Direct difunctionalization of alkynes with sulfinic acids and molecular iodine: A simple and convenient approach to (E)-β-iodovinyl sulfones

Article abstract of DOI:10.1039/c4ra13998d

A simple and convenient approach for the construction of β-iodovinyl sulfones has been developed via direct difunctionalization of alkynes with sulfinic acids and molecular iodine. The present reaction provides a highly efficient approach to a diverse range of substituted (E)-β-iodovinyl sulfones in moderate to good yields with excellent stereo- and regio-selectivities but no need for any metal catalyst or additives.

Full text of DOI:10.1039/c4ra13998d

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Direct difunctionalization of alkynes with sulfinic
acids and molecular iodine: a simple and
Cite this: RSC Adv., 2015, 5, 4416
convenient approach to (E)-b-iodovinyl sulfones†
*
Wei Wei, Jiangwei Wen, Daoshan Yang, Huijun Jing, Jinmao You and Hua Wang
A simple and convenient approach for the construction of b-iodovinyl sulfones has been developed via
direct difunctionalization of alkynes with sulfinic acids and molecular iodine. The present reaction
provides a highly efficient approach to a diverse range of substituted (E)-b-iodovinyl sulfones in
moderate to good yields with excellent stereo- and regio-selectivities but no need for any metal catalyst
or additives.
Received 6th November 2014
Accepted 9th December 2014
DOI: 10.1039/c4ra13998d
www.rsc.org/advances
As an important class of functionalized alkenes, b-halovinyl copper catalyzed iodosulfonylation of alkynes with aryl sul-
sulfones have drawn great attention from chemists, since they nates and MI (M ¼ K or Li).9 Unfortunately, these established
can serve as not only key structural motifs of biologically active methods might suffer from some obvious limitations such as
compounds and materials but also versatile building blocks for the low atom economy, the use of transition-metal catalyst, and
various organic transformations in synthetic chemistry.1 In view stoichiometric amounts of bases, toxic or potentially dangerous
of their importance, considerable efforts have been made to oxidants. Therefore, the development of simple, efficient, atom-
construct these frameworks.2 From the synthetic standpoint, economic, and environmentally-benign method for the
the direct difunctionalization of alkynes with sulfonyl halides construction of b-iodovinyl sulfones still remains a highly
represents one of most straightforward and useful tools for the desirable.
construction of b-halovinyl sulfones because of its advantages
With our growing interest in developing new and more effi-
in terms of synthetic efficiency and atom economy.3 Through cient ways for the construction of sulfone-containing organic
this route, both sulfone and halide functionalities can be compounds,10 we herein report a simple and convenient
introduced into the organic frameworks via the cascade C–S and approach for the synthesis of b-iodovinyl sulfones via the direct
C–Hal bond formation. In the past few decades, various b-bro- difunctionalization of alkynes with sulnic acids and molecular
movinyl and b-chlorovinyl sulfones have been effectively iodine (eqn (1)). The present reaction provides an efficient
synthesized via the difunctionalization of alkynes.2,3 Neverthe- approach to various substituted b-iodovinyl sulfones in
less, few examples for the construction of b-iodovinyl sulfones moderate to good yields with excellent stereo- and regio-
were reported owing to the instability of sulfonyl iodide.4 In selectivities making it unnecessary for any metal catalyst or
2002, Nair and co-workers reported a cerium(IV) ammonium additives.
nitrate (CAN) mediated reaction of alkynes with aryl sulnates
leading to b-iodo vinyl sulfones in the presence of KI.5 In 2010,
Kuhakarn et al. described PhI(OAc)2/KI-mediated reaction of
alkynes with aryl sulnates to give b-iodovinyl sulfones.6 In
2013, Li reported a convenient procedure for the synthesis of
(E)-b-iodovinyl sulfones through the TBHP mediated reaction of
aryl acetylenes with sulfonylhydrazides and iodine.7 Kuhakarn
et al. reported iodine mediated iodosulfonation reaction of
alkynes with sodium p-toluenesulnate in the presence of
1.5 equiv. of NaOAc.8 Very recently, Taniguchi demonstrated a
(1)
Initially, the reaction among phenylacetylene 1a, benzene-
sulnic acid 2a, and molecular iodine was investigated in DME
(1,2-dimethoxyethane) at room temperature under air. To our
delight, the desired product was obtained in 61% yield (Table 1,
entry 1). Preliminary exploration found that higher yields up to
88% were obtained when the reaction temperature was raised
further to 100 ꢀC (Table 1, entries 2–4). Among the solvents
tested, apparently, DME was found to the most efficient reac-
tion medium for this reaction (entry 4). 1,4-Dioxane, DMA
(1,1-dimethoxytrimethylamine), DCE (1,2-dichloroethane) and
CH3CN might also be effective (Table 1, entries 5–8).
The Key Laboratory of Life-Organic Analysis and Key Laboratory of Pharmaceutical
Intermediates and Analysis of Natural Medicine, School of Chemistry and Chemical
Engineering, Qufu Normal University, Qufu 273165, Shandong, China. E-mail:
huawang_qfnu@126.com
† Electronic supplementary information (ESI) available: Experimental details. See
DOI: 10.1039/c4ra13998d
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Nevertheless, lower yields were obtained when the reactions
were performed separately in DMF, DMSO, toluene, and H2O
(Table 1, entries 9–12). The proportion of the substrates could
also affect this transformation evidenced by the further opti-
mization, showing that the optimal proportion of phenyl-
acetylene, molecular iodine, and benzenesulnic acid was
1 : 1 : 2 (Table 1, entries 4, 13–15).
Table 2 Results for difunctionalization of alkynes with sulfinic acids
and molecular iodinea,b
Under the optimized conditions, the scope and limitations
of the reactions of various alkynes with sulnic acids were
investigated and the results are shown in Table 2. Accordingly,
alkynes bearing an electron-donating group (e.g., Me and OMe)
or an electron-withdrawing group (e.g., F, Cl, Br and CN) are
found to be tolerant in these transformations, and the corre-
sponding products were obtained in good to excellent yields
(3aa–3ia). It is noteworthy that this protocol could be tailored
for heteroaromatic alkyne (e.g., 3-ethynylthiophene) and
internal alkyne (e.g., prop-1-ynylbenzene) leading to the desired
products in 62% and 70% yields, respectively (3ja and 3ka).
Also, 1-ethynylnaphthalene could be employed in the reaction
to generate the desired product 3la in high yield. Nevertheless,
the corresponding products were obtained in relatively low
yields when ethyl propiolate and 1-hexyne 1n were used as the
substrates (3ma and 3na). In addition to benzenesulnic acid,
all substituted benzenesulnic acids containing either electron-
rich or electron-decient groups were suitable for this reaction
to furnish the corresponding products in good yields (3ab–3bd).
Even the sterically-hindered substituted arylsulnic acids
(e.g., 2-(triuoromethyl)benzenesulnic acid and 2-bromo-
benzenesulnic acid) and the bulky naphthalene-2-sulnic acid
Table 1 Optimization of the reaction conditionsa
Entry
Solvent
T (ꢀC)
Yieldb (%)
1
2
3
4
5
6
7
8
DME
DME
DME
DME
1,4-Dioxane
DMA
DCE
CH3CN
DMF
DMSO
Toluene
H2O
25
60
80
61
72
78
88
85
76
72
71
52
22
55
38
53c
69d
87e
100
100
100
100
100
100
100
100
100
100
100
100
9
10
11
12
13
14
15
DME
DME
DME
a
a
Reaction conditions: alkynes 1 (0.5 mmol), sulnic acids 2 (1 mmol),
Reaction conditions: phenylacetylene 1a (0.5 mmol), benzenesulnic
I2 (0.5 mmol), DME (2 mL), 100 ꢀC, 12–24 h. b Isolated yields based on 1.
acid 2a (1 mmol), I2 (0.5 mmol), solvent (2 mL), 25–100 ꢀC, 12 h.
b
c
d
Isolated yields based on 1a. 1a (0.5 mmol), 2a (0.5 mmol). 1a (0.6
mmol), 2a (0.5 mmol). e 1a (0.5 mmol), 2a (1.2 mmol).
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could also work well to produce the b-iodovinyl sulfones
(3ae–3ag) efficiently under the reaction conditions. Unfortu-
nately, when alkylsulnic acids such as methanesulnic acid
triuoromethanesulnic acid were used as the substrates, the
corresponding products were not obtained.
Notably, the present reaction can be effectively scaled up to
gram scale with the similar efficiency (2.96 g, with 80% yield for
the model reaction), suggesting that this simple protocol could
be employed as a practical method to access b-iodovinyl
sulfones. Furthermore, the synthetic utility of this reaction was
also investigated. When the resulting b-iodovinyl sulfones were
used to react with alkynes, the desired alkynylation products
were obtained in high yields (eqn (2)). Moreover, acetylenic
sulfones are an important class of synthetic intermediate.11
When stoichiometric amounts of K2CO3 was added into the
present model reaction system under the standard conditions,
the corresponding acetylenic sulfone 5aa was isolated in 78%
yield (eqn (3)). Interestingly, when alkenes reacted with sulnic
acids and molecular iodine in DCE, the corresponding (E)-vinyl
sulfones were obtained in good yields (eqn (4)). Therefore, the
developed reaction system can provide a simple, convenient,
and metal-free synthetic method to access vinylsulfone struc-
tural motifs, which extensively exist in various nature products,
biologically active compounds, and pharmaceuticals.12
Scheme 1 Possible reaction pathway.
(5)
Based the above experiments and referring to the previous
studies,4–10,13 the possible reaction pathways are proposed and
demonstrated in Scheme 1. Firstly, the sulfonyl radical 4 was
generated from sulnic acids under air. Subsequently, the
sulfonyl radical addition to alkyne 1 gives the alkenyl radical 5,
which further interacted with molecular iodine leading to the
formation of the desired b-iodovinyl sulfone 3 (Path A). Mean-
while, another pathway involving the direct iodosulfonylation of
alkynes with sulfonyl iodides that generated in situ from
molecular iodine and sulnic acids might also be involved in
the present reaction (Path B).6,7
In conclusion, we have developed a simple and efficient
method for the synthesis of (E)-b-iodovinyl sulfones via the
direct difunctionalization of alkynes with sulnic acids and
molecular iodine. The developed protocol provides an alterna-
tive and highly attractive route to various (E)-b-iodovinyl
sulfones from the simple and readily available starting mate-
rials, and especially it avoids the use of any transition-metal
catalyst, and stoichiometric amounts of bases, toxic or poten-
tially dangerous oxidants. Such a new synthesis methodology
for (E)-b-iodovinyl sulfones would nd the potential applica-
tions in the elds of synthetic and pharmaceutical chemistry.
(2)
(3)
(4)
Acknowledgements
This work was supported by the National Natural Science
Foundation of China (no. 21302109, 21302110, and 21375075),
the Taishan Scholar Foundation of Shandong Province, the
Excellent Middle-Aged and Young Scientist Award Foundation
of Shandong Province (BS2013YY019), and the Scientic
Research
Foundation
of
Qufu
Normal
University
It is known that sulfonyl radical species are easily generated
from sulnic acids under air.10b–d,13 Therefore, a radical process
might be presumably involved in the present reaction system.
As shown in eqn (5), when TEMPO (2,2,6,6-tetramethyl-1-
(BSQD 2012020).
References
piperidinyloxy),
a
well-known radical radical-capturing
1 For selected examples, see: (a) J. T. Palmer, D. Rasnick,
J. L. Klaus and D. Bromme, J. Med. Chem., 1995, 38, 3193;
(b) L. Ni, X. S. Zheng, P. K. Somers, L. K. Hoong, R. R. Hill,
E. M. Marino, K.-L. Suen, U. Saxena and C. Q. Meng,
Bioorg. Med. Chem. Lett., 2003, 13, 745; (c) I. Forristal,
species, was added into this reaction system, the present reac-
tion was completely inhibited as expected. It suggests that a
radical pathway might be involved in this transformation.
4418 | RSC Adv., 2015, 5, 4416–4419
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Paper
J. Sulfur Chem., 2005, 26, 163; (d) D. C. Meadows and
RSC Advances
6 P. Katrun, S. Chiampanichayakul, K. Korworapan,
M. Pohmakotr, V. Reutrakul, T. Jaipetch and C. Kuhakarn,
Eur. J. Org. Chem., 2010, 5633.
7 X. Q. Li, X. S. Xu and X. H. Shi, Tetrahedron Lett., 2013, 54,
3071.
8 T. Sawangphon, P. Katrun, K. Chaisiwamongkhol,
M. Pohmakotr, V. Reutrakul, T. Jaipetch, D. Soorukram
and C. Kuhakarn, Synth. Commun., 2013, 43, 1692.
9 N. Taniguchi, Tetrahedron, 2013, 70, 1984.
J. Gervay-Hague, Med. Res. Rev., 2006, 26, 793; (e) R. Ettari,
E. Nizi, M. E. D. Francesco, M.-A. Dude, G. Pradel, R. Vicik,
T. Schirmeister, N. Micale, S. Grasso and M. Zappala,
J. Med. Chem., 2008, 51, 988; (f) V. Aranapakam,
G. T. Grosu, J. M. Davis, B. Hu, J. Ellingboe, J. L. Baker,
J. S. Skotnicki, A. Zask, J. F. DiJoseph, A. Sung, M. A. Sharr,
L. M. Killar, T. Walter, G. Jin and R. Cowling, J. Med.
Chem., 2003, 46, 2361; (g) J. N. Desrosiers and
A. B. Charette, Angew. Chem., Int. Ed., 2007, 46, 5955; (h) 10 (a) W. Wei, C. Liu, D. Yang, J. Wen, J. You, Y. Suo and
M. N. Noshi, A. El-Awa, E. Torres and P. L. Fuchs, J. Am.
Chem. Soc., 2007, 129, 11242.
2 For selected examples, see: (a) Y. Amiel, Tetrahedron Lett.,
1971, 8, 661; (b) Y. Amiel, J. Org. Chem., 1974, 39, 3867; (c)
N. Taniguchi, Synlett, 2011, 1308; (d) X. Huang and
D.-H. Duan, Chem. Commun., 1999, 1741; (e) X. Huang,
H. Wang, Chem. Commun., 2013, 49, 10239; (b) W. Wei,
J. Wen, D. Yang, J. Du, J. You and H. Wang, Green Chem.,
2014, 16, 2988; (c) W. Wei, J. Li, D. Yang, J. Wen, Y. Jiao,
J. You and H. Wang, Org. Biomol. Chem., 2014, 12, 1861; (d)
W. Wei, J. Wen, D. Yang, M. Wu, J. You and H. Wang, Org.
Biomol. Chem., 2014, 12, 7678.
D. Duan and W. Zheng, J. Org. Chem., 2003, 68, 1958; (f) 11 (a) H. Qian and X. Huang, Tetrahedron Lett., 2002, 43, 1059;
X. Li, X. Shi, M. Fang and X. Xu, J. Org. Chem., 2013, 78,
9499; (g) Y. Gao, W. Wu, Y. Huang, K. Huang and H. Jiang,
Bioorg. Chem. Front., 2014, 1, 361.
(b) N. Riddell and W. Tam, J. Org. Chem., 2006, 71, 1934; (c)
H. Suzuki and H. Abe, Tetrahedron Lett., 1996, 37, 3717.
12 (a) G. Wang, U. Mahesh, G. Y. J. Chen and S. Q. Yao, Org.
Lett., 2003, 5, 737; (b) J. J. Reddick, J. Cheng and
W. R. Roush, Org. Lett., 2003, 5, 1967; (c) B. A. Frankel,
M. Bentley, R. G. Kruger and D. G. McCafferty, J. Am.
Chem. Soc., 2004, 126, 3404; (d) M. Uttamchandani, K. Liu,
R. C. Panicker and S. Q. Yao, Chem. Commun., 2007, 1518;
(e) D. C. Meadows, T. Sanchez, N. Neamati, T. W. North
and J. Gervay-Hague, Bioorg. Med. Chem., 2007, 15, 1127.
13 (a) Q. Lu, J. Zhang, G. Zhao, Y. Qi, H. Wang and A. W. Lei,
J. Am. Chem. Soc., 2013, 135, 11481; (b) Q. Lu, J. Zhang,
F. Wei, Y. Qi, H. Wang, Z. Liu and A. W. Lei, Angew. Chem.,
Int. Ed., 2013, 52, 7156; (c) T. Shen, Y. Yuan, S. Song and
N. Jiao, Chem. Commun., 2014, 50, 4115.
3 (a) Y. Amiel, J. Org. Chem., 1971, 36, 3691; (b) Y. Amiel, J. Org.
Chem., 1971, 36, 3697; (c) H. Mataunoto, T. Nakano,
K. Ohkawa and Y. Nagai, Chem. Lett., 1978, 363; (d)
X. Y. Liu, X. H. Duan, Z. L. Pan, Y. Han and Y. M. Liang,
Synlett, 2005, 1752; (e) X. Zeng, L. Ilies and E. Nakamura,
Org. Lett., 2012, 14, 954; (f) S. R. Dubbaka and P. Vogel,
Chem.–Eur. J., 2005, 11, 2633; (g) U. Wille, Chem. Rev.,
2013, 113, 813.
4 (a) W. E. Truce and G. C. Wolf, J. Org. Chem., 1971, 36, 1727;
(b) W. E. Truce, D. L. Heuring and G. C. Wolf, J. Org. Chem.,
1975, 39, 238.
5 V. Nair, A. Augustine and T. D. Suja, Synthesis, 2002, 2259.
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