Suzuki reaction

Suzuki Reaction with its reaction mechanism and applications.

1. SUZUKI REACTION SUZUKI MIYAURA REACTION SUZUKI COUPLING REACTION SUBMITTED BY : RINSHANA FATHIMA ABDUL AZEEZ FIRST YEAR M.PHARM PHARMACEUTICAL CHEMISTRY AL SHIFA COLLEGE OF PHARMACY

2. Suzuki reaction is the Pd catalysed cross coupling reaction [1] between the boronic / organoboronic acids / organoboranes with organic halides [2] , triflates, etc under basic conditions [3] which leads to the formation of carbon carbon single bonds. [4] This reaction is commonly used for synthesising biaryl compounds.

3. GENERAL SCHEME

4. STEP 1 - Oxidative Addition - 2 groups adds to the metal. MECHANISM

5. STEP 2 - Hydroxide attacks Pd, kicking off X

6. STEP 3 - Lewis base (OH － ) attacks Lewis acid (B) The Organo Boron has only 3 bonds around it and it is sp 2 hybrised with an empty p orbital, making it a very good lewis acid.

7. STEP 4 - Transmetallation. Carbon will attach to a metal that has an electronegativity closer to it. Electronegativity Values C = 2.5 B = 2.0 Pd = 2.4

8. STEP 5 - Reductive Elimination - 2 groups are removed from a metal.

9. ADVANTAGES Mild reaction conditions. (From 20-80℃) Commercial availability of many boronic acids. The inorganic by-products are easily removed from the reaction mixture, making the reaction suitable for industrial processes

10. Generally aryl halides react sluggishly. By-products such as self-coupling products are formed because of solvent-dissolved oxygen. DISADVANTAGES

11. Development of catalysts facilitating coupling of unreactive aryl halides. Eg: Ni catalysts have been used as catalysts for coupling aryl chlorides, for the following reasons. No handling of air or moisture - sensitive material is necessary. A wide variety of functional groups are tolerated and unsymmetrical biaryls are obtained in high yields. ADVANCEMENTS

12. Xenbucin 1, an analgesic drug, was synthesized in 4 steps using two different routes. The biaryl fragment could successfully be produced via a Pd/C catalysed Suzuki coupling [5] SYNTHETIC APPLICATIONS

13. Boscalid, a fungicide is prepared via Suzuki reaction. [6]

14. In Valsartan, the biaryls can easily be prepared by this reaction. [6]

15. The formal total synthesis of Oximidine by G.A.Molander et al. was done by using this reaction. [4]

16. The key step in the total synthesis of Myxalamide A by C.H. Heathcock et al. was Suzuki Cross-Coupling.

17. The natural anti tumour product Epothilone A was synthesized in the laboratory by J.S. Panek by using the Suzuki Cross Coupling Reaction.

18. REFERENCE Jie Jack Li; Name Reactions: A Collection of Detailed Mechanisms and Synthetic Applications Fifth Edition; Springer Science & Business Media, 30-Jan-2014; Page no. 544 Benny K G Theng; Clay Mineral Catalysis of Organic Reactions; CRC Press, 27-Jul-2018; Page No.2016 Ranjit S. Dhillon; Hydroboration and Organic Synthesis : 9-Borabicclo [3.3.1] nonane (9-BBN); Springer Science & Business Media; 01 - May - 2007; Page No. 523 Laszlo Kurti, Barbara Czako; Strategic Applications of Named Reactions in Organic Synthesis; Elsevier, 29-Apr-2005; Page no. 37

19. Noora KuulojaTuula KylmäläYoujun XuRobert Franzén; Synthesis of Xenbucin using Suzuki reaction catalyzed by Pd/C in water; Central European Journal of Chemistry; September 2008, Volume 6, Issue 3, pp 390–392 .A. MAUREEN ROUHI, C&EN WASHINGTON;FINE CHEMICALS Suzuki-coupling chemistry takes hold in commercial practice, from small-scale synthesis of screening compounds to industrial production of active ingredients; American Chemical Society; September 6, 2004 Volume 82, Number 36 pp. 49-58

20. THANK YOU