Wang Cong-Shuai, Wei Liang, Fu Cong, Wang Xin-Heng, Wang Chun-Jiang
Engineering Research Center of Organosilicon Compounds & Materials, Ministry of Education, College of Chemistry and Molecular Sciences, Wuhan University, Wuhan 430072, China.
State Key Laboratory of Elemento-Organic Chemistry, Nankai University, Tianjin 300071, China.
Org Lett. 2021 Oct 1;23(19):7401-7406. doi: 10.1021/acs.orglett.1c02574. Epub 2021 Sep 17.
Atropoisomeric biaryl motifs are widely found in natural products and bioactive compounds as well as chiral catalysts and ligands. Various efficient approaches have been disclosed for the construction of chiral six-six biaryl skeletons. In contrast, the enantioselective synthesis of axially chiral arylindoles through the strategy of construction, other than the asymmetric functionalization of indoles, remain a challenging task. Herein we report an efficient Pd(0)/()-Segphos-catalyzed atroposelective Cacchi reaction of 2-alkynylanilines with sterically congested naphthyl halides, which afforded an array of naphthyl-C3-indoles in high yields with good to excellent atroposelectivities. The addition of water and the modulation of the manipulation procedure by premixing the palladium complex and the naphthyl halide were the keys to success. The conformational stability of the obtained axially chiral naphthyl-C3-indole containing a synthetically more-valuable free NH moiety is revealed through kinetic experiments.
轴手性联芳基结构广泛存在于天然产物、生物活性化合物以及手性催化剂和配体中。已经公开了各种构建手性六-六联芳基骨架的有效方法。相比之下，除了吲哚的不对称官能化之外，通过构建策略对轴向手性芳基吲哚进行对映选择性合成仍然是一项具有挑战性的任务。在此，我们报道了一种高效的Pd(0)/()-Segphos催化的2-炔基苯胺与空间位阻较大的萘基卤化物的轴手性Cacchi反应，该反应以高收率和良好至优异的轴手性选择性得到了一系列萘基-C3-吲哚。水的加入以及通过预混钯配合物和萘基卤化物来调节操作程序是成功的关键。通过动力学实验揭示了所得到的含有合成上更有价值的游离NH部分的轴向手性萘基-C3-吲哚的构象稳定性。
