Copper-catalyzed addition of water affording highly substituted furan and unusual formation of naphthofuran ring from 3-(1-alkenyl)-2-alkene-1-al

Article abstract of DOI:10.1016/j.tetlet.2009.10.125

We have developed a novel one-pot reaction to generate highly substituted furan through the addition of water followed by oxidation and unusual cyclization to naphthofuran ring under the same reaction condition.

Full text of DOI:10.1016/j.tetlet.2009.10.125

Tetrahedron Letters 51 (2010) 273–276
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Tetrahedron Letters
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Copper-catalyzed addition of water affording highly substituted furan and
unusual formation of naphthofuran ring from 3-(1-alkenyl)-2-alkene-1-al
*
Rathin Jana, Sunanda Paul, Anup Biswas, Jayanta K. Ray
Department of Chemistry, Indian Institute of Technology, Kharagpur 721302, India
a r t i c l e i n f o
a b s t r a c t
Article history:
We have developed a novel one-pot reaction to generate highly substituted furan through the addition of
water followed by oxidation and unusual cyclization to naphthofuran ring under the same reaction
condition.
Received 4 September 2009
Revised 22 October 2009
Accepted 28 October 2009
Available online 30 October 2009
Ó 2009 Elsevier Ltd. All rights reserved.
Keywords:
Furan
Naphthofuran
Copper catalyzed
Sonogashira coupling
1. Introduction
catalyst and solvent to optimize the reaction conditions. The re-
sults are summarized in Table 1
Highly substituted furans are an important class of heterocyclic
compounds which are not only present as key structural unit in
many natural products but also useful building blocks in synthetic
chemistry.1 One of the reliable approaches for their synthesis is the
cyclization of allenyl ketones and 3-alkyn-1-ones2 by use of transi-
tional metals catalyst. Larock, Oh and Yamamoto have indepen-
dently reported Au-, Pt- and Cu-catalyzed synthesis of
substituted furans from the 2-alkenyl-1-one.3 It has been
suggested that a metal salt can facilitate the reaction by its dual
function, that is, Lewis acid to activate the carbonyl group and
co-ordination of metal with alkynes.
Finally, we conclude that our optimization condition was CuCl
(10 mol %), 10 equiv H2O in 2–3 mL DMF, heated at 95–100 °C for
12–14 h. We next examined the scope of this reaction with differ-
ent 3-(1-alkynyl)-2-alkene-1-als (2a–2h) to obtain the furan ring
in moderate to good yield which are shown in Table 2.
The mechanism presumably involves copper-catalyzed 1,6-
addition of water. In cycle A copper co-ordinates with carbonyl
oxygen to activate the adjacent triple bond, followed by 5-exo-
dig cyclization. Then 1,6-addition of water and consequently aerial
Herein, we report a synthetic approach towards the highly
substituted furan4 by a cuprous chloride-catalyzed sequential
one-pot reaction of 2a–2h through cyclization and 1,6-addition
of water as a nucleophile followed by oxidation (Scheme 1).
The convergent approach involved the preparation of the
precursors 2a–2o which were efficiently synthesized from bro-
movinylaldehydes by Sonogashira coupling5 as per Scheme 2.
The initial experiment was carried out by heating the mixture of
compound 2a, H2O (10 equiv) and CuCl in DMF at 95–100 °C in an
open flask for 12–14 h (Table 1, entry 1). A furan ring resulted from
the substrate 2a. By shortening the reaction time to 6 h and lower-
ing the temperature to 80 °C, very low yields were obtained (Table
1, entries 2–3). The reaction was then attempted by changing the
Ph
O
Ph
Cu(I), H2O
O
DMF, air
CHO
2a-2h
3a-3h
Scheme 1. Synthesis of substituted furan ring by copper-catalyzed reaction.
Ar
Br
O
Ar
H
PBr3, DMF
CHCl3
CuI, Pd(PPh3)2Cl2
Et3N
CHO
2a-2o
CHO
1a-1o
* Corresponding author.
E-mail address: jkray@chem.iitkgp.ernet.in (J.K. Ray).
Scheme 2. Synthesis of starting materials.
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.10.125

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R. Jana et al. / Tetrahedron Letters 51 (2010) 273–276
Table 1
Cu(I)
Ph
Optimization studiesa
Cu(I)
O
Ph
Ph
O
Ph
O
O
H
O
CHO
2a
3a
Ph
Cu
Entry
Catalyst
Solvent
Temp (°C)
Time (h)
Yield (%)
aerial oxidation
Cycle A
1
2
3
4
5
6
7
CuCl
CuCl
CuBr
CuBr
CuCl
CuCl
CuBr
DMF
DMF
DMF
DMF
CH3CN
Toluene
CH3CN
95
80
80
95
85
95
85
12
6
6
13
12
14
12
68
25
20
61
30
20
15
O
H+
Ph
HO
O
H2O
Cu+
Ph
a
All the reactions were carried out in the presence of 10 equiv H2O, in open flask.
O
Table 2
1,6 addition of H2O
Copper-catalyzed synthesis of furana
Scheme 3. Proposed mechanism for the formation of furan ring.
Entry
Reactants
Products
Yield (%)
68
Ph
O
Ph
Ar
1
Ar
O
Ar
O
CHO
2a
O
O
3a
CHO
Ph
O
CuCl, air
H O
Ph
+
DMF,
2
2
3
66
64
Z
Z
Z
O
3i-3o
4i-4o
Minor
CHO
Ph
Me
2i-2o
Me
O
2b
3b
Major
Ph
Scheme 4. Synthesis of substituted furan and naphthofuran ring.
O
CHO
oxidation of alcohols lead to furan ring. The plausible mechanism
of this reaction is outlined below (Scheme 3).
2c
3c
Ph
O
Ph
During the course of our reaction an interesting result was ob-
tained, when the reactants (2i–2o) were treated with cuprous
chloride under the same reaction conditions to afford fused napht-
hofuran along with small amount of 1,6-addition product (Scheme
4). Then we generalized our reaction with different substituent and
in every case we obtained the naphthofuran in moderate to good
yield. The results are shown in Table 3.
The ORTEP structure of naphthofuran of 3j is shown below
(Scheme 5).
The plausible mechanism of this reaction is described in
Scheme 6. Cu(I) first co-ordinates with the triple bond to activate
4
5
6
68
69
58
O
CHO
2d
2e
3d
O
Ph
Ph
O
CHO
3e
Ph
O
Ph
Ph
Ph
O
CHO
C17
2f
3f
C16
C18
CHO
O
C15
Ph
C19
C14
7
8
60
65
C11
Ph
O
2g
C12
O1
3g
Me
C7
Me
C3
C6
C4
Ph
O
O
C2
C1
C8
C9
Ph
OHC
C5
C10
O2
3h
2h
C13
a
Reagents and conditions: CuCl (10 mol %), H2O (10 equiv) and DMF (2–3 mL),
heated at 95–100 °C for 12–14 h.
Scheme 5.

R. Jana et al. / Tetrahedron Letters 51 (2010) 273–276
275
Table 3
Copper-catalyzed synthesis of furan and naphthofuran ring
Entry
Reactants
Products
Yield (%)
Ph
Ph
Ph
O
O
O
1
65 and 20
63 and 25
65 and 25
50 and 45
CHO
MeO
3i
MeO
MeO
4i
2i
Ph
Ph
O
Ph
O
O
CHO
Ph
2
3
4
OMe
3j
4j
OMe
2j
OMe
Ph
O
Ph
O
O
MeO
MeO
MeO
CHO
3k
4k
2k
Ph
Ph
Ph
O
O
O
CHO
3l
4l
2l
pTol
pTol
pTol
O
O
O
MeO
MeO
MeO
CHO
5
62 and 30
3m
4m
2m
mTol
mTol
O
mTol
O
O
MeO
MeO
MeO
CHO
6
58 and 30
3n
4n
2n
pTol
pTol
pTol
O
O
O
CHO
7
62 and 20
OMe
3o
4o
OMe
OMe
2o
Reagents and conditions: CuCl (10 mol %), H2O (10 equiv) and DMF (2–3 mL), heated at 95–100 °C for 12–14 h.
the carbonyl group to form oxonium complex B. Then water mol-
ecule attacks at the carbon atom adjacent to the oxygen atom to
form intermediate C. Then ring opening followed by the reaction
with the atmospheric oxygen molecule to form D, which undergoes
rearrangement in the presence of water to afford 1,4-dicarbonyl
compound E with the elimination of formic acid. This dicarbonyl

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R. Jana et al. / Tetrahedron Letters 51 (2010) 273–276
Ph
Cu+
Ph
Ph
O
Cu
Cu+
O+
H+
O
H
O-H
O=O
MeO
H2O
A
MeO
MeO
C
B
Ph
H2O
Ph
Ph
O
O
O
O
O
O
O
O-H
MeO
H
MeO
H
D
MeO
E
F
Ph
O-H
Ph
O
O
MeO
MeO
H
G
H
Scheme 6. Proposed mechanism for the formation of naphthofuran ring.
compound forms naphthofuran ring with the elimination of water
molecule is shown in Scheme 6.
13C NMR (CDCl3, 100 MHz) d: 55.32, 100.21, 107,57, 112.53,
118.21, 122.46, 123.97, 124.58, 124.65 (2C), 124.82, 128.17,
128.77 (2C), 130.63, 131.46, 151.33, 155.33, 156.70.
In conclusion, we have developed a new methodology for the syn-
thesis of highly substituted furan ring by the addition of water and
unusual formation of naphthofuran ring from 3-(1-alkynyl)-2-
alkene-1-al derivatives at the same reaction condition. This reaction
is also helpful for synthesis of some furoquinone-based natural
products.
HRMS: calcd for C19H15O2 [M++H]: 275.1072; found 275.1073.
Acknowledgements
We thank CSIR, New Delhi, for the fellowships and we also
thank D.S.T. for providing funds for the project and creating
400 MHz NMR facility under the IRPHA programme.
2. Typical experimental procedure for the synthesis of furan ring
Compounds 2a (1 equiv), CuCl (10 mol %), H2O (10 equiv) and
DMF (2–3 mL) were placed in a two-necked round-bottomed
flask. Then the mixture was heated to 95–100 °C for 12–14 h.
After cooling, the reaction mixture was diluted with water, ex-
tracted with ether (20 mL Â 3) and dried over anhydrous Na2SO4.
The solvent was evaporated and the crude product was purified
by preparative thin layer chromatography (petroleum ether/ethyl
acetate 20:1).
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2009.10.125.
References and notes
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Marshall, J. A.; Wang, X.-J. J. Org. Chem. 1991, 56, 960; (d) Fukuda, Y.; Shiragami,
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3. Spectral data of representative compounds
3.1. Compound 4i
1H NMR (CDCl3, 200 MHz) d: 2.72 (m, 2H), 2.91 (m, 2H), 3.85 (s,
3H), 6.87 (m, 2H), 7.39 (s, 1H), 7.43–7.56 (m, 3H), 7.94 (dd, 2H,
J = 8.4 Hz, J = 1.6 Hz), 8.60 (d, 1H, J = 8.4 Hz).
13C NMR (CDCl3, 50 MHz) d: 19.02, 30.61, 55.31, 111.83, 114.08,
121.00, 125.28, 128.10 (2C), 129.64 (2C), 130.34, 131.51, 131.99,
138.78, 139.46, 140.21, 145.92, 160.11, 184.35.
HRMS: calcd for C20H17O3 [M++H]: 305.1178; found 305.1128.
3.2. Compound 3i
5. (a) Liang, Y.; Xie, Y.-X.; Li, J.-H. J. Org. Chem. 2006, 71, 379; (b) Li, P.; Wang, L.; Li,
H. Tetrahedron 2005, 61, 8633; (c) Gholap, A. R.; Venkatesan, K.; Pasricha, R.;
Daniel, T.; Lahoti, R. J.; Srinivasan, K. V. J. Org. Chem. 2005, 70, 4869; (d) Yi, C.;
Hua, R. J. Org. Chem. 2006, 71, 2535; (e) Gelman, D.; Buchwald, S. L. Angew.
Chem., Int. Ed. 2003, 42, 5993; (f) Elangovan, A.; Wang, Y.-H.; Ho, T.-I. Org. Lett.
2003, 5, 1841.
White solid, mp 156–158 °C 1H NMR (CDCl3, 400 MHz); 3.95 (s,
3H), 7.28 (m, 2H), 7.35 (t, 1H, J = 7.6 Hz), 7.47 (m, 3H), 7.64 (q, 2H,
J = 8.8 Hz), 7.93 (d, 2H, J = 8 Hz), 8.07 (d, 1H, J = 8.8 Hz).