One‐Pot Asymmetric Oxidative Dearomatization of 2‐Substituted Indoles by Merging Transition Metal Catalysis with Organocatalysis to Access C2‐Tetrasubstituted Indolin‐3‐Ones

• Published in: Advanced synthesis & catalysis Vol. 364; no. 7; pp. 1277 - 1285
• Main Authors: Zhao, Yong‐Long, An, Jian‐Xiong, Yang, Fen‐Fen, Guan, Xiang, Fu, Xiao‐Zhong, Li, Zong‐Qin, Wang, Da‐Peng, Zhou, Meng, Yang, Yuan‐Yong, He, Bin
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 30.03.2022; Wiley Subscription Services, Inc
• Subjects: Aldehydes; Asymmetry; C2-tetrasubstituted indolin-3-ones; Catalysis; Chemistry; Chemistry, Applied; Chemistry, Organic; Drug resistance; Indoles; Ketones; organocatalysis; oxidative dearomatization; Oxidizing agents; Physical Sciences; Proline; Science & Technology; Substitutes; transition metal catalysis; Transition metals; TANDEM REACTIONS; CONCISE TOTAL-SYNTHESIS; ANNULATION; C2-tetrasubstituted indolin-3-ones; STRATEGY; SPIRO-PSEUDOINDOXYL; QUATERNARY; MICHAEL ADDITION; oxidative dearomatization; organocatalysis; 2-ALKYNYLANILINES; AEROBIC OXYGENATION; transition metal catalysis; 2-ARYLBENZOXAZINONE DERIVATIVES
• ISSN: 1615-4150; 1615-4169
• DOI: 10.1002/adsc.202101498

A one‐pot approach for the asymmetric synthesis of C2‐tetrasubstituted indolin‐3‐ones from 2‐substituted indoles was developed via merging transition metal catalysis with organocatalysis. This strategy involves two processes, including CuI catalyzed oxidative dearomatization of 2‐substituted indoles using O2 as green oxidant, and followed by an proline‐promoted asymmetric Mannich reaction with ketones or aldehydes. A series of C2‐tetrasubstituted indolin‐3‐ones were obtained in 35–86% yields, 2:1‐>20:1 dr and 48–99% ee. Moreover, the synthetic 2‐tetrasubstituted indolin‐3‐ones could be easily transformed into 1H‐[1,3] oxazino [3,4‐a]indol‐5(3H)‐ones via a [4+1] cyclization process. In addition, the synthetic compound 3 s show certain antibacterial activity against S. aureus ATCC25923 and multi‐drug resistance bacterial strain of S. aureus (20151027077) and its MIC values up to 8 μg/mL and 16 μg/mL, respectively.