Sonogashira Coupling: Alkynes with Halides

Abstract

Sonogashira coupling reaction takes place between the terminal alkynes and organohalides to yield a coupled product with a new carbon–carbon σ bond. It is a  catalytic reaction where palladium is used as a catalyst and copper is used as a co-catalyst, in the presence of a base.

The mechanism of Sonoghashira coupling involves two catalytic cycles: a palladium (Pd) cycle and a copper (Cu) cycle. The Pd-catalytic cycle further encloses three main steps: oxidative addition, transmetallation, and reductive elimination; while the Cu-catalytic cycle intersects the Pd cycle for transmetallation.

The Pd-catalytic cycle begins with oxidative addition of Pd(0) into an organohalide to form a Pd(II) intermediate.

Simultaneously, through the Cu cycle, alkynyl copper is generated from Cu(I) halide and terminal alkyne in the presence of the base. As the Pd cycle and Cu cycle intersect, transmetallation occurs with alkynyl copper exchanging its organyl group with the halide of the Pd(II) intermediate.

Finally, by reductive elimination, the coupled product is released. Simultaneously, Pd(II) is reduced to Pd(0) which takes part in the next Pd cycle.

Protocol

In Sonogashira  reactions, a terminal alkyne reacts with an aryl or a vinyl halide to form a coupled product. The reaction includes two catalytic cycles: One involves a palladium catalyst, and the other requires a copper co-catalyst in the presence of a base.

The Pd -catalytic cycle encloses three main steps: oxidative addition, transmetallation, and reductive elimination. The Cu-catalytic cycle intersects the Pd cycle for transmetallation.

The Sonogashira reaction begins with an oxidative addition step involving the insertion of Pd(0) into an organohalide, giving a Pd(II) intermediate.

The Cu cycle generates alkynyl copper from Cu(I) halide and the terminal alkyne in the presence of a base.

In the transmetallation step, alkynyl copper interchanges its organyl group with the halide in the Pd(II) intermediate.

Finally, reductive elimination releases the coupled product with a new C–C σ bond. Simultaneously, Pd(II) reduces to Pd(0) that participates in the next Pd cycle.

The Sonogashira reaction preserves the stereochemistry of the double bond in the vinyl group.