NAME : PRANAV ARUN PATIL

ROLL NO: A007

SR NO. TOPIC PAGE NO.

1 Introduction
2 -Bonding of Pd with olefins.
3 Application in C-C bond
formation.
4 Cross-coupling of organometallics
and halides
5 Representative reactions:
Heck reaction
Suzuki-miayura coupling
Sonogashira reaction
6 References
• Palladium (Pd), named after the asteroid Pallas, is arguably the most versatile and ubiquitous metal in
modern organic synthesis.1,2 Palladium-mediated processes have become essential tools, spanning
countless applications in the syntheses of natural products, polymers, agrochemicals, and pharmaceuticals.
• In part, this far reaching scope is due to palladium’s ability to participate in catalytic transformations, as well
as its high functional group tolerance. Nearly every area of organic synthesis has been impacted by this
versatile transition metal, which has fundamentally changed the way retrosynthetic analysis is approached.
• In fact, there are a number of well-known name reactions that feature this metal, including the Heck, Suzuki,
Stille, and Buchwald-Hartwig cross-couplings; the Wacker process. In addition, Pd also enables
hydrogenation; hydrogenolysis; carbonylation; the formation of C–C, C–O, C–N, cycloisomerization; and
even pericyclic reactions.
• Palladium-based methods often proceed under mild conditions affording high yields, with excellent levels
of stereo-, regio-, and chemoselectivity. Domino catalysis, where multiple transformations are carried out in
a single operation, is also a powerful extension of this chemistry.
(a) (𝟐 -Alkene)palladium(Ⅱ) complexes:

The -complexes formed from palladium(Ⅱ) and monosubstituted or 1,2-disubstituted alkenes are
activated to nucleophiles, enabling reactions of the type

to be brought about; XH is usually water, an alcohol, a carboxylic acid, or a primary or secondary

amine.
The sequence of reactions, illustrated for ethylene and with water as the nucleophile, is:
 By carrying out the reaction in air and in the presence of a catalytic amount of CuCl2, Pd(0) is reoxidized
in situ,

so that only a catalytic quantity of Pd(n) is needed.

This is the basis of an important industrial method {Wacker process) for manufacturing acetaldehyde.
Monosubstituted alkenes bond to palladium through the unsubstituted carbon atom so that, for example,
reaction with water gives methyl ketones,

(b) (𝟑 -Allyl)palladium complexes:

(i) Formation. The complexes can be made from either alkenes or allyl compounds which possess
reasonable leaving groups.
• From alkenes. Reaction with PdCl2 gives, via the -alkene complex, the allylpalladium complex as a
chlorine-bridged dimer:
• From allyl compounds,with Pd(Ⅱ): Allyl acetates and other allyl compounds with leaving groups react
with by either the n-alkene route or formation of a -allylpalladium bond,

• From allyl compounds, with Pd(o): Reactions corresponding to those of allyl compounds with PdCl2
take place with Pd(PPh3)4 to give an 18-electron allyl complex which dissociates,

Since Pd(o) is regenerated on reaction with a nucleophile, only a catalytic quantity is required.
 ➢ Carbonylation:

▪ The carbonylation reaction provides one of the most useful synthetic means in transition metal-
catalyzed organic reactions.
▪ Clarification of mechanistic details in these carbonylation reactions depends much on understanding
of elementary processes of organotransition metal complexes related to the carbonylation reactions,
particularly of the behavior of the coordinated CO ligand.
▪ Two principal processes are possible for a coordinated CO ligand to be transformed in to another
type of ligand that can be later released from the transition metal complex as a product of catalytic
reaction.
▪ One is the CO insertion into a metal-to-carbon bond (eq 1) and the other is attack of an external
reagent on the coordinated CO.
▪ These elementary processes, when combined with other elementary processes such as oxidative addition
and reductive elimination, can be used to construct catalytic cycles for introducing carbon monoxide
selectively into organic compounds by means of transition metal complexes.

▪ As an example, the elementary steps involved in the palladium-catalyzed carbonylation of

a bromoarene are shown below, where oxidative addition is followed by CO insertion and reductive
cleavage by whichever nucleophile (Nu = OH, OR, NR2 or F) is present in the system.
 ➢ Alkene Isomerization:

▪ Reversible β-hydride eliminations provide a mechanism for interconverting regioisomers of an alkene,

and the following reaction sequence also illustrates another point about the reductive elimination step: it
is a syn elimination, and the C–Pd and C–H bonds have to eclipse one another for the Pd–H bond to form.
▪ Oxidative addition of the aryl iodide to a palladium(0) complex, formed from Pd(OAc)2 by reduction,
gives the active palladium(II) complex ArPdOAcL2.
▪ Carbopalladation occurs as expected on an electron-rich alkene to give the product of aryl
addition to the oxygen end of the alkene in a syn fashion. β-Hydride elimination must occur away
from the aryl group because there is only one C–H bond syn to the C–Pd bond.
▪ The alkene has moved one position round the ring.

▪ Hydropalladation in the reverse sense gives a new σ complex, which could eliminate either the
black or the green hydrogens. Elimination of the green H gives the enol ether, which is the most
stable alkene possible due to conjugation.
▪ Palladium is very sensitive to steric effects and generally forms less hindered complexes where
possible, so the palladium(II) complexes the face of the enol ether anti to Ar1.
▪ This in turn controls all the subsequent steps, which must be syn, leading to a final product with
anti stereochemistry.
▪ The requirement for syn β-hydride elimination also explains the regiochemical preference of the
elimination. In the σ-bonded cyclic structure there is only one hydrogen (green) that is syn to the
palladium; the one on the carbon bearing the naphthyl substituent is anti and cannot be eliminated.
▪ A cross-coupling reaction is a reaction where two different fragments are joined. Cross-couplings are a
subset of the more general coupling reactions. Often cross-coupling reactions require metal catalysts.
One important reaction type is this:

▪ These reactions are used to form carbon–carbon bonds but also carbon-heteroatom bonds.Cross-
coupling reaction are a subset of coupling reactions.
▪ Many mechanisms exist reflecting the myriad types of cross-couplings, including those that do not
require metal catalysts.Often, however, cross-coupling refers to a metal-catalyzed reaction of a
nucleophilic partner with an electrophilic partner.
▪ In such cases, the mechanism generally involves
reductive elimination of R-R' from LnMR(R') (L = spectator
ligand). This intermediate LnMR(R') is formed in a two
step process from a low valence precursor LnM. The
oxidative addition of an organic halide (RX) to LnM gives
LnMR(X). Subsequently, the second partner undergoes
transmetallation with a source of R'−. The final step is
reductive elimination of the two coupling fragments to
regenerate the catalyst and give the organic product
▪ Catalysts are often based on palladium, which is
frequently selected due to high functional group
tolerance. Organopalladium compounds are generally
stable towards water and air.

▪ The leaving group X in the organic partner is usually a

halide, although triflate, tosylate and other
pseudohalide have been used. Chloride is an ideal
group due to the low cost of organochlorine
compounds. Frequently, however, C–Cl bonds are too
inert, and bromide or iodide leaving groups are
required for acceptable rates.
 ➢ Heck Reaction :
• The Heck reaction couples an alkene with an organic halide or triflate R1–X to form a new alkene.

• This palladium catalysed addition of aryl,vinyl, or substituted vinyl groups to organic halides or trifl
ates is one of the most synthetically useful palladium-catalysed reactions.

• The mechanism involves the oxidative addition of the

halide, insertion of the olefin, and elimination of the
product by a β-hydride elimination process. A base
then regenerates the palladium(0) catalyst. The
whole process is a catalytic cycle.

• The Heck reaction favours one isomer, and when the

alkene is polarized by an electron-withdrawing group
the new C–C bond forms at the other end of the
alkene.
Examples :

➢ Suzuki-Miayura coupling:
• The Suzuki-Miayura reaction is the coupling of an aryl or vinylic boronic ester with an aryl or vinyl halide
using a palladium catalyst.
• It is a powerful cross coupling reaction that allows for the
synthesis of conjugated olefins and biaryls.

• Other organoboranes that are also effective in Suzuki coupling

include the following:

• The basic steps in the cross-coupling reaction include:

1. oxidative addition of the aryl or vinyl halide to Pd(0), followed
by
2. Transmetallation (the transfer of an organic ligand from the
organometallic reagent to the resulting Pd(II) intermediate).
3. The disubstituted Pd(II) intermediate then undergoes a
reductive elimination, which generates the carbon-carbon
bond coupling product and regenerates the catalytically
active Pd(0) oxidation level.
➢ Sonogashira Reaction:

• The Sonogashira reaction is a cross-coupling reaction used in organic synthesis to form carbon–
carbon bonds. It employs a palladium catalyst as well as copper co-catalyst to form a carbon–carbon
bond between a terminal alkyne and an aryl or vinyl halide.

• The reaction can be carried out under mild conditions, such as at room temperature, in aqueous
media, and with a mild base, which has allowed for the use of the Sonogashira cross-coupling
reaction in the synthesis of complex molecules.

The palladium cycle:

❖ Palladium precatalyst species are activated under reaction conditions to form a reactive Pd(0)
compound, A
❖ The active Pd0 catalyst is involved in the oxidative addition step with the aryl or vinyl halide
substrate to produce Pd(II) species B and activating aryl halide substrate for the reaction.
❖ Acetylene is activated in the second, Pd(II) mediated cycle. Phenylacetylene was proven
to form Pd monoacetylide complex D as well as Pd bisacetylide complex F under mild
reaction conditions.
❖ Both activated species,
namely complexes B
and F, are involved in
the transmetallation
step, forming complex
C and regenerating D.
❖ The resulting
products of
reductive
elimination,
disubstituted
alkyne product as
well as regenerated
Pd(0) catalytic
species, complete
the Pd(0) catalytic
cycle.
➢ Organic chemistry, Clayden, Greeves, Warren and Wothers, oxford press

➢ Palladium in organic synthesis, Tsuji

➢ Principle of organic synthesis, R.O.C. Norman and J.M. Coxon, third edition, Nelson thornes

➢ Advanced organic chemistry, Part B, Francis A. Carey, Richard J. Sundberg, fifth edition,
Springer.