precursors of 1-haloalkynes are highly sensitive molecules
that are prone to rapid decomposition.1,2,6
mination of 3. Repeating this reaction sequence sequentially
would allow the rapid construction of polyyne systems.
Finally, cross-coupling with a monosubstituted acetylene or
another type of coupling partner should afford the desired
unsymmetrical polyyne 5. The key to the success of this
iterative scheme lies in the in situ one-pot desilylative bro-
mination, which avoids the complication encountered with
isolating sensitive terminal alkynes. One of the salient fea-
tures of this protocol is that it allows the preparation of even-
and odd-numbered polyynes10 by controlling the number of
iterations of the chain growth cycle.
The instability of terminal diynes and higher polyynes can
be circumvented, for the preparation of symmetrical polyynes,
by employing an in situ generation/dimerization protocol.2a,3,6c
In the case of unsymmetrical polyynes, the rather limited
synthetic approaches have been reviewed.3 For example,
Tykwinski and co-worker7 employed an alkylidene carbenoid
rearrangement toward the synthesis of naturally occurring
unsymmetrical polyynes. Their protocol eliminates the need
for unstable acetylenic precursors required for coupling
approaches. Gung and co-workers8 reported the successful
one-pot three-component Cadiot-Chodkiewicz reaction to
construct the unsymmetrical tetrayne unit. Very recently,
Gung9 also reported the successful preparation of an unsym-
metrical 1,3,5-polyyne ((S)-(E)-15,16-dihydrominquartynoic
acid) via an in situ generated terminal alkyne/cross-coupling
protocol. In addition, Mori and co-workers5b reported the
CuI-catalyzed cross-coupling of chloroalkynes with alkynyl-
silanes, which are generally more stable than their corre-
sponding terminal alkynes. Although this method seems to
be promising for the future preparation of unsymmetrical
higher polyynes, an appropriate combination of chloroalkynes
and alkynylsilanes is essential for clean formation of the
desired cross-coupled products. Herein we report an alterna-
tive protocol for the synthesis of unsymmetrical polyynes
that uses a two-step homologation sequence.
To test the feasibility of our approach, we conducted our
initial studies with the simple terminal alkyne 6 (Scheme
2). Conversion of alkyne 6 to the known bromoalkyne 711
Scheme 2. Synthesis of Unsymmetrical Polyynes
Scheme 1 depicts a general outline of our iterative pro-
tocol. We envisioned that the bromoalkyne 2, which can be
Scheme 1. General Iterative Protocol for Synthesis of
Unsymmetrical Polyynes
was achieved readily in good yield (82%) with AgNO3 and
NBS12 in acetone. At this point, we decided to employ bulky
(trialkylsilyl)acetylenes as the cross-coupling partners for the
homologation reactions because it had previously been
reported that trimethylsilyl (TMS) acetylene decomposes,
possibly by a desilylation pathway, under the basic conditions
of the coupling reaction such that no desired cross-coupling
product can usually be isolated.13 When we used the bulkier
triisopropylsilyl (TIPS) acetylene, the desired cross-coupling
product 8 was obtained under standard Cadiot-Chodkiewicz
obtained from the simple terminal alkyne 1, could be ho-
mologated by one acetylene unit through cross-coupling with
the trialkylsilylacetylene 4 and subsequent desilylative bro-
(5) (a) Alami, M.; Ferri, F. Tetrahedron Lett. 1996, 37, 2763-2766. (b)
Nishihara, Y.; Ikegashira, K.; Mori, A.; Hiyama, T. Tetrahedron Lett. 1998,
39, 4075-4078. (c) Sinclair, J. A.; Brown, H. C. J. Org. Chem. 1976, 41,
1078-1079. (d) Miller, J. A.; Zweifel, G. Synthesis 1983, 128-130. (e)
Miyaura, N.; Yamada, K.; Suzuki, A. Tetrahedron Lett. 1979, 20, 3437-
3440. (f) Wityak, J.; Chan, J. B. Synth. Commun. 1991, 21, 977-979.
(6) (a) Haley, M. M.; Bell, M. L.; English, J. J.; Johnson, C. A.; Weakley,
T. J. R. J. Am. Chem. Soc. 1997, 119, 2956-2957. (b) Patel, G. N.; Chance,
R. R.; Turi, E. A.; Khanna, Y. P. J. Am. Chem. Soc. 1978, 100, 6644-
6649. (c) Haley, M. M.; Bell, M. L.; Brand, S. C.; Kimball, D. B.; Pak, J.
J.; Wan, W. B. Tetrahedron Lett. 1997, 38, 7483-7486.
(7) Shi Shun, A. L. K.; Tykwinski, R. R. J. Org. Chem. 2003, 68, 6810-
6813.
(8) (a) Gung, B. W.; Dickson, H. Org. Lett. 2002, 4, 2517-2519. (b)
Gung, B. W.; Kumi, G. J. Org. Chem. 2003, 68, 5956-5960.
(9) Gung, B. W.; Kumi, G. J. Org. Chem. 2004, 69, 3488-3492.
(10) For the synthesis of odd-numbered polyynes, see: Rubin, Y.; Lin,
S. S.; Knobler, C. B.; Anthony, J.; Boldi, A. M.; Diederich, F. J. Am. Chem.
Soc. 1991, 113, 6943-6946.
(11) (a) Hoshi, M.; Shirakawa, K. Synlett 2002, 1101-1104. (b) Abele,
E.; Rubina, K.; Abele, R.; Gaukhman, A.; Lukevics, E. J. Chem. Res., Synop.
1998, 618-619.
(12) (a) Hofmeister, H.; Annen, K.; Laurent, H.; Wiechert, H. Angew.
Chem., Int. Ed. Engl. 1984, 23, 727-729. (b) Basak, S.; Srivastava, S.; le
Noble, W. J. J. J. Org. Chem. 1987, 52, 5095-5099.
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