1. AMITY UNIVERSITY SUZUKI AND SONOGASHIRA CROSS COUPLING REACTION
RAJASTHAN
SUZUKI AND SONOGASHIRA CROSS COUPLING REACTION
PRESENT BY
Subhrangsu Sekhar Dey
M.Sc - Applied

2. Transmetallation: Transfer of alkyl group from one metal to another
Introduction of Cross Coupling Reaction
Typically use a transition metal catalyst and an organometallic precursor
Most involve a “transmetallation step”
Transmetallation: Transfer of alkyl group from one metal to another
Typical trend: Can transfer from more electropositive to less electropositive metals

3. Suzuki Cross Coupling Reaction
Reported in 1979 by Akira Suzuki and N. Miyaura
Commonly referred to as the Suzuki cross-coupling
Palladium catalyzed cross-coupling between organoboron compounds and organic halides leading to the formation of carbon-carbon bonds.

4. REACTION MECHANISM

5. OXIDATIVE ADDITION The rate determining step of the catalytic cycle
Couples the palladium catalyst to the alkyl halide
which gives rise to the organopalladium complex
The complex is initially in the cis conformation but
isomerizes to the trans conformation
Stereochemistry with vinyl halides are retained but
inversion of stereochemistry occurs with allylic or
benzylic halides

6. TRANSMETALATION
The role of base is to activate the boron-containing reagent, and also facilitate the formation of R1Pd- OR from R1Pd-X.
Reaction does not occur in the absence of base.
Exact mechanism is unclear.

7. REDUCTIVE ELIMINATION
This final step gives the desired product and it also regenerates the palladium catalyst so that it can participate again in the catalytic cycle.
Require the complex to revert back to the cis
conformation before reductive elimination can occur

8. ADVANTAGES Mild Reaction Conditions
Availability of common boronic acids
Inorganic by-products are easily removed from reaction mixture.
Stereoselective
Less toxic than other competitive methods, (ie. Boronic acids are environmentally safer and less toxic than organostannanes)
Reaction will take place in the presence of other functional groups (ie. protecting group is not always necessary)
Relatively cheap reagents, easy to prepare, and GREEN!

9. Typically use a palladium catalyst in the 0 oxidation state:
Typically, triphenylphosphine and triorthotolylphosphine is the ligand used to activate the palladium.
Can also be ligandless such as Pd/C
Easier to handle (other ligands may be air-sensitive)
Remove by simple filtration (recover, purify, and reuse)
In recent years, Nickel catalysts have become popular:
Not as expensive as Pd
More abundant than Pd
Need higher catalyst loading
Mechanism not fully understood
VARIATION
The first nickel catalyzed cross-coupling reaction was reported by Miyaura and co-workers in 1996 using aryl chlorides and boronic acids, Miyaura and Inada reported in 2000 that an cheaper TRIPHENYL, fact that this reaction can be run in biphasic(aqueous and organic

10. APPLICATION INDUSTRIAL APPLICATION Polyene antibiotic
Cost-effective for use in the synthesis of intermediates for pharmaceuticals or fine chemicals.
SYNTHETIC APPLICATION
Isolated from the bacterium Myxococcus xanthus.
The Suzuki coupling has been used on a citronellal derivative for the synthesis of caparratriene, a natural product that is highly activeagainst leukemia.
The last step in thesynthesis of Myxalamide A
Observed to have antibiotic and antifungal activity

11. Sonogashira cross-coupling reaction
The Sonogashira cross-coupling reaction was first reported by Kenkichi Sonogashira, Yasuo Tohda, and Nobue Hagihara in their 1975 publication.
Sonogashira uses both palladium and copper catalysts simultaneously which inceases the reactivity.
Highly useful reaction in the alkynylation of aryl and alkenyl halides

12. MECHANISM

13. Copper-free reaction/Variation
SCOPE AND LIMITATION
The Sonogashira coupling is applied in the synthesis
of cross-conjugated oligo(phenylene enynylene)s and
phenanthroline derivatives.
Copper-free reaction/Variation
Unwanted dimerization
To avoid the formation of the homocoupling products

14. APPLICATION Its applications pharmaceuticals, natural products,
organic materials, and nanomaterials.
Sonogashira reaction use in the synthesis of tazarotene, which is a treatment for psoriasis and acne
The preparation of SIB-1508Y, also known as Altinicline, which is a potential treatment for Parkinson’s disease, Alzheimer’s disease, Tourette syndrome, schizophrenia, and attention deficit hyperactivity disorder (ADHD).

15. Thank You