Palladium-catalyzed aminosulfonylation of aryl iodides by using Na 2SO3 as the SO2 source

Article abstract of DOI:10.1002/ejoc.201402212

We realized an interesting palladium-catalyzed aminosulfonylation of aryl iodides by using Na₂SO₃ as a cheap SO₂ source. In most cases, the yields were comparable to those reported by using the 1,4-diazabicyclo[2.2.2]octane bis(sulfur dioxide) adduct (DABCO·2SO ₂, DABSO) as the SO₂ source. Copyright

Full text of DOI:10.1002/ejoc.201402212

SHORT COMMUNICATION
DOI: 10.1002/ejoc.201402212
Palladium-Catalyzed Aminosulfonylation of Aryl Iodides by using Na2SO3 as
the SO2 Source
Wanfang Li,[a] Haoquan Li,[a] Peter Langer,[a] Matthias Beller,[a] and Xiao-Feng Wu*[a]
Keywords: Synthetic methods / Cross-coupling / Aminosulfonylation / Palladium / Sulfur
We realized an interesting palladium-catalyzed aminosulf-
onylation of aryl iodides by using Na2SO3 as a cheap SO2
source. In most cases, the yields were comparable to those
reported by using the 1,4-diazabicyclo[2.2.2]octane bis(sulfur
dioxide) adduct (DABCO·2SO2, DABSO) as the SO2 source.
may be attributed to the multiple coordination patterns of
SO2 with transition metals.[2a] As a pilot exploration, Willis
and co-workers realized the aminosulfonylation of aryl hal-
ides by using DABSO as a SO2 equivalent (DABSO = 1,4-
diazabicyclo[2.2.2]octane bis(sulfur dioxide) adduct,
DABCO·2SO2).[7] Afterwards, many sulfonylation reactions
Introduction
Over the past decades, carbon monoxide has evolved in
metal-catalyzed carbonylation reactions as an inexpensive
and clean C1 source.[1] The most important catalytic trans-
formation of CO is its insertion into metal–carbon bonds
to generate acyl metal intermediates, which can be trapped
by various nucleophiles. Having certain similarities in coor-
dination chemistry with CO, SO2 also undergoes many in-
sertion reactions to form sulfinato metal complexes.[2] How-
ever, these complexes, especially those with transition met-
als, cannot easily be attacked by nucleophiles as acyl metal
intermediates can (Scheme 1).[3] Incorporation of SO2 into
organic molecules is of great interest, as the sulfonyl moiety
(–SO2–) occurs in many useful organic compounds.[4] Tradi-
tionally, the introduction of a sulfonyl group is realized by
using sulfuric acid, oleum, or chlorosulfonic acid.[5] The di-
rect utilization of SO2 as a sulfonyl source would be an
extremely efficient method.
[9]
were developed with DABSO[8] and K2S2O5 as SO2
sources. DABSO is a stable solid at room temperature; thus,
it is easy to handle if used as a surrogate for toxic SO2 gas
in many cases.[10] It is now commercially available but still
relatively expensive.[11] Moreover, its preparation also em-
ploys a large over amount of SO2.[12] In view of the accumu-
lated experience in catalytic manipulations of CO, H2, and
CO2 in our group, we started a project to investigate the
catalytic transformation of SO2 into sulfonyl-containing
compounds.
Results and Discussion
For safety and convenience issues, we used the cheap and
widely available raw materials sodium sulfite (Na2SO3) and
concentrated sulfuric acid (H2SO4) to produce SO2 at room
temperature. Our reaction set up is depicted in Figure 1.
For palladium-catalyzed carbonylation reactions, such a
two-chamber reactor has already gathered more atten-
tion.[13] In tube A, the SO2 gas is generated ex situ and con-
ducted into reaction tube B through a poly(propene) pipe.
The drying tube between A and B was omitted because
moisture was reported to accelerate SO2 insertion reac-
tions.[14] Before the reactants and catalyst were loaded, the
whole system was evacuated through the Schlenk line, and
thus, the SO2 gas would fill the two tubes (see the Support-
ing Information for details). The SO2 pressure was roughly
calculated to be approximately 150 kPa on the basis of the
amount of sodium sulfite and the system volume. Besides,
SO2 is highly soluble in organic solvents; thus, the actual
pressure should be lower and safe enough for the reac-
tion.[15]
Scheme 1. Pd-catalyzed carbonylation and sulfonylation reactions.
The insertion of SO2 into R–M bonds (in which M =
Mg, Li) has been reported for the synthesis of sulfonamides
and sulfones.[6] However, similar processes proved to be un-
successful in transition-metal-catalyzed sulfonylations. This
[a] Leibniz-Institut für Katalyse e.V. an der Universität Rostock,
Albert-Einstein-Strasse 29a, 18059 Rostock, Germany
E-mail: xiao-feng.wu@catalysis.de
www.catalysis.de
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201402212.
Eur. J. Org. Chem. 2014, 3101–3103
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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W. Li, H. Li, P. Langer, M. Beller, X.-F. Wu
SHORT COMMUNICATION
Notably, if DABCO (2.2 equiv.) was used as the base, the
product was obtained in only 23% yield. This implied that
DABSO might be more than a surrogate for SO2, but a
detailed reaction mechanism has not been mentioned in
previous studies. Other ligands, for example, dppp and Bu-
PAd2 only gave moderate yields. Upon lowering the catalyst
loading to 1 mol-%, the yield dropped to 41% after 24 h
(Table 1, entry 12). Other solvents such as DMF and 1,2-
dichloroethane (DCE) also gave lower yields (Table 1, en-
tries 15 and 16). Therefore, the optimized conditions were
assigned as the following: P(tBu)3 as the ligand, Cs2CO3 as
the base, and 1,4-dioxane as the solvent.
Having the optimized reaction conditions in hand, we
next extended the aminosulfonation reaction to other sub-
strates (Table 2). In most cases, the yields were moderate to
good. Alkyl groups in the ortho and meta positions led to
a clear decrease in the yield. For example, an ortho-methyl
group led to 34% yield of 1f. In general, electron-donating
Figure 1. Ex situ generation of SO2 for aminosulfonylation.
In the initial report by Willis,[7] they stated that gaseous
SO2 failed to give the desired aminosulfonylation products
by using a variety of nucleophiles and catalysts. Herein, we
found that under similar reaction conditions, gaseous SO2
could also be directly used to synthesize sulfonamides.
We started our initial studies with 4-iodotoluene and N-
aminomorpholine. First, triphenylphosphine (PPh3) was
used as the ligand and DABCO was used as the base, but
only 7% yield of 1a was obtained (Table 1, entry 1). Upon
using Cs2CO3, the yield increased significantly to 44%
(Table 1, entry 3). The nature of the base clearly affected
the reaction (Table 1, entries 4–10). To our delight, the
product was isolated in 93% yield if P(tBu)3 was used as the
ligand and Cs2CO3 was used as the base (Table 1, entry 10).
Table 2. Pd-catalyzed aminosulfonation of aryl halides by using
gaseous SO2.[a]
Table 1. Optimization of the aminosulfonylation of 4-iodotol-
uene.[a]
Entry Ligand
Base
Yield[b] [%]
1
2
3
PPh3
PCy3
PPh3
DABCO
DABCO
Cs2CO3
7
15
44
4
5
6
7
8
9
10
11
12[d]
13[e]
14
15[f]
16[g]
P(tBu)3·HBF4
P(tBu)3·HBF4
P(tBu)3·HBF4
P(tBu)3·HBF4
P(tBu)3·HBF4
P(tBu)3·HBF4
P(tBu)3·HBF4
P(tBu)3·HBF4
P(tBu)3·HBF4
dppp
DABCO
DABCO (1 equiv.)
CsF
KF
NaOAc
KOH
Cs2CO3
Cs2CO3 (1.2 equiv.)
Cs2CO3
Cs2CO3
23
54
52
34
–
44
93 (75)[c]
21
41
60
56
53
BuPAd2
P(tBu)3·HBF4
P(tBu)3·HBF4
Cs2CO3
Cs2CO3
Cs2CO3
22
[a] Reaction conditions: 4-Iodotoluene (0.25 mmol), N-amino-
morpholine (1.5 equiv.), Pd(OAc)2 (10 mol-%), ligand (20 mol-%),
base (2.2 equiv.), 1,4-dioxane (1 mL), 80 °C, 16 h. Cy = cyclohexyl,
dppp = 1,3-bis(diphenylphosphino)propane, Ad = adamantyl.
[b] Yield of isolated product. [c] Yield in parentheses was obtained
by using DABSO. [d] Pd(OAc)2 (1 mol-%) and ligand (2 mol-%),
24 h. [e] Ligand (10 mol-%). [f] In DCE. [g] In DMF.
[a] Yield of isolated product; n.t.: not detected owing to unselective
reactions. n.d.: not detected owing to unreactive reactions; n.r.: no
reaction. [b] 4-Nitro-1-iodobenzene was recovered for an unknown
reason.
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Palladium-Catalyzed Aminosulfonylation of Aryl Iodides
groups on the phenyl rings gave better yields. 4-Bromo-1-
iodobenzene gave desired product 1l in 84% yield, and
bromobenzene was correspondingly unreactive even under
harsher conditions. For cyano (see 1p) and acetyl groups
(see 1q) on the aryl iodides, unselective reactions were ob-
served. The use of a single N-heterocycle was attempted,
but unfortunately formation of 1s was not observed. Other
nucleophiles such as morpholine, piperidine, and aniline
were also used in the reaction, but the desired products were
not detected.[7,8b]
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Conclusions
In summary, we realized the first palladium-catalyzed
aminosulfonylation of aryl iodides by using ex situ gener-
ated SO2. In most cases, the yields were comparable to
those reported by using DABSO as the SO2 source. This
success promises rich chemistry in palladium-catalyzed sulf-
onylation reactions by using SO2, just as the use of CO
did in carbonylation reactions. More sulfonylation reactions
with the use of this simple, cheap, and safe method for the
generation of SO2 are underway in our laboratory.
Experimental Section
General Procedure: Two Schlenk tubes (10 mL) were connected by
a short plastic pipe through their side arms (Figure 1). Concen-
trated sulfuric acid (0.5 mL) was added into tube A and Na2SO3
(500 mg) was put in the funnel. The air in the funnel was excluded
by argon flow. Then, the whole system was vacuumed through the
Schlenk line, and the stopcock of Schlenk tube B was closed. Next,
the aryl iodide (0.25 mmol), Pd(OAc)2 (5.61 mg, 25 μmol),
HP(tBu)3BF4(14.51 mg, 50 μmol), Cs2CO3 (171 mg, 0.525 mmol),
and 1,4-dioxane (1 mL) were added under an atmosphere of argon.
Then, 4-aminomorpholine (36 μL, 0. 375 mmol) was added, and
the argon gas in tube B was carefully removed by the Schlenk line.
Finally, the stopcocks of the funnel and Schlenk tube B were
opened slowly, and the whole system was filled with SO2. Schlenk
tube B was immersed in an oil bath, and the contents were stirred
at 80 °C for 16 h. After cooling to room temperature, the mixture
was filtered through Celite and then purified by flash column
chromatography to give the pure product.
Supporting Information (see footnote on the first page of this arti-
cle): Experimental details, characterization data, and copies of the
1H NMR and 13C NMR spectra of all final products.
Acknowledgments
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Russ. J. Inorg. Chem. 2010, 55, 1322–1329.
The authors thank the State of Mecklenburg-Vorpommern, the
Bundesministerium für Bildung und Forschung (BMBF) and the
Deutsche Forschungsgemeinschaft for financial support.
Received: March 6, 2014
Published Online: April 7, 2014
Eur. J. Org. Chem. 2014, 3101–3103
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3103