Palladium‐Catalyzed Intermolecular [4+1] Spiroannulation by C(sp3)−H Activation and Naphthol Dearomatization

• Published in: Angewandte Chemie International Edition Vol. 58; no. 5; pp. 1474 - 1478
• Main Authors: Tan, Bojun, Bai, Lu, Ding, Pin, Liu, Jingjing, Wang, Yaoyu, Luan, Xinjun
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 28.01.2019; Wiley Subscription Services, Inc
• Edition: International ed. in English
• Subjects: Activation; Aromatic compounds; Cascade chemical reactions; Chemistry; Chemistry, Multidisciplinary; Coupling; Coupling (molecular); cyclization; C−H activation; dearomatization; Halides; Naphthol; Palladium; Physical Sciences; Science & Technology; spiro compounds; AROMATIC FUNCTIONALIZATION; METHOXY GROUPS; ANNULATION; ALKYLATION; dearomatization; EFFICIENT SYNTHESIS; ALKYNES; cyclization; spiro compounds; C(SP)-H BOND ACTIVATION; ASYMMETRIC ALLYLIC DEAROMATIZATION; C-H activation; palladium; ARYL IODIDES; C−H activation
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201813202

A novel palladium‐catalyzed [4+1] spiroannulation was developed by using a C(sp3)−H activation/naphthol dearomatization approach. This bimolecular domino reaction of two aryl halides was realized through a sequence of cyclometallation‐facilitated C(sp3)−H activation, biaryl cross‐coupling, and naphthol dearomatization, thus rendering the rapid assembly of a new class of spirocyclic molecules in good yields with broad functional‐group tolerance. Preliminary mechanistic studies indicate that C−H cleavage is likely involved in the rate‐determining step, and a five‐membered palladacycle was identified as the key intermediate for the intermolecular coupling. Two types of halides: A palladium‐catalyzed [4+1] spiroannulation of two types of aryl halides has been developed for the rapid construction of a new class of spirocycles. This intermolecular domino process was realized through a sequence of C(sp3)−H cleavage, unsymmetrical biaryl coupling, and naphthol dearomatization.