Novel ruthenium- and platinum-catalyzed sequential reactions: Synthesis of tri- and tetrasubstituted furans and pyrroles from propargylic alcohols and ketones

Article abstract of DOI:10.1002/anie.200351170

Two cats. in the same pot: The two catalysts [Cp*RuCl(μ₂-SMe)₂RuCp*Cl] (1) and PtCl₂ (2) promote a sequence of catalytic cycles in the same medium. Trior tetrasubstituted furans or pyrroles are afforded in moderate to good yields with high regioselectivities from the catalyzed reactions of propargylic alcohols with ketones or with ketones and anilines, respectively (see scheme; cats.=catalysts).

Full text of DOI:10.1002/anie.200351170

Angewandte
Chemie
One-Pot Sequential Reactions
Novel Ruthenium- and Platinum-Catalyzed
Sequential Reactions: Synthesis of Tri- and
Tetrasubstituted Furans and Pyrroles from
Propargylic Alcohols and Ketones**
Yoshiaki Nishibayashi, Masato Yoshikawa,
Youichi Inada, Marilyn Daisy Milton,
Masanobu Hidai,* and Sakae Uemura*
Studies on multiple catalysts within the same medium to
obtain desired products from simple starting materials are
one of the current and important topics in synthetic chemis-
try.[1] The action of multiple catalysts lessens the reaction time
and the yield loss by avoiding the isolation and purification of
intermediates in multiple step sequences. Some interesting
results in which multiple and different transition metal
catalysts work in the same medium were reported,[2] but in
most cases the reaction conditions, such as reaction temper-
ature and reaction atmosphere, need to be changed on the
way, or the successive addition of catalysts is necessary
according to the reaction steps.[3]
Quite recently, we reported the ruthenium-catalyzed
efficient propargylic substitution reactions of propargylic
alcohols with various heteroatom- and carbon-centered
nucleophiles to give the corresponding functionalized prop-
argylic products in high yields with complete regioselectiv-
ities.[4] Noteworthy, the reactions are catalyzed only by
thiolate-bridged diruthenium complexes[5]
such
as
[Cp*RuCl(m2-SR)2RuCp*Cl] (Cp* = h5-C5Me5; R = Me (1a),
iPr (1b), nPr (1c)). The result prompted us to investigate the
transition metal-catalyzed sequential reaction of functional-
ized propargylic products, which have a terminal alkyne,
because organic compounds with a terminal alkyne are
known to be converted into more valuable compounds by
various transition metal catalysts.[6,7] We have now found a
novel sequential reaction system by using heterobimetallic
[*] Prof. Dr. S. Uemura, Dr. Y. Nishibayashi, M. Yoshikawa, Y. Inada,
Dr. M. D. Milton
Department of Energy and Hydrocarbon Chemistry
Graduate School of Engineering
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
E-mail: hidai@rs.noda.sut.ac.jp
[**] 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.
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
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DOI: 10.1002/anie.200351170
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Table 1: Reaction of propargylic alcohol (2) with acetone in the presence
catalysts to give the corresponding tri- and tetra-substituted
of [Cp*RuCl(m-SMe)2RuCp*Cl] (1a) and PtCl2.[a]
furans and pyrroles in moderate to high yields with complete
regioselectivity from the reaction of propargylic alcohols with
ketones in the presence of a catalytic amount of both 1a and
PtCl2. In this reaction system, two different catalysts simulta-
neously promote their catalytic cycles in the same medium.
Preliminary results are described herein.
R
catalyst
R
+
+
H2O
O
O
OH
2
3
Entry
R
Cat (mol%)
t [h] Yield of 3 [%][b]
1
2
3
4
Ph (2a)
Ph (2a)
Ph (2a)
Ph (2a)
Ph (2a)
1a (10) and PtCl2 (20) 36 3a, 64 (75)[c]
1a (10) and PtCl2 (20) 72 3a, 69
1a (10) and PtCl2 (10) 100 3a, (83)[c]
1a (5) and PtCl2 (10)
1a (10) and AuCl3 (20) 36 3a, (36)[c,d]
Treatment of 1-phenyl-2-propyn-1-ol (2a) in acetone in
the presence of 1a (10 mol%), NH4BF4 (20 mol%), and PtCl2
(20 mol%) at reflux temperature for 36 h afforded 2,5-
dimethyl-3-phenylfuran (3a) in 75% yield as measured by
GLC (64% yield of the isolated product; Table 1, entry 1). A
prolonged reaction time improved the yield of 3a (Table 1,
entries 2and 3). The reaction proceeded even in the presence
of smaller quantities of 1a (5 mol%) and PtCl2 (10 mol%;
Table 1, entry 4). Noteworthy, the bimetallic system of 1a and
PtCl2 is essential to promote the catalytic formation of 3a
effectively. Other transition-metal complexes, such as
Pd(OAc)2, [PdCl2(MeCN)2] and PdCl2 were ineffectual,
110 3a, (74)[c]
5
6
7
p-MeC6H4 (2b) 1a (10) and PtCl2 (20) 72 3b, 65
p-MeOC6H4 (2c) 1a (10) and PtCl2 (20) 36 3c, 52
8
9
p-FC6H4 (2d)
p-ClC6H4 (2e)
1a (10) and PtCl2 (20) 72 3d, 57
1a (10) and PtCl2 (20) 72 3e, 74
10
11
12
13
p-CF3C6H4 (2 f) 1a (10) and PtCl2 (20) 36 3 f, 54
2-naphthyl (2g) 1a (10) and PtCl2 (20) 72 3g, 64
¼
Ph2C CH- (2h) 1a (10) and PtCl2 (20) 36 3h, 29
cyclohexyl (2i)
1a (10) and PtCl2 (20) 36 3i, 0
[a] All the reactions of 2 (0.60 mmol) with acetone (30 mL) were carried
out in the presence of catalysts and NH4BF4 (20 mol%) at reflux
temperature. [b] Yield of isolated compound. [c] Yield obtained by GLC.
[d] 3-Phenyl-2,5-hexanedione was also formed with 27% yield obtained
by GLC.
[8]
while AuCl3 worked effectively but an intermediate dike-
tone was also formed (see below; Table 1, entry 5). The use of
various propargylic alcohols resulted in the formation of the
corresponding 3-aryl and 3-alkenyl substituted 2,5-dimethyl-
furans (3b–3h) in moderate to high
Table 2: Reaction of propargylic alcohol (2) with ketone in the presence of [Cp*RuCl(m-SMe)2RuCp*Cl]
(1a) and PtCl2.[a]
yields with a complete regioselec-
tivity (Table 1, entries 6–12).
Yield of 3, %[b]
Unfortunately, the reaction of 1-
cyclohexyl-2-propyn-1-ol did not
proceed at all (Table 1, entry 13).
Reactions of propargylic alco-
Entry
2
Ketone
Furan (3)
1
2
3
R=Ph (2a)
R=p-MeC6H4 (2b)
R=p-FC6H4 (2d)
R=Ph, 72 (3j)
R=p-MeC6H4, 78 (3k)
R=p-FC6H4, 65 (3l)
hols with other ketones were sim-
ilarly carried out. Typical results
are shown in Table 2. Formation of
the corresponding 3-aryl-2,4,5-tri-
methylfurans (3j–3l) was observed
in the reactions of propargylic
alcohols (2a, 2b, 2d) with 2-buta-
none (Table 2; entries 1–3). The
reaction of 2a with 3-pentanone
under the same reaction conditions
gave 2-ethyl-3,5-dimethyl-4-phe-
nylfuran (3m) in 85% yield
(Table 2, entry 4). Noteworthy, the
formation of other regioisomers of
furans was not observed in all
cases. The reactions of various
propargylic alcohols with cyclohex-
anone gave the expected 3-aryl-2-
methyl-4,5,6,7-tetrahydrobenzo-
furans (3n–3p) in high yields
(Table 2, entries 5–7). From 2a
4[c]
R=Ph (2a)
85 (3m)
5
6
7
R=Ph (2a)
R=p-FC6H4 (2d)
R=p-ClC6H4 (2e)
R=Ph, 75 (3n)
R=p-FC6H4, 75 (3o)
R=p-ClC6H4, 69 (3p)
8
R=Ph (2a)
66 (3q)
9
R=Ph (2a)
0 (3r)
[a] All the reactions of 2 (0.60 mmol) with ketone (30 mL) were carried out in the presence of 1a
(0.06 mmol), PtCl2 (0.12 mmol) and NH4BF4 (0.12 mmol) at reflux temperature for 36 h. [b] Isolated
yield. [c] For 72 h.
and cycloheptanone, 2-methyl-3-phenyl-5,6,7,8-tetrahydro-
4H-cyclohepta[b]furan (3q) was obtained in 66% yield, but
no reaction occurred with cyclopentanone (Table 2, entries 8
and 9, respectively).
To obtain some information of the reaction mechanism,
the relationship between the product yields and the reaction
time was investigated in the reaction between 2a and acetone
in the presence of 1a and PtCl2 (Figure 1). This time profile
indicates the following: At first, 2a is transformed rapidly into
g-ketoalkyne (4a) by the catalysis of 1a (Scheme 1, step a).[4b]
Then, hydration of the alkyne moiety in 4a by the produced
H2O slowly gives the 1,4-diketone, 5a, by the catalysis of PtCl2
(Scheme 1, step b).[9] Intramolecular cyclization of the pro-
duced diketone then follows, which results in the formation of
the furan, 3a, also by the catalysis of PtCl2 (Scheme 1,
step c).[9b] This result clearly indicates that two different
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Figure 1. Time profile of the reaction of propargylic alcohol (2a) with
acetone in the presence of [Cp*RuCl(m-SMe)2RuCp*Cl] (1a; 10 mol%)
and PtCl2 (20 mol%).
Scheme 2. Reactions of 1-phenyl-2-propyn-1-ol with ketones and ani-
lines in the presence of [Cp*RuCl(m-SMe)2RuCp*Cl] and PtCl2.
imines (7a).[11] Cyclization of 7a catalyzed by PtCl2 may
produce the substituted pyrrole (6a). It was confirmed that
the reaction of 4a with aniline in the presence of PtCl2
afforded 6a in 77% isolated yield [Eq. (2)]. This result
indicates that sequential three-component coupling reaction
by the catalysis of 1a and PtCl2 occurs in the same medium.
The bimetallic system of 1a and PtCl2 can be applied to
other sequential catalytic reactions. A typical example is
shown in Scheme 3. The reaction of propargylic alcohol (2a)
with 5-methyl-2-furylmethanol in the presence of a catalytic
amount of both 1a and PtCl2 in 1,2-dichloroethane at 608C for
18 h afforded the corresponding phenol derivative 8a in 58%
yield.[12] Propargylation of the furylmethanol with 2a was
promoted by 1a to give the corresponding furylmethyl
propargylic ether,[4a] which was subsequently transformed
into the corresponding phenol derivative by the so far known
catalysis of PtCl2.[13]
Scheme 1. Reaction of 1-phenyl-2-propyn-1-ol with acetone in the pres-
ence of [Cp*RuCl(m-SMe)2RuCp*Cl] and PtCl2.
catalysts, such as 1a and PtCl2, can promote their catalytic
cycles in the same medium. Separately, the transformation
of 4a into 3a and 5a was confirmed in the presence of PtCl2
[Eq. (1)]. However, even upon adding stoichiometric
In summary, we have found novel ruthenium- and
platinum-catalyzed sequential reactions to afford the corre-
sponding tri- and tetra-substituted furans or pyrroles[14] from
propargylic alcohols with ketones, or with ketones and
anilines, respectively, in moderate to good yields with high
regioselectivities. Two different kinds of catalysts 1a and
PtCl2 sequentially promote each catalytic cycle in the same
medium. Some phenol derivatives can also be prepared from
propargylic alcohols and furylmethanol by this bimetallic
amounts of water to 4a, its conversion into 3a via 5a was
slower than that in the present reaction system, thus showing
that the coexistence of 1a and PtCl2 promotes this conversion
more smoothly.
When the above new catalytic reactions were carried out
in the presence of aniline derivatives (5 equiv relative to 2a),
the corresponding tri- and tetra-substituted pyrroles (6) were
produced in moderate isolated yields with complete regiose-
lectivity (Scheme 2).[10] No formation of the corresponding
furans and other regioisomers of 6 was observed in all cases.
Nucleophilic attack of anilines on the carbon-carbon triple
bond in 4a catalyzed by PtCl2 may give the corresponding
Scheme 3. Reaction of 1-phenyl-2-propyn-1-ol with 5-methyl-2-furylme-
thanol in the presence of [Cp*RuCl(m-SMe)2RuCp*Cl] and PtCl2.
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3031; Angew. Chem. Int. Ed. 2000, 39, 2909, and references
therein.
system. Further investigations involving the elucidation of the
detailed reaction mechanism and broadening the scope of this
sequential catalytic systems are currently in progress.
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Experimental Section
A typical experimental procedure for the reaction of 1-phenyl-2-
propyn-1-ol (2a) with acetone catalyzed by [Cp*RuCl(m2-SMe)2-
RuCp*Cl] (1a) and PtCl2 is described below. Complex 1a (38 mg,
0.06 mmol), NH4BF4 (12mg, 0.12mmol), and PtCl
(31 mg,
2
0.12mmol) were placed in a 50 mL flask under N 2. Anhydrous
acetone (30 mL) was added, and then the mixture was magnetically
stirred at room temperature. After the addition of 2a (79 mg,
0.60 mmol), the reaction flask was kept at reflux temperature for 36 h.
The solvent was concentrated under reduced pressure by an aspirator,
and then the residue was purified by TLC (SiO2) with EtOAc-hexane
(1/9) to give 2,5-dimethyl-3-phenylfuran[15] (3a) as a colorless oil
1
(66.5 mg, 0.38 mmol, 64% yield); H NMR (270 MHz, CDCl3): d =
2.28 (s, 3H), 2.40 (s, 3H), 6.10 (s, 1H), 7.21–7.37 ppm (m, 5H);
13C NMR (67.5 Hz, CDCl3): d = 12.9, 13.4, 106.9, 121.4, 126.0, 127.3,
128.5, 134.5, 145.8, 149.7 ppm.
[8] A. Stephen, K. Hashmi, L. Schwarz, J.-H. Choi, T. M. Frost,
Angew. Chem. 2000, 112, 2382; Angew. Chem. Int. Ed. 2000, 39,
2285.
Received: February 13, 2003 [Z51170]
[9] a) W. Hiscox, P. W. Jennings, Organometallics 1990, 9, 1997;
b) W. Baidossi, M. Lahav, J. Blum, J. Org. Chem. 1997, 62, 669;
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[10] A novel one-pot pyrrole synthesis has been reported, see R. U.
Braun, K. Zeitler, T. J. J. Muller, Org. Lett. 2001, 3, 3297.
Keywords: domino reactions · heterocycles · homogeneous
catalysis · platinum · ruthenium
.
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