有機リン化合物を活用した触媒および合成反応の開発

使用有机磷化合物的催化剂和合成反应的开发

• 批准号: 22KJ0075
• 负责人: 游 震生
• 金额: $ 1.09万
• 依托单位: Hokkaido University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for JSPS Fellows
• 财政年份: 2023
• 资助国家: 日本
• 起止时间: 2023-03-08 至 2024-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22KJ0075/
• 关键词: Organophosphorus reagent; Aryl fluorides; Reaction mechanism; DFT calculation

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.

最初的合成计划是通过顺序保护，ullmann耦合和磷化来构建笼子结构。然而，实验结果表明，直接对2-碘苯酚的直接保护是一个挑战。因此，MOMCL用于保护碘苯酚，受保护产物和甲基胺之间的ULLMANN耦合以37％的产率递送了苯胺。然而，与PCL3的反应导致了复杂的混合物，这被认为是由于MOM的原位脱脚以及另一方面与PCL3.的反应性缓慢，我先前开发了一种NI催化的芳二磷式磷式化反应，在芳基氟化物和H-磷酸盐之间产生相应的芳基膦酸酯。在无需预激活的情况下，将广泛的芳基氟化物（包括富含电子和电子中性）的芳基氟化物进行了功能化。但是，机械洞察力，尤其是磷试剂的作用，仍未解决。该项目的目标是通过使用计算方法揭示催化中磷试剂的未知行为。基于基于实验和计算研究的机械研究，提出的原位生成的KOP（OR）2可以将Ni（II）复合物降低为Ni（0）物种。接下来，KOP（OR）2和芳基氟化物的缔合的解离会产生催化物种，其中磷酸盐形成了强烈的电子粉状二聚体配体系统，用于在低能屏障中执行C-F氧化添加。

项目成果

Nickel-Catalyzed Defluorophosphonylation of Aryl Fluorides

• DOI: 10.1021/acs.joc.2c02048
• 发表时间: 2022-11-04
• 期刊: JOURNAL OF ORGANIC CHEMISTRY
• 影响因子: 3.6
• 作者: You，Zhensheng;Masuda，Yusuke;Sawamura，Masaya
• 通讯作者: Sawamura，Masaya