A coupling reaction in organic chemistry is a general term for a variety of reactions where two hydrocarbon fragments are coupled with the aid of a metal catalyst.

1. By
MUHAMMAD SHAKAIB QURESHI
M.PHIL-CHEMISTRY
CHEM-2017-717
INSTITUTE OF CHEMISTRY
SHAH ABDUL LATIF UNIVERSITY KHAIRPUR MIRS
COUPLING REACTIONS
INSTITUTE OF CHEMISTRY
SHAH ABDUL LATIF UNIVERSITY
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1.SUZUKI-MIYAURA REACTION--1979
2.SONOGASHIRA REACTION--1975

2. TABLE OF CONTENT
• Introduction
• Suzuki Miyaura Reaction
– Oxidative Addition, Transmetalation, Reductive
Elimination
– Mechanism and Example
– Why Palladium is used in Suzuki Reaction
– Advantages and Application
• Sonogashira Reaction
– Mechanism
– Example
– Application
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3. COUPLING REACTIONS
• A coupling reaction in organic chemistry is a
general term for a variety of reactions where
two hydrocarbon fragments are coupled with the
aid of a metal catalyst.
• It is divided into two broad classes
– Homocoupling, in which two identical partners are
couple to form a new molecule i.e Wurtz coupling
– Hetro Coupling/ C-C Cross Coupling, C-C Bond
formation Between Organohalide R’—X (E) and a
Organometallic R’’—M (Nu) in the presence of
Transition Metal Catalyst, usually Palladium (Pd), i-e
Suzuki Miyaura Reaction, Sonogashira Reaction etc
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4. Suzuki—Miyaura Reaction
Wurtz Coupling
Take place in the presence of Palladium Catalyst,
catalyzed cross—coupling C—C Bond Forming
reaction Between Aryl-vinyl and Boronic Acid.
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5. Suzuki—Miyaura Reaction
Getting Start
• OXIDATION ADDITION
• 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 is coupled with the
alkyl halide to yield an
organopalladium complex.
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6. 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 to the
palladium(II) complex.
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7. REDUCTIVE ELIMINATION
• The final step is the
reductive elimination
step where the
palladium(II) complex
eliminates the product
and regenerates the
palladium(0) catalyst.
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8. Suzuki—Miyaura Reaction
Mechanism
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11. PHARMACEUTICAL PRODUCT
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Singulair (montelukast) is a
leukotriene inhibitor.
Leukotrienes are chemicals your
body releases when you breathe
in an allergen (such as pollen).
These chemicals cause swelling
in your lungs and tightening of
the muscles around your
airways, which can result in
asthma symptoms.
Sensipar (cinacalcet) decreases
levels of parathyroid hormone
(PTH), calcium, and phosphorous
in the body.
Sensipar is used to
treat hyperparathyroidism
(overactive functioning of the
parathyroid glands) in people
who are on long-term dialysis for
kidney disease.
Celebrex is used to treat pain or
inflammation caused by many
conditions such
as arthritis, ankylosing
spondylitis, and menstrual pain.
Celebrex is used to treat juvenile
rheumatoid arthritis in children
who are at least 2 years old.

12. WHY PALLADIUM CATALYST?
• Due to two main reasons
– Simultaneously availability of Empty and filled
Non-bonding Orbital, because of the Synergic
bonding occurs.
– Ready and reversible oxidation and reduction
under one set reaction condition.
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13. ADVANTAGE OF SUZUKI REACTION
• 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!
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14. APPLICATION
• INDUSTRIALAPPLICATION
• 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 the synthesis of Myxalamide A Observed
to have antibiotic and antifungal activity
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15. SONOGASHIRA REACTION
Pd-cataltzed coupling reaction of terminal Alkynes with Aryl or vinyl halides
using an amine base and CuI as Co—catalyst
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16. SONOGASHIRA REACTION
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17. SONOGASHIRA REACTION
• THE PALLADIUM CYCLE
• An inactive palladium PdII catalyst is activated by a
reduction to the Pd0 compound.
• The active palladium catalyst is the 14 electron compound
Pd0L2, complex A, which reacts with
the aryl or vinyl halide in an oxidative addition to produce
a PdII intermediate, complex B. This step is believed to be
the rate-limiting step of the reaction.
• Complex B reacts in a transmetallation with the
copper acetylide, complex F, which is produced in the
copper cycle, to give complex C, expelling the copper
halide, complex G.
• Both organic ligands are trans oriented and convert to cis
in a trans-cis isomerization to produce complex D.
• In the final step, complex D undergoes reductive
elimination to produce the alkyne, with regeneration of the
palladium catalyst.
• THE COPPER CYCLE
• It is suggested that the presence of base results in the
formation of a pi-alkyne complex, complex E, which
makes the terminal proton on the alkyne more acidic,
leading to the formation of the copper acetylide,
compound F.
• Compound F continues to react with the palladium
intermediate B, with regeneration of the copper halide, G. 17

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20. APPLICATION OF SONOGASHIRA REACTION
• 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).
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21. THANK YOU
• Think Like a Proton and
Stay Positive.
Muhammad Shakaib Qureshi
M.Phil Chemistry
Email
muhammad.shakaib786@gmail.com
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