Pt-catalyzed regio- and stereoselective pyridylthiolation of terminal alkynes

Article abstract of DOI:10.1016/j.tetlet.2004.11.023

Three-component cross-coupling reactions among 3-iodopyridynes, terminal alkynes and ArSK took place in the presence of Pt-catalyst to give pyridine derivatives with conjugated vinyl groups in moderate yields.

Full text of DOI:10.1016/j.tetlet.2004.11.023

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 117–119
Pt-catalyzed regio- and stereoselective pyridylthiolation
of terminal alkynes
Takayoshi Hirai, Hitoshi Kuniyasu* and Nobuaki Kambe*
Department of Molecular Chemistry and Frontier Research Center, Graduate School of Engineering,
Osaka University, Suita, Osaka 565-0871, Japan
Received 20 August 2004; revised 28 October 2004; accepted 4 November 2004
Abstract—Three-component cross-coupling reactions among 3-iodopyridynes, terminal alkynes and ArSK took place in the
presence of Pt-catalyst to give pyridine derivatives with conjugated vinyl groups in moderate yields.
Ó 2004 Elsevier Ltd. All rights reserved.
The reactions utilizing organic sulfur compounds as
reactants of transition-metal catalyzed reactions are
now ubiquitous, although a misconception that sulfur-
containing compounds should poison the catalysts once
had been prevailed among many chemists.1 We have
been interested in the reactivities of organic sulfur
compounds as ligands of transition metals2 and recently
discovered one simple principle to simultaneously
introduce carbon and sulfur functionalities into alkynes
with the aid of the Pt-catalyst.3 Herein described is an
approach to synthesize functionalized pyridine deriva-
tives by applying the carbothiolation prototype.
First, the reaction of (3-pyridyl)C(O)SPh (1a, 1.0mmol)
with 1-octyne (2a, 1.2mmol) was attempted in toluene
(0.5mL) in the presence of Pt(PPh3)4 (0.05mmol) to
O
R
cat. Pt(PPh3)4
R
N
N
SPh
+
SPh
+
+
SPh
R
N
SPh
R = n-C6H13
3a
18%
4a
10%
5a
28%
1a
2a
Pt(0)
- 3a
1a
O
R
N
Pt
SPh
Pt
SPh
6a
N
8a
- CO
2a
N
Pt
SPh
7a
Scheme 1. The route to Pt-catalyzed pyridylthiolation of 2a by 1a (PPh3 on Pt omitted).
Keywords: Alkyne; Carbothiolation; Platinum.
*
Corresponding authors. Tel.: +81 6 6879 7389; fax: +81 6 6879 7390; e-mail: kuni@chem.eng.osaka-u.ac.jp
0040-4039/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.11.023

118
T. Hirai et al. / Tetrahedron Letters 46 (2005) 117–119
anticipate the formation of Z-(3-pyridyl)CH@C(n-C6H13)-
(SPh) (3a) through oxidative addition of thioester (1a)
to Pt(0) to give (3-pyridyl)C(O)Pt(SPh) (6a), decarbony-
lation to afford 3-pyridyl-Pt-SPh (7a), insertion of 1-
octyne (2a) into an S–Pt bond of 7a4 to yield vinylplati-
num (8a) and following reductive elimination of 3a with
the regeneration of Pt(0) (Scheme 1). No starting thio-
ester (1a) remained after 24h; however, contrary to the
cases of arylthiolation3b and thienylthiolation,3d the
yield of the anticipated 3a was unsatisfactory (18%)
and the formations of many by-products including
CH2@C(SPh)(n-C6H13) (4a) (10%) and 3-pyridyl-SPh
(5a) (28%) were also confirmed.
On the other hand, the reaction using (2-pyridyl)-
C(O)SPh (1b) was sluggish (36% conversion after 24h)
to afford Z-(2-pyridyl)CH@C(n-C6H13)(SPh) (3b) in
22% yield.
Thus, we next examined the syntheses of 3a using the
combination of reagents of 3-pyridyl-X (9; X = Cl, Br,
and I) with PhSM (10; M = Li, Na, K, and Sn(n-Bu)3)
as the sources of generation of 3-pyridyl-Pt-SPh (7a)
through oxidative addition of 3-pyridyl-X (9) to Pt(0)
to produce 3-pyridyl-Pt-X (11)5 and following transmetal-
lation with thiolate (10) (Scheme 2), instead of oxidative
addition of thioester to Pt(0) and decarbonylation
(Scheme 1).
R
N
cat. Pt(PPh3)4
+
SPh
R
+
PhSM
N
X
R = n-C6H13
3a
9
2a
10
Pt(0)
Among examined (Table 1, entries 1–6), the combined
use of 3-pyridyl-I (9a) and PhSK (10c) brought about
the best result; 3a was isolated in 78% yield together
with 14% of 3-pyridyl-SPh (5a) and 8% of (Z,Z)-(3-pyri-
dyl)(n-C6H13)C@CHCH@C(n-C6H13)(SPh) (12a) (entry
3).6 The conversions were low in the cases of employing
PhSLi (10a), 3-pyridyl-Br (9b), and 3-pyridyl-Cl (9c)
(entries 1, 5, and 6), while fairly comparable yields of
3a with that of using PhSK (10c) were resulted in when
PhSNa (10b) and PhSSn(n-Bu)3 (10d) were exploited in
the reactions with 3-pyridyl-I (9a) (entries 2 and 4).
These results demonstrated that the efficiency of the
pyridylthiolation could significantly depend on how
intermediate 3-pyridyl-Pt-SPh (7a) was produced in situ.
The Pt-catalyzed reaction of 3-pyridyl-I (9a) with PhSK
(10c) in the absence of alkyne led to the formation of 3-
- 3a
9
R
N
Pt
SPh
Pt X
N
11
8a
10
2a
N
Pt SPh
7a
Scheme 2. The route to Pt-catalyzed pyridylthiolation of 2 by 9 and
10.
Table 1. Pt-catalyzed pyridylthiolation of 2a by 9 and 10a
R
N
cat. Pt(PPh3)4
+
+
R
ArSM
SAr
N
X
R = n-C6H13
9
10
3
2a
Entry
9
X
10
Ar
M
3
Yield of 3b
1
9a
9a
9a
9a
9b
9c
9a
9a
9d
9d
3-I
3-I
10a
10b
10c
10d
10c
10c
10e
10f
10c
10c
Ph
Ph
Ph
Ph
Ph
Ph
Li
Na
3a
3a
3a
3a
3a
3a
3c
3d
3b
3b
3c
72d
78e
67
5
2
3
3-I
3-I
K
Sn(n-Bu)3
4f
5
3-Br
3-Cl
3-I
K
K
K
K
K
K
6
0
7
p-BrC6H4
p-MeOC6H4
65
65
7g
0i
8
3-I
2-I
9
10h
Ph
Ph
2-I
a Unless otherwise noted, 9 (1.0mmol), 10 (1.1mmol), 2a (1.2mmol), Pt(PPh3)4 (0.05mmol), and toluene (0.5mL) under reflux for 24h.
b Isolated yield.
c Compounds 9a (80% recovered), 4a (54% based on 10a), and (3-pyridyl)(R)C@CHCH@C(R)(SPh) (12a) (9% based on 9a).
d Compound 9a (11% recovered), 4a (3%), and (12a) (3%).
e Compounds 5a (14%) and 12a (8%).
f Compounds 10d (1.5mmol), Pt(PPh3)4 (0.10mmol) under reflux for 30h.
g (2-Pyridyl)SPh (5b) (91%).
h Without Pt(PPh3)4.
i Compounds 9d (9% recovered), 5b (91%).

T. Hirai et al. / Tetrahedron Letters 46 (2005) 117–119
119
Table 2. Examples of Pt-catalyzed pyridylthiolation of 2 with 9a and
10ca
2. The reaction using the aliphatic alkynes 2b and 2c
gave the pyridylthiolation products 3e and 3f in modest
yields (entries 1 and 2). The ratios of 3 and 5 were signifi-
cantly dependent on the nature of alkynes. Although
predominant amounts of 3-pyridyl-SPh (5a) were pro-
duced when phenylacetylene (2d) and its derivative (2e)
were used, highly conjugated pyridine derivatives 3g
and 3h were synthesized by simple procedures, respec-
tively (entries 3 and 4). The reaction of 5-hexynenitrile
(2f) gave the corresponding adduct 3i in 34% yield
together with many by-products (entry 5). The protec-
tion of hydroxyl group hardly influenced the result of
the reaction (entries 6 and 7). Neither internal alkyne
(2i) nor propargyl bromide (2j) was active for the
present transformation (entries 8 and 9).
R
N
cat. Pt(PPh3)4
N
SPh
+
+
+
R
PhSK
SPh
N
I
3
5a
9a
10c
2
Entry
1
2
Yield (%)
of 3b
Yield (%)
of 5ab
C8H17-n
3e
77
16
16
2b
2c
2
3f
72
23
3c
4
3g
56
53
Ph
In conclusion, this paper provides a convenient method
for the synthesis of pyridine derivatives with 3-vinyl
functionality. Further study is now continued to unveil
the versatility of Pt-catalyzed carbothiolation chemistry.
2d
2e
2f
C6H4-p-OMe
3h
44
34
50
50
5d
6e
7
3i
27
(CH2)3CN
(CH2)4OH
OTHP
3j
22
References and notes
2g
3k
3l
21
1. (a) Ogawa, A. In Main Group Metals in Organic Synthesis;
Yamamoto, H., Oshima, K., Eds.; Wiley-VCH: Weinheim,
2004; pp 813–866; (b) El Ali, B.; Alper, H. In Handbook of
Organopalladium Chemistry for Organic Synthesis; Negishi,
E., Wiley, J., Eds.; Wiley-Interscience: New York, 2002;
Chapter VI. 2.1.1.2; (c) Ogawa, A. In Handbook of
Organopalladium Chemistry for Organic Synthesis; Negishi,
E., Wiley, J., Eds.; Wiley-Interscience: New York, 2002,
Chapter VII. 6; (d) Kuniyasu, H. In Catalytic Heterofunc-
2h
H7C3
2i
C3H7
8
ND
ND
8
CH2Br
9
3m
ND
2j
a Compounds 9a (1.0mmol), 10c (1.1mmol), 2 (1.2mmol), Pt(PPh3)4
(0.05mmol), and toluene (0.5mL) under reflux for 24h.
b Isolated yield.
c 30h.
tionalization; Togni, A., Grutzmacher, H., Eds.; Wiley-
¨
d Compounds 10c (1.5mmol), 2a (1.5mmol), and Pt(PPh3)4
(0.10mmol).
VCH: Weinheim, 2001; pp 217–251; (e) Kondo, T.;
Mitsudo, T. Chem. Rev. 2000, 100, 3205; (f) Ogawa, A. J.
Organomet. Chem. 2000, 611, 463; (g) Han, L.-B.; Tanaka,
M. Chem. Commun. 1999, 395; (h) Beletskaya, I.; Moberg,
C. Chem. Rev. 1999, 99, 3435.
e Pt(PPh3)4 (0.10mmol).
pyridyl-SPh (5a) (14%) with the recovery of 3-pyridyl-I
(9a) (77%), while no reaction proceeded when the solu-
tion of 3-pyridyl-I (9a) and PhSK (10c) was just refluxed
without catalyst, proving that Pt-complex also catalyzed
the production of 3-pyridyl-SPh (5a). The reactions
using p-BrC6H4SK (10e) and p-MeOC6H4SK (10f) also
afforded the desired pyridylthiolation products 3c and
3d in moderate yields (entries 7 and 8). However, due
to the high susceptibility of 2-iodopyridine (9d) to nucleo-
philic substitution by PhSK (10c) even in the absence
of catalyst (entry 10), the yield of 3b was not improved
by this combination of reagents (entry 9). When the
reaction of 1-octyne (2a) with 3-pyridyl-I (9a) and PhSK
(10c) was conducted in the presence of Pd(PPh3)4 in-
stead of Pt(PPh3)4, a mixture of 3a (5%), 3-pyridyl-
SPh (5a) (40%) and (Z,Z)-(3-pyridyl)(n-C6H13)C@
CHCH@C(n-C6H13)(SPh) (12a) (2%) was produced.
Both Pt(norbornene)3 and Pt(norbornene)3/P(n-Bu)3
were ineffective as catalysts for the formation of 3a.
2. (a) Kuniyasu, H.; Sugoh, K.; Moon, S.; Kurosawa, H. J.
Am. Chem. Soc. 1997, 119, 4669; (b) Kuniyasu, H.;
Maruyama, A.; Kurosawa, H. Organometallics 1998, 17,
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Sugoh, K.; Kurosawa, H. J. Org. Chem. 1999, 64, 7305; (d)
Ohtaka, A.; Kuniyasu, H.; Kinomoto, M.; Kurosawa, H. J.
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5. It has already reported that the oxidative addition of 3-
bromopyridine to Pd(PPh3)4 gave Pd(3-pyridyl)Br(PPh3)2.
Isobe, K.; Nakamura, Y.; Miwa, T.; Kawaguchi, S. Bull.
Chem. Soc. Jpn. 1987, 60, 149–157.
6. For the synthetic utility of vinyl sulfides, see: (a) Trost, B.
M. A.; Lavoie, C. J. Am. Chem. Soc. 1983, 105, 5075; (b)
Magnus, P.; Quagliato, D. J. Org. Chem. 1985, 50,
1621.
The scope and limitations of the present Pt-catalyzed
pyridylthiolation of alkynes were summarized in Table