Synthesis of gem-dihaloenynes and butatrienes from gem-dihalovinyl derivatives

Article abstract of DOI:10.1016/j.tetlet.2012.06.060

gem-Dihaloenynes were synthesized in high yields from 1,1,4,4-tetrahalo-1, 3-butadienes through the Fritsch-Buttenberg-Wiechell (FBW) rearrangement mediated by an organolithium compound. Butatriene derivatives could be obtained efficiently via an organoli

Full text of DOI:10.1016/j.tetlet.2012.06.060

Tetrahedron Letters 53 (2012) 4555–4557
Contents lists available at SciVerse ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Synthesis of gem-dihaloenynes and butatrienes from
gem-dihalovinyl derivatives
Tianhao Meng a, Hui-Jun Zhang b, Zhenfeng Xi b,c,
⇑
a Beijing National Laboratory for Molecular Sciences (BNLMS), Institute of Chemistry, Chinese Academy of Sciences (CAS), Beijing 100190, China
b Beijing National Laboratory of Molecular Sciences (BNLMS), Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education,
College of Chemistry, Peking University, Beijing 100871, China
c State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry (SIOC), CAS, Shanghai 200032, China
a r t i c l e i n f o
a b s t r a c t
Article history:
gem-Dihaloenynes were synthesized in high yields from 1,1,4,4-tetrahalo-1,3-butadienes through the
Fritsch–Buttenberg–Wiechell (FBW) rearrangement mediated by an organolithium compound.
Butatriene derivatives could be obtained efficiently via an organolithium-mediated reaction of o-halo-
(2,2-dihalovinyl)benzenes.
Received 7 May 2012
Revised 5 June 2012
Accepted 12 June 2012
Available online 18 June 2012
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Butatriene
Cumulene
gem-Dihaloolefin
gem-Dihaloenyne
Fritsch–Buttenberg–Wiechell (FBW)
rearrangement
o-Halo-(2,2-dihalovinyl)benzenes
1,1,4,4-Tetrahalo 1,3-butadiene
gem-Dihalovinyl compounds are useful building blocks in
organic synthesis.1,2 When such a compound is treated with a base
such as an organolithium, an alkyne may be generated via the Frit-
sch–Buttenberg–Wiechell (FBW) rearrangement (Scheme 1).3,4 On
the other hand, butatrienes are interesting compounds both struc-
turally and synthetically.5,6 The most common synthetic method
for butatrienes is via a halolithio carbenoid intermediate generated
by a single metal-halo exchange of a gem-dihaloalkene with an
organolithium reagent.5 Reductive coupling of the halolithio carb-
enoid intermediate is usually promoted by a transition metal, such
as a copper salt, to afford the corresponding butatriene derivative.5
In some cases, butatriene derivatives can be also generated via di-
rect dimerization of the carbenoid intermediates.7 As by-products
in these reactions, disubstituted acetylenes might be formed via
the FBW rearrangement.
gem-dihalovinyl compounds 2, o-halo-(2,2-dihalovinyl)benzenes,
can also be readily obtained in high yields. As our continued inter-
est in the synthetic applications of such polyhalo-substituted con-
jugated systems, we subjected such compounds under the FBW
rearrangement conditions. gem-Dihaloenynes were generated in
high yields via n-BuLi-mediated transformation of 1,1,4,4-tetra-
halo-1,3-butadienes in hexane. Further applications of gem-dihalo-
enynes were demonstrated. Butatriene derivatives could also be
obtained efficiently via an organolithium-mediated reaction of
o-halo-(2,2-dihalovinyl)benzenes in THF.5,6 The structure of one
butatriene derivative was determined by single-crystal X-ray
structural analysis.5
FBW
R
R
X
X
Rearrangement
In recent years, we have been interested in the preparation and
synthetic applications of polyhalo compounds including gem-diha-
lo vinylic moieties, aiming at utilizing the potential synergistic
effect among functional groups on conjugated systems.8,9 As
shown in Scheme 2, we have developed an efficient synthetic
method for 1,1,4,4-tetrahalo 1,3-butadienes 1. Similarly, the
R
R
(X = Br, I)
R'Li
1,2-shift
R
Li
X
R
R
- LiX
R
⇑
Corresponding author. Tel.: +86 10 6275 9728; fax: +86 10 6275 1708.
E-mail address: zfxi@pku.edu.cn (Z. Xi).
Scheme 1. The Fritsch–Buttenberg–Wiechell (FBW) rearrangement.
0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2012.06.060

4556
T. Meng et al. / Tetrahedron Letters 53 (2012) 4555–4557
SiMe3
Pd2(dba)3 (2.5 mol %)
SPhos (10 mol %)
PhB(OH)2 (2.2 equiv)
SiMe3
ZrCp2
SiMe3
SiMe3
R
R
R
R
R
R
Cp2ZrBu2
1) NXS
X
X'
Ph
Br
- 78 oC to r.t.
THF
2) NX'S or X'2
CuCl
R
Ph
R
Br
3a-b
R
Cs2CO3 (3 equiv)
Toluene, 110 oC, 2 h
SiMe3
4a: R = Bu, 76%
4b: R = Hex, 71%
2 eq.
1a:
Br
R = Bu, X = X' = Br, 92%
SiMe3
1b: R = Hex, X = X' = Br, 94%
1c: R = Bu, X = Br, X' = I, 88%
R
R
R
Scheme 4. Suzuki–Miyaura coupling of gem-dibromoenynes 3.
Br2
X
X'
X
1d:
R = Hex, X = Br, X' = I, 80%
- 78 oC
CH2Cl2
X'
1e: R = Pr, X = Br, X' = I, 82%
R
1f:
R = Bu, X = Cl, X' = I, 79%
Br
SiMe3
R
1
R
R
SiMe3
SiMe3
1 eq. n-BuLi
Hexane, - 78 oC
Cp2ZrPh2
NBS or I2
SiMe3
R
X
X
90 oC
toluene
CuCl
Zr
R
Br
X
5: X = Br, R = Bu, 86%
X
R
Cp2
R
SiMe3
Br
R
2a:
R = Bu, X = Br, 91%
X
X
Br2
1 eq. n-BuLi
THF, - 78 oC
2b: R = Hex, X = Br, 87%
X
X
- 78 oC
CH2Cl2
2c:
R = Me, X = I, 75%
2
X
X
2
X
R
R
R
6
Scheme 2. Synthesis of polyhalo-substituted conjugated systems.
Br
or
Li
6a: X = Br, R = Bu, 53%
6b: X = Br, R = Hex, 54%
6c: X = I, R = Me, 46% (E/Z)
Li
Br
X
7
X
8
R
Br
2 eq. t-BuLi
Scheme 5. Synthesis of butatrienes 6.
Br
R
THF, - 78 oC
Br
Br
3a: R = Bu, 53%
R
R
3b: R = Hex, 54%
Br
Br
R
Br
2 eq. t-BuLi
Br
R
Hexane, - 78 oC
1a-b
3a: R = Bu, 66%
3b: R = Hex, 61%
Br
R
R
R
1 eq. n-BuLi
Hexane, - 78 oC
I
Br
Br
R
Br
Br
1c-e
3a: R = Bu, 95%
3b: R = Hex, 88%
3c: R = Pr, 95%
Figure 1. Single-crystal X-ray structure of E-6c with 30% thermal ellipsoids.
Hydrogen atoms are omitted for clarity. Selected bond lengths [Å]: C1–C6 1.406(5),
C6–C7 1.485(5), C7–C8 1.505(5), C7–C9 1.328(5), C9–C90 1.261(7), C1–I1 2.103(3).
Br
Bu
Br
Bu
Bu
1 eq. n-BuLi
Hexane, - 78 oC
I
Cl
organolithium reagent. In these cases, t-BuLi was too reactive
and the reaction gave a mixture of products. The best condition
was realized when n-BuLi was applied in hexane solution. As
shown in Scheme 3, the gem-dibromoenynes 3a–c could be ob-
tained in excellent isolated yields.10 To the best of our knowledge,
this is the first example of gem-dihaloenynes synthesis via the FBW
rearrangement of 1,1,4,4-tetrahalo 1,3-butadienes.11
Cl
Bu
Br
1f
3d: 98%
Scheme 3. Synthesis of gem-dihaloenynes 3.
Similarly, as shown in Scheme 3, when the Cl, Br, I-mixed poly-
halo conjugated butadiene 1f was treated with n-BuLi in hexane,
the corresponding gem-dihaloenyne 3d was generated quantita-
tively as the sole isomer.
Synthetic application of the gem-dihaloenyne derivatives was
preliminarily demonstrated (Scheme 4). Thus compounds 3a and
3b were subjected to the Suzuki–Miyaura cross-coupling reaction
condition, which afforded the diphenyl-substituted enynes 4a
and 4b in 76% and 71% isolated yields, respectively.11c
Butatriene derivatives could be obtained efficiently via an orga-
nolithium-mediated reaction of o-halo-(2,2-dihalovinyl)benzenes.
As given in Scheme 5, when the o-bromo-(2,2-dibromovinyl)ben-
zene derivative 2a was treated with n-BuLi in hexane, the corre-
Initially, the 1,1,4,4-tetrabromo-1,3-butadiene 1a–b was trea-
ted with t-BuLi in THF (Scheme 3). The expected gem-dib-
romoenyne 3a–b could be generated, but in moderate yields.
When the reaction was carried out in hexane using t-BuLi, the
gem-dibromoenyne derivatives 3a and 3b were obtained in 66%
and 61% isolated yields, respectively. The yields increased but were
not satisfied. This is probably due to the relatively low reactivity of
the C(sp2)-Br bond. In fact, when n-BuLi was used instead of t-BuLi,
no lithio-bromo exchange was observed under the above reaction
condition in THF or in hexane. Therefore, to achieve a higher
lithio-halo exchange rate and better yields, the C(sp2)-I bond-con-
taining derivatives 1c–e were synthesized and treated with an

T. Meng et al. / Tetrahedron Letters 53 (2012) 4555–4557
4557
4. For recent examples on polyyne synthesis via the FBW rearrangement, see: (a)
Spantulescu, A.; Luu, T.; Zhao, Y.; McDonald, R.; Tykwinski, R. R. Org. Lett. 2008,
10, 609–612; (b) Kendall, J.; McDonald, R.; Ferguson, M. J.; Tykwinski, R. R. Org.
Lett. 2008, 10, 2163–2166; (c) Luu, T.; Morisaki, Y.; Cunningam, N.; Tykwinski,
R. R. J. Org. Chem. 2007, 72, 9622–9629; (d) Eisler, S.; Slepkov, A. D.; Elliott, E.;
Luu, T.; McDonald, R.; Hegmann, F. A.; Tykwinski, R. R. J. Am. Chem. Soc. 2005,
127, 2666–2667; (e) Tobe, R.; Umeda, R.; Iwasa, N.; Sonoda, M. Chem. Eur. J.
2003, 9, 5549–5559; (f) Shi, S.; Annabelle, L. K.; Chernike, E. T.; Eisler, S.;
Tykwinski, R. R. J. Org. Chem. 2003, 68, 1339–1347; (g) Rezaei, H.; Yamanoi, S.;
Chemla, F.; Normant, J. F. Org. Lett. 2000, 2, 419–421; (h) Eisler, S.; Tykwinski, R.
R. J. Am. Chem. Soc. 2000, 122, 10736–10737.
sponding FBW rearrangement product, the o-bromophenyl acety-
lene 5 was exclusively formed and obtained in 86% isolated yield.
However, when the reaction was carried out in THF, butatriene
derivatives 6 mainly as E-isomers were obtained as the major
products,12 via direct dimerization of the carbenoid intermediates
7 and/or 8. The butatriene derivative 6c was obtained as a mixture
of 1:1 E/Z isomers. In addition, when the R group was butyl, we
also detected trace amount of the Z-form butatriene by the NMR
spectra.
Obviously, the solvent polarity and coordination ability seem
crucial for these two different transformations. Hexane is found
to be the most effective solvent for the FBW rearrangement, while
most polar solvents such as THF will afford butatriene derivatives
as major products. The structure of E-6c was confirmed by single-
crystal X-ray structural analysis (Fig. 1).13
5. For a recent review on butatriene synthesis, see: Leroyer, L.; Maraval, V.;
Chauvin, R. Chem. Rev. 2012, 112, 1310–1343.
6. (a) Fu, X.; Chen, J.; Li, G.; Liu, Y. Angew. Chem., Int. Ed. 2009, 48, 5500–5504; (b)
Liu, Y.; Gao, H.; Zhou, S. Angew. Chem., Int. Ed. 2006, 45, 4163–4167; (c) Uno, H.;
Kasahara, K.; Nibu, N.; Nagaoka, S.; Ono, N. J. Org. Chem. 2000, 65, 1615–1622;
(d) Moken, P. A.; Bachand, P. C.; Swenson, D. C.; Burton, D. J. J. Am. Chem. Soc.
1993, 115, 5430–5439; (e) Iyoda, M.; Tanaka, S.; Otani, H.; Nose, M.; Oda, M. J.
Am. Chem. Soc. 1988, 110, 8494–8500.
7. (a) Kobrich, G.; Heinemann, H.; Zundorf, W. Tetrahedron 1967, 23, 656–684; (b)
Komatsu, K.; Kamo, H.; Tsuji, R.; Takeuchi, K. J. Org. Chem. 1993, 58, 3219–3221;
(c) Knorr, R.; Pires, C.; Freudenreich, J. J. Org. Chem. 2007, 72, 6084–6090.
8. (a) Liang, Y.; Meng, T.; Zhang, H.-J.; Xi, Z. Synlett 2011, 911–914; (b) Zhang, H.-
J.; Wei, J.; Zhao, F.; Liang, Y.; Wang, Z.; Xi, Z. Chem. Commun. 2010, 46, 7439–
7441. see also:; (c) Xi, Z. Acc. Chem. Res. 2010, 43, 1342–1451; (d) Wang, Q.;
Zhang, W.-X.; Lin, C.; Xi, Z. Chin. Sci. Bull. 2010, 55, 2915–2923; (e) Xi, Z. Sci.
China Chem. 2009, 39, 1115–1124; (f) Liu, G.; Song, Z.; Wang, C.; Xi, Z. Chin. J.
Org. Chem. 2007, 27, 837–846.
In summary, we developed a convenient synthesis of gem-
dihaloenynes from 1,1,4,4-tetrahalo-1,3-butadienes through the
Fritsch–Buttenberg–Wiechell (FBW) rearrangement. Butatriene
derivatives were also obtained efficiently.
Acknowledgments
9. (a) Zhang, H.-J.; Song, Z.; Wang, C.; Bruneau, C.; Xi, Z. Tetrahedron Lett. 2008, 49,
624–627; (b) Xi, Z.; Song, Z.; Liu, G.; Liu, X.; Takahashi, T. J. Org. Chem. 2006, 71,
3154–3158; (c) Xi, Z.; Liu, X.; Lu, J.; Bao, F.; Fan, H.; Li, Z.; Takahashi, T. J. Org.
Chem. 2004, 69, 8547–8549.
This work was supported by the Natural Science Foundation of
China, and the Major State Basic Research Development Program
(2011CB808700).
10. Preparation of gem-dibromoenynes 3: To a stirred solution of 1,1,4,4-mixed-
tetrahalo-1,3-butadiene (5 mmol) in dry hexane (20 mL) at ꢀ78 °C (acetone/
dry ice) was added n-BuLi (3.2 mL, 1.6 M in hexane) dropwise. After 5 min the
reaction was completed, and the suspended mixture was filtered to remove
solid residue, then it was washed with hexane (3 ꢁ 10 mL). The combined
filtrates were concentrated under reduced pressure to give the pure product of
gem-dibromoenynes 3 without further purification.
Supplementary data
Supplementary data (experimental procedures and character-
ization data for all new compounds and copies of NMR spectra)
associated with this article can be found, in the online version, at
http://dx.doi.org/10.1016/j.tetlet.2012.06.060.
Compound 3a, yellow oil, isolated yield 95% (1.5 g); 1H NMR (400 MHz, CDCl3)
d: 0.93 (t, J = 7.3 Hz, 6H, CH3), 1.31–1.59 (m, 8H, CH2), 2.29–2.37 (m, 4H, CH2);
13C NMR (100 MHz, CDCl3) d: 13.53 (CH3), 13.84 (CH3), 19.37 (CH2), 21.89
(CH2), 22.03 (CH2), 29.67 (CH2), 30.42 (CH2), 36.82 (CH2), 79.39 (quat. C), 94.47
(quat. C), 98.81 (quat. C), 131.44 (quat. C). HRMS (EI, m/z) calcd for
[C12H18Br2]+: 321.9755; found 321.9750.
References and notes
11. For gem-dihaloenyne synthesis using other methods, see: (a) Fang, Y.-Q.;
Lifchits, O.; Lautens, M. Synlett 2008, 413–417; (b) Azyat, K.; Jahnke, E.; Rankin,
T.; Tykwinski, R. R. Chem. Commun. 2009, 433–435; (c) Rankin, T.; Tykwinski, R.
R. Org. Lett. 2003, 5, 213–216; (d) Martín, R.; Rodríguez, M. R.; Buchwald, S. L.
Angew. Chem., Int. Ed. 2006, 45, 7079–7082.
12. Typical Procedure for the preparation of butatrienes 6: In a 50 mL of flask, o-halo-
(2,2-dihalovinyl)benzene 2 (1.0 mmol) was dissolved in dry THF (5 mL) at
ꢀ78 °C. n-BuLi (0.6 mL, 1.6 M in hexane) was added dropwise very slowly and
the reaction was stirred at room temperature for 15 min. The solvent of the
reaction mixture was evaporated under vacuum and hexane (20 mL) was
added. After that, the suspended mixture was filtered to remove solid residue.
The filtrate was purified by chromatography to give the butatriene product
(eluent: pentane).
1. For reviews on gem-dihalovinyl systems, see: (a) Chelucci, G. Chem. Rev. 2012,
112, 1344–1462; (b) Legrand, F.; Jouvin, K.; Evano, G. Isr. J. Chem. 2010, 50, 588–
604; (c) Wang, J.-R.; Manabe, K. Synthesis 2009, 1405–1427; (d) Xu, B.; Ma, S.
Chin. J. Org. Chem. 2001, 21, 252–262.
2. (a) Meng, T.; Zhang, W.-X.; Zhang, H.-J.; Liang, Y.; Xi, Z. Synthesis 2012. http://
dx.doi.org/10.1055/s-0032-1316613.; For recent examples on synthetic
applications of gem-dihalovinyl compounds, see: (b) Ye, S.; Liu, J.; Wu, J.
Chem. Commun. 2012, 48, 5028–5030; (c) He, H.-F.; Dong, S.; Chen, Y.; Yang, Y.;
Le, Y.; Bao, W. Tetrahedron 2012, 68, 3112–3116; (d) Zhou, W.; Chen, W.; Wang,
L. Org. Biomol. Chem. 2012, 10, 4172–4178; (e) Chen, W.; Zhang, Y.; Zhang, L.;
Wang, M.; Wang, L. Chem. Commun. 2011, 47, 10476–10478; (f) Wang, Z.-J.;
Yang, F.; Lv, X.; Bao, W. J. Org. Chem. 2011, 76, 967–970; (g) Qin, X.-R.; Cong, X.-
F.; Zhao, D.-B.; You, J.-S.; Lan, J.-B. Chem. Commun. 2011, 47, 5611–5613; (h)
Newman, S. G.; Lautens, M. J. Am. Chem. Soc. 2010, 132, 11416–11417; (i) Wang,
Z.-J.; Yang, J.-G.; Yang, F.; Bao, W. Org. Lett. 2010, 12, 3034–3037; (j) Xu, H.;
Zhang, Y.; Huang, J.; Chen, W. Org. Lett. 2010, 12, 3704–3707; (k) Arthuls, M.;
Pontikis, R.; Florent, J.-C. Org. Lett. 2009, 11, 4608–4611; (l) Bryan, C. S.;
Braunger, J. A.; Lautens, M. Angew. Chem., Int. Ed. 2009, 48, 7064–7068; (m) Ye,
W.; Mo, J.; Zhao, T.; Xu, B. Chem. Commun. 2009, 3246–3248; (n) Newman, S.
G.; Aureggi, V.; Bryanand, C. S.; Lautens, M. Chem. Commun. 2009, 5236–5238;
(o) Chai, D. I.; Lautens, M. J. Org. Chem. 2009, 74, 3054–3061; (p) Bryan, C. S.;
Lautens, M. Org. Lett. 2008, 10, 4633–4636; (q) Viera, T. O.; Meaney, L. A.; Shi,
Y.-L.; Alper, H. Org. Lett. 2008, 10, 4899–4901; (r) Fang, Y.-Q.; Lautens, M. J. Org.
Chem. 2008, 73, 538–549; (s) Sun, C.; Xu, B. J. Org. Chem. 2008, 73, 7361–7364.
3. For reviews on the Fritsch–Buttenberg–Wiechell (FBW) rearrangement, see: (a)
Knorr, R. Chem. Rev. 2004, 104, 3795–3850; (b) Stang, P. J. Chem. Rev 1978, 78,
383–405.
Compound 6a, Yellow oil, isolated yield 53% (126 mg); 1H NMR (300 MHz,
CDCl3): d = 0.80 (t, J = 7.2 Hz, 6H, CH3), 1.31–1.48 (m, 8H, CH2), 2.61 (t,
J = 7.1 Hz, 4H, CH2), 7.09–7.59 (m, 8H, CH); 13C NMR (75 MHz, CDCl3): d = 13.86
(2 CH3), 22.25 (2 CH2), 30.36 (2 CH2), 36.40 (2 CH2), 120.63 (2 quat. C), 122.35
(2 quat. C), 127.08 (2 CH), 128.44 (2 CH), 130.03 (2 CH), 133.46 (2 CH), 140.99
(2 quat. C), 158.63 (2 quat. C). HRMS (EI, m/z) calcd for [C24H26Br2]+: 474.0381,
found 474.0389.
13. For single-crystal X-ray structural analysis of butatriene derivatives, see: (a)
Reichmann, B.; Drexler, M.; Weibert, B.; Szesni, N.; Strittmatter, T.; Fischer, H.
Organometallics 2011, 30, 1215–1223; (b) Suzuki, N.; Ohara, N.; Nishimura, K.;
Sakaguchi, Y.; Nanbu, S.; Fukui, S.; Nagao, H.; Masuyama, Y. Organometallics 2011,
30, 3544–3548; (c) Mathur, P.; Avasare, V. D.; Mobin, S. M. J. Clust. Sci. 2009, 20,
399–415;(d) Akkerman,F. A.;Lentz, D. Angew.Chem., Int.Ed. 2007, 46, 4902–4904;
(e) Bachman, R. E.; Fiseha, A.; Pollack, S. K. J. Chem. Cryst. 1999, 29, 457–462.