Suzuki Reaction.

Suzuki reaction is mainly organometallic reaction where the coupling partner are boron derivative couple with alkyl halide in the presence of Pd catalyst to give the carbon carbon single bond product.
In this study we can see the details about the machanism of suzuki coupling, with the role of ligands, base, solvents.
In addition it include the different example and applications of suzuki coupling reaction, along with advatanges and disadvantages.

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1. SUZUKI REACTION Presented by Ashvini.B.Tanpure Department of Pharmacetical Technology (Process Chemistry) M.Tech .(Pharm), Sem -II National Institute of Pharmaceutical Education and Research SAS,Nagar . 1

2. The Suzuki reaction is an   organic reaction, classified as a cross-coupling reaction , where the coupling partners are a  boronic acid and an  organohalide  and the  catalyst is a palladium(0) complex .  It was first published in 1979 by Akira Suzuki, and he shared the 2010 Nobel Prize in Chemistry with Richard F. Heck and  Ei-ichi Negishi  for their contribution to the discovery and development of palladium-catalyzed cross-couplings in organic synthesis .  This reaction is also known as the Suzuki– Miyaura reaction or simply as the Suzuki coupling. It is widely used to synthesize  polyolefins ,  styrenes , and substituted biphenyls.  The general scheme for the Suzuki reaction is a carbon-carbon single bond is formed by coupling an  organoboron  species (R 1 -BY 2 ) with a halide (R 2 -X) using a palladium catalyst and a base. What is S uzuki Reaction…. 2

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4. Catalytic cycle 4

5. The first step is the oxidative addition of palladium to the halide  to form the  organopalladium  species  . Reaction (metathesis) with base gives intermediate  which via  transmetalation with the boronate complex (produced by reaction of the boronic acid  with base) forms the  organopalladium   species. Boronate complex is produced by reaction of boronic acid with base.   Reductive elimination of the desired product  restores the original palladium catalyst  which completes the catalytic cycle. Steps of the Catalytic cycle- Oxidative Addition Transmetalation Reductive Elimination Machanism Of Suzuki Reaction 5

6. In most cases the oxidative addition is the  rate determining step of the catalytic cycle .   During this step, the palladium catalyst is oxidized from palladium(0) to palladium(II). The palladium catalyst  1  is coupled with the alkyl halide  2  to yield an organopalladium complex  3 . As seen in the diagram below, the oxidative addition step breaks the carbon-halogen bond where the palladium is now bound to both the halogen and the R group. 1. Oxidative Addition 6

7. Transmetalation is an organometallic reaction where ligands are transferred from one species to another. In the case of the Suzuki coupling the ligands are transferred from the organoboron species  6  to the palladium(II) complex  4  where the base that was added in the prior step is exchanged with the R 1  substituent on the organoboron species to give the new palladium(II) complex  8 . The organoboron compounds do not undergo transmetalation in the absence of base and it is therefore widely believed that the role of the base is to activate the organoboron compound as well as facilitate the formation of R 2 -Pd ll -O t Bu from R 2 -Pd ll -X . 2. Transmetalation 7

8. The final step is the reductive elimination step where the palladium(II) complex ( 8 ) eliminates the product ( 9 ) and regenerates the palladium(0) catalyst( 1 ). 3. Reductive Elimination 8

9. The ligand plays an important role in the Suzuki reaction. Typically, the phosphine ligand is used in the Suzuki reaction . Phosphine ligand increases the electron density at the metal center of the complex and therefore helps in the oxidative addition step. In addition, the bulkiness of substitution of the phosphine ligand helps in the reductive elimination step. However, N-heterocyclic carbenes ligand has recently been used in this cross coupling, due to the instability of the phosphine ligand under Suzuki reaction conditions. N-Heterocyclic carbenes are more electron rich and more bulkier than the phosphine ligand. Therefore, both the steric and electronic factors of the N-heterocyclic carbene ligand help to stabilize active Pd (0) catalyst. Role of Ligands 9

10. The Suzuki coupling reaction is different from other coupling reactions in that it can be run in biphasic organic-water, water-only, or no solvent . Use of water as a solvent system is also attractive because of the economic and safety advantages. Frequently used in solvent systems for Suzuki coupling are  toluene , THF ,  dioxane , and   DMF. T he main role of the base in the reaction mechanism is to increase the reactivity of the boronic acid toward the Pd –halide complex by converting it into the respective organoborate . The most frequently used bases are K 2 CO 3 ,KO t Bu,Cs 2 CO 3 , K 3 PO 4 ,  NaOH , and   NEt 3. Role of Solvent & Base. 10

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13. A vailability of common boronic acids. M ild reaction conditions, and its less toxic nature . It is easy to remove the inorganic by-products from the reaction mixture . T his reaction is preferable because it uses relatively cheap and easily prepared reagents. more economical, eco-friendly, and practical to use with a variety of water-soluble reagents . A wide variety of reagents can be used for the Suzuki coupling, e.g., aryl- or vinyl- boronic acids and aryl- or vinyl-halides . In addition to many different type of halides being possible for the Suzuki coupling reaction, the reaction also works with  pseudohalides  such as  triflates  ( OTf ), as replacements for halides. Advantages 13

14. Generally aryl halides react sluggishly By-products such as self – Coupling products are formed because of solvent-dissolved oxygen. Disadvantages 14

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