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 ZnCl 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.

A magnesium bisamide-mediated halogen dance of bromothiophenes is described. The thienylmagnesium species generated in situ is more stable than the corresponding thienyllithium species, which was applied to trap the transient anion species with several electrophiles, such as allyl iodide, phenyl isocyanate, and tributylstannyl chloride. The utility of the magnesium bisamide-mediated halogen dance is useful in the concise synthesis of a medicinally advantageous compound via a one-pot, ester-directed halogen dance/Negishi cross coupling.

Selective trapping of (4,5-dibromo-2-thienyl)lithium, known to undergo halogen dance, was achieved in a flow microreactor. This transient thienyllithium, generated by mixing 2,3-dibromothiophene and lithium diisopropylamide at –78 °C for 1.6 seconds, reacted with benzaldehyde. The reaction system is also applicable to other carbonyl compounds to afford the corresponding adducts in good yields. Moreover, the established conditions permit the conversion of 2,5-dibromothiophene into a mixture of the two constitutional isomers. The contrasting results are discussed on the basis of the reaction pathway.