2. 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. 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.
Suzuki Cross Coupling Reaction
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. 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.
TRANSMETALATION
7. 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
REDUCTIVE ELIMINATION
8. 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!
ADVANTAGES
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
10. Polyene antibiotic
Cost-effective for use in the synthesis of intermediates for
pharmaceuticals or fine chemicals.
INDUSTRIAL APPLICATION
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
APPLICATION
11. 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
Sonogashira cross-coupling reaction
13. The Sonogashira coupling is applied in the synthesis
of cross-conjugated oligo(phenylene enynylene)s and
phenanthroline derivatives.
SCOPE AND LIMITATION
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).
Editor's Notes
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
