Rapid copper-catalyzed friedel-crafts alkylation of indoles in 25 Minutes

• Published in: Journal of organometallic chemistry Vol. 1011; pp. 123119 - 123126
• Main Authors: Zhu, Wenli, Yang, Tianbao, Huang, Mingmin, Tang, Niu, Li, Chenhan, Tong, Chunyi, Yin, Shuang-Feng, Kambe, Nobuaki, Abdukader, Ablimit, Qiu, Renhua
• Format: Journal Article
• Language: English
• Published: LAUSANNE Elsevier B.V 01.05.2024; Elsevier
• Subjects: 25 min, c-3 selectivity; 3,3′-diindolylmethane; Anticancer activities; Chemistry; Chemistry, Inorganic & Nuclear; Chemistry, Organic; Copper-catalyzed; Physical Sciences; Science & Technology; Anticancer activities; Copper-catalyzed; 3,3′-diindolylmethane; 25 min, c-3 selectivity; APOPTOSIS; ACTIVATION; ONE-POT SYNTHESIS; BIS(INDOLYL)METHANES; CONDENSATION; 25 min c-3 selectivity; FACILE; EFFICIENT; 3,3 '-diindolylmethane
• ISSN: 0022-328X; 1872-8561
• DOI: 10.1016/j.jorganchem.2024.123119

•The reaction is conducted under air atmosphere and the only by-product is H2O.•Only simple indole and ketones/aldehydes are needed and the products are generated with high C-3 selectivity. The protocol shows tolerance toward a broad range of functional groups at room temperature.•30 examples of products were prepared smoothly. The yield of gram-scale synthesis could be up to 97 %.•This method exhibits a shorter time as fast as 1 min. Desired diindolymethanes were synthesized between 1 and 25 min.•Most of the obtained DIMs exhibit anticancer activities in human breast cancer cell lines MCF-7. The obtained DIMs 5i (IC50 = 6.709 μM) and 5j (IC50 = 5.699 μM) showed good anticancer activities toward MCF-7 cell. Herein, a protocol for the rapid synthesis of 3,3′-Diindolylmethanes (DIMs) via coppercatalyzed Friedel-Crafts alkylation of indoles in 25 min has been developed. This protocol also has the advantage of H2O as a by-product, room temperature and air condition, prefunctionalization-free of indoles, good C-3 selectivity of indoles, broad substrate scope, good reactivity (TON of up to 19.6, TOF of 972 h-1) and excellent to quantitative yields. Notably, the obtained DIMs 5i (IC50 = 6.709 μM) and 5j (IC50 = 5.699 μM) exhibit good anticancer activities toward MCF-7 cells (human breast cancer cells). [Display omitted]