良好的应用前景。

Direct functionalization of inert C-H bonds is one of the most important, but challenging areas in synthetic chemistry. In this respect, radical translocation of vinyl radicals has become a powerful strategy for the direct C-H bond functionalization. However, a 5-exo cyclization typically occurs after the initial 1,5-HAT of vinyl radicals, thus limiting the application of this strategy in organic synthesis. As such, seeking new reaction modes for the vinyl radical-induced remote C-H bond functionalization is highly desirable. In this project, a novel remote intermolecular C-H bond functionalization, including fluorination, arylation, heteroarylation, alkylation, oxygenation, desaturation, and other reactions, of internal alkynes is proposed, in which heteroatom- or aryl-directed beta-regioselective radical addition to C-C triple bonds is used for avoiding the traditional 5-exo cyclization. In the meanwhile, an unprecedented internal alkyne radical addition/1,5-HAT/reductive 5-endo cyclization cascade reaction is proposed in the absence of additional functional groups, which may give a direct access to highly functionalized five-membered rings. Finally, the synthetic utility of proposed methods will be evaluated on the fast synthesis of biologically active molecules like Magnofargesin. The designed reactions are featured with excellent regio-, stereo-, and site-selectivity, thus offering facile access to thermodynamically unfavorable (Z)-alkenes or highly functionalized five-membered rings, which are difficult to access via traditional methods. Therefore, we believe that the methods described here should be valuable for chemical synthesis.