Palladium/Silver-Cocatalyzed Tandem Reactions of Oxabenzonorbornadienes with Substituted Arylacetylenes: A Simple Method for the Preparation of 1,2-Diarylethanones and 1,2-Diarylacetylenes

Article abstract of DOI:10.1021/acs.organomet.5b00551

The effective synthesis of 1,2-diarylethanones was achieved using palladium(II) acetate [Pd(OAc)₂] and silver triflate (AgOTf) as cocatalysts from various oxabenzonorbornadiene derivatives and substituted arylacetylenes via tandem reactions under mild conditions. Exploration of the oxabenzonorbornadiene substrates showed that the 1,2-diarylacetylenes were obtained from adjacent alkoxy substituted oxabenzonorbornadiene derivatives. Preliminary mechanistic studies indicate that the AgOTf served as an indispensable catalyst, and the mechanism of the tandem reaction was proposed.

Full text of DOI:10.1021/acs.organomet.5b00551

Article
pubs.acs.org/Organometallics
Palladium/Silver-Cocatalyzed Tandem Reactions of
Oxabenzonorbornadienes with Substituted Arylacetylenes: A Simple
Method for the Preparation of 1,2-Diarylethanones and 1,2-
Diarylacetylenes
Jingchao Chen,†,§ Shanshan Liu,†,§ Yongyun Zhou, Sifeng Li, Chengyuan Lin, Zhaoxiang Bian,
and Baomin Fan*
†
†
‡
‡
,†
†YMU-HKBU Joint Laboratory of Traditional Natural Medicine, Yunnan Minzu University, Kunming 650500, Yunnan, China
‡School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China
*
S Supporting Information
ABSTRACT: The effective synthesis of 1,2-diarylethanones
was achieved using palladium(II) acetate [Pd(OAc) ] and
2
silver triflate (AgOTf) as cocatalysts from various oxabenzo-
norbornadiene derivatives and substituted arylacetylenes via
tandem reactions under mild conditions. Exploration of the
oxabenzonorbornadiene substrates showed that the 1,2-
diarylacetylenes were obtained from adjacent alkoxy sub-
stituted oxabenzonorbornadiene derivatives. Preliminary
mechanistic studies indicate that the AgOTf served as an
indispensable catalyst, and the mechanism of the tandem
reaction was proposed.
INTRODUCTION
biological activities, including protein tyrosine phosphatase
11
■
inhibitory activity and antimicrobial activity. As an extension
of our previous work, we further studied the generation of 1,2-
diphenylethanones. Herein, we report the palladium/silver-
cocatalyzed tandem reactions of oxabenzonorbornadienes with
arylacetylenes. Furthermore, 1,2-diarylacetylenes, widely used
The reactions of norbornadiene derivatives with terminal
alkynes are quite versatile and can be regarded as an obvious
evidence for the diversity of organic reactions. Various
norbornadienes and terminal alkynes can undergo ring-opening
1
2
3
reactions, addition reactions, [2 + 1] cycloaddition reactions,
12
as polymers and liquid crystals materials, could be smoothly
4
5
[
2 + 2] cycloaddition reactions, and other reactions to afford
produced according to the electronic property of the
substitutional groups on the phenyl ring of oxabenzonorborna-
dienes.
6
cyclic products using transition-metal catalysts or Lewis acids.
On the other hand, Lewis acids can play an important role as
additives in the transition-metal-catalyzed reactions of
norbornadiene derivatives, which had been demonstrated by
the pioneering work of Lautens’ group. This methodology was
also proved to be effective in the nickel-catalyzed ring-opening
7
RESULTS AND DISCUSSION
■
Initial trials were carried out by testing phosphine ligands for
the tandem reaction of oxabenzonorbornadiene with phenyl-
acetylene. As shown in Table 1, the tandem reaction of
oxabenzonorbornadiene 1a with phenylacetylene 2a (3 equiv)
in the presence of AgOTf and Pd complexes generated by
reaction of oxa/azabenzonorbornadienes with terminal alkynes
8
by Cheng’s group. It is quite interesting and necessary to
explore the utility of the combination of transition-metal
catalysts and Lewis acids in the catalytic reactions of
norbornadiene derivatives, especially those with terminal
alkynes. Recently, by employing copper(I) triflate, our group
has established an efficient palladium/copper cocatalytic system
for asymmetric ring-opening reaction of azabenzonorborna-
dienes with terminal alkynes. By switching the Lewis acid from
copper(I) triflate to silver triflate and fine-tuning the reaction
conditions, we realized the highly enantioselective ring-opening
reaction of oxabenzonorbornadienes with terminal alkynes.
palladium(II) acetate [Pd(OAc) ] and phosphine ligands was
2
studied. The result indicated that (rac)-Binap, xantphos, and
DPEphos gave good yields (62−79% yields, entries 1−3),
whereas DPPF, DPPB, and PPh3 were inefficient in this
reaction (entries 4−6). It could be observed that (rac)-Binap
resulted in the best yield. Other palladium precatalysts in
combination with (rac)-Binap were also investigated. Most of
palladium precursors could promote the reaction to give
9
1
0
During the course of our investigation, 1,2-diphenylethanone
was separated as a byproduct and attracted our attention, since
it possesses a common skeleton that demonstrates particular
Received: June 29, 2015
©
XXXX American Chemical Society
A
DOI: 10.1021/acs.organomet.5b00551
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
Table 1. Ligand and Palladium Screening for Palladium-
Catalyzed Tandem Reaction of Oxabenzonorbornadienes
and Phenylacetylene
to 70% (entry 8). The temperature experiments indicated that
the reaction temperature of 55 °C was optimal (entries 9−11).
The results of the tandem reactions of a variety of terminal
alkynes 2a−m and oxabenzonorbornadiene 1a in the presence
a
of Pd(OAc) (5% mol)/AgOTf (10% mol) and (rac)-Binap
2
(
3% mol) in toluene at 55 °C are summarized in Table 3.
b
entry
[M]
ligand
time (h)
yield (%)
Table 3. Pd-Catalyzed Reactions of 1a with Various
Terminal Alkynes
a
1
2
3
4
5
6
7
8
9
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(acac)2
PdBr2
(±)-Binap
xantphos
DPEphos
Dppf
22
27
4
79
75
62
48
48
48
22
36
5
trace
trace
trace
78
Dppb
b
entry
Ar
2
time (h)
yield (%)
PPh3
(±)-Binap
(±)-Binap
(±)-Binap
(±)-Binap
(±)-Binap
(±)-Binap
(±)-Binap
1
2
Ph
2a
2b
2c
2d
2e
2f
1
1
96
91
90
96
92
95
95
90
96
92
90
93
94
63
4-MeOC H4
6
(CF CO ) Pd
54
3
2-MeOC H4
1
3
2
2
6
10
11
12
13
Pd(C HF O )
22
36
17
46
67
4
3-MeOC H4
1
5
6
2
2
6
PdCl2
PdI2
C H Pd Cl
65
5
3,5-di-MeOC H3
0.3
0.5
1
6
71
6
4-FC H4
6
27
7
4-PhOC H4
2g
2h
2i
6
10
2
2
6
a
8
4-CF OC H
0.5
1
Reaction conditions: 2a (0.9 mmol), 2a:1a:[Pd]:ligand:[Ag]
3:1:0.05:0.06:0.1) in THF (2 mL) at 35 °C under argon for
indicated period of time. Isolated yield by column chromatography.
3
6
4
(
9
4-BrC H
6 4
b
10
11
12
4-MeC H4
2j
1
6
Pd(C HF O ) = palladium(II) hexafluoroacetylacetonate.
4-OHCH C H
2k
2l
1
5
6
2
2
2
6
4
C H Pd Cl = allyl-palladium(II) chloride dimer.
6
10
2
2
4-CF C H
4
0.5
13
3
6
1
3
4-CNC H4
2m
6
acceptable yields (54−78% yields, entries 7−12) under the
same conditions, but C H Pd Cl showed lower catalytic
a
Reaction conditions: 2a (0.6 mmol), 2a:1a:[Pd]:Binap:[Ag]
6
10
2
2
(3:1:0.05:0.03:0.1), in toluene (2 mL) at 55 °C under argon for
indicated period of time. Isolated yield by column chromatography.
activity (27% yield, entry 13). Thus, Pd(OAc) was found to be
b
2
the most effective palladium precursor.
Therefore, Pd(OAc)2 and (rac)-Binap were selected to
investigate solvent and temperature effects (Table 2). Among
Generally, all of the terminal aromatic alkynes reacted with 1a
smoothly to provide the corresponding products in excellent
yields (entries 1−13). Arylacetylenes with substituents of
different electronic properties were suitable to give the
corresponding products. In particular, the terminal alkyne
a
Table 2. Optimization of Reaction Conditions
with −CH OH on the aromatic ring also afforded a high yield
2
(
entry 11).
b
entry
solvent
temp (°C)
time (h)
yield (%)
To extend the scope of substrates, substituted oxabenzo-
1
2
3
4
5
DCE
35
35
35
35
35
35
35
35
rt
2
2
complex
complex
81
norbornadiene derivatives 1a−f were examined (Table 4).
Except for 1b, which bears an electron-donating group and gave
a moderate yield (entry 2), the tandem reactions of most
oxabenzonorbornadienes with phenylacetylene 2a proceeded
smoothly to afford the corresponding products in good yields
(entries 1, 3−6).
Further investigation of this tandem reaction was performed
by testing additional oxabenzonorbornadiene derivatives with
adjacent alkoxy substituted on the phenyl ring (Table 5).
Interestingly, we could obtain another kind of product in good
yields when we employed adjacent alkoxy substituted
oxabenzonorbornadiene derivatives 1g−i as substrates to
react with phenylacetylene 2a.
DCM
DME
2
THF
22
2
79
dioxane
toluene
toluene
toluene
toluene
toluene
toluene
79
6
2
86
c
7
2
92
d
8
1.5
17
1
70
c
9
93
c
1
0
55
75
96
c
1
1
0.5
87
a
Reaction conditions: 2a (0.9 mmol), 2a:1a:[Pd]:Binap:[Ag]
3:1:0.05:0.03:0.1), in solvent (2 mL) under argon for indicated
period of time. Isolated yield by column chromatography. 3 mol %
(
b
c
In order to investigate the reaction mechanism, we have
d
10
(
±)-Binap was used. 9 mol % (±)-Binap was used.
prepared a possible reaction intermediate 4 and subjected it
to the synthesis of 3ab (Table 6). It was found that this
the test solvents, DME, dioxane, and toluene were more
effective (79−86% yields, entries 3−6) than DCE and DCM
transformation did not proceed without catalyst (entry 1).
However, when a mixture of Pd(OAc) , (±)-Binap, and AgOTf
2
(
entries 1 and 2) in the present reaction. Toluene was the most
was used as catalyst, the ketone product 3ab was obtained in
high yield (entry 2). However, no desired product 3ab was
detected in the absence of AgOTf when Pd(OAc)2 and
(±)-Binap were used (entry 3). Interestingly, the trans-
formation proceeded smoothly when AgOTf was used alone
suitable solvent (entry 6). The dosage of the ligand had a
strong effect on the yield. For example, using 3 mol % (rac)-
Binap obtained 92% yield within 2 h (entry 7). However, by
increasing (rac)-Binap to 9 mol %, the product yield decreased
B
DOI: 10.1021/acs.organomet.5b00551
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
a
Table 4. Pd-Catalyzed Tandem Reactions of Substituted
Oxabenzonorbornadienes with Phenylacetylene 2a
Table 6. Study of the Transformation from 4 to 3ab
a
e
entry
1
conditions
temp (°C) time (h) yield (%)
70
35
70
55
60
3
NR
b
2
Pd(OAc) /(±)-Binap, AgOTf
93
2
c
3
d
Pd(OAc) /(±)-Binap
60
2
complex
2
4
AgOTf
98
a
b
Reactions were carried out in toluene (2 mL) under argon. 5 mol %
c
Pd(OAc) , 3 mol % Binap, and 10 mol % AgOTf were used. 5 mol %
2
d
Pd(OAc) and 3 mol % Binap were used. 15 mol % AgOTf was used.
2
e
Isolated yield by column chromatography.
the carbon−carbon double bond, the intermediate E is formed.
Following β-hydrogen elimination, the C−O bond is broken,
producing the intermediate F. After a simple cation exchange,
G is afforded as a byproduct, which is observed in the beginning
of this tandem reaction.
Next, with adjacent alkoxy substitutions on oxabenzonor-
bornadiene, a relatively favorable intermediate H is generated
from F by the leaving of the hydroxyl group (Path A). Then,
the corresponding proton elimination affords the 1,2-diary-
lacetylene I. However, in most cases, F is transferred to the
silver intermediate K by intramolecular nucleophilic addition
(
Path B). The following proton elimination and cation
a
Reaction conditions: 2a (0.6 mmol), 2a:1a:[Pd]:Binap:[Ag]
exchange afford the 1,2-diarylethanone M.
(
3:1:0.05:0.03:0.1), in toluene (2 mL) at 55 °C under argon for
b
indicated period of time. Isolated yield by column chromatography.
CONCLUSION
■
We describe the effective synthesis of 1,2-diarylethanones from
the oxabenzonorbornadiene derivatives and substituted aryla-
cetylenes using Pd(OAc)2 and AgOTf as cocatalyst. 1,2-
Diarylacetylene derivatives were also obtained from adjacent
alkoxy substituted oxabenzonorbornadiene derivatives. On the
basis of the mechanism study, a plausible reaction pathway that
generates both 1,2-diarylethanones and 1,2-diarylacetylenes was
proposed.
Table 5. Reaction of Adjacent Alkoxy Substituted
Oxabenzonorbornadienes and 2a under Pd/Ag Catalytic
Conditions
a
EXPERIMENTAL SECTION
■
General Method. The reactions and manipulations were
performed under an atmosphere of argon using standard Schlenk
techniques and drybox (Mikrouna, Supper 1220/750). Anhydrous
toluene, DME, THF, and dioxane were distilled from sodium
benzophenone ketyl prior to use. Anhydrous toluene was distilled
from calcium hydride and stored under argon. Absolute MeOH and
isopropyl alcohol were distilled from magnesium and stored under
1
13
argon. H NMR and C NMR spectra were recorded on a Bruker-
Avance 400 MHz spectrometer, and CDCl3 was used as solvent.
Chemical shifts (δ) were reported in ppm with tetramethylsilane as
internal standard, and J values were given in Hz. High-resolution mass
spectra (HRMS) were performed on a VG Autospec-3000
spectrometer. Column chromatography was performed with silica gel
a
Reaction conditions: 2a (0.6 mmol), 2a:1a:[Pd]:Binap:[Ag]
(
3:1:0.05:0.03:0.1), in toluene (2 mL) at 55 °C under argon for
b
indicated period of time. Isolated yield by column chromatography.
(
200−300 mesh).
(entry 4). Therefore, this result suggested that AgOTf served as
Typical Procedure for Palladium/Silver-Cocatalyzed Tan-
dem Reactions of Oxabenzonorbornadienes with Terminal
Alkynes. Pd(OAc) (3.4 mg, 0.015 mmol), (±)-Binap (5.6 mg, 0.009
an indispensable catalyst in the present transformation.
On the basis of the above experiments, a plausible
mechanism for this novel tandem reaction is shown in Figure
2
mmol), and 1.0 mL of toluene were added to a Schlenk tube under an
argon atmosphere. The resulting solution was stirred at room
temperature for 30 min. Then, a solution of CF SO Ag (7.7 mg,
1
. The arylacetylene reacts with the complex of Pd(OAc) and
±)-Binap to produce palladium acetylide species B, which
2
3
3
(
0
.03 mmol) was added, and the mixture was stirred for an additional
10 min. After the addition of oxabenzonorbornadiene 1a (43.2 mg, 0.3
coordinates with silver-activated oxabenzonorbornadiene to
afford D. By the migratory insertion of an arylethynyl group to
mmol) in toluene (1.0 mL), the mixture was stirred for an additional
C
DOI: 10.1021/acs.organomet.5b00551
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
Figure 1. Mechanism for palladium/silver-cocatalyzed tandem reaction of oxabenzonorbornadiene and terminal alkyne.
1
0 min. After the last addition of terminal alkyne 2a (100 μL, 0.9
J.; Fan, C.; Li, S.; Yu, L.; Huang, C.; Tsang, W.; Kwong, F. Y. Angew.
Chem., Int. Ed. 2012, 51, 7821−7824. (d) Gatineau, D.; Giordano, L.;
Buono, G. J. Am. Chem. Soc. 2011, 133, 10728−10731.
mmol), the mixture was stirred at 55 °C under an argon atmosphere
with TLC monitoring until achieving the complete consumption of 1a.
After vacuum evaporation of the solvent, the residue was purified by
silica gel column chromatography to provide the desired product 3aa
(3) (a) Bigeault, J.; Giordano, L.; Buono, G. Angew. Chem., Int. Ed.
2
005, 44, 4753−4757. (b) Tenaglia, A.; Marc, S. J. Org. Chem. 2006,
(
73.1 mg, 96% yield).
7
1, 3569−3575. (c) Bigeault, J.; Giordano, L.; de Riggi, I.; Gimbert, Y.;
Buono, G. Org. Lett. 2007, 9, 3567−3570. (d) Gatineau, D.; Moraleda,
ASSOCIATED CONTENT
D.; Naubron, J. V.; Bu
Asymmetry 2009, 20, 1912−1917.
4) (a) Burton, R. R.; Tam, W. J. Org. Chem. 2007, 72, 7333−7336.
b) Fan, B.; Li, X.; Peng, F.; Zhang, H.; Chan, A. S. C.; Shao, Z. Org.
̈
rgi, T.; Giordano, L.; Buono, G. Tetrahedron:
■
* Supporting Information
S
(
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.organo-
met.5b00551.
(
Lett. 2010, 12, 304−306. (c) Hu, J.; Yang, Q.; Yu, L.; Xu, J.; Liu, S.;
Huang, C.; Wang, L.; Zhou, Y.; Fan, B. Org. Biomol. Chem. 2013, 11,
Preparation method of oxabenzonorbornadienes, charac-
terization data, and NMR spectra (PDF)
2
294−2301. (d) Yang, Q.; Yu, L.; Xu, J.; Li, S.; Liu, S.; Chen, H.;
Zhou, Y.; Wang, L.; Fan, B. Tetrahedron: Asymmetry 2014, 25, 957−
9
61.
AUTHOR INFORMATION
Corresponding Author
E-mail: FanBM@ynni.edu.cn.
Author Contributions
These authors contributed equally.
Notes
The authors declare no competing financial interest.
(5) (a) Sambaiah, T.; Huang, D. J.; Cheng, C.-H. J. Chem. Soc. Perkin
■
Trans. 1 2000, 195. (b) Tenaglia, A.; Marc, S. J. Org. Chem. 2008, 73,
397−1402. (c) Rayabarapu, D. K.; Sambaiah, T.; Cheng, C.-H.
Angew. Chem., Int. Ed. 2001, 40, 1286−1288.
6) Kohno, K.; Nakagawa, K.; Yahagi, T.; Choi, J.; Yasuda, H.;
Sakakura, T. J. Am. Chem. Soc. 2009, 131, 2784−2785.
7) (a) Lautens, M.; Fagnou, K.; Yang, D. J. Am. Chem. Soc. 2003,
1
*
(
§
(
1
2
25, 14884−14892. (b) Lautens, M.; Hiebert, S. J. Am. Chem. Soc.
004, 126, 1437−1447. (c) Lautens, M.; Hiebert, S.; Renaud, J. L. Org.
Lett. 2000, 2, 1971−1973. (d) Lautens, M.; Fagnou, K.; Hiebert, S.
Acc. Chem. Res. 2003, 36, 48−58. (e) Lautens, M.; Hiebert, S.; Renaud,
J. L. J. Am. Chem. Soc. 2001, 123, 6834−6849.
ACKNOWLEDGMENTS
We thank the National Natural Science Foundation of China
21362043, 21162040, 21302162), the Government of Yunnan
■
(
(8) (a) Rayabarapu, D. K.; Chiou, C. F.; Cheng, C. H. Org. Lett.
Province (2012FB170), and the State Key Laboratory of
Elemento-organic Chemistry, Nankai University (201302), for
financial support.
2
1
002, 4, 1679−1682. (b) Duan, J. P.; Cheng, C. H. Organometallics
995, 14, 1608−1618. (c) Rayabarapu, D. K.; Cheng, C. H. Acc. Chem.
Res. 2007, 40, 971−983.
(
9) Fan, B.; Li, S.; Chen, H.; Lu, Z.; Liu, S.; Yang, Q.; Yu, L.; Xu, J.;
Zhou, Y.; Wang, J. Adv. Synth. Catal. 2013, 355, 2827−2832.
10) Liu, S.; Li, S.; Chen, H.; Yang, Q.; Xu, J.; Zhou, Y.; Yuan, M.;
Zeng, W.; Fan, B. Adv. Synth. Catal. 2014, 356, 2960−2964.
11) (a) Dufresne, C.; Roy, P.; Wang, Z.; Asante-Appiah, E.;
REFERENCES
■
(
(
1) (a) Nishimura, T.; Tsurumaki, E.; Kawamoto, T.; Guo, X.;
Hayashi, T. Org. Lett. 2008, 10, 4057−4060. (b) Chen, H.; Li, S.; Xu,
(
J.; Yang, Q.; Liu, S.; Zhou, Y.; Huang, C.; Fan, B. Huaxue Xuebao
Cromlish, W.; Boie, Y.; Forghani, F.; Desmarais, S.; Wang, Q.; Skorey,
K.; Waddleton, D.; Ramachandran, C.; Kennedy, B. P.; Xu, L.;
Gordon, R.; Chan, C. C.; Leblanc, Y. Bioorg. Med. Chem. Lett. 2004,
14, 1039−1042. (b) Fokialakis, N.; Lambrinidis, G.; Mitsiou, D. J.;
Aligiannis, N.; Mitakou, S.; Skaltsounis, A. L.; Pratsinis, H.; Mikros, E.;
2
013, 71, 1243−1247. (c) Mo, D. L.; Chen, B.; Ding, C. H.; Dai, L. X.;
Ge, G. C.; Hou, X. L. Organometallics 2013, 32, 4465−4468.
2) (a) Tenaglia, A.; Giordano, L.; Buono, G. Org. Lett. 2006, 8,
315−4318. (b) Chang, Y. C.; Kuo, C. J.; Li, C. S.; Liu, C. H. J.
Organomet. Chem. 2006, 691, 4982−4989. (c) Fan, B.; Yang, Q.; Hu,
(
4
D
DOI: 10.1021/acs.organomet.5b00551
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
Alexis, M. N. Chem. Biol. 2004, 11, 397−406. (c) Li, H.; Xue, J.; Shi,
L.; Gui, S.; Zhu, H. Eur. J. Med. Chem. 2008, 43, 662−667.
(
12) (a) Tour, J. M. Chem. Rev. 1996, 96, 537−553. (b) Martin, R.
E.; Diederich, F. Angew. Chem., Int. Ed. 1999, 38, 1350−1377.
c) Bunz, U. H. F. Chem. Rev. 2000, 100, 1605−1644. (d) Chinchilla,
R.; Najera, C. Chem. Rev. 2007, 107, 874−922.
(
́
E
DOI: 10.1021/acs.organomet.5b00551
Organometallics XXXX, XXX, XXX−XXX