Palladium‐Catalyzed Heck Type Regioselective β‐Vinylation of Thiophenes Using a Bromo Substituent as Traceless Directing Group

• Published in: European journal of organic chemistry Vol. 27; no. 4
• Main Authors: Liu, Linhao, Doucet, Henri
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 22.01.2024; Wiley Subscription Services, Inc; Wiley-VCH Verlag
• Subjects: Aromatic compounds; Catalysis; Chemical reactions; Chemical Sciences; Chemical synthesis; Chemistry; Chemistry, Organic; Coupling; Heck reaction; homogeneous catalysis; migration; Organic chemistry; Palladium; Physical Sciences; Science & Technology; Thiophenes; thiophenes; ACTIVATION; DIRECT ARYLATION; MECHANISM; Heck reaction; C-H FUNCTIONALIZATION; CROSS-COUPLING REACTIONS; HETEROARENES; homogeneous catalysis; BOND ARYLATION; migration; palladium; ARYL; OLEFIN
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.202300986

Functionalization of β‐C−H bonds of thiophenes such as their vinylation is more challenging than for their α‐positions. The use of Pd‐catalysis allowed us to vinylate such thienyl β‐positions. Oxidative addition of 2‐(2‐bromoaryl)thiophenes to palladium followed by a Pd 1,4‐migration activates these thienyl β‐C−H positions, then, classical Pd‐catalyzed Heck reaction gives the β‐vinylated 2‐arylthiophene derivatives. In the course of this coupling reaction, the bromide substituent on the aryl unit acts as a traceless directing group. It should also be mentioned that the created C−C bond results from the functionalization of two C−H bonds. This synthesis scheme tolerates a range of substituents on both the aryl ring and the alkene. In addition, this procedure employs an easily available air‐stable catalyst and an inexpensive base. This reaction allows the programmed Pd‐catalyzed synthesis of 2,3,5‐trisubstituted thiophenes using first Suzuki C2‐coupling, then Pd‐catalyzed direct C5‐arylation and finally Pd 1,4‐migration Heck C3‐vinylation. Palladium‐catalyzed 1,4‐migration associated to Heck vinylation provides a new tool in traceless C−H bond functionalization at β‐position of thiophenes.