Dearomative Aminocarbonylation of Arenes via Bifunctional Coordination to Chromium

• Published in: Angewandte Chemie International Edition Vol. 61; no. 41; pp. e202210312 - n/a
• Main Authors: Wang, Ming‐Yang, Wu, Cheng‐Jie, Zeng, Wei‐Long, Jiang, Xu, Li, Wei
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 10.10.2022; Wiley Subscription Services, Inc
• Edition: International ed. in English
• Subjects: Amide; Amides; Aminocarbonylation; Aromatic compounds; Chemistry; Chemistry, Multidisciplinary; Chromium; Coordination; Dearomatization; Modular construction; Physical Sciences; Praziquantel; Science & Technology; Selectivity; Trifluoromethylation; PALLADIUM-CATALYZED AMINOCARBONYLATION; ASYMMETRIC-SYNTHESIS; TRANSITION-METAL-COMPLEXES; ARYLATION; CARBONYL-COMPOUNDS; C-H ACTIVATION; Trifluoromethylation; COUPLING REACTIONS; Chromium; Dearomatization; Amide; OLEFINS; DIVERSITY; Aminocarbonylation; DERIVATIVES
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.202210312

Amides are ubiquitous in physical and life sciences. Given the significant abundance of arenes, dearomative aminocarbonylation of arenes would lead to a large and underexplored chemical space for amide discovery. However, such reactions are challenging due to the high degree of resonance stabilization and selectivity issues. Herein, we disclose an unprecedented dearomative trifluoromethylative aminocarbonylation of arenes via bifunctional coordination to chromium, providing a modular platform for the construction of amides possessing trifluoromethyl (CF3) groups and three‐dimensional rings. Its versatility further enabled a switchable difluoromethylation or trifluoromethylation aminocarbonylation of arene C−H bonds. A possible mechanism was proposed based on control experiments. Finally, the synthetic utility was well demonstrated by diverse applications in the total synthesis of CF3‐functionalized amide‐type drugs, including praziquantel, nateglinide, maraviroc and alloyohimbane. A dearomative trifluoromethylative aminocarbonylation of arenes via bifunctional coordination to chromium has been firstly developed for amide construction, which expands the boundary of aminocarbonylations from conventional C=C bond substrates to arenes. Furthermore, a switchable 1,2‐difunctionalization of arene C−H bonds and concise synthesis of amide‐type drug analogs were successfully achieved.