Highly regioselective palladium-catalyzed double hydroselenation of terminal alkynes with benzeneselenol in the presence of acetic acid

Article abstract of DOI:10.1246/cl.130641

Palladium diacetate (Pd(OAc)₂), in the presence of acetic acid, is found to exhibit excellent catalytic activity for the double hydroselenation of terminal alkynes with benzeneselenol to yield the corresponding diselenoketals regioselectively.

Full text of DOI:10.1246/cl.130641

doi:10.1246/cl.130641
Published on the web August 10, 2013
1383
Highly Regioselective Palladium-catalyzed Double Hydroselenation
of Terminal Alkynes with Benzeneselenol in the Presence of Acetic Acid
Takuma Ikeda, Taichi Tamai, Masayuki Daitou, Yoshiaki Minamida, Takenori Mitamura,
Hiroki Kusano, Akihiro Nomoto, and Akiya Ogawa*
Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University,
1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 599-8531
(Received July 9, 2013; CL-130641; E-mail: ogawa@chem.osakafu-u.ac.jp)
Palladium diacetate (Pd(OAc)2), in the presence of acetic
acid, is found to exhibit excellent catalytic activity for the
double hydroselenation of terminal alkynes with benzeneselenol
to yield the corresponding diselenoketals regioselectively.
dithioketals regioselectively.4 In the case of the double hydro-
selenation of alkynes with selenols, the use of excess amounts
of selenols compared with alkynes is presumed to cause metal
selenide aggregation efficiently. Therefore, catalytic double
hydroselenation is more difficult to achieve than the correspond-
ing double thiolation. To achieve the catalytic double addition
of selenols to alkynes, the reaction conditions for the desired
double hydroselenation of alkynes using excess amounts of
selenols have been investigated in detail.
The palladium-catalyzed double hydroselenation of
1-octyne with benzeneselenol was conducted under several
reaction conditions, and the results are shown in Table 1. As the
previously reported double hydrothiolation of terminal alkynes
with thiols was conducted using Pd(OAc)2 as a catalyst, THF
as solvent, and H2O as an additive, similar conditions were
employed for the double hydroselenation (Entry 1). When the
Selenols are representative parent selenium molecules for
the synthesis of various organoselenium compounds via nucle-
ophilic substitution, addition, and oxidation.1 In particular,
addition to carbon-carbon unsaturated bonds is one of the most
important methods for the synthesis of alkyl, vinyl, and allyl
selenides; ionic addition and radical addition are usually
employed for this purpose. Although the transition-metal-
catalyzed addition of heteroatom compounds to alkynes,
alkenes, and allenes is applicable to a series of heteroatom
compounds, few examples of such reactions have been reported
for organoselenium compounds.2 This is likely attributable to
the widespread belief that organoselenium compounds are
representative catalyst poisons. Indeed, compared with organo-
sulfur compounds, the transition-metal-catalyzed addition of
organoselenium compounds, especially selenols, is a class of
reactions that is difficult to achieve efficiently. This inefficiency
is probably caused by the formation of a selenium-bridge
between the metal atoms, leading to the formation of metal
selenide aggregates that are not soluble in conventional organic
solvents. Recently, however, our study group and others have
developed a series of transition-metal-catalyzed addition of
selenols to alkynes and allenes.3 For example, Pd(OAc)2 with
pyridine efficiently catalyzes the Markovnikov addition of
selenols to terminal alkynes,3a and [PdCl2(PPh3)2]-catalyzed
hydroselenation selectively proceeds via the Markovnikov
addition and double bond isomerization (Scheme 1).3f
Table 1. Palladium-catalyzed double hydroselenation of
1-octynea
catalyst (5 mol%)
additive (1 equiv)
PhSe SePh
SePh
nPen
nHex
PhSeH
nHex
+
+
solvent (0.05 mL)
40 oC, 20 h
1a
2
5a
4a
Yield/%b
Entry Catalyst
Additive Solvent
5a
4ac
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(OAc)2
Pd(OAc)2
Pd(OAc)2
H2O
AcOH
PhOH
MeOH THF
HCld
THF
THF
THF
57
(73)
73
31
67
0
20
0
6
6
16
0
0
12
7
12
0
8
THF
THF
H2SO4
p-TsOH THF
The success of these palladium-catalyzed addition reactions
of selenols to alkynes is based on controlling the suppression
of palladium selenide aggregates via coordination with excess
amounts of alkynes. Very recently, we have developed the
palladium-catalyzed double hydrothiolation of terminal alkynes
with two equivalents of thiols to afford the corresponding
0
AcOH
AcOH
AcOH
AcOH
AcOH
AcOH
AcOH
acetone
49
53
55
60
53
67
49
7
EtOH
MeCN
CHCl3
benzene
Et2O
1,4-dioxane
THF
THF
10 Pd(OAc)2
11 Pd(OAc)2
12 Pd(OAc)2
13 Pd(OAc)2
14 Pd(OAc)2
15 [PdCl2(PPh3)2] AcOH
16 [PdCl2(PhCN)2] AcOH
17 [Pd2(dba)2]
18 [Pd(PPh3)4]
19 [Pt(PPh3)4]
7
8
SePh
cat. Pd(OAc)2, pyridine
cat. [PdCl2(PPh3)2]
24
15
5
23
19
R
R
R
0
56
7
3
PhSeH
+
AcOH
AcOH
AcOH
THF
THF
THF
SePh
1
2
0
4
a1-Octyne (0.1 mmol), PhSeH (0.2 mmol). bDetermined by
1H NMR. Value in parenthesis is isolated yield. cObtained as a
Scheme 1. Regioselective hydroselenation of terminal al-
kynes.
d
E/Z mixture (ca. 1:1). Aqueous HCl (12 M) was used.
Chem. Lett. 2013, 42, 1383-1385
© 2013 The Chemical Society of Japan
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1384
Table 2. Palladium-catalyzed double hydroselenation of alky-
Pd(OAc)2-catalyzed reaction of 1-octyne (1a, 0.1 mmol) with
two equivalents of benzeneselenol (2) was conducted in the
presence of H2O (1 equiv) in THF at 40 °C for 20 h, the double
hydroselenation of 1-octyne proceeded regioselectively to afford
the desired diselenoketal 5a in 57% yield along with vinyl
selenide 4a (which was formed by the sequential Markovnikov
addition and double bond isomerization). Changing the additive
from H2O to AcOH led to the selective formation of the desired
3a (Entry 2). PhOH and HCl were also effective for double
hydroselenation, but only small amounts of 4a were formed
concomitantly (Entries 3 and 5). Strong acids such as H2SO4 and
p-TsOH inhibited hydroselenation, probably because the catalyst
was decomposed (Entries 6 and 7). Next, we examined double
hydroselenation using AcOH as an additive by varying the
solvents (Entries 8-14). Double hydroselenation proceeded in a
variety of solvents such as nonpolar-aprotic solvent (benzene
[empirical solvent parameter ETN: 0.111], Et2O [0.117], 1,4-
dioxane [0.164], THF [0.207], CHCl3 [0.259]), polar-aprotic
solvent (acetone [0.355], MeCN [0.460]), and protic solvent
(EtOH [0.654]).5 Among these, THF showed the best results.
Therefore, we next focused on double hydroselenation using
AcOH as an additive and THF as a solvent in the presence of
several transition-metal catalysts (Entries 15-19). Double hydro-
selenation was found to be very sensitive to the catalyst used.
Palladium chloride derivatives were ineffective for double
hydroselenation, although monohydroselenation proceeded to
afford vinyl selenide 4a in low yields. [Pd2(dba)2] showed
catalytic activity for double selenation. However, zero-valent
palladium and platinum complexes were ineffective.
nesa
Pd(OAc)2 (5 mol%)
AcOH (1 equiv)
PhSe SePh
PhSeH
R
+
R
THF, 40 oC, 20 h
Yield/%b
1
2
5
Entry
Alkyne
nHex
PhSe SePh
nHex
1a
5a
1
2
80 (73)
59
PhSe SePh
PhSe SePh
PhSe SePh
HO2C
1b
1c
5b
HO2C
3
4
5
Cl
5c (87)
Cl
MeO
MeO
1d
1e
5d (34)
5e 32
PhSe SePh
Ph
Ph
PhSe SePh
6c
1f
5f
73
Fe
Fe
b
aAlkyne (0.5 mmol), PhSeH (1.0 mmol), THF (2.0 M). Deter-
mined by 1H NMR. Values in parenthesis are isolated yield. cIn
the absence of AcOH, Pd(OAc)2 (2 mol%), THF, 40 °C, 16 h.
Table 2 shows the results of the palladium-catalyzed double
hydroselenation of terminal alkynes with benzeneselenol under
the optimized reaction conditions (Table 1, Entry 2).6 The
carboxylic group and chloro group tolerate double hydrosele-
nation, and the corresponding diselenoketals 5b and 5c were
obtained in moderate to good yields (Entries 2 and 3). Propargyl
ether 1d also afforded the corresponding diselenoketal 5d in
fair yield (Entry 4). Aromatic alkynes such as phenylacetylene
regioselectively afforded diselenoketal 5e in moderate yield
(Entry 5). The formed diselenoketals 5 are synthetically useful
because they can be easily transferred to ¡-selenoanion species
upon treatment with butyllithium.1 In the absence of AcOH, the
yield of the double hydroselenation products decreased. For
example, the double hydroselenation of 1c afforded 61% of 5c,
whereas only a trace amount of diselenoketal 5d was obtained.
Moreover, the Pd(OAc)2-catalyzed reaction of 1b in the absence
of AcOH yielded 5% of 5b along with its cyclization product
(48%, £-(phenylseleno)-£-valerolactone) formed via intramo-
lecular cyclization with elimination of PhSeH. The present
double hydroselenation can be applied to alkyne 1f having a
ferrocenyl group. The Pd(OAc)2-catalyzed reactions of 1f with
PhSeH in the presence and absence of AcOH afforded the
corresponding diselenoketal 5f in 33% and 73% yields,
respectively without any decomposition of the ferrocenyl group
(Entry 6). The structure of 5f was unambiguously determined by
X-ray crystal analysis (see Supporting Information). In general,
aromatic diselenoketals (ArC(SePh)2R) are known to be unstable
in the presence of selenols and undergo reduction to give the
corresponding selenides (ArCH(SePh)R).7,8 Accordingly, in the
case of 1f, the presence of AcOH accelerates the reduction to
FcCH(SePh)CH3, resulting in decrease in the yield of 5f.
Table 3. Hydroselenation of vinyl selenide 3a with PhSeHa
catalyst (5 mol%)
additive (1 equiv)
PhSe SePh
SePh
PhSeH
nHex
+
THF (2 M), 40 oC
nHex
3a
2
5a
Entry
Catalyst
Additive
Time/h
Yield/%b
1
2
3
4
5
6
none
none
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
none
AcOH
none
none
AcOH
AcOH
20
20
10
20
10
20
NRc
NRc
45
72
50
79
aVinyl selenide 3a (0.2 mmol), PhSeH (0.2 mmol). bDeter-
1
c
mined by H NMR. No reaction.
To obtain further information about the mechanistic path-
ways of the double hydroselenation reaction, we examined the
reaction of vinyl selenide 3a, as a monohydroselenation product,
with PhSeH under various reaction conditions; the results of the
same are summarized in Table 3.
In the absence of palladium catalyst, the addition of PhSeH
to 3a did not proceed even in the presence of acetic acid (Entries
1 and 2). When Pd(OAc)2 was used in the absence of AcOH,
hydroselenation of 3a gradually proceeded to afford diseleno-
ketal 5a in 45% yield for 10 h and in 72% yield for 20 h (Entries
3 and 4, respectively). The use of AcOH in the presence of
Pd(OAc)2 somewhat accelerated the hydroselenation of 3a
(Entries 5 and 6). These results clearly indicate that the second
hydroselenation (i.e., hydroselenation of 3a) requires a palla-
Chem. Lett. 2013, 42, 1383-1385
© 2013 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/

1385
Pd(OAc)2
2PhSeH
+
Hirao, Tetrahedron Lett. 1998, 39, 5213. c) A. Ogawa,
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D. A. Malyshev, I. P. Beletskaya, G. G. Aleksandrov, I. L.
Eremenko, J. Organomet. Chem. 2003, 679, 162. e) V. P.
Ananikov, M. A. Kabeshov, I. P. Beletskaya, G. G.
Aleksandrov, I. L. Eremenko, J. Organomet. Chem. 2003,
687, 451. f) I. Kamiya, E. Nishinaka, A. Ogawa, Tetra-
hedron Lett. 2005, 46, 3649. g) V. P. Ananikov, N. V. Orlov,
I. P. Beletskaya, Organometallics 2007, 26, 740. h) V. P.
Ananikov, K. A. Gayduk, I. P. Beletskaya, V. N. Khrustalev,
M. Y. Antipin, Chem.®Eur. J. 2008, 14, 2420. i) V. P.
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M. Y. Antipin, Eur. J. Inorg. Chem. 2009, 1149. j) T. Ozaki,
M. Kotani, H. Kusano, A. Nomoto, A. Ogawa, J. Organo-
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S. Atobe, A. Nomoto, M. Sonoda, A. Ogawa, Organo-
metallics 2011, 30, 6766.
2
-2AcOH
aggregation
SePh
[Pd(SePh)2]n
Pd(SePh)2
A
catalyst poisoning
R
R
1
3
cat. Pd PhSeH
PhSe SePh
PhSeH
(or AcOH)
SePh
Pd(SePh)
R
R
B
5
Scheme 2. A possible pathway for double hydroselenation of
terminal alkynes.
dium catalyst; AcOH is not essential for this process. Accord-
ingly, the first hydroselenation (i.e., hydroselenation of terminal
alkyne) requires both Pd(OAc)2 and AcOH when excess
amounts of PhSeH relative to the alkyne are employed.
4
5
T. Mitamura, M. Daitou, A. Nomoto, A. Ogawa, Bull. Chem.
Soc. Jpn. 2011, 84, 413.
a) C. Reichardt, Solvents and Solvent Effects in Organic
Chemistry, VCH, Weinheim, 1988, Chap. 7 and Appendix,
pp. 339-410. b) C. Reichardt, Chem. Rev. 1994, 94, 2319.
c) C. Reichardt, Solvents and Solvent Effects in Organic
Chemistry, Wiley-VCH, Weinheim, 2003, Chap. 7 and
Appendix, pp. 389-475. doi:10.1002/3527601791.
A possible pathway for the present palladium-catalyzed
double hydroselenation of terminal alkynes is shown in
Scheme 2. Palladium diacetate undergoes a ligand-exchange
reaction with two equivalents of benzeneselenol to afford
palladium diselenide A.9 Then, the selenopalladation of the
terminal alkynes occurs regioselectively to form vinylpalladium
intermediates B, the protonolysis of which with benzeneselenol
(and/or acetic acid) affords vinyl selenides 3 with the recovery
of palladium selenides A. The formed vinyl selenides 3 undergo
further addition of benzeneselenol in the presence of palladium
catalyst to afford diselenoketals 5. If the palladium selenide A
aggregates to form a polymeric structure, it loses its catalytic
activity. Therefore, AcOH may act not only as a proton source
for B but also as an inhibitor for the aggregation of A.
In summary, we have developed a highly regioselective
double hydroselenation of terminal alkynes with two equivalents
of benzeneselenol. The mechanistic details of the double
hydroselenation and its application to the development of the
transition-metal-catalyzed reactions of other selenium com-
pounds are now under investigation.
6
General procedure: In a two-necked 10-mL flask with a
magnetic stirring bar under N2 atmosphere were placed
Pd(OAc)2 (0.025 mmol), freshly distilled THF (0.25 mL),
1-octyne (0.5 mmol), benzeneselenol (0.2 mmol), and acetic
acid (0.1 mmol) in that order. The reaction was conducted at
40 °C for 20 h, and then the resulting solution was filtered
through Celite with ethyl acetate as an eluent. Concentration
in vacuo, and purification by preparative TLC (silica gel,
eluent: hexane) provided 2,2-bis(phenylselanyl)octane (5a)
[103971-60-4]: Slight yellow oil; 1H NMR (400 MHz,
CDCl3): ¤ 0.88 (t, 3H, J = 8.0 Hz), 1.23-1.30 (m, 6H),
1.37 (quint, 5H), 1.75-1.79 (m, 2H), 7.22-7.38 (m, 6H),
7.66-7.68 (m, 4H); 13C NMR (100 MHz, CDCl3): ¤ 14.0,
22.5, 24.7, 28.1, 29.2, 31.7, 41.5, 64.2, 128.4, 128.9, 132.1,
136.8; 77Se NMR (75 MHz, CDCl3): ¤ 508.1; IR (NaCl):
3055, 2955, 2928, 2855, 1577, 1474, 1435, 1369, 1300,
1180, 1119, 1049, 1022, 999, 914, 740, 690 cm¹1. The
selected spectral and analytical data for the double hydro-
selenation products, 5b, 5c, 5d, and 5f are shown in
Supporting Information. Supporting Information is available
electronically on the CSJ-Journal Web site, http://www.
csj.jp/journals/chem-lett/index.html.
This work was supported in part by a Grant-in-Aid for
Scientific Research for JSPS Fellows (No. 2510638). T.T. thanks
the Japan Society for the Promotion of Science for the Research
Fellowship for Young Scientists.
This paper is dedicated to Professor Teruaki
Mukaiyama in celebration of the 40th anniversary of the
Mukaiyama aldol reaction.
7
8
M. Clarembeau, A. Cravador, W. Dumont, L. Hevesi, A.
Krief, J. Lucchetti, D. Van Ende, Tetrahedron 1985, 41,
4793.
References and Notes
The formation of reduction products, selenides, was con-
firmed by NMR spectroscopy. For example, spectral data
1
2
A. Nomoto, A. Ogawa, in The Chemistry of Organic
Selenium and Tellurium Compounds, ed. by Z. Rappoport,
Wiley, Chichester, 2012, Vol. 3, Chap. 11, pp. 623-688.
A. Ogawa, in Hydrofunctionalization in Topics in Organo-
metallic Chemistry, ed. by V. P. Ananikov, M. Tanaka,
Springer, Berlin, 2012, Vol. 43, pp. 325¹360. doi:10.1007/
3418_2011_19.
1
of reduction product of 5e are shown in below. H NMR
(400 MHz, CDCl3): ¤ 1.75 (t, 3H, J = 6.9 Hz), 4.56 (q,
J = 6.9 Hz, 1H), 7.17-7.29 (m, 8H), 7.42-7.45 (m, 2H);
13C NMR (100 MHz, CDCl3): ¤ 22.3, 42.6, 127.0, 127.3,
127.9, 128.4, 128.9, 129.9, 135.5, 143.7.
In our previous paper, we described that the reaction of
Pd(OAc)2 with 2 equivalents of PhSeH led to the formation
of palladium selenide complex and AcOH: see ref 3b.
9
3
a) H. Kuniyasu, A. Ogawa, K.-I. Sato, I. Ryu, N. Sonoda,
Tetrahedron Lett. 1992, 33, 5525. b) A. Ogawa, A. Kudo, T.
Chem. Lett. 2013, 42, 1383-1385
© 2013 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/