Negishi cross coupling

What is Negishi cross coupling?

In 1977, Negishi et al. were the first to report on a reaction now commonly known as the Negishi cross-coupling, Negishi coupling, or Negishi reaction. This reaction involves the coupling of an aryl or alkenylzinc, zirconium, or aluminum reagent with an alkenyl or aryl halide or triflate, catalyzed by palladium or nickel. Specifically, the reaction is mediated by an organozinc reagent and can be used with alkenyl or aryl halides/triflates. Additionally, the zirconium-based coupling is referred to as the zirconium-Negishi reaction.

Negishi cross coupling is an organic chemical reaction in which two different organometallic compounds are coupled together through the action of a transition metal catalyst, such as palladium or nickel. The reaction was discovered by the Japanese chemist Ei-ichi Negishi in the 1970s and is named after him..

Negishi cross coupling reaction
Negishi cross coupling
Negishi cross coupling reaction
Negishi cross coupling

Negishi cross coupling typically proceeds through an intermediate called a “metallacyclobutane,” which is a four-membered ring compound that is formed when the two organometallic compounds react with the transition metal catalyst. The intermediate can then be hydrolyzed to produce the final product..

One of the key features of the Negishi cross coupling is that it allows for the synthesis of a wide range of compounds, including polymers, natural products, and pharmaceuticals. The reaction can also be used to selectively functionalize specific bonds in a compound, making it a useful tool for the synthesis of complex molecules..

Negishi cross coupling can be performed under a variety of conditions, including both acidic and basic conditions. The choice of conditions depends on the specific reactants and desired product, and can be influenced by factors such as the stability of the intermediate and the ability to control the regiochemistry of the reaction..


Negishi cross coupling is a useful tool for synthesizing a wide range of compounds and has a wide range of applications in the field of organic chemistry..

Mechanism of reaction

Negishi cross coupling mechanism
Reaction mechanism of Negishi cross coupling