有機リン化合物を活用した触媒および合成反応の開発

最初的合成计划是通过顺序的硅基保护、乌尔曼偶联和磷化来构建笼状结构。然而，实验结果表明，2-碘酚的直接硅基保护是一个挑战。因此，利用MOMCl保护碘酚，保护产物与甲基胺之间的Ullmann偶联以37%的收率传递苯胺。然而，与PCl3的反应导致了复杂的混合物，这被认为是由于MOM的原位脱保护和与PCl3的反应活性缓慢。另一方面，我之前开发了一种镍催化的氟芳基和h -膦酸盐之间的去氟膦化反应，以产生相应的膦酸芳基。广泛的芳基氟化物，包括富电子和电子中性的，在不需要预活化的情况下被功能化。然而，机理的洞察力，特别是磷试剂的作用，仍然没有解决。该项目的目的是利用计算方法揭示磷试剂在催化中的未知行为。基于实验和计算的机制研究表明，原位生成的KOP(OR)2可以将Ni（II）络合物还原为Ni(0)种。接下来，KOP(OR)2的解离和芳基氟化物的结合产生催化物质，其中亚磷酸盐形成一个强给电子二聚体配体体系，在低能垒中进行C-F氧化加成。

The initial synthetic plan was the construction of the cage structure by sequential silyl protection, Ullmann coupling, and phosphination. However, the experimental result suggested direct silyl protection of 2-iodophenol was a challenge. Hence, MOMCl was used to protect iodophenol, Ullmann coupling between the protected product and methyl amine delivered the aniline in 37% yield. However, the reaction with PCl3 resulted in a complex mixture, which was thought to be due to in situ deprotection of MOM and the sluggish reactivity with PCl3.On the other hand, I previously developed a Ni-catalyzed defluorophosphonylation reaction between aryl fluorides and H-phosphonates to produce the corresponding aryl phosphonates . A wide range of aryl fluorides, including electron-rich and electron-neutral ones, were functionalized without the requirement of pre-activation. However, the mechanistic insight, especially the role of phosphorus reagents, was remained unresolved. The target of this project was to reveal the unknown behaviors of phosphorus reagents in catalysis by using computational methods. Mechanistic studies based on both experimental and computational investigations suggested in situ generated KOP(OR)2 could reduce Ni(II) complex to Ni(0) species. Next, dissociation of KOP(OR)2 and association of aryl fluorides generate catalytic species, in which the phosphite forms a strong electron-donating dimeric ligand system for performing C-F oxidative addition in a low energy barrier.