Rhodium-catalyzed carbothiolation reaction of 1-alkylthio-1-alkynes

Article abstract of DOI:10.1016/j.tetlet.2010.12.065

A rhodium complex derived from RhH(PPh₃)₄ and Me ₂PhP catalyzed the carbothiolation reaction of 1-alkylthio-1-alkynes and 1,4-diaryl-1,3-butadiynes giving (Z)-4-alkylthio-4-aryl-3-arylethynyl-3- buten-1-ynes. Terminal alky

Full text of DOI:10.1016/j.tetlet.2010.12.065

Tetrahedron Letters 52 (2011) 920–922
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Rhodium-catalyzed carbothiolation reaction of 1-alkylthio-1-alkynes
Mieko Arisawa a, Yui Igarashi a, Yoko Tagami a, Masahiko Yamaguchi a,b, , Chizuko Kabuto a
⇑
a Department of Organic Chemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba, Sendai 980-8578, Japan
b WPI Research Center, Advanced Institute for Materials Research, Tohoku University, Aoba, Sendai 980-8577, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
A rhodium complex derived from RhH(PPh3)4 and Me2PhP catalyzed the carbothiolation reaction of 1-
alkylthio-1-alkynes and 1,4-diaryl-1,3-butadiynes giving (Z)-4-alkylthio-4-aryl-3-arylethynyl-3-buten-
1-ynes. Terminal alkynes such as 1-decyne and (t-butylthio)acetylene underwent the carbothiolation
reaction using a RhH(PPh3)4-dppb catalyst. The reactions proceeded via cis-addition with C–C bond for-
mation at the less hindered acetylene carbon.
Received 11 November 2010
Revised 9 December 2010
Accepted 16 December 2010
Available online 21 December 2010
Ó 2011 Published by Elsevier Ltd.
The carbothiolation reaction1 of alkynes is a straightforward
method of synthesizing alkenylsulfur compounds starting from
organosulfur compounds with the insertion of a two carbon unit.
The reaction involves the formation of a C–C bond and a C–S bond
at a C–C triple bond along with the C–S bond cleavage in the
original organosulfur compound, and all three processes need to
proceed effectively. Transition metal catalysis is an attractive
method for this transformation, and the reaction of organosulfur
compounds with strained or polarized C–S bonds using thiranes,2
thiocarbonates,3 thiocarbamates,4 thiocyanates,5 and thioesters6
has been carried out. The decarboxylative carbothiolation reaction
of thioesters was also reported.7 The reaction of the less polarized
C–S bond, however, was not well investigated with the exception
of allyl sulfides8 and intramolecular reactions.9 Described in this
Letter is the carbothiolation reaction of 1-alkylthio-1-alkynes with
1,3-butadiynes, 1-decyne, and 1-(t-butylthio)acetylene.
3 were determined by NMR studies. The isomer (Z)-3 exhibited
NOE between the methylenethio protons at d 2.46 and the o-pro-
tons of the arylvinyl group at d 7.50, and HMBC cross peaks were
observed between these protons and an olefin carbon at d 155.0.
Similar NMR observations were made for the (E)-3 isomer. The
butylthio and p-methoxyphenyl groups therefore should be
located on a same olefinic carbon in both isomers. NOE was
observed between the isopropyl methine protons of (E)-3 at d
0.93 and the o-protons of arylvinyl group at d 7.38 as well as the
isopropyl methine protons at d 0.93 and the o-protons of arylethy-
nyl group at d 7.44. The results indicated the (E)-stereochemistry of
(E)-3, which in turn determined the (Z)-stereochemistry of (Z)-3.
1
2
p-MeOC6H4
n-C4H9S
C6H4OMe-p
RhH(PPh3)4 (5 mol%)
Si(i-Pr)3
It was previously found in our laboratory that rhodium
1
n-C4H9S
complexes cleave the C–S bonds of 1-organothio-1-alkynes,10
Me2PhP (15 mol%)
+
thioesters,11 and
a
-organothio ketones,12 and that organosulfur
DMI, 135 °C, 6 h
Si(i-Pr)3
p-MeOC6H4
compounds undergo the organothio exchange reaction with disul-
fides. It was therefore considered interesting to apply the method
to the carbothiolation reaction with alkynes employing the organo-
rhodium intermediates formed in these reactions. This method can
be useful for the synthesis of novel organothio enynes.
2
C6H4OMe-p
OMe
(Z)-3
66%
HMBC
HMBC
n-C5H11
When an equimolar mixture of 1,4-bis(p-methoxyphenyl)-1,
3-butadiyne 1 and 1-triisopropylsilyl-2-(butylthio)acetylene 2 in
dimethylimidazolidinone (DMI) was heated at 135 °C for 6 h in
the presence of RhH(PPh3)4 (5 mol %) and Me2PhP (15 mol %),
(Z)-1-triisopropylsilyl-4-(p-methoxyphenyl)-3-(p-methoxyphenyl-
ethynyl)-4-butylthio-3-buten-1-yne (Z)-3 was obtained in 66%
yield (Scheme 1). The compound (Z)-3 slowly isomerized to (E)-3
on standing at room temperature. The structures of (Z)-3 and (E)-
n-C3H7
Si(i-Pr)3
H δ 7.44
δ 2.44
CHS
δ 155.8
δ 2.46
CHS
H
H
NOE
δ 155.0
NOE
δ 7.50
H
H
δ 7.38
Si(i-Pr)2
NOE
C6H4OMe-p
MeO
MeO
HMBC
H
HMBC
δ 0.93
(Z)-3
NOE
(E)-3
⇑
Corresponding author.
E-mail address: yama@mail.pharm.tohoku.ac.jp (M. Yamaguchi).
Scheme 1.
0040-4039/$ - see front matter Ó 2011 Published by Elsevier Ltd.
doi:10.1016/j.tetlet.2010.12.065

M. Arisawa et al. / Tetrahedron Letters 52 (2011) 920–922
921
Table 1
for higher yield, and the yield decreased to 35% and 8% at 125 °C
and 100 °C, respectively. The reaction exhibited notable solvent
effect. The reaction using aromatic solvents such as toluene and
chlorobenzene gave small amounts of the product (<20%).
Rhodium-catalyzed carbothiolation reaction of 1-alkylthio-1-alkynes and
1,3-butadiynes
R2
R1S
R2
RhH(PPh3)4 (5 mol%)
Me2PhP (15 mol%)
R1S
Ar
1-Alkylthio-1-alkynes with triisopropyl, 2,4,6-trimethylphenyl,
and 2,6-dimethylphenyl groups provided good yields of the prod-
ucts compared with phenylacetylene (Table 1, entries 1–5). Yields
lowered with aliphatic acetylenes (entries 6–8). As for the alkylthio
moiety, hexylthio, and cyclohexylthio derivatives reacted smoothly
but not t-butylthio derivatives (entries 1 and 2). The effect of the
aryl substituent on the 1,3-butadiynes was observed, and those
with electron donating p-substituents gave higher yields of the
products (entries 1 and 9–11). The reaction of a dialkyl substituted
1,3-butadiyne proceeded in a low yield (entry 15).
The carbothiolation reaction of 1-alkynes also proceeded under
the rhodium-catalyzed conditions. The reaction of 1-decyne 5 and
2 in the presence of RhH(PPh3)4 (5 mol %) and dppb (15 mol %) in
DMI at 75 °C for 6 h gave (Z)-4-butylthio-1-triisopropylsilyl-3-
dodecen-1-yne (Z)-6 in 38% yield (Scheme 2). The reaction pro-
ceeded at lower temperatures than that of 1,3-butadiynes. Isomer
(E)-6 was not detected. The structure of (Z)-6 was determined by
NOE between the vinyl proton at d 5.55 and octyl methylene pro-
tons at d 2.26 as well as that between the butylthio methylene pro-
ton at d 2.85 and the methylene protons at d 2.26. The C–C bond
formation occurred at terminal carbon of 5. Although Me2PhP used
in the reaction of 1,3-butadiynes also promoted the reaction of 5
and 2 giving (Z)-6 (44%), the product was accompanied by the iso-
mer (E)-6 (21%). It was, however, noted that (E)-6 was not the car-
bothiolation product but the addition product of 1-butanethiol to
1-triisopropylsilyl-1,3-dodecadiyne 7, which was formed by the
coupling reaction of 2 and 5. Correspondingly, when 7 was reacted
with 1-octanethiol in the presence of RhH(PPh3)4 (5 mol %) and
+
DMI, 135 °C, 6 h
Ar
Ar
Ar
Entry
Ar
R1
R2
Yield (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
p-MeOC6H4
n-C4H9
cyclo-C6H11
n-C6H13
n-C6H13
n-C6H13
n-C6H13
n-C6H13
n-C4H9
n-C4H9
n-C4H9
n-C4H9
n-C4H9
n-C4H9
n-C4H9
n-C4H9
i-Pr3Si
66
48
58
55
30
23
13
11
46
43
Trace
47
28
28
17
2,4,6-Me3C6H2
2,6-Me2C6H3
C6H5
(CH2)5C(OMe)
t-Bu
n-C4H9
i-Pr3Si
i-Pr3Si
i-Pr3Si
i-Pr3Si
i-Pr3Si
i-Pr3Si
i-Pr3Si
p-MeC6H4
Ph
p-ClC6H4
1-Naphthyl
2-Naphthyl
9-Anthyl
n-C4H9
t-Bu
n-HexS
p-MeOC6H4
C6H4OMe-p
(Z)-4
NOE
n-C7H15
n-C8H17
Si(i-Pr)3
Figure 1. ORTEP view of (Z)-4 (only one molecule) with thermal ellipsoid drawin at
40% probability level.
RhH(PPh3)4 (5 mol%)
Me2PhP (15 mol%)
CHS
H
δ 5.26
7
+
H
δ 2.30
DMI, 135 °C, 6 h
n-C8H17SH
n-C7H15
75%
Si(i-Pr)3
The X-ray analysis of the product (Z)-4 derived from 1 and 2-(t-
butyl)-1-(hexylthio)acetylene (Table 1, entry 7) confirmed the
structure (Fig. 1).13 The ethynylation occurred at the carbon-2 of
1 and the C–S bond formation at the carbon-1, and the carbothio-
lation proceeded via cis-addition.
The ligand effect was substantial on the carbothiolation reac-
tion, and only 4% yield of (Z)-3 was obtained without the phos-
phine. Bidentate ligands such as dppe, dppb, dppBz, and dppf
were not effective. The yields of (Z)-3 were comparable or less than
10% using (p-MeOC6H4)3P, (p-ClC6H4)3P, cyclo-C6H11Ph2P, Me3P,
and Et3P. An elevated high reaction temperature was also required
Scheme 3.
Si(i-Pr)3
n-C4H9S
t-BuS
Si(i-Pr)3
H
RhH(PPh3)4 (10 mol%)
dppb (30 mol%)
n-C4H9S
t-BuS
2
+
(Z)-9a 50%
DMI, 75 °C, 6 h
+
8
St-Bu
S
n-C3H7
CH2S
δ 89.3
n-C4H9S
H
δ 1.48
(E)-10a 16%
t-BuS
δ 141.6
HMBC
H
S
Si(i-Pr3)
δ 1.39 H
RS
Si(i-Pr)3
RhH(PPh3)4 (5 mol%)
dppb (15 mol%)
NOE
δ 6.19
RS
+
NOE
n-C8H17
H
DMI, 75 °C, 6 h
(E)-10a
HMBC
n-C8H17
5
R = n-C4H9 (Z)-6 38%
R = cyclo-C6H11 23%
R = Ph 35%
Scheme 4.
Si(i-Pr)3
n-C3H7
NOE
n-C3H7
CHS
δ 2.85
H
CHS
NOE
n-C4H9S
St-Bu
H
δ 5.26
RhH(PPh3)4 (10 mol%)
dppb (30 mol%)
H
δ 2.30
11
+
H
δ 5.55
H
H
(E)-10a
50%
δ 2.26
n-C7H15
DMI, 75 °C, 6 h
t-BuS
n-C7H15
(Z)-6
NOE
Si(i-Pr)3 (E)-6
8
Scheme 2.
Scheme 5.

922
M. Arisawa et al. / Tetrahedron Letters 52 (2011) 920–922
Table 2
1-alkylthio-1-alkynes proceeded with 1,3-butadiynes, 1-decyne,
and (t-butylthio)ethyne. The carbothiolation reaction of 1-alkyl-
thio-1-alkynes has not yet been identified. The C–C bond formation
occurred at the less hindered carbon atom of alkynes (Fig. 2) with
the cis-stereochemistry.
In a two-necked flask equipped with a reflux condenser were
placed tetrakis(triphenylphosphine)hydriderhodium (5 mol %,
17.3 mg), dimethylphenylphosphine (15 mol %, 6.4 lL), 1-butyl-
thio-2-(triisopropylsilyl)ethyne 2 (0.30 mmol, 81.2 mg) and 1,4-
bis(4-methoxyphenyl)-1,3-butadiyne 1 (0.30 mmol, 78.7 mg) in
1,3-dimethyl-2-imidazolidinone (0.75 mL) under an argon atmo-
sphere, and the solution was heated at 135 °C for 6 h. Then, the sol-
vent was removed under reduce pressure, and the residue was
purified by flash column chromatography on silica gel giving (Z)-
3 (105.3 mg, 66%).
Rhodium-catalyzed carbothiolation reaction of 1-organothio-1-alkynes and 8
R2
St-Bu
R1S
R2
RhH(PPh3)4 (10 mol%)
dppb (30 mol%)
R1S
R1S
+
+
DMI, 75 °C., 6 h
t-BuS
t-BuS
t-BuS
H
(E)-10
(Z)-9
8
Entry
R1
R2
Yield (%)
(E)-10
(Z)-9
1
2
3
4
5
n-C4H9
n-C6H13
Ph
i-Pr3Si
i-Pr3Si
i-Pr3Si
50
42
39
34
17
16
15
Trace
14
4
n-C6H13
n-C6H13
2,4,6-Me3C6H2
1-Adamantyl
Acknowledgments
This work was supported by a Grant-in-Aid for Scientific
Research (No. 21229001), the GCOE program, and the WPI Initia-
tive from JSPS. M.A. expresses her thanks to the Grant-in-Aid for
Scientific Research (No. 22689001) and to the Asahi Glass
Foundation.
Ar
Ar
n-C8H17
H
t-BuS
H
Figure 2. The C–C bond formation sites in the carbothiolation reaction.
Supplementary data
Me2PhP (15 mol %) in DMI at 135 °C for 6 h, the (E)-adduct was
obtained in 75% yield without forming the (Z)-isomer (Scheme
3). In addition, no isomerization of (Z)-6 to (E)-6 was observed un-
der the rhodium-catalyzed conditions.
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2010.12.065.
1-(t-Butylthio)acetylene 8 was a good substrate for the carbo-
thiolation reaction. The reaction of 2 and 8 gave (Z)-4-(butyl-
thio)-4-(t-butylthio)-1-triisopropylsilyl-3-buten-1-yne (Z)-9a in
50% yield, which was accompanied by (E)-4-(butylthio)-1,4-bis(t-
butylthio)-3-buten-1-yne (E)-10a in 16% yield (Scheme 4). The
structure of (E)-10a was determined by NOE and HMBC experi-
ments. The minor product (E)-10a was formed by the butylthio
transfer from 2 to 8 giving 1-(t-butylthio)-2-butylthioacetylene
11, which underwent the carbothiolation reaction with 8. The
mechanism was confirmed by an independent reaction of 11 and
References and notes
1. A review. Kuniyasu, H.; Kambe, N. J. Synth. Org. Chem. Jpn. 2009, 67, 701.
2. Choi, N.; Kabe, Y.; Ando, W. Tetrahedron Lett. 1991, 32, 4573.
3. Hua, R.; Takeda, H.; Onozawa, S.; Abe, Y.; Tanaka, M. J. Am. Chem. Soc. 2001, 123,
2899.
4. Toyofuku, M.; Fujiwara, S.; Shin-ike, T.; Kuniyasu, H.; Kambe, N. J. Am. Chem.
Soc. 2005, 127, 9706.
5. Kamiya, I.; Kawakami, J.; Yano, S.; Nomoto, A.; Ogawa, A. Organometallics 2006,
25, 3562.
6. Minami, Y.; Kuniyasu, H.; Miyafuji, K.; Kambe, N. Chem. Commun. 2009, 3080.
7. 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. and references cited
therein.
8. Hua, R.; Takeda, H.; Onozawa, S.; Abe, Y.; Tanaka, M. Org. Lett. 2007, 9, 263.
9. Nakamura, I.; Sato, T.; Yamamoto, Y. Angew. Chem., Int. Ed. 2006, 45, 4473;
Nakamura, I.; Sato, T.; Terada, M.; Yamamoto, Y. Org. Lett. 2008, 10, 2649.
10. Arisawa, M.; Fujimoto, K.; Morinaka, S.; Yamaguchi, M. J. Am. Chem. Soc. 2005,
127, 12226.
11. Arisawa, M.; Kubota, T.; Yamaguchi, M. Tetrahedron Lett. 2008, 49, 1975.
12. Arisawa, M.; Toriyama, F.; Yamaguchi, M. Chem. Pharm. Bull. 2010, 58, 1349.
13. Crystal Data Monoclinic Pa, Cell Dimensions: a = 18.943(7), b = 11.891(5),
c = 24.688(10) Å, b = 96.535(2)°, Z = 8, T = 173 K, Crystallographic data
excluding structure factors have been deposited with the Cambridge
Crystallographic Data Centre as supplementary publication number CCDC
795726. A copy of the data can be obtained free of charge from CCDC, 12 Union
Road, Cambridge CB2 1EZ, UK or e-mail: deposit@ccdc.cam.ac.uk.
8
giving (E)-10a (Scheme 5). Similarly to that of 1-decyne
5(Scheme 2), the C–C bond formation of 8 occurred at the terminal
carbon by cis-addition. The high reactivity of 8 compared with
1-decyne 5 may be partly due to the interaction of the sulfur atom
with rhodium.
Several 1-alkylthio- and 1-phenylthio-1-alkynes were reacted
with 8, and the carbothiolated products (Z)-9 were obtained as
well as butylthio transfer products (E)-10 (Table 2). Not only triiso-
propylsilylacetylene but also 2,4,6-trimethylphenylacetylene and
(1-adamantyl)acetylene underwent the carbothiolation reaction
with 8.
In summary, in the presence of a rhodium complex and an
appropriate phosphine ligand, the carbothiolation reaction of