Palladium-catalyzed alkynylselenation of acetylenedicarboxylates leading to enyne selenides and application to synthesis of multisubstituted aryl selenides

Article abstract of DOI:10.1016/j.tetlet.2010.04.125

Upon treatment of a mixture of alkynyl selenides and acetylenedicarboxylates with Pd(OAc)₂/P(o-tol)₃/K ₂CO₃/H₂O-catalytic system, the alkynylselenation of acetylenedicarboxylates takes place to give t

Full text of DOI:10.1016/j.tetlet.2010.04.125

Tetrahedron Letters 51 (2010) 3538–3541
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Palladium-catalyzed alkynylselenation of acetylenedicarboxylates leading to
enyne selenides and application to synthesis of multisubstituted aryl selenides
*
Takenori Mitamura, Akiya Ogawa
Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, 1-1 Gakuen-cho, Nakaku, Sakai, Osaka 599-8531, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Upon treatment of a mixture of alkynyl selenides and acetylenedicarboxylates with Pd(OAc)2/P(o-tol)3/
K2CO3/H2O-catalytic system, the alkynylselenation of acetylenedicarboxylates takes place to give the cor-
responding alkynylvinyl selenides. Furthermore, alkynyl selenides undergo the intermolecular [2+2+2]
cycloaddition reaction in the presence of PdCl2(PPh3)2 as a catalyst, affording the corresponding
multisubstituted aryl selenides selectively.
Received 25 March 2010
Revised 23 April 2010
Accepted 28 April 2010
Available online 22 May 2010
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
Palladium-catalyzed reaction
Alkynyl selenide
Alkynylselenation
[2+2+2] Cycloaddition
Multisubstituted aryl selenides
Organoselenium compounds are focused on a material chemis-
try, biology, and organic synthesis, because of their unique reactiv-
ities, properties, and biological activities, and therefore, the
development of the convenient methods for the preparation of
organoselenium compounds is one of the important topics.1 Tran-
sition-metal-catalyzed methods are expected to be one of the pow-
erful tools for the selective construction of organoselenium
compounds.2 Recently, the transition-metal-catalyzed reactions
of organochalcogen compounds is extended: for example, the
selective addition to alkynes based on the catalytic activation of
Ch—Ch,3 Ch—H,4 Ch—E,5 and Ch—C6 bonds has been discovered
in last two decades (Ch = S, Se; E = B, Si, Ge, Sn, P, etc.; C = C(O)R,
allyl, CN).7 Although characteristic reactivities and synthetic utili-
ties of organosulfur compounds by the combination of transition
metal catalysts have been disclosed, the research area of transi-
tion-metal-catalyzed reactions of organoselenium compounds is
still remained undeveloped. During the course of our studies, we
focused on alkynyl selenides,8,9 which have a spC–Se bond, and
examined the reactions in the presence of transition metal com-
plexes for the purpose of the development of novel transition-me-
tal-catalyzed reactions of organoselenium compounds.
3a in 9% yield (entry 1).10 Thus, we screened palladium complexes
and additives such as phosphines. When Pd(OAc)2 was used along
with P(o-Tol)3, K2CO3, and H2O in this reaction, the yield of the de-
sired alkynylselenation increased to 42% (entry 2).11 Other phos-
phines such as P(p-Tol)3, P(OMe)3, PnBu3, PCy3, and DPPE (entries
3—7), and other palladium complexes such as Pd(OAc)2 and
Pd(dba)2 (entries 8 and 9) were less effective for this alkynylsele-
nation. In contrast, the use of PdCl2 as a catalyst produced a sele-
nide 4a bearing multisubstituted aryl group (entry 10).12 The
structure of the product 4a was determined by X-ray crystal anal-
ysis, as shown in Figure 1. This product 4a was generated most
probably via a PdCl2-catalyzed [2+2+2] cycloaddition of 1a with 2
equivalents of 2a.13,14 In addition, when PdCl2(PPh3)2 and
PdCl2(PhCN)2 were employed for the reaction of 1a with 2a, the
yields of 4a increased (entries 11 and 12). NiCl2(PPh3)2 and
RhCl(PPh3)3 indicated poor efficiency for the alkynylselenation
and the [2+2+2] cycloaddition of alkynyl selenide (entries 13 and
14).
We next examined the palladium-catalyzed reactions of alkynyl
selenides with acetylenedicarboxylates by use of Pd(OAc)2/P(o-
Tol)3/K2CO3/H2O catalytic system. The results of the alkynylselena-
tion of 2 with several alkynyl selenides 1 are summarized in Ta-
ble 2. Similar conditions could be employed with aryl substituted
alkynyl selenides 1b and 1c, and alkyl substituted alkynyl selenide
1d successfully (entries 3—5). When the phenyl group of 1a was re-
placed by other aryl groups, the corresponding alkynylvinyl sele-
nides 3e and 3f were obtained in similar yields (entries 6 and 7).
The ORTEP diagram of 3f (Z isomer) is shown in Figure 2. The ste-
reochemistry of vinyl unit is unambiguously determined. In the
We first examined the palladium-catalyzed reaction of alkynyl
selenide 1a with diethyl acetylenedicarboxylate (2a) in toluene
upon heating at 115 °C for 16 h (Table 1). When the reaction was
performed in the presence of Pd(PPh3)4, a novel alkynylselenation
of 2a occurred, affording the corresponding alkynylvinyl selenide
* Corresponding author. Tel./fax: +81 72 254 9290.
E-mail address: ogawa@chem.osakafu-u.ac.jp (A. Ogawa).
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.04.125

T. Mitamura, A. Ogawa / Tetrahedron Letters 51 (2010) 3538–3541
3539
Table 1
Table 2
Screening of palladium catalystsa
The palladium-catalyzed alkynylselenation with alkynyl selenidesa,b
Ph
Pd(OAc)2/P(o-Tol)3
K2CO3, H2O
R1
SeR2
CO2R3
SePh
PhSe
R1
CO2R3
Ph
SePh
CO2Et
catalyst
EtO2C
+
EtO2C
Ph
1a
+
R2Se
R3O2C
+
toluene
115 ºC, 16 h
R3O2C
toluene
115 ºC, 16 h
CO2Et
CO2Et
EtO2C
1
2
3
CO2Et
4a
EtO2C
3a
2a
Entry
1
R1
R2
2
R3
2a Et-
2b Me- 3a0 40 (33)
3
Yieldc (%) [E/Z]d
Entry
Catalyst
Yield of 3ab (%)
Yield of 4ab (%)
1
2
3
4
5
6
7
1a C6H5–
1a C6H5–
1b 4-Me-C6H4– C6H5–
1c 4-NC-C6H4– C6H5–
1d CH3(CH2)3– C6H5–
C6H5–
C6H5–
3a 42 (36)
81/19
86/14
79/21
82/18
77/23
75/25
58/42
1c
Pd(PPh3)4
9
ND
2d,e
3c,d
4c,d
5d,g
6c,d
7c,d,f
8e
Pd(OAc)2/P(o-Tol)3
Pd(OAc)2/P(p-Tol)3
Pd(OAc)2/P(OMe)3
Pd(OAc)2/PnBu3
Pd(OAc)2/PCy3
Pd(OAc)2/DPPE
Pd(OAc)2
Pd(dba)2
PdCl2
PdCl2(PPh3)2
PdCl2(PhCN)2
NiCl2(PPh3)2
RhCl(PPh3)3
42 (36)
Trace
Trace
Trace
Trace
Trace
14
2a Et-
2a Et-
2a Et-
3b 40 (34)
3c 42 (38)
3d 37 (31)
3e 39 (36)
ND
ND
24
6
13
8
Trace
5
5
1e C6H5–
1f C6H5–
4-Me-C6H4– 2a Et-
4-Cl-C6H4– 2a Et-
3f
43 (36)
a
Reaction conditions: 1 (0.2 mmol), 2 (2 equiv), Pd(OAc)2 (10 mol %), P(o-tol)3
(30 mol %), K2CO3 (20 mol %), toluene (1 mL), H2O (ca. 1 mmol), 115 °C, 16 h.
9
7
58
9e
b
Formally, 1,2-addition products of benzeneselenol or diphenyl diselenide to 2
10e,g
11g
12g
13c,g
14c,g
were also obtained as byproducts.
81 (70)
64 (61)
ND
Yields were determined by 1H NMR and values in parenthesis are isolated yield.
c
8
ND
7
Determined by 1H NMR.
d
ND
a
Reaction conditions: 1a (0.2 mmol), 2a (2 equiv), catalyst (10 mol %), toluene
(1 mL), 115 °C, 16 h.
b
Yields were determined by GC, and values in parenthesis are isolated yield.
The starting material 1a was recovered mainly.
Phosphine ligand (30 mol %), K2CO3 (20 mol %), and H2O (ca. 1 mmol) were
c
d
added.
e
The fragmentation products of 1a, for example, diphenyl diselenide, were
obtained.
f
DPPE (20 mol %) was used as phosphine.
Compound 2a (3 equiv) was employed.
g
Figure 2. ORTEP diagram of 3f (Z isomer).
Table 3 represents the scope and limitation of the palladium-
catalyzed [2+2+2] cycloaddition of various alkynyl selenides 1 with
2. Dimethyl acetylenedicarboxylate (2b) could be also employed
for this cycloaddition (entry 2). Several functionalities such as
methyl, pentyl, methoxy, chloro, and cyano substituents were tol-
erant of this reaction condition, forming the corresponding sele-
nides 4 in good yields (entries 3—7). Similar conditions can be
employed with 1d having aliphatic alkynyl group and 1j having tri-
methylsilyl group (entries 8 and 9). In contrast, the reaction of 1k
and 1l bearing ester or methoxymethyl groups provided the corre-
sponding selenides 4k and 4l, respectively, in lower yields (entries
10 and 11), and 1m having amino group did not afford 4m (entry
12). Alkynyl selenides having substituted aryl and aliphatic seleno
groups underwent the desired cycloaddition reactions, producing
4n, 4e, 4f, 4o, and 4p in good yields (entries 13—17). In addition,
this [2+2+2] cycloaddition could be employed with alkynyl sul-
fide 5a, affording the corresponding sulfide 6a successfully (Eq.
1). When the reaction was carried out using diphenylacetylene,
ethyl 2-butynolate, ethyl phenylpropiolate, 4-phenyl-3-butyn-2-
one, ethyl propiolate, and phenylacetylene, oligomerization of
alkynes and fragmentation of alkynyl selenide proceeded pre-
dominantly.
Figure 1. ORTEP diagram of 4a.
cases of other alkynes such as ethyl propiolate, phenylacetylene,
ethyl 2-butynorate, and ethyl phenylpropiolate, no desired product
was obtained, and instead, oligomerization of alkynes and frag-
mentation of alkynyl selenide took place.

3540
T. Mitamura, A. Ogawa / Tetrahedron Letters 51 (2010) 3538–3541
Table 3
Supplementary data
The palladium-catalyzed [2+2+2] cycloaddition of alkynyl selenidea,b
Entry
Alkynyl selenide
Product
Yieldc (%)
Supplementary data (general experimental procedure and char-
acterization date for alkynylselenation products, [2+2+2] cycload-
dition products, and new alkynyl selenides) associated with this
article can be found, in the online version, at doi:10.1016/
j.tetlet.2010.04.125.
R1
SePh
SePh
EtO2C
EtO2C
R1
CO2Et
CO2Et
1
1a
1a
1b
1g
1h
1i
R1 = H–
H–
4a
4a0
4b
4g
4h
4i
70
60
64
68
58
71
52
References and notes
2d
3
Me-
nPen-
MeO-
Cl-
1. For the review, see for example: (a) Nogueira, C. W.; Zeni, G.; Rocha, J. B. T.
Chem. Rev. 2004, 104, 6255; (b) Perin, G.; Lenardão, E. J.; Jacob, R. G.; Panatieri,
R. B. Chem. Rev. 2009, 109, 1277; (c) Organoselenium Chemistry; Wirth, T., Ed.;
Springer: Berlin, 2000; Vol. 208; (d) Ogawa, A. In Main Group Metals in Organic
Synthesis; Yamamoto, H., Oshima, K., Eds.; Wiley-VCH: Weinheim, 2004; Vol. 2,
p 813.
2. For recent reviews, see: (a) Ogawa, A. J. Organomet. Chem. 2000, 611, 463; (b)
Kondo, T.; Mitsudo, T. Chem. Rev. 2000, 100, 3205; (c) Beletskaya, I.; Moberg, C.
Chem. Rev. 2006, 106, 2320; (d) Kuniyasu, H.; Kambe, N. Chem. Lett. 2006, 35,
1320; (e) Kuniyasu, H.; Kambe, N. J. Synth. Org. Chem. Jpn. 2009, 67, 701; (f)
Kuniyasu, H. In Catalytic Heterofunctionalization; Togni, A., Grüzmacher, H.,
Eds.; Wiley-VCH: Weinheim, 2001; p 217.
3. For the transition-metal-catalyzed activation of Ch–Ch bond, see: (a) Kuniyasu,
H.; Ogawa, A.; Miyazaki, S.; Ryu, I.; Kambe, N.; Sonoda, N. J. Am. Chem. Soc.
1991, 113, 9796; (b) Kondo, T.; Uenoyama, S.; Fujita, K.; Mitsudo, T. J. Am. Chem.
Soc. 1999, 121, 482; (c) Nishiyama, Y.; Kawamatsu, H.; Sonoda, N. J. Org. Chem.
2005, 70, 2551; (d) Ananikov, V. P.; Orlov, N. V.; Kabeshov, M. A.; Beletskaya, I.
P.; Starikova, Z. A. Organometallics 2008, 27, 4056.
4. For the transition-metal-catalyzed activation of Ch–H bond, see: (a) Ogawa, A.;
Ikeda, T.; Kimura, K.; Hirao, T. J. Am. Chem. Soc. 1999, 121, 5108; (b) Han, L.-B.;
Zhang, C.; Yazawa, H.; Shimada, S. J. Am. Chem. Soc. 2004, 126, 5080; (c) Cao, C.;
Fraser, L. R.; Love, J. A. J. Am. Chem. Soc. 2005, 127, 17614; (d) Kamiya, I.;
Nishinaka, E.; Ogawa, A. J. Org. Chem. 2005, 70, 696; (e) Ananikov, V. P.; Orlov,
N. V.; Beletskaya, I. P.; Khrustalev, V. N.; Antipin, M. Y.; Timofeeva, T. V. J. Am.
Chem. Soc. 2007, 129, 7252.
5. For the transition-metal-catalyzed activation of Ch–E bond, see: (a) Ishiyama,
T.; Nishijima, K.; Miyaura, N.; Suzuki, A. J. Am. Chem. Soc. 1993, 115, 7219; (b)
Han, L.-B.; Tanaka, M. J. Am. Chem. Soc. 1998, 120, 8249; (c) Han, L.-B.; Tanaka,
M. Chem. Lett. 1999, 28, 863; (d) Nishiyama, Y.; Kawamatsu, H.; Funato, S.;
Tokunaga, K.; Sonoda, N. J. Org. Chem. 2003, 68, 3599.
6. For the transition-metal-catalyzed activation of Ch–C bond, see: (a) Hirai, T.;
Kuniyasu, H.; Kato, T.; Kurata, Y.; Kambe, N. Org. Lett. 2003, 5, 3871; (b)
Toyofuku, M.; Fujiwara, S.; Shin-ike, T.; Kuniyasu, H.; Kambe, N. J. Am. Chem.
Soc. 2005, 127, 9706; (c) Kuniyasu, H.; Kato, T.; Inoue, M.; Terao, J.; Kambe, N. J.
Organomet. Chem. 2006, 691, 1873; (d) Yamashita, K.; Takeda, H.; Kashiwabara,
T.; Hua, R.; Shimada, S.; Tanaka, M. Tetrahedron Lett. 2007, 48, 6655; (e)
Toyofuku, M.; Fujiwara, S.; Shin-ike, T.; Kuniyasu, H.; Kambe, N. J. Am. Chem.
Soc. 2008, 130, 10504; (f) Toyofuku, M.; Murase, E.; Fujiwara, S.; Shin-ike, T.;
Kuniyasu, H.; Kambe, N. Org. Lett. 2008, 10, 3957; (g) Arisawa, M.; Suwa, K.;
Yamaguchi, M. Org. Lett. 2009, 11, 625.
4
5
6
7
1c
NC-
4c
SePh
SePh
R2
EtO2C
EtO2C
R2
CO2Et
CO2Et
8
9
1d
1j
R2
TMS-
=
nBu-
4d
4j
4k
41
4m
54
42
26
24
ND
10e
11e
12e
1k
11
1m
EtO2C–
MeOCH2–
Me2NCH2–
SeR3
SeR3
EtO2C
EtO2C
Ph
Ph
CO2Et
CO2Et
13
14
15
16
17
1n
1e
1f
1o
1p
R3 = 4-MeO-C6H4–
4-Me-C6H4–
4-CI-C6H4–
4-F-C6H4–
Et-
4n
4e
4f
4o
4p
72
63
60
59
85
a
Reaction conditions: 1 (0.2 mmol), 2a (3 equiv), PdCl2(PPh3)2 (10 mol %), tolu-
ene (1 mL), 115 °C, 16 h.
The corresponding diselenide and/or monoselenide were obtained as
byproducts.
b
c
Isolated yield.
d
Dimethyl acetylenedicarboxylate (2b, 3 equiv) was used in place of 2a.
Instead of the desired reaction, [2+2+2] cycloaddition of three molecules of 2a
e
took place predominantly, and the starting material 1 was recovered unchanged.
7. For the transition-metal-catalyzed activation of C–S bond, see: (a) Kuniyasu,
H.; Ohtaka, A.; Nakazono, T.; Kinomoto, M.; Kurosawa, H. J. Am. Chem. Soc.
2000, 122, 2375; (b) Hua, R.; Takeda, H.; Onozawa, S.; Abe, Y.; Tanaka, M. J. Am.
Chem. Soc. 2001, 123, 2899; (c) Kamiya, I.; Kawakami, J.; Yano, S.; Nomoto, A.;
Ogawa, A. Organometallics 2006, 25, 3562; (d) Hua, R.; Takeda, H.; Onozawa, S.;
Abe, Y.; Tanaka, M. Org. Lett. 2007, 9, 263; (e) Yamashita, F.; Kuniyasu, H.;
Terao, J.; Kambe, N. Org. Lett. 2008, 10, 101; (f) Minami, Y.; Kuniyasu, H.;
Kambe, N. Org. Lett. 2008, 10, 2469; (g) Arisawa, M.; Tagami, Y.; Yamaguchi, M.
Tetrahedron Lett. 2008, 49, 1593; For the insertion of alkynes into an S–Pt Bond,
see: (h) Kuniyasu, H.; Takekawa, K.; Yamashita, F.; Miyafuji, K.; Asano, S.; Takai,
Y.; Ohtaka, A.; Tanaka, A.; Sugoh, K.; Kurosawa, H.; Kambe, N. Organometallics
2008, 27, 4788.
8. For the synthesis transition-metal complex of alkynyl selenide, see: (a) Hill, A.
F.; Hulkes, A. G.; White, A. J. P.; Williams, D. J. Organometallics 2000, 19, 371; (b)
Taher, D.; Pritzkow, H.; Walfort, B.; Lang, H. J. Organomet. Chem. 2006, 691, 793.
9. For the transition-metal catalyzed reaction of alkynyl selenide used as
acetylene, see: (a) Huang, X.; Sun, A. J. Org. Chem. 2000, 65, 6561; (b)
Koketsu, M.; Yang, H. O.; Kim, Y. M.; Ichihashi, M.; Ishihara, H. Org. Lett. 2001, 3,
1705; (c) Kim, H.; Lee, C. J. Am. Chem. Soc. 2005, 127, 10180; (d) Cai, M.; Wang,
Y.; Hao, W. Eur. J. Org. Chem. 2008, 2983.
SPh
PdCl2(PPh3)2 (10 mol%)
toluene, 115oC, 16 h
EtO2C
EtO2C
Ph
SPh
+
2a
ð1Þ
Ph
CO2Et
CO2Et
6a, 40%
5a
3 equiv
In summary, we have developed a new palladium-catalyzed
reaction of alkynyl selenides with acetylenedicarboxylates. Alky-
nylselenation of acetylenedicarboxylates with alkynyl selenides
has been attained by use of Pd(OAc)2/P(o-Tol)3/K2CO3/H2O-cata-
lytic system, leading to alkynylvinyl selenides. In contrast, the
treatment of alkynyl selenides with PdCl2(PPh3)2 catalyst in the
presence of acetylenedicarboxylates, has been found to afford
multisubstituted aryl selenides selectively via the [2+2+2] cycload-
dition reaction.
10. Alkynylvinyl selenides can be converted into the corresponding selenophene
derivatives, see: (a) Takimiya, K.; Kunugi, Y.; Konda, Y.; Ebata, H.; Toyoshima,
Y.; Otsubo, T. J. Am. Chem. Soc. 2006, 128, 3044; (b) Kesharwani, T.; Worlikar, S.
A.; Larock, R. C. J. Org. Chem. 2006, 71, 2307; (c) Alves, D.; Luchese, C.; Nogueira,
C. W.; Zeni, G. J. Org. Chem. 2007, 72, 6726; (d) Stein, A. L.; Alves, D.; da Rocha, J.
T.; Nogueira, C. W.; Zeni, G. Org. Lett. 2009, 10, 4983.
Acknowledgments
This work is supported by Grant-in-Aid for Scientific Research
(B, 19350095), from the Ministry of Education, Culture, Sports, Sci-
ence and Technology, Japan, and Kyoto-Advanced Nanotechnology
Network. T.M. also thanks Japan Society for the Promotion of Sci-
ence (JSPS) for the Research Fellowship for Young Scientists.
11.
A plausible pathway for the palladium-catalyzed alkynylselenation may
include the following steps (Eq. 2): (1) the oxidative addition of 1 into Pd
complex to form palladium selenide species A; (2) the sequential
selenopalladation or alkynylpalladation of 2; (3) the reductive elimination of
alkynylvinyl selenide 3 with regeneration of the Pd catalyst.

T. Mitamura, A. Ogawa / Tetrahedron Letters 51 (2010) 3538–3541
3541
R1
PdLn
14. The palladium-catalyzed [2+2+2] cycloaddition of alkynyl selenides may
proceed via the following pathways (Eq. 3): path involves
2
R2Se
A
1
Pd
Ln
A
chloropalladation of 1, sequential insertion of two molecules of 2, and
intramolecular cyclization to form 4 with recovery of the Pd catalyst; path B
includes chloropalladation of 2, insertion of
1 and 2, and intramolecular
cyclization to give 4 with elimination of the Pd catalyst.
ð2Þ
CO2R3
R1
CO2R3
R3O2C
R3O2C
R2Se
or
Pd
Ln
3
R1O2C
CO2R1
R2Se
PdLn
R1
_ PdLn
R1O2C
1
2
Cl
PdLn
SeR2
B
C
PdLn
Cl
LnPdCl2
R1
R1O2C
Path A
D
R2Se
R1
12. There are a few reports for the synthesis of multisubstituted aryl selenides, see:
(a) Osuka, A.; Ohmasa, N.; Suzuki, H. Synthesis 1982, 857; (b) MacNicol, D. D.;
Mallison, P. R.; Murphy, A.; Sym, G. J. Tetrahedron Lett. 1982, 23, 4131; (c)
Engman, L.; Hellberg, J. S. E. J. Organomet. Chem. 1985, 296, 357; (d) Kumar, N.;
Milton, M. D.; Singh, J. D. Tetrahedron Lett. 2004, 45, 6611; (e) Shi, M.; Lu, J.-M. J.
Org. Chem. 2006, 71, 1920.
13. PdCl2-catalyzed [2+2+2] cycloaddition reactions of acetylenes proceed via
chloropalladation of acetylenes, see: Metal Catalyzed Cascade Reactions; Müller,
T. J. J., Ed.; Springer: Berlin, 2006; Vol. 19.
E
4
ð3Þ
Path B
2
Cl
PdLn
CO2R3
R3O2C
1 and 2
F