One-pot conversion of 1,1-dibromoalkenes into internal alkynes by sequential Suzuki-Miyaura and dehydrobromination reactions

Article abstract of DOI:10.1016/j.tetlet.2007.07.050

A protocol for the one-pot synthesis of internal alkynes from 1,1-dibromoalkenes is reported. The method is hinged upon the Suzuki-Miyaura cross-coupling of 2-aryl- or 2-heteroaryl-1,1-dibromoalkenes with aryl or heteroaryl boronic acids or borate esters

Full text of DOI:10.1016/j.tetlet.2007.07.050

Tetrahedron Letters 48 (2007) 6514–6517
One-pot conversion of 1,1-dibromoalkenes into internal alkynes
by sequential Suzuki–Miyaura and dehydrobromination reactions
Giorgio Chelucci,a,* Francesca Capitta,a Salvatore Baldinoa and Gerard A. Pinnab
a
`
Dipartimento di Chimica, Universita di Sassari, via Vienna 2, I-07100 Sassari, Italy
`
Dipartimento Farmaco Chimico Tossicologico, Universita di Sassari, Via Muroni 23, I-07100 Sassari, Italy
b
Received 28 May 2007; revised 5 July 2007; accepted 9 July 2007
Available online 13 July 2007
Abstract—A protocol for the one-pot synthesis of internal alkynes from 1,1-dibromoalkenes is reported. The method is hinged upon
the Suzuki–Miyaura cross-coupling of 2-aryl- or 2-heteroaryl-1,1-dibromoalkenes with aryl or heteroaryl boronic acids or borate
esters followed by dehydrobromination of the intermediate coupled products. Yields up to 89% were obtained.
ꢀ 2007 Elsevier Ltd. All rights reserved.
Alkynes are useful and versatile intermediates in organic
synthesis.1 Amongst the several approaches described in
the literature to obtain such compounds, some of them
use 1,1-dibromoalkenes as starting points. Thus, the
treatment of gem-dibromoalkenes with a strong base
such as NaHMDS,2 t-BuOK,3 DBU4 or NaOH/phase-
transfer agents5 yields 1-bromoalkynes, whereas the
use of 2 equiv of n-BuLi (more rarely MeLi or t-BuLi)
produces the related lithium-acetylides, that can be
quenched with MeOH to give terminal alkynes or
trapped with various electrophiles to furnish the corre-
sponding internal alkynes.6 1,1-Dibromoalkenes are
precursor of intermediate alkylidene carbenes that can
generate, by a 1,2-migration process, terminal or inter-
nal alkynes according to whether the group bonded to
the alkene of the alkylidene carbene is a hydrogen or
an alkyl, alkenyl or aryl group, respectively.7 Finally,
internal alkynes have been directly obtained by coupling
of 2-alkyl and 2-aryl-1,1-dibromoalkenes with organost-
annanes under Stille coupling conditions (Pd2dba3,
TFP, DIPEA, DMF and 80 ꢁC).8 This method is very
effective for the synthesis of internal alkynes, but org-
anostannanes generally suffer from toxicity and environ-
mental concerns, as well as issues associated to the
purification of the final products.
use of organostananes utilized in the Stille coupling.10
Moreover, a variety of organoboron compounds are
now commercially available or readily prepared from a
variety of starting points via transmetallation or hyd-
roboration reactions.9
Since the Suzuki–Miyaura reaction of 1,1-dibromo-
alkenes with alkyl,11 alkenyl,11,12 alkynyl,13 aryl14a,b
and heteroaryl14b boronic acids and organotrifluorobo-
rates11 has proven to be successful for the synthesis of
tri- and tetrasubstituted olefins and also the stereoselec-
tive formation of (Z)-1-aryl- or (Z)-alkenyl-1-bromo-1-
alkenes,11–14 it was of interest to explore the feasibility
to obtain internal alkynes from 1,1-dibromoalkenes
exploiting this reaction.
Herein we report the one-pot conversion of 1,1-di-
bromoalkenes into internal alkynes by sequential Suzuki
and dehydrobromination reactions.
As a model substrate for our studies we prepared
(Z)-1-[1-bromo-2-(4-methoxyphenyl)vinyl]benzene 2a
(Scheme 1) starting from dibromide 1-(2,2-dibromovin-
yl)-4-methoxybenzene 1a and phenylboronic acid under
the optimized reaction conditions established by Shen
for the Suzuki–Miyaura coupling of 1,1-dibromoalkenes
with arylboronic acids [Pd2dba3, TFP, Na2CO3, 1,4-
dioxane, H2O, 65 ꢁC, and 4–6 h]14a (Scheme 1).
Organoboron compounds used in the Suzuki–Miyaura
cross-coupling9 represent a valuable alternative to the
With bromoalkene 2a in hand, we devoted our attention
to find a method for its dehydrobromination that should
have been compatible with the aqueous conditions of
the Suzuki–Miyaura reaction. When 10 equiv of NaOH
Keywords: Alkynes; Alkenes; 1,1-Dibromoalkenes; Suzuki–Miyaura
reaction; Palladium catalysts.
*
Corresponding author. Tel.: +39 079 229539; fax: +39 079 229559;
e-mail: chelucci@uniss.it
0040-4039/$ - see front matter ꢀ 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.07.050

G. Chelucci et al. / Tetrahedron Letters 48 (2007) 6514–6517
Br
Ph
6515
a
b
Br
Br
MeO
MeO
MeO
1a
2a
Ph
3a
Scheme 1. Reagents and conditions: (a) PhB(OH)2, Pd2dba3 (2.5%), TFP (15%), Na2CO3 (2.0 equiv), 1,4-dioxane, H2O, 65 ꢁC and 4 h; (b) Table 1.
Table 1. Dehydrobromination of 2aa
(Table 1, entry 1), whereas partial conversion of the
starting material was obtained at 65 ꢁC (entry 2). The
addition of the phase-transfer catalyst Bu4N(HSO4)
greatly improved the reaction, but the yield was moder-
ate (entry 3). Finally, nearly quantitative yield was
obtained when Bu4N(OH)Æ30H2O was added to the
mixture and stirring was continued at 65 ꢁC for 1 h
(entry 4).
Entry Base (equiv)
T/t
(ꢁC/h) (%)
Conv.b Yieldc
(%)
1
2
3
4
NaOH (10.0)
NaOH (10.0)
NaOH (10.0)/Bu4N(HSO4) (1.0) 65/4
Bu4N(OH)Æ30H2O (5.0) 65/1
25/24
65/15
0
65
—
—
72
100
100
>95
a The reaction was carried out at 1.0 mmol scale with Na2CO3
(2.0 equiv) in a mixture of 1,4-dioxane (5 mL) and H2O (2 mL).
b Determined by 1H NMR.
Based on these results a sequential one-pot process was
then examined. Thus, the Suzuki–Miyaura coupling of
1a with phenylboronic acid (1.05 equiv) was accom-
plished using tris(2-furyl)phophine (TFP, 15 mol %)
and tris(dibenzylideneacetone)dipalladium (Pd2dba3,
2.5 mol %) in 1,4-dioxane and aqueous cesium
c Isolated yields after flash chromatography.
were added to a mixture of 2a in 1,4-dioxane and aque-
ous Na2CO3, no reaction occurred at room temperature
Table 2. Synthesis of alkynes from 1,1-dibromoalkenesa
Pd2dba3, TFP, boronic acid
or borate ester R1B(OR2)2
R1
Bu4N(OH)
Br
R1
R
R
R
Cs2CO3, H2O,
65 ºC, 1 h
Br
Br
1,4-dioxane, 65 ºC
R, R1 = aryl and/or heteroaryl
Entry
1
Dibromide
Boronic acid or borate ester
Product
Yieldb (%)
56
Br
B(OH)2
MeO
Br
MeO
4a
3a
1a
Br
B(OH)2
2
3
76
89
Br
4a
3b
3c
1b
Cl
Cl
Br
B(OH)2
Br
4a
1c
Br
B(OH)2
O2N
4
82
67
Br
O2N
4a
3d
1d
Br
B(OH)2
5
6
Br
N
N
3e
3f
4a
1e
Br
B(OH)2
79
O
Br
O
4a
1f
(continued on next page)

6516
G. Chelucci et al. / Tetrahedron Letters 48 (2007) 6514–6517
Table 2 (continued)
Entry
Dibromide
Boronic acid or borate ester
Product
Yieldb (%)
48
O
B
Br
Br
7
8
Br
Br
O
N
N
1b
4b
3g
3h
O
S
B
35
63
S
O
1b
4c
Cl
Cl
Br
O
B
9
10
11
Br
N
N
O
N
4b
1c
3i
3j
Br
Br
O
B
O
82
67
Br
N
N
N
N
N
4b
1e
1e
O
S
Br
S
O
3k
4c
a Reaction conditions: 1,1-dibromoalkene (1.0 mmol), boronic acid or ester (1.05 equiv), Pd2dba3 (2.5 mol %), TFP (15.0 mol %), Cs2CO3 (1.0 M in
H2O, 2.0 mL, 2.0 equiv), 1,4-dioxane (5 mL), 65 ꢁC, 6–12 h; then Bu4N(OH)Æ30H2O (4 g, 5.0 equiv), 65 ꢁC, 1 h.
b Isolated yields after flash chromatography.
R1
Br
R
R1
R
R
R
CHO
Br
Br
Scheme 2.
carbonate (2.0 equiv)15 at 65 ꢁC and once all the dibro-
mide has been converted (6 h and TLC monitoring),
Bu4N(OH)Æ 30H2O was added. After stirring for a fur-
ther 1 h the related terminal alkyne 3a was obtained in
56% yield.
the intermediate coupled products afford internal alky-
nes in moderate to good yields. Given the easy availabil-
ity of a variety of organoboron compounds, this
protocol represents a valuable alternative to the Stille
reaction to prepare this important class of compounds.
The last but not the least, 1,1-dibromoalkenes are easily
obtainable in high yields from the related aldehydes6,17
and so the total process offers a convenient and simple
route for aldehyde to internal alkynes homologation
(Scheme 2). Further studies on this subject are currently
in progress.
With a suitable protocol in hand, the scope of this meth-
odology was examined by first using various 1,1-di-
bromoalkenes (Table 2) and phenylboronic acid as a
prototype of boronic acids. Under the optimized reac-
tion conditions,16 the corresponding alkynes were ob-
tained in moderate to good yields with both electron
rich (Table 1, entries 1 and 2) and deficient 1,1-di-
bromoalkenes (entries 3–5). These results did not change
substantially when both p-excessive and p-deficient het-
eroaromatic substituents (entries 5 and 6) were used.
Some representative examples of 1,1-dibromoalkenes
were finally cross-reacted with the electron deficient
boronate ester 4b (entries 7,9 and 10) and electron rich
boronate ester 4c (entries 8 and 11) to give the corres-
ponding alkynes in satisfactory yields.
Acknowledgements
Financial support from MIUR (PRIN 2003033857-Chi-
ral ligands with nitrogen donors in asymmetric catalysis
by transition metal complexes. Novel tools for the syn-
thesis of fine chemicals) and from the University of Sas-
sari is gratefully acknowledged by G.C.
In summary, the palladium catalyzed Suzuki–Miyaura
coupling of 2-aryl- or 2-heteroaryl-1,1-dibromoalkenes
with aryl or heteroaryl boronic acids or borate esters
and the subsequent one-pot dehydrobromination of
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6517
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16. Typical procedure for the preparation of alkynes 3a–k:
A mixture of 1-(2,2-dibromovinyl)-4-nitrobenzene (1d)
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