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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.
Zheng, Yun Fa
