A copper-catalyzed three-component reaction of triethoxysilanes, sulfur dioxide, and hydrazines

Article abstract of DOI:10.1021/ol5018849

A three-component reaction of triethoxysilanes, sulfur dioxide, and hydrazines catalyzed by copper(II) acetate is reported, leading to N-aminosulfonamides in good yields. Not only triethoxy(aryl)silanes but also triethoxy(alkyl)silanes are compatible during the process of insertion of sulfur dioxide. Additionally, diethoxydiarylsilanes are suitable under the conditions as well.

Full text of DOI:10.1021/ol5018849

Letter
pubs.acs.org/OrgLett
A Copper-Catalyzed Three-Component Reaction of Triethoxysilanes,
Sulfur Dioxide, and Hydrazines
Xianbo Wang,† Lijun Xue,‡ and Zhiyong Wang*,‡
†Department of Chemistry, Nanchang University, 999 Xuefu Road, Nanchang 330031, P. R. China
‡School of Chemistry and Chemical Engineering, Chongqing University, 174 Shazhengjie, Chongqing 400044, P. R. China
S
* Supporting Information
ABSTRACT: A three-component reaction of triethoxysilanes,
sulfur dioxide, and hydrazines catalyzed by copper(II) acetate is
reported, leading to N-aminosulfonamides in good yields. Not only
triethoxy(aryl)silanes but also triethoxy(alkyl)silanes are compatible
during the process of insertion of sulfur dioxide. Additionally,
diethoxydiarylsilanes are suitable under the conditions as well.
Scheme 1. A Copper-Catalyzed Aminosulfonylation of
Arylsilanes with the Insertion of Sulfur Dioxide
alladium-catalyzed cross-coupling reactions employing
1−3
Psilylated molecules have been well developed,
which
provide an efficient and powerful method for the formation of a
new C−C bond in organic synthesis. Among the couplings, the
Hiyama2a and Hiyama−Denmark2b reactions are well-known.
Recently, copper-catalyzed coupling reactions of silylated
compounds have been developed.4,5 For instance, Riant
described the synthesis of enynes via a copper-catalyzed
cross-coupling reaction of vinylsiloxanes with bromoalkynes.5a
Giri reported the copper-catalyzed reaction of arylsilanes with
aryl iodides.5c Due to the advantages of copper catalysts in
organic transformations, broadening the applications of copper-
catalyzed couplings of silylated compounds would be attractive
and highly desirable.
the first example of a copper-catalyzed aminosulfonylation of
arylsilanes, which proceeds through an insertion reaction of
sulfur dioxide in the presence of hydrazines.
A model reaction of triethoxy(phenyl)silane 1a, sulfur
dioxide, and morpholin-4-amine 2a was selected. The studies
were initially performed in the presence of CuF2 (10 mol %) in
DCE at 80 °C with a balloon of oxygen. Different fluorides
were screened first. It was found that the reaction worked
efficiently when CsF was employed, leading to the desired
product 3a in 20% yield (TBAF: 10%; NaF: trace; KF: 13%;
LiF: trace; data not shown in Table 1). No reaction occurred
without the addition of a copper catalyst. We also examined
other oxidants; however, no better results were observed
(Table 1, entries 2−5). Further exploration of copper catalysts
revealed that the reaction worked efficiently in the presence of
copper(II) acetate, producing the corresponding product 3a in
27% yield (Table 1, entries 6−12). Different solvents were then
screened (Table 1, entries 13−18), which indicated that 1,4-
dioxane was the best choice (46% yield). The yield was lower
when the reaction temperature was changed (data not shown in
Table 1). We also explored the reaction in the presence of
various ligands (including phosphine ligands and nitrogen
ligands; see Supporting Information (SI)). Gratifyingly, the
transformation afforded the desired product 3a in 71% yield
when X-Phos was employed (Table 1, entry 19; for other
results, see SI).
Recently, the insertion of sulfur dioxide into small organic
molecules has attracted growing interest.6−9 So far, continuous
efforts have been made in this area, especially in the
aminosulfonylation process. DABCO-bis(sulfur dioxide) and
inorganic metal sulfides have been utilized as a source of sulfur
dioxide in the aminosulfonylation reaction. The electrophiles
include aryl halides,7 arylboronic acids,8 aryldiazonium tetra-
fluoroborates,9 etc. For example, Willis described the utilization
of DABCO-bis(sulfur dioxide) in a palladium-catalyzed
coupling reaction of aryl iodides and hydrazines.7a Mascitti
and Toste reported the synthesis of sulfinates from a gold-
catalyzed reaction of boronic acids and potassium metabisulfi-
te.8b Wu also provided an efficient route to N-aminosulfona-
mides through an insertion reaction of sulfur dioxide with
aryldiazonium salt and hydrazines under extremely mild
conditions.9a
Due to the importance of sulfonylamide10 as a pharmaco-
phore in drug discovery as well as our interest in Hiyama
couplings, we envisioned that a copper-catalyzed coupling
reaction of silylated molecules could be developed combined
with the insertion of sulfur dioxide (Scheme 1). It is known that
sulfur dioxide is produced enormously annually in industry. It
will be attractive if this approach is feasible. Herein, we disclose
Received: June 30, 2014
Published: July 17, 2014
© 2014 American Chemical Society
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dx.doi.org/10.1021/ol5018849 | Org. Lett. 2014, 16, 4056−4058

Organic Letters
Letter
Table 1. Initial Studies for the Copper-Catalyzed Three-
Component Reaction of Triethoxyphenylsilane 1a, Sulfur
Dioxide, and Morpholin-4-amine 2a
Scheme 2. A Copper-Catalyzed Three-Component Reaction
of Triethoxysilanes, Sulfur Dioxide, and Hydrazines
a
a
b
entry
[Cu]
CuF2
oxidant
O2
solvent
DCE
yield (%)
1
20
trace
8
2
CuF2
Ag2CO3
PhI(OAc)2
oxone
K2S2O8
O2
DCE
3
CuF2
DCE
4
CuF2
DCE
10
15
27
8
5
CuF2
DCE
6
Cu(OAC)2
CuI
DCE
7
O2
DCE
8
CuSCN
CuBr2
O2
DCE
10
14
17
16
19
11
46
21
9
9
O2
DCE
10
11
12
13
14
15
16
17
18
CuCl2
O2
DCE
Cu2O
O2
DCE
Cu(OTf)2
Cu(OAC)2
Cu(OAC)2
Cu(OAC)2
Cu(OAC)2
Cu(OAC)2
Cu(OAC)2
Cu(OAC)2
O2
DCE
O2
tBuOH
1,4-dioxane
toluene
DMF
O2
O2
O2
O2
MeCN
THF
38
32
71
O2
c
19
O2
1,4-dioxane
a
a
Reaction conditions: [Cu] (0.03 mmol), ligand (0.06 mmol),
Reaction conditions: Cu(OAc)2 (0.03 mmol), X-Phos (0.06 mmol),
triethoxyphenylsilane 1a (0.30 mmol), DABCO·(SO2)2 (0.60
mmol), morpholin-4-amine 2a (0.60 mmol), “F” (0.60 mmol),
oxidant, solvent (2.0 mL), 80 °C. Isolated yield based on
triethoxyphenylsilane 1a. In the presence of X-Phos. For the result
triethoxysilanes 1 (0.30 mmol), DABCO·(SO2)2 (0.60 mmol),
hydrazines 2 (0.60 mmol), CsF (0.60 mmol), O2, 1,4-dioxane (2.0
mL), 80 °C. Isolated yield based on triethoxysilane 1.
b
c
by employing other ligands, please see Supporting Information.
investigated. The result is presented in Scheme 3. Excellent
yields were obtained for these cases. For instance, diethoxy-
diphenylsilane 4a reacted with DABCO-bis(sulfur dioxide) and
morpholin-4-amine 2a, producing the corresponding product
3a in almost quantitative yield. The reaction proceeded well
After establishing the optimal conditions, the copper-
catalyzed three-component reaction of triethoxysilanes, sulfur
dioxide, and hydrazines was then explored. The result is
summarized in Scheme 2. It was found that all reactions worked
well to give rise to the corresponding N-aminosulfonamides in
moderate to good yields: (1) Different functional groups
including electron-donating and -withdrawing groups attached
on the aromatic ring of triethoxy(aryl)silanes were all
compatible under the standard conditions (products 3a−3f).
(2) The reaction employing triethoxy(vinyl)silane proceeded
smoothly as well to generate the desired product 3g. (3) Not
only triethoxy(aryl)silanes but also triethoxy(alkyl)silanes are
suitable during the process of insertion of sulfur dioxide. For
the reactions of triethoxy(octyl)silane, it is noteworthy that the
β-elimination of hydrogen is minimized during the trans-
formation. For example, coupling of triethoxy(octyl)silane,
sulfur dioxide, and morpholin-4-amine 2a afforded the expected
product 3i in 72% yield. Additionally, triethoxy(methyl)silane
reacted with DABCO-bis(sulfur dioxide) and morpholin-4-
amine well, leading to N-morpholinomethanesulfonamide 3j in
65% yield. These results are interesting, since it is the first
example with the insertion of sulfur dioxide for the preparation
of N-aminoalkylsulfonamides. (4) Other hydrazines were all
good partners in this three-component reaction (compounds
3k−3q). (5) No reaction occurred when amines or anilines
were utilized as the replacement for hydrazines (data not shown
in Scheme 2), which was similar to previous reports.
Scheme 3. A Copper-Catalyzed Three-Component Reaction
a
of Diethoxydiarylsilanes, Sulfur Dioxide, and Hydrazines
a
Reaction conditions: Cu(OAc)2 (0.03 mmol), X-Phos (0.06 mmol),
diethoxydiarylsilane 4 (0.30 mmol), DABCO·(SO2)2 (0.60 mmol),
morpholin-4-amine 2a (0.60 mmol), CsF (0.60 mmol), O2, 1,4-
dioxane (2.0 mL), 80 °C. Isolated yield based on diethoxydiarylsilane
4.
Furthermore, reactions of diethoxydiarylsilanes with sulfur
dioxide and hydrazines under the above conditions are
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Organic Letters
Letter
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chloro)phenylsilane was employed. A good yield for product
3h was observed also when diethoxydi(naphthalen-2-yl)silane
was utilized in the reaction.
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In conclusion, we have discovered a copper-catalyzed three-
component reaction of triethoxysilanes, sulfur dioxide, and
hydrazines, leading to N-aminosulfonamides in moderate to
good yields. Not only triethoxy(aryl)silanes but also triethoxy-
(alkyl)silanes are compatible during the process of insertion of
sulfur dioxide. Additionally, diethoxydiarylsilanes are suitable
under the conditions as well. This method provides an excellent
alternative to N-aminosulfonamides. Moreover, employing
triethoxysilanes or diethoxydiarylsilanes in the insertion of
sulfur dioxide would broaden the copper-catalyzed coupling
reactions.
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ASSOCIATED CONTENT
* Supporting Information
Experimental details, compound characterization, and spectra.
This material is available free of charge via the Internet at
http://pubs.acs.org.
■
S
AUTHOR INFORMATION
Corresponding Author
■
*E-mail: zwang@cqu.edu.cn.
Notes
(8) (a) Ye, S.; Wu, J. Chem. Commun. 2012, 48, 7753. (b) Johnson,
M. W.; Bagley, S. W.; Mankad, N. P.; Bergman, R. G.; Mascitti, V.;
Toste, F. D. Angew. Chem., Int. Ed. 2014, 53, 4404.
The authors declare no competing financial interest.
(9) (a) Zheng, D.; An, Y.; Li, Z.; Wu, J. Angew. Chem., Int. Ed. 2014,
53, 2451. (b) Zheng, D.; Li, Y.; An, Y. Wu, J. Chem. Commun. 2014,
50, 8886.
(10) (a) Bartholow, M. Top 200 Drugs of 2011. Pharmacy Times.
http://www.pharmacytimes.com/publications/issue/2012/July2012/
Top-200-Drugs-of-2011, accessed on Jan 9, 2013. (b) Drews, J. Science
2000, 287, 1960. (c) DeBergh, J. R.; Niljianskul, N.; Buchwald, S. L. J.
Am. Chem. Soc. 2013, 135, 10638.
ACKNOWLEDGMENTS
■
Financial support from the National Natural Science
Foundation of China (No. 21302236), Fundamental Research
Funds for the Central Universities (CDJRC11220001,
CQDXWL-2013-023), and the Scientific Research Foundation
for the Returned Overseas Chinese Scholars, State Education
Ministry ([2013]693) is gratefully acknowledged.
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