Ruthenium-catalyzed propargylic substitution reaction of propargylic alcohols with thiols: A general synthetic route to propargylic sulfides

Article abstract of DOI:10.1021/ja027754t

A novel cationic methanethiolate-bridged diruthenium complex [Cp*RuCl(μ₂-SMe)₂RuCp*(OH₂)]OTf (1e) has been disclosed to promote the catalytic propargylic substitution reaction of propargylic alcohols bearing not only termi

Full text of DOI:10.1021/ja027754t

Published on Web 11/23/2002
Ruthenium-Catalyzed Propargylic Substitution Reaction of Propargylic
Alcohols with Thiols: A General Synthetic Route to Propargylic Sulfides
Youichi Inada,† Yoshiaki Nishibayashi,† Masanobu Hidai,*,‡ and Sakae Uemura*,†
Department of Energy and Hydrocarbon Chemistry, Kyoto UniVersity, Sakyo-ku, Kyoto 606-8501, Japan, and
Department of Materials Science and Technology, Science UniVersity of Tokyo, Noda, Chiba 278-8510, Japan
Received July 18, 2002
Table 1. Reaction of Propargylic Alcohol (2a) with Thiolsa
We recently disclosed the ruthenium-catalyzed efficient pro-
pargylic substitution reactions of propargylic alcohols with various
heteroatom- and carbon-centered nucleophiles to afford the corre-
sponding propargylic products in high yields.1 The reactions are
catalyzed only by thiolate-bridged diruthenium complexes2 such
yield of
3, %
b
run
thiol
catalyst
as [Cp*RuCl(µ2-SR)2RuCp*Cl] (Cp* ) η5-C5Me5; R ) Me (1a),
iPr (1b), nPr (1c)) and [Cp*RuCl(µ2-SiPr)2RuCp*(OH2)]OTf
(OTf ) OSO2CF3; 1d). The reactions proceeded more smoothly in
the presence of a catalytic amount of NH4BF4. In these catalytic
substitution reactions, available substrates were unfortunately strictly
limited to the propargylic alcohols bearing terminal alkyne group
because the reactions proceeded via allenylidene intermediates,
which can be produced only from this type of propargylic alcohols.
On the other hand, some other groups have already found transition
metal-catalyzed propargylic substitution reactions of propargylic
phosphates and acetates with nitrogen (Cu and Ti),3a,b oxygen (Ti),3c
and carbon-centered (Ir)3d nucleophiles, but a catalytic reaction with
a sulfur-centered nucleophile to afford the corresponding propargylic
sulfides has not yet been reported, probably due to the long known
fact that sulfur-containing compounds act as catalyst poisons
because of their strong coordinating properties.4 During our ongoing
study on the catalytic propargylic substitution reactions, we recently
found a general synthetic method for propargylic sulfides. Namely,
a novel cationic methanethiolate-bridged diruthenium complex
[Cp*RuCl(µ2-SMe)2RuCp*(OH2)]OTf (1e) (Chart 1) has been
1
2
3
4
5
6
7
nBuSH
nBuSH
nBuSH
nBuSH
nBuSH
[Cp*RuCl(µ-SMe)2Cp*Ru(OH2)]OTf (1e) 3aa, 92
[Cp*RuCl(µ-SMe)2Cp*Ru(OH2)]OTf (1e) 3aa, 79c
[Cp*RuCl(µ-SiPr)2Cp*Ru(OH2)]OTf (1d) 3aa, 92
[Cp*RuCl(µ-SMe)2Cp*RuCl] (1a)d
[Cp*RuCl(µ-SiPr)2Cp*RuCl] (1b)d
3aa, trace
3aa, trace
cC6H11SH
[Cp*RuCl(µ-SMe)2Cp*Ru(OH2)]OTf (1e) 3ab, 93
Me2CHCH2CH2SH [Cp*Ru(Cl(µ-SMe)2Cp*Ru(OH2)]OTf (1e) 3ac, 76
a All the reactions of 2a (0.30 mmol) with thiol (1.50 mmol) were carried
out in the presence of catalyst (0.015 mmol) in ClCH2CH2Cl (8 mL) at 60
°C for 1 h. b Isolated yield. c At room temperature for 3 h. d No reaction
proceeded even in the presence of NH4BF4.
bridged diruthenium complexes (1a-1c), which were known to
promote the propargylic substitution reactions of propargylic
alcohols bearing terminal alkyne group with various heteroatom-
and carbon-centered nucleophiles,1 did not work at all, even in the
presence of NH4BF4 (Table 1, runs 4 and 5). When other simple
alkanethiols such as cyclohexanethiol and 3-methyl-1-butanethiol
were used in place of 1-butanethiol, the corresponding propargylic
sulfides (3ab and 3ac) were obtained in 93 and 76% yields,
respectively (Table 1, runs 6 and 7). The most characteristic feature
of this reaction is the direct use of propargylic alcohols as effective
propargylating reagents where the reaction occurs in an environ-
mentally friendly manner, with the only stoichiometric byproduct
being water (H2O).
Chart 1
Reactions of 2a with thiols containing functional groups have
been carried out in the presence of 1e (5 mol %) at 60 °C for 1 h.6
Typical results are shown in Table 2. In all cases, 2a was completely
consumed, and the corresponding propargylic sulfides (3ad-3ag)
were obtained in good to excellent yields. Functional groups, such
as phenyl (Table 2, run 1), methoxycarbonyl (Table 2, run 2), chloro
(Table 2, run 3), and hydroxyl (Table 2, run 4), in thiols did not
affect this catalytic reaction. The reaction of 1-alkenyl-substituted
propargylic alcohol 2b with 1-butanethiol gave the allylpropargylic
sulfide 3ba in 96% isolated yield (Table 2, run 5). Unfortunately,
a similar reaction of dialkynyl-substituted alcohol 2c did not proceed
(Table 2, run 6). Other various alkyl- and aryl-substituted propar-
gylic alcohols (2d-2h) reacted with thiols to afford the corre-
sponding propargylic sulfides (3da-3ha) in excellent yields with
complete regioselectivity (Table 2, runs 7-14).7
disclosed to promote the catalytic propargylic substitution reaction
of propargylic alcohols bearing not only terminal alkyne group but
also internal alkyne group with thiols. Preliminary results on this
catalytic reaction are described here.
First, we investigated the substitution reaction of propargylic
alcohols bearing an internal alkyne group such as 1,3-diphenyl-2-
propyn-1-ol (2a). Treatment of 2a with 1-butanethiol in 1,2-
dichloroethane in the presence of 1e (5 mol %) at 60 °C for 1 h
afforded 1-butyl 1,3-diphenyl-2-propynyl sulfide (3aa) in 92%
isolated yield (Table 1, run 1).5 No other products or regioisomers
of 3aa were detected by GLC and 1H NMR. The reaction proceeded
even at room temperature, but a slightly prolonged reaction time
(3 h) was required (Table 1, run 2). The complex with the sterically
demanding SiPr group exhibited almost the same catalytic activity
in this reaction (Table 1, run 3). It is noteworthy that neutral thiolate-
Next, we examined the substitution reaction of propargylic
alcohols bearing terminal alkyne group such as 1-phenyl-2-propyn-
1-ol (4a) with thiols in the presence of 1e (5 mol %) at 60 °C for
1 h.8 Thus, a variety of thiols such as 1-butanethiol, 1-octanethiol,
3-methyl-1-butanethiol, cyclohexanethiol, phenylmethanethiol, and
3-chloropropanethiol could be employed to give the corresponding
* Corresponding author. E-mail: uemura@scl.kyoto-u.ac.jp.
† Kyoto University.
‡ Science University of Tokyo.
9
15172
J. AM. CHEM. SOC. 2002, 124, 15172-15173
10.1021/ja027754t CCC: $22.00 © 2002 American Chemical Society

C O M M U N I C A T I O N S
Table 2. Reaction of Propargylic Alcohols (2) with Thiols in the
Presence of 1ea
that the reaction of propargylic alcohols bearing a terminal alkyne
group 4 with thiols may proceed via other reactive intermediates.
On the other hand, a stoichiometric reaction of the cationic complex
1e with a propargylic alcohol bearing an internal alkyne group (2a)
1
at room temperature was investigated by H NMR in CD2Cl2, but
yield of
3, %
b
no intermediates were observed. Addition of an excess amount of
1-butanethiol to this reaction mixture led to the formation of the
sulfide 3aa together with 1e. These results indicate that the
intermediates of this catalytic reaction are too labile to be identified.
Although direct evidence of the reactive intermediates has not yet
been obtained, we suppose that the present catalytic reactions
between propargylic alcohols and thiols may proceed via (η-
propargyl)ruthenium species10 at the diruthenium site. Nucleophilic
attack of a thiol to this species affords the corresponding propargylic
sulfides. Further investigation to elucidate the detailed reaction
mechanism is currently in progress.
In summary, we have found a highly selective and efficient
propargylic substitution reaction of propargylic alcohols with thiols
catalyzed by the cationic diruthenium complex 1e.11 The Nicholas
reaction has been found to be the most reliable tool for selective
propargylation of nucleophiles by using a stoichiometric amount
of cationic propargyl complexes [(propargyl)Co2(CO)6]+.12 How-
ever, only a few studies on the propargylation of thiols by the
Nicholas reaction have been reported,13 and the preparative methods
for propargylic sulfides by other methods are quite limited so far.14
run
propargylic alcohol
thiol
1
2
3
2a, R1 ) Ph, R2 ) H, R3 ) Ph
2a, R1 ) Ph, R2 ) H, R3 ) Ph
2a, R1 ) Ph, R2 ) H, R3 ) Ph
R4 ) Ph
3ad, 70
R4 ) CH2CH2CO2Me 3ae, 92
R4 ) CH2CH2CH2Cl 3af, 90
4c 2a, R1 ) Ph, R2 ) H, R3 ) Ph
R4 ) CH2CH2OH
3ag, 52
3ba, 96
3ca, trace
3da, 87
5
6
7
8
9
2b, R1 ) Ph2CdCH, R2 ) H, R3 ) Ph R4 ) nBu
2c, R1 ) PhCtC, R2 ) H, R3 ) Ph
2d, R1 ) Ph, R2 ) H, R3 ) nBu
2d, R1 ) Ph, R2 ) H, R3 ) nBu
2e, R1 ) Ph, R2 ) H, R3 ) nhexyl
R4 ) nBu
R4 ) nBu
R4 ) CH2CH2CHMe2 3db, 90
R4 ) nBu
R4 ) nBu
3ea, 83
3fa, 86
10 2f, R1 ) Ph, R2 ) H, R3 ) tBu
11 2f, R1 ) Ph, R2 ) H, R3 ) tBu
R4 ) CH2CH2CHMe2 3fb, 87
12 2g, R1 ) p-MeC6H4, R2 ) H, R3 ) Ph R4 ) nBu
3ga, 90
13 2g, R1 ) p-MeC6H4, R2 ) H, R3 ) Ph R4 ) CH2CH2CHMe2 3gb, 92
14 2h, R1 ) Ph, R2 ) Me, R3 ) Ph R4 ) nBu
3ha, 84
a All the reactions of 2 (0.30 mmol) with thiol (1.50 mmol) were carried
out in the presence of 1e (0.015 mmol) in ClCH2CH2Cl (8 mL) at 60 °C
for 1 h. b Isolated yield. c 10 mol % of 1e was used.
Table 3. Reaction of Propargylic Alcohols Bearing Terminal
Alkyne Group with Thiolsa
Supporting Information Available: Experimental procedures and
spectral data for all of the new compounds and crystallographic data
for 1e (cif). This material is available free of charge via the Internet at
http://pubs.acs.org.
yield of
5, %
b
run
propargylic alcohol
thiol
R3 ) nBu
1
2
3
4
5
6
7
8
4a, R1 ) Ph, R2 ) H
5aa, 86
5ab, 87
5ac, 88
5ad, 82
5ae, 79
5af, 79
5ag, 24
5ba, 83
5ca, 84
5da, 94
5ea, 62
5fa, 47
5ga, 60
4a, R1 ) Ph, R2 ) H
R3 ) noctyl
R3 ) CH2CH2CHMe2
R3 ) cC6H11
R3 ) PhCH2
R3 ) CH2CH2CH2Cl
R3 ) Ph
4a, R1 ) Ph, R2 ) H
4a, R1 ) Ph, R2 ) H
References
4a, R1 ) Ph, R2 ) H
4a, R1 ) Ph, R2 ) H
(1) (a) Nishibayashi, Y.; Wakiji, I.; Hidai, M. J. Am. Chem. Soc. 2000, 122,
11019. (b) Nishibayashi, Y.; Wakiji, I.; Ishii, Y.; Uemura, S.; Hidai, M.
J. Am. Chem. Soc. 2001, 123, 3393. (c) Nishibayashi, Y.; Yoshikawa,
M.; Inada, Y.; Hidai, M.; Uemura, S. J. Am. Chem. Soc. 2002, 124, 11846.
(2) Nishibayashi, Y.; Yamanashi, M.; Wakiji, I.; Hidai, M. Angew. Chem.,
Int. Ed. 2000, 39, 2909 and references therein.
(3) (a) Imada, Y.; Yuasa, M.; Nakamura, I.; Murahashi, S.-I. J. Org. Chem.
1994, 59, 2282. (b) Mahrwald, R.; Quint, S. Tetrahedron Lett. 2001, 42,
1655. (c) Mahrwald, R.; Quint, S. Tetrahedron 2000, 56, 7463. (d)
Matsuda, I.; Komori, K.; Itoh, K. J. Am. Chem. Soc. 2002, 124, 9072.
(4) Hegedus, L. L.; McCabe, R. W. Catalyst Poisoning; Marcel Dekker: New
York, 1984.
(5) Other di- and monoruthenium complexes such as [CpRuCl(PPh3)2]
(Cp ) η5-C5H5), [RuCl2(PPh3)3], [RuCl2(p-cymene)]2, [(indenyl)RuCl-
(PPh3)2], and [Cp*RuCl(µ2-Cl)2RuCp*Cl] were ineffective for the pro-
pargylic substitution reaction.
(6) Unfortunately, no propargylic substitution reactions of 2a with alcohols,
amines, acetone, and silyl enol ethers in the presence of 1e occurred under
similar reaction conditions.
(7) In contrast to the reaction of 2,4-diphenyl-3-butyn-2-ol (2h) (Table 2,
run 14), the reaction of 1,1,3-triphenyl-2-propyn-1-ol with nBuSH at 60
°C for 16 h afforded not the corresponding propargylic product but 1,3,3-
triphenyl-2-propen-1-one in 80% yield as a sole product.
(8) Previously, the reaction of 4a with p-toluenethiol in the presence of 1a
(5 mol %) and NH4BF4 (10 mol %) was carried out at 60 °C for 4 h, but
the corresponding propargylic sulfide was obtained in only 53% yield.12
(9) When (R)-4a was treated with nBuSH at room temperature, racemic 5aa
was formed.
(10) (a) Shuchart, C. E.; Willis, R. R.; Wojcicki, A. J. Organomet. Chem. 1992,
424, 185. (b) Chen, C.-T. Coord. Chem. ReV. 1999, 190-192, 1143. (c)
Wojcicki, A. Inorg. Chem. Commun. 2002, 5, 82 and references therein.
(11) Independently, Mitsudo and co-workers reported the propargylic substitu-
tion reaction with propargylic carbonates with thiols catalyzed by
monoruthenium complexes such as CpRuCl(PPh3)2 and CpRuCl(cod) at
100 °C, but available substrates were strictly limited to the propargylic
carbonates bearing an internal alkyne group: Kondo, T.; Kanda, Y.; Baba,
A.; Fukuda, K.; Nakamura, A.; Wada, K.; Morisaki, Y.; Mitsudo, T. J.
Am. Chem. Soc. 2002, 124, 12960.
4a, R1 ) Ph, R2 ) H
4b, R1 ) p-MeC6H4, R2 ) H
4c, R1 ) p-FC6H4, R2 ) H
4d, R1 ) 2-naphthyl, R2 ) H
4e, R1 ) cC6H11, R2 ) H
4f, R1 ) Ph2CdCH, R2 ) H
4g, R1 ) Ph, R2 ) Ph
R3 ) nBu
9
R3 ) nBu
10
11
12c
13d
R3 ) nBu
R3 ) nBu
R3 ) nBu
R3 ) nBu
a All the reactions of 4 (0.60 mmol) with thiol (3.00 mmol) were carried
out in the presence of 1e (0.03 mmol) in ClCH2CH2Cl (15 mL) at 60 °C
for 1 h. b Isolated yield. c For 6 h. d For 24 h.
alkyl 1-phenyl-2-propynyl sulfide (5aa-5af) in good yields with
complete regioselectivity. Typical results are shown in Table 3.
Other isomers and products were not observed in the reaction
mixture. The use of benzenethiol led to the formation of phenyl
1-phenyl-2-propynyl sulfide (5ag) in a lower yield (Table 3, run
7). Various propargylic alcohols reacted smoothly to give the
corresponding sulfides in good to excellent yields as shown in runs
8-13 of Table 3, although in the cases of 1-alkenyl-substituted
alcohol 4f and 1,1-diaryl-substituted alcohol 4g the reaction became
slower.9
A stoichiometric reaction of the allenylidene complex 6 with
1-butanethiol did not afford the corresponding propargylic sulfide
5aa (eq 1). This is in sharp contrast to our previous finding that
(12) Nicholas, K. M. Acc. Chem. Res. 1987, 20, 207 and references therein.
(13) (a) Gelling, A.; Jeffery, J. C.; Povey, D. C.; Went, M. J. J. Chem. Soc.,
Chem. Commun. 1991, 349. (b) Bennett, S. C.; Gelling, A.; Went, M. J.
J. Organomet. Chem. 1992, 439, 189. (c) Gelling, A.; Mohmand, G. F.;
Jeffery, J. C.; Went, M. J. J. Chem. Soc., Dalton Trans. 1993, 1857.
(14) (a) Kondo, T.; Mitsudo, T. Chem. ReV. 2000, 100, 3205 and references
therein. (b) Reddy, T. I.; Varma, R. S. Chem. Commun. 1997, 621.
the nucleophilic attack of alcohols and carbon-centered nucleophiles
on the electrophilic Cγ atom in allenylidene intermediates such as
6 gave the corresponding propargylic products.1 The results indicate
JA027754T
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J. AM. CHEM. SOC. VOL. 124, NO. 51, 2002 15173