Nickel-catalyzed tetramerization of alkynes: Synthesis and structure of octatetraenes

Article abstract of DOI:10.1021/ol201814q

In the presence of a catalytic system comprised of NiBr₂(dppe) and Zn, arylacetylenes undergo tetramerization to form linear octatetraenes, generally in good to excellent yields. The structure of the coupling products was verified by X-ray crystallography.

Full text of DOI:10.1021/ol201814q

ORGANIC
LETTERS
2011
Vol. 13, No. 18
4794–4797
Nickel-Catalyzed Tetramerization of
Alkynes: Synthesis and Structure of
Octatetraenes†
Tsun-Cheng Wu, Jheng-Jhih Chen, and Yao-Ting Wu*
Department of Chemistry, National Cheng Kung University, No. 1 Ta-Hsueh Road,
70101 Tainan, Taiwan
ytwuchem@mail.ncku.edu.tw.
Received July 6, 2011
ABSTRACT
In the presence of a catalytic system comprised of NiBr2(dppe) and Zn, arylacetylenes undergo tetramerization to form linear octatetraenes,
generally in good to excellent yields. The structure of the coupling products was verified by X-ray crystallography.
Alkynes are ideal building blocks and synthons for a
variety of interesting and important π-conjugated molecules.
The unique reactivity of the sp-hybridized carbon provides an
essential method for the construction of carbonꢀcarbon
† Metal-Catalyzed Reactions of Alkynes. Part XI. Part X: Hsu, S.-F.; Ko,
C.-W.; Wu, Y.-T. Adv. Synth. Catal. 2011, 353, 1756.
(1) (a) Acetylene Chemistry: Chemistry, Biology, and Material Science;
Stang, P. J., Tykwinski, R. R., Diederich, F., Eds.; Wiley-VCH: Weinheim, 2005.
(b) Carbon-Rich Compounds: From Molecules to Materials; Haley, M. M.,
Tykwinski, R. R., Eds.; Wiley-VCH: Weinheim, 2006.
(2) For dimerization of internal alkynes, see: (a) Sakabe, K.; Tsurugi,
H.; Hirano, K.; Satoh, T.; Miura, M. Chem.;Eur. J. 2010, 16, 445. (b)
Eisch, J. J.; Adeosun, A. A.; Birmingham, J. M. Eur. J. Inorg. Chem.
2007, 39. (c) Jaroschik, F.; Nief, F.; Le Goff, X.-F.; Ricard, L. Organo-
metallics 2007, 26, 1123. For cyclobutadiene complex, see:(d) Wolf, R.;
Schnoeckelborg, E.-M. Chem. Commun. 2010, 2832. For dimerization
of terminal alkynes forming enynes, see:(e) Trost, B. M.; Sorum, M. T.;
bonds.1 One such method for carbonꢀcarbon bond construc-
tion is the metal-catalyzed self-reaction of alkynes. Transition-
metal catalysts are used in these reactions to increase the
efficiency of alkyne coupling. There are numerous examples
of reactions of this type, including (cyclo)dimerization,2
(cyclo)trimerization,3 and cyclotetramerization.4 In contrast
to these reactions, we recently observed that linear tetraenes 2
can be directly generated from alkynes 1using nickel catalysts.
Compounds 2 should be suitable precursors for the synthesis
of polycyclic aromatic hydrocarbons, and these linearly con-
jugated oligoenes could possess interesting properties in
material science.5 Herein, this study investigates the scope
and limitations of this reaction and analyzes the structures of
the coupling products.
Heating diphenylacetylene (1a) in acetonitrile with a
mixture of NiBr2(dppe) and Zn gave octatetraene 2a in
low yield (entry 1 in Table 1).6 Systematic studies of the
reaction conditions have revealed that a nickel cata-
lyst, water, solvent, and temperature all crucially affect
€
Chan, C.; Harms, A. E.; Ruhter, G. J. Am. Chem. Soc. 1997, 119, 698
and references therein.
(3) For recent reviews for formal [2 þ 2 þ 2] cyclotrimerizations, see:
(a) Tanaka, K. Chem.;Asian J. 2009, 4, 508. (b) Chopade, P. R.; Louie,
J. Adv. Synth. Catal. 2006, 348, 2307. For a rare cycloisomerization, see:
(c) Wu, Y.-T.; Kuo, M.-Y.; Chang, Y.-T.; Shin, C.-C.; Wu, T.-C.; Tai,
C.-C.; Cheng, T.-H.; Liu, W.-S. Angew. Chem., Int. Ed. 2008, 47, 9891.
Linear and angular trimerization of terminal alkynes forms dienynes,
see:(d) Wu, Y.-T.; Lin, W.-C.; Liu, C.-J.; Wu, C.-I. Adv. Synth. Catal.
2008, 350, 1841 and references therein.
(4) For Ni-catalyzed protocols, see: (a) Wender, P. A.; Christy, J. P.;
Lesser, A. B.; Gieseler, M. T. Angew. Chem., Int. Ed. 2009, 48, 7687 and
references therein. (b) Goswami, A.; Ito, T.; Saino, N.; Kase, K.;
Matsunoa, Okamoto, S. Chem. Commun. 2009, 439. For review, see:
(c) Saito, S. In Modern Organonickel Chemistry; Tamaru, Y., Ed.; Wiley-
VCH: Weinheim, 2005; p 171. For copper-mediated examples, see: (d)
Yamamoto, Y.; Ohno, T.; Itoh, K. Chem.;Eur. J. 2002, 8, 4734. (e)
Takahashi, T.; Sun, W.; Nakajima, K. Chem. Commun. 1999, 1595. For
review, see:(f) Takahashi, T.; Li, Y. In Titanium and Zirconium in
Organic Synthesis; Marek, I., Ed.; Wiley-VCH: Weinheim, 2002, p 50.
(5) Reviews for applications of oligoenes in material science, see: (a)
Dalton, L. R.; Sullivan, P. A.; Bale, D. H. Chem. Rev. 2010, 110, 25. (b)
Meier, H. Angew. Chem., Int. Ed. 2005, 44, 2482. (c) Schwab, P. F. H.;
Smith, J. R.; Michl, J. Chem. Rev. 2005, 105, 1197. (d) Martin, R. E.;
Diederich, F. Angew. Chem., Int. Ed. 1999, 38, 1350. (e) Electronic
Materials: The Oligomer Approach; M€ullen, K., Wegner, G., Eds.; Wiley-
VCH: Weinheim, 1998.
(6) The catalytic system comprised of NiBr2(dppe), and Zn is also
used in the cocyclotrimerization of alkynes; see: (a) Hsieh, J. C.; Cheng,
C. H. Chem. Commun. 2008, 2992. (b) Hsieh, J. C.; Cheng, C. H. Chem.
Commun. 2005, 2459. (c) Jeevanandam, A.; Korivi, R. P.; Huang, I. W.;
Cheng, C. H. Org. Lett. 2002, 4, 807.
r
10.1021/ol201814q
Published on Web 08/15/2011
2011 American Chemical Society

this reaction. Adding 2 equiv of water dramatically in-
creased the yield of octatetraene 2a, whereas its absence
or large excess inhibited the reaction (entries 1ꢀ3 in
Table 1). Unlike other solvents, such as methanol, o-xylene,
to the results of an isotopic experiment that was per-
formed with deuterium oxide.
The reactivity of many alkynes 1 was investigated
(Table 2). Most of them generated the corresponding
cycloadducts 2 in moderate to good yields. Sterically
congested and/or electron-deficient substituents strongly
reduced the reaction efficiency and gave diarylalkenes
and/or tetraarylbutadienes as byproducts in considerable
quantities (entries 5, 7, and 10 in Table 2). Unlike other
Table 1. Optimization of Reaction Conditions for Preparing 2aa
Table 2. Preparation of Octatetraenes 2 from Alkynes 1a
temp
conv
(%)
yield
(%)b
entry
catalyst
solvent
[°C]
1
NiBr2(dppe)
NiBr2(dppe)
NiBr2(dppe)
NiBr2(dppe)
NiBr2(dppe)
NiBr2(dppe)
NiBr2(dppe)
NiBr2(dppe)
NiBr2(dppe)
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3OH
o-xylene
dioxane
DMF
130
130
130
110
80
40
100
78
100
65
0
22c
79
66d
82
61
0
2
3
4
5
6
80
7
110
110
110
110
110
110
110
110
110
49
54
86
23
89
0
6
8
19
13
14
65e
0
9
10
11
12
13
14
15
NiBr2 3H2O
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
3
NiCl2(PPh3)2
NiCl2(acac)2
NiBr2(dme)
NiCl2(dppp)
NiCl2(dppe)
40
51
60
10
31
29
a A mixture of alkyne 1a (1.0 mmol), Ni catalyst (5 mol %), Zn (1.0
mmol), and water (2.0 mmol) in a solvent (2.5 mL) was heated for 24 h.
acac = acetylacetone. The conversion of 1a was determined by GC MS.
b Isolated yield for 2a. c No additional water was added. d Water (40
mmol) was used. e Hexaphenylbenzene (21%) was obtained.
1,4-dioxane, and DMF, acetonitrile yielded excellent re-
sults (entries 6ꢀ9 in Table 1). Catalyst NiBr2(dppe) was
found to absolutely outperform the other catalysts listed in
Table 1. NiCl2(PPh3)2 formed a significant amount of
hexaphenylbenzene as a byproduct. Apparently, reactions
that were conducted at 110 °C were better thanthose run at
80 or 130 °C (entries 2, 4, and 5 in Table 1). Under the
optimal conditions, 2a was obtained in 82% yield and a
large-scale synthesis gave a slightly low yield (73%,
entry 1 in Table 2). Although the 1H NMR spectrum of
2a has been reported elsewhere, the small difference
between the data in the literature7 and the analytical
data obtained herein motivated us to further reanalyze
its structure by X-ray crystallography.8 Octatetraene
2a can also be generated by oxidative addition of
2,3,4,5-tetraphenyl-1-ziconacyclopentadiene,7 but the
protocol developed herein is more efficient and con-
venient. The protons at positions C1 and C8 in 2a
mainly (>91%) come from the added water, according
a Reaction scale: alkyne 1 (1.0 mmol). The conversion of 1 was
determined by GC MS. b Isolated yield for 2. c Reaction was conducted
with 10 mmol of 1a. d Containing an inseparable byproduct (approxi-
mately 5%). e The reaction was conducted with NiBr2(dppe) (10 mol %)
and Zn (3.0 mmol). f 3n was isolated in 74% yield.
examples, di(2-thiophenyl)ethyne (1n) produced tricyclo-
[3.2.1.02,7]oct-3-ene 3n (entry 14 in Table 2).8 This undesired
product should be produced from a octatetraene derivative
(see below). Notably, 4-octyne and phenylacetylene cannot
be used in this reaction because they mainly furnished
benzene derivatives by formal [2 þ 2 þ 2] cyclotrimerization.
The steric effects rather than the electronic properties
of substituents in asymmetric alkynes dominated the
regioselectivity in the coupling reaction. For instance,
(7) Takahashi, T.; Liu, Y.; Iesato, A.; Chaki, S.; Nakajima, K.;
Kanno, K.-i. J. Am. Chem. Soc. 2005, 127, 11928.
(8) X-ray crystallographic data for compounds 2a (CCDC-823434),
3n (CCDC-823438), 4 (CCDC-823439), syn-6b (CCDC-823436), and
anti-6b (CCDC-823437) can be obtained from the Cambridge Crystallo-
graphic Data Centre via www.ccdc.cam.ac.uk/const/retrieving.html.
1-phenyl-1-propyne (1o) generated 4 as the major product
(Scheme 1), whereas 1-(phenylethynyl)-4-(trifluoromethyl)-
benzene (1p) gave complex regioisomers. Pure 4 was
obtained by crystallization (see Supporting Information).8
Org. Lett., Vol. 13, No. 18, 2011
4795

Scheme 1. Reaction of 1-Phenyl-1-propyne (1o)
Scheme 3. Proposed Mechanism
Underthe optimal conditionsdeveloped herein, diyne5b
produced a mixture of 8b (13%) and 9b (78%) by cycliza-
tion and formal [(2 þ 2) þ 2] cycloaddition,9 respectively
(Scheme 2). This undesired result can be improved by
treating diynes 5 with more catalyst (10 mol %) and zinc
(3 equiv), giving good yields of the coupling products 6,
accompanied by small amounts of 8 (approximately 10%).
Compounds 6 were obtained in two stereoisomeric forms,
which can onlybedistinguished byX-ray crystallography.8
The anti-stereoisomers were determined to be the major
products. Apparently, 6 should be generated from the
expected products 7 through in situ reduction. An attempt
was made to produce 7a by oxidizing 6a using DDQ (2,
3-dichloro-5,6-dicyanobenzoquinone). Interestingly, the
reaction with excess DDQ at 110 °C formed compound
9a in 81% yield.10,11
Scheme 2. Reaction of Diynes 5
Scheme 3 presents a putative reaction mechanism of the
tetramerization of alkyne 1 based on the literature and the
findings of the above experiments. Zinc reduces the precatalyst
[Ni]X2 to generate Ni(0), which undergoes oxidative cycload-
dition with alkyne 1 to furnish 1-nickellacyclopentadiene 11.
As suggested by Eisch et al.,12 the dimerization of 11 yields
complex 12,13,14 which reacts with water to produce com-
plex 14 via intermediate 13. The crowded environment in
14 promotes the Ni-mediated cisꢀtrans isomerization at
positions C3ꢀC6 to form 10. The presence of 3n perhaps
supports isomerization (see below). Reductive elimination
of 10 gives the desired product 2 and Ni(0) species.
Notably, nickel oxide is the possible byproduct of this
catalytic cycle, and it can eventually be transformed into
the active Ni(0) complex by reduction with zinc. The
selective formation of 4 should depend on the reactivity
€
(9) For Rh-catalyzed [(2 þ 2) þ 2] cycloaddition of 5 with alkynes,
see: (a) Wu, Y.-T.; Linden, A.; Siegel, J. S. Org. Lett. 2005, 7, 4353. (b)
Wu, Y.-T.; Hayama, T.; Baldridge, K. K.; Linden, A.; Siegel, J. S. J. Am.
Chem. Soc. 2006, 128, 6870.
(12) Eisch, J. J.; Piotrowski, A. M.; Han, K. I.; Kruger, C.; Tsay,
Y. H. Organometallics 1985, 4, 224. For X-ray crystallographic structure
of a 10-membered dinuclear nickellacycle, see: Ramakrishna., T. V. V.;
Sharp, P. R. Organometallics 2004, 23, 3079.
(10) For examples for the DDQ-mediated dehydrogenative cross-
coupling reaction, see: Zhang, Y.; Li, C.-J. J. Am. Chem. Soc. 2006, 128,
4242.
(13) As shown in Scheme 2, a high loading of catalysts selectively
yields compounds 6, and this result may be evidence of the dimeric
mechanism.
(11) The reaction should be through a radical-type cyclization, and
the intermediate can be isolated in good yield (89%) when the reaction
was conducted under mild conditions (50 °C); see Supporting
Information.
(14) For other proposed mechanism for the dimerization of 1-nick-
ellacyclopentadienes, see: (a) Wilke, G. Pure Appl. Chem. 1978, 50, 677.
(b) Lawrie, C. J.; Gable, K. P.; Carpenter, B. K. Organometallics 1989, 8,
2274.
4796
Org. Lett., Vol. 13, No. 18, 2011

and the stability of 1-nickellacyclopentadienes. Other
regioisomers of 15 should also be generated, but they
would easily form butadienes and [2 þ 2 þ 2] cycload-
ducts. Like other tetraaryl-substituted complexes, 15
undergoes dimerization to form 16, and the carbonꢀ
carbon bond formation occurs at the carbon with
the phenyl substituent, rather than the one with the
methyl group.
The reaction of acyclic conjugated tetraenes in the
literature provided very useful information for establishing
a reasonable mechanism of the formation of the unusual
product 3n.15 Based on careful analysis of the structure of
3n determined by X-ray crystallography,8 the key inter-
mediate of the cascade reaction should be tetraene 17,
which can be generated from 14n by reductive elimination.
Compound 17 undergoes 6π electrocyclization15,16 and a
subsequent intramolecular DielsꢀAlder reaction17 to give
3n via cyclohexadiene 18.
In conclusion, this work provided a simple approach for
generating octatetraenes 2 directly from alkynes 1. Further
studies of the physical properties of these molecules and
their use in synthesizing new polycyclic aromatic hydro-
carbons are currently underway.
Acknowledgment. This work was supported by the Na-
tional Science Council of Taiwan (NSC 98-2113-M-006-
002-MY3). We also thank Prof. S.-L. Wang and Ms. P.-L.
Chen (National Tsing Hua University, Taiwan) for the
X-ray structure analyses.
(15) (a) Skropetaa, D.; Rickards, R. W. Tetrahedron Lett. 2007, 48,
3281. (b) Marvell, E. N.; Seubert, J.; Vogt, G.; Zimmer, G.; Moy, G.;
Siegmann, J. R. Tetrahedron 1978, 34, 1323.
(16) Tetraene 17 should not be generated from 2n by thermolytic
transꢀcis isomerization. When a solution of 2a in diphenyl ether was
heated at 200 °C for 24 h, compound 3a was not obtained.
(17) (a) Heimbach, P.; Ploner, K.-J.; Thornel, F. Angew. Chem., Int.
Ed. Engl. 1971, 10, 276. (b) Ng, S. M.; Beaudry, C. M.; Trauner, D. Org.
Lett. 2003, 5, 1701. (c) Giomi, D.; Nesi, R.; Turchi, S.; Mura, E. J. Org.
Chem. 2000, 65, 360.
Supporting Information Available. Experimental pro-
cedures and characterizations, NMR spectra, and crystal
data. This material is available free of charge via the
Internet at http://pubs.acs.org.
Org. Lett., Vol. 13, No. 18, 2011
4797