Copper-free palladium-catalyzed Sonogashira and Hiyama cross-couplings using aryl imidazol-1-ylsulfonates

Article abstract of DOI:10.1016/j.tetlet.2010.03.110

Aryl imidazylates are effective electrophilic partners in copper-free palladium-catalyzed Hiyama and Sonogashira cross-coupling reactions. The Sonogashira cross-coupling of estron-3-yl imidazylate afforded the corresponding phenylacetylene derivative in e

Full text of DOI:10.1016/j.tetlet.2010.03.110

Tetrahedron Letters 51 (2010) 2971–2974
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Tetrahedron Letters
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Copper-free palladium-catalyzed Sonogashira and Hiyama cross-couplings
using aryl imidazol-1-ylsulfonates
a
a
a
a
b
Steven J. Shirbin , Berin A. Boughton , Steven C. Zammit , Shannon D. Zanatta , Sebastian M. Marcuccio ,
a
a,
*
Craig A. Hutton , Spencer J. Williams
a
School of Chemistry and Bio21 Molecular Science and Biotechnology Institute, 30 Flemington Rd., University of Melbourne, Parkville, Victoria 3010, Australia
Advanced Molecular Technologies, Unit 1, 7-11 Rocco Drive, Scoresby, Victoria 3179, Australia
b
a r t i c l e i n f o
a b s t r a c t
Article history:
Aryl imidazylates are effective electrophilic partners in copper-free palladium-catalyzed Hiyama and
Sonogashira cross-coupling reactions. The Sonogashira cross-coupling of estron-3-yl imidazylate afforded
the corresponding phenylacetylene derivative in excellent yield.
Received 2 February 2010
Revised 17 March 2010
Accepted 26 March 2010
Available online 31 March 2010
Ó 2010 Elsevier Ltd. All rights reserved.
Transition metal-catalyzed cross-coupling reactions have ma-
tured to the point where they now represent major cornerstones
of organic synthesis. While halides are the most common electro-
philic partners for these reactions, in recent years the use of various
Method A:
imidazole (6 equiv), SO Cl
2
2
OH
OH
THF, -70 °C to rt
R
1–3
3–5
sulfonates such as mesylates,
nates (e.g., triflates,
tosylates , and fluoroalkylsulfo-
5
,6
nonaflates,7 and tetraflates ) have been
8
N
O
N
reported. These sulfonates have allowed the use of phenols as
chemical feedstocks for cross-coupling reactions, however, mesy-
S
Method B:
R
O O
1
,9
lates and tosylates commonly suffer from poor reactivity. Fluor-
oalkylsulfonates exhibit improved reactivity but suffer from a lack
R
8
of stability and a higher cost of preparation. Moreover, the byprod-
Im SO , Cs CO
3
2
2
2
ucts obtained by the use of either halides or sulfonates are classified
THF, rt
as genotoxic, dissuading from their use on scale.9
Imidazolyl-1-sulfonates (imidazylates) have been widely de-
ployed as leaving groups for nucleophilic substitution reactions
Scheme 1. Preparation of aryl imidazylates.
10
in the carbohydrate and nucleoside arenas. Goddard-Borger and
Stick reported the development of imidazolylsulfonylazide hydro-
industry. Each of these reactions has the advantage of producing
little waste from the ‘nucleophilic’ component. Only a proton is lost
from the alkyne coupling partner in Sonogashira reactions. In Hiy-
ama couplings a relatively benign silyl group is released and the
use of HOMSiÒ reagents (o-hydroxymethylphenyldimethylsilyl
groups) allows for recycling of the resultant siloxane byproduct.17
Protocols have been reported for Hiyama couplings of aryl and vinyl
11
chloride as a stable diazotransfer reagent. More recently, Alban-
9
12
eze-Walker et al. reported the first use of aryl imidazylates in
Suzuki-Miyaura and Negishi cross-coupling and carbonylation
reactions. Aryl imidazylates, being electron-deficient aryl sulfa-
mates, exhibit reactivity similar to triflates but are cheaper to pre-
pare, especially on scale, and produce non-toxic leaving group
1
8
19
derived byproducts, imidazole and sulfate.9 More recently, aryl
chlorides, aryl arenesulfonates, and mesylates. Herein, we report
the development of protocols allowing the use of aryl imidazylates
in Sonogashira and Hiyama reactions providing environmentally-be-
nign syntheses of arylacetylenes and biaryls.
imidazylates have been used in the palladium-catalyzed formation
1
3
of aryl phosphonates
oxazoles.
and palladium-catalyzed arylation of
1
4
The Sonogashira15 and Hiyama16 reactions are highly effective
processes for the construction of sp–sp and sp –sp carbon–carbon
bonds, respectively. The resulting products are highly valued in
natural product and materials synthesis and in the pharmaceutical
Several methods were investigated for the preparation of aryl
imidazylates. While the procedure of Albaneze-Walker et al.
Scheme 1, Method B) was effective for electron-rich phenols, no
product was obtained for the electron-poor phenols, 4-nitrophenol
and 4-acetylphenol. An alternative procedure using sulfuryl
2
2
2
9
(
Ò
*
Corresponding author. Tel.: +61 3 8344 2422; fax: +61 3 9347 8124.
HOMSi (2-HydrOxyMethylphenyl)dimethyl Silanes) is a registered trade mark of
E-mail address: sjwill@unimelb.edu.au (S.J. Williams).
Advanced Molecular Technologies Pty Ltd.
0
040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.03.110

2
972
S. J. Shirbin et al. / Tetrahedron Letters 51 (2010) 2971–2974
Table 1
Our initial Sonogashira studies investigated the use of Ph
Pd(OAc) and Et NH with the activated 4-nitrophenyl substrate
Table 1). Using a THF/H O solvent system, no cross-coupled
3
P,
Optimization of the Sonogashira reaction of aryl imidazylates
2
2
(
2
product was obtained owing to hydrolysis of the substrate. Grat-
ifyingly, a 60% yield was obtained in dry DMSO (entry 1).
Screening different bases led to an optimized yield of 93% using
triethylamine (entries 1–6). When applied to 4-acetylphenyl imi-
dazylate, a 73% yield was obtained (entry 7), however, an im-
phenylacetylene
N
Pd(OAc)2 (0.1 equiv)
O
N
S
O O
ligand, base (1.5 equiv)
DMSO, 65 °C, 18 h
R
R
3 4
proved yield was obtained using K PO (81%, entry 8). With
Entry
R
Ligand (equiv)
Base
Yielda (%)
the electron-rich substrate, 4-methoxyphenyl imidazylate, a dra-
matically reduced yield was obtained (23%, entry 9). Conse-
quently, we next investigated the bulky biarylphosphine
ligands SPhos and XPhos, which are known to promote the for-
1
2
3
4
5
6
7
8
9
0
1
2
4-NO
2
2
2
2
2
2
PPh
PPh
PPh
PPh
PPh
PPh
PPh
PPh
PPh
3
3
3
3
3
3
3
3
3
(0.1)
(0.1)
(0.1)
(0.1)
(0.1)
(0.1)
(0.1)
(0.1)
(0.1)
Et
Et
2
NH
N
60
93
0
4-NO
4-NO
4-NO
4-NO
4-NO
4-Ac
3
DABCO
DBU
0
0
mation of highly reactive 12-electron monovalent Pd -com-
Cs
2
CO
3
37
78
73
81
23
43
72
93
20,21
plexes.
Comparison of protocols for water-mediated catalyst
K
3
PO
4
2
2
preactivation (entry 10) versus a premixed catalyst preparation
Et
3
N
2
0
4-Ac
K
K
K
K
K
3
PO
PO
PO
PO
PO
4
4
4
4
4
(entry 11) revealed that the latter provided superior results. Fi-
nally, XPhos proved superior to SPhos (entries 11 and 12).
Next, the scope of the palladium-catalyzed reaction of a range of
imidazylates was investigated under the optimized conditions.23
As shown in Table 2, palladium-catalyzed Sonogashira couplings
furnished the corresponding diarylacetylenes in generally good
yields, with similar results seen for electron-rich, electron-poor,
ortho-substituted, and bicyclic imidazylates. A poorer yield was ob-
tained for the quinoline imidazylate (entry 6).
4-MeO
4-MeO
4-MeO
4-MeO
3
3
3
3
b
c
1
1
1
SPhos (0.2)
SPhos (0.2)
XPhos (0.2)c
a
b
c
Isolated yield.
Water-mediated catalyst preactivation as described in Ref. 22.
A catalyst stock solution was used as decribed in Ref. 20.
As a test case to illustrate the use of imidazylates of more com-
plex phenols for which the corresponding halides are unavailable,
we applied the optimized protocol to estron-3-yl imidazylate. As
chloride and imidazole (Scheme 1, Method A) proved effective for
the synthesis of imidazylates from these low pK phenols (67%
a
from 4-nitrophenol; 52% from 4-acetylphenol).
Table 2
Palladium-catalyzed Sonogashira reactions of aryl imidazylates with phenylacetylene
phenylacetylene
Pd(OAc) (0.1 equiv)
2
N
O
N
S
XPhos (0.2 equiv), K PO
3
4
O O
DMSO, 65 °C, 18 h
R
R
Entry
1
Substrate
Yielda (%)
89b
OSO Im
2
O N
2
OSO Im
2
2
97
O
OSO Im
2
3
4
5
93
91
80
MeO
OSO Im
2
Me
OSO Im
2
Me
OSO Im
2
6
7
57b
87
N
OSO Im
2
a
Isolated yield.
Triethylamine as a base.
b

S. J. Shirbin et al. / Tetrahedron Letters 51 (2010) 2971–2974
2973
O
O
phenylacetylene
Pd(OAc)2 (0.1 equiv)
H
H
XPhos (0.2 equiv), K PO
H
H
3
4
RO
Im SO , Cs CO
3
DMSO, 65 °C, 18 h
Ph
R = H
R = SO Im (81%)
2
2
2
91%
THF, rt, 16 h
2
Scheme 2. Sonogashira cross-coupling of estrone imidazylate and phenylacetylene.
Table 3
Hiyama cross-coupling reactions with 4-methoxyphenyl HOMSi reagent
OMe
N
O
N
S
O O
Pd(dppf)Cl (0.05 equiv)
2
R
R
+
+
H O (0.1 equiv), DMSO
2
OMe
K CO , 65 °C, 18 h
2
3
O
Si
Si
HO
Entry
Substrate
Yielda (%)
1
2
3
4
5
4-Nitrophenyl
4-Methoxyphenyl
4-Acetylphenyl
2-Methylphenyl
2-Naphthyl
76
72
76
36
99
b,c
b
a
b
c
Isolated yield.
Reaction run at 65 °C.
1
equiv of dppf added.
expected, the cross-coupled product was obtained in an excellent
as starting materials, which is of particular value when the corre-
sponding halide is unavailable.
9
1% yield (Scheme 2).
We next examined the use of aryl imidazylates in the Hiyama
reaction. Nakao et al. have demonstrated that the use of HOMSi re-
agents allows the recovery of the released silicon auxiliary, as a
cyclic silyl ether, and that this may be recycled for the preparation
of new HOMSi reagents.17 Again, we were unable to establish a
cross-coupling protocol with aryl imidazylates under aqueous con-
Acknowledgments
We thank the Australian Research Council for financial support.
Ethan Goddard-Borger is thanked for helpful advice.
24
ditions. However, using Pd(dppf)Cl
2
as a source of palladium in
Supplementary data
25
dry DMSO, with K CO as a base under copper-free conditions
2
3
26
afforded the expected products in good yields. We obtained sim-
ilar results for electron-rich, electron-poor, and bicyclic imidazy-
lates, and a somewhat poorer yield with the ortho-substituted 2-
methylphenyl imidazylate (Table 3).
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2010.03.110.
References and notes
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1
1
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1
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3. General procedure for the Pd-catalyzed Sonogashira coupling of aryl imidazylates:
A dry, screw-capped test tube containing Pd(OAc)
2
(0.10 equiv) and XPhos