Sonogashira Couplings of Aryl Bromides:
Room Temperature, Water Only, No Copper
Bruce H. Lipshutz, David W. Chung, and Brian Rich
Org.Lett. ASAP Article
Presentation By Nora Jameson
Current Lit 08/30/2008
Nora Jameson @ Wipf Group
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Sonogashira Coupling:
Possible Catalytic Cycle
Seminal Publications:
K. Sonogashira,Y. Tohda, N. Hagihara. Tetrahedron Letters 1975 16 (50): 4467–4470
Andrew G. Myers and Peter S. Dragovich Org. Synth 1998 Coll.Vol. 9: 117
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Sonogashira Coupling as a Tool in Organic Synthesis
A. S. Karpov, T. J. J. Müller, Synthesis, 2003, 2815-2826.
H
SiMe3
Br
SiMe3
H
Pd(PPH3)2Cl2 / CuI
O
N
N
Br
benzene / NEt3
90C / 2d
O
O
O
N
N
Br
N
Br
O
O
N
O
O
S. Liu, C. Michel, M. Schmittel, Org. Lett., 2000, 2(25); 3959-3962.
I
OMOM
O
OH
H
PPh3, PdCl2(PPh3)2
HO
O
OMOM
O
Et3N, CuI
O O
O
K. Y. Tsang, M. A. Brimble, J. B. Bremmer, Org. Lett., 2003, 5(23); 4425-4427.
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No Copper Sonogashira Couplings
A. R. Gholap, K.Venkatesan, R. Pasricha, T. Daniel, R. J. Lahoti, K.V. Srinivasan, J. Org. Chem., 2005, 70, 4869-4872.
C. Yi, R. Hua, J. Org. Chem., 2006, 71, 2535-2537.
Y. Liang, Y.-X. Xie, J.-H. Li, J. Org. Chem., 2006, 71, 379-381.
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Aqueous Cross-Coupling
I
X2 R
H
H
R
[Pd]/Et3N
CH3CN/H2O, R.T.
R
C. Li, D. Chen, C. W. Costello, Org. Proc. Res. Dev., 1997, 1 (4), 325 -327.
HO
Pd/C, K2CO3
X
ArB(OH)2
H2O, R.T., 12h
HO
Ar
H. Sakurai, T. Tsukuda, T. Hirao, J. Org. Chem., 2002, 67(8); 2721-2722.
A. Bino, M. Ardon, and E. Shirman, Science,
8 April 2005 308: 234-235
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Micellar Catalysis
J. H. M. Heijnen, V. G. de Bruijn, L. J. P. van den Broeke and J. T. F. Keurentjes Chem. Engineering and Processing Vol. 42, 3, 2003, Pages 223-230
perfluorooctanoic acid
D. C. Berndt, M. E. Ayoub, M. H. Akhavan-Tafti, Int. J. of Chem. Kinetics, Vol 19, 6, 1987, 513-518
Brij® 30
Triton®-X100
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Aqueous Mediated Coupling
The use of PTS: micellar catalyst
PTS (n = ca. 13)
Pd(dtbpf)Cl2, Et3N
Br
(H2O)2B
2% wt PTS, rt, 5h
Lipshutz, B. H. et al. Org. Lett. 2008, 10, 1333.
OBn
O
OBn
I
Pd(dtbpf)Cl2, Et3N
BnO
N
Ts
OTBS
O
15% wt PTS, rt
BnO
N
Ts
OTBS
Lipshutz, B. H.; Taft, B. R. Org. Lett. 2008, 10, 1329.
Nora Jameson @ Wipf Group
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Title Paper Sonogashira Couplings of Aryl Bromides:
Room Temperature, Water Only, No Copper
Unprecedented Sonogashira cross-coupling in water at ambient temperatures
Absence of both copper and organic solvent
Use of commercially available reagents
Nora Jameson @ Wipf Group
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Ligand Studies
i-Pr
Me
P(Cy)2
i-Pr
i-Pr
Fe
N
P(tBu)2
PdCl2
i-Pr
P(tBu)2
i-Pr
X-Phos
1
N
Me
P(Cy)2
i-Pr
Pd Cl
P(Cy)2
i-Pr
Pd(dtbpf)Cl2
2
NeolystTMCX31
3
(Cy-vBRIDP)
4
5 R = Cy (Cy-cBRIDP)
6 R - tBu (cBRIDP)
degassed solvents used for X-Phos, obtained best results with commercially available ligand and
catalyst
using catalyst 6 obtained similar results using degassed or nondegassed solvent
Br
R
R'
H 1% PdCl2(CH3CN)2, X-Phos
R'
Cs2CO3, 3%PTS, H2O, rt
R
Suzuki, K.; Fontaine, A.; Hori,Y.; Kobayashi, T. Synlett 2007, 3206–3208.
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Reaction Scope
alkyne
Ar-Br
base
product
time
yield
Ph
Br
O2N
Ph
Br
Cs2CO3
99%
20h
C10H21-n
C10H21-n
Et3N
18h O2N
99%
Et3N
21h
98%
Br
Br
O
(CH2)4Cl
(CH2)4Cl
(n-Bu)3Nc
23h
0%
(n-Oct)3Nc
23h
0%
O
Using PdCl2(CH3CN)2 + Ligand 1 in 3% PTS/H2O at rt
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Conclusions
Cl
O
N
H
Br
(CH2)9-OH
Cl
3% Pd(OAc)2, 6% ligand 6
N
H
6% PTS/H2O, Et3N, rt, 6h
Cl
O
Cl
(CH2)9-OH
Aryl bromide Sonogashira Coupling in aqueous solvent
Absence of copper and organic solvents
Reactions at ambient temperatures
Use of PTS as micellar catalyst
Possible applications in industrial chemistry
Nora Jameson @ Wipf Group
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