Synthesis of β-Keto Sulfones via Coupling of Aryl/Alkyl Halides, Sulfur Dioxide and Silyl Enolates through Metal-Free Photoinduced C–X Bond Dissociation

Article abstract of DOI:10.1002/adsc.201700525

A photoinduced sulfonylative coupling of aryl/alkyl halides, DABCO?(SO₂)₂ (1,4-diazabicyclo[2.2.2]octane-sulfur dioxide), and silyl enolates under metal-free conditions has been developed, giving rise to β-keto sulfones in good yields. This transformation proceeds smoothly at room temperature under ultraviolet irradiation with good tolerance of various functional groups. Aryl iodides/bromides and alkyl halides are all good substrates in the sulfonylative reaction. A plausible mechanism is proposed, which proceeds through a radical process under photoinduced conditions. (Figure presented.).

Full text of DOI:10.1002/adsc.201700525

Title: Synthesis of β-Keto Sulfones via Coupling of Aryl/Alkyl
Halides, Sulfur Dioxide and Silyl Enolate through Metal-Free
Photoinduced C-X Bond Dissociation
Authors: Xinxing Gong, Yechun Ding, Xiaona Fan, and Jie Wu
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To be cited as: Adv. Synth. Catal. 10.1002/adsc.201700525
Link to VoR: http://dx.doi.org/10.1002/adsc.201700525

10.1002/adsc.201700525
Advanced Synthesis & Catalysis
FULL PAPER
DOI: 10.1002/adsc. 201((will be filled in by the editorial staff))
Synthesis of β-Keto Sulfones via Coupling of Aryl/Alkyl
Halides, Sulfur Dioxide and Silyl Enolate through Metal-Free
Photoinduced C-X Bond Dissociation
Xinxing Gong,[a] Yechun Ding,[b] Xiaona Fan,[*,b] and Jie Wu[*,ac]
[a]
Department of Chemistry, Fudan University, 220 Handan Road, Shanghai 200433, China
Fax: (+86)-21-65641740
E-mail: jie_wu@fudan.edu.cn
[b]
Gannan Medical University Collaborative Innovation Center for Gannan Oil-tea Camellia Industrial Development, 1
Yixueyuan Road, Ganzhou, Jiangxi 341000, China
Fax: (+86)-797-8169600
E-mail: fxn918@126.com
[c]
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of
Sciences, 345 Lingling Road, Shanghai 200032, China
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.((Please
delete if not appropriate))
Abstract:
aryl/alkyl
A
photoinduced sulfonylative coupling of Keywords: Aryl/alkyl halide; sulfonylative coupling; sulfur
halides, DABCO·(SO2)2 (1,4- dioxide; photoinduced; silyl enolate
diazabicyclo[2.2.2]octane-sulfur dioxide), and silyl enolates
under metal-free conditions is developed, giving rise to β-
keto sulfones in good yields. This transformation proceeds
smoothly at room temperature under ultraviolet irradiation
with good tolerance of various functional groups. Aryl
iodides/bromides and alkyl halides are all good substrates in
the sulfonylative reaction.
A plausible mechanism is
proposed, which undergoes through a radical process under
photoinduced conditions.
the application of sulfur dioxide in organic synthesis
has been developed rapidly.[5-8] For instance, Willis and
Introduction
co-workers
reported
the
first
example
of
Coupling reactions of aryl/alkyl halides under aminosulfonylation through
a
palladium-catalyzed
transition metal catalysis have been well established in reaction of aryl iodides, DABCO·(SO2)2, and
organic synthesis,[1] and this strategy has been applied hydrazines.[4a] This method could be further extended to
broadly in total synthesis of natural products and aryl bromides and inorganic sulfites.[7a] However, the
pharmaceuticals.[2] Compared with the carbonylative nucleophile was restricted to hydrazines, and
coupling reactions, the sulfonylative couplings with the transformations were not successful when other
insertion of sulfur dioxide are less explored, probably nucleophiles were employed in the reactions under
due to its toxicity and handling problem of gaseous transition metal catalysis (Scheme 1, eq. a).[5] Since
form. However, from the point view of environment aryl/alkyl halides are easily available or accessible,
and the importance of sulfonyl unit in pharmaceuticals, exploration of methods for the insertion of sulfur
argrochemicals, materials and organic synthesis,[3] dioxide starting from aryl/alkyl halides is highly
methods development through the insertion of sulfur desirable.
dioxide into small molecules is highly demanded. Since
The photoinduced couplings of aryl halides have
the first introduction of sulfur dioxide surrogate of appeared as a powerful alternative for the carbon-
DABCO·(SO2)2 in sulfonylative coupling reactions,[4] carbon and carbon-heteroatom bond formation.[9,10] In
1
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10.1002/adsc.201700525
Advanced Synthesis & Catalysis
the presence of visible or ultraviolet light, aryl radicals (DMSO), or MeOH (Table 1, entries 2-4). Gratifyingly,
via electron transfer would be produced through Ar-X the corresponding β-keto sulfone 3a was generated in
bond dissociation under mild conditions. In some cases, 15% yield when 1,2-dichloroethane (DCE) was utilized
the photoinduced reactions could be performed in the as the solvent (Table 1, entry 5). The yield was
absence of photocatalysis.[11] Thus, couplings of aryl improved to 28% when the solvent was replaced by
halides under metal-free photoinduced conditions MeCN (Table 1, entry 6). The addition of additives was
would be feasible and promising.
subsequently explored (Table 1, entry 7-14). However,
Recently, we described the insertion of sulfur dioxide no better results were obtained. Different ratio of
through radical process starting from aryldiazonium reactants was then investigated. It was found that the
salts and the sulfur dioxide surrogate of reaction proceeded efficiently with the ratio of
DABCO·(SO2)2.[6a,b] Since the photoinduced Ar-X bond substrates 1a/2a/DABCO·(SO2)2 (2:1:1), leading to the
dissociation also underwent radical intermediates, we corresponding product 3a in 48% yield (Table 1, entry
envisioned that sulfonylative couplings of aryl halides 15). Lower concentration of the transformation was
with the insertion of sulfur dioxide under photoinduced examined, which afforded the desired product 3a in
conditions might be practicable. Moreover, we expected 72% yield (Table 1, entry 16).
that other types of nucleophiles (such as C-nucleophiles,
Scheme 1, eq. b) could participate in the transformation. Table 1. Initial studies for the reaction of iodobenzene 1a
Additionally, alkyl halides might be employed as the with trimethyl((1-phenylvinyl)oxy)silane 2a. [a]
substrates since β-hydrogen elimination would be
I
avoided during the process under photoinduced
O
UV
DABCO (SO2)2
+
+
SO2Ph
conditions instead of transition metal catalysis. Very
recently, we discovered that the sulfonylative coupling
of aryl/alkyl halides, sulfur dioxide, and hydrazines
under UV irradiation could proceed smoothly.[6c]
Encouraged by this result, we conceived that C-
nulceophiles such as silyl enolate could be utilized in
the sulfonylative coupling of aryl/alkyl halides as well.
Herein, we disclose our recent efforts for the synthesis
of β-keto sulfones through a photoinduced sulfonylative
coupling of aryl/alkyl halides, DABCO·(SO2)2, and silyl
enolates under metal-free conditions.
solvent
Ph
OTMS
Ph
1a
2a
3a
Entry
1
Additive
Solvent
Yield (%)
trace
trace
trace
trace
15
-
1,4-dioxane
DMF
2
-
3
-
DMSO
MeOH
DCE
4
-
5
-
-
6
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
28
7
TBAI
TBAB
TBAF
CsF
KF
I2
29
8
22
a) previous reports
9
n.d.
n.d.
n.d.
n.d.
25
transition metal
R2
N NH2
R1
"N"-nucleophile
R2
HN N
Ar SO2 R1
catalysis
10
11
12
13
14
15[b]
16[b,c]
+
+
Ar
X
"SO2"
KI
other nucleophiles: unsuccessful
CuI
-
trace
48
b) this work
SO2R
UV
metal-free
OSiMe3
-
72
+
+
Aryl/alkyl
X
"SO2"
[a]
Ar
"C"-nucleophile
Reaction conditions: iodobenzene 1a (0.20 mmol), silyl
enolate 2a (0.40 mmol), DABCO·(SO2)2 (0.20 mmol), additive
(0.40 mmol), solvent (4.0 mL), N2, overnight. Isolated yield
based on iodobenzene 1a.
iodobenzene 1a (0.40 mmol), silyl enolate 2a (0.20 mmol),
DABCO·(SO2)2 (0.20 mmol). Isolated yield based on silyl
enolate 2a. [c] The reaction occurred in MeCN (8.0 mL).
Ar
O
[b]
The reaction was performed with
Scheme 1 Photoinduced sulfonylative coupling of aryl/alkyl
halides, sulfur dioxide, and silyl enolates
Results and Discussion
Under the optimized conditions shown above, we
then explored the substrate scope of the photoinduced
sulfonylative coupling of aryl/alkyl iodides 1, sulfur
dioxide, and silyl enolates 2. The results are presented
in Table 2. It was found that all reactions worked well,
providing the corresponding β-keto sulfones 3 in
moderate to good yields. Different functional groups
were all compatible under the standard conditions. For
example, the acetyl-substituted product 3i was
furnished in 77% yield. 3-Pyridinyl iodide was a good
partner as well, which afforded the corresponding
product 3j in 56% yield. It was notable that aryl
For the initial investigation, iodobenzene 1a with silyl
enolate 2a was selected as the model substrates to
explore the optimal reaction conditions for
sulfonylative coupling. The results are summarized in
Table 1. At the beginning, this photoinduced reaction
was carried out in 1,4-dioxane at room temperature
under N2 atmosphere overnight. However, no positive
result was obtained. Other solvents were further
screened (Table 1, entries 2-6). Similar results were
observed when the reaction was performed in N,N-
Dimethylformamide (DMF), Dimethyl sulfoxide
2
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10.1002/adsc.201700525
Advanced Synthesis & Catalysis
O
chloride was inert under the photoinduced conditions,
giving rise to the chloro-subsituted β-keto sulfones 3g
in 77% yield. Reactions of alkyl iodides were also
examined, providing the desired products 3p-s in
moderate yields. However, for the substrates of alkyl
iodides, only 1o alkyl iodides were effective in the
reaction to provide the corresponding products.
DABCO (SO2)2
O2
S
Br
UV
+
R
Ph
KI (4.0 equiv.)
MeCN
R
Ph
OTMS
4
2a
3b: R = 4-Me, 50% yield
3c: R = 4-tBu, 54% yield
3d: R = 2-Me, 47% yield
3g: R = 4-Cl, 36% yield
3h: R = 4-F, 63% yield
Table 2. Photoinduced sulfonylative coupling of aryl/alkyl
iodides 1, sulfur dioxide, and silyl enolates 2 [a]
Scheme 2 Photoinduced sulfonylative coupling of aryl
bromides 4, sulfur dioxide, and silyl enolate 2a
DABCO (SO2)2
I
O
UV
+
SO2Ph
n.d.
TEMPO, MeCN Ph
2a
Ph
OTMS
1a
3a
DABCO (SO2)2
+
O
I
O
O2
S
UV
MeCN
Ph
O
Ph
OTMS
6, 53% yield
5
2a
Scheme 3. Investigation of mechanism
As mentioned above, aryl radicals would be
produced through Ar-X bond dissociation under
ultraviolet irradiation. We postulated that the reaction
would probably undergo a radical process. Therefore,
2.0 equivalent of 2,2,6,6-tetramethylpiperidinooxy
(TEMPO) was added in the model reaction of Table 1
under the standard reaction conditions (Scheme 3). As
expected, no desired product was detected. Moreover,
1-(allyloxy)-2-iodobenzene 5 was employed in the
photoinduced sulfonylative coupling, leading to the
corresponding β-keto sulfone 6 in 53% yield. This
result also demonstrated that a radical process would be
involved.
[a] Isolated yield based on silyl enolate 2.
O
DABCO (SO2)2
UV
B
R X
R
S
R
O
1
A
To further expand the application of this synthetic
route, the photoinduced sulfonylative coupling of aryl
bromides was then explored. To our surprise, the
reactions failed to produce the corresponding products
under the above conditions, possibly due to the lower
reactivity of aryl bromides. Inspired by Li’s work,[12]
we finally discovered that the reactions proceeded well
in the presence of potassium iodide. The results are
shown in Scheme 2. We reasoned that the addition of
potassium iodide could facilitate the conversion of aryl
DABCO
X
Ar
OSiMe3
2
SO2R
SO2R
X
SO2R
OSiMe3
DABCO
SiMe3
O
Ar
O
Ar
Ar
X
C
3
D
DABCO
Scheme 4. A plausible mechanism for the photoinduced
bromide to aryl iodide.[12] Thus, the presence of sulfonylative coupling of aryl/alkyl halides
potassium iodide would greatly promote this
transformation to provide the desired products.
Based on the above experiments and our previous
reports, we proposed a plausible radical pathway for the
photoinduced sulfonylative coupling as shown in
Scheme 4. The photoinduced aryl/alkyl−X bond
3
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10.1002/adsc.201700525
Advanced Synthesis & Catalysis
dissociation under ultraviolet irradiation would happen
to generate radical A and iodo/bromo radical. Radical A
would subsequently react with DABCO·(SO2)2 to
produce the corresponding sulfonyl radical B, with the
release of DABCO. Sulfonyl radical B would then
undergo addition to the double bond of silyl enolate 2,
providing alkyl radical C. Followed by combination
J = 8.4 Hz, 2H), 7.60 (t, J = 7.3 Hz, 1H), 7.53 (d, J =
8.4 Hz, 2H), 7.46 (t, J = 7.7 Hz, 2H), 4.73 (s, 2H), 1.33
(s, 9H). 13C NMR (100 MHz, CDCl3): δ 188.1, 158.2,
135.8, 134.3, 129.3, 128.8, 128.4, 126.2, 63.5, 35.3,
31.0.
1-Phenyl-2-(o-tolylsulfonyl)ethan-1-one
(3d).[13]
1
with iodo/bromo radical would afford compound D. White solid, 24.7 mg (45% yield); H NMR (400 MHz,
Desilylation with the release of halide promoted by
DABCO would give rise to the desired β-keto sulfone 3.
CDCl3): δ 7.95 (d, J = 7.7 Hz, 2H), 7.89 (d, J = 7.9 Hz,
1H), 7.62 (t, J = 7.4 Hz, 1H), 7.50 (m, 3H), 7.38 – 7.30
(m, 2H), 4.76 (s, 2H), 2.73 (s, 3H). 13C NMR (100 MHz,
CDCl3): δ 187.9, 138.3, 136.9, 135.8, 134.3, 134.2,
132.8, 130.5, 129.4, 128.8, 126.6, 62.9, 20.5.
Conclusion
2-((3-Methoxyphenyl)sulfonyl)-1-phenylethan-1-
one (3e).[15] White solid, 38.9 mg (67% yield); 1H NMR
(400 MHz, CDCl3): δ 7.95 – 7.86 (m, 2H), 7.58 (t, J =
7.4 Hz, 1H), 7.47 – 7.37 (m, 4H), 7.32 (d, J = 1.7 Hz,
1H), 7.16 – 7.09 (m, 1H), 4.70 (s, 2H), 3.78 (s, 3H). 13C
NMR (100 MHz, CDCl3): δ 187.9, 159.9, 139.8, 135.7,
134.3, 130.3, 129.3, 128.8, 120.9, 120.6, 112.8, 63.4,
55.7.
2-([1,1'-Biphenyl]-4-ylsulfonyl)-1-phenylethan-1-
one (3f).[16] White solid, 56.5 mg (85% yield); 1H NMR
(400 MHz, CDCl3): δ 7.95 (d, J = 8.2 Hz, 4H), 7.73 (d,
J = 8.3 Hz, 2H), 7.60 (m, 3H), 7.52 – 7.41 (m, 5H),
4.78 (s, 2H). 13C NMR (100 MHz, CDCl3): δ 188.1,
147.1, 139.0, 137.2, 135.7, 134.4, 129.3, 129.1, 129.1,
128.9, 128.7, 127.8, 127.4, 63.5.
In conclusion, we have disclosed a photoinduced
sulfonylative
coupling of
aryl/alkyl
halides,
DABCO·(SO2)2, and silyl enolates under metal-free
conditions. This transformation proceeds smoothly at
room temperature under ultraviolet irradiation with
good tolerance of various functional groups, giving rise
to β-keto sulfones in good yields. Aryl
iodides/bromides and alkyl halides are all good
substrates in the sulfonylative reaction. A plausible
mechanism is proposed, which undergoes through a
radical process under photoinduced conditions. Further
exploration involving the insertion of sulfur dioxide is
currently underway.
Experimental Section
2-((4-Chlorophenyl)sulfonyl)-1-phenylethan-1-one
1
(3g).[13] White solid, 45.1 mg (77% yield); H NMR
General experimental procedure for the photoinduced
sulfonylative coupling of aryl/alkyl iodides 1, sulfur
dioxide, and silyl enolates 2. Silyl enolate 2 (0.20
mmol) in acetonitrile (8.0 mL) was added to a mixture
of aryl/alkyl iodide 1 (0.40 mmol) and DABCO·(SO2)2
(0.25 mmol) at N2 atmosphere. The mixture was stirred
under ultraviolet radiation at room temperature. After
12 hours, the solvent was evaporated under reduced
pressure. The residue was purified directly by flash
column chromatography (n-hexane/EA=4:1) to give the
corresponding product 3.
(400 MHz, CDCl3): δ 7.94 (d, J = 7.4 Hz, 2H), 7.84 (d,
J = 8.6 Hz, 2H), 7.64 (t, J = 7.4 Hz, 1H), 7.57 – 7.43 (m,
4H), 4.75 (s, 2H). 13C NMR (100 MHz, CDCl3): δ 187.9,
141.1, 137.0, 135.5, 134.5, 130.2, 129.5, 129.2, 128.9,
63.3.
2-((4-Fluorophenyl)sulfonyl)-1-phenylethan-1-one
1
(3h).[13] White solid, 44.4 mg (80% yield); H NMR
(400 MHz, CDCl3): δ 7.97 – 7.89 (m, 4H), 7.64 (t, J =
7.4 Hz, 1H), 7.50 (t, J = 7.8 Hz, 2H), 7.22 (t, J = 8.5 Hz,
2H), 4.75 (s, 2H). 13C NMR (100 MHz, CDCl3): δ
1
187.96, 166.1 (d, JCF =256.0 Hz), 135.6, 134.5, 131.7,
1-Phenyl-2-(phenylsulfonyl)ethan-1-one
(3a).[13]
131.6, 129.2, 128.9, 116.5 (d, 2JCF =23.0 Hz), 63.39.
2-((4-Acetylphenyl)sulfonyl)-1-phenylethan-1-one
(3i).[17] White solid, 46.5 mg (77% yield); 1H NMR (400
MHz, CDCl3): δ 8.14 (d, J = 8.4 Hz, 2H), 8.05 (d, J =
8.4 Hz, 2H), 7.98 (d, J = 7.6 Hz, 2H), 7.68 (t, J = 7.4
Hz, 1H), 7.54 (t, J = 7.7 Hz, 2H), 4.83 (s, 2H), 2.70 (s,
3H). 13C NMR (100 MHz, CDCl3): δ 196.6, 187.8,
142.2, 141.1, 135.5, 134.6, 129.2, 129.1, 128.9, 128.9,
63.1, 26.9.
White solid, 37.4 mg (72% yield); 1H NMR (400 MHz,
CDCl3): δ 7.91 (dd, J = 12.6, 7.7 Hz, 4H), 7.71 – 7.58
(m, 2H), 7.54 (t, J = 7.7 Hz, 2H), 7.47 (t, J = 7.7 Hz,
2H), 4.75 (s, 2H). 13C NMR (100 MHz, CDCl3): δ 188.0,
138.7, 135.7, 134.4, 134.2, 129.2, 129.2, 128.8, 128.5,
63.4.
1-Phenyl-2-tosylethan-1-one (3b).[13] White solid,
1
34.0 mg (62% yield); H NMR (400 MHz, CDCl3): δ
7.95 (d, J = 7.6 Hz, 2H), 7.76 (d, J = 8.2 Hz, 2H), 7.62
(t, J = 7.4 Hz, 1H), 7.48 (t, J = 7.7 Hz, 2H), 7.34 (d, J =
8.1 Hz, 2H), 4.72 (s, 2H), 2.44 (s, 3H). 13C NMR (100
MHz, CDCl3): δ 188.1, 145.3, 135.7, 134.3, 129.8,
129.3, 128.8, 128.6, 63.6, 21.7.
1-Phenyl-2-(pyridin-3-ylsulfonyl)ethan-1-one
1
(3j).[16] White solid, 29.1 mg (56% yield); H NMR
(400 MHz, CDCl3): δ 9.12 (s, 1H), 8.89 (d, J = 3.9 Hz,
1H), 8.22 (d, J = 8.0 Hz, 1H), 7.94 (d, J = 7.5 Hz, 2H),
7.65 (t, J = 7.4 Hz, 1H), 7.51 (t, J = 7.8 Hz, 3H), 4.82 (s,
2H). 13C NMR (100 MHz, CDCl3): δ 187.8, 154.6,
149.5, 136.7, 135.4, 135.3, 134.7, 129.1, 129.0, 123.6,
63.3.
2-((4-(tert-Butyl)phenyl)sulfonyl)-1-phenylethan-1-
1
one (3c).[14] White solid, 38.1 mg (61% yield); H NMR
(400 MHz, CDCl3): δ 7.92 (d, J = 7.6 Hz, 2H), 7.81 (d,
4
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10.1002/adsc.201700525
Advanced Synthesis & Catalysis
2-(Butylsulfonyl)-1-phenylethan-1-one
(3k).[18] CDCl3): δ 8.12 – 7.90 (m, 2H), 7.66 (d, J = 5.5 Hz, 1H),
White solid, 25.9 mg (54% yield); 1H NMR (400 MHz, 7.61 – 7.45 (m, 2H), 4.58 (d, J = 13.3 Hz, 2H), 3.26 (m,
CDCl3): δ 8.02 (d, J = 7.4 Hz, 2H), 7.66 (t, J = 7.4 Hz, 2H), 1.90 (m, 2H), 1.40 (m, 8H), 0.94 – 0.80 (m, 3H).
1H), 7.53 (t, J = 7.8 Hz, 2H), 4.57 (s, 2H), 3.42 – 3.11 13C NMR (100 MHz, CDCl3): 189.3, 135.8, 134.6,
(m, 2H), 1.97 – 1.81 (m, 2H), 1.51 (dd, J = 14.9, 7.4 Hz, 129.3, 129.0, 59.5, 53.7, 31.4, 28.7, 28.3, 22.5, 21.9,
2H), 0.98 (t, J = 7.4 Hz, 3H). 13C NMR (100 MHz, 14.0. HRMS (ESI) calcd for C15H23O3S+: 283.1362
CDCl3): δ 189.3, 135.7, 134.6, 129.3, 129.0, 59.8, 53.4, (M+H+), found: 283.1359.
23.9, 21.6, 13.5.
2-(Octylsulfonyl)-1-phenylethan-1-one (3s). White
2-(Phenylsulfonyl)-1-(p-tolyl)ethan-1-one (3l).[19] solid, 30.2 mg (51% yield); H NMR (400 MHz,
White solid, 47.6 mg (87% yield); 1H NMR (400 MHz, CDCl3): δ 8.02 (d, J = 7.8 Hz, 2H), 7.66 (t, J = 7.2 Hz,
CDCl3): δ 7.89 (d, J = 7.6 Hz, 2H), 7.83 (d, J = 8.1 Hz, 1H), 7.53 (t, J = 7.5 Hz, 2H), 4.57 (s, 2H), 3.37 – 3.14
2H), 7.65 (t, J = 6.3 Hz, 1H), 7.54 (m, 2H), 7.26 (t, J = (m, 2H), 1.97 – 1.80 (m, 2H), 1.51 – 1.39 (m, 2H), 1.29
3.7 Hz, 2H), 4.71 (s, 2H), 2.41 (s, 3H). 13C NMR (100 (m, 8H), 0.87 (m, 3H). 13C NMR (100 MHz, CDCl3):
MHz, CDCl3): δ 187.5, 145.6, 138.8, 134.2, 133.3, 189.3, 135.7, 134.6, 129.3, 129.0, 59.5, 53.7, 31.7, 29.0,
1
129.5, 129.4, 129.2, 128.5, 63.4, 21.8.
28.9, 28.3, 22.6, 21.9, 14.0. HRMS (ESI) calcd for
1-(4-Methoxyphenyl)-2-(phenylsulfonyl)ethan-1-
C16H25O3S+: 297.1519 (M+H+), found: 297.1525.
one (3m).[20] White solid, 47.4 mg (78% yield); H
2-(((2,3-Dihydrobenzofuran-3-yl)methyl)sulfonyl) -
1
NMR (400 MHz, CDCl3): δ 7.94 (d, J = 8.9 Hz, 2H), 1-phenylethan-1-one (6). Colourless oil, 33.2 mg (53%
7.75 (d, J = 8.2 Hz, 2H), 7.33 (d, J = 8.1 Hz, 2H), 6.95 yield); 1H NMR (400 MHz, CDCl3): δ 8.01 (d, J = 7.5
(d, J = 8.9 Hz, 2H), 4.66 (s, 2H), 3.89 (s, 3H), 2.44 (s, Hz, 2H), 7.68 (t, J = 7.4 Hz, 1H), 7.54 (t, J = 7.7 Hz,
3H). 13C NMR (100 MHz, CDCl3): δ 186.3, 164.5, 2H), 7.27 (d, J = 5.6 Hz, 1H), 7.19 (t, J = 7.7 Hz, 1H),
145.3, 135.7, 131.9, 129.8, 128.9, 128.6, 114.0, 63.6, 6.91 (t, J = 7.5 Hz, 1H), 6.83 (d, J = 8.0 Hz, 1H), 4.76 (t,
55.6, 21.7.
1-(4-Chlorophenyl)-2-(phenylsulfonyl)ethan-1-one
J = 9.2 Hz, 1H), 4.71 – 4.52 (m, 3H), 4.15 (dt, J = 11.7,
4.6 Hz, 1H), 3.77 (dd, J = 14.0, 2.9 Hz, 1H), 3.50 (dd, J
1
(3n).[13] White solid, 47.0 mg (80% yield); H NMR = 14.0, 10.8 Hz, 1H). 13C NMR (100 MHz, CDCl3): δ
(400 MHz, CDCl3): δ 7.89 (m, 4H), 7.69 (t, J = 7.5 Hz, 189.1, 159.7, 135.5, 134.9, 129.4, 129.3, 129.1, 126.7,
1H), 7.57 (t, J = 7.8 Hz, 2H), 7.47 (d, J = 8.6 Hz, 2H), 124.4, 121.0, 110.1, 75.8, 60.5, 57.5, 36.0. HRMS (ESI)
4.70 (s, 2H). 13C NMR (100 MHz, CDCl3): δ 186.8, calcd for C17H17O4S+: 317.0842 (M+H+), found:
141.2, 134.4, 134.0, 130.7, 129.3, 129.2, 128.5, 63.6.
1-(4-Fluorophenyl)-2-(phenylsulfonyl)ethan-1-one
317.0854.
1
(3o).[19] White solid, 45.1 mg (81% yield); H NMR
Acknowledgements
(400 MHz, CDCl3): δ 8.05 – 7.96 (m, 2H), 7.91 – 7.85
(m, 2H), 7.69 (t, J = 7.5 Hz, 1H), 7.57 (t, J = 7.8 Hz,
2H), 7.16 (t, J = 8.5 Hz, 2H), 4.71 (s, 2H). 13C NMR
(100 MHz, CDCl3): δ 186.4, 166.5 (d, 1JCF = 257.0 Hz),
Financial support from National Natural Science
Foundation of China (Nos. 21672037, 21532001) is
gratefully acknowledged.
2
138.5, 134.4, 132.3, 132.2, 129.3, 128.5, 116.2 (d, JCF
= 22.0 Hz), 63.6.
2-(Pentylsulfonyl)-1-phenylethan-1-one (3p). White
solid, 29.1 mg (57% yield); H NMR (400 MHz,
CDCl3): δ 8.02 (d, J = 7.7 Hz, 2H), 7.65 (t, J = 7.1 Hz,
1H), 7.52 (t, J = 7.5 Hz, 2H), 4.57 (s, 2H), 3.32 – 3.13
(m, 2H), 1.99 – 1.79 (m, 2H), 1.45-1.38 (m, 4H), 0.93 (t,
J = 7.0 Hz, 3H). 13C NMR (100 MHz, CDCl3): 189.3,
135.7, 134.6, 129.3, 129.0, 59.5, 53.7, 30.4, 22.1, 21.6,
13.7. HRMS (ESI) calcd for C13H19O3S+: 255.1049
(M+H+), found: 255.1057.
Supporting Information Available:
1
1
Experimental procedure, characterization data, H, &
13C NMR spectra of compounds 3.
References
[1] Transition Metal Reagents and Catalysts, Edited by
J. Tsuji, John Wiley & Sons, Ltd, 2000.
[2] a) K. C. Nicolaou, P. G. Bulger, D. Sarlah, Angew.
Chem. Int. Ed. 2005, 44, 4442; b) K. C. Nicolaou, P.
G. Bulger, D. Sarlah, Angew. Chem. Int. Ed. 2005,
44, 4490.
2-(Hexylsulfonyl)-1-phenylethan-1-one (3q). White
solid, 30.1 mg (56% yield); H NMR (400 MHz,
1
CDCl3): δ 8.02 (d, J = 7.9 Hz, 2H), 7.66 (t, J = 7.3 Hz,
1H), 7.53 (t, J = 7.5 Hz, 2H), 4.57 (s, 2H), 3.37 – 3.15
(m, 2H), 1.89 (m, 2H), 1.49 – 1.42 (m, 2H), 1.33 (m,
4H), 0.90 (t, J = 6.2 Hz, 3H). 13C NMR (100 MHz,
CDCl3): 189.3, 135.7, 134.6, 129.3, 129.0, 59.5, 53.7,
31.1, 28.0, 22.3, 21.8, 13.9. HRMS (ESI) calcd for
C14H21O3S+: 269.1206 (M+H+), found: 269.1196.
[3] a) Y. Harrak, G. Casula, J. Basset, G. Rosell, S.
Plescia, D. Raffa, M. G. Cusimano, R. Pouplana, M.
D. Pujol, J. Med. Chem. 2010, 53, 6560; b) D. A.
Smith, R. M. Jones, Curr. Opin. Drug Discovery
Dev. 2008, 11, 72; c) Y. Noutoshi, M. Ikeda, T.
Saito, H. Osada, K. Shirasu, Front Plant Sci. 2012, 3,
245; d) M. Bartholow, Top 200 Drugs of 2011.
2-(Heptylsulfonyl)-1-phenylethan-1-one (3r). White
solid, 30.6 mg (54% yield); H NMR (400 MHz,
Pharmacy
Times.
1
5
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10.1002/adsc.201700525
Advanced Synthesis & Catalysis
http://www.pharmacytimes.com/publications/issue/2
012/July2012/Top-200-Drugs-of-2011, accessed on
July 18, 2016; e) For a list of topdrugs by year, see:
http://njardarson.lab.arizona.edu/content/top-
pharmaceuticals-poster, accessed on July 18, 2016; f)
J. Drews, Science 2000, 287, 1960; g) M. J. El-Hibri,
S. A. Weinberg, In Encyclopedia of Polymer Science
h) D. Zheng, R. Mao, Z. Li, J. Wu, Org. Chem.
Front. 2016, 3, 359; i) R. Mao, D. Zheng, H. Xia, J.
Wu, Org. Chem. Front. 2016, 3, 693; j) K. Zhou, H.
Xia, J. Wu, Org. Chem. Front. 2016, 3, 865; k) J.
Yu, R. Mao, Q. Wang, J. Wu, Org. Chem. Front.
2017, 4, 617; l) T. Liu, D. Zheng, J. Wu, Org. Chem.
Front. 2017, 4, 1079.
and Technology, Ed. H. F. Mark, Wiley: New York, [8] a) W. Zhang, M. Luo, Chem. Commun., 2016, 52,
2014, 179; h) N.-W. Liu, S. Liang, G. Manolikakes,
Synthesis 2016, 48, 1939; i) N. S. Simpkins,
Sulfones in Organic Synthesis, Pergamon Press,
Oxford, 1993; j) Y. Fang, Z. Luo, X. Xu, RSC Adv.
2016, 6, 5966; k) J. Aziz, S. Messaoudi, M. Alami,
A. Hamze, Org. Biomol. Chem. 2014, 12, 9743.
[4] a) B. Nguyen, E. J. Emmet, M. C. Willis, J. Am.
Chem. Soc. 2010, 132, 16372; b) E. J. Emmet, C. S.
Richards-Taylor, B. Nguyen, A. Garcia-Rubia, R.
Hayter, M. C. Willis, Org. Biomol. Chem. 2012, 10,
4007; c) L. Martial, Synlett. 2013, 24, 1595.
2980; b) J. Sheng, Y. Li, G. Qiu, Org. Chem. Front.
2017, 4, 95; c) A. T. Davies, J. M. Curto, S. W.
Bagley, M. C. Willis, Chem. Sci. 2017, 8, 1233; d)
B. Du, Y. Wang, W. Sha, P. Qian, H. Mei, J. Han,
Y. Pan, Asian J. Org. Chem. 2017, 6, 153; e) A. L.
Tribby, I. Rodríguez, S. Shariffudin, N. D. Ball, J.
Org. Chem. 2017, 82, 2294; f) N.-W. Liu, S. Liang,
G. Manolikakesa, Adv. Synth. Catal, 2017, 359,
1308; g) D. Zheng, M. Chen, L. Yao, J. Wu, Org.
Chem. Front. 2016, 3, 985; h) T. Liu, D. Zheng, Y.
Ding, X. Fan, J. Wu, Chem. Asian J. 2017, 12, 465;
i) Y. Xiang, Y. Li, Y. Kuang, J. Wu, Chem. Eur. J.
2017, 23, 1032.
[5] For reviews: a) G. Liu, C. Fan, J. Wu, Org. Biomol.
Chem. 2015, 13, 1592; b) P. Bisseret, N. Blanchard,
Org. Biomol. Chem. 2013, 11, 5393; c) A. S. [9] For reviews, see: a) T. P. Yoon, M. A. Ischay, J. Du,
Deeming, E. J. Emmett, C. S. Richards-Taylor, M.
C. Willis, Synthesis 2014, 46, 2701.
Nat. Chem. 2010, 2, 527; b) J. M. R. Narayanam, C.
R. J. Stephenson, Chem. Soc. Rev. 2011, 40, 102; c)
J. Xuan, W.-J. Xiao, Angew. Chem. Int. Ed. 2012, 51,
6828; d) L. Shi, W. Xia, Chem. Soc. Rev. 2012, 41,
7687; e) Y.-M. Xi, H. Yi, A. Lei, Org. Biomol.
Chem. 2013, 11, 2387; f) C. K. Prier, D. A. Rankic,
D. W. C. MacMillan, Chem. Rev. 2013, 113, 5322; g)
D. M. Schultz, T. P. Yoon, Science 2014, 343, 985;
h) M. N. Hopkinson, B. Sahoo, J.-L. Li, F. Glorius,
Chem. Eur. J. 2014, 20, 3874; i) J. Xuan, Z.-G.
Zhang, W.-J. Xiao, Angew. Chem. Int. Ed. 2015, 54,
15632; j) J.-R. Chen, X.-Q. Hu, L.-Q. Lu, W.-J.
Xiao, Chem. Soc. Rev. 2016, 45, 2044; k) S. Protti,
M. Fagnoni, D. Ravelli, ChemCatChem 2015, 7,
1516; l) M. D. Karkas, B. S. Matsuura, C. R. J.
Stephenson, Science 2015, 349, 1285; m) R.
Brimioulle, D. Lenhart, M. M. Maturi, T. Bach,
Angew. Chem. Int. Ed. 2015, 54, 3872; n) D. Ravelli,
M. Fagnoni, A. Albini, Chem. Soc. Rev. 2013, 42, 97;
o) T. P. Yoon, ACS Catal. 2013, 3, 895; p) M. A.
Ischay, T. P. Yoon, Eur. J. Org. Chem. 2012, 3359;
q) N. Hoffmann, ChemSusChem 2012, 5, 352; r) J.
W. Tucker, C. R. J. Stephenson, J. Org. Chem. 2012,
77, 1617.
[6] a) D. Zheng, J. Yu, J. Wu, Angew. Chem. Int. Ed.
2016, 55, 11925; b) D. Zheng, Y. An, Z. Li, J. Wu,
Angew. Chem. Int. Ed. 2014, 53, 2451; c) Y. Li, D.
Zheng, H. Xia, J. Wu, Org. Chem. Front. 2016, 3,
574; d) W. Li, H. Li, P. Langer, M. Beller, X.-F.
Wu, Eur. J. Org. Chem. 2014, 3101; e) W. Li, M.
Beller, X.-F. Wu, Chem. Commun. 2014, 50, 9513;
f) X. Wang, L. Xue, Z. Wang, Org. Lett. 2014, 16,
4056; g) A. S. Deeming, C. J. Russell, M. C. Willis,
Angew. Chem. Int. Ed. 2015, 54, 1168; h) C. C.
Chen, J. Waser, Org. Lett. 2015, 17, 736; i) A. S.
Deeming, C. J. Rusell, A. J. Hennessy, M. C. Willis,
Org. Lett. 2014, 16, 150; j) B. N. Rocke, K. B.
Bahnck, M. Herr, S. Lavergne, V. Mascitti, C.
Perreault, J. Polivkova, A. Shavnya, Org. Lett. 2014,
16, 154; k) E. J. Emmett, B. R. Hayter, M. C. Willis,
Angew. Chem. Int. Ed. 2013, 52, 12679; l) E. J.
Emmett, B. R. Hayter, M. C. Willis, Angew. Chem.
Int. Ed. 2014, 38, 10204; m) A. Shavnya, S. B.
Coffey, A. C. Smith, V. Mascitti, Org. Lett. 2013,
15, 6226; n) M. W. Johnson, S. W. Bagley, N. P.
Mankad, R. G. Bergman, V. Mascitti, F. D. Toste,
Angew. Chem. Int. Ed. 2014, 53, 4404; o) A. [10] For selected examples, see: a) J. A. Terrett, J. D.
Shavnya, K. D. Hesp, V. Mascitti, A. C. Smith,
Angew. Chem. Int. Ed. 2015, 54, 13571; p) A. S.
Deeming, C. J. Russell, M. C. Willis, Angew. Chem.
Int. Ed., 2016, 55, 747; q) A. S. Tsai, J. M. Curto, B.
N. Rocke, A. R. Dechert-Schmitt, G. K. Ingle, V.
Mascitti, Org. Lett. 2016, 18, 508.
Cuthbertson, V. W. Shurtleff, D. W. C. MacMillan,
Nature 2015, 524, 330; b) C. C. Nawrat, C. R.
Jamison, Y. Slutskyy, D. W. C. MacMillan, L. E.
Overman, J. Am. Chem. Soc. 2015, 137, 11270; c) J.
Jin, D. W. C. MacMillan, Nature 2015, 525, 87; d)
X.-Q. Hu, J.-R. Chen, Q. Wei, F.-L. Liu, Q.-H.
Deng, A. M. Beauchemin, W.-J. Xiao, Angew.
Chem. Int. Ed. 2014, 53, 12163; e) Y. Masuda, N.
Ishida, M. Murakami, J. Am. Chem. Soc. 2015, 137,
14063; f) M. El Khatib, R. A. M. Serafim, G. A.
Molander, Angew. Chem. Int. Ed. 2016, 55, 254; g)
J. C. Tellis, D. N. Primer, G. A. Molander, Science
2014, 345, 433; h) H.-Q. Do, S. Bachman, A. C.
Bissember, J. C. Peters, G. C. Fu, J. Am. Chem. Soc.
2014, 136, 2162; i) A. C. Bissember, R. J. Lundgren,
[7] a) S. Ye, J. Wu, Chem. Commun. 2012, 48, 10037;
b) S. Ye, J. Wu, Chem. Commun. 2012, 48, 7753; c)
S. Ye, H. Wang, Q. Xiao, Q. Ding, J. Wu, Adv.
Synth. Catal. 2014, 356, 3225; d) Y. An, D. Zheng,
J. Wu, Chem. Commun. 2014, 50, 11746; e) Y. Luo,
X. Pan, C. Chen, L. Yao, J. Wu, Chem. Commun.
2015, 51, 180; f) D. Zheng, Y. Li, Y. An, J. Wu,
Chem. Commun. 2014, 50, 8886; g) D. Zheng, Y.
Kuang, J. Wu, Org. Biomol. Chem. 2015, 13, 10370;
6
This article is protected by copyright. All rights reserved.

10.1002/adsc.201700525
Advanced Synthesis & Catalysis
S. E. Creutz, J. C. Peters, G. C. Fu, Angew. Chem.,
Int. Ed. 2013, 52, 5129.
[11] For review, see: G. Qiu, Y. Li, J. Wu, Org. Chem.
Front. 2016, 3, 1011.
[12] L. Li, W. Liu, H. Zeng, X. Mu, G. Cosa, Z. Mi, C.
Li, J. Am. Chem. Soc. 2015, 137, 8328.
[13] Q. Lu, J. Zhang, G. Zhao, Y. Qi, H. Wang, A. Lei, J.
Am. Chem. Soc. 2013, 135, 11481.
[14] Y. Xia, X. Chen, L. Qu, K. Sun, X. Xia, W. Fu, X.
Chen, Y. Yang, Y. Zhao, C. Li, Asian J. Org. Chem.
2016, 5, 878.
Lett. 2011, 13, 208.
[16] H. Jiang, Y. Cheng, Y. Zhang, S. Yu, Eur. J. Org.
Chem. 2013, 5485.
[17] W. Wei, J. Wen, D. Yang, M. Wu, J. You, H. Wang,
Org. Biomol. Chem. 2014, 12, 7678.
[18] A. S. Deeming, C. J. Russell, A. J. Hennessy, M. C.
Willis, Org. Lett. 2014, 16, 150.
[19] Q. Lu, J. Zhang, P. Peng, G. Zhang, Z. Huang, H.
Yi, J. T. Millercd, A. Lei, Chem. Sci. 2015, 6, 4851.
[20] X. Tang, L. Huang, Y. Xu, J. Yang, W. Wu, H.
Jiang, Angew. Chem. Int. Ed. 2014, 53, 4205.
[15] G. C. Tsui, Q. Glenadel, C. Lau, M. Lautens, Org.
7
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FULL PAPER
Synthesis of β-Keto Sulfones
via Coupling of Aryl/Alkyl
Halides, Sulfur Dioxide and
Silyl Enolate through Metal-
Free Photoinduced C-X Bond
Dissociation
Aryl/alkyl
+
X
O
UV
MeCN
O O
S
+
Ar
OTMS
Ar
aryl/alkyl
DABCO.(SO2)2
X = I, Br
25 examples
36-87% yield
metal-free sulfonylative coupling of aryl/alkyl halides
room temperature
Adv. Synth. Catal. 2017, Volume, Page – Page
Xinxing Gong, Yechun Ding, Xiaona Fan,* and
Jie Wu*
8
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