Mechanochemical Pd(II)-Catalyzed Direct and C-2-Selective Arylation of Indoles

Abstract

A mechanochemical method for the preparation of synthetically useful 2-arylindoles is developed using Pd(II) as the catalyst in the absence of phosphine ligands in a ball-mill. The developed protocol is highly C-2 selective and tolerant of structural variations with electron-rich and electron-deficient substituents both in indoles and iodoarenes. Arylation is possible in both unprotected indoles and Nprotected indoles with the electron-donating group with the former substrate being relatively slower to react and little less yielding. Indoles with a deactivated five-membered ring could also take part in the reaction with ease. The scalability of the reaction was demonstrated by conducting the reaction in the gram scale. In general, the reactions were achieved in a shorter time than the conventional methods.

Sustainable protocols for direct C–H bond arylation of (hetero)arenes

“…In 2019, Banerjee and co-workers described a mechanochemical protocol for the C2 regioselective direct C-H bond arylation of indoles 390 with aryl iodides as arylating agents. 413 In particular, reactions were carried out with Pd(OAc) 2 (5 mol%) as the catalyst, silver acetate (1.2 equiv.) as the base, acetic acid (0.5 equiv.)…”

Recent Advances in C—H Bond Functionalization under Mechanochemical Conditions

“…为探究该机械化学方法的 C-H 键活化机理, 作者 通过 KIE 实验, 证明了连续两步 C-H 键活化中的第一 步导向基团的碳氢键活化为该反应的决速步骤, 而第二 步芳烃的碳氢键活化则是快步骤(Scheme 12). 图式 9 机械力促进锰催化吲哚 C-H 键烯基化反应 Scheme 9 Mechanochemical Mn catalyzed C-H bond alkenylation of indoles 2019 年, Banerjee 等 [27] 克级放大反应同样也能得到类似的高收率. 与溶剂中进 行的反应相比 [16] , 该方法以廉价的钴催化剂代替铑、铱 等贵金属催化剂, 反应时间由通常超过 10 h 缩短至 30 min.…”

In Situ Preparation of Palladium Nanoparticles for C‐2 Selective Arylation of Indoles in Agro‐Waste Extract Based Mixed Solvents

“…[4] At present, directing group strategy is one of the most commonly used technique to control the reaction site and regioselectivity. [5] In addition, heterogeneous catalysis, [6] mechanochemistry, [7] and microwave chemistry [8] also have successfully showed their considerable potential in the direct C-2 selective arylation of indoles. However, there still exist some intrinsic drawbacks, such as the installation of directing group, poor C2/C3 selectivity, and addition of external ligand, base, additive, and equivalent oxidant, need to be solved.…”