PALLADIUM CATALYSED REACTIONS

Presented by :
A . Sowmya
HT.NO:20004P-1029
M. Pharmacy 1st year, 1st semester
Department of pharmaceutical
chemistry
Kakatiya University, Warangal.
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CONTENTS
 Introduction
 Metallic derivatives of pyridine

 Palladium catalysed reactions

 Cross coupling reactions

 Oxidation and Reduction Reactions of Pyridine

 Conclusion

 References

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METALLIC DERIVATIVES OF PYRIDINE

 Pyridine Reaction with lithium:

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 Pyridine Reaction with Mercury:

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PALLADIUM CATALYSED REACTIONS
Transition-metal-catalyzed reactions are the most
important area in synthetic organic chemistry. They
have been used extensively in the ring synthesis.

Transition metals have a unique ability to activate

various organic compound and through this activation
they can catalyse the formation of new bonds.

In general, transition metals, and in particular

palladium, have been of importance per the
development of reactions for the formation of Carbon-
Carbon bonds. 5
 In 2005 ,the Nobel prize in chemistry was awarded
to metal catalysed reactions for the formation of
Carbon-Carbon double bonds.
 Again the noble prize in chemistry is awarded to the
formation of C-C single bonds through palladium-
catalysed cross-coupling reactions.

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CROSS COUPLING REACTIONS
 The reaction occurs between organometallic with
organic halide with the aid of a metal containing
catalyst.
 Coupling reaction can be divided into main
classes, cross coupling 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.
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GENERAL MECHANISM OF PALLADIUM
CATALYZED REACTIONS

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 STEPS INVOLVED IN PALLADIUM
CATALYZED REACTIONS
 Each cycle starts by oxidative addition of an organohalide (I, Br, Cl)
to a palladium(0) species a triflate or diazonium salt to generate an
organo-palladium(II) species.

 The second step of the reaction is the transmetallation process. In this

process an organic moiety is transferred from a main group metal, e.g.
Mg, Cu, Zn, Sn, B or Si, to a metal that is more electronegative, such
as palladium, to give a diorganopalladium complex.

 In the last step of the reaction, this complex undergoes a reductive

elimination to create a carbon-carbon bond and the palladium catalyst
is regenerated. 9
TYPES OF COUPLING REACTIONS
 The Heck Reaction
 The Stille Reaction

 The Suzuki Reaction

 The Sonogashira Reaction

 The Negishi Reaction

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THE HECK REACTION
 The C-C coupling between Aryl/Vinyl and
Activated alkenes in presence of base is referred
as “HECK REACTION”.

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MECHANISM OF HECK REACTION

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MECHANISM OF HECK REACTION
 Step A is the oxidative addition of a polar substrate onto
a palladium catalyst to form a tetrasubstituted complex.
 Step B is the migratory insertion of an olefin into the
system.
 Step C is the β-Hydride Elimination of the alkene.
 Step D is the addition of base to the palladium to
regenerate the starting catalyst and close the cycle.

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THE STILLE REACTION
 The reaction between Alkyl stannaners and
Aryl/Aliphatic halides in presence of palladium catalyst
gives rise to Alkyl-Aryl/Aliphatic compound is referred
as “STILLE REACTION”.

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MECHANISM OF STILLE REACTION

The catalytic cycle involves an oxidative addition of a halide or

pseudohalide (2) to a palladium catalyst (1),
transmetalation of 3 with an organotin reagent (4),
and reductive elimination of  5 to yield the coupled product (7)
and the regenerated palladium catalyst (1) 15
THE SUZUKI REACTION
 The reaction between Alkyl boranes and Aryl/Aliphatic
halides in presence of palladium catalyst gives rise to
Alkyl-Aryl/Aliphatic compounds is referred as
“SUZUKI REACTION”.

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MECHANISM OF SUZUKI REACTION

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 THE OXIDATIVE ADDITION STEP
 In this step, the oxidation of the catalytic palladium takes place.
It is oxidized form palladium(0) to palladium(II). This step is
generally the rate determining step of the cycle. The reaction in
this step is the coupling of the alkyl halide with the palladium
catalyst. The product formed in this step is an organopalladium
complex where the carbon-halogen bond is broken and the
palladium inserts itself in between the R group and the halogen.
This step can be illustrated as

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THE TRANSMETALATION STEP
 In this step, an organometallic reaction occurs and
a ligand transfer takes place from the organoboron specimen to
the palladium(II) complex. The organoborane compound reacts
with the first intermediate upon the addition of a base. This
gives another palladium(II) complex as shown below.

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THE REDUCTIVE ELIMINATION STEP
 Now, the palladium(II) complex proceeds to eliminate the
required product and is converted into the palladium(0) form.
Thus the catalyst is regenerated and the catalytic cycle is
ended. This step can be illustrated as:

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THE SONOGASHIRA REACTION
 The reaction takes place between terminal Alkyl and
Aryl/Vinyl halide in presence of palladium catalyst is
referred as “SONOGASHIRA REACTION”.

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THE NEGISHI REACTION

 The reaction between organo halides or triflates and organo

zinc compounds in presence of nickel-catalyst or palladium-
catalyst to form Carbon-Carbon bonds is referred as
“NEGISHI REACTION”.

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MECHANISM OF NEGISHI REACTION

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MECHANISM OF NEGISHI REACTION
 The Negishi cross-coupling reaction is the organic reaction of an
organohalide with an organozinc compound to give the coupled
product using a palladium or nickel catalyst. The palladium
catalyzed mechanism begins with oxidative addition of the
organohalide to the Pd(0) to form a Pd(II) complex.
 Transmetalation with the organozinc then follows where the R
group of the organozinc reagent replaces the halide anion on the
palladium complex and makes a zinc(II) halide salt. Reductive
elimination then gives the final coupled product, regenerates the
catalyst, and the catalytic cycle can begin again.

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OXIDATION OF PYRIDINE:
 Oxidation of pyridine occurs at nitrogen to give pyridine
N-oxide.
 Pyridine N-oxide is formed by oxidation of pyridine in
the presence of hydrogen peroxide or peracid

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REDUCTION OF PYRIDINE:
 Pyridine is easily reduce to hexahydropyridin or
piperdine by a variety of method including hydrogen
over raney nickel,rubidium at 60C palladium charcoal
with acetic acid,1,4 dihydropyridine has however been
obtained by the reduction of pyridine with
trimethylsilane.

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CONCLUSION
 Palladium is the most versatile and ubiquitous metal in
modern organic synthesis .
 It is used as catalyst has allowed the discovery of new
reactions.
 Heck, Negishi and Suzuki cross coupling together with
other Pd catalyzed reactions are frequently used in drug
synthesis.
 The study of Pd complexes is still in progress, so new
reactions , impossible to perform so far, could appear in
the future.

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REFERENCE
1. J.A Joule and k. Mills, Heterocyclic chemistry,
fifth edition, page no:54-65, 75-85
2. G.D Guptha, Basic organometallic chemistry,
page no:287-308, palladium catalysed C-C and
C-N cross coupling reactions.
3. Bhupinder Mehta and Manju Mehta, Organic
chemistry, 2nd edition page no 901-923
4. O.P Agarwal , Organic chemistry, page no:949-
976
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