FeBr3-catalyzed dibromination of alkenes and alkynes

Article abstract of DOI:10.1016/j.cclet.2011.05.005

The dibromination of alkenes and alkynes with bromosuccinimide and sodium bromide catalyzed by FeBr₃ under mild conditions has been developed. The trans-dibromo compounds were exclusively obtained with excellent yields.

Full text of DOI:10.1016/j.cclet.2011.05.005

Available online at www.sciencedirect.com
Chinese Chemical Letters 22 (2011) 1195–1198
www.elsevier.com/locate/cclet
FeBr3-catalyzed dibromination of alkenes and alkynes
*
Yun Fa Zheng, Jian Yu, Guo Bing Yan , Xu Li, Song Luo
Department of Chemistry, Lishui University, Lishui 323000, China
Received 21 January 2011
Available online 18 July 2011
Abstract
The dibromination of alkenes and alkynes with bromosuccinimide and sodium bromide catalyzed by FeBr3 under mild
conditions has been developed. The trans-dibromo compounds were exclusively obtained with excellent yields.
# 2011 Guo Bing Yan. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
Keywords: Dibromination; Alkenes and alkynes; Iron catalyst
Bromo derivatives are very important intermediates in organic synthesis, because the bromine group can easily be
transformed into other functionalities [1]. In addition, they have found wide applications as pharmaceuticals,
agrochemicals and other speciality chemicals [2].
The dibromination of alkenes and alkynes has received significant interest in recent years. The classical
bromination involves the use of elemental bromine that is difficult to manipulate due to its toxicity and high vapor
pressure [3]. Alternative brominating agents, perbromide (Br3À), such as tetrabutylammonium tribromide
(TBABr3), pyridinium tribromide (PyHBr3) and pentylpyridinium tribromide, are commercially available and
safer to handle [4]. Nevertheless, their preparation still involves direct contact with elemental bromine. A
possible solution to avoid this reagent is oxidative bromination where metal bromide or hydrobromic acid is used
in combination with a suitable oxidant, such as hydrogen peroxide, ceric ammonium nitrate, sodium
metaperiodate, and so on [5]. However, these reactions suffer from the major drawbacks that are the occurrence of
side reactions, low selectivity and the limitation of substrates. Ross and Shi reported two independent sources of
Br+ and BrÀ (NBS/Bu4NBr, NBS/LiBr) were used in the system for the dibromination of carbon–carbon
unsaturated bonds, respectively [6]. Although the mechanism was not yet clear, they believed that molecular Br2
generated in situ was the real brominating agent. The development of more convenient and effective Lewis acid
mediators for the addition of electrophiles to alkynes and alkenes is desirable. Wang and co-workers developed an
effective and mild FeX3-promoted strategy for the synthesis of alkenyl halides by the addition of benzylic
alcohols to aromatic alkynes [7]. Iron complexes have recently emerged as promising catalysts in various
transformations, as they are inexpensive, easily available and nontoxic [8]. Herein, we wish to report an iron-
catalyzed dibromination of alkenes and alkynes with N-bromosuccinimide (NBS) and sodium bromide under mild
conditions.
* Corresponding author.
E-mail address: gbyan@lsu.edu.cn (G.B. Yan).
1001-8417/$ – see front matter # 2011 Guo Bing Yan. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
doi:10.1016/j.cclet.2011.05.005

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Y.F. Zheng et al. / Chinese Chemical Letters 22 (2011) 1195–1198
Table 1
Optimization of FeBr3-catalyzed dibromination of phenylacetylene 1a.a
Br
Ph
FeBr3 (10 mmol%)
Br
Br
+
+NBS
+
MBr
Ph
Ph
Br
Solvent, N2, 60 0C
.
1a
2a
3a
Entry
MBr
Solvent
Yield (%)e
2a/3af
1
2
NaBr
NaBr
NaBr
NaBr
NaBr
NaBr
KBr
PhMe
DCE
Trace
26
/
12:1
19:1
13:1
10:1
10:1
17:1
18:1
16:1
12:1
15:1
/
3
MeCN
THF
88
4
53
5
Dioxane
DMF
37
6
43
7
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
65
8
LiBr
70
9
n-Bu4NBr
NaBr
–
63
10b
11c
12d
36
25
NaBr
Trace
a
Unless otherwise noted, the reaction conditions are as follows: 1a (0.3 mmol), NBS (1.5 equiv.), MBr (1.5 equiv.), FeBr3 (0.1 equiv.), solvent
(3 mL), 60 8C, under N2.
Without FeBr3.
b
c
Without NaBr.
d
Without NBS.
e
Isolated yield.
Ratio determined by 1H NMR.
f
On the outset of this investigation, we used phenylacetylene 1a as model substrate with bromosuccinimide and
sodium bromide to screen suitable reaction conditions. The results are summarized in Table 1. When FeBr3 was used
as catalyst, the reaction was found to proceed more efficiently in a polar solvent than in nonpolar solvent (Table 1,
entries 1–6). The trans-dibromo compound (2a) was exclusively obtained with good yield in MeCN (Table 1, entry 3),
whereas the reaction gave in moderate yields and the ratios of 2a to 3a significantly decreased in DCE, THF, dioxane
and DMF (Table 1, entries 2, 4–6). Other metal bromides, such as KBr, LiBr and n-Bu4NBr resulted in diminished
yields and the ratios of 2a to 3a dropped slightly (Table 1, entries 7–9). Several control experiments demonstrated that
dibromo compounds were obtained in 36% and 25% yields in the absence of FeBr3 or NaBr, and the ratio of 2a to 3a
decreased (Table 1, entries 10 and 11). Only a trace amount of desired product could be detected by GC–MS, when the
reaction was carried out without bromosuccinimide (Table 1, entry 12).
Under the optimized conditions, the substrate scope of this reaction was investigated. The results are summarized in
Table 2. Aromatic terminal alkynes with either electron-donating or electron-withdrawing functional groups, such as
methyl, tert-butyl, methoxy and chloro groups, smoothly converted to the trans-dibromo compounds in good yields
under the standard conditions (Table 2, entries 1–5). However, for amino-substituted aromatic alkynes, only small
amount of the desired product was detected by GC–MS (Table 2, entry 6). For internal alkynes, 1,2-diphenylethyne did
not afford the dibromo compound under the optimized conditions (Table 2, entry 7). In addition, the reaction was also
suitable for the dibromination of alkenes and gave high yields (Table 2, entries 8–10).
Although the detailed mechanism for this process awaits further investigation, a dual activation of both the carbon–
carbon unsaturated bonds and NBS by Lewis acid (FeBr3) might greatly enhance the reactivity (Scheme 1), which is
similar to the gold-catalyzed halogenation of aromatics with N-halosuccinimides reported by Wang [9].
In summary, we have developed an efficient iron-catalyzed dibromination of alkenes and alkynes with NBS and
NaBr under mild conditions. This methodology represents an efficient, straightforward, and safer alternative to the
hazardous molecular Br2 protocols. Further investigation of the detailed mechanism and the scope of substrates is
currently underway in our lab.

Y.F. Zheng et al. / Chinese Chemical Letters 22 (2011) 1195–1198
1197
Table 2
FeBr3-catalyzed dibromination of alkenes and alkynes 1.a
Entry
Alkynes and alkenes (1)
Major product (2)
Yield (%)b
2/3c
Br
H
1a
1
88
19:1
Br
2a
Br
1b
2
3
4
5
92
84
93
78
>19:1
>19:1
>19:1
>19:1
H
Br
2b
Br
Br
1c
H
H
Br
Br
2c
MeO
1d
MeO
2d
Cl
1e
Br
Cl
H
Br
2e
H2N
H2N
6
Trace
/
Br
1f
H
Br
2f
1g
7
8
/
/
/
/
Br
88
1h
2h
Br
Br
9
92
90
/
/
1i
2i
Br
Br
10
1j
2j
Br
a
Unless otherwise noted, the reaction conditions are as follows: 1 (0.5 mmol), NBS (1.5 equiv.), NaBr (1.5 equiv.), FeBr3 (0.1 equiv.), solvent
(3 mL), 60 8C, under N2.
Isolated yield.
b
c
Ratio determined by 1H NMR.

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Y.F. Zheng et al. / Chinese Chemical Letters 22 (2011) 1195–1198
FeBr3
Br-
O
Br
N
O
FeBr3
Scheme 1. Mechanistic rationale.
Acknowledgment
We are grateful for the financial support by Lishui University Opening Foundation for advanced talents.
References
[1] R.C. Larock, Comprehensive Organic Transformations, 2nd ed., Wiley-VCH, New York, 1999.
[2] (a) A. Buttler, J.V. Walker, Chem. Rev. 93 (1993) 1937;
(b) G.W. Gribble, Chem. Soc. Rev. 28 (1999) 335.
[3] N. Proust, J.C. Gallucci, L.A. Paquette, J. Org. Chem. 73 (2008) 6279.
[4] (a) C. Ye, J.M. Shreeve, J. Org. Chem. 69 (2004) 8561;
(b) V. Kavala, S. Naik, B.K. Patel, J. Org. Chem. 70 (2005) 4267;
(c) M.L. Yao, M.S. Reddy, L. Yong, et al. Org. Lett. 12 (2010) 700.
[5] (a) G.K. Dewkar, S.V. Narina, A. Sudalai, Org. Lett. 5 (2003) 4501;
(b) A.V. Joshi, M. Baidossi, S. Mukhopadhyay, et al. Org. Process Res. Dev. 8 (2004) 568;
(c) T. Mahammad, A. Shaikh, J. Org. Chem. 71 (2006) 5043.
[6] (a) M. Finkelstein, S.A. Hart, S.D. Ross, et al. J. Org. Chem. 51 (1986) 3548;
(b) L.X. Shao, M. Shi, Synlett 8 (2006) 1269.
[7] K. Ren, M. Wang, L. Wang, Eur. J. Org. Chem. 3 (2010) 565.
[8] C. Bolm, J. Legros, J.L. Paih, et al. Chem. Rev. 104 (2004) 6217.
[9] F.Y. Mo, J.M. Yan, J.B. Wang, et al. Angew. Chem. Int. Ed. 49 (2010) 2028.