Zhou Jun, Zhao Zhengyu, Kiyono Tatsuki, Matsuno Ayaka, Escorihuela Jorge, Shibata Norio
Department of Nanopharmaceutical Sciences, Nagoya Institute of Technology Gokiso, Showa-ku Nagoya 466-8555 Japan
Department of Life Science and Applied Chemistry, Nagoya Institute of Technology Gokiso, Showa-ku Nagoya 466-8555 Japan.
Chem Sci. 2024 Oct 1;15(42):17418-24. doi: 10.1039/d4sc04357j.
The construction of C(sp)-C(sp) bonds is pivotal in organic synthesis; however, traditional methods involving alkyl halides are often limited by substrate tolerance and bond dissociation energies, particularly with alkyl fluorides. Herein, we report a silylboronate-mediated cross-coupling strategy that circumvents these challenges, enabling the efficient formation of C(sp)-C(sp) bonds between alkyl fluorides and aryl alkanes under mild conditions. Various alkyl fluorides have also been effectively utilized, demonstrating the versatility and broad applicability of this approach. The use of diglyme is critical for this transformation which encapsulates potassium cations and enhances the reaction efficiency. Conventional alkyl halides, including chlorides, bromides, and iodides, are also suitable for this transformation. Density functional theory (DFT) calculations were conducted on the silylboronate-mediated coupling reactions for the first time. Interestingly, while experimental results suggest a radical mechanism, DFT calculations indicate a preference for an ionic pathway.
C(sp) - C(sp)键的构建在有机合成中至关重要；然而，涉及卤代烃的传统方法往往受到底物耐受性和键离解能的限制，尤其是对于烷基氟化物。在此，我们报道了一种硅硼酸酯介导的交叉偶联策略，该策略规避了这些挑战，能够在温和条件下实现烷基氟化物与芳基烷烃之间高效形成C(sp) - C(sp)键。各种烷基氟化物也得到了有效利用，证明了该方法的通用性和广泛适用性。二甘醇二甲醚的使用对这种转化至关重要，它能包裹钾阳离子并提高反应效率。传统的卤代烃，包括氯化物、溴化物和碘化物，也适用于这种转化。首次对硅硼酸酯介导的偶联反应进行了密度泛函理论（DFT）计算。有趣的是，虽然实验结果表明是自由基机理，但DFT计算表明更倾向于离子途径。
