The coupling reaction is a 2A-B→A-A type reaction, which is a process in which a certain chemical reaction is carried out by two organic units to obtain an organic molecule, which includes a radical coupling reaction and a transition metal catalyzed coupling reaction. The narrowly defined coupling reaction refers to a carbon-carbon bond forming reaction involving an organometallic catalyst. In conclusion, coupling reactions with multiple reaction pathways are widely used in organic synthesis. Figure 1 is a schematic diagram of the mechanism of the coupling reaction. The first step is the oxidative addition of an organic halide (Ar-Br) to the catalyst. In the second step, the second coupling agent (R-MgBr) is subjected to metal transfer, and the two coupling agents are placed in the same metal center while eliminating the functional groups. The final step is to eliminate the reducibility of the two coupled fragments to regenerate the catalyst and to obtain the desired product.
Figure 1. The schematic diagram of the mechanism of the coupling reaction
The most common catalyst for the coupling reaction is palladium, but more and more reactions use nickel. There are of course other catalysts, including copper, platinum, iron, cobalt and amines. Palladium is a strong catalyst and is often used due to its high functional group tolerance and low sensitivity of organic palladium compounds to water and air. Nickel catalysts are cheaper, easier to remove, and less toxic. And they typically require a high energy matrix or cocatalyst such as a Photoredox catalyst.
Coupling reactions are mostly used in the pharmaceutical industry and in the preparation of conjugated organic materials.
Figure 2. The diagram of heck reaction
Figure 3. The diagram of Negishi coupling reaction