One-Pot Halogen Dance/Negishi Coupling of Dibromothiophenes for Regiocontrolled Synthesis of Multiply Arylated Thiophenes

Abstract

One-pot halogen dance/Negishi cross-coupling of readily available 2,5-dibromothiophenes is described. A lithium diisopropylamide (LDA)-mediated halogen dance reaction resulted in the formation of thermodynamically stable α-lithiodibromothiophenes, which were transmetalated with ZnCl₂ and subjected to Negishi cross-coupling to provide the corresponding arylated dibromothiophenes in one pot. The resultant β-bromo group was much less reactive than the remaining α-bromo group, which was used in a one-pot double Suzuki-Miyaura cross-coupling, enabling facile synthesis of multiply arylated thiophenes.

Keywords: cross-coupling; halogen dance; one-pot reaction; palladium; thiophene.