Department of Chemistry, Indian Institute of Technology Bombay, Powai, Mumbai 400076, India.
Tokyo Tech World Research Hub Initiative (WRHI), Laboratory for Chemistry and Life Science, Tokyo Institute of Technology, Tokyo 152-8550, Japan.
J Am Chem Soc. 2020 Jul 15;142(28):12453-12466. doi: 10.1021/jacs.0c05223. Epub 2020 Jul 2.
Controlling remote selectivity and delivering novel functionalities at distal positions in arenes are an important endeavor in contemporary organic synthesis. In this vein, template engineering and mechanistic understanding of new functionalization strategies are essential for enhancing the scope of such methods. Herein, -C-H allylation of arenes has been achieved with the aid of a palladium catalyst, pyrimidine-based auxiliary, and allyl phosphate. 1,1,1,3,3,3-Hexafluoroisopropanol (HFIP) was found as a critical solvent in this transformation. The role of HFIP throughout the catalytic cycle has been systematically studied. A broad substrate scope with phenethyl ether, phenol, benzylsulfonyl ester, phenethylsulfonyl ester, phenylacetic acid, hydrocinnamic acid, and 2-phenylbenzoic acid derivatives has been demonstrated. Interestingly, conformationally flexible arenes have also been selectively allylated at the -position using allyl phosphate. A combination of H NMR, P NMR, ESI-MS, kinetic experiments, and density functional theory (DFT) computations suggested that reaction proceeds through a ligand-assisted -C-H activation, allyl addition forming a Pd-π-allyl complex which is then followed by a turnover determining the C-C bond formation step leading to the allylated product.
在当代有机合成中，控制远程选择性并在芳环的远端位置赋予新功能是一项重要的工作。在这方面，模板工程和对新功能化策略的机理理解对于扩展这些方法的范围至关重要。在此，在钯催化剂、嘧啶基辅助试剂和烯丙基磷酸酯的帮助下，芳基实现了 -C-H 烯丙基化。在这种转化中，1,1,1,3,3,3-六氟异丙醇（HFIP）被发现是一种关键溶剂。系统研究了 HFIP 在整个催化循环中的作用。该反应具有广泛的底物范围，包括苯乙醚、苯酚、苄基砜酯、苯乙基砜酯、苯乙酸、肉桂酸和 2-苯基苯甲酸衍生物。有趣的是，使用烯丙基磷酸酯还可以选择性地对构象灵活的芳环进行 -C-H 烯丙基化。H NMR、P NMR、ESI-MS、动力学实验和密度泛函理论（DFT）计算的组合表明，反应通过配体辅助的 -C-H 活化进行，烯丙基加成形成 Pd-π-烯丙基配合物，然后是决定 C-C 键形成步骤的周转率，导致烯丙基化产物的形成。
