Bu4N[AuCl4]-catalyzed synthesis of highly substituted furans from 2-(1-alkynyl)-2-alken-1-ones in ionic liquids: An air-stable and recyclable catalytic system

Article abstract of DOI:10.1055/s-2006-947363

The cyclization of 2-(1-alkynyl)-2-alken-1-ones proceeded smoothly in the presence of various nucleophiles with a catalytic amount of Bu ₄N[AuCl₄] in [bmim]BF₄, leading to the formation of highly substituted furans. This s

Full text of DOI:10.1055/s-2006-947363

1962
LETTER
Bu4N[AuCl4]-Catalyzed Synthesis of Highly Substituted Furans from
2-(1-Alkynyl)-2-alken-1-ones in Ionic Liquids: An Air-Stable and Recyclable
Catalytic System
Synthesis of
Highl
u
y Substituted
e
Furans yuan Liu,a Zhenliang Pan,a Xingzhong Shu,a Xinhua Duan,a Yongmin Liang*a,b
a
State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, P. R. of China
Fax +86(931)8912582; E-mail: liangym@lzu.edu.cn
b
State Key Laboratory of Solid Lubrication, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou 730000,
P. R. of China
Received 6 April 2006
Initial studies have been carried out on 2-phenylethynyl-
2-cyclohexen-1-one (1a) and methanol (1.5 equiv) using
Bu4N[AuCl4] as catalyst in CH2Cl2 at room temperature
for three hours. It afforded high yield (92%) of desired
product 2a (Scheme 1). It is notable that nearly the same
yield was obtained using [bmim]BF4 as the solvent, in-
stead of CH2Cl2.11 Subsequently, the recyclability of the
cyclization reaction with gold catalyst in [bmim]BF4 was
examined (Table 1). The system was recycled and reused
for five runs without any significant loss of catalyst activ-
ity. To prove the stability of the catalyst, the system was
reused for the sixth run after being exposed to air for two
weeks. Satisfactorily, the catalytic system still remained
good activity. The experimental process was quite simple
and easy. The product was extracted from the reaction
mixture by addition of diethyl ether and the recovered ion-
ic liquid layer was pumped for several minutes and reused
for the next reaction directly.12
Abstract: The cyclization of 2-(1-alkynyl)-2-alken-1-ones pro-
ceeded smoothly in the presence of various nucleophiles with a
catalytic amount of Bu4N[AuCl4] in [bmim]BF4, leading to the for-
mation of highly substituted furans. This system is air-stable and
recyclable. The catalyst is inexpensive and readily available.
Key words: gold-catalyzed, cyclization reaction, ionic liquids,
furans, recyclable
Furans are an important class of heterocyclic compounds
that are extensively used as synthetic building blocks1 and
appear as a subunit in many natural products and
substances of relevance for industry.2 Considerable effort
has been directed toward the development of new and
efficient methodologies for the synthesis of furans.3 A
particularly effective approach to the synthesis of func-
tionalized furans is through the transition-metal-catalyzed
cyclization of an alkynyl or allenyl ketone,4 epoxide,5 cy-
cloisomerizations of (Z)-2-en-4-yn-1-ols,6 or electrophilic
cyclization of alk-3-yne-1,2-diols,7 etc. Among them,
much attention has been paid to the synthesis of furan
derivatives by gold-catalyzed.5c,6c,8 Recently, Larock has
reported an interesting AuCl3-catalyzed cyclization of 2-
(1-alkynyl)-2-alken-1-ones leading to the formation of
highly substituted furans.8a Although this method is gen-
eral, it is a considerable drawback that a highly air-sensi-
tive and expensive metal catalyst is often lost at the end of
the reaction. Hence, a process for recycling the catalytic
system is of importance. The analogous cyclization reac-
tion has been achieved using Cu(I) catalyst in DMF.9
However, high-temperature was required in the reaction.
O
Ph
O
1 mol% Bu4N[AuCl4]
[bmim]BF4, r.t.
Ph
+
MeOH
OMe
1a
2a
Scheme 1
Table 1 Recycling of Bu4N[AuCl4]-Catalyzed Cyclization
a
Reaction in [bmim]BF4
Runs
1
2
3
4
5
6
Yield (%)b 90 (88) 88 (89) 89 (89) 88 (87) 86 (85) 85
We are interested in the development of a new air-stable,
inexpensive and recyclable gold catalyst. To our best
knowledge, there are no reports of the recyclability of the
catalyst, though several reports have been presented in the
literature by gold catalyst for the synthesis of furans.
Herein, we wished to report an efficient recyclable
cyclization reaction of 2-(1-alkynyl)-2-alken-1-ones10 by
a more economical approach using Bu4N[AuCl4] as
catalyst in ionic liquids to multiply substituted furans.
a The reaction was carried out using 0.2 mmol of 1a, 1.5 equiv of nu-
cleophile, 1 mol% of catalyst in 1.0 mL of [bmim]BF4 at r.t. for 3 h.
b Isolated yield. In parentheses: isolated yields of the cyclization re-
action performed on a 1.0 mmol scale.
Having established the recyclability and reusability of this
system, we next investigated its performance for the cy-
clization reaction of various 2-(1-alkynyl)-2-alken-1-ones
1 with nucleophiles.13 The results are summarized in
Table 2. Treatment of 1a with allylic alcohol or propar-
gylic alcohol, the substrate underwent smooth cyclization
reaction giving rise to the corresponding furans in 80%
and 88% yields, respectively (Table 2, entries 2 and 3).
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Advanced online publication: 24.07.2006
DOI: 10.1055/s-2006-947363; Art ID: W07406ST
© Georg Thieme Verlag Stuttgart · New York

LETTER
Synthesis of Highly Substituted Furans
1963
a
Table 2 Bu4N[AuCl4]-Catalyzed Cyclization Reaction of 2-(1-alkynyl)-2-alken-1-ones in [bmim]BF4
Entry
Substrate
Nucleophile
Products
Time (h)
Isolated yield (%)
R1
O
R1
O
Nu
1
2
3
R1 = Ph
1a
MeOH
Nu = MeO
2a
3
3
3
90
80
88
1a
OH
O
2b
2c
1a
OH
O
4
5
6
1a
1a
1a
3
3
3
74
96
85
OH
O
2d
2e
OH
O
OH
O
O
O
I
I
2f
O
7
8
1a
1a
3
5
73
52
O
2g
NMe2
NMe2
2h
9
10
11
R1 = p-MeOC6H4
1b
MeOH
MeOH
MeOH
MeO
2i
3
3
3
85
97
76
R1 = p-O2NC6H4
1c
MeO
2j
Ph
O
Ph
O
O
O
OMe
1d
2k
12
MeOH
3
82
O
Ph
Ph
MeO
Ph
Ph
Ph
Ph
O
1e
2l
a The reaction was carried out using 0.2 mmol of 1, 1.5 equiv of nucleophile, 1 mol% of catalyst in 1.0 mL of [bmim]BF4 at r.t.
The reaction of the secondary alcohol i-PrOH with 1a pro- yield of the furan 2g (Table 2, entry 7). Furthermore, elec-
ceeded smoothly to afford product 2d in 74% yield tron-rich arenes such as N,N-dimethylaniline were
(Table 2, entry 4). Benzylic alcohols worked very well in effective nucleophiles in the gold-catalyzed cyclization
our experiment, and the desired products were obtained in reaction (Table 2, entry 8). Alkynes bearing either elec-
high yields (Table 2, entries 5 and 6). The weak nucleo- tron-rich or electron-poor aryl groups were treated with
philes such as 1,3-cyclohexanedione also led to a good methanol under the standard conditions, the correspond-
Synlett 2006, No. 12, 1962–1964 © Thieme Stuttgart · New York

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X. Liu et al.
LETTER
(5) (a) Lo, C. Y.; Guo, H.; Lian, J. J.; Shen, F. M.; Liu, R. S. J.
Org. Chem. 2002, 67, 3930. (b) Marshall, J. A.; DuBay, W.
J. J. Am. Chem. Soc. 1992, 114, 1450. (c) Hashmi, A. S. K.;
Sinha, P. Adv. Synth. Catal. 2004, 346, 432.
(6) (a) Gabriele, B.; Salerno, G.; Lauria, E. J. Org. Chem. 1999,
64, 7687. (b) Seiller, B.; Bruneau, C.; Dixneuf, P. H. J.
Chem. Soc., Chem. Commun. 1994, 493. (c) Liu, Y.; Song,
F.; Song, Z.; Liu, M.; Yan, B. Org. Lett. 2005, 7, 5409.
(7) Bew, S. P.; Knight, D. W. Chem. Commun. 1996, 1007.
(8) (a) Yao, T.; Zhang, X.; Larock, R. C. J. Am. Chem. Soc.
2004, 126, 11164. (b) Suhre, M. H.; Reif, M.; Kirsch, S. F.
Org. Lett. 2005, 7, 3925. (c) For a review of gold catalysis,
see: Hashmi, A. S. K. Gold Bull. 2004, 37, 51.
(9) Patil, N. T.; Wu, H.; Yamamoto, Y. J. Org. Chem. 2005, 70,
4531.
(10) For the synthesis of furans by the electrophilic cyclization of
the same substrate, see: (a) Yao, T.; Zhang, X.; Larock, R.
C. J. Org. Chem. 2005, 70, 7679. (b) Liu, Y.; Zhou, S. Org.
Lett. 2005, 7, 4609.
ing furans were obtained in good yields (Table 2, entries
9 and 10). Employing chromone (1d) and acyclic 2-alken-
1-one (1e) as substrate, the cyclization reaction proceeded
well with methanol to give the products 2k and 2l in 76%
and 82% yield, respectively (Table 2, entries 11 and 12).
In summary, we have developed an efficient synthesis of
highly substituted furans through the cyclization of 2-(1-
alkynyl)-2-alken-1-ones with various nucleophiles by a
recyclable gold catalyst in ionic liquid. This method offers
the following competitive advantages: (i) recyclability of
the catalyst without significant loss of catalytic activity;
(ii) use of readily available, inexpensive catalysts; (iii)
simple and easy operation.
Acknowledgment
The authors thank the NSFC-20021001, NSFC-20572038 and the
‘Hundred Scientist Program’ from the Chinese Academy of
Sciences for the financial support.
(11) Representative Procedure.
To the appropriate 2-(1-alkynyl)-2-alken-1-one (0.2 mmol)
and nucleophile (1.5 equiv) in [bmim]BF4 (1 mL) was added
Bu4N[AuCl4] (1 mol%). The mixture was stirred at r.t. for
3 h unless otherwise specified. The mixture was extracted
with Et2O (2 × 5 mL). The isolated ether layer was
concentrated in vacuo and the residue was purified by flash
chromatography on silica gel.
References and Notes
(1) Maier, M. Organic Synthesis Highlights II; Waldmann, H.,
Ed.; VCH: Weinheim, 1995, 231.
(2) Donnelly, D. M. X.; Meegan, M. J. Comprehensive
Heterocyclic Chemistry, Vol. 4; Katritzky, A. R.; Rees, C.
W., Eds.; Pergamon: New York, 1984, 657.
(12) Recycling Procedure.
To the 2-phenylethynyl-2-cyclohexen-1-one (1.0 mmol) and
MeOH (1.5 equiv) in [bmim]BF4 (3 mL) was added
Bu4N[AuCl4] (1 mol%). The mixture was stirred at r.t. for
3 h. The product was extracted from the reaction mixture by
addition of Et2O (2 × 20 mL). The ether layer was separated.
The ionic liquid layer containing Au catalyst was pumped
for several minutes and reused for the next reaction.
(13) Spectral Data of the Representative Product 2a.
1H NMR (300 MHz, CDCl3): d = 1.79–1.93 (m, 2 H), 1.94–
2.05 (m, 2 H), 2.59–2.75 (m, 2 H), 3.43 (s, 3 H), 4.28 (t,
J = 3.9 Hz, 1 H), 6.64 (s, 1 H), 7.18–7.23 (m, 1 H), 7.31–7.36
(m, 2 H), 7.60–7.63 (m, 2 H). 13C NMR (75 MHz, CDCl3):
d = 18.8, 23.2, 28.3, 56.1, 72.3, 105.3, 119.9, 123.3, 126.8,
128.5, 131.1, 152.2, 152.8.
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Synlett 2006, No. 12, 1962–1964 © Thieme Stuttgart · New York