The document discusses palladium-catalyzed cross-coupling reactions, which were awarded the 2010 Nobel Prize in Chemistry. It summarizes the key reactions including Suzuki, Negishi, Stille, Sonogashira, and Heck reactions. These reactions involve the coupling of organic electrophiles and nucleophiles through oxidative addition, transmetallation, migratory insertion, and reductive elimination steps using a palladium catalyst. The document also discusses the mechanisms and factors influencing these important C-C bond forming reactions.

1. Presented By:
Rashmi Gaur
Research Scholar
C /o Prof. R.K Sharma

2. Prof. Akira Suzuki
Prof. Richard
F. Heck Prof. Ei-ichi
Negishi
1. Importance of chemical processes in
the pharmaceutical and industries.
2. The key steps in building complex
molecules from simple precursors.
The Nobel Prize was
awarded jointly to
Richard F. Heck, Ei-ichi
Negishi and Akira
Suzuki for Palladium-
catalyzed C-C cross
coupling reaction in
2010.

3. 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 also used).

4. 5.
HECK
(1972)
4.
SONOGASHIRA
(1975)
3.
NEGISHI
(1977)
2. STILLE
(1978)
1. SUZUKI-
MIYAURA
(1979)

6. Negishi- M= Organiozincompound
Suzuki- M= Organoboran compound
Stille-M= organotin compound
Heck-Mizoroki
Negishi –R1-M= Organozinc compound
Stille- R1-M = Organotin compound
Suzuki- R1-M = Organoborane compound

8. CuI can increase the
reaction rate and
ability to scavenge
the free ligand.

9. • Variable oxidation states and coordination number
Metals are Lewis acid (electron deficient):- origin of
Chemical reactivity.
There are some other type of lewis acid.
One way
interaction only.

10. RepulsionTwo major reasons are:-
1. Simultaneous availability of empty and filled non bonding orbitals ,
because of that Synergic bonding occurres.
2. Ready and reversible oxidation and reduction under one set of reaction
condition.
Charge polarization can be cancelled. Hence required very less energy
barrier.
Two way
interaction

11. Palladium is a d-block transition metal.
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 its ligands.
 Pd may easily participate in concerted processes due to
its closely lying HOMO and LUMO energies.
Pd complexes tend to be less sensitive to oxygen and
are less toxic.

12. The oxidative addition of organic electrophiles (halides, sulfonates, and
related activated compounds) to Pd(0) is the first step in cross-coupling.
• Increases both the oxidation state and coordination number of a
metal centre.
• In order for the oxidative addition to succeed, the formation of a low-
coordinate Pd(0)-species is required (e.g. the formation of 14-electron
Pd-species, L2Pd(0)).
• Oxidative additions may proceed via two major pathways that depend
on the metal center and the substrates (also any added additives,
metal-bound ligands and solvent).

13. Concerted Mechanism : Normally found in addition of non-polar
reagents and aryl halides. Retention of configuration is in case of
chiral A-B reagents.
SN2 Mechanism : Its an associative bimolecular process. Often
found in oxidative additions of polar reagents and in polar
solvents. Oxidative addition of C(sp3)-X electrophiles to Pd(0)
complexes PdL4 (L =phosphine) takes place usually by this
mechanism. Results in inversion of configuration

14.  Predominant retention in noncoordinating solvents as benzene, CH2Cl2,
tetrahydrofuran (THF), or acetone.
 On the other hand, in coordinating solvents such as MeCN or dimethylsulfoxide
(DMSO), complete or near-complete inversion was observed .
 Electron-withdrawing substituents on aryl electrophiles led to rate acceleration.
Higher the electron density on metal , more favours the oxidative addition.
Electron rich and bulky phosphine ligands, enhances reactivity of transition metal

15. • Transmetallation reactions involve the transfer of an
organic group R from one metal M to another one M.
Transmetallation in the Suzuki Reaction:
• Due to the low nucleophilicity of the borane reagents
(compared with organostannanes, for example), the Suzuki
reaction requires the use of base in order to take place.
• The main role of base is to generate a more reactive borate by
coordination of hydroxide to boron, which will react with the
intermediate R-Pd(II)-X complex.

16. • It is the reverse of oxidative addition.
• Reductive elimination involves the elimination or expulsion of
a molecule from a transition metal complex. In the process of
this elimination, the metal centre is reduced by two electrons.
• The groups being eliminated must be in a mutually cis
orientation

17. • A carbometallation reaction is defined by the addition of a
carbon-metal bond of an organometallic 1 across a carbon-
carbon multiple bond 2, leading to a new organometallic 3, in
which the newly formed carbon-metal bond can be used for
further transformations.
• This step is subsequently followed by a syn-insertion process
.(resulting in a σ-organopalladium intermediate ).
• This process is sensitive not only to steric but also electronic
factors, which in turn influences the regiochemical outcome of
the reaction.

18. β-
The beta-hydride elimination can either be a vital step in
a reaction or an unproductive side reaction.
.

19. • β-Hydride elimination may occur if a β-hydrogen is accessible.
• C-C bond rotation of intermediate D is required, as well as a coordination
vacancy on the metal centre.
• Then cis β-hydrogen elimination takes place, generating a coordinated
palladium hydride complex E. The hydridopalladium species is subsequently
liberated from E, producing complex F and the free Mizoroki-Heck product G

20. • All the C-C cross-couplings reaction broadly follow the same
catalytic cycle, which involves number of processes.
• Heck reaction follows a slightly different pathway from other
C-C couplings.
• Rate-determining step depends on the nature of the
electrophile, nucleophile, and the ligands on palladium.
• Recently many C-C coupling reactions catalyzed by Ni(0), Pt(0),
or Cu(I) also. May follow the similar reaction schemes.
• 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 prizes pathway.

21. Metal-Catalyzed Cross-Coupling Reactions, 2nd Edition. Wiley -
Edited by Armin de Meijere, Franois Diederich
https://www.youtube.com/watch?v=B3Oz90EfNO0(Nobel Prize
Lectures in Uppsala 2010 - Chemistry Laureate Ei-ichi Negishi)

22. Any Questions?