Tetrabromobutatriene: Completing the perhalocumulene series

Article abstract of DOI:10.1021/ol049734x

Tetrabromobutatriene, C₄Br₄, can be prepared directly from dibromobutadiyne by reaction with Br₂ at -25°C in concentrated hexanes solution. The cumulene precipitates out of the reaction mixture as a yellow powder. Under palladium-catalyzed coupling conditions, C₄Br₄ can undergo allylic rearrangement, giving a mixture of products, including some with butenyne backbones. However, in furan solution, C₄Br₄ reacts cleanly at its central double bond to give the furan Diels-Alder adduct. Under Suzuki conditions, this adduct reacts at the furan double bond rather than at bromide.

Full text of DOI:10.1021/ol049734x

ORGANIC
LETTERS
2004
Vol. 6, No. 13
2081-2083
Tetrabromobutatriene: Completing the
Perhalocumulene Series
Pei-Hua Liu, Lei Li, Jeffrey A. Webb, Yi Zhang, and Nancy S. Goroff*
Department of Chemistry, State UniVersity of New York,
Stony Brook, New York 11794-3400
nancy.goroff@sunysb.edu
Received February 14, 2004 (Revised Manuscript Received May 17, 2004)
ABSTRACT
Tetrabromobutatriene, C Br4, can be prepared directly from dibromobutadiyne by reaction with Br2 at −25 °C in concentrated hexanes solution.
4
The cumulene precipitates out of the reaction mixture as a yellow powder. Under palladium-catalyzed coupling conditions, C Br4 can undergo
4
allylic rearrangement, giving a mixture of products, including some with butenyne backbones. However, in furan solution, C Br4 reacts cleanly
4
at its central double bond to give the furan Diels−Alder adduct. Under Suzuki conditions, this adduct reacts at the furan double bond rather
than at bromide.
The perhalocumulenes 1-4 are attractively simple com-
pounds with unusual structures (Figure 1). Of these, tet-
tetraiodobutatriene (4),3 bringing the number of known
perhalocumulenes to three. Unlike the previous syntheses
of 1 and 2, we prepared 4 via electrophilic halogenation,
starting from diiodobutadiyne. Here, we present the synthesis
and properties of compound 3, the last to be made in the
series of perhalocumulenes.
The perhalocumulenes have particular promise as starting
materials for the synthesis of larger cross-conjugated mol-
ecules and materials. After preparing 4, we searched for ways
to use it as a substrate for Stille- or Sonagashira-type
couplings. However, compound 4 is extremely unstable in
most solvents, undergoing disproportionation to give
1,1,2,3,4,4-hexaiodobutatriene (C4I6, 5) plus unknown carbon-
rich byproducts.3 Compound 4 is more stable in benzene or
carbon tetrachloride, but its solubility in these solvents is
too poor for effective reaction. We have not yet found reliable
conditions for coupling 4 to either aryl or alkynyl com-
pounds.
Figure 1. Perhalocumulenes 1-4.
rafluorobutatriene (1) was first reported in 1959 by Martin
and Sharkey.1 Heinrich and Roedig prepared compound 2
in 1968,2 and in 2002, we reported the synthesis of
(2) Heinrich, B.; Roedig, A. Angew. Chem., Int. Ed. Engl. 1968, 7, 375-
376.
(1) Martin, E. L.; Sharkey, W. H. J. Am. Chem. Soc. 1959, 81, 5256-
5258.
(3) Webb, J. A.; Liu, P.-H.; Malkina, O. L.; Goroff, N. S. Angew. Chem.,
Int. Ed. 2002, 41, 3011-3014.
10.1021/ol049734x CCC: $27.50 © 2004 American Chemical Society
Published on Web 05/29/2004

Like 4, perbromocumulene 3 might also act as a substrate
for palladium-catalyzed couplings, and it is an interesting
target in its own right. We therefore decided to pursue the
synthesis of compound 3. The methodology used to make
compound 4 can be applied to the preparation of 3, with
some caveats. First, the major difficulty in making 4 is
overiodination to give hexaiodobutadiene (5). Because
bromine addition occurs even more readily, overbromination
of 3 is a greater problem. In addition, dibromobutadiyne (6)
can explode at room temperature when neat, even under
argon.4 Thus, careful handling and low temperatures are
required for any reactions using 6, and it must be prepared
shortly before use.
lizing agent, we obtained suitable crystals for X-ray analysis.
In these crystals, each phenazine nitrogen is 3.05 Å from a
bromine atom, consistent with weak Lewis acid-base
interactions between them (Figure 2).7
Despite these difficulties, we have now found conditions
under which bromination of compound 6 will lead to
cumulene 3 (Scheme 1). Dropwise addition of bromine to a
Scheme 1
concentrated solution of freshly prepared 6 (1.1 equiv) in
hexanes at -25 °C leads to formation of a yellow precipitate,
compound 3. The remaining filtrate is a complex mixture
that contains 1,1,2,3,4,4-hexabromobutadiene (7) as the major
component.5 Under these conditions, the yield of pure 3 is
about 30-40%.
Figure 2. Crystal structure of 3 with phenazine, showing (a) the
intermolecular N-Br interactions which provide order in the crystal
and (b) the overall packing of the molecules.
Neat compound 3 is stable to above its melting temperature
of 102-104 °C. (Unlike 2,2 compound 3 does not dimerize
to form a [4]radialene.) Compound 3 decomposes in solution
over time, but more slowly than compound 4. The NMR
spectrum of 3 in DMSO-d6 includes only two peaks, at 65.5
and 153.6 ppm. By analogy to compound 4, we assign the
lower-frequency peak to C-1 and C-4, and the higher peak
to C-2 and C-3. The IR absorptions of 3 match calculations
well: 777 and 1634 cm-1 (KBr pellet) vs 771 and 1703 cm-1
calculated (B3LYP/6-31G*).6
Although compounds 1-4 have similar structures, they
have distinctly different properties. Compound 1, the earliest
identified of the four, is the least stable.1,8 At or near its
boiling temperature of -5 °C, liquid 1 detonates violently.
In the gas phase, it explodes in the presence of oxygen and
slowly forms polymeric material in inert atmosphere. In
contrast, compounds 2-4 are stable solids at room temper-
ature. Compound 2 is also stable in solution and has been
used as a starting material for reactions such as nucleophilic
addition-elimination to make perthiocumulenes.9 Our past
efforts to carry out similar reactions using 4 as a substrate
have been hampered by its poor solubility and stability in
solution.
Compound 3 does not readily form X-ray quality single
crystals alone. However, by using phenazine as a cocrystal-
(4) Dembinski, R.; Bartik, T.; Bartik, B.; Jaeger, M.; Gladysz, J. A. J.
Am. Chem. Soc. 2000, 122, 810-822.
(5) Straus, F.; Kollek, L.; Hauptmann, H. Ber. 1930, 63B, 1886-1899.
(6) (a) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.;
Robb, M. A.; Cheesemen, J. R.; Zakrzewski, V. G.; Montgomery, J. A.;
Startmann, R. E.; Burant, J. C.; Dapprich, S.; Millam, J. M.; Daniels, A.
D.; Kudin, K. N.; Strain, M. C.; Farkas, O.; Tomasi, J.; Barone, V.; Cossi,
M.; Cammi, R.; Mennucci, B.; Pomelli, C.; Adamo, C.; Clifford, S.;
Ochterski, J.; Petersson, G. A.; Ayala, P. Y.; Cui, Q.; Morokuma, K.; Malick,
D. K.; Rabuck, A. D.; Raghavachari, K.; Foresman, J. B.; Cioslowski, J.;
Ortiz, J. V.; Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz, P.; Komaromi,
I.; Gomperts, R.; Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham, M. A.;
Peng, C. Y.; Nanaykkara, A.; Gonzalez, C.; Challacombe, M.; Gill, P. M.
W.; Johnson, B. G.; Chen, W.; Wong, M. W.; Andres, J. L.; Head-Gordon,
M.; Replogle, E. S.; Pople, J. A. Gaussian 98, Revision A.5; Gaussian,
Inc.: Pittsburgh, PA, 1998. (b) Becke, A. D. J. Chem. Phys. 1996, 104,
1040-1046.
Compound 3 is soluble and moderately stable in solution.
In examining its chemistry, we focused first on its potential
as a substrate for palladium-catalyzed aryl couplings to make
targets such as tetraphenyl cumulene 8.10 We have found,
however, that Suzuki couplings give undesirable mixtures
of products (Figure 3). The makeup of the product mixture
(7) Metrangolo, P.; Resnati, G. Chem.sEur. J. 2001, 7, 2511-2519.
(8) Bach, A.; Lentz, D.; Luger, P.; Messerschmidt, M.; Olesch, C.;
Patzschke, M. Angew. Chem., Int. Ed. 2002, 41, 296-299.
(9) (a) Roedig, A.; Zaby, G.; Scharf, W. Chem. Ber. 1977, 110, 1484-
1491. (b) Roedig, A.; Zaby, G. Lieb. Ann. Chem. 1979, 1614-1625.
2082
Org. Lett., Vol. 6, No. 13, 2004

Scheme 2
of furan to 3 is clean and high yielding (Scheme 2). This
reaction, carried out at room temperature over 48 h, gives
adduct 14 in 96% yield. With adduct 14 in hand, we
attempted the Suzuki coupling with phenylboronic acid
(Scheme 3). Unfortunately, we isolate compounds 16 and
Figure 3. Desired product (8) and actual products (9-13) of the
Suzuki coupling of phenyl boronic acid to 3.
Scheme 3
depends on the solvent, the temperature, and the amount of
phenyl boronic acid used, but in all cases allylic rearrange-
ment competes with the desired coupling reactions, leading
to enynes such as 10-12. Reaction in benzene provides a
small amount of monophenylcumulene 9 (14%), in addition
to 10 and 11, but no other cumulenes. In THF/H2O (4:1),
diphenylbutadiyne (13) is a major product, along with the
enynes 10-12. In all cases, the reactions are not synthetically
useful. Similarly, Stille coupling with phenyltributyltin at
room temperature in toluene11 gives a mixture of products,
of which enyne 11 appears to be the major component,
although no purification was attempted. Experimental details
for these reactions are provided in the Supporting Informa-
tion.
To use compound 3 as a starting material for making
substituted cumulenes requires a method to protect the central
double bond from allylic rearrangment. For this purpose, we
turned to the Diels-Alder reaction. Calculations (B3LYP/
6-31G*) indicate that the LUMO of 3 is located almost
entirely on the central double bond, and it is lower in energy
than the LUMO of dimethyl acetylenedicarboxylate. Diels-
Alder addition, followed by palladium coupling and then a
retro-Diels-Alder reaction, would provide a potential syn-
thetic route to substituted cumulenes such as 8.
17 from this reaction, instead of the desired 15, indicating
palladium insertion at the “wrong” double bond of 14.12
Appropriate conditions for preparing tetraaryl cumulenes
from 3 remain elusive. Nonetheless, compound 3 persists as
an attractive substrate for further synthetic manipulation
because of its solubility and relative stability. The Diels-
Alder reaction of 3 with furan gives a single product in high
yield. Efforts will continue toward finding a synthetic route
from 3 to larger cumulene derivatives.
Acknowledgment. We acknowledge the National Science
Foundation (CHE-9984937 and CHE-0131146) for support
of this research. We thank R. Tykwinski for helpful discus-
sions and O. Nduka for help in identifying compounds 16
and 17.
In practice, the Diels-Alder reaction works well. Unlike
the palladium-coupling reactions of 3, Diels-Alder addition
(10) (a) Zweig, A.; Hoffmann, A. K. J. Am. Chem. Soc. 1962, 84, 3278-
3284. (b) Sisenwine, S. F.; Day, A. R. J. Org. Chem. 1967, 32, 1770-
1773. (c) Jasiobedzki, W.; Kujda, J.; Wozniak-Kornacka, J.; Zelechowski,
K. Bull. Pol. Acad. Sci. Chem. 1996, 44, 215-234. (d) Dyker, G.; Borowski,
S.; Henkel, G.; Kellner, A.; Dix, I.; Jones, P. G. Tetrahedron Lett. 2000,
41, 8259-8262.
(11) Littke, A. F.; Schwarz, L.; Fu, G. C. J. Am. Chem. Soc. 2002, 124,
6343-6348.
(12) For previous reports of similar reactions, see: (a) Duan, J.-P.; Cheng,
C.-H. Tetrahedron Lett. 1993, 34, 4019-4022. (b) Moinet, C.; Fiaud, J.-C.
Tetrahedron Lett. 1995, 36, 2051-2052. (c) Montalbetti, C.; Savignac, M.;
Geneˆt, J.-P.; Roulet, J.-M.; Vogel, P. Tetrahedron Lett. 1996, 37, 2225-
2228.
Supporting Information Available: Experimental pro-
cedures and spectroscopic characterization for all new
compounds, computational details, and crystallographic data
for the cocrystals of 3 and 16 (Ar ) p-C6H5OMe) with
phenazine. This material is available free of charge via the
Internet at http://pubs.acs.org.
OL049734X
Org. Lett., Vol. 6, No. 13, 2004
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