Synthesis of stereo-defined 1,1,4,4-tetrahalo- and 1,1,4,4-mixed-tetrahalo-1,3-butadienes

Article abstract of DOI:10.1016/j.tetlet.2007.11.152

Stereo-defined 1,1,4,4-tetrahalo- and 1,1,4,4-mixed-tetrahalo-1,3-butadienes were obtained in excellent yields via desilylation-halogenation of their corresponding 1,4-bis(trimethylsilyl)-1,4-dihalo-1,3-dienes, which could be readily prepared from the zir

Full text of DOI:10.1016/j.tetlet.2007.11.152

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Tetrahedron Letters 49 (2008) 624–627
Synthesis of stereo-defined 1,1,4,4-tetrahalo- and
1,1,4,4-mixed-tetrahalo-1,3-butadienes
Hui-Jun Zhang a,b, Zhiyi Song a, Chao Wang a, Christian Bruneau b,*, Zhenfeng Xi a,c,
*
a Beijing National Laboratory for Molecular Sciences (BNLMS), Key Laboratory of Bioorganic Chemistry and Molecular Engineering
of Ministry of Education, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China
b Institut de Chimie, UMR 6226, CNRS-Universite´ de Rennes 1, Catalyse et Organome´talliques, Campus de Beaulieu, 35042 Rennes Cedex, France
c State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China
Received 21 September 2007; revised 16 November 2007; accepted 23 November 2007
Abstract
Stereo-defined 1,1,4,4-tetrahalo- and 1,1,4,4-mixed-tetrahalo-1,3-butadienes were obtained in excellent yields via desilylation–
halogenation of their corresponding 1,4-bis(trimethylsilyl)-1,4-dihalo-1,3-dienes, which could be readily prepared from the zircono-
cene-mediated high-yield and high-regioselective cyclo-dimerization of 1-trimethylsilyl-1-alkynes followed by halogenation. These
poly-functionalized gem-dihalodienes are potentially useful building blocks.
Ó 2007 Elsevier Ltd. All rights reserved.
Keywords: 1,1,4,4-Tetrahalo-1,3-butadienes; Desilylation–halogenation; gem-Dihaloalkenes; Zirconacyclopentadienes
X
Our results on the discovery and development of
organo-bi-metallic reagents1–3 have demonstrated that
1,4-dihalo-1,3-butadienes (Type I in Fig. 1) are of unique
properties for organic synthesis because of the cooperative
effect between the vinylhalide moiety and the butadienyl
skeleton.1–6 At the same time, gem-dihalovinyl systems
(Type II in Fig. 1), as a class of important and versatile
building blocks, have been applied widely in organic syn-
thesis.7–13 As our continued interest in the cooperative
effect between the vinylhalide moiety and the butadienyl
skeleton, we anticipated that a remarkable cooperative
effect between the two gem-dihalovinyl moieties and the
butadienyl skeleton in 1,1,4,4-tetrahalo- and 1,1,4,4-
mixed-tetrahalo-butadienes (Type III in Fig. 1) may lead
to unexpected interesting reaction patterns and syntheti-
cally useful methods. Although several cases of special
types of tetrahalobutadienes have been reported in the lit-
erature,14,15 we developed an alternative, versatile and con-
X
X
X
X'
X'
X'
X'
I
II
III
1,4-dihalo-
butadienes
1,1-dihalo-
alkenes
1,1,4,4-tetrahalo-
butadienes
Fig. 1. Types of haloalkenes. X, X0 = I, Br, or Cl.
venient method for the preparation of 1,1,4,4-tetrahalo-
and 1,1,4,4-mixed-tetrahalo-butadienes, via a conceptually
new strategy shown in Scheme 1.
1-Trimethylsilyl-1-alkynes are well known to undergo
zirconocene-mediated high-yield and high-regioselective
cyclo-dimerization to afford zirconacyclopentadienes 3
(Scheme 1).4,5,16 Halogenation of zirconacyclopentadienes
3 will give their corresponding 1,4-bis(trimethylsilyl)-1,4-
dihalo-1,3-dienes 2 in excellent yields.4,5,16 Then, desilyl-
ation–halogenation process should afford the expected
1,1,4,4-tetrahalo- and 1,1,4,4-mixed-tetrahalo-butadienes
1. In this Letter, we report results obtained following the
strategy given in Scheme 1.
*
Corresponding authors. Tel.: +86 10 6275 9728; fax: +86 10 6275 1708
(Z.X.).
E-mail address: zfxi@pku.edu.cn (Z. Xi).
0040-4039/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.11.152

H.-J. Zhang et al. / Tetrahedron Letters 49 (2008) 624–627
625
SiMe3
Me3Si
SiMe3
Cp2ZrBu2
SiMe3
X
X
Desilylation/
halogenation
SiMe3
ZrCp2
SiMe3
NBS
CuCl
R
R
R
R
X
X
Br
Br
X
X
- 78 oC to r.t.
1h
X = I or Br
SiMe3
SiMe3
2
2Ba: isolated
yield: > 70%
1
Halogenation
SiMe3
Br
Br
Br2
Br
Br
Br
Br
Zirconocene-mediated
homo-coupling of
silylated alkynes
R
R
SiMe3
SiMe3
ZrCp2
SiMe3
in CH2Cl2
- 78 o
+
R
R
C
Cp2Zr(II)
+
SiMe3
2Ba
1Ba: 85%
SiMe3
3
Scheme 3. Preparation of 1,2-bis(dibromomethylene)cyclohexane.
Scheme 1. New strategy for the synthesis of 1,1,4,4-tetrahalo-1,3-
butadienes.
zirconocene species, as shown in Scheme 4.18 Bromination
of these intermediates using NBS in the presence of CuCl
afforded the dibromo styrene derivatives 2C in high
isolated yields with perfect selectivity. Then, similar
desilylation/bromination process gave gem-dibromovinyl-
2-bromobenzene derivatives 1C, a new type of polyhalides.
Both 1Ca and 1Cb were obtained in excellent yields.
Unfortunately, several trials for desilylation/iodination
and desilylation/chlorination under similar reaction condi-
tions were ended in vein.
As discussed above, this strategy afforded polyhalides of
types 1A, 1B and 1C, all are brominated compounds. Since
polyhalides with different halides should have more inter-
esting and more complicated properties, and much more
difficult to be prepared, particularly when regio- and
stereo-selectivity are concerned. We then tried to synthesise
polyhalides with different halides following the above sim-
ple strategy. To realize this synthesis, we firstly obtained
diiodo compounds 2D–F by iodination of their corres-
ponding zirconacyclopentadienes.4,5 Then, as given in
Scheme 5, bromination of these diiodo compounds
afforded their corresponding mixed polyhalo conjugated
butadienes 1D–F. (1Z,3Z)-1,4-Dibromo-1,4-diiodo-2,3-
dibutyl-1,3-butadiene 1Da and (1Z,3Z)-1,4-dibromo-1,4-
diiodo-2,3-dihexyl-1,3-butadiene 1Db were formed highly
selectively in 89% and 85% isolated yields, respectively.
Firstly, we tried to prepare 1,1,4,4-tetrahalo-1,3-butadi-
enes 1A. Obviously, the type of 1,1,4,4-tetrahalides 1A may
be generated via desilylation/halogenation of their corres-
ponding 1,4-bis(trimethylsilyl)-1,3-butadienes 2A. Excel-
lent procedures for the one-pot preparation of 2A have
been reported starting from 1-trimethylsilyl-1-alkynes
and low valent zirconocene species (Negishi reagent,
Cp2ZrBu2).16 As shown in Scheme 2, a variety of 2A could
be isolated in high yields, generally in more than 90% iso-
lated yields. After several trials, we found these compounds
could be highly selectively desilylated and brominated
using Br2 at ꢀ78 °C in CH2Cl2 solvent. As expected,
1,1,4,4-tetrabromo-1,3-butadienes 1Aa and 1Ab were
obtained in 92% and 94% isolated yields, respectively.17
To the best of our knowledge, this method represents a
novel methodology for these potentially useful polyhalo
conjugated dienes. It should be pointed out that, when
the substituents (R) at positions 2 and 3 were Ph groups,
the desilylation/bromination process did not work well,
affording product 1Ac in much lower yield.
Similarly, a different type of tetrabromobutadienes, 1,2-
bis(dibromomethylene)-cyclohexane 1Ba was obtained in
85% isolated yield (Scheme 3).
Zirconaindene intermediates 3C could be readily gener-
ated via pair-selective cross-coupling of one molecule of
benzene and one molecule of normal alkyne on low valent
(1Z,2Z)-1,2-bis(bromoiodomethylene)cyclohexane
1Ea
was obtained in 89% isolated yield. The structure of 1Ea
Cp2ZrPh2
SiMe3
SiMe3
ZrCp2
SiMe3
NBS
CuCl
2 equiv.
R
R
R
R
90 o
C
Cp2ZrBu2
Ph-H
Br
Br
R
SiMe3
- 78 oC to r.t.
1h
R
R
SiMe3
Br
NBS
CuCl
Me3Si Cp2Zr
SiMe3
SiMe3
2A: isolated
Zr
yields > 90%
Br
Br
Cp2
SiMe3
R
2C: isolated
R
R
Br2
R
3C
Br
Br
yield >90%
Br
Br
R
R
SiMe3
Br
Br
Br
in CH2Cl2
- 78 o
R
Br2
C
Br
SiMe3
1Aa: R = Bu, 92%
1Ab: R = Hex, 94%
1Ac: R = Ph, 20%
Br
2C
Br
2A
1Ca: R = Bu, 91%
1Cb: R = Hex, 87%
Scheme 2. Preparation of 1,1,4,4-tetrabromo-2,3-disubstituted-1,3-buta-
diene derivatives.
Scheme 4. Preparation of gem-dibromovinyl-2-bromobenzene derivatives.

626
H.-J. Zhang et al. / Tetrahedron Letters 49 (2008) 624–627
SiMe3
SiMe3
for example, NBS as the first halogenation reagent,
R
SiMe3
I
R
R
followed by a more reactive halogenation reagent, for
example, I2 and CuCl as promoter.19 As given in Scheme
6, different types of polyhalides 1G,H from the abovemen-
tioned 1D–F, (Z)-1,1,4-tribromo-4-iodo-2,3-disubstituted-
1,3-butadiene derivatives 1Ga,b and (Z)-1-(bromoiodo-
methylene)-2-(dibromomethylene)-cyclohexane 1Ha were
generated in excellent yields. The structure of 1Ha was con-
firmed by single-crystal X-ray structural analysis (Fig. 2).
To achieve one-pot synthesis of 1,1,4,4-tetrabromo-1,3-
dienes directly from 1-trimethylsilyl-1-alkynes via zircona-
cyclopentadienes 3 but without isolation of 2, bromine
was added directly to the reaction mixture containing
2Aa. However, in THF, the desilylation/bromination pro-
cess did not work, leaving 2Aa unchanged although excess
bromine in CCl4 solution was used. In CH2Cl2, tribromides
were obtained at ꢀ78 °C with high selectivity and at ele-
vated temperature tetrabromides and unknown byproducts
were both obtained.
I
I
I
I
I
SiMe3
2D
SiMe3
2E
2F
R
I
Br
Br
Br
Br
I
R
I
I
I
I
R
Br
1Da:
1Ea: 89%
1Fa:
R = Bu, 89%
1Db:
R = Hex, 85%
R = Bu, 88%
1Fb:
R = Hex, 91%
Scheme 5. Preparation of (1Z,3Z)-1,4-dibromo-1,4-diiodo-2,3-disubsti-
tuted-1,3-butadiene derivatives and 1-((Z)-2-bromo-2-iodovinyl)-2-iodo-
benzene derivatives.
was confirmed by single-crystal X-ray structural analysis
(Fig. 2). Similarly, substituted 1-((Z)-2-bromo-2-iodovi-
nyl)-2-iodobenzene derivatives 1Fa and 1Fb were obtained
in 88% and 91% isolated yield, respectively.
More complicated polyhalides with different halides
were also obtained following a similar procedure, with
the main point of preparation of the key intermediates,
the 1,4-mixed-dihalo-1,3-butadienes via step-by-step halo-
genation of zirconacyclopentadienes. The point to be
successful was to use a less reactive halogenation reagent,
In summary, we have developed a synthetically useful
method for the preparation of interesting but otherwise
unavailable polyhalo conjugated dienes, following a new
strategy. Further synthetic application for organic synthe-
sis is in progress in our laboratory.
Acknowledgments
Mr. Di Liu did some experiments. This work was sup-
ported by the Natural Science Foundation of China, the
Major State Basic Research Development Program
(2006CB806105), Henan Province Innovation Fund, and
international joint supervision of Ph.D. grant from the
Ambassade de France in China. The Cheung Kong
Scholars Programme, Qiu Shi Science & Technologies
Foundation, BASF, Eli Lilly China and Dow Corning
Corporation are gratefully acknowledged.
Supplementary data
Supplementary data associated with this article can be
found, in the online version, at doi:10.1016/j.tetlet.
2007.11.152.
Fig. 2. X-ray structures of 1Ea (left, CCDC 658988) and 1Ha (right,
CCDC 658989).
SiMe3
References and notes
SiMe3
R
R
R
R
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Br
I
ZrCp2
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1,4-bis(trimethylsilyl)-2,3-disubstituted-1,3-butadienes (1.0 mmol in
5.0 mL of CH2Cl2) was added dropwise 4.0 mmol Br2 at ꢀ78 °C,
and the mixture was stirred for 2 h at the same temperature. Then the
resulting mixture was treated with 10.0 mL of 15% NaHSO3 at
ꢀ78 °C. The mixture was stirred at this temperature for 10 min and
then warmed to room temperature. The mixture was maintained at
ambient temperature for 30 min and was extracted with ether
(3 ꢁ 10.0 mL). The combined organic layer was washed with satu-
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evaporation of the solvent, column chromatography on silica gel with
petroleum afforded the title product. 5,6-Bis(dibromomethylene)-
1
decane (1Aa): colorless liquid, isolated yield 92% (443 mg); H NMR
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(m, 2H, CH2), 2.45–2.55 (m, 2H, CH2); 13C NMR (CDCl3) d 13.8
(2CH3), 22.9 (2CH2), 28.7 (2CH2), 36.2 (2CH2), 89.9 (2 quart C),
145.2 (2 quart C); HRMS calcd for C12H18Br4 477.8142, found
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