Mechanism and synthetic application of suzuki reaction

The Suzuki reaction is an organic reaction, classified as a cross-coupling reaction, where the coupling partners are a boronic acid and an organohalide catalyzed by 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.

1. 1 Mechanism & Synthetic Application of SUZUKI REACTION Presented by Rudraprasad Sahoo M. Pharm 1 st semester Department of Pharmaceutical Chemistry Institute of Pharmacy & Technology, Salipur .

2. Contents Stats about Akira Suzuki Reagents and solvent systems About the chemical reaction Mechanism of Suzuki reaction Some synthetic uses of Suzuki reaction References 2

3. Some stats about Akira Suzuki Born September 12, 1930 Place- Mukawa , Hokkaidō,Japan Nationality - Japanease Alma mater Hokkaidō University Known for Suzuki reaction Awards Nobel Prize for Chemistry ( 2010) Person of Cultural Merit ( 2010) Order of Culture (2010 ) 3

4. The reagents and solvents Reagents Palladium metal Sodium tert. Butoxide Organoborane compounds Sodium Carbonate Solvents Benzene Toluene Tetrahydro Furan Dimethyl Formamide 4

5. What is Suzuki reaction The Suzuki reaction is an organic reaction, classified as a cross-coupling reaction, where the coupling partners are a boronic acid and an organohalide catalyzed by a palladium complex. 5

6. Mechanism of Suzuki reaction 1. The first step is the oxidative addition of palladium to the halide to form the organo-palladium species. 2. Reaction with base gives intermediates which via transmetalation with the boronate complex , forms the organo-palladium species . 3. Boronate complex is produced by reaction of boronic acid with base. 4. Reductive elimination of the desired product restores original palladium catalyst that completes the reaction cycle. 6

7. Mechanism of S uzuki reaction 7

8. Oxidative Addition 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 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. 8

9. Continued 9

10. Transmetalation 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 R1 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 R2-Pdll-OtBu from R2-Pdll-X . 10

11. Continued 11

12. Reductive Elimination 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 ). Ridgway et al. have shown the reductive elimination proceeds with retention of stereochemistry . 12

13. Continued 13

14. Synthetic application of Suzuki reaction Besides a wide range of industrial uses, The synthetic application of Suzuki reaction is the synthesis of some complex natural compounds like caparratriene, a derivative of citronellel, an anti leukemic drug . 14

15. Industrial uses of the Suzuki reaction Another example is the coupling of 3-pyridylborane and 1-bromo-3-(methylsulfonyl)benzene that formed an intermediate that was used in the synthesis of a potential central nervous system agent. 15 3-pyridylborane 1-bromo-3- ( methylsulfonyl)benzene

16. Reference   Miyaura , Norio; Yamada, Kinji ; Suzuki, Akira (1979).  "A new stereospecific cross-coupling by the palladium- catalyzed reaction of 1-alkenylboranes with 1-alkenyl or 1-alkynyl halides". Tetrahedron Letters.  20  (36): 3437–3440. doi:10.1016/S0040-4039(01)95429-2. hdl:2115/44006 .   Miyaura , Norio; Suzuki, Akira (1979). " Stereoselective synthesis of arylated (E)-alkenes by the reaction of alk-1-enylboranes with aryl halides in the presence of palladium catalyst". Chem. Comm.   (19): 866–867. doi:10.1039/C39790000866 .   Miyaura , Norio; Suzuki, Akira (1995). "Palladium- Catalyzed Cross-Coupling Reactions of Organoboron Compounds". Chemical Reviews.  95  (7): 2457–2483. CiteSeerX 10.1.1.735.7660. doi:10.1021/cr00039a007.   Nobelprize.org. "The Nobel Prize in Chemistry 2010". Nobel Prize Foundation. Retrieved 2013-10-25.   Suzuki, Akira (1991). "Synthetic Studies via the cross-coupling reaction of organoboron derivatives with organic halides". Pure Appl. Chem.  63  (3): 419–422. doi:10.1351/pac199163030419.   Miyaura , Norio; Suzuki, Akira (1979). "Palladium- Catalyzed Cross-Coupling Reactions of Organoboron Compounds". Chemical Reviews.  95  (7): 2457–2483. CiteSeerX 10.1.1.735.7660. doi:10.1021/cr00039a007. (Review) 16

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