A highly regioselective cyanothiolation of alkynes via oxidative addition of thiocyanates to tetrakis(triphenylphosphine)palladium(0) catalyst

Article abstract of DOI:10.1021/om0600442

Tetrakis(triphenylphosphine)palladium(0) catalyzes the highly regioselective addition of phenyl thiocyanate (PhSCN) to terminal alkynes, which attains the simultaneous introduction of thio and cyano groups to the internal and terminal positions of alkynes, respectively. This reaction may proceed via the oxidative addition of PhSCN to Pd(PPh₃)₄, which forms Pd(SPh)(CN)(PPh₃)₂ as the key intermediate.

Full text of DOI:10.1021/om0600442

3
562
Organometallics 2006, 25, 3562-3564
A Highly Regioselective Cyanothiolation of Alkynes via Oxidative
Addition of Thiocyanates to
Tetrakis(triphenylphosphine)palladium(0) Catalyst
†
‡
†
,§
Ikuyo Kamiya, Jun-ichi Kawakami, Shigenobu Yano, Akihiro Nomoto,* and
,
§
Akiya Ogawa*
DiVision of Material Science, Nara Women’s UniVersity, Kitauoyanishi-machi, Nara 630-8506, Japan,
Takeda Pharmaceutical Company Limited, 2-17-85 Jusohonmachi, Yodogawa-ku, Osaka 532-0024, Japan,
and Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture UniVersity, 1-1
Gakuen-cho, Nakaku, Sakai, Osaka 599-8531, Japan
ReceiVed January 17, 2006
Summary: Tetrakis(triphenylphosphine)palladium(0) catalyzes
the highly regioselectiVe addition of phenyl thiocyanate (PhSCN)
to terminal alkynes, which attains the simultaneous introduction
of thio and cyano groups to the internal and terminal positions
of alkynes, respectiVely. This reaction may proceed Via the
oxidatiVe addition of PhSCN to Pd(PPh3)4, which forms Pd-
the first example of transition-metal-catalyzed cyanothiolation
of terminal alkynes with thiocyanates, which attains simulta-
neous introduction of both sulfur and cyano groups into carbon-
carbon triple bonds with an excellent regioselectivity.
Table 1 indicates the results of catalytic cyanothiolation using
several transition metal complexes. Among the complexes
examined (entries 1-9), only zerovalent palladium complexes
such as Pd(PPh3)4 indicated a catalytic activity toward the
desired cyanothiolation of 1-octyne, and interestingly the
corresponding 3-phenylthionon-2-enenitrile was obtained with
an excellent regioselectivity (entry 9). To optimize the reaction
(SPh)(CN)(PPh3)2 as the key intermediate.
Transition-metal-catalyzed reactions of organic silicon, boron,
and tin compounds provide very useful methods for selective
introductions of heterofunctions as well as carbon-carbon bond
forming reactions based on the characteristic features of these
1
conditions, the Pd(PPh ) -catalyzed cyanothiolation of 1-octyne
heteroatoms. In contrast, the transition-metal-catalyzed reactions
3 4
was examined under several reaction conditions (entries 10-
of group 16 heteroatom compounds have been largely unex-
plored, partly because these compounds are believed to be
14). The reaction is greatly influenced by the solvent employed.
2
The reaction in CH CN resulted in the low yield of the
catalyst poisons for transition-metal-catalyzed reactions. In
991, we disclosed an efficient transition-metal-catalyzed ad-
3
cyanothiolation product (entry 14), whereas the reactions in THF
1
3
(entry 13) or benzene (entry 11) afforded higher yields.
dition of organic disulfides to alkynes, and after this report,
several synthetically useful transition-metal-catalyzed addition
reactions of organosulfur compounds to unsaturated compounds
7
Consequently, upon heating at 120 °C in benzene, the desired
product is obtained in good yield with an excellent regioselec-
tivity (entry 11).
were developed by us and other groups.4 Herein we report
-6
*
To whom correspondence should be addressed. E-mail:
(5) (a) Kuniyasu, H.; Ogawa, A.; Sato, K.; Ryu, I.; Kambe, N.; Sonoda,
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K.; Miyaura, N.; Suzuki, A. J. Am. Chem. Soc. 1993, 115, 7219-7225. (c)
B a¨ ckvall, J. E.; Erickson, A. J. Org. Chem. 1994, 59, 5850-5851. (d)
Ogawa, A.; Kawakami, J.; Sonoda, N.; Hirao, T. J. Org. Chem. 1996, 61,
4161-4163. (e) Kuniyasu, H.; Sugoh, K.; Su, M. S.; Kurosawa, H. J. Am.
Chem. Soc. 1997, 119, 4669-4677. (f) Gareau, Y.; Orellana, A. Synlett
1997, 803-804. (g) Han, L.-B.; Tanaka, M. J. Am. Chem. Soc. 1998, 120,
8249-8250. (h) Kondo, T.; Uenoyama, S.; Fujita, K.; Mitsudo, T. J. Am.
Chem. Soc. 1999, 121, 482-483. (i) Ogawa, A.; Ikeda, T.; Kimura, K.;
Hirao, T. J. Am. Chem. Soc. 1999, 121, 5108-5109. (j) Han, L.-B.; Tanaka,
M. Chem. Lett. 1999, 863-864. (k) Kondo, T.; Morisaki, Y.; Uenoyama,
S.; Wada, K.; Mitsudo, T. J. Am. Chem. Soc. 1999, 121, 8657-8658. (l)
Xiao, W.-J.; Alper, H. J. Org. Chem. 1999, 94, 9646-9652. (m) Arisawa,
M.; Yamaguchi, M. Org. Lett. 2001, 3, 763-764. (n) Arisawa, M.; Kozuki,
Y.; Yamaguchi, M. J. Org. Chem. 2003, 68, 8964-8967. (o) Ananikov, V.
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2001.
ogawa@chem.osakafu-u.ac.jp.
†
Nara Women’s University.
Takeda Pharmaceutical Company Limited.
Osaka Prefecture University.
‡
§
(
1) (a) Miura, K.; Hosomi, A. In Main Group Metals in Organic
Synthesis; Yamamoto, H., Oshima, K., Eds.; Wiley-VCH: Weinheim, 2004;
Vol. 2, Chapter 10. (b) Orita, A.; Otera, J. In Main Group Metals in Organic
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1
. (d) Tang, J.; Hayashi, T. In Catalytic Heterofunctionalization; Togni,
A., Gr u¨ zmacher, H., Eds.; Wiley-VCH: Weinheim, 2001; Chapter 3. (e)
Davies, A. G. Organotin Chemistry; VCH: Weinheim, 1997. (f) Ojima, I.
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Wiley-Interscience: Chichester, 1989.
(
2) Hegedus, L. L.; McCabe, R. W. Catalyst Poisoning; Marcel Dek-
ker: New York, 1984.
3) Kuniyasu, H.; Ogawa, A.; Miyazaki, S.; Ryu, I.; Kambe, N.; Sonoda,
N. J. Am. Chem. Soc. 1991, 113, 9796-9803.
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(
(
Synthesis; Yamamoto, H., Oshima, K., Eds.; Wiley-VCH: Weinheim, 2004;
Vol. 2, Chapter 15. (b) Alonso, F.; Beletskaya, I. P.; Yus, M. Chem. ReV.
004, 104, 3079-3159. (c) El Ali, B.; Alper, H. In Handbook of
2
Organopalladium Chemistry for Organic Synthesis; Negishi, E., Ed.;
Wiley: New York, 2002; Chapter VI.2.1.1.2. (d) Ogawa, A. In Handbook
of Organopalladium Chemistry for Organic Synthesis; Negishi, E., Ed.;
Wiley: New York, 2002; Chapter VII.6. (e) Kuniyasu, H. In Catalytic
Heterofunctionalization; Togni, A., Gr u¨ zmacher, H., Eds.; Wiley-VCH:
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1
4
00, 3205-3220. (g) Ogawa, A. J. Organomet. Chem. 2000, 611, 463-
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Beletskaya, I.; Moberg, C. Chem. ReV. 1999, 99, 3435-3461.
1
0.1021/om0600442 CCC: $33.50 © 2006 American Chemical Society
Publication on Web 06/23/2006

Communications
Organometallics, Vol. 25, No. 15, 2006 3563
Table 1. Transition-Metal-Catalyzed Cyanothiolation of
(entries 3 and 5). Although the cyanothiolation of phenyl-
acetylene in solvent proceeds very slowly, the reaction in
the absence of solvent takes place much more smoothly (84%,
entry 6). Similarly, the reaction of 4-ethynyltoluene in
the absence of benzene afforded the cyanothiolation product in
good yield (81%, entry 7). On the other hand, the addition
of aliphatic thiocyanate such as n-butyl thiocyanate resulted
in a fairly low yield of the cyanothiolation product (entry
1
-Octynea
entry
1
catalyst
solvent
temp, °C time, h yield, %c
RhH(CO)(PPh3)3
CH3CN
C6H6
CH3CN
C6H6
C6H6
C6H6
C6H6
CH2Cl2
C6H6
C6H6
C6H6
140
120
120
120
120
140
120
120
120
80
67
24
65
24
24
62
24
20
24
24
66
66
66
66
0
0
0
0
0
0
0
0
12
9
b
2
3
NiCl2
8
).
b
4
b
5
Pd2(dba)3
PdCl2
To get some information about the real catalyst in this
6
cyanothiolation reaction, an equimolar reaction of Pd(PPh3)4
with PhSCN in benzene was conducted at room temperature,
which provided a yellow solid (complex A) [eq 1].
b
7
PdCl2(PPh)3
Pt(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
b
8
9
1
1
1
1
1
0
1
2
3
4
120
140
120
120
61
49
42
12
Pd(PPh ) + PhSCN
8 Pd(SPh)(CN)(PPh ) (1)
benzene, rt
3
4
3 2
C6H6
THF
CH3CN
1
equiv
complex A
a
From the IR spectrum of complex A, the CN bond absorption
For the detailed procedure of cyanothiolation, see the Supporting
b
c
1
Information. Catalyst (3 mol%). Determined by H NMR.
was observed clearly and the elemental analysis strongly
8
suggested the formation of Pd(SPh)(CN)(PPh3)2. These results
Table 2. Pd(PPh
3
)
4
-Catalyzed Cyanothiolation of Terminal
Alkynesa
impelled us to focus on the crystal structure of complex A, and
we obtained the X-ray crystal structure of complex A (Figure
9
1
). This tetracoordinated palladium complex bears -SPh and
-CN groups in the trans position in an almost square arrange-
ment. Intramolecular π-π interaction between two phenyl
groups (S-Ph and P(2)-Ph) was observed. This result indicates
the first example where the oxidative addition of PhSCN to Pd-
(
(
PPh3)4 proceeds with the cleavage of a sulfur-cyano bond
PhS-CN) not a carbon-sufur bond (Ph-SCN).
1
0
(
6) For transition-metal-catalyzed reactions which attain simultaneously
introduction of sulfur functions and carbon-carbon bond formation, see:
a) Kuniyasu, H.; Ogawa, A.; Miyazaki, S.; Ryu, I.; Kambe, N.; Sonoda,
(
N. J. Am. Chem. Soc. 1991, 113, 9796-9893. (b) Ogawa, A.; Takeba, M.;
Kawakami, J.; Ryu, I.; Kambe, N.; Sonoda, N. J. Am. Chem. Soc. 1995,
1
17, 7564-7565. (c) Ogawa, A.; Kawakami, J.; Mihara, M.; Ikeda, T.;
Sonoda, N.; Hirao, T. J. Am. Chem. Soc. 1997, 119, 12380-12381. (d)
Xiao, W.-J.; Vasapollo, G.; Alper, H. J. Org. Chem. 1999, 64, 9646-9652.
(
4
e) Xiao, W.-J.; Vasapollo, G.; Alper, H. J. Org. Chem. 2000, 65, 4138-
144. (f) Hua, R.; Takeda, H.; Onozawa, S.; Abe, Y.; Tanaka, M. J. Am.
Chem. Soc. 2001, 123, 2899-2900. (g) Sugoh, K.; Kuniyasu, H.; Sugae,
T.; Ohtaka, A.; Takai, Y.; Tanaka, A.; Machino, C.; Kambe, N.; Kurosawa,
H. J. Am. Chem. Soc. 2001, 123, 5108-5109. (h) Kawakami, J.; Mihara,
M.; Kamiya, I.; Takeba, M.; Ogawa A.; Sonoda, N. Tetrahedron 2003, 59,
3
521-3526. (i) Kawakami, J.; Takeba, M.; Kamiya, I.; Sonoda, N.; Ogawa,
A. Tetrahedron 2003, 59, 6559-6567. (j) Kuniyasu, H.; Kurosawa, H.
Chem. Eur. J. 2002, 8, 2661-2665. (k) Knapton, D. J.; Meyer, T. Y. Org.
Lett. 2004, 6, 687-689. (l) Knapton, D. J.; Meyer, T. Y. J. Org. Chem.
2
2
005, 70, 785-796. (m) Hirai, T.; Kuniyasu, H.; Kambe, N. Chem. Lett.
004, 33, 1148-1150. (n) Hirai, T.; Kuniyasu, H.; Kambe, N. Tetahedron
Lett. 2005, 46, 117-119. (o) Kuniyasu, H.; Kato, T.; Asano, S.; Ye, J. H.;
Ohmori, T.; Morita, M.; Hiralke, H.; Fujiwara, S.; Terao, J.; Kurosawa,
H.; Kambe, N. Tetrahedron Lett. 2006, 47, 1141-1144.
(7) See Supporting Information (method A).
(
8) For yellow solid: anal. calcd (%) for C43H35NP2PdS: C 67.41, H
4
.60, N 1.83; found: C 67.89, H 4.66, N 1.97; IR (KBr) ν ) 2130 (CN)
-
1
3
1
cm ; 79% yield, mp 229-230 °C; P NMR (500 MHz, CDCl3) δ 26.2.
9) Crystallographic data for complex A: Pd(SPh)(CN)(PPh3)2‚H2O,
monoclinic, P21/c (#14), a ) 18.859(2) Å, b ) 9.659(1) Å, c ) 21.970(2)
a
Reaction conditions: Pd(PPh3)4 (10 mol%), alkyne (1.0 mmol),
(
thiocyanate (1.0 mmol), 120 °C, 66 h, benzene (1 mL) (method A: entries
b
1
-3 and 8), without benzene (method B: entries 4-7). Isolated yield.
3
3
Å, â ) 105.588(5)°, V ) 3854.8(8) Å , Z ) 4, Dcalc ) 1.351 g/cm . The
intensity data were collected at 23 °C on a Rigaku RAXIS imaging plate
area detector with graphite-monochromated Mo KR radiation. The 34 726
independent reflections were measured over a 2θ range of 6.0-55.0°. All
non-hydrogen atoms were refined anisotropically. Full matrix least-squares
refinement using 4454 reflections converged to final agreement factors R1-
c
d
E/Z ratios were determined by differential NOE mesurements. Determined
1
e
f
by H NMR. 20 h. Not determined.
Table 2 represents the results of Pd(PPh3)4-catalyzed cyan-
othiolation of terminal alkynes under the optimized reaction
conditions. This procedure can be applied to both aliphatic and
aromatic alkynes. 1-Octyne and 5-methyl-1-hexyne underwent
palladium-catalyzed highly regio- and stereoselective cyanothio-
lation, providing the corresponding (2E)-3-phenylthioalk-2-
enenitrile in good yields (entries 1 and 2). Functionalities such
as cyano and olefinic groups tolerated the reaction conditions
[
I > 3σ(I)] ) 0.042, wR2[I > 3σ(I)] ) 0.049 with GOF ) 1.017. The
structure was solved by direct methods using SIR92 and refined by full-
matrix least squares on F. Drawings were generated using ORTEP-III
(Burnett & Johnson, 1996). Selected bond lengths (Å): Pd(1)-S(1) 2.338-
(
1), Pd(1)-C(43) 1.980(4), Pd(1)-P(1) 2.339(1), Pd(1)-P(2) 2.327(1);
angles (deg): P(1)-Pd(1)-S(1) 92.49(5), P(2)-Pd(1)-S(1) 84.38(5), P(1)-
Pd(1)-C(2) 88.0(2), P(2)-Pd(1)-C(2) 95.0(2), P(1)-Pd(1)-P(2) 176.32-
(4), S(1)-Pd(1)-C(2) 178.5(1).

3
564 Organometallics, Vol. 25, No. 15, 2006
Communications
Scheme 1. A Possible Reaction Pathway for
Cyanothiolation
3 2
Figure 1. Morecular structure of Pd(SPh)(CN)(PPh ) .
Furthermore, the reaction of phenyl thiocyanate with 1-octyne
In summary, we have developed the highly selective pal-
ladium-catalyzed cyanothiolation of terminal alkynes with
thiocyanates. The reaction proceeds via oxidative addition of
thiocyanates to palladium(0), which was clearly indicated by
the first X-ray crystal structure analysis of the intermediate
complex (Pd(SPh)(CN)(PPh3)2). This process provides a useful
method for the catalytic introduction of both thio and cyano
groups into the internal and terminal positions of alkynes,
respectively, with excellent regioselectivities.
using complex A as a catalyst afforded the corresponding
1
1
cyanothiolation product in 58% yield, regioselectively [eq 2].
These results suggest that complex A reacts with alkynes to
give the cyanothiolation product probably via either a thiopal-
ladation or a cyanopalladation process, followed by reductive
elimination, as shown in Scheme 1.
Acknowledgment. This research was supported by a Grant-
in-Aid for Scientific Research on Priority Areas (A) (No.
(
10) (a) Wood, J. L. In Organic Reaction; Adams, A., Ed.; Wiley: New
1
4044063) “Exploitation of Multi-Element Cyclic Molecules”
York, 1946; Vol. 3, Chapter 6. (b) Wolf, G. C. J. Org. Chem. 1974, 39,
from the Ministry of Education, Culture, Sports, Science and
Technology, Japan. We gratefully acknowledge emeritus Profes-
sor Noboru Sonoda (Osaka University) for his helpful sugges-
tions. We also thank Mr. Yoshihiro Higuchi for experimental
supports.
3
1
454-3455. (c) Giffard, M.; Cousseau, J. J. Chem. Soc., Chem. Commun.
979, 1026-1027. (d) Guy, R. G.; Cousins, S.; Farmer, D. M.; Henderson,
A. D.; Wilson, C. L. Tetrahedron 1980, 36, 1839-1842. (e) Giffard, M.;
Cousseau, J. J. Organomet. Chem. 1980, 201, C1-C4. (f) Giffard, M.;
Cousseau, J.; Gouin, L.; Crahe, M. R. Tetrahedron 1985, 41, 801-810.
(
g) Giffard, M.; Cousseau, J.; Gouin, L. J. Organomet. Chem. 1985, 287,
2
87-303. (h) Giffard, M.; Cousseau, J.; Gouin, L.; Crahe, M. R.
Tetrahedron 1986, 42, 2243-2252.
11) Atempted stoichiometric reaction of complex A with 1-octyne did
Supporting Information Available: Experimental procedures
and spectral and analytical date. This material is available free of
charge via the Internet at http://pubs.acs.org.
(
not proceed. This fact suggests that the reductive elimination step may be
the rate-determining step, because the presence of excess amounts of PhSCN
in this reaction of complex A with 1-octyne affords the corresponding
cyanothiolation products.
OM0600442