Tetrabutylammonium fluoride-induced dehydrobromination of vinyl bromides to terminal acetylenes

Article abstract of DOI:10.1016/j.tetlet.2007.07.174

Tetrabutylammonium fluoride (TBAF) was found to be a mild and efficient base for the dehydrobromination of vinyl bromides. Treatment of various 2-bromo-1-alkenes with TBAF·3H₂O in DMF yielded terminal acetylenes in high yields without undue regard to the presence of water.

Full text of DOI:10.1016/j.tetlet.2007.07.174

Tetrahedron Letters 48 (2007) 6856–6859
Tetrabutylammonium fluoride-induced dehydrobromination
of vinyl bromides to terminal acetylenes
Masaru Okutani and Yuji Mori*
Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya 468-8503, Japan
Received 12 July 2007; revised 25 July 2007; accepted 26 July 2007
Available online 31 July 2007
Abstract—Tetrabutylammonium fluoride (TBAF) was found to be a mild and efficient base for the dehydrobromination of vinyl
bromides. Treatment of various 2-bromo-1-alkenes with TBAFÆ3H2O in DMF yielded terminal acetylenes in high yields without
undue regard to the presence of water.
Ó 2007 Elsevier Ltd. All rights reserved.
Terminal acetylenes are an important functional group
SiMe3
OH
SiMe3
OH
H
H
H
H
H
H
H
H
O
O
and widely used in organic synthesis. Recent progress
with transition metal-catalyzed carbon–carbon coupling
reactions such as Sonogashira coupling reactions,
Pauson–Khand reactions, and metatheses has also pro-
ven the importance of terminal acetylenes.1 Dehydro-
bromination of vinyl bromides is a simple method for
the preparation of terminal acetylenes, and many proce-
dures have been reported: NaNH2 in liquid NH3,2 KOt-
Bu in THF,3 NaOMe in DMSO,4 NaH in DMSO or
DMF,5 LDA in THF,6 KH in THF,7 DBU in THF,8
n-BuLi in Et2O,9 and t-BuLi in pentane–Et2O.10 The
common disadvantages of these methods are the
requirement of a strong base and anhydrous reaction
conditions due to the low acidity of olefinic protons. It
is therefore useful to find a new method that can tolerate
moisture or water.
BnO
BnO
BnO
BnO
TBAF
Br
O
O
THF, 50 °C
87%
H
H
1
2
Tetrabutylammonium fluoride is a versatile and popular
reagent widely used in organic chemistry for many fluo-
ride-assisted reactions such as deprotection of silyl
ethers,13 acetals,14 esters,15 carbamates,16 and N-sulfo-
nyl groups,17 as well as desilylation18 and fluorination.19
Moreover, TBAF has been used as a mild base in a vari-
ety of base-catalyzed reactions such as aldol-type con-
densation reactions,20 Michael-type reactions,21 and
the opening reaction of small rings,22 and has also been
employed as a promoter in homo- and cross-coupling
reactions23 and cyclization reactions for carbocycles24
and heterocycles.25 Recently, TBAF has been reported
to be an efficient base for the dehydrohalogenation of al-
kyl halides to alkenes.26 However, there has been no
study on the reaction of 2-bromo-1-alkenes with TBAF.
An analogue to this reaction found in the literature is
the silicon-assisted dehydrohalogenation of bromo- or
chlorovinyltrimethylsilanes.8,27 We wish to report herein
the TBAF-induced terminal alkyne-forming reaction of
2-bromo-1-alkenes.28
During the course of our synthetic studies of polycyclic
ethers, we discovered an unexpected reaction of vinyl
bromide 1 with tetrabutylammonium fluoride (TBAF)
in THF. The reaction product obtained was the dehy-
drobromination product 2 instead of the desired desily-
lation compound.11 Considering that the commercially
available TBAF (1 M in THF) contains approximately
5% water,12 the acetylene formation in the presence of
water is quite interesting and stimulated us to investigate
the dehydrobromination of vinyl bromides with TBAF.
Initial experiments in dehydrobromination were carried
out using vinyl bromide 3 in order to establish the opti-
mal reaction conditions (Table 1). Treatment of 3 with
1.0 equiv of TBAF (1 M in THF) in THF at 60 °C
resulted in reducing the reaction conversion to only a
*
Corresponding author. Tel.: +81 52 839 2658; fax: +81 52 834
8090; e-mail: mori@ccmfs.meijo-u.ac.jp
0040-4039/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.07.174

M. Okutani, Y. Mori / Tetrahedron Letters 48 (2007) 6856–6859
6857
Table 1. Optimization of reaction conditions of dehydrobromination
of 3 with TBAF at 60 °C
5). We next examined the effects of solvent on shorten-
ing the reaction times. No reaction was observed with
the halogenated solvent CH2Cl2 or a polar protic solvent
such as MeOH. It has been recognized that the basic
property of the fluoride ion increases in polar aprotic
solvents such as DMF, MeCN, and DMSO.27 In the
present case, DMF was found to be an acceptable sol-
vent, qualitatively as good and better than THF in terms
of reaction times. Acetonitrile was found to be inferior
when compared to THF. In the reaction with DMF,
TBAFÆ3H2O was selected as the reagent because it is
readily available as a stable salt. The quantity of TBAF
required to complete the reaction was then evaluated. It
was found that 5.0 equiv of TBAFÆ3H2O was needed to
complete the reaction at 60 °C in a few hours (entries 9–
11). Other fluoride salts such as CsF and KF were
shown to be ineffective for this dehydrobromination.
OMe Br
OMe
TBAF 3H2O
solvent
60 °C
MeO
MeO
3
4
Entry
Solvent
TBAF
(equiv)
Time
(h)
Conversiona
(%)
Isolated
yield (%)
1
2
3
4
5
6
7
8
9
THF
THF
THF
THF
THF
DMF
DMF
DMF
DMF
DMF
DMF
1.0
2.0
3.0
4.0
5.0
1.0
2.0
3.0
5.0
5.0
5.0
25
25
25
25
25
25
25
25
1
44
58
82
92
97
55
72
92
90
97
99
40
52
74
84
85
50
65
83
—
—
91
10
11
2
3
Next, we extended the optimized dehydrobromination
conditions to various vinyl bromides: the results are rep-
resented in Table 2.29 We were delighted to find that the
reaction is quite general and that many substances toler-
ate the optimized reaction conditions, giving products in
good to high yields. Vinyl bromides containing a hydro-
xy group were also found to give the corresponding acet-
ylenes in good yields (entries 2, 5, and 6). It is notable
that only trace amounts (<2%) of allenic products were
detected in the experiments listed in entries 2, 5, and 6,
a Conversions of entries 1–8 were determined based on the recovered 3.
The experiments of entries 9–11 were carried out in an NMR tube
using DMF-d7, and the conversions were determined by 1H NMR.
44% value after 25 h (entry 1). Increasing the quantity of
TBAF improved the conversion yield, and 5.0 equiv of
TBAF was necessary for complete conversion (entry
Table 2. Dehydrobromination of vinyl bromides with TBAF (5.0 equiv) in DMF at 60 °C
Entry
Substrate
Time (h)
Product
Isolated yield (%)
93
Br
1
4
R
R
R = C9H19
OH Br
OH
R
2
3
95
R
R = C9H19
Br
3
4
2
90
91
BnO
MeO
BnO
MeO
Br
1.5
OH Br
OH
5
6
3
3
92
82
OH
OH Br
t-Bu
t-Bu
H
H
Me
Me
H
Me
O
O
Br
Me
7
3
78 (+ allene 9%)
O
O
O
O
H
H
H
(continued on next page)

6858
M. Okutani, Y. Mori / Tetrahedron Letters 48 (2007) 6856–6859
Table 2 (continued)
Entry
Substrate
Time (h)
3
Product
Isolated yield (%)
70 (+ allene 17%)
H
H
H
H
H
Ph
O
Ph
O
Br
8
9
O
O
O
O
H
H
H
OBn
OBn
BnO
BnO
OBn
H
BnO
BnO
OBn
4.5
77 (+ allene 11%)
Br
O
H
O
SiMe3
OH
SiMe3
OH
H
O
H
O
BnO
BnO
10
2
92
Br
BnO
O
BnO
O
H
H
H
H
H
H
58, 5709–5716; (d) Corey, E. J.; Yu, C. M.; Kim, S. S.
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were formed in the dehydrobromination of the vinyl
bromides derived from glucose (entries 7–9). The reason
for this remarkable difference in the allene formation is
not clear and under scrutiny. Vinyl bromides having a
carbonyl group were not found to be suitable because
of the concurrent aldol reaction,20 giving a mixture of
products.
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¨
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In conclusion, TBAF was found to be an efficient and
mild base in the dehydrobromination of vinyl bromides
to terminal acetylenes. The reaction can be carried out
by using TBAFÆ3H2O in DMF, and the water tolerance
and the absence of metal salts make this method attrac-
tive. This procedure provides a reasonable alternative to
other methods that require strong bases and anhydrous
conditions. We are currently examining the scope and
limitations of this method.
´
´
´
7. Guzman-Duran, A.; Guzman, E.; Pannell, K. H.; Lloyd,
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´
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Acknowledgment
11. Unpublished results.
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This work was supported by a Grant-in-Aid for Scien-
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29. Typical procedure for 3: Vinyl bromide
3 (270 mg,
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1.0 mmol) was dissolved in 5 mL of a 1 M solution of
TBAFÆ3H2O in DMF, and the reaction mixture was
heated at 60 °C for 4 h. The mixture was diluted with Et2O
and the organic phase was washed with water and brine.
The organic layer was separated, dried over anhydrous
MgSO4, and filtered. The solvent was removed in vacuo
and the residue was purified by flash chromatography (8%
ethyl acetate in hexane) to give acetylene 4 (173 mg, 91%).