COMPANY PROFILE
PARTNER FOR COOPERATION
VUOS
Cross coupling reactions
Cross coupling reactions
A coupling reaction in organic chemistry is a catch-all
term for a variety of reactions where two hydrocarbon
fragments are coupled with the aid of a metal catalyst with
formation of a new carbon-carbon bond in the product.
Cross couplings involve reactions 2between two different
partners
and homocouplings couple
two identical partners,
SYNTHESIA,
AGROFERT
HOLDING, a.s.
100%
a.s.
100%
VUOS developed all types of cross
couplings reactions which are widely used in the
production of organic specialties mainly for production
of pharmaceutical intermediates and many others
organic specialties.
2
VUOS – PARTNER FOR COOPERATION
VUOS, a.s.
SUZUKI REACTION
The reaction is a coupling of an aryl- or vinyl-boronic acid with
an aryl-halide catalyzed by a palladium complex.
R
HO
B
X
catalyst
R'
R
R'
HO
It is widely used to synthesize poly-olefins, styrenes, and
substituted biphenyls.
3
Example
AGROFERT
HOLDING, a.s.
Br
100%
SYNTHESIA,
O Ha.s.
B
OH
COOH
COOH
I
OH
B
OH
C H3
3
VUOS – PARTNER FOR COOPERATION
C H3
VUOS, a.s.
100%
NEGISHI REACTION
The cross coupling reaction involving an organozinc compound,
an organic halide and a nickel or palladium catalyst creating a
new carbon-carbon covalent bond.
catalyst
R
X
R' Zn X
R
R'
It can be used for syntheses of wide range of organic.
4
Example
CN
C F3
ZnBr
CN
F 3C
Br
N H2
N H2
Br
Zn
Cl
4
VUOS – PARTNER FOR COOPERATION
KUMADA REACTION
The cross coupling is useful for generating carbon-carbon bonds
by the reaction of a Grignard reagent and an organic halide.
R
R' M g X
X
catalyst
R
R'
The reaction allows many synthetic applications, especially
creaction of polythiophenes, useful in organic electronic devices.
5
Example
O C 2H 5
C H3
M gBr
Cl
H 5C 2O
C H3
H 5C 2O
S
Br
Mg
Br
5
VUOS – PARTNER FOR COOPERATION
O C 2H 5
S
HIYAMA REACTION
The reaction is a palladium-catalyzed cross-coupling reaction of
organosilanes with organic halides to form carbon-carbon bonds.
R
X
R'
catalyst
SiR'' 3
R
R'
This reaction has been applied to the synthesis of natural products.
Example
6
OH
Si
O
O
I
Br
Si O H
C H 3O
6
VUOS – PARTNER FOR COOPERATION
C H 3O
STILLE REACTION
The reaction is a cross-coupling an organotin compound with
an sp2-hybridized organic halide catalyzed by palladium.
R
X
catalyst
R' Sn(R'')3
R
R'
The reaction continues to be exploited industrially, especially
for pharmaceuticals.
Example
O
7
O
Cl
S n(C 4 H 9 ) 3
O
H 3C
H 3C
O
Br
C H 3O O C
7
C H3
S n(C 4 H 9 ) 3
VUOS – PARTNER FOR COOPERATION
C H 3O O C
C H3
HECK REACTION
The reaction is a coupling of an unsaturated halide (or triflate)
with an alkene and a base and palladium catalyst to form
a substituted alkene.
R'
catalyst
R
X
R'
R
This reaction is of great importance, as it allows one to do
substitution reactions on planar centers.
8
Example
I
O
OH
I
O
8
VUOS – PARTNER FOR COOPERATION
OH
SONOGASHIRA REACTION
The reaction is a cross-coupling reaction using a palladium catalyst
to form a carbon–carbon bond between a terminal alkyne and an aryl
or vinyl halide.
catalyst
HC
C
R
R'
X
R' C
C
R
The Sonogashira cross-coupling reaction has been employed in a
wide variety of areas.
9
Example
O
O
OH
O
O
I
OH
I
I
9
VUOS – PARTNER FOR COOPERATION
BUCHWALD–HARTWIG AMINATION
The reaction is used for the synthesis of carbon–nitrogen bonds
via the palladium-catalyzed cross-coupling of amines with aryl halides.
R
R'
NH
X
catalyst
R'
R
N
R''
R''
The development of the reaction allowed for the facile synthesis of aryl
amines, replacing to an extent harsher methods while significantly
expanding the repertoire of possible C–N bond formation.
10
Example
Br
Cl
C H 3N H C 2H 5
Br
N
O
O
H 2N
Br
(C 2 H 5 ) 2 N
10
VUOS – PARTNER FOR COOPERATION
NH
(C 2 H 5 ) 2 N
FUKUYAMA REACTION
The reaction is a coupling taking place between a thioester and
an organozinc halide in the presence of a palladium catalyst.
O
O
catalyst
R' Zn X
R
S
R
R''
R'
Advantages are high chemoselectivity, mild reaction conditions and the
use of less-toxic reagents.
11
Example
O
C F3
S
S
I
Zn
O
C F3
O
O
S
O
11
Zn
Cl
O
VUOS – PARTNER FOR COOPERATION
O
O
α-ARYLATION REACTION
This coupling reaction between arylhalide and organic compound
containing C-O group by using a palladium-complex catalyst.
O
O
catalyst
Ar
X
R'
R'
R
R
Ar
Advantages are mild reaction conditions and high chemoselectivity.
Example
12
C H3
C H3
C H3
C H3
Br
O
O
O
Br
O
C H3
O
O
H 3C
12
VUOS – PARTNER FOR COOPERATION
INTRODUCTION OF CARBOXYLIC GROUP
This reaction is a coupling between arylhalide and cabron dioxide.
As catalyst can be used a palladium-complex catalyst activated
with organometallic compound.
catalyst
R
X
CO2
R
COOH
This reaction allows to expand a posibilities of carboxylic group
introducing.
13
Example
F 3C
C F3
F 3C
C F3
CO2
Br
COOH
COOH
Br
CO2
O
13
O
VUOS – PARTNER FOR COOPERATION
14
14