Suzuki coupling reaction involves the coupling of an organohalide and boronic acid. The Suzuki coupling reaction was first published by a Japanese chemist named Akira Suzuki in 1979. In 2010, Akira Suzuki and Richard F. Heck shared the Nobel prize in chemistry. The Suzuki coupling reaction is otherwise known as Suzuki–Miyaura reaction. In this article, we will be discussing the reaction mechanism and applications of the Suzuki coupling reaction in detail.
Suzuki coupling reaction is a coupling reaction taking place between the halide ion and organoboron specimen. The reaction takes place exclusively in the presence of a base and palladium catalyst. The reactants are subjected to heat in the presence of the palladium catalyst. As a result, a coupling reaction between the halide ion and boronic acid results in forming a C-C single bond.
The general equation used to represent the Suzuki coupling reaction is given below.
To understand the overall mechanism of the Suzuki reaction, we must view the process from the perspective of the catalyst being used. In most cases, palladium is used as a catalyst. The mechanism of the Suzuki reaction can be summarized into three significant steps, which are as follows.
1. Oxidative addition
3. Reductive elimination
Step 1: Oxidative addition
The first step in the mechanism of the Suzuki reaction is the oxidation of the palladium catalyst. The oxidative addition of the catalyst palladium to the alkyl halide is a slow process, determining the reaction rate.
Palladium undergoes oxidation to palladium(II) from palladium(0). The oxidized palladium couples with the haloalkane to give rise to an organopalladium complex. The process of the addition of oxidized palladium to the haloalkane is termed oxidative addition. As a result of oxidative addition, the carbon-halogen (C-X) bond is broken, and both of them are bound to the palladium ion. Oxidative addition is the rate-determining step of the Suzuki reaction.
Step 2: Transmetalation
Transmetalation refers to an organometallic reaction where ligand molecules transfer from one entity to another.
In the transmetalation of the Suzuki reaction, the transfer of ligands takes place from the species containing organoboron to the palladium(II) complex. Therefore, the transmetalation reaction takes place exclusively in the presence of a base like sodium hydroxide.
Step 3: Reductive elimination
The last step in the Suzuki reaction is the reductive elimination of palladium catalyst. The palladium(II) complex eliminates the end product from the reaction mixture. During this process, the palladium(II) complex is again transformed into palladium(0). This is how the regeneration of palladium catalyst and formation of the end product takes place.
In the entire process of the Suzuki reaction, the ligand is known to play a crucial role. The most commonly used ligand in the Suzuki reaction is the phosphate ligand. The primary function of the phosphate ligand is to increase the density of electrons at the complex’s metal center. This is how the phosphate ligand supports the oxidative addition step of the Suzuki reaction. In addition to this, the phosphate ligand supports the reductive elimination step with the help of bulky substitution.
There are many organic reactions similar to the Suzuki coupling reaction. However, the Suzuki coupling reaction offers numerous advantages over the other reactions. The various advantages of the Suzuki coupling reaction are given below.
● The easy availability or accessibility of common boronic acids is the most significant advantage of the Suzuki reaction.
● Additionally, this reaction is less toxic and involves very mild reaction conditions, thereby making it eco-friendly.
● Compared to other organozinc and organic compounds, organoboron compounds are safe and less harmful.
● The reactants involved in the Suzuki reaction are highly economical and can be prepared readily.
● A vast range of reagents can be used in the Suzuki reaction. Water, a universal solvent, can also be used.
● All types of halides respond to the Suzuki reaction. Additionally, pseudohalides like triflates can be replaced with halides for the Suzuki reaction.
● The reaction is highly flexible and feasible. Hence it is widely accepted.
The high flexibility and feasibility offered by the Suzuki coupling reaction made it widely acceptable. As a result, the Suzuki coupling reaction is today used to synthesize a wide variety of organic compounds. Let us now have a look at a few critical applications of the Suzuki reaction.
● Synthesis of intermediates
One of the practical uses of the Suzuki coupling reaction is the synthesis of intermediates essential for pharmaceutical manufacturing processes. For example, significant biological compounds like CI-1034 are synthesized using this reaction. Another significant example is the synthesis of an intermediate used in the preparation of a powerful CNS agent. This intermediate is produced by the coupling of 1-Bromo-3-(methylsulfonyl)benzene and 3-pyridyl borane.
● Synthesis of complexes
The Suzuki coupling reaction is used for the production of complex compounds such as caparratriene. Caparratriene is known to have therapeutic effects against leukemia which the coupling reaction of citronellal can obtain. Likewise, many such significant complexes are manufactured with the help of the Suzuki coupling reaction.