AgOTf-Catalyzed Tandem Reaction of Oxabenzonorbornadienes with Arylacetylenes

Article abstract of DOI:10.1002/cjoc.201500392

A tandem isomerization/hydroarylation reaction of oxabenzonorbornadienes and arylacetylenes was realized by using AgOTf as catalyst. 1,1-Diarylethylenes could be easily generated as products in moderate to good yields in this tandem reaction.

Full text of DOI:10.1002/cjoc.201500392

COMMUNICATION
DOI: 10.1002/cjoc.201500392
AgOTf-Catalyzed Tandem Reaction of Oxabenzonorborna-
dienes with Arylacetylenes
Yongyun Zhou, Shanshan Liu, Hualei Chen, Jingchao Chen, Weiqing Sun,
Sifeng Li, Qingjing Yang, and Baomin Fan*
YMU-HKBU Joint Laboratory of Traditional Natural Medicine, Yunnan Minzu University,
Kunming, Yunnan 650500, China
A tandem isomerization/hydroarylation reaction of oxabenzonorbornadienes and arylacetylenes was realized by
using AgOTf as catalyst. 1,1-Diarylethylenes could be easily generated as products in moderate to good yields in
this tandem reaction.
Keywords silver, tandem reaction, catalyze, 1,1-diarylethylene, oxabenzonorbornadiene
the same reactions of oxabenzonorbornadienes.[21] Obvi-
ously, Lewis acids had played an important role in the
catalytic procedures of these reactions. It should be
noted that Lewis acids, for example Fe(OTf)3, had also
been successfully used as catalyst for the hydroal-
kynylation reaction of norbornadiene derivatives.[22] For
better understanding the effects of Lewis acids in such
reactions, it is necessary to explore the catalytic activ-
ities of Lewis acids in the reactions between oxaben-
zonorbornadienes and terminal alkynes. Herein, we re-
port a AgOTf catalyzed tandem isomerization/hydro-
arylation reaction of oxabenzonorbornadienes and ary-
lacetylenes.
Introduction
The reactions between oxabenzonorbornadienes and
terminal alkynes demonstrate the versatile power of cat-
alysts in organic synthesis. By using different metal
complexes as catalysts, tremendous reactive diversities
have been achieved for these reactions, with molecules
having different structures generated. For example, [2＋
1],[1,2] [2＋2],[3-10] and [2＋2＋2][11-13] cycloaddition
reactions, as well as ring-opening reactions[14] and hy-
droalkynylation reactions,[15] have been reported for
oxabenzonorbornadienes and terminal alkynes with
various cyclic compounds as products. Despite of these
reported reactions, it is still interesting and desirable to
develop new catalytic reactions for oxabenzonorborna-
dienes and terminal alkynes by employing new cata-
lysts.
Experimental
General
Over the past several years, our group had been
devoted to studying the transition-metal-catalyzed
asymmetric reactions of norbornadiene derivatives,
especially those with terminal alkynes. We had estab-
lished two effective chiral iridium catalysts for the
asymmetric hydroalkynylation reaction[16,17] and asym-
metric [2＋2] cycloaddition reaction[18,19] of norbor-
nadiene derivatives with terminal alkynes respectively.
Recently, we had found that the combination of
Pd(OAc)2/(R)-xyl-Binap and CuOTf could form a high
efficient co-catalytic system for the asymmetric ring
opening reaction of azabenzonorbornadienes with vari-
ous terminal alkynes.[20] By fine tuning the catalytic
system to be Pd(OAc)2/(R)-xylyl-Phanephos and AgOTf,
the new catalytic system was proved to be suitable for
The reactions and manipulations were performed
under an argon atmosphere by using standard Schlenk
techniques and a drybox (Mikrouna, Supper 1220/750).
Anhydrous toluene, DME (dimethoxyethane), THF
(tetrahydrofuran), and dioxane were distilled from so-
dium benzophenoneketyl prior to use. Anhydrous DCE
(1,2-dichloroethane) was distilled from calcium hydride
and stored under argon.1H NMR and 13C NMR spectra
were recorded on a Bruker-Avance 400 MHz spec-
trometer. CDCl3 was used as solvent. Chemical shifts (δ)
were reported with tetramethylsilane as an internal
standard, and J values were reported in Hz. High-reso-
lution mass spectra (HRMS) were obtained on a VG
Autospec-3000 spectrometer. Column chromatography
was performed using silica gel (200－300 mesh).
*
E-mail: adams.bmf@hotmail.com; Fax: 0086-871-65913103
Received June 1, 2015; accepted July 9, 2015; published online August 12, 2015.
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/cjoc. 201500392 or from the author.
Chin. J. Chem. 2015, 33, 1115—1118
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Zhou et al.
COMMUNICATION
Typical procedure for AgOTf-catalyzed tandem re-
action of oxabenzonorbornadiene with terminal al-
kyne
Scheme 2 AgOTf-catalyzed isomerization and hydroarylation
reactions
OH
Under the protection of argon, AgOTf (5.1 mg, 0.02
mmol), oxabenzanorbornadiene (28.8 mg, 0.2 mmol),
and 1.0 mL DCE were added to a Schlenk tube. The
solution obtained was stirred at room temperature. 10
min later, arylacetylene (44 µL, 0.4 mmol) and 1.0 mL
DCE were added, and the Schlenk tube was sealed with
a rubber septum and moved to an oil bath. The mixture
was stirred at 90 ℃ (bath temperature) until the reac-
tion was complete. After vacuum evaporation of the
reaction solvent, the residue was purified by column
chromatography on silica gel to yield the 1,1-diaryl-
ethylene product.
AgOTf
O
DCE, 90 °C
20 min, 94% yield
1b
OH
5
OH
Ph
AgOTf
Ph
+
DCE, 90°C
16 h, 90% yield
5
2a
3ba
as catalysts (Table 1). It was observed that Zn(OTf)2 and
Fe(OTf)2 were ineffective in this reaction (Entries 2 and
3). Fe(OTf)3 was proved to be a poor catalyst for the
transformation, and after 42 h of heating and stirring,
3ba was obtained in only 17% yield (Entry 4). Both
CuOTf and Cu(OTf)2 could catalyze the desired reac-
tion, with the latter showing higher efficiency and pro-
ducing the hydroarylation product in 85% yield (Entry
6). Changing the anion of the silver salt did not enhance
the efficiency of the catalyst (Entries 7 and 8). AgOTf
was proved to be the best catalyst for this transforma-
tion.
Results and Discussion
Initially, we selected norbornadiene 1a to react with
phenylacetylene 2a under the promotion of AgOTf
(Scheme 1). After 22 h of heating and stirring, phenyla-
cetylene was completely consumed, and the hydroal-
kynylation product 4 was isolated in 20% yield. En-
couraged by this result, oxabenzonorbornadiene 1b was
employed as a substrate for the reaction. Interestingly,
1,1-diarylethylene 3ba was generated, along with a
small amount of naphthol 5 instead of the expected hy-
droalkynylation product. It was observed that, under the
catalysis of AgOTf, oxabenzonorbornadiene 1b could
be almost quantitatively isomerized to naphthol 5 in a
very short time.[23] We also observed that under the
same catalytic condition, naphthol 5 could react with
phenylacetylene 2a to generate the hydroarylation
product 3ba in 90% yield in 16 h (Scheme 2). Thus, a
silver-catalyzed tandem ring-opening isomerization and
hydroarylation procedure for oxabenzonorbornadiene
1b and phenylacetylene 2a could be proposed for the
generation of 1,1-diarylethylene 3ba.[24,25]
Table 1 Screening of different Lewis acids as catalyst in hy-
droarylation reaction of naphthol (5) and phenylacetylene (2a)a
OH
OH
Lewis Acid
DCE, 90 °C
Ph
Ph
5
2a
3ba
Entry
Metal catalyst
AgOTf
Time/h
Yieldb/%
90
1
2
3
4
5
6
7
8
16
24
24
42
42
28
16
16
Zn(OTf)2
Fe(OTf)2
Fe(OTf)3
CuOTf
n. r.
n. r.
17
Scheme 1 AgOTf-catalyzed reactions between norbornadiene
or oxabenzonorbornadiene and phenylacetylene
59
Ph
Cu(OTf)2
AgSbF6
85
AgOTf
+
Ph
＜5
°
DCE, 90 C
22 h, 20% yield
1a
AgBF4
57
2a
4
a Reagents and conditions: naphthol (5; 0.2 mmol), phenylacety-
lene (2a; 0.4 mmol), metal salt (10 mol%), DCE (2 mL), reflux.
b Isolated yield.
OH
OH
AgOTf
DCE, 90 °C
Ph
+
+
O
Ph
Using AgOTf as a catalyst, the solvent and reaction
temperature for the hydroarylation reaction of naphthol
5 and phenylacetylene 2a were further optimized; the
results are summarized in Table 2. As shown, DCE was
the best solvent because the highest yield was achieved
within the shortest reaction time (Entry 5). It was ob-
served that the yield of the product decreased signifi-
cantly with the decreasing of reaction temperature (En-
tries 6 and 7). Thus, the optimum reaction conditions for
trace
5
72 h, 74% yield
3ba
1b
2a
Since the hydroarylation reaction was observed to be
the speed-controlling step for the generation of
1,1-diarylethylene 3ba in this tandem procedure,[26] the
catalytic conditions for this step were further examined
by using naphthol 5 and phenylacetylene 2a as standard
substrates. First, a series of Lewis acids were screened
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Chin. J. Chem. 2015, 33, 1115—1118

AgOTf-Catalyzed Tandem Reaction of Oxabenzonorbornadienes with Arylacetylenes
this speed-controlling step could be determined using
AgOTf as the catalyst, in DCE solvent and at 90 ℃,
which should also be the best condition for the entire
tandem reaction.
Table 3 AgOTf-catalyzed tandem isomerization/hydroarylation
reaction of oxabenzonorbornadienes and arylacetylenesa
R1 OH
R1
R2
R2
R2
R2
AgOTf
Ar
O
+
Table 2 Screening of the solvents and temperaturea
DCE, 90 °C
Ar
R1 R3
R1 R3
1b - 1e
OH
OH
2a - 2e
3ba - 3ee
AgOTf
Ph
Ph
Oxabenzonor-
bornadiene
Entry
1
Arylacetylene
Time/h Yieldb/%
5
2a
3ba
Entry Solvent
Temperature/℃
Time/h
Yieldb/%
O
72
68
91
72
48
74
25
48
66
83
1b
2a
1
THF
Toluene
Dioxane
DME
90
90
90
90
90
70
50
23
42
42
37
16
52
72
24
71
48
53
90
56
39
2
3
4
5
6
7
Me
2b
O
2
3
4
5
1b
DCE
DCE
OCF3
2c
O
DCE
1b
a Reagents and conditions: naphthol (5; 0.2 mmol), phenylacety-
lene (2a; 0.4 mmol), AgOTf (10 mol%), DCE (2 mL). b Isolated
yield.
Br
2d
O
1b
To further probe the generality of this methodology,
several substituted oxabenzonorbornadienes and ary-
lacetylenes were used as substrates in this silver-cata-
lyzed tandem reaction system. The results are presented
in Table 3, which demonstrate that the electronic prop-
erties of the substituents on the phenyl ring had a dis-
tinct effect on the yield of the reactions (Entries 1－5).
The reaction of oxabenzonorbornadiene and phenyl
acetylene afforded the hydroarylation product in good
yield (74%) (Entry 1). However, electron-donating
groups on the aromatic rings of terminal alkynes re-
sulted in a lower yield (Entry 2). Substituents with elec-
tron-withdrawing groups on the aromatic rings of ter-
minal alkynes were well tolerated in this tandem reac-
tion (Entry 3－5). It should be noted that the terminal
alkyne with an F group on the aromatic ring afforded
the hydroarylation product in good yield (83%) (Entry
5). Several other substituted oxabenzonorbornadiene
derivatives were also examined and proved to be suit-
able substrates (Entry 6－8). In particular, 4-monosub-
stituted oxabenzonorbornadiene also afforded the cor-
responding product in 66% yield (Entry 7).
F
O
1b
2e
2e
Me
O
F
6
66
62
Me
1c
O
F
F
7
8
67
48
66
38
2e
2e
Me
1d
Br
Br
O
1e
a Reagents and conditions: oxabenzonorbornadienes (1b－1e, 0.2
mmol), arylacetylene (2a－2e, 0.4 mmol), AgOTf (10 mol%),
DCE (2 mL). b Isolated yield.
On the basis of literature[23] and our own observa-
tions, the proposed mechanism for this novel tandem
reaction is shown in Scheme 3. The catalytic cycle is
initiated by the coordination of oxabenzonorbornadiene
with silver ion to generate the active silver complex A,
which undergoes ring-opening reaction to afford the
silver alkoxide species B. Subsequently, intermediate B
might be in equilibrium with isomer C that generates
side-product 5 from silver alkoxide D by proton elimi-
nation and the following cation exchange. However, as
reaction time prolonged, the silver alkoxide D coordi-
nates with arylacetylene to generate complex E, which
gives intermediate F by nucleophilic addition. Finally,
the tandem reaction product 3ba is obtained by cation
exchange.
Conclusions
In summary, a tandem isomerization/hydroarylation
reaction of oxabenzonorbornadienes and arylacetylenes
has been developed. 1,1-Diarylethylenes could be gen-
erated in yields of up to 83% when using AgOTf as
Chin. J. Chem. 2015, 33, 1115—1118
© 2015 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
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1117

Zhou et al.
COMMUNICATION
Scheme 3 Proposed mechanism for AgOTf-catalyzed tandem reaction of oxabenzonorbornadiene with arylacetylene
OH
O
Ag+
5
1b
Ph
OAg
OAg
Ag+
O
E
D
A
H+
OAg
Ph
OAg
+
OAg
+
F
H+
OH
B
C
+ Ag+
Ph
3ba
(a) Rayabarapu, D. K.; Chiou, C.-F.; Cheng, C.-H. Org. Lett. 2002, 4,
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Zhou, Y.-Y.; Huang, C.; Fan, B.-M. Acta Chim. Sinica 2013, 71,
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Acta Chim. Sinica 2014, 72, 1144; (d) Qian, Y.-L.; Chen, B.; Jin,
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a catalyst. This reaction provides an attractive method
for the facile and economical construction of 1,1-diaryl-
ethylenes, which are important motifs in both naturally
occurring and biologically active compounds.
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Chin. J. Chem. 2015, 33, 1115—1118