Oxysulfonylation of Alkenes with Sulfonyl Hydrazides under Transition-Metal-Free Conditions

Article abstract of DOI:10.1002/ejoc.201501613

A novel method to synthesise β-keto sulfones is demonstrated by Br?nsted acid promoted oxysulfonylation of alkenes with sulfonyl hydrazides under transition-metal-free conditions. The reaction selectively affords structurally diverse β-keto sulfones in good to excellent yields in a 9:1 mixture of acetonitrile/water.

Full text of DOI:10.1002/ejoc.201501613

DOI: 10.1002/ejoc.201501613
Communication
Oxysulfonylation
Oxysulfonylation of Alkenes with Sulfonyl Hydrazides under
Transition-Metal-Free Conditions
Congrong Liu*[a] Lianghui Ding,[a] Guang Guo,[a] and Weiwei Liu[b]
Abstract: A novel method to synthesise ꢀ-keto sulfones is conditions. The reaction selectively affords structurally diverse
demonstrated by Brønsted acid promoted oxysulfonylation of ꢀ-keto sulfones in good to excellent yields in a 9:1 mixture of
alkenes with sulfonyl hydrazides under transition-metal-free acetonitrile/water.
Introduction
Alkenes as versatile and readily available building blocks are
frequently employed in a broad range of chemical transforma-
tions.[1] Among these transformations, 1,2-difunctionalization of
(1)
carbon–carbon double bonds is one of the most powerful
methods for the introduction of functional groups into target
compounds.[2] In this regard, the oxysulfonylation of alkenes
has emerged as an ideal strategy for the synthesis of ꢀ-keto
sulfones, which are very versatile compounds in organic chem-
istry because of their biological properties[3] and widespread
synthetic applications.[4] While recent years have witnessed a
number of reports on the construction of ꢀ-keto sulfones,[5,6]
most of them require transition-metal catalysts, expensive rea-
gents, relatively complicated or harsh reaction conditions, and
have only narrow substrate scopes. Therefore, a new general,
convenient, green and sustainable approach for the oxysulfon-
ylation of alkenes is still necessary.
Results and Discussion
Initially, treatment of benzenesulfonyl hydrazide (1a) with styr-
ene (2a; 1.5 equiv.) and 10 mol-% of trifluoroacetic acid in nitro-
methane under air at 70 °C led to the formation of ꢀ-keto sulf-
one 3a in 40 % yield (Table 1, Entry 1). Control experiments
indicated that dioxygen is essential for the desired reaction, and
a slightly better yield (46 %) was obtained from the reaction
with dioxygen under normal pressure (Table 1, Entries 2 and 3).
Table 1. Optimization of the reaction conditions.[a]
Sulfonyl hydrazides are readily accessible, and they have
been employed to form hydrazones and heterocycles, which
have versatile applications in organic chemistry.[7] Moreover,
sulfonyl hydrazides can be utilized as aryl sources through the
cleavage of their carbon–sulfur bonds,[8] and as sulfenylating
agents through the cleavage of their sulfur–nitrogen bonds.[9]
In contrast, the reports that sulfonyl hydrazides are utilized as
sulfonyl source are very few. Recently, Wang and co-workers
described a synthesis of ꢀ-keto sulfones using sulfonyl hydraz-
ides as sulfonyl sources.[10] However, a toxic heavy metal cata-
lyst is used, and the efficiency of the method is rather poor.
Herein we report an efficient and green synthesis of ꢀ-keto sulf-
ones by trifluoroacetic acid catalyzed oxysulfonylation of alk-
enes with sulfonyl hydrazides and dioxygene in a 9:1 mixture
of acetonitrile/water [Equation (1)].
Entry
Catalyst
Oxidant
Solvent
Yield [%][b]
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17[c]
CF3COOH
CF3COOH
CF3COOH
CF3COOH
CF3COOH
CF3COOH
CF3COOH
CF3COOH
CF3COOH
CF3COOH
CF3COOH
H2SO4
HCl
TsOH
tartaric acid
benzoic acid
CF3COOH
air
none
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
MeNO2
MeNO2
MeNO2
dioxane
toluene
40
0
46
31
0
65
27
trace
49
53
81
56
62
70
48
32
70
MeCN
1,2-dichloroethane
water
DMSO
EtOH
MeCN/H2O (9:1)
MeCN/H2O (9:1)
MeCN/H2O (9:1)
MeCN/H2O (9:1)
MeCN/H2O (9:1)
MeCN/H2O (9:1)
MeCN/H2O (9:1)
[a] School of Environment Engineering, Nanjing Institute of Technology,
1 Hongjingdadao, Nanjing, Jiangsu 211167, China
E-mail: congrong@njit.edu.cn
[b] Communication Engineering College, Nanjing Institute of Technology,
1 Hongjingdadao, Nanjing, Jiangsu 211167, Chinas
Supporting information and ORCID(s) from the author(s) for this article
are available on the WWW under http://dx.doi.org/10.1002/
ejoc.201501613.
[a] Reaction conditions: 1a (0.2 mmol), 2a (0.3 mmol), catalyst (10 mol-%),
solvent (2.0 mL), oxidant (if any, 1 atm), 70 °C, 15 h. [b] Isolated yields. [c]
CF3COOH (5 mol-%).
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Communication
To improve the yield, we screened a range of common solvents
and found that the use of acetonitrile led to the formation of
ꢀ-keto sulfone 3a in 65 % yield (Table 1, Entries 4–10). To our
delight, the use of a 9:1 mixture of MeCN/H2O dramatically en-
hanced the yield up to 81 % (Table 1, Entry 11). Replacment of
trifluoroacetic acid by a few other Brønsted acids led to much
lower yields (Table 1, Entries 12–15). Further efforts to decrease
the amount of trifluoroacetic acid resulted in a lower yield
(Table 1, Entry 17).
Encouraged by our preliminary findings, we investigated the
substrate scope for the oxysulfonylation of sulfonyl hydrazides
with styrene (2a). In the presence of 10 mol-% of trifluoroacetic
acid and dioxygen under normal pressure, a range of arene-,
and heteroarenesulfonyl hydrazides smoothly reacted with styr-
ene to give structurally diverse ꢀ-keto sulfones in good to excel-
lent yields (Table 2, Entries 1–9). It is noteworthy that either an
electron-withdrawing or an electron-donating group was intro-
duced into the ꢀ-keto sulfone product by employing an arene-
sulfonyl hydrazide bearing such a group on the aromatic ring.
Furthermore, alkanesulfonyl hydrazids also could smoothly re-
act with styrene (2a) to give the corresponding ꢀ-keto sulfone
3j, and as expected, lower yields were obtained for the oxy-
sulfonylation of styrene with less reactive sulfonyl hydrazides
(Table 2, Entry 10).
Table 3. Oxysulfonylation of benzenesulfonyl hydrazide (1a) with alkenes.[a]
Entry
2, R
3
Yield [%][b]
1
2
3
4
5
7
8
9
10
2b, 4-MeC6H4
2c, 4-MeOC6H4
2d, 4-ClC6H4
2e, 4-BrC6H4
2f, 4-NCC6H4
2h, 2-ClC6H4
2i, 1-naphthyl
2j, 2-naphthyl
2k,CH3(CH2)5
3k
3l
81
60
85
82
59
79
70
67
0
3m
3n
3o
3p
3q
3r
3s
[a] Reaction conditions: 1 (0.2 mmol), 2a (0.3 mmol), CF3COOH (10 mol-%),
MeCN/H2O (9:1; 2.0 mL), O2 (1 atm), 70 °C, 15 h. [b] Isolate yields.
It is known that the generation of sulfonyl radicals is initiated
by oxidation of sulfonyl hydrazides to give diazenes in the pres-
ence of dioxygen.[11] Therefore, the reaction mechanism may
be a radical pathway. When a stoichiometric amount of TEMPO
(2,2,6,6-tetramethyl-1-piperidinyl oxyl, a well-known radical-
capturing species) was added to this reaction mixture, no reac-
tion took place at all [Equation (2)]. This control experiment
supports the aforementioned hypothesis.
Table 2. Oxysulfonylation of sulfonyl hydrazides with styrene (2a).[a]
(2)
Entry
1, R
3
Yield [%][b]
According to our experimental results and the generally ac-
cepted mechanism for sulfonyl radical formations from sulfonyl
hydrazides,[12] we propose the following reaction pathway for
the trifluoroacetic acid catalyzed oxysulfonylation reaction of
alkenes and sulfonyl hydrazides. As shown in Scheme 1, it is
presumed that the generation of sulfonyl radicals 7 is initiated
by oxidation of sulfonyl hydrazides to give diazene 5 in the
1
2
3
4
5
6
7
8
9
1a, Ph
3a
3b
3c
3d
3e
3f
3g
3h
3i
81
83
71
72
74
79
70
77
71
60
1b, 4-MeC6H4
1c, 4-MeOC6H4
1d, 4-AcNHC6H4
1e, 4-FC6H4
1f, 4-ClC6H4
1g, 4-BrC6H4
1h, 2-naphthyl
1i, 2-thienyl
1j, Me(CH2)7
10
3j
[a] Reaction conditions: 1 (0.2 mmol), 2a (0.3 mmol), CF3COOH (10 mol-%),
MeCN/H2O (9:1; 2.0 mL), O2 (1 atm), 70 °C, 15 h. [b] Isolate yields.
A few other types of alkenes were examined in oxysulfonyl-
ation reactions with benzenesulfonyl hydrazide (1a) under the
standard reaction conditions. Generally, reactions of aryl-
ethenes bearing electron-withdrawing groups (Cl, Br and CN) or
electron-donating groups (Me and OMe) with benzenesulfonyl
hydrazide proceeded smoothly and afforded the corresponding
products in good to excellent yields (Table 3, Entries 1–7). 1-
Vinylnaphthalene and 2-vinylnaphthalene both reacted well to
afford the corresponding ꢀ-keto sulfones in good yields
(Table 3, Entries 8–9). Nevertheless, the oxysulfonylation reac-
tion was not applicable to less reactive alkylethenes such as 1-
octene (Table 3, Entry 10).
Scheme 1. Proposed reaction pathways.
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Communication
[2] a) B. C. Giglio, V. A. Schmidt, E. J. Alexanian, J. Am. Chem. Soc. 2011, 133,
13320–13322; b) H. Wang, Y. Wang, D. Liang, L. Liu, J. Zhang, Q. Zhu,
Angew. Chem. Int. Ed. 2011, 50, 5678–5681; Angew. Chem. 2011, 123,
5796; c) Z.-Q. Wang, W.-W. Zhang, L.-B. Gong, R.-Y. Tang, X.-H. Yang, Y.
Liu, J.-H. Li, Angew. Chem. Int. Ed. 2011, 50, 8968–8970; Angew. Chem.
2011, 123, 9130; d) W. Wei, J. X. Ji, Angew. Chem. Int. Ed. 2011, 50, 9097–
9099; Angew. Chem. 2011, 123, 9263; e) W. Wei, C. Liu, D. Yang, J. Wen,
J. You, Y. Suo, H. Wang, Chem. Commun. 2013, 49, 10239–10232; f) Y. Su,
X. Sun, G. Wu, N. Jiao, Angew. Chem. Int. Ed. 2013, 52, 9808–9811; Angew.
Chem. 2013, 125, 9990; g) C.-R. Liu, M.-B. Li, Chin. J. Chem. 2013, 31,
1274–1278; h) C.-R. Liu, F.-L. Yang, T.-T. Wang, Chin. J. Chem. 2014, 32,
387–390.
presence of dioxygen and trifluoroacetic acid. Thereafter, addi-
tion of sulfonyl radical 7 to alkenes produces the reactive alkyl
radical 8, which can be trapped by dioxygen under the present
conditions and forms the peroxy radical 9. Finally, this peroxy
radical 9 couples with an HOO· species, produces tetroxide 10,
which decomposes, and furnishes product 3.
Conclusions
[3] C. Curti, M. Laget, A. O. Carle, A. Gellis, P. Vanelle, Eur. J. Med. Chem. 2007,
42, 880–883.
We have developed an efficient and green method to synthe-
sise ꢀ-keto sulfones from alkenes and sulfonyl hydrazides. In
the presence of 10 mol-% of trifluoroacetic acid, a range of
alkenes smoothly underwent oxysulfonylation with sulfonyl
hydrazides and dioxygen in a 9:1 mixture of acetonitrile/water
to give structurally diverse ꢀ-keto sulfones in moderate to excel-
lent yields. Studies of the detailed mechanism of this process
and its application are ongoing.
[4] a) D. J. Procter, J. Chem. Soc. Perkin Trans. 1 2000, 835–839; b) H. Yang,
R. G. Carter, L. N. Zakharov, J. Am. Chem. Soc. 2008, 130, 9238–9241; c)
A. Kumar, M. K. Muthyala, Tetrahedron Lett. 2011, 52, 5368–5370.
[5] a) G. E. Vennstra, B. Zwaneburg, Synthesis 1975, 519–523; b) Y.-Y. Xie, Z.-
C. Chen, Synth. Commun. 2001, 31, 3145–3147; c) A. R. Katritzky, A. A.
Abdel-Fattah, M. Y. Wang, J. Org. Chem. 2003, 68, 1443–1445 and referen-
ces therein; d) C. Lai, C. Xi, Y. Jiang, R. Hua, Tetrahedron Lett. 2005, 46,
513–516; e) T. Zweifel, M. Nielsen, J. Overgaard, C. B. Jacobsen, K. A.
Jogensen, Eur. J. Org. Chem. 2011, 47–50; f) N. Samakkanad, P. Katrun, T.
Techajaroonjit, S. Hlekhlai, M. Pohmakotr, V. Reutrakul, T. Jaipetch, D.
Soorukram, C. Kuhakarn, Synthesis 2012, 44, 1693–1696; g) Q. Q. Lu, J.
Zhang, G. L. Zhao, Y. Qi, H. M. Wang, A. W. Lei, J. Am. Chem. Soc. 2013,
135, 11481–11484.
Experimental Section
General Procedure for the Oxysulfonylation of Alkenes with
Sulfonyl Hydrazides: To a solution of sulfonyl hydrazide 1
(0.20 mmol) in MeCN/H2O (9:1; 2.0 mL), under oxygen (1 atm) at
room temperature, were added alkene 2 (0.30 mmol) and TFA
(2.2 mg, 0.020 mmol). The mixture was stirred at 70 °C for 20 h,
cooled to room temperature, and directly purified by preparative
thin layer chromatography on silica gel, eluting with petroleum
ether/ethyl acetate (10:1 to 3:1), to give compound 3.
[6] a) B. M. Trost, D. P. Curran, Tetrahedron Lett. 1981, 22, 1287–1289; b) C. R.
Holmquist, E. J. Roskamp, Tetrahedron Lett. 1992, 33, 1131–1134; c) N.
Kamigata, K. Udodaira, T. Shimizu, J. Chem. Soc. Perkin Trans. 1 1997,
783–186; d) A. R. Kartrizky, A. A. Ashraf, A. Fattah, M. Y. Wang, J. Org.
Chem. 2003, 68, 1443–1445.
[7] a) Z. Shao, H. Zhang, Chem. Soc. Rev. 2012, 41, 560–572; b) J. Barluenga,
C. Valds, Angew. Chem. Int. Ed. 2011, 50, 7486–7489; Angew. Chem. 2011,
123, 7626; c) R. O. Hutchins, M. K. Hutchins in Comprehensive Organic
Synthesis, vol. 8 (Eds.: B. M. Trost, I. Fleming), Pergamon, Oxford, 1991,
pp. 327–350.
[8] F. L. Yang, X. T. Ma, S.-K. Tian, Chem. Eur. J. 2012, 18, 1582–1585.
[9] a) F. L. Yang, S.-K. Tian, Angew. Chem. Int. Ed. 2013, 52, 4929–4933;
Angew. Chem. 2013, 125, 5029; b) F. L. Yang, F. X. Wang, T. T. Wang, Y. J.
Wang, S. K. Tian, Chem. Commun. 2014, 50, 2111–2113; c) C.-R. Liu, L.-H.
Ding, Org. Biomol. Chem. 2015, 13, 2251–2254.
Acknowledgments
We are grateful for the financial support from the National Nat-
ural Science Foundation of China (no. 21202154), the Natural
Science Foundation of The Jiangsu Higher Education Institutes
of China (15KJB150007), the Nanjing Institute of Technology
Scientific Research Foundation for Introducing Talents (no.
YKJ201329, YKJ201326, YKJ201318, YKJ201419), and the Nan-
jing Institute of Technology.
[10] W. Wei, C. L. Liu, D. S. Yang, J. W. Wen, J. M. You, Y. R. Suo, H. Wang,
Chem. Commun. 2013, 49, 10239–10241.
[11] a) T. Taniguchi, Y. Sugiura, H. Zaimoku, H. Ishibashi, Angew. Chem. Int. Ed.
2010, 49, 10154–10158; Angew. Chem. 2010, 122, 10352; b) T. Taniguchi,
H. Zaimoku, H. Ishibashi, Chem. Eur. J. 2011, 17, 43074311; c) T. Taniguchi,
A. Idota, H. Ishibashi, Org. Biomol. Chem. 2011, 9, 3151–3155; d) X. Q. Li,
X. S. Xu, C. Zhou, Chem. Commun. 2012, 48, 12240–12242.
[12] a) G. A. Russell, J. Am. Chem. Soc. 1957, 79, 3871–3874; b) J. A. Howard,
K. U. Ingold, J. Am. Chem. Soc. 1968, 90, 1058–1061; c) H. R. Lucas, L. Li,
A. A. Narducci Sarjeant, M. A. Vance, E. I. Solomon, K. D. Karlin, J. Am.
Chem. Soc. 2009, 131, 3230–3233; d) T. Taniguchi, Y. Sugiura, H. Zaimoku,
H. Ishibashi, Angew. Chem. Int. Ed. 2010, 49, 10154–10157; Angew. Chem.
2010, 122, 10352; e) T. Taniguchi, H. Zaimoku, H. Ishibashi, Chem. Eur. J.
2011, 17, 4307–4310; f) T. Taniguchi, A. Idota, H. Ishibashi, Org. Biomol.
Chem. 2011, 9, 3151–3155; g) Q. Liu, R. Jackstell, M. Beller, Angew. Chem.
Int. Ed. 2013, 52, 13871–13873; Angew. Chem. 2013, 125, 14115; h) C.
Liu, D. Liu, A. Lei, Acc. Chem. Res. 2014, 47, 3459–3470; i) S. Tang, Y. Wu,
W. Q. Liao, R. P. Bai, C. Liu, A. Lei, Chem. Commun. 2014, 50, 4496–4499;
j) S. Tang, K. Liu, C. Liu, A. Lei, Chem. Soc. Rev. 2015, 44, 1070–1082.
Keywords: Alkenes · Oxysulfonylation · Sulfonyl hydrazides ·
Oxidation · Trifluoroacetic acid
[1] a) J. Ruan, J. Xiao, Acc. Chem. Res. 2011, 44, 614–626; b) C. M. Rayner, in
Organosulfur Chemistry: Synthetic Aspects (Ed.: P. Page), Academic Press,
London, 1995, pp. 8–19; c) N. T. S. Phan, M. Van Der Sluys, C. W. Jones,
Adv. Synth. Catal. 2006, 348, 609–679; d) F. Alonso, I. P. Beletskayab, M.
Yus, Tetrahedron 2005, 61, 11771–11835; e) M. Oestreich, Eur. J. Org.
Chem. 2005, 783–792; f) F. L. Yang, X. T. Ma, S. K. Tian, Chem. Eur. J. 2012,
18, 1582–1585; g) A. Deb, S. Manna, A. Modak, T. Patra, S. Maity, D. Maiti,
Angew. Chem. Int. Ed. 2013, 52, 9747–9750; Angew. Chem. 2013, 125,
9929; h) C.-R. Liu, D.-J. Chen, F.-L. Yang, Chin. J. Chem. 2014, 32, 1095–
1098.
Received: December 28, 2015
Published Online: January 26, 2016
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