Palladium/Norbornene‐Catalyzed C−H Alkylation/Alkyne Insertion/Indole Dearomatization Domino Reaction: Assembly of Spiroindolenine‐Containing Pentacyclic Frameworks

• Published in: Angewandte Chemie International Edition Vol. 57; no. 18; pp. 5151 - 5155
• Main Authors: Bai, Lu, Liu, Jingjing, Hu, Wenjie, Li, Kunyu, Wang, Yaoyu, Luan, Xinjun
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 23.04.2018; Wiley Subscription Services, Inc
• Edition: International ed. in English
• Subjects: Alkylation; Alkynes; Cascade chemical reactions; Catalysis; Chemical reactions; Chemistry; Chemistry, Multidisciplinary; cyclizations; C−H activation; dearomatization; heterocycles; Hydrogen bonds; Indoles; Insertion; Molecular chains; Organic chemistry; Palladium; Physical Sciences; Science & Technology; ARYLATIVE DEAROMATIZATION; dearomatization; EFFICIENT SYNTHESIS; AROMATIC-COMPOUNDS; cyclizations; SEQUENTIAL REACTIONS; ASYMMETRIC ALLYLIC DEAROMATIZATION; C-H activation; COOPERATIVE CATALYSIS; heterocycles; REGIOSELECTIVE SYNTHESIS; palladium; ARYL IODIDES; TETRASUBSTITUTED HELICAL ALKENES; STRAINED ALKENES; C−H activation
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201801894

Reported is a highly chemoselective intermolecular annulation of indole‐based biaryls with bromoalkyl alkynes by using palladium/norbornene (Pd/NBE) cooperative catalysis. This reaction is realized through a sequence of Catellani‐type C−H alkylation, alkyne insertion, and indole dearomatization, by forming two C(sp2)−C(sp3) and one C(sp2)−C(sp2) bonds in a single chemical operation, thus providing a diverse range of pentacyclic molecules, containing a spiroindolenine fragment, in good yields with excellent functional‐group tolerance. Preliminary mechanistic studies reveal that C−H bond cleavage is likely involved in the rate‐determining step, and the indole dearomatization might take place through an olefin coordination/insertion and β‐hydride elimination Heck‐type pathway. A sequence of three: A novel palladium/norbornene (NBE) catalyzed intermolecular annulation of indole‐derived aryl iodides with tethered bromoalkyl alkynes has been developed for the rapid construction of pentacyclic scaffolds containing a spiroindolenine fragment. This reaction was realized through a C−H alkylation, alkyne insertion, and indole dearomatization sequence.