Department of Chemistry, Indian Institute of Technology Bombay, India.
Department of Chemistry, University of Pittsburgh, Pittsburgh, PA, 15260, USA.
Angew Chem Int Ed Engl. 2017 Nov 20;56(47):14903-14907. doi: 10.1002/anie.201708449. Epub 2017 Oct 25.
The regioselective conversion of C-H bonds into C-Si bonds is extremely important owing to the natural abundance and non-toxicity of silicon. Classical silylation reactions often suffer from poor functional group compatibility, low atom economy, and insufficient regioselectivity. Herein, we disclose a template-assisted method for the regioselective para silylation of toluene derivatives. A new template was designed, and the origin of selectivity was analyzed experimentally and computationally. An interesting substrate-solvent hydrogen-bonding interaction was observed. Kinetic, spectroscopic, and computational studies shed light on the reaction mechanism. The synthetic significance of this strategy was highlighted by the generation of a precursor of a potential lipophilic bioisostere of γ-aminobutyric acid (GABA), various late-stage diversifications, and by mimicking enzymatic transformations.
由于硅的丰富度和无毒特性，将 C-H 键转化为 C-Si 键的区域选择性转化非常重要。经典的硅烷化反应通常存在官能团兼容性差、原子经济性低和区域选择性不足等问题。在此，我们披露了一种模板辅助的甲苯衍生物对位硅烷化的区域选择性方法。设计了一种新的模板，并通过实验和计算分析了选择性的起源。观察到一种有趣的底物-溶剂氢键相互作用。动力学、光谱和计算研究揭示了反应机制。通过生成潜在亲脂性 γ-氨基丁酸 (GABA) 的生物等排体前体、各种后期多样化以及模拟酶转化，突出了该策略的合成意义。
