Nickel-catalyzed cocyclotrimerization of arynes with diynes; a novel method for synthesis of naphthalene derivatives

Article abstract of DOI:10.1039/b415691a

The NiBr₂(dppe)-Zn system effectively catalyzes the [2 + 2 + 2] cocyclotrimerization of arynes with diynes, leading to substituted naphthalene derivatives in moderate to good yields. This cocyclotrimerization reaction shows excellent tolerance of functional groups and leads to products of 5- to 7-membered fused-ring sizes. The Royal Society of Chemistry 2005.

Full text of DOI:10.1039/b415691a

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Nickel-catalyzed cocyclotrimerization of arynes with diynes; a novel
method for synthesis of naphthalene derivatives{
Jen-Chieh Hsieh and Chien-Hong Cheng*
Received (in Cambridge, UK) 13th October 2004, Accepted 14th March 2005
First published as an Advance Article on the web 23rd March 2005
DOI: 10.1039/b415691a
CsF (2.0 mmol) and NiBr2(dppe) (0.025 mmol, dppe: bis(diphenyl-
The NiBr2(dppe)–Zn system effectively catalyzes the [2 + 2 + 2]
phosphino)ethane) in acetonitrile (2.0 mL) at 80 uC for 12 h
afforded 1,2,3,4-tetrahydroanthracene (3a) in 86% yield in addition
to a mixture of dimer (y0.2 mmol)9 and trimer (y0.02 mmol) of
diyne 2a (vide infra). The structure of 3a was confirmed by its 1H
NMR, 13C NMR and mass data.
cocyclotrimerization of arynes with diynes, leading to sub-
stituted naphthalene derivatives in moderate to good yields.
This cocyclotrimerization reaction shows excellent tolerance of
functional groups and leads to products of 5- to 7-membered
fused-ring sizes
To understand the nature of this nickel-catalyzed carbocycliza-
tion, the effect of the solvent and metal complex used on the
reaction of 1a with 2a was investigated. NiBr2(PPh3)2, and
NiBr2(dppm) did not show any catalytic activity for the reaction,
while NiBr2(dppb) and Pd(PPh3)4 gave 3a in 54 and 29% yields,
respectively. The use of CoI2(PPh3)2 as catalyst afforded only
triphenylene without the desired cocyclotrimerization product.
NiBr2(dppe) was found to be the best catalyst producing product
3a in 86% yield and with only a trace of triphenylene. The solvent
used for the catalytic reaction was also critical. No reaction
occurred in toluene, whereas THF afforded only a trace of 3a.
CH3CN was the best solvent when NiBr2(dppe) was used as the
catalyst.
The transition-metal mediated [2 + 2 + 2] cocyclotrimerization of
alkynes is a powerful method for the construction of polycyclic
compounds in one step.1 Although this cycloaddition has been
known for decades, the control of both regio- and chemoselectivity
remains a great challenge to organic chemists. Recently, the
cyclotrimerization of arynes and alkynes has attracted considerable
attention. Perez et al. revealed the cyclotrimerization of arynes
catalyzed by palladium to give triphenylenes.2 Both the Perez and
the Yamamoto groups reported the cyclotrimerization of benzynes
and alkynes catalyzed by palladium complexes leading to the
formation of phenanthrene derivatives.3 In the area of nickel-
catalyzed trimerization, Ikeda and co-workers have developed an
array of important methods.4 In addition, our interest in nickel
and cycloaddition chemistry5,6 encouraged us to explore the
possibility of using diynes in the cocyclotrimerization with
benzynes. Herein, we wish to report the first example of a
nickel-catalyzed [2 + 2 + 2] cocyclotrimerization of a benzyne with
a diyne, providing an efficient method for the synthesis of
naphthalene derivatives (Scheme 1). Notably, the naphthalene
skeleton is found as a precursor in a number of active biological
chemical products7 and polycyclic aromatic electronic materials.8
Treatment of benzyne precursor (1a, 0.50 mmol) with octa-1,7-
diyne (2a, 1.0 mmol) in the presence of zinc powder (0.075 mmol),
This nickel-catalyzed cocyclotrimerization reaction was success-
fully extended to various substituted diynes and the results are
listed in Table 1. Thus, 1a reacts with hepta-1,6-diyne (2b) and
nona-1,8-diyne (2c) to provide the corresponding cocyclotrimer-
ization products, 3b and 3c, in 89% and 84% yield. The results of
entries 1 to 3 reveal a good fused-ring size tolerance within the
present reaction. Similarly, functional diynes (2d–g) underwent [2 +
2 + 2] cycloaddition to produce naphthalene derivatives 3d–g in
good yields (Scheme 1, Table 1, entries 4–7).
Under similar reaction conditions, diynes 2h–j possessing at least
one internal alkyne moiety, also underwent [2 + 2 + 2]
cocyclotrimerization with 1a to give products 3h–3j in 55, 47 and
41%, respectively. The observed lower product yield reflects that
the present nickel-catalyzed cocyclotrimerization is sensitive to the
substituent attached to the triple bond of the diynes. A small
amount of homotrimerization product ([2 + 2 + 2]) of benzynes
was observed in each of these reactions. No cocyclotrimerization
of benzyne with more bulky disubstituted diynes, such as 1,8-
diester and 1,8-diphenyl-1,7-octadiynes, was observed.
The present method can also be applied to the cocyclotrimer-
ization of substituted benzynes. Treatment of 4-methylbenzyne,
4,5-dimethylbenzyne and naphthyne precursors (1b–d) with octa-
1,7-diyne (2a) in the presence of NiBr2(dppe), zinc powder and
CsF in acetonitrile at 80 uC for 12 h furnished naphthalene
derivatives 3k, 3n, and 3o in 62, 59, and 37% yields. In the same
fashion, 1b reacted with hepta-1,6-diyne (2b) and dimethyl 2,2-
(diprop-2-ynyl)malonate (2e) to give naphthalene derivatives 3l
and 3m in 56 and 63% yields, respectively.
Scheme 1
{ Electronic supplementary information (ESI) available: experimental
details. See http://www.rsc.org/suppdata/cc/b4/b415691a/
*chcheng@mx.nthu.edu.tw
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Chem. Commun., 2005, 2459–2461 | 2459

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Table 1 Results of [2 + 2 + 2] cocyclotrimerization of diynes with
benzynes catalyzed by nickel complex NiBr2(dppe)a
Entry
1
1
2
Product
Yield (%)b
86
1a
2a
Scheme 2
The reaction of hex-5-ynenitrile (2k) with 1a is interesting. Two
products 3p and 3p9, a phenanthrene and a naphthalene derivative,
respectively, in 56 : 11 molar ratio were observed with a combined
yield of 67% (Scheme 2). The major product 3p was produced by
the reaction of two benzynes with one hex-5-ynenitrile during the
cyclotrimerization. The minor product, a quinoline derivative, 3p9
was formed from a [2 + 2 + 2] cocyclotrimerization of the carbon–
carbon triple and the nitrile group in a hex-5-ynenitrile molecule
and a benzyne moiety. The low reactivity of the nitrile moiety
likely accounts for the low yield of 3p9.
2
3
1a
1a
2b
2c
89
84
4
5
1a
1a
2d
2e
71
79
The foregoing results reveal that the present catalytic reaction is
sensitive to the substituent on the diyne and benzyne moieties.
Terminal diynes are most reactive and give high yields of the
cocyclotrimerization products. Monosubstituted diynes undergo
[2 + 2 + 2] cocyclotrimerization but with lower yields. For the
disubstituted internal diynes, only deca-2,8-diyne (2j) reacts with
benzyne to give the expected product; other bulkier disubstituted
diynes gave no or trace amount of the desired products. meta-
Substituted benzynes are also somewhat less reactive. It is also
worth pointing out here that, whilst not specifically detailed, ortho-
substituted benzyne derivatives gave no or very low yield of the
expected products.
6
7
8
1a
1a
1a
2f
87
74
55
2g
2h
Based on the above results and known organometallic
chemistry, a plausible mechanism is proposed to account for the
formation of naphthalene products (Scheme 3). The catalytic
reaction is likely to be initiated by the reduction of the Ni(II)
species to a Ni(0) species by zinc metal. Coordination of both C–C
triple bonds of diyne to the Ni(0) center 4 followed by
cyclometalation produces a nickelacyclopentadiene intermediate
5.10 Benzyne coordination and then insertion into a Ni(II)–carbon
9
1a
1a
2i
2j
47
41
10
11
12
13
14
15
1b
1b
1b
1c
1d
2a
2b
2e
2a
2a
62
56
63
59
37
a
Unless stated otherwise, all reactions were carried out using
benzyne precursor (1) (0.50 mmol), diyne (2) (1.0 mmol),
NiBr2(dppe) (5.0 mol%), CsF (2.0 mmol) and Zn (15.0 mol%) in
b
CH3CN (2.0 mL) at 80 uC under N2 for 12 h. Isolated yields based
on benzyne precursor used.
Scheme 3
2460 | Chem. Commun., 2005, 2459–2461
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We thank the National Science Council of the Republic of
China (NSC-93-2113-M-007-033) for the support of this research.
Jen-Chieh Hsieh and Chien-Hong Cheng*
Department of Chemistry, National Tsing Hua University, Hsinchu,
30013, Taiwan. E-mail: chcheng@mx.nthu.edu.tw;
Fax: +886-3-5724698; Tel: +886-3-5721454
Scheme 4
Notes and references
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Scheme 5
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bond of
5
gives
a
nickelacycloheptatriene intermediate 6.
Subsequent reductive elimination of 6 affords product 3 and
regenerates the Ni(0) catalyst. This mechanism appears likely in
view of the formation of diyne dimer 7 and trimer 89 (Scheme 4) in
the reaction that can only be formed from intermediate 5.
An alternative mechanism (Scheme 5) involves the coordination
of a triple bond of diyne 2 and a benzyne to the nickel center to
produce a five-membered nickelacyclopentadiene intermediate 9.
An intramolecular insertion of the C–C triple bond into the
adjacent Ni(II)–carbon bond yields intermediate 6. Further
reductive elimination affords the final product 3. This pathway
also explains very well the formation of product 3, but fails to
account for the formation of diyne dimer and trimer in the
reaction.
In conclusion, we have developed a new methodology for the
[2 + 2 + 2] cocyclotrimerization of arynes with diyne catalyzed by
nickel complexes. This is the first report that a diyne can undergo
cycloaddition with a benzyne with excellent tolerance of functional
groups and fused-ring sizes to furnish naphthalene derivatives in
moderate to good yields. Further studies to determine the exact
mechanistic pathway for this useful reaction are currently under
way.
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