Ammonium iodide-induced sulfonylation of alkenes with DMSO and water toward the synthesis of vinyl methyl sulfones

Article abstract of DOI:10.1039/c4cc07606k

A novel ammonium iodide-induced sulfonylation of alkenes with DMSO and water toward the synthesis of vinyl methyl sulfones is described. The process proceeded smoothly under metal-free conditions with high stereoselectivity and good functional group toler

Full text of DOI:10.1039/c4cc07606k

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COMMUNICATION
Ammonium iodide-induced sulfonylation of alkenes with DMSO and
water toward the synthesis of vinyl methyl sulfones†
Xiaofang Gao, Xiaojun Pan, Jian Gao, Huawen Huang, Gaoqing Yuan*, and Yingwei Li*
Received (in XXX, XXX) Xth XXXXXXXXX 20XX, Accepted Xth XXXXXXXXX 20XX
5
DOI: 10.1039/b000000x
A novel ammonium iodide-induced sulfonylation of alkenes
with DMSO and water toward the synthesis of vinyl methyl
sulfones is described. The process proceeded smoothly under
metal-free conditions with high stereoselectivity and good
10 functional group tolerance. The reaction mechanism was
revealed to proceed through a domino reaction of oxidation
and elimination after the radical addition to alkenes.
Vinyl sulfones are important compounds in organic and
medicinal chemistry due to their versatile reactivities and
15 potential biological activities.1 In the last decades, the
synthesis of vinyl sulfones has attracted more and more
attention from chemists.2ꢀ6 Traditional pathways for the
preparation of vinyl sulfones typically include the direct
oxidation of vinyl sulfides and Heck reaction of ary halides
20 with vinyl sulfones.2,3 However, these methods suffer from
poor selectivity or expensive starting materials. In recent
years, some efficient metalꢀcatalyzed approaches have been
investigated such as crossꢀcoupling reactions of olefins and its
derivatives (vinyl halides, stannanes, and arylboronic acids)
25 with sulfone reagents including sulfinate salts, sulfonyl
chlorides, or sulfonyl hydrazides (Scheme 1a).4 Recently,
some researchers have achieved this transformation in the
absence of transitionꢀmetal catalysts.5 Despite remarkable
improvement and efficiency of such reactions, the discovery
30 of sulfone sources from inexpensive and readily available
reagents is highly desired. Very recently, Loh and coꢀworkers
published an alternative Cuꢀcatalyzed methyl sulfonylation of
alkynes using DMSO and O2 as a methyl sulfone source (–
SO2Me) (Scheme 1b).6 Herein, we disclose a novel and
35 efficient ammonium iodideꢀinduced sulfonylation of alkenes
in which DMSO and H2O are used as the starting materials to
provide the source of –SO2Me (Scheme 1c). To the best of
our knowledge, such a route for the synthesis of vinyl methyl
sulfones has not been reported under metal free conditions.
50 Scheme 1 Different routes for the synthesis of vinyl methyl
sulfones.
screening a variety of reaction parameters, the sulfonylation
of 1a gave 2a in an excellent yield with sole stereoselectivity
under the standard conditions (Table 1, entry 1: 4.0 equiv
55 NH4I, 0.5 mL H2O, 1.0 mL DMSO, at 130 oC for 24 h;
optimization details, see SI). The effects of the other factors
on the reaction are shown in entries 2–13. Neither the organic
tetrabutylammonium iodide (nꢀBu4NI) nor the inorganic KI
did afford the desired product (entries 2 and 3), suggesting
60 that iodide anion is not the real form for NH4I participated in
this conversion. No desired transformation was observed
employing similar ammonium salt NH4Br (entry 4), ruling out
+
the function of NH4 in this reaction. When using 2.0 equiv of
I2 instead of 4.0 equiv of NH4I, 2a was not obtained with only
65 benzoic acid as the product, whereas 15% yield of 2a was
determined with 0.5 equiv of I2 (entries 5 and 6). In addition,
when the reaction was performed with aqueous ammonia, the
yield of the product was not improved (entry 7). However, in
the presence of catalytic amounts of I2, no desired product
70 was obtained only recovering the unreacted styrene (entry 8).
These results clearly indicated that I2 was indeed the actual
form to promote this conversion and its concentration had a
great impact on the selectivity of reaction. It was also
observed that both the adding amount of NH4I and reaction
75 temperature were important parameters for a high yield
(entries 10–12). In the absence of water, the yield of the target
product dramatically decreased (entry 13).
40
Using styrene (1a) and DMSO as the substrates, optimal
conditions were first examined for the sulfonylation. After
School of Chemistry and Chemical Engineering, South China University
of Technology, Guangzhou, 510640, P. R. China
45 Eꢀmail: gqyuan@scut.edu.cn, liyw@scut.edu.cn
† Electronic Supplementary Information (ESI) available: Detailed
experimental procedures, characterization of products, and NMR spectral
charts. See DOI: 10.1039/b000000x/
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DOI: 10.1039/C4CC07606K
Table 1 Effect of various factors on the reaction.
1,1ꢀdisubstituted olefins. This isomerization result is
35 consistent with the previous studies by Jiang 4b and Li.5c
Table 2 Scope of alkene substrates.a
Entry
Variation from the standard conditions
Yield/%a
1
2
3
4
5
6
7
none
98
0
Bu4NI instead of NH4I
KI instead of NH4I
2a: R1 = H; 24 h, 98%
2b: R1 = Me; 24 h, 94%
2c: R1 = OMe; 24 h, 75%
2d: R1 = tBu; 24 h, 82%
2e: R1 = F; 20 h, 99%
2f: R1 = Cl; 22 h, 96%
2g: R1 = Br; 26 h, 95%
2h: R1 = CO2Me; 30 h, 93%
2i: R1 = CN; 22 h, 92%
2j: R1 = NO2; 28 h, 96%
2k: R1 = CF3; 20 h, 99%
0
O
S
NH4Br instead of NH4I
2.0 equiv of I2 instead of NH4I
0.5 equiv of I2 instead of NH4I
0.5 equiv of I2 + 0.5mL NH3.H2O instead of
NH4I
0
O
R1
0
O
S
O
15
17
O
R1
3
2
2l: R1 = (3-Me); 24 h, 92%
2m: R1 = (3-CF3); 20 h, 98%
2n: R1 = (2-Me); 24 h, 90%
S
O
2o: 24 h, 88%
8
10 mol % I2 instead of NH4I
HI instead of NH4I
0
O
O
Ph
S
O
S
9
8
O
S
O
S
F
F
O
Ph
10
11
12
13
14b
15c
16c
1.0 equiv of NH4I
0
O
O
100 oC instead of 130 oC
120 oC instead of 130 oC
without adding H2O
under N2 atmosphere
adding TEMPO
0
2q: 24 h, 89%
2r: 24 h, 88%
2p: 36 h, 68%
SO2Me
39
12
91
0
O
S
O
S
O
N
O
S
2s: 30 h, 73%
2u
: 24 h, 87%
2t: 40 h, 58%
adding BHT
0
O
S
O
S
O
S
Ph
O
a Determined by 1H NMR (internal standard: 1,3,5ꢀtrimethyl
benzene). b Run for 32 h. c 1.0 equiv of radical trapper was used.
Ph
Ph
O
O
2v: 36 h, 86%b
2w: 24 h, 0%
2x: 24 h, 46%
42 h, 85%c
With the optimal conditions in hand, we next evaluated the
substrates scope and limitations of our protocol (Table 2 and
3). In general, the reactions of alkenes bearing electronꢀ
withdrawing groups gave slightly higher yields of product
than those containing electronꢀdonating moieties, as well as
much faster reaction rates (2a–2n). All of the reactions
proceeded with excellent regioselectivity, and various
40 a Reaction conditions: alkene (1 mmol), NH4I (4.0 equiv), H2O (0.5 mL),
DMSO (1.0 mL) and 130 oC . Isolated yield. b Cisꢀβꢀmethyl styrene. c
Transꢀβꢀmethyl styrene.
5
Table 3 Scope of 1,1ꢀdisubstituted alkene substrates.a
10 functional groups such as methyl, methoxyl, fluoro, chloro,
bromo, ester, cyanide, nitro, and trifluoromethyl groups at the
meta or para positions of the aromatic ring were reasonably
well tolerated under the standard conditions. The reaction of
disubstituted alkenes was also efficient (2o,2q). Polyaryl
15 substrates such as 2ꢀnaphthalene and 9ꢀphenanthrene retarded
the reaction even after an extended reaction time, albeit in
moderate yields (2s–2t), possibly due to the steric
interference. In addition, heteroaromatic olefins proceeded
smoothly to afford the target products in good yields (2r, 2u).
20 Gratifyingly, interminal alkenes were also productive,
exclusively forming (E)ꢀsulfonyl product (2v) either from the
cisꢀ or transꢀβꢀmethyl styrene. However, allylbenzene failed
to give the corresponding product (2w), and the similar result
was also observed with alkyl alkenes as substrates. On the
25 contrary conjugated diene afforded the target product in a
moderate yield (2x), indicating that conjugative effect played
an important role in stabilizing the intermediate.7
45
a Reaction conditions: as shown in Table 2. Isolated yield.
Moreover, the reaction is scalable and practical as an
excellent yield (95%) of 2a was obtained when the reaction
was performed on a 10.0 mmol scale (eq 1).8
Interestingly, when αꢀmethylstyrene (1y) was applied as
substrate, isomerization product (2y) was obtained instead of
30 the desired vinyl sulfone (Table 3). Other similar olefins were
tested under the standard conditions, obtaining the isomerized
products in good yields (2z–2ab) as well. These results
suggested that a different elimination protocol was existed for
50
In order to investigate the reaction mechanism, a series of
control experiments were carried out. Under the protection of
N2, the target product 2a could be obtained in an excellent
55 yield (Table 1, entry 14), indicating that the oxygen atom of
2
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DOI: 10.1039/C4CC07606K
sulfone group in 2a does not come from O2. The isotopic
labeling experiment with H218O was conducted (eq 2).8 These
experimental results make sure that one oxygen atom of the
sulfone group of 2a is from H2O and the other results from
DMSO. The deuterium labeling experiment with DMSOꢀd6
(eq 3) confirms that methylthiyl (MeS) originates from
DMSO. Further, a reaction profile was obtained in the
sulfonylation of styrene (1a) under the standard conditions
(Figure 1). Within reaction time 4 h, 2ꢀ(methylthio)ꢀ1ꢀ
50 the details of reaction mechanism and applications in organic
synthesis are currently underway in our laboratory.
5
10 phenylethanol (3a) was firstly detected in 20% yield, and
then 2ꢀ(methylsulfonyl)ꢀ1ꢀphenylethanol (4a) and (E)ꢀ(2ꢀ
(methylsulfonyl)vinyl) benzene (2a) were produced. During
the reaction process, 3a and 4a remained a low concentration
in the reaction mixture and disappeared at the end of reaction.
15 Simultaneously, the concentration of 2a increased with the
reaction time, thus implying that 3a and 4a were the
intermediates in this conversion. Indeed, discrete 3a and 4a
both could be completely converted to 2a under the otherwise
identical conditions.8 In addition, when the reaction was
20 performed in the presence of a stoichiometric amount of
TEMPO or BHT under the standard conditions, 2a was not
obtained (Table 1, entries 15 and 16). These results suggested
that the present reaction presumably proceeded through a
radical pathway.
Scheme 2 Proposed reaction mechanism.
We thank the National Natural Science Foundation of
55 China (21172079, 21322606, and 21436005), and
Guangdong
Natural
Science
Foundation
25
(10351064101000000) for financial support.
Notes and references
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2 (a) M. Tiecco, L. Testaferri, M. Tingoli, D. Chianelli and M.
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65
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A. Battace, T. Zair, H. Doucet and M. Santelli, Synthesis, 2006, 20,
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70 4 (a) N. Taniguchi, Synlett. 2011, 9, 1308; (b) X. Li, Y. Xu, W. Wu, C.
Jiang, C. Qi and H. Jiang, Chem. Eur. J., 2014, 20, 1; (c) M. Bian, F.
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Figure 1 Reaction profile in the NH4Iꢀinduced sulfonylation of
1a.
Based on the above results,
a plausible reaction
30 mechanism is proposed in Scheme 2. First, the radical initiator
I2 and precursor MeSH are generated through a series of
reactions, as shown in equations 4–6.9ꢀ11 Then, I2 is
decomposed to form iodine radical (eq 7),12 which attacks on
75
80
85
M.Beller and M. K. Tse, Org. Lett., 2007, 9, 3405.
5 (a) S. Tang, Y. Wu, W. Liao, R. Bai, C. Liu and A. Lei, Chem.
Commun., 2014, 50, 4496; (b) Y. Xu, X. Tang, W. Hu, W. Wu and H.
Jiang, Green Chem., 2014, 16, 3720; (c) X. Li, X. Xu and C. Zhou,
Chem. Commun., 2012, 48, 12240; (d) S. Liang, R. Zhang, G. Wang,
S. Chen and X. Yu, Eur. J. Org. Chem., 2013, 7050; (e) P. Katrun, S.
Chiampanichayakul, K. Korworapan, M. Pohmakotr, V. Reutrakul, T.
Jaipetch and C. Kuhakarn, Eur. J. Org. Chem., 2010, 5633.
MeSH to give
a
methylthiyl radical MeS· (eq 8).13
35 Subsequently, the radical MeS· is added to the alkene to
generate a radical intermediate I.14 At the same time, The
MeS· abstracts hydrogen from water to afford hydroxyl
radical (OH·). The rapid coupling reaction between the radical
intermediate I and OH· produces intermediate 3a, which is
40 further oxidized by DMSO15 and H2O2 resulting from selfꢀ
coupling of the radical OH·,16 to form intermediate 4a.
Finally, with the assistance of newly formed sulfone group, 2a
is generated via acidꢀcatalysed dehydration of 4a.
In conclusion, we have developed a novel and efficient
45 protocol of ammonium iodideꢀinduced sulfonylation of olefins
with DMSO and water, achieving excellent stereoselectivity
and high functional group tolerance. In addition, this
procedure provides a new valuable method of generating
methylthiyl radical (MeS·) from DMSO. Further studies on
6
7
8
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