O-Dihaloarenes as aryne precursors for nickel-catalyzed [2 + 2 + 2] cycloaddition with alkynes and nitriles

Article abstract of DOI:10.1039/b801870g

o-Dihaloarenes acting as aryne precursors react with acetylenes and nitriles catalyzed by the NiBr₂(dppe)/dppe/Zn system to give substituted naphthalene, phenanthridine or triphenylene derivatives depending on the reaction conditions in moderat

Full text of DOI:10.1039/b801870g

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O-Dihaloarenes as aryne precursors for nickel-catalyzed [2 + 2 + 2]
cycloaddition with alkynes and nitrilesw
Jen-Chieh Hsieh and Chien-Hong Cheng*
Received (in Cambridge, UK) 1st February 2008, Accepted 26th March 2008
First published as an Advance Article on the web 6th May 2008
DOI: 10.1039/b801870g
o-Dihaloarenes acting as aryne precursors react with acetylenes
and nitriles catalyzed by the NiBr2(dppe)/dppe/Zn system to
give substituted naphthalene, phenanthridine or triphenylene
derivatives depending on the reaction conditions in moderate to
excellent yields with good tolerance of functional groups.
phine ligand such as PPh3 provided lower yield of product 3a
but higher yields in triphenylene. Thus, NiBr2(PPh3)2 and
NiCl2(PPh3)2 gave 3a in 35 and 33% yields, respectively, with
a substantial amount of triphenylene. Nickel complexes
NiBr2(L2) where L2 are dppm, dppe, dppp and dppb gave 3a
in 56, 76, 61 and 44% yields, respectively. NiBr2(dppe) was
found to be the best catalyst in this investigation producing 3a
in 76% yield with a trace of triphenylene. Palladium and
cobalt complexes Pd(PPh3)4, Pd(dba)2, PdCl2(PPh3)2 and
CoI2(dppe) are inactive for this reaction. The catalytic reaction
was more favorable using polar solvents. For example, THF,
DMF and CH3CN afforded 3a in 71, 68 and 76% yields,
respectively, but nonpolar solvents toluene and o-xylene gave
only 3a in lower yields of 53 and 47%, respectively. This study
indicated that CH3CN was the best solvent when Ni(dppe)Br2
was used as the catalyst.
In recent years, benzyne chemistry has attracted considerable
attention, particularly in metal-catalyzed organic reactions
employing arynes as p-components. A key to the relighted
interest is the discovery of a mild method for the in situ
generation of arynes at moderate temperature from o-silyl
aryltriflate.1 Although several methods for the generation of
arynes are known, only very few of them are useful in
transition metal-catalyzed organic reactions involving arynes
as a substrate.2,3 Our interest in metal-catalyzed benzyne
reaction4 and cyclization reactions with o-diiodoarenes5
prompted us to explore the possibility of using o-diiodoarenes
as a possible benzyne source for the catalytic cyclization
reactions. In this paper, we report the synthesis of naphthalene
derivatives via a nickel-catalyzed cyclization of substituted
diiodobenzenes with alkynes or nitriles. The catalytic reaction
likely involves a nickel-assisted generation of benzyne as a key
step. Controlled synthesis of polysubstituted naphthalene,
phenanthridine and triphenylene derivatives is important due
to the unique electronic, and biological properties of these
compounds. A vast number of biologically active natural
products6,7 and antibiotics possess a simple naphthalene
skeleton. Also, naphthalene compounds have found applica-
tion as chiral reagents,6 semiconductors, and various electro-
nic devices.8,9 In spite of the wide usage, polysubstituted
naphthalenes are difficult to prepare.10
The effect of temperature on the product yield was
also investigated. No desired product 3a was formed and large
amount of 2a was recovered, if the reaction temperature
was below 60 1C. The product yields increased as the reaction
temperature increased. However, the reaction became
complicated and gave a lower yield of 3a for temperatures
4100 1C. The best reaction temperature appears to be around
100 1C. The presence of extra dppe significantly diminished
the self cyclotrimerization of alkyne 2a. The reaction with
additional dppe provided 3a in 94% yield and trace
triphenylene. As
a result, we employed Ni(dppe)Br2,
dppe and zinc in acetonitrile at 100 1C as the catalyst system
for the following cycloaddition of o-diiodoarenes with
disubstituted alkynes.
The nickel-catalyzed cycloaddition reaction was successfully
extended to various disubstituted acetylenes and the results are
listed in Table 1. Thus, 1a reacted smoothly with dipropyl,
dimethoxymethyl, dialkoxycarbonyl and diaryl acetylenes,
2b–g, to provide the corresponding cycloaddition products
3b–g in moderate to excellent yields (entries 2–7). The sub-
stituted diiodobenzene 1b–d bearing dimethyl, dimethoxy and
dioxole moieties on the aryl ring also underwent cyclization
with alkynes. Thus, treatment of 1b with 2a and 2f afforded 3h
and 3i in 66 and 94% yields, respectively (entries 8, 9). The
reaction of 1c with 2a and 2f gave 3j and 3k in 68 and 96%
yields, respectively (entries 10, 11). Diiobenzodioxole 1d re-
acted with 2a and 2d to afford 3l and 3m in 63 and 58% yields,
respectively (entries 12, 13). Diiodobenzene 1e with four
electron-withdrawing fluoro groups also underwent the nick-
el-catalyzed cycloaddition reaction with 2a and 2d to give 3n
and 3o in slightly lower yields (entries 14, 15). These results
demonstrate that the nickel-catalyzed cycloaddition reaction
has excellent tolerance of functional groups. Under the same
Treatment of 1,2-diiodobenzene 1a with diethylacetylene 2a
in the presence of Ni(dppe)Br2, dppe (bis(diphenylphosphi-
no)ethane) and zinc powder in acetonitrile at 100 1C for 48 h
afforded 1,2,3,4-tetraethylnaphthalene 3a in 94% yield. The
structure of 3a that is derived from one molecule of 1a and two
molecule of 2a was confirmed by its 1H, 13C NMR and
mass data.
The above optimized catalytic reaction conditions were
obtained by studying the effect of solvent and metal complex
used on the reaction of 1a with 2a. In the absence of either
nickel catalyst or zinc powder, no cycloaddition product 3a
was observed. The nickel complex with monodentate phos-
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
w Electronic supplementary information (ESI) available: Preparation
and characterization. See DOI: 10.1039/b801870g
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Table 1 Results of nickel-catalyzed cycloaddition of o-diiodoarenes
with disubstituted alkynesa
The nickel-catalyzed reaction can be smoothly extended to
various diynes to furnish the corresponding naphthalenes
(Table 2). Thus, 1a reacts with 1,6-heptadiyne (4a) and 1,7-
octadiyne (4b) to provide the naphthalene products, 5a and 5b,
in 63 and 39% yields, respectively (entries 1, 2). Similarly,
terminal diynes, 4c–e, underwent cycloaddition with 1a to
produce naphthalene derivatives 5c–e in moderate yields (en-
tries 3–5). The reaction of internal diynes, 4f–i, with 1a
resulted in higher yields of the corresponding naphthalene
products 5f–i (entries 6–8). This is probably because of the
lower reactivity of self cyclization of the internal diynes. In a
similar manner, the more electron rich 1,2-diiodoarenes 1b–d
reacted with internal diynes to afford naphthalene products in
81–84% yields (entries 10–12). On the other hand, diiodoben-
zene 1e bearing electron-withdrawing fluoro groups reacted
with 4f to give naphthalene derivatives 5m in lower 51% yield
(entry 13).
The foregoing results reveal that the present catalytic reac-
tion can tolerate various functional groups on the acetylene,
diyne and o-diiodoarene. Diaryl acetylenes (Table 1) and
terminal diaryl diynes (Table 2) gave higher yields of the
[2 + 2 + 2] cycloadducts because they are less reactive in
forming homocyclotrimerization products. Diiodoarenes
Table 2 Results of nickel-catalyzed cycloaddition of o-diiodoarenes
with diynesa
a
Unless stated otherwise, all reactions were carried out using
o-diiodoarene (1) (0.50 mmol), acetylene (2) (3.0 mmol), NiBr2(dppe)
(10.0 mol%), dppe (10.0 mol%) and Zn (3.0 equiv.) in CH3CN
(1.0 mL) at 100 1C under N2 for 48 h.bIsolated yields based on
1,2-diiodoarene.
conditions, 1,2,4,5-tetraiodobenzene (1f) reacted with
four equivalents of diphenyl acetylene (2f) to provide octa-
phenylanthracene in 64% yield (entry 16). Presumably, 1f
underwent [2 + 2 + 2] cycloaddition twice with 2f consuming
4 equivalents of 2f.
a
Unless stated otherwise, all reactions were carried out using
o-diiodoarene (1) (0.50 mmol), diyne (4) (1.5 mmol), NiBr2(dppe)
(10.0 mol%), dppe (10.0 mol%) and Zn (3.0 equiv.) in CH3CN
(1.0 mL) at 100 1C under N2 for 48 h.bIsolated yields based on
1,2-diiodoarene.
In addition, o-dibromoarenes 1g,h also successfully reacted
with 2a and 2f to give the corresponding products 3a, 3f, 3q
and 3r in 51–85% yield (entries 17–20).
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organic synthesis (Scheme 2(B)).1 The pathway for the forma-
tion of benzynes in these reactions involves the elimination
reaction of intermediate 11,1b,11 similar in structure to 8, to
yield benzynes and a metal salt.
Another possible pathway for the nickel-catalyzed synthesis
of naphthalene derivatives shown in Tables 1 and 2 involves
stepwise insertion of two alkyne moieties into the oxidative
addition product of o-dihaloarene with nickel(0) (see inter-
mediate 8) followed by cyclization. Although this pathway
cannot be excluded totally, it is difficult to explain the regio-
chemistry of product 5 shown in Table 2.
Scheme 1
consisting of electron-donating groups provided better yields
on reaction with diphenyl acetylene than with dialkyl and
dialkoxycarbonyl acetylenes.
We thank the National Science Council of the Republic of
China (NSC-95-2119-M-007-005) for the support of this
research.
To our surprise, when diiodobenzene was heated in the
presence of NiBr2(dppe) and zinc without additional dppe, the
reaction produced a new [2 + 2 + 2] cyclization product,
phenanthridine, in addition to the expected triphenylene. The
yield of phenanthridine increased as the relative amount of
solvent increased. As shown in Scheme 1, with the same
amounts of the nickel catalyst, zinc metal, diiodobenzene
and acetonitrile used in Table 1, the catalytic reaction pro-
vided triphenylene as the major product in about 60% yield.
However, as the amount of acetonitrile solvent was increased
from 1.0 to 2.5 ml, phenanthridine, 6a, became the major
product in 76% yield. It is clear from the structure of 6a that
the new cocyclotrimerization product is from two molecules of
diiodobenzene and an acetonitrile molecule. Under similar
reaction conditions, other nitriles also underwent cocyclotri-
merization with diiodoarenes to give the corresponding phe-
nanthridine11 derivatives 6b–e in moderate to good yields.
Compared with the known benzyne chemistry,12,13 the
results of the above nickel-catalyzed reactions strongly suggest
that the products including triphenylenes, naphthalenes and
phenanthridines are likely due to [2 + 2 + 2] cycloaddition of
arynes with alkynes or nitriles. As shown in Scheme 2(A), the
aryne intermediate is probably generated from the oxidative
addition of o-dihaloarene to a nickel(0) complex to give 8,
followed by a b-halogen elimination to afford 9. Reduction of
9 gives Ni–aryne complex 10. The latter then reacts with
alkynes or nitriles to afford the final organic products. How-
ever, the detailed pathways are not yet clear. It is noteworthy
that the stoichiometric reactions of o-dihaloarenes with nick-
el(0) complex to give complexes similar to 8 and further
reaction with sodium metal to give nickel–benzyne complexes
has been reported previously.12,13 In addition, the reaction of
o-dihaloarenes with alkaline metals, magnesium or n-butyl
lithium to give benzynes, are known and are widely used in
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Scheme 2
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2994 | Chem. Commun., 2008, 2992–2994