Download Suzuki coupling in LC synthesis

Suzuki Coupling in LC Synthesis
Yu Ding
Nov 17 2003
Different Types of Liquid Crystal
CN
I
C5H11O
OC5H11
C5H11O
C5H11O
OC5H11
OC5H11
II
O
O
III
Na
What is Suzuki Coupling
Pd catalyst
B(OH)2 +
X
aq.base, DME reflux
Y
Z
X= I , Br, Cl, OSO2.sat. flourocarbon
Base= Na(OH)2, Na2CO3, K2CO3, K3PO4...
Pd catalyst= Pd(PPh3)4, PdCl2(PPh3)2, Pd(OAc)2...
Y
Z
Why Choose Organoboron Compounds
Advantage of Organoboronic acids:






Tolerate wide range of function groups
Commercially available
Thermal stable, inert to oxygen and water
Can be crystallized from water or alcohols
Reaction can be carried out under aqueous conditions
Nontoxic by-product
General Mechanism
Preparation of Organoboron Compounds
+
H3O
ArMgX
+
i
RLi
ArB(OH)2
B(OMe)3
+ B(OPr )3
HCl
Li[R-B(OPri)3]
R-B(OPri)2
R= alkyl, aryl, 1-alkenyl, and 1-alkynyl
(RO)2B-B(OR)2
B(OR)2
X
Y
PdCl2(dppf)
KOAc
DMSO,80 0C
Y
Reaction Conditions

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

Pd(PPh3)4 or PdCl2( PPh3)2 with aq. Na2CO3 in DME
Palladium catalysts with or without a phosphine
ligand
Some other bases: Et3N, NaHCO3, CsCO3,TlCO3,
K3PO4, have been used
Homogenous or heterogeneous conditions e.g.
K2CO3 suspended in toluene
Cross-coupling of Aryl Bromide and
Aryl Iodide
PhB(OH)2
+
Pd(PPh3)4
Br
CH2COCH3
0
CsF/DME at 100 C
Ph
CH2COCH3
85%
PhB(OH)2
+
I
NO2
Catalyst
Ph
0
aq. K2CO3, Acetone, 65 C
Catalyst: Pd(PPh3)4 ( 8h,23%); PhPd(PPh3)2( 0.33h,53%); Pd(OAc)2(0.75h,98%)
NO2
Bulky Effect in the Cross-coupling
Pd(PPh3)4
B(OH)2
+
Ar
ArX
aq.Ba(OH)2, DME, 800C
ArX:2-MeOC6H4I (80%), 2-ClC6H4I (94%), 2-Bromonaphthalene (86%)
Reaction activity for mesitylboronic acid to the basic strength:
Ba(OH)2 > NaOH > Na2CO3> NaHCO3
O
B
+
O
CHO
Pd(PPh3)4
Ar
ArX
K3PO4, DMF,800C
CHO
ArX: iodomesitylene (73%), 2-MOMOC6H4I (85%), 2-MeO2CC6H4I (63%)
By-products in the Cross-coupling
MeO
MeO
B(OH)2
Br
+
O
MeO
aq. Na2CO3, DME
Pd(PAr3)4
MeO
MeO
MeO
O
O
OMe
O
Ar
+
MeO
Ar= Ph
54%
27%
Ar= o-MeOC6H5
79%
3%
OMe
Direct Ortho-Metallation-Boronation
Cl
HO
HOH2C
CPh3
N N
N
N
C4H9
Br
B(OH)2
Cl
CPh3
N N
N
N
Pd(OAc)2
aq. Na2CO3, THF/DME, reflux
95%
C4H9
Cross-coupling with Aryl Triflates and
Aryl Chloride
Ar
OTf
ArB(OH)2
Pd(PPh3)4
K2CO3,Toluene, 900C
BocHN
BocHN
CO2Me
CO2Me
75%-94%
0.5% Pd2(dba)3
1% PtBu3
O
Cl + (HO)2B
O
3.3 equiv. KF
THF/RT
90%
High Dielectric Biaxiality Ferroelectric
Liquid Crystal Mixture
F
F
R(O)
(O)R'
F
I
F
R(O)
F
F
(O)R'
II
F
R(O)
(O)R'
III
F
F
F
R(O)
(O)R'
IV
Synthetic Approach to Compounds III
F
F
F
i) n-Buli,THF
ii)R"CH2CHO,THF
iii)NH4Cl,H2O
F
F
HO
F
P2O5,Pentane
R"
R"
H2,Pd/C
ethanol-THF
F
R'
III
Br
R
Pd(PPh3)4
2M Na2CO3/DME
F
F
F
i)n-BuLi,THF
B(OH)2
ii)(MeO)3B,THF
iii)10%HCl
R
F
Transition Temperatures for
Compounds III
F
R
F
F
R'
Extended Triphenylenes
OR
RO
Br
OR
Br
(HO)2B
Br
Br
Br
Br
OR
OR
RO
OR
OR
Pd(PPh3)4
aq.K2CO3
toluene/EtOH
OR
RO
OR
OR
OR
OR
J.Mater.Chem,2000,10,1519-1525
Observation Transition Temperature
Compounds
Observed Transition temperature
(0C)
R=C6H13
Cr 111 Col 126 I
R=C8H17
Cr 85 Col 104 I
R=C10H21
Cr 74 Col 103 I
R=C12H25
Cr 47 Col 101 I
Conclusion
Suzuki coupling reaction represents one of most
straightforward methods of carbon-carbon bond
formation
The reaction proceeds under mild conditions
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

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
unaffected by the presence of water,air
broad range of functionality
yield nontoxic by-products
It has been widely applied in academic and
industrial lab.