cross coupling reaction

2. DEPARTMENT OF CHEMISTRY AND SCHOOL OF BASIC AND APPLIED SCIENCE GUIDED BY:- Dr. VIRENDRA SINGH ASSOCIATE PROFESSOR CENTRE OF CHEMISTRY SCHOOL OF BASIC AND APPLIED SCIENCE CENTRAL UNIVERSITY OF PUNJAB SUBMITTED BY:- RAJESH SAHOO M.sc CHEMISTRY (Specialized Applied Chemistry) 20Mschac10

3. Palladium- Catalysed Cross- Coupling Reactions 2010 Nobel Prize Awarded to Richard Heck, Ei-ichi Negishi, and Akira Suzuki AlfredNobel

4. CONTENTS:- CROSS COUPLING REACTION WHAT IS C-C CROSS COUPLING IMPORTANCE OF COUPLING REACTION MECHANISM OF COUPLING REACTION WHY PALLADIUM ? DIFFERENT TYPE OF COUPLING RECTIONS CONCLUSION

5. COUPLING REACTION • A coupling reaction in organic chemistry is a general term for a variety of reactions where two fragments are joined together with the aid of a metal catalyst . • Coupling reactions can be divided into two main classes, cross couplings in which two different molecules react to form one new molecule. • The other type of coupling is homocoupling, in this reaction two similar molecules coupling together to form a new molecule

6. What are C-C cross couplingreactions? • The C-C bond formation between an organic electrophile (RX) and a nucleophile (Organometallic R’M or R’-C=C) in the presence of a transition metal catalyst,usually Pd (even Cu, Ni, Fe etc are alsoused)

7. Mainfeatures • Common metal used in this field is Pd,in addition to Zn, Ni, Cu, B, andSn • Most of coupling reactions are air andwater sensitive?? • But, some coupling reactions can becarried out in aqueoussolutions

8. Applications of Coupling Reactions • Coupling reactions are employed in the synthesis of several pharmaceutical products. • Many conjugated polymers are prepared via coupling reactions that involve the use of a metal catalyst • Many natural products can be obtained via certain coupling reactions. For example, benzylisoquinoline alkaloids can be synthesized with the help of the Sonogashira cross-coupling reaction

9. Important couplingreactions R-MgBr

11. Palladium is a d-block transitionmetal. • Pd favours the formation of tetrahedral d10 and square planar d8 complexes of low oxidation states (0 and II respectively). • This feature affords Pd good electron-donating and electron-accepting capabilities, allowing fine-tuning by altering the electronic properties of itsligands. • Pd may easily participate in concerted processes due to its closely lying HOMO and LUMOenergies. • Pd complexes tend to be less sensitive to oxygen and are lesstoxic.

12. Cross coupling between aryl or alkyl Grignard with aryl or vinylhalocarbon

15. APPLICATION OF KUMADA COUPLING:- Synthesis of Aliskiren The Kumada coupling is suitable for large-scale, industrial processes, such as drug synthesis. The reaction is used to construct the carbon skeleton of aliskiren (trade name Tekturna), a treatment for hypertension

18. The catalytic cycle for the Heck reaction involves a seriesof transformations around the palladium catalyst. The palladium(0) compound required in this cycle is generally prepared in situ from a palladium(II)precursor Step A is an oxidative addition in which palladium inserts itself in the aryl to bromide bond Palladium then forms a π complex with the alkene (3) In step B the alkene inserts itself in the palladium - carbon bond in a syn addition step Step C is a beta-hydride elimination step with the formation of a new palladium - alkene π complex (5) This complex is destroyed in the next step The palladium(0) compound is regenerated by reductive elimination of the palladium(II) compound by potassium carbonate in the final step,D

19. ADVANCES OF HECK REACTION:- Ionic liquid Heck reaction In the presence of an ionic liquid a Heck reaction proceeds in absence of liquid (bmim)PF6 are immobilized inside the cavities of reversed-phase silica gel. In this way the reaction proceeds in water and the catalyst is re-usable. Heck oxyarylation In the Heck oxyarylation modification the palladium substituent in the syn-addition intermediate is displaced by a hydroxyl group and the reaction product contains a dihydrofuran ring. Amino-Heck reaction n the amino-Heck reaction a nitrogen to carbon bond is formed. In one example, an oxime with a strongly electron withdrawing group reacts intramolecular with the end of a diene to form a pyridine compound. The catalyst is tetrakis(triphenylpaphosphorus ligand. In one modification palladium acetate and the ionic hosphine)palladium(0) and the base is triethylamine

20. The general scheme for the Suzuki reaction is shown below where a carbon-carbon single bond is formedby coupling an organoboron species (R1-BY2)with a halide (R2-X) using a palladium catalyst and abase.

21. REACTIONMECHANISM

22. Nigishicoupling Pd or Ni catalysed couplingorganozinc compounds with aryl, vinyl, benzyl halides.

23. Nigishicoupling

24. All the C-C cross-couplings reaction broadly follow the same catalytic cycle, which involves number ofprocesses. • Heckreactionfollowsaslightlydifferentpathwayfromother • C-Ccouplings. • Rate-determining step depends on the nature of the electrophile, nucleophile, and the ligands onpalladium. • Recently many C-C coupling reactions catalyzed by Ni(0),Pt(0), • or Cu(I) also. Mayfollowthe similar reactionschemes. • Future scope is that various transition metals are available, you can try some other organic reaction with some other metal and can lead to be a new Nobel prizespathway.

25. References • Palladium- Catalysed Cross-Coupling: A Historical Contextual Perspectiveto the 2010 Nobel Prize Dr. Carin C. C. Johansson Seechurn, Dr. Matthew O. Kitching • https://en.wikipedia.org/wiki/Coupling_reaction • Organic chemistry. 2nd edition, David R. Klein, wiley publication house , December 2013 • P Prediger, Allan R d Silva, C Roque, D Correia, of3-arylpropylamines using Heck arylations. The total synthesis of cinacalcet hydrochloride, alverine,and tolpropamine, Tetrahedron, 70(20),PP:-3333-3341