Yan Sheng-Yi, Han Ye-Qiang, Yao Qi-Jun, Nie Xing-Liang, Liu Lei, Shi Bing-Feng
Department of Chemistry, Zhejiang University, Hangzhou, 310027, China.
State Key Laboratory of Elemento-organic Chemistry, Nankai University, Tianjin, 300071, China.
Angew Chem Int Ed Engl. 2018 Jul 16;57(29):9093-9097. doi: 10.1002/anie.201804197. Epub 2018 Jun 19.
Enantioselective functionalizations of unbiased methylene C(sp )-H bonds of linear systems by metal insertion are intrinsically challenging and remain a largely unsolved problem. Herein, we report a palladium(II)-catalyzed enantioselective arylation of unbiased methylene β-C(sp )-H bonds enabled by the combination of a strongly coordinating bidentate PIP auxiliary with a monodentate chiral phosphoric acid (CPA). The synergistic effect between the PIP auxiliary and the non-C -symmetric CPA is crucial for effective stereocontrol. A broad range of aliphatic carboxylic acids and aryl bromides can be used, providing β-arylated aliphatic carboxylic acid derivatives in high yields (up to 96 %) with good enantioselectivities (up to 95:5 e.r.). Notably, this reaction also represents the first palladium(II)-catalyzed enantioselective C-H activation with less reactive and cost-effective aryl bromides as the arylating reagents. Mechanistic studies suggest that a single CPA is involved in the stereodetermining C-H palladation step.
通过金属插入对线性体系中未活化的亚甲基C(sp³)-H键进行对映选择性官能团化本质上具有挑战性，并且在很大程度上仍是一个未解决的问题。在此，我们报道了一种钯(II)催化的未活化亚甲基β-C(sp³)-H键的对映选择性芳基化反应，该反应通过强配位双齿PIP助剂与单齿手性磷酸(CPA)的组合实现。PIP助剂与非C2对称CPA之间的协同效应对于有效的立体控制至关重要。可以使用多种脂肪族羧酸和芳基溴，以高收率(高达96%)和良好的对映选择性(高达95:5 e.r.)提供β-芳基化脂肪族羧酸衍生物。值得注意的是，该反应也代表了首例使用反应活性较低且成本效益高的芳基溴作为芳基化试剂的钯(II)催化对映选择性C-H活化反应。机理研究表明，单个CPA参与了立体决定性的C-H钯化步骤。
