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

Abstract

AbstractFunctionalization 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.