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甲硅烷基保护、Ullmann偶联和膦化来构建笼状结构。然而，实验结果表明，直接甲硅烷基保护的2-碘苯酚是一个挑战。因此，MOMCl用于保护碘苯酚，保护产物与甲胺之间的Ullmann偶联以37%的收率得到苯胺。然而，与PCl 3的反应产生了一个复杂的混合物，这被认为是由于在原位脱保护和PCl 3的反应缓慢。另一方面，我以前开发了一个镍催化的芳基氟和H-膦酸酯之间的脱氟膦酰基化反应，以产生相应的芳基膦酸酯。广泛的芳基氟化物，包括富电子和电子中性的，功能化，而无需预活化。然而，机制的见解，特别是磷试剂的作用，仍然没有得到解决。本项目的目标是利用计算方法揭示磷试剂在催化反应中的未知行为。基于实验和计算研究的机理研究表明，原位生成的KOP（OR）2可以将Ni（II）络合物还原为Ni（0）物种。接下来，KOP（OR）2的解离和芳基氟化物的缔合产生催化物质，其中亚磷酸酯形成强的供电子二聚配体系统，用于在低能垒下进行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.