I--catalyzed methyl-oxygen bond cleavage in 2-methoxyfurans. An efficient synthesis of butenolides

Article abstract of DOI:10.1021/jo048430l

(Chemical Equation Presented) An efficient I^--catalyzed methyl-oxygen bond cleavage in 2-methoxyfurans was observed. The subsequent C-C bond formation occurred at the 5-position to afford substituted butenolides. The structures of the final pro

Full text of DOI:10.1021/jo048430l

wish to report a I--catalyzed reaction of 2-alkoxyfurans
with organic iodides to form substituted butenolides.
I--Catalyzed Methyl-Oxygen Bond
Cleavage in 2-Methoxyfurans. An Efficient
Synthesis of Butenolides
Under the catalysis of a Lewis acid, the O-X bond
(X ) Si, COMe) of 2-substituted furans, such as 2-siloxy5-7
and 2-acetoxy,8 was cleaved to react with electrophiles
at the 5-position of furans. For 2-boroxyfurans,9 these
reactions can occur in the absence of a catalyst. However,
similar reactions with 2-alkoxyfurans are limited to
protonation with TsOH10,11 or oxidation with MnO2-
HCl.12 A stoichiometric TMSI-mediated reaction of 2-meth-
oxyfuran with R,â-unsaturated ketones has been re-
ported.13 BF3-mediated reactions of 2-methoxyfuran with
allylic alcohols have also been reported.14 Recently, our
group has reported that inorganic halides can serve as
catalysts in the cleavage of C-C bonds in a series of
reactions, such as the ring-opening of cyclopropenes15 and
Shengming Ma,* Lianghua Lu, and Ping Lu
State Key Laboratory of Organometallic Chemistry,
Shanghai Institute of Organic Chemistry, Chinese Academy
of Sciences, 354 Fenglin Lu, Shanghai 200032, P. R. China
masm@mail.sioc.ac.cn
Received September 7, 2004
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An efficient I--catalyzed methyl-oxygen bond cleavage in
2-methoxyfurans was observed. The subsequent C-C bond
formation occurred at the 5-position to afford substituted
butenolides. The structures of the final products were
determined by the X-ray diffraction study.
Butenolides are an important structure unit in natural
products and intermediates in organic synthesis.1 Buteno-
lide-containing compounds are considered as potential
insecticides, bactericides, fungicides, antibiotics, cyclo-
oxygenase inhibitors, phospholiphase A2 inhibitors, etc.2
Chemists have developed many ways to synthesize these
interesting compounds.3 Recently, our group also has
reported some methods for the synthesis of butenolides
by transition metal-promoted or -catalyzed cyclization
reactions of 2,3-allenoic acids/esters.4 In this paper, we
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10.1021/jo048430l CCC: $30.25 © 2005 American Chemical Society
Published on Web 12/31/2004
J. Org. Chem. 2005, 70, 1063-1065
1063

TABLE 1. Effects of Solvents on the Reaction of 1a and
2aa
TABLE 2. Effects of Catalysts on the Reaction of 1a and
2aa
Na2CO3 allylic iodide
time yield
(h) (%)
entry
cat.
allylic iodide
time (h)
yield (%)
entry cat.
(equiv)
(equiv)
solvent
1
NaI
1.2
1.2
2.0
1.2
1.2
1.2
10.5
48
79
60
57
60
75
61
1
2
NaIb
NaI
NaI
NaI
NaI
NaI
NaI
NaI
NaI
-
1.0
0.6
0.5
0.5
0.5
0.5
0.5
0.1
-
1.2
2.0
2.0
2.0
2.0
2.0
2.0
1.2
1.2
1.2
DMFc
CH2Cl2
CH3CN
11
15
2
LiI
3b
4
KIc
33
22
18
34
NR
8
LiBr
NaBrd
LiCl
3
5
6
14.5
22
4
toluenec 14.5 trace
5
dioxanec 34
39
60
70
72
6
acetone
THF
10
15
13
a The reaction was carried out using 0.25-0.5 mmol of 1a and
2a in 1-2 mL of solvent under reflux. b The solvent was acetone.
c 0.5 equiv of K2CO3 was used. d 20 mol % NaBr was used.
7
8
THF
9
THF
10.5 79
10
-
THF
10
NR
TABLE 3. NaI-Catalyzed Reaction of 2-Methoxy
3,5-Disubstituted Furans with Organic Iodidesa
a The reaction was carried out using 0.25-0.5 mmol of 1a,
Na2CO3, and 2a in 1-2 mL of solvent under reflux. b 20 mol %
NaI was used. c The reaction was conducted at 80 °C.
cycloisomerization of alkylidene cyclopropyl ketones.16 In
this context, an I--catalyzed direct alkyl-oxygen cleavage
of 2-alkoxyfurans and the subsequent reaction with
organic halides will be reported.
2-Methoxy-3-methoxycarbonyl-5-phenylfuran 1a, which
was easily available from the reaction of phenylacetyl-
ene with diazomethylmalonate under the catalysis of
Rh2(OAc)4,17 could react with allylic iodide 2a to form
5-allyl-3-methoxycarbonyl-5-phenylbutenolide 3aa in 15%
yield under the catalysis of NaI in DMF (eq 1).
On the basis of this promising result, the solvent effects
were further investigated and some typical results are
listed in Table 1. Among the solvents tested, THF and
acetone were the best, while CH2Cl2, CH3CN, toluene,
and dioxane were all inferior (Table 1). Further research
proved that the base was not necessary in this reaction
(Table 1, entry 9) while in the absence of NaI, no reaction
was observed (Table 1, entry 10). Different inorganic
catalysts were also tested in this reaction (Table 2) with
NaI affording the best results (Table 2, entry 1).
With the optimized conditions in hand, the scope of this
reaction was explored. Some typical results are sum-
marized in Table 3. It could be seen from Table 3 that
R1 can be an alkyl group, benzyl, or an aryl group.
Different organic iodides were tested in this reaction
(entries 2-10, Table 3). Basically, reactive sp3 organic
a The reaction was carried out using 0.25-0.5 mmol of 1a and
2a in 1-2 mL of solvent under reflux. b 2.0 equiv of allylic iodide
were used. c 10 mol % Na2CO3 was used. d The reaction was
carried out with 3.0 equiv of MeI in a sealed tube.
iodides all could participate the reaction. However, the
alkyl iodides showed much lower reactivity. The struc-
tures of 3 were established by a single-crystal X-ray
diffractional study of 3ae.18 It should be noted that the
(18) X-ray data for compound 3ae: C17H16O6, Mw ) 316.30, mono-
clinic, space group P2(1)/n, Mo KR, final R indices [I > 2σ(I)], R1 )
0.0455, wR2 ) 0.0801, a ) 904395(11) Å, b ) 11.5890(14) Å, c )
15.0764(18) Å, R ) 90°, â ) 104.516(2)°, γ ) 90 ° V ) 1596.6 3) Å3, T
(16) Ma, S.; Lu, L.; Zhang, J. J Am. Chem. Soc. 2004, 126, 9645.
(17) (a) Padwa, A.; Kassir, J.; Xu, S. L. J. Org. Chem. 1991, 56, 6971.
(b) Batsila, C.; Kostakis, G.; Hadjiarapoglou, L. P. Tetrahedron Lett.
2002, 43, 5997.
) 293(2) K, Z ) 4, reflections collected/unique: 9566/3722 (Rint
)
0.0605), parameters 273. CCDC 244480 contains the supplementary
crystallographic data.
1064 J. Org. Chem., Vol. 70, No. 3, 2005

SCHEME 1. A Plausible Mechanism for the
Reaction of 1 and 2
in-situ formed MeI may leave the reaction mixture due
to its low bp (41-43 °C) under the current reaction
conditions, which excluded the formation of 5-methyl-
butenolides.
A detailed study showed that a mixture of 4-methyl-
substituted and 4-ethyl-substituted products 3ab and
3ag was formed when EtI was used as the iodide (eq 2),
indicating that MeI was generated in situ in this NaI-
catalyzed reaction. Indeed, 3ab was formed in 17% yield
after 21 h from the treatment of 1a with 10 mol % NaI
in the absence of any organic iodide (eq 3). To explore
the source of Me in the structure of the product 3ab in
eq 2, we designed a deuterium-labeling experiment. From
eq 4, it can be concluded that both the added CD3I and
the in-situ-generated MeI participated the reaction.
C-O bond in the ester group may be attributed to the
acetal-like structure. Due to the easy availability of the
starting materials, simple operation, and mild conditions,
this method will show its utility in the synthesis of
butenolides. Further studies in this area are being
pursued in our laboratory.
Experimental Section
General Procedure for NaI-Catalyzed Reaction of
2-Methoxyfuran with Organic Iodides. In a flame-dried
argon-flushed flask, a solution of 1a (116 mg, 0.5 mmol), 2a (101
mg, 0.6 mmol), and NaI (8 mg, 0.05 mmol) in 2 mL of dry THF
was stirred for 10.5 h under reflux. After evaporation, the
residue was purified by column chromatography (eluent: pe-
troleum ether/Et2O ) 5/1) on silica gel to afford 3aa (102 mg,
79%): liquid; 1H NMR (300 MHz, CDCl3) δ 7.58-7.66 (m, 2 H),
7.37-7.44 (m, 3 H), 5.84 (s, 1 H), 5.63-5.77 (m, 1 H), 5.12-5.25
(m, 2 H), 3.77 (s, 3 H), 2.93 (dd, J ) 13.8, 6.9 Hz, 1 H), 2.80 (dd,
J ) 13.8, 7.8 Hz, 1 H); 13C NMR (75.4 MHz, CDCl3) δ 173.3,
167.9, 154.1, 130.6, 130.2, 128.7, 127.4, 125.1, 120.6, 101.9, 60.2,
53.3, 38.6; MS m/z 258 (M+, 9.08), 217 (100); IR (neat) 1806,
1743, 1648, 1235 cm-1. Anal. Calcd for C15H14O4: C, 69.79; H,
5.46. Found: C, 69.53; H, 5.57.
According to the results mentioned above, a plausible
catalytic cycle for this reaction is depicted in Scheme 1.
The attack of I- at the methyl group19 led to the cleavage
of the methyl-oxygen bond with the formation of MeI
and intermediate 4,7d,9 which would react with an organic
iodide to afford 3.
In conclusion, we have observed a very mild cleavage
of the methyl-oxygen bond of 2-methoxyfurans under the
catalysis of I-, which was followed by the formation of a
new C-C bond with organic halides at the 5-position of
the furans to afford butenolides. The higher reactivity
of the targeted carbon-methoxy bond than that of the
Acknowledgment. Financial support from the Na-
tional Natural Science Foundation of China and the
Major State Basic Research Development Program
(Grant No. G2000077500) are greatly appreciated.
Supporting Information Available: Typical experimen-
tal procedure and analytical data for all products not listed in
the text. This material is available free of charge via the
Internet at http://pubs.acs.org.
(19) (a) Arbuzov, B. A. Pure Appl. Chem. 1964, 9, 307. (b) Krapcho,
A. P.; Glynn, G. A.; Grenon, B. J. Tetrahedron Lett. 1967, 215.
JO048430L
J. Org. Chem, Vol. 70, No. 3, 2005 1065