Propargylation of aromatic compounds with propargylic alcohols catalyzed by a cationic diruthenium complex

Article abstract of DOI:10.1002/anie.200250532

Two metals are better than one: The cationic methanethiolate-bridged diruthenium complex 1 (Cp* = C₅Me₅, OTf = CF₃SO₃) promotes the catalytic propargylation of aromatic compounds with propargylic alcohols bearing not only terminal alkyne but also internal alkyne units, reactions that can not be carried out with some mononuclear catalysts. This reaction provides a general and environmentally friendly (atom economical, only H₂O as byproduct) method for the synthesis of a variety of propargylated aromatic compounds.

Full text of DOI:10.1002/anie.200250532

Angewandte
Chemie
The reactions are only catalyzed by thiolate-bridged diruthe-
nium complexes, such as [Cp*RuCl(m2-SR)2RuCp*Cl][2]
(Cp* = h5-C5Me5; R = Me (1a), iPr (1b), nPr (1c)). In this
catalytic reaction, usable propargylic reagents were unfortu-
nately strictly limited to the propargylic alcohols bearing
terminal acetylene groups, because the reactions proceeded
by an electrophilic aromatic-substitution reaction at the g-
carbon of the allenylidene intermediates, which can only be
produced from this type of propargylic alcohol.[3a–c] During
our study of the catalytic propargylation of aromatic com-
pounds, we have now found that a cationic methanethiolate-
bridged diruthenium complex [Cp*RuCl(m2-SMe)2RuCp*-
(OH2)]OTf (1d; OTf = CF3SO3)[3d] promotes the catalytic
propargylation of aromatic compounds with propargylic
alcohols bearing not only terminal acetylene but also internal
acetylene units. The reaction described herein provides a
general preparative synthetic method for a variety of
propargylated aromatic compounds. The most characteristic
features of this reaction are its high atom economy and
environmental friendliness, the only stoichiometric by-prod-
uct being water (H2O).
C-H Activation with Ru
We investigated the propargylation of 2-methylfuran with
propargylic alcohols, such as 1,3-diphenyl-2-propyn-1-ol (2a),
with internal acetylene units. Treatment of 2-methylfuran
with 2a in 1,2-dichloroethane in the presence of 1d (5 mol%)
at 608Cfor 1 h afforded 5-methyl-2-(1,3-diphenyl-2-propy-
nyl)furan (3aa) in 88% isolated yield (Table 1; entry 1).
Propargylation of Aromatic Compounds with
Propargylic Alcohols Catalyzed by a Cationic
Diruthenium Complex**
Yoshiaki Nishibayashi, Youichi Inada,
Masato Yoshikawa, Masanobu Hidai,* and
Sakae Uemura*
Table 1: Propargylation of 2-methylfuran with 1,3-diphenyl-2-propyn-1-ol
(2a).[a]
Ph
Ph
We have recently disclosed that the ruthenium-catalyzed
propargylation of aromatic compounds with propargylic
alcohols affords the corresponding propargylated aromatic
compounds in good yields with a complete regioselectivity.[1]
Ph
5 mol% cat.
Ph
+
+
H2O
O
ClCH2CH2Cl
60 °C, 1 h
O
OH
2a
3aa
Entry
Catalyst
Yield [%][b]
[*] Prof. Dr. S. Uemura, Dr. Y. Nishibayashi, Y. Inada, M. Yoshikawa
Department of Energy and Hydrocarbon Chemistry
Graduate School of Engineering
1
2[c]
3
4
5
6
7
8
9
[Cp*RuCl(m-SMe)2Cp*Ru(OH2)]OTf (1d)
[Cp*RuCl(m-SMe)2Cp*Ru(OH2)]OTf (1d)
[Cp*RuCl(m-SiPr)2Cp*Ru(OH2)]OTf (1e)
[Cp*RuCl(m-SMe)2Cp*RuCl] (1a)[d]
[Cp*RuCl(m-SiPr)2Cp*RuCl] (1b)[d]
[CpRuCl(PPh3)2]
[RuCl2(PPh3)3]
[{RuCl2(p-cymene)}2]
[(indenyl)RuCl(PPh3)2]
[Cp*RuCl(m2-Cl)2RuCp*Cl]
88
50
81
0
0
0
0
0
0
0
Kyoto University, Yoshida, Sakyo-ku, Kyoto 606-8501 (Japan)
Fax: (+81)75-753-3573
E-mail: uemura@scl.kyoto-u.ac.jp
Prof. Dr. M. Hidai
Department of Materials Science and Technology
Faculty of Industrial Science and Technology
Tokyo University of Science, Noda, Chiba 278-8510 (Japan)
Fax: (+81)471-23-9362
10
E-mail: hidai@rs.noda.sut.ac.jp
[a] All of the reactions of 2-methylfuran (1.500 mmol) with 2a
[**] This work was supported by a Grant-in-Aid for Scientific Research
(No. 13305062) from the Ministry of Education, Science, Sports,
and Culture of Japan.
(0.300 mmol) were carried out in the presence of catalyst (0.015 mmol)
in ClCH2CH2Cl (8 mL) at 608C for 1 h. [b] Isolated yield. [c] At room
temperature for 5 h. [d] No reaction even in the presence of NH4BF4.
Angew. Chem. Int. Ed. 2003, 42, 1495 – 1498
DOI: 10.1002/anie.200250532
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Communications
Neither other products nor regioisomers of 3aa were detected
Next, the propargylation of various aromatic compounds
with 2a was examined in the presence of 1d (5 mol%) at
608C. Typical results are summarized in Table 3. The corre-
sponding propargylic compounds (4aa–4ad) were obtained
from a variety of heterocyclic compounds such as furan, 2,3-
dimethylfuran, pyrrole, and 2-methylthiophene in good yields
with a complete regioselectivity (Table 3; entries 1–4). In all
cases, propargylation occurred selectively at the a position of
heterocyclic rings. These results indicate that the reaction
proceeds electrophilically. In the cases of electron-rich arenes
such as 1,3-dimethoxybenzene, 1,3,5-trimethoxybenzene, an
acetanilide derivative, and phenol, the corresponding prop-
argylated benzene derivatives (4ae–4ah) were obtained in
91%, 73%, 41%, and 80% isolated yields, respectively
(Table 3; entries 5–8). Although the reaction of 2-methoxy-
naphthalene with 2a gave 1-propargylic naphthalene (4ai) in
94% yield (Table 3; entry 9), that of 2-naphthol afforded the
unexpected 3H-naphtho[2,1-b]pyrane (5a) in 21% yield with
the formation of unidentified compounds (Scheme 1).[4] The
by GLCand 1H NMR. The reaction proceeded even at room
temperature, but a longer reaction time was required to
obtain 3aa even in 50% isolated yield (Table 1; entry 2). The
complex with the sterically demanding SiPr group (1e)
exhibited a slightly lower catalytic activity (Table 1; entry 3).
It is noteworthy that neutral thiolate-bridged diruthenium
complexes (1a and 1b), which are known to promote the
propargylation of aromatic compounds with propargylic
alcohols bearing terminal acetylene groups,[1] did not work
at all (Table 1; entries 4 and 5). Other di- and monoruthenium
complexes such as [CpRuCl(PPh3)2] (C =ph5-C5H5),
[RuCl2(PPh3)3],
[{RuCl2(p-cymene)}2],
[(indenyl)-
RuCl(PPh3)2], and [Cp*RuCl(m2-Cl)2RuCp*Cl] were ineffec-
tive for this catalytic propargylation (Table 1; entries 6–10).
Reactions of 2-methylfuran with other propargylic alco-
hols bearing internal acetylene units have been similarly
carried out. Typical results are shown in Table 2. The
Table 2: Propargylation of 2-methylfuran with propargylic alcohols (2).[a]
Ph
Ph
+
Ph
+
R3
OH
R2
5 mol% 1d
Ph
R3
O
R2
R1
H2O
R1
ClCH2CH2Cl
5 mol% 1d
OH
+
+
H2O
60 °C, 1 h
2a
O
ClCH2CH2Cl
O
OH
2
5a
60 °C, 1 h
3
Scheme 1. Reaction of 1,3-diphenyl-2-propyn-1-ol with 2-naphthol.
Entry
Propargylic alcohol
Yield of 3 [%][b]
R1
R2
R3
high yield formation of 1-propargylated azulene (4aj) was
observed in the reaction of azulene with 2a (Table 3;
entry 10). No propargylation occurred under these reaction
conditions, however, when naphthalene, anisole, 1,4-dime-
thoxybenzene, p-xylene, toluene, and N,N-dimethylaniline
were used as aromatic compounds.
The complex 1d also catalyzed the propargylation of
aromatic compounds with propargylic alcohols bearing ter-
minal acetylene groups.[1] In fact, the treatment of 2-methyl-
furan with 1-phenyl-2-propyn-1-ol in the presence of 1d
(5 mol%) at 608Cfor 1 h afforded 2-methyl-5-(1-phenyl-2-
propynyl)furan (6a) in quantitative yield (Scheme 2), show-
1
2
3
4
5
6
7[d]
8[d]
2b
2c
2d
2e
2 f
2g
2h
2i
Ph
Ph
Ph
p-MeC6H4
H
H
H
H
nBu
tBu
n-hexyl
Ph
Ph
Ph
3ab, 91
3ac, 80
3ad, 83
3ae, 91
3af, 60
3ag, 49[c]
3ah, 20[e]
3ai, 0[f]
¼
Ph2C CH
H
Ph
Me
Et
Me
Me
H
Ph
Ph
[a] All of the reactions of 2-methylfuran (1.500 mmol) with 2
(0.300 mmol) were carried out in the presence of 1d (0.015 mmol) in
ClCH2CH2Cl (8 mL) at 608C for 1 h. [b] Isolated yield. [c] 2,4-Diphenyl-1-
buten-3-yne (20%) was formed. [d] For 3 h. [e] 2-Methyl-4-phenyl-1-
buten-3-yne (40%) was formed. [f] No reaction.
Ph
5 mol% 1d
Ph
corresponding 2-propargylic furans (3ab–3ae) were obtained
from various alkyl and aryl substituted propargylic alcohols
(2b–2e) in excellent yields with a complete regioselectivity
(Table 2; entries 1–4). The reaction with 1-alkenyl substituted
propargylic alcohol (2 f) gave the corresponding propargylic
furan (3af) in 60% isolated yield (Table 2; entry 5). The
propargylation of 2-methylfuran with 1,1-disubstituted prop-
argylic alcohol such as 2,4-diphenyl-3-butyn-2-ol (2g)
afforded the expected propargylic furan (3ag) in slightly
lower yield, but together with the formation of 2,4-diphenyl-
1-buten-3-yne in 20% yield (Table 2; entry 6). Similarly, the
reaction with 1,1-dialkyl substituted propargylic alcohol gave
both the corresponding propargylated furan (3ah) in only
20% yield and the conjugated enyne in 40% yield (Table 2;
entry 7). On the other hand, no propargylation proceeded
when 1-alkyl substituted propargylic alcohol such as 2i was
used (Table 2; entry 8).
+
+
H2O
O
ClCH2CH2Cl
O
OH
60 °C, 1 h
6a
Scheme 2. Propargylation of 2-methylfuran with 1-phenyl-2-propyn-1-ol.
ing that the cationic complex exhibited almost the same
catalytic activity as the neutral diruthenium complex 1a.[1]
Thus, the novel cationic methanethiolate-bridged diruthe-
nium complex 1d promotes the catalytic propargylation of a
variety of aromatic compounds with propargylic alcohols
bearing not only terminal acetylene but also internal acety-
lene groups.
A 1H NMR spectroscopy investigation was carried out by
mixing a stoichiometric amount of 1d and 2a at room
temperature in CD2Cl2, but no formation of intermediates
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Chemie
Table 3: Propargylation of aromatic compounds with 2a.[a]
identified. Although direct evi-
dence of the reactive intermediates
has not yet been obtained, we
believe that the catalytic reaction
with propargylic alcohols with inter-
nal acetylene units may proceed via
(h-propargyl)ruthenium species.[5,6]
An electrophilic attack of the (h-
propargyl)ruthenium complexes on
aromatic compounds should afford
the corresponding propargylated
aromatic products. On the other
hand, the propargylation of aro-
matic compounds with propargylic
alcohols bearing terminal acetylene
groups is considered to proceed by
electrophilic attack of the cationic
Cg atom in the allenylidene inter-
mediate, as shown previously.[1]
Entry
Aromatic compound
t [h]
Product
Yield [%][b]
71
Ph
Ph
Ph
1
2
4aa
4ab
4ac
4ad
O
O
O
Ph
2
3
4
2
17
1
41
60
88
O
Ph
Ph
Ph
Ph
N
H
NH
S
S
In summary, we have now found
Ph
that the cationic diruthenium com-
plex 1d promotes the catalytic
propargylation of aromatic com-
pounds with propargylic alcohols
bearing not only terminal acetylene
but also internal acetylene units.
The catalytic reaction described
here provides a general and envi-
ronmentally friendly preparative
synthetic method (atom economi-
cal, only H2O as byproduct) for a
variety of propargylated aromatic
compounds. The electrophilic aro-
matic-substitution reaction by free
propargylic cations has been
reported, but the products are
either propargylated or allenylated
aromatic products and/or a mixture
of them, depending on the substitu-
ents of the propargylic cations.[7,8]
Also, the well known Nicholas reac-
tion requires several steps and uses
Ph
MeO
MeO
OMe
OMe
OMe
5
6
7
3
1
4ae
4af
4ag
91
73
41
OMe
Ph
Ph
MeO
OMe
OMe
OMe
Ph
Ph
H
N
MeO
H
N
OMe
20
O
O
OMe
OH
OMe
Ph
Ph
8
9
20
1
4ah
4ai
4aj
80
94
91
OH
Ph
Ph
OMe
a
stoichiometric
amount
of
OMe
[Co2(CO)8] for the preparation of
these compounds.[9,10] Some propar-
gylated aromatic compounds are
useful monomers in the field of
material science. Further investiga-
tions for the elucidation of the
detailed reaction mechanism and
broadening the scope of this cata-
lytic propargylation are currently in
progress.
Ph
Ph
10
25
[a] All of the reactions of aromatic compound (1.500 mmol) with 2a (0.300 mmol) were carried out in
the presence of 1d (0.015 mmol) in ClCH2CH2Cl (8 mL) at 608C. [b] Isolated yield.
was observed. The addition of an excess amount of 2-
Experimental Section
methylfuran to this reaction mixture, however, led to the
1d: 1a (965 mg, 1.52 mmol)[3a,b] was placed in a 50-mL flask under N2.
Anhydrous THF (20 mL) was added, and then the mixture was stirred
with a magnetic stirrer at room temperature for 5min. After the
addition of AgOTf (398 mg, 1.52 mmol), the reaction flask was kept
high-yield formation of 3aa together with an almost complete
recovery of 1d. These results may indicate that the inter-
mediates of this catalytic reaction are too labile to be
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1497

Communications
at room temperature for 20 h. Then, the solvent was removed under
M. E. Pauly, N. P. Rath, J. Chem. Soc. Chem. Commun. 1994, 49;
d) J.-Y. LeBrazidec, P. J. Kocienski, J. D. Connolly, K. W. Muir, J.
Chem. Soc. Perkin Trans. 1 1998, 2475; e) R. Guo, J. R. Green,
Chem. Commun. 1999, 2503.
reduced pressure, and the residue was recrystallized from CH2Cl2/n-
hexane to give black crystals of 1d (1.02 g, 1.26 mmol, 82%);
1H NMR (270 MHz, CDCl3): d = 1.63 (s, 30H), 2.51 (s, 6H),
3.30 ppm (brs, 2H); 13C NMR (67.5 Hz, CDCl3) d = 1.1, 10.5,
96.5 ppm; elemental analysis calcd (%) for C23H38ClF3O4Ru2S3: C
35.91, H 4.98; found: C35.78, H 4.71.
A typical reaction of 2-methylfuran with 1,3-diphenyl-2-propyn-
1-ol (2a) catalyzed by 1d: 1d was placed in a 20-mL flask (12.2 mg,
0.015 mmol) under N2. Anhydrous ClCH2CH2Cl (8 mL) was added,
and then the mixture was magnetically stirred at room temperature
for 5 min. After the addition of 2a (62.6 mg, 0.300 mmol) and 2-
methylfuran (123.2 mg, 1.500 mmol), the reaction flask was kept at
608Cfor 1 h. The solvent was concentrated under reduced pressure
(aspirator), and then the residue was purified by column chromatog-
raphy on SiO2 with EtOAc/hexane (1/9) as eluent to give 5-methyl-2-
(1,3-diphenyl-2-propynyl)furan (3aa) as a pale yellow oil (71.8 mg,
0.264 mmol, 88% yield); 1H NMR (270 MHz, CDCl3): d = 2.23 (s,
3H), 5.20 (s, 1H), 5.88 (d, J = 3.0 Hz, 1H), 6.12 (d, J = 3.0 Hz, 1H,)
7.27–7.47 ppm (m, 10H); 13C NMR (67.5 Hz, CDCl3): d = 13.7, 37.9,
83.7, 87.7, 106.1, 107.2, 123.2, 127.1, 127.7, 127.9, 128.1, 128.4, 131.6,
139.0, 151.6, 151.7 ppm; elemental analysis calcd (%) for C20H16O: C
88.20, H 5.92; found: C88.38, H 6.09.
Received: November 12, 2002 [Z50532]
ꢀ
Keywords: alkynes · aromatic substitution · C H activation ·
ruthenium · S ligands
.
[1] Y. Nishibayashi, M. Yoshikawa, Y. Inada, M. Hidai, S. Uemura,
J. Am. Chem. Soc. 2002, 124, 11846.
[2] The thiolate-bridged diruthenium complexes have been found to
provide unique bimetallic reaction sites for activation and
transformation of various terminal alkynes, see: Y. Nishibayashi,
M. Yamanashi, I. Wakiji, M. Hidai, Angew. Chem. 2000, 112,
3031; Angew. Chem. Int. Ed. 2000, 39, 2909, and references
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1498
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Angew. Chem. Int. Ed. 2003, 42, 1495 – 1498