Nickel-catalyzed three-component [2+2+2] cycloaddition reaction of arynes, alkenes, and alkynes

Full text of DOI:10.1002/anie.200902006

Angewandte
Chemie
DOI: 10.1002/anie.200902006
Multicomponent Reactions
Nickel-Catalyzed Three-Component [2+2+2] Cycloaddition Reaction
of Arynes, Alkenes, and Alkynes**
Zaozao Qiu and Zuowei Xie*
Table 1: Optimization of the three-component cycloaddition reaction.[a]
Transition-metal-mediated cycloadditions of alkynes and
alkenes serve as a powerful strategy to construct a wide
range of compounds, since complexation of the metal center
to an olefin or alkyne significantly modifies the reactivity of
this moiety.[1] Arynes, a class of very reactive analogues of
alkynes, have recently been reported to undergo metal-
catalyzed conversion.[2–11] For example, the cyclotrimerization
of arynes[2] and the cocyclization of arynes with alkynes,[3]
allylic halides,[4] or activated alkenes[5] can all be catalyzed by
palladium. Palladium can also catalyze three-component
Entry
Catalyst
Loading
[mol%]
Yield of 4a [%][b]
(4a:5a:6a)[c]
cross-coupling reactions of arynes, allylic halides[6] (allylic
epoxides[7] and aromatic halides[8]), and alkynyl stannanes[6a]
(boronic acids[6b]) to form substituted benzenes, and three-
component cyclization of arynes, aryl halides, and alkynes[9] or
alkenes[10] to produce phenanthrene derivatives. In contrast,
nickel-catalyzed transformations of arynes are much less
explored.[11]
Very recently, we reported the nickel-mediated three-
component [2+2+2] cycloaddition of carboryne with acti-
vated alkenes and alkynes to give dihydrobenzocarboranes.[12]
In view of the similar reactivity pattern between carboryne
and benzyne,[13] we extended our research to include arynes
and found that nickel can efficiently catalyze three-compo-
nent [2+2+2] cyclization of arynes, alkenes, and alkynes to
afford a series of substituted dihydronaphthalenes that cannot
be prepared from readily available starting materials.[14] These
new findings are reported herein.
1
2
3
4
5
6
7
8
9
10
11
12
13
[Ni(PPh3)4]
10
10
10
10
10
10
10
5
10
10
10
10
10
50 (55:<2:43)
52 (67:8:25)
[NiCl2(PPh3)2]/Zn (1:3)
[NiCl2(PnBu3)2]/Zn (1:3)
[NiCl2(dppe)]/Zn (1:3)
[NiCl2(dppp)]/Zn (1:3)
[Ni(cod)2]
0 (<2:51:47)
11 (17:32:51)
0 (<1:27:72)
72 (90:<5:<5)
73[d] (90:<5:<5)
72 (90:<5:<5)
51 (55:<2:43)
21 (23:16:61)
0 (<2:37:61)
0 (<2:52:46)
0 (<1:88:11)
[Ni(cod)2]
[Ni(cod)2]
[Ni(cod)2]/PPh3 (1:2)
[Ni(cod)2]/dppe (1:1)
[Pd(dba)2]
[PdCl2(PPh3)2]/Zn (1:3)
[Pd(PPh3)4]
[a] Conditions: 1a (0.3 mmol), 2a (0.6 mmol), 3a (0.36 mmol), and CsF
(0.9 mmol) in CH3CN (1 mL) at room temperature for 5 h. [b] Yields of
isolated 4a. [c] Ratio determined by 1H NMR spectroscopy on the crude
product mixture. [d] The reaction was carried out at 508C.
In an initial attempt, a solution of benzyne precursor 1a
(1 equiv, 2-(trimethylsilyl)phenyltriflate), methyl acrylate 2a
(2 equiv), and diphenylacetylene 3a (1.2 equiv) in CH3CN in
the presence of [Ni(cod)2] (cod = 1,5-cyclooctadiene;
10 mol%) and CsF (3 equiv) was stirred at room temperature
for 5 h to give the cyclization product 4a in 72% yield
(Table 1, entry 6). Subsequent work focused on optimization
of this reaction (Table 1). Changing the ligand from cod to
PPh3 or adding PPh3 to [Ni(cod)2] led to a large decrease in
the yield of isolated 4a from 72% to 50% (Table 1, entries 1
and 9). Addition of bidentate ligand dppe (dppe = 1,2-
bis(diphenylphosphino)ethane) further decreased the yield
of isolated 4a to 21% (Table 1, entry 10). No detectable
amount of 4a was observed when [NiCl2(PnBu3)2]/Zn or
[NiCl2(dppp)]/Zn
(dppp = 1,3-bis(diphenylphosphino)pro-
pane) was used as catalyst (Table 1, entries 3 and 5). In
contrast, palladium complexes such as [Pd(dba)2] (dba =
dibenzylideneacetone), [PdCl2(PPh3)2]/Zn, and [Pd(PPh3)4]
did not mediate three-component benzyne–alkene–alkyne
cyclization; rather, they catalyzed two-component benzyne–
alkene–benzyne cycloaddition and cross-coupling[15] to afford
9,10-dihydrophenanthrene 5a and methyl 3-(1,1’-biphenyl-2-
yl)-2-propenate 6a (Table 1, entries 11–13). These results
showed that 1) both the metal and ligand have a significant
effect on the reactions; 2) activated alkene is more reactive
than alkyne, otherwise two-component benzyne–alkyne–
benzyne cycloaddition products should be observed; and
3) [Ni(cod)2] exhibited the highest catalytic activity in three-
component [2+2+2] cyclization. The same results were
observed when the catalyst loading was decreased from
10 mol% to 5 mol% (Table 1, entry 8) or the reaction
[*] Z. Qiu, Prof. Dr. Z. Xie
Department of Chemistry and
Center of Novel Functional Molecules
The Chinese University of Hong Kong
Shatin, N.T., Hong Kong (China)
Fax: (+852)2603-5057
E-mail: zxie@cuhk.edu.hk
[**] This work was supported by grants from the Research Grants
Council of the Hong Kong Special Administration Region (Project
No. 404108) and the Chinese University of Hong Kong.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.200902006.
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temperature was increased from room temperature (208C) to
508C (Table 1, entry 7).
The scope and limitations of this Ni-catalyzed cyclization
process were then examined with various alkenes and aryne
precursors. The results were summarized in Table 2. Acrylates
2a,b,c gave very high yields (72–76%) of the corresponding
isolated cocyclization products 4a,b,c (Table 2, entries 1–3).
Methyl vinyl ketone (2d) and acrylonitrile (2e) offered very
low yields of the desired aryne–alkene–alkyne cocyclization
products 4d (3%) and 4e (15%), respectively (Table 2,
Table 2: Nickel-catalyzed three-component cycloaddition of arynes with
activated alkenes and diphenylacetylene.[a]
Table 3: Nickel-catalyzed three-component cycloaddition of benzyne
with methyl acrylate and various alkynes.[a]
Entry
1
1
2
4
Yield
[%][b]
Entry
1
3
4
Yield
[%][b]
76
72
74
71
78
71
2
3
1a
1a
2
3
4
1a
1a
3
4
5
6
7
75
68
32
66
5
6
7
15
–
2a
2a
–
29[c]
8
9
2a
46[c]
8
9
19
63[c]
2a
57[c,d]
10
47[c]
[a] Conditions:
1
(0.3 mmol), 2 (0.6 mmol), 3a (0.6 mmol), CsF
(0.9 mmol) in CH3CN (1 mL) at room temperature for 5 h. [b] Yields of
isolated products. [c] The reaction was carried out at room temperature
overnight. [d] 4h:4h’=1.3:1. The ratio was estimated by 1H NMR
spectroscopy.
[a] Conditions: 1a (0.3 mmol), 2a (0.6 mmol), 3 (0.6 mmol), and CsF
(0.9 mmol) in CH3CN (1 mL) at room temperature for 5 h. [b] Yields of
isolated products. [c] 3 mmol of alkyne was used.
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entries 4 and 5). In these reactions, the major products were
aryne–alkene–aryne cyclization species. If unactivated
alkenes were used, no desired products 4 were detected.
Functionalized aryne precursors with electron-donating
groups (1c,d,e) were less effective, producing dihydronaph-
thalene derivatives 4 f,g,h/h’ in moderate yields (Table 2,
entries 7–9). The electron-poor benzyne precursor 1b
afforded a complex inseparable mixture (Table 2, entry 6).
Various alkynes were compatible with this nickel-cata-
lyzed cocyclization reaction and gave the desired products 4
in very good yields (Table 3). Excellent regioselectivity was
observed for all unsymmetrical alkynes because of the
polarity of these molecules (Table 3, entries 1–8). It is note-
Experimental Section
General procedure: CH3CN (1 mL), alkyne (0.6 mmol), alkene
(0.6 mmol), and aryne precursor (0.3 mmol) were added to a flask
containing [Ni(cod)2] (0.015 mmol) and CsF (0.9 mmol) under a
nitrogen atmosphere. The reaction mixture was stirred at room
temperature for 5 h. The mixture was extracted with diethyl ether,
and the resulting solution was dried over Na2SO4 and concentrated to
dryness in vacuo. The residue was subjected to column chromatog-
raphy on silica gel (40–230 mesh) using hexane/ethyl acetate as eluent
to give the product.[17]
Received: April 15, 2009
Published online: June 25, 2009
Keywords: arynes · cyclization · homogeneous catalysis · nickel ·
=
ꢀ
worthy that no C C or C N insertion product was observed
when 3 f or 3g was used as the starting material (Table 3,
entries 5 and 6). In case of methyl 2-butynoate (3i), the low
yield was due to the trimerization of 3i catalyzed by Ni0
(Table 3, entry 8).[1a,16]
.
three-component reactions
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readily available starting materials.
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[17] Experimental details and complete characterization data are
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