Tuning of regioselectivity in inorganic iodide-catalyzed alkylation of 2-methoxyfurans via electronic and steric effects

Article abstract of DOI:10.1002/adsc.201100337

In the presence of inorganic iodide, the methoxy C-O bond in 2-methoxyfurans may be cleaved to afford the corresponding lactonic anion. Due to the presence of an electron-withdrawing group at the 3-position, the alkylation with normal organic iodides occu

Full text of DOI:10.1002/adsc.201100337

FULL PAPERS
DOI: 10.1002/adsc.201100337
Tuning of Regioselectivity in Inorganic Iodide-Catalyzed
Alkylation of 2-Methoxyfurans via Electronic and Steric Effects
Jie Chen,a Shengjun Ni,a and Shengming Maa,b,*
a
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of
Sciences, 345 Lingling Road, Shanghai 200032, Peopleꢀs Republic of China
Shanghai Key Laboratory of Green Chemistry and Chemical Process, Department of Chemistry, East China Normal
b
University, 3663 North Zhongshan Road, Shanghai 200062, Peopleꢀs Republic of China
Fax : (+86)-21-6260-9305; e-mail: masm@mail.sioc.ac.cn
Received: May 1, 2011; Revised: December 10, 2011; Published online: April 13, 2012
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.201100337.
Abstract: In the presence of inorganic iodide, the iodide as the catalyst. With magnesium iodide as the
À
methoxy C O bond in 2-methoxyfurans may be catalyst, the 5-allylation occurred highly regioselec-
cleaved to afford the corresponding lactonic anion. tively. As a whole, the 3- vs. 5-alkylation selectivity
Due to the presence of an electron-withdrawing may be determined by the relative steric hindrance
group at the 3-position, the alkylation with normal at the 3- and 5-positions and the electronic effect of
organic iodides occurred at the 3-position highly re- the allylic iodides. A rationale was proposed.
gioselectively. However, when electron-deficient al-
lylic iodides with an electron-withdrawing group at
the 2-position were used the 5-alkylation products Keywords: alkylation; C O bond cleavage; furans;
were formed as the major products with sodium lactones; regioselectivity
À
Introduction
Results and Discussion
Butenolides are found as key structural elements in In 2003, our group reported that inorganic halides can
À
many bioactive natural products and important phar- serve as catalysts in the cleavage of C C bonds in
maceuticals.[1] Consequently, numerous synthetic a series of reactions, such as the ring-opening of cy-
pathways to this class of compounds have been devel- clopropenes[8] and cycloisomerization of alkylidenecy-
oped.[2] In the past decades, the catalytic coupling of clopropyl ketones.[9] Then, the catalyst-controlled re-
2-silyoxyfurans or 2-acetoxyfurans using Lewis acids gioselective cycloisomerization of cyclopropenyl ke-
has emerged as a prominent strategy for butenolide tones[10] or cyclopropenyl carboxylates[11] affording
synthesis.[3] For 2-alkoxyfurans, these reactions can differently substituted methoxyfurans was also devel-
also occur, but they are mainly limited to protonation oped by our group. Herein, we wish to report the
with TsOH·H2O,[4] or oxidation with MnO2-HCl.[5] In highly regioselective alkylation of 2-methoxyfurans
1981, a stoichiometric TMSI-mediated reaction of 2- resulting from cycloisomerizations of cyclopropenyl
methoxyfuran with a,b-unsaturated ketones was re- carboxylates at the 3- or 5-position to synthesize dif-
ported.[6] Then, BF3-mediated reactions of 2-methoxy- ferent butenolides with inorganic iodide as the cata-
furan with allylic alcohols were also reported.[7] To lyst in dependence on the steric effects of the sub-
date, the synthesis of butenolides via alkylation is pri- stituents in the furans as well as the electronic effect
marily focused on the alkylation of 2-methoxyfurans of the organic iodides (Scheme 1).
at the 5-position, whereas alkylation of 2-methoxyfur-
Due to the electronic effect of the a-alkoxycarbon-
ans at the 3-position has received relatively little at- yl group, 3-position alkylation may be expected. Ini-
tention.
tially, the NaI-catalyzed alkylation of 1a with organic
iodide 2a was tested. The reaction proceeded smooth-
ly to afford butenolide 3aa with the alkylation occur-
ring highly selectively at the 3-position of 1a in the
presence of a catalytic amount of NaI in THF at 808C
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Tuning of Regioselectivity in Inorganic Iodide-Catalyzed Alkylation of 2-Methoxyfurans
highly selectively at the 3-position of 2-methoxyfuran
1
1 according to H NMR spectroscopic analysis of the
crude reaction mixture forming 3.
Then different allylic iodides were explored in the
reaction (Table 2). When allylic iodides 2i–2m were
used as the substrates, the alkylation reaction also oc-
curred highly selectively at the 3-position of 2-me-
thoxyfuran 1 with a regioselectivity of up to >99:1
(Table 2, entries 1–7). With 2-methoxyfuran 1c and al-
lylic iodide 2i as the substrates, the reaction could
also occur, albeit in a relatively low yield (Table 2,
entry 8). However, in some cases, trace amounts of
the 5-allylation products 4 were formed (Table 2, en-
tries 1, 3, 4, and 7).
Scheme 1. Inorganic iodide-catalyzed reaction of 2-methoxy-
furan and different organic iodides.
Surprisingly, when electron-deficient allylic iodides
[Eq. (1)].[12] The structure of butenolide 3aa was fur- with R5 being CO2Me, CO2Et, CO2-n-Bu, CN, COPh,
ther confirmed by a corresponding gHMQC experi- or SO2Ph were used as the substrates, the allylation
ment and X-ray diffraction study (Figure 1).[13]
reaction occurred at both the 3-position and the 5-po-
sition of 1 to give a mixture of butenolides 3 and 4
with the 5-alkylation product butenolide 4 being the
major one, which is different from what was reported
previously by us.[12] In addition, when 2-methoxyfuran
1c with R2 being SO2Ph and allylic iodide 2n were
used, the product 4cn was formed with a regioselectivi-
ty of >99:1, although some unidentified products
were also formed (Table 3, entry 9). Interestingly, it
was observed that with a bulky R1 group at the 5-po-
sition, the amount of 3 increased. When R1 is tert-
butyl, 3 becomes the major product again (Table 3,
entry 11). These results indicate that the regioselctivi-
ty in the reaction was affected by the relative steric
effect of R1 and R2 of the 2-methoxyfuran 1 and the
Under the same conditions, different 2-methoxyfur- electronic effect of R5 in allylic iodide 2. The struc-
ans 1 and organic iodides 2 were investigated. The re- ture of butenolide 4ao was further confirmed by its
sults are summarized in Table 1. It can be seen that X-ray diffraction studies (Figure 2).[14]
R1 can be an alkyl group (Table 1, entries 1–3) or
In order to improve the regioselectivity in the 5-al-
phenyl group (Table 1, entries 4–8). Basically, MeI lylation reaction, we have tried some other inorganic
(Table 1, entry 1), BnI (Table 1, entry 2), ICH2CO2Et iodides. When KI and CuI were used, the reaction is
(Table 1, entries 3 and 4), and iodomethyl ketones rather slow. When 0.1 equivalent of LiI was used,
(Table 1, entries 5–8) could participate in the reaction 12% of 3bn and 84% of 4bn with 1:7 regioselectivity
smoothly. Herein, all the alkylation reactions occurred were obtained (Table 4).
Figure 1. ORTEP representation of 3aa.
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Table 1. NaI-catalyzed alkylation of 2-methoxyfuran 1 with organic iodide 2.[a]
Entry
R1/R2 (1)
R (2)
Time [h]
Isolated yield of 3 [%]
1
2
3
4
5
6
7
8
n-C4H9/CO2Me (1b)
n-C4H9/CO2Me (1b)
n-C4H9/CO2Me (1b)
Ph/CO2Me (1a)
Ph/CO2Me (1a)
Ph/CO2Me (1a)
Me (2b)[b]
Bn (2c)
16
22
8
17
11
6
81 (3bb)
81 (3bc)
69 (3bd)
86 (3ad)
83 (3ae)
86 (3af)
90 (3ag)
86 (3ah)
EtO2CCH2 (2d)
EtO2CCH2 (2d)
CH3COCH2 (2e)
PhCOCH2 (2f)
2-naphthylCOCH2(2g)
p-PhC6H4COCH2 (2h)
Ph/CO2Me (1a)
Ph/CO2Me (1a)
11
6
[a]
The reaction was carried out using 0.20 mmol of 1 and 0.24 mmol of 2 in 2 mL of THF at 808C.
2.4 equiv. of MeI were used.
[b]
Table 2. NaI-catalyzed reaction of 2-methoxy-3,5-disubstituted furans 1 with allylic iodides 2.[a]
Entry
R1/R2 (1)
R3/R4/R5 (2)
Time [h]
Isolated yield of 3 [%]
1
2
3
4
5
6
7
8
n-Bu/CO2Me (1b)
n-Bu/CO2Me (1b)
n-Bu/CO2Me (1b)
Ph/CO2Me (1a)
Ph/CO2Me (1a)
Ph/CO2Me (1a)
Ph/CO2Me (1a)
Ph/SO2Ph (1c)
H/H/H (2i)[b]
H/H/Ph (2j)
H/H/Me (2k)
H/H/H (2i)[b]
Ph/H/H (2l)
H/H/Ph (2j)
Me/Me/H (2m)
H/H/H (2i)
16
49
18
22
10
48
22
12
14
22
14
76 (3bi)[c]
66 (3bj)
80 (3bk)[d]
82 (3ai)[e]
92 (3al)
60 (3aj)
86 (3am)[f]
23 (3ci)[g]
19 (3di)
9
10
11
n-Bu/COOH (1d)
n-Bu/COMe (1e)
H/H/H (2i)
H/H/H (2i)
H/H/H (2i)
45 (3ei)[h]
79 (3fi)
n-Bu/CON(Me)
N
[a]
The reaction was carried out using 0.20 mmol of 1 and 0.40 mmol of 2 in 2 mL of THF at 808C.
1.2 equiv. of 2i were used.
The regioselectivity of 3/4 is >73:1, if any.
The selectivity of 3/4 is 20:1.
The selectivity of 3/4 is 27:1.
The selectivity of 3/4 is 35:1.
[b]
[c]
[d]
[e]
[f]
[g]
[h]
The reaction was carried out using 1c (0.45 mmol), 2i (0.90 mmol), 10 mol% NaI, and 10 mol% Na2CO3 in THF (2 mL).
1
The regioselectivity of 3/4 is >12:1 as determined by H NMR analysis of the crude product, if any.
When 0.1 equivalents of MgI2 was used as the cata- uct 3bn was subjected to the above reaction condi-
lyst, the alkylation of 2-methoxyfuran 1b and 1g with tions. However, no 5-allylation product 4bn was ob-
electron-deficient allylic iodides 2n–2o and 2r–2s oc- served with 3bn being recovered in 84% yield as de-
1
curred at the 5-position in good yields with up to termined by H NMR spectroscopic analysis of the
>99:1 regioselectivity (Scheme 2). The regioselectivi- crude reaction mixture (Scheme 3). This result indi-
ty with MgI2 as the catalyst is obviously much higher cates that 5-allylation product 4bn was not produced
than that with NaI.
through a [3,3]-sigmatropic rearrangement of 3-alky-
In order to understand the mechanism for the for- lation product 3bn.[15]
mation of 5-alkylation product 4bn, 3-allylation prod-
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Tuning of Regioselectivity in Inorganic Iodide-Catalyzed Alkylation of 2-Methoxyfurans
Table 3. NaI-catalyzed reaction of 2-methoxy-3,5-disubstituted furans 1 with allylic iodides 2.[a]
Entry
R1/R2 (1)
R5 (2)
Time [h]
3:4[b]
Isolated yield [%] of 3
Isolated yield [%] of 4
1
2
3
4
5
6
7
8
n-Bu/CO2Me (1b)
n-Bu/CO2Me (1b)
n-Bu/CO2Me (1b)
n-Bu/CO2Me (1b)
Ph/CO2Me (1a)
Ph/CO2Me (1a)
Ph/CO2Me (1a)
Ph/CO2Me (1a)
n-Bu/SO2Ph (1c)
c-hexyl/CO2Me (1g)
t-Bu/CO2Me (1h)
CO2Et (2n)
CN (2o)
11
11
21
48
8
17
24
11
36
17
24
1:5
1:6
1:2
1:10
1:7
1:5
1:5
1:6
–
11 (3bn)
8 (3bo)
21 (3bp)
6 (3bq)
10 (3ar)
17 (3an)
13 (3as)
11 (3ao)
– (3cn)
65 (4bn)
63 (4bo)
45 (4bp)
68 (4bq)
78[d] (4ar)
76 (4an)
82 (4as)
71 (4ao)
50 (4cn)
50 (4gn)
21 (4hn)
SO2Ph (2p)[c]
COPh (2q)[c]
CO2Me (2r)
CO2Et (2n)
CO2-n-Bu (2s)
CN (2o)
9[e]
10
11
CO2Et (2n)
CO2Et (2n)
CO2Et (2n)
1:2
2.5:1
28 (3gn)
59 (3hn)
[a]
The reaction was carried out using 0.20 mmol of 1 and 0.40 mmol of 2 in 1 mL of THF at 808C.
The ratio was determined by H NMR analysis of the crude reaction mixture.
1.5 equiv. of iodides were used.
98% purity determined with mesitylene as the internal standard.
Two unidentified products were formed in the reaction.
[b]
[c]
[d]
[e]
1
Figure 2. ORTEP representation of 4ao.
Table 4. Inorganic iodide-catalyzed reaction of 2-methoxyfuran 1b with organic iodide 2n.
Entry
Inorganic iodide
Time
3bn:4bn[a]
Yield [%][a] of 3bn
Yield [%][a] of 4bn
Recovery of 1b [%][a]
1
2
3
KI
CuI
LiI
4.5 d
4.5 d
10.5 h
–
–
1:7
–
–
12
19
20
84
47
46
–
[a]
1
These data were determined by H NMR analysis of the crude product.
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Scheme 2. MgI2-catalyzed reaction of 2-methoxyfurans 1b and 1g with organic iodides 2n–2o and 2r–2s.
the distribution of the negative charge in I, when the
normal organic alkyl or allylic iodides were used in
this reaction, the butenolides 3 were obtained by reac-
tion at the 3-position (cycle a); When allylic iodides
with an electron-deficient C=C bond were used as
substrates, 5-allylation products 4 are obtained as the
major or as the only product via the Michael addition
and elimination process shown in II (cycle b).
Scheme 3. MgI2-catalyzed reaction of butenolide 3bn.
According to these results, a plausible mechanism
The one-pot cycloisomerization and alkylation reac-
for this reaction is depicted in Scheme 4. First, the tions were also tested (Scheme 5). The sequentially
attack of iodide anion at the methyl group of 1a led Ru-catalyzed cycloisomerization of cyclopropenyl di-
to the cleavage of the methyl-oxygen bond with the carboxylate 6 and NaI-catalyzed alkylation of furan
formation of MeI and the delocalized intermediate with iodomethane 2b could afford butenolide 3ab in
I.[16] Due to the stabilizing effect of the electron-with- 74% total yield with >99:1 regioselectivity in a one-
drawing methoxycarbonyl group at the 3-position on pot manner. Using the same strategy, butenolide 4ar
Scheme 4. The plausible reaction mechanism.
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Tuning of Regioselectivity in Inorganic Iodide-Catalyzed Alkylation of 2-Methoxyfurans
Scheme 5. One-pot cycloisomerization and alkylation reactions of cyclopropenyl dicarboxylate 6.
could be obtained in 72% total yield and 96:4 regiose-
lectivity with MgI2 as the catalyst and allylic iodide 2r
as the allylation reagent.
Starting Materials
MgI2 was purchased from Aldrich or Alfa Aesar. RuCl2
AHCTUNGTRENNUNG
(PPh3)2,[17] cyclopropenyl dicarboxylate 6,[18] and 2-methoxy-
furans 1[11] were prepared according to the published proce-
dures.
Conclusions
2-Methoxy-3-(hydroxycarbonyl)-5-butylfuran (1d)[19]
In conclusion, we have observed a highly regioselec-
tive alkylation of 2-methoxyfurans at the 3- or 5-posi-
tion using organic iodides to synthesize different but-
To a three-neck, 100 mL, round-bottomed flask were added
sequentially 2-methoxyfuran 1b (1.700 g, 8 mmol), 20 mL of
H2O, 20 mL of MeOH, and NaOH (0.800 g, 20 mmol) and
the resulting mixture was stirred at 908C. After 2 h the reac-
tion was over as monitored by TLC. The resulting mixture
was cooled to room temperature and carefully acidified by
addition of 40 mL of 1M aqueous HCl. Then 20 mL of ethyl
ether were added and the aqueous layer was extracted with
ethyl ether (4ꢂ20 mL). The combined organic layer was
dried over Na2SO4, filtered, and concentrated by rotary
evaporation. Recrystallization with hexane afforded the de-
sired product 1d as a solid; yield:1.346 g (85%); mp 204–
2068C. 1H NMR (300 MHz, CDCl3): d=10.44 (bs, 1H,
COOH), 6.19 (s, 1H, CH=), 4.10 (s, 3H, OCH3), 2.51 (t, J=
7.5 Hz, 2H, CH2), 1.63–1.53 (m, 2H, CH2), 1.43–1.31 (m,
2H, CH2), 0.93 (t, J=7.4 Hz, 3H, CH3); 13C NMR
(100 MHz, CDCl3): d=168.8, 162.0, 146.3, 106.0, 90.7, 58.0,
29.5, 27.2, 22.0, 13.7; MS (EI): m/z=198 (M+, 22.84), 155
(100); IR (neat): n=3141, 3037, 2958, 2932, 2871, 2750,
2610, 2570, 1799, 1742, 1655, 1590, 1491, 1474, 1464, 1440,
1378, 1294, 1280, 1252, 1161, 1139, 1102, 1087 cmÀ1; anal.
calcd. for C10H14O4: C 60.59; H 7.12; found: C 60.42; H 7.08.
ACHTUNGTRENNUNGenolides. The alkylation at the 3-positon of 2-methox-
yfurans can be achieved with up to >99/1 regioselec-
tivity using NaI as catalyst with normal alkyl, allylic
iodides and a-iodoketones. The allylation at the 5-
positon of 2-methoxyfurans can be achieved with up
to >99/1 regioselectivity using MgI2 as the catalyst
with allylic iodides bearing an electron-deficient C=C
bond. Further synthetic applications and the mecha-
nism investigations of the alkylation reaction are cur-
rently underway in our laboratory.
Experimental Section
1H and 13C NMR spectra were recorded on the instruments
operating at 300 or 400 (1H), 75 or 100 MHz (13C), respec-
tively, in CDCl3. Chemical shifts (d) are given in parts per
million (ppm) with the residual peak of CHCl3 at 7.260 ppm
or TMS at 0.000 ppm as the internal standard. Infrared spec-
tra were recorded from thin films of pure samples. Mass and
HR-mass spectra were carried out in EI or ESI mode. Thin
layer chromatography was performed on pre-coated glass-
backed plates and visualized with UV light at 254 nm. Flash
column chromatography was performed on silica gel (10–40
m). THF used in the experiments was refluxed in the pres-
ence of sodium wire using diphenyl ketone as indicator and
distilled right before use.
2-Methoxy-3-acetyl-5-butylfuran (1e)[20]
To a one-neck, 100-mL, round-bottomed flask were added
sequentially 1d (793 mg, 4 mmol) and 50 mL of THF. 10 mL
of CH3Li (1.6M in diethyl ether, 16 mmol) were added
dropwise to the mixture at 08C within 15 min and the result-
ing mixture was stirred at 08C for 2 h. The reaction was
quenched with 20 mL of saturated aqueous NH4Cl solution.
The separated aqueous layer was extracted with Et2O (3ꢂ
20 mL). The combined organic layer was washed with brine,
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dried over anhydrous Na2SO4, and concentrated by rotary
evaporation. Purification by column chromatography on
silica gel (eluent: petroleum ether/ethyl acetate=20/1) af-
forded the desired product 1e as an oil; yield: 125 mg
53.7, 43.2; MS (ESI): m/z=439 (M+Na+, 81Br), 437 (M+
+
+
Na+, 79Br), 434 (M+NH4 , 81Br), 432 (M+NH4 , 79Br), 417
(M+H+, 81Br), 415 (M+H+, 79Br); IR (neat): n=1800,
1742, 1681, 1587, 1493, 1446, 1400, 1351, 1286, 1227, 1117,
1071, 1006 cmÀ1; anal. calcd. for C20H15O5Br: C 57.85; H
3.64; found: C 57.73; H 3.48.
1
(16%). H NMR (300 MHz, CDCl3): d=6.24 (s, 1H, CH=),
4.09 (s, 3H, CH3), 2.50 (t, J=7.5 Hz, 2H, CH2), 2.35 (s, 3H,
CH3), 1.62–1.52 (m, 2H, CH2), 1.41–1.33 (m, 2H, CH2), 0.93
(s, J=7.4 Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3): d=
191.7, 161.3, 146.7, 104.9, 101.8, 57.5, 29.4, 28.3, 27.1, 22.0,
13.7; MS (EI): m/z=196 (M+, 26.85), 153 (100); IR (neat):
n=2957, 2932, 2873, 1659, 1593, 1469, 1417, 1378, 1355,
1280, 1262, 1134, 1086, 1061, 1020 cmÀ1; HR-MS (EI): m/z=
196.1098, calcd. for C11H16O3 (M+): 196.1099.
Compounds 3 and 4 were prepared according to this pro-
cedure.
3-(Methoxycarbonyl)-3-methyl-5-butyl-2(3H)-
furanone (3bb)
The reaction of NaI (3 mg, 0.02 mmol), 2-methoxyfuran 1b
(43 mg, 0.20 mmol), and organic iodide 2b (30 mL, d=
2.28 gmLÀ1, 68 mg, 0.48 mmol) in 2 mL of THF afforded
3bb (eluent: petroleum ether/ethyl acetate=20/1) as an oil;
2-Methoxy-3-{[N-methoxy
ACHTUNGERTN(NUNG N-methyl)amino]car-
bonyl}-5-butylfuran (1f)[21]
1
yield: 35 mg (81%). H NMR (400 MHz, CDCl3): d=5.19 (t,
To a solution of 40 mg of 1d (0.20 mmol) in 2 mL of THF at
08C were added 83 mL of triethylamine (d=0.73,
0.60 mmol). Then 17 mL of freshly distilled methanesulfonyl
chloride (d=1.48, 0.22 mmol) were added dropwise. The re-
sulting mixture was stirred at 08C for 10 min. To this suspen-
sion were added 19 mg of N,O-dimethylhydroxylamine
(0.31 mmol) and the reaction was stirred at 08C for 1 h. The
reaction mixture was quenched with 1.2 mL of H2O at 08C
and diluted with 1.2 mL of Et2O in the test tube. The sepa-
rated aqueous layer was extracted with Et2O (3ꢂ1.2 mL).
The combined organic layer was washed with brine, dried
over anhydrous Na2SO4, and concentrated by rotary evapo-
ration. Purification by column chromatography on silica gel
(eluent: petroleum ether/ethyl acetate=2/1) afforded the
J=1.2 Hz, 1H, CH=), 3.72 (s, 3H, CO2CH3), 2.31 (td, J=
7.5, 1.4 Hz, 2H, CH2), 1.60–1.48 (m, 2H, CH2), 1.54 (s, 3H,
CH3), 1.41–1.30 (m, 2H, CH2), 0.91 (t, J=7.2 Hz, 3H, CH3);
13C NMR (100 MHz, CDCl3): d=175.7, 169.2, 157.7, 105.6,
54.9, 53.1, 27.6, 27.5, 21.9, 20.2, 13.6; MS (EI): m/z=212
(M+, 7.48), 153 (100); IR (neat): n=2958, 2936, 2874, 1802,
1743, 1676, 1452, 1435, 1375, 1243, 1197, 1105, 1060 cmÀ1
;
HR-MS (EI): m/z=212.1046, calcd. for C11H16O4 (M+):
212.1049.
3-(Methoxycarbonyl)-3-benzyl-5-butyl-2(3H)-
furanone (3bc)
The reaction of NaI (3 mg, 0.010 mmol), 2-methoxyfuran 1b
(42 mg, 0.20 mmol), and organic iodide 2c (53 mg,
0.24 mmol) in 2 mL of THF afforded 3bc (eluent: petroleum
ether/ethyl acetate=20/1) as an oil; yield: 46 mg (81%).
1H NMR (300 MHz, CDCl3): d=7.30–7.19 (m, 3H, Ar-H),
7.16–7.09 (m, 2H, Ar-H), 5.14 (s, 1H, CH=), 3.77 (s, 3H,
CO2CH3), 3.36 (d, J=13.2 Hz, 1H, one proton of PhCH2),
3.32 (d, J=14.7 Hz, 1H, one proton of PhCH2), 2.13 (t, J=
7.2 Hz, 2H, CH2), 1.34–1.20 (m, 2H, CH2), 1.13–0.95 (m,
2H, CH2), 0.79 (t, J=7.2 Hz, 3H, CH3); 13C NMR
(100 MHz, CDCl3): d=174.4, 168.5, 157.6, 134.4, 130.0,
128.2, 127.2, 103.2, 61.0, 53.2, 39.9, 27.41, 27.39, 21.4, 13.6;
MS (EI): m/z=288 (M+, 2.82), 91 (100); IR (neat): n=2957,
2933, 2872, 1801, 1744, 1677, 1604, 1496, 1455, 1435, 1380,
1239, 1122, 1078, 1058, 1014 cmÀ1; HR-MS (EI): m/z=
288.1365, calcd. for C17H20O4 (M+): 288.1362..
1
desired product 1f as an oil; yield: 38 mg (78%). H NMR
(300 MHz, CDCl3): d=6.22 (s, 1H, CH=), 4.04 (s, 3H,
CH3), 3.66 (s, 3H, CH3), 3.27 (s, 3H, CH3), 2.51 (t, J=
7.4 Hz, 2H, CH2), 1.63–1.53 (m, 2H, CH2), 1.43–1.31 (m,
2H, CH2), 0.93 (t, J=7.4 Hz, 3H, CH3); 13C NMR (75 MHz,
CDCl3): d=164.1, 160.4, 145.4, 106.1, 92.4, 60.9, 58.0, 33.1,
29.6, 27.2, 22.0, 13.7; MS (EI): m/z=241 (M+, 8.99), 181
(100); IR (neat): n=3505, 3140, 2957, 2934, 2873, 1647,
1597, 1466, 1389, 1355, 1267, 1249, 1179, 1150, 1054 cmÀ1
;
HR-MS (EI): m/z=241.1316, calcd. for C12H19NO4 (M+):
241.1314.
Alkylation Reaction of 2-Methoxyfurans
3-(Methoxycarbonyl)-3[2-(4-bromophenyl)-2-oxoethyl]-5-
phenyl-2(3H)-furanone (3aa); representative procedure: To
a Schlenk reaction tube with a screw cap, evacuated and
backfilled with argon, were added sequentially NaI (3 mg,
0.02 mmol), 2-methoxyfuran 1a (46 mg, 0.20 mmol), 1 mL of
THF, organic iodide 2a (78 mg, 0.24 mmol), and 1 mL of
THF. The resulting mixture was stirred at 808C and after
11 h the reaction was over as monitored by TLC. Evapora-
tion and column chromatography on silica gel (eluent: pe-
troleum ether/ethyl acetate=15/1) afforded the desired
product 3aa as a solid; yield: 76 mg (93%); mp 126–1278C
(petroleum ether/ethyl acetate). 1H NMR (400 MHz,
CDCl3): d=7.83–7.79 (m, 2H, Ar-H), 7.68–7.59 (m, 4H, Ar-
H), 7.43–7.39 (m, 3H, Ar-H), 6.07 (s, 1H, CH=), 4.16 (d, J=
18.4 Hz, 1H, one proton of CH2), 3.78 (s, 3H, COCH3), 3.50
(d, J=18.4 Hz, 1H, one proton of CH2); 13C NMR
(100 MHz, CDCl3): d=194.2, 173.5, 167.6, 155.2, 134.4,
132.1, 130.2, 129.6, 129.1, 128.7, 127.5, 125.2, 102.5, 57.1,
3-(Methoxycarbonyl)-3-(2-ethoxy-2-oxoethyl)-5-butyl-
2(3H)-furanone (3bd)
The reaction of NaI (3 mg, 0.02 mmol), 2-methoxyfuran 1b
(42 mg, 0.20 mmol), and organic iodide 2d (52 mg,
0.24 mmol) in 2 mL of THF afforded 3bd (eluent: petroleum
ether/ethyl acetate=20/1) as an oil; yield: 39 mg (69%).
1H NMR (300 MHz, CDCl3): d=5.32 (s, 1H, CH=), 4.13 (q,
J=7.2 Hz, 2H, CO2CH2), 3.74 (s, 3H, CO2CH3), 3.16 (d, J=
16.8 Hz, 1H, one proton of CH2), 2.89 (d, J=16.8 Hz, 1H,
one proton of CH2), 2.34 (t, J=7.4 Hz, 2H, CH2), 1.63–1.50
(m, 2H, CH2), 1.45–1.30 (m, 2H, CH2), 1.24 (t, J=7.2 Hz,
3H, CH3), 0.92 (t, J=7.4 Hz, 3H, CH3); 13C NMR
(100 MHz, CDCl3): d=173.8, 169.1, 167.7, 159.2, 103.1, 61.1,
56.6, 53.4, 38.2, 27.7, 27.4, 21.9, 14.0, 13.6; MS (ESI): m/z=
+
317 (M+MeOH+H+), 307 (M+Na+), 302 (M+NH4 ), 285
1120
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ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2012, 354, 1114 – 1128

Tuning of Regioselectivity in Inorganic Iodide-Catalyzed Alkylation of 2-Methoxyfurans
(M+H+); IR (neat): n=2959, 2935, 2874, 1805, 1742, 1677,
1435, 1410, 1374, 1346, 1223, 1114, 1031 cmÀ1; HR-MS
(ESI): m/z=285.1334, calcd. for C14H21O6 (M+H+):
285.1333.
1227, 1112, 1070, 1043 cmÀ1; anal. calcd. for C20H16O5: C
71.42, H 4.79; found: C 71.46, H 4.75.
3-(Methoxycarbonyl)-3-[2-(naphthalen-2-yl)-2-oxo-
ethyl]-5-phenyl-2(3H)-furanone (3ag)
3-(Methoxycarbonyl)-3-(2-ethoxy-2-oxoethyl)-5-
phenyl-2(3H)-furanone (3ad)
The reaction of NaI (3 mg, 0.02 mmol), 2-methoxyfuran 1a
(46 mg, 0.20 mmol), and organic iodide 2g (71 mg,
0.24 mmol) in 2 mL of THF afforded 3ag (eluent: petroleum
ether/ethyl acetate=20/1) as a solid; yield: 69 mg (90%);
mp 105–1078C (petroleum ether/ethyl acetate). 1H NMR
(400 MHz, CDCl3): d=8.50 (s, 1H, Ar-H), 8.02–7.95 (m,
2H, Ar-H), 7.89 (t, J=8.2 Hz, 2H, Ar-H), 7.70–7.55 (m, 4H,
Ar-H), 7.45–7.40 (m, 3H, Ar-H), 6.14 (s, 1H, CH=), 4.38 (d,
J=17.6 Hz, 1H, one proton of CH2), 3.81 (s, 3H, CO2CH3),
3.68 (d, J=18.0 Hz, 1H, one proton of CH2); 13C NMR
(100 MHz, CDCl3): d=195.0, 173.8, 167.8, 155.0, 135.8,
132.9, 132.3, 130.2, 129.6, 128.9, 128.71, 128.67, 127.8, 127.6,
127.0, 125.2, 123.4, 102.8, 57.2, 53.7, 43.5; MS (ESI): m/z=
441 (M+MeOH+Na+), 419 (M+MeOH+H+), 409 (M+
Na+), 387 (M+H+); IR (neat): n=1800, 1737, 1679, 1627,
1596, 1494, 1469, 1449, 1434, 1359, 1274, 1253, 1225, 1187,
1149, 1119, 1069, 1042 cmÀ1; HR-MS (ESI): m/z=387.1240,
calcd. for C24H19O5 (M+H+): 387.1227.
The reaction of NaI (3 mg, 0.02 mmol), 2-methoxyfuran 1a
(46 mg, 0.20 mmol), and organic iodide 2d (51 mg,
0.24 mmol) in 2 mL of THF afforded 3ad[12] (eluent: petrole-
um ether/ethyl acetate=20/1) as a solid; yield: 52 mg
(86%). mp 62–648C (petroleum ether/ethyl acetate) [lit.:
62–658C (petroleum ether/ethyl acetate)]. 1H NMR
(400 MHz, CDCl3): d=7.66–7.63 (m, 2H, Ar-H), 7.44–7.40
(m, 3H, Ar-H), 5.99 (s, 1H, CH=), 4.18–4.08 (m, 2H,
CO2CH2), 3.77 (s, 3H, CO2CH3), 3.30 (d, J=16.8 Hz, 1H,
one proton of CH2), 3.01 (d, J=16.8 Hz, 1H, one proton of
CH2), 1.21 (t, J=7.2 Hz, 3H, CH3); 13C NMR (100 MHz,
CDCl3): d=173.0, 169.1, 167.4, 155.3, 130.4, 128.7, 127.4,
125.2, 101.9, 61.3, 57.2, 53.6, 38.5, 14.0; MS (ESI): m/z=327
+
(M+Na+), 322 (M+NH4 ), 305 (M+H+); IR (neat): n=
1797, 1748, 1722, 1649, 1494, 1460, 1449, 1432, 1403, 1391,
1373, 1348, 1286, 1259, 1226, 1203, 1156, 1125, 1095, 1081,
1044, 1027, 1001 cmÀ1.
3-(Methoxycarbonyl)-3-[2-(biphenyl-4-yl)-2-oxo-
ethyl]-5-phenyl-2(3H)-furanone (3ah)
3-(Methoxycarbonyl)-3-(2-oxopropyl)-5-phenyl-
The reaction of NaI (3 mg, 0.02 mmol), 2-methoxyfuran 1a
(46 mg, 0.20 mmol), and organic iodide 2h (77 mg,
0.24 mmol) in 2 mL of THF afforded 3ah as a solid; yield:
70 mg (86%); mp 91–928C (petroleum ether/ethyl acetate).
1H NMR (300 MHz, CDCl3): d=8.04 (d, J=8.4 Hz, 2H, Ar-
H), 7.74–7.59 (m, 6H, Ar-H), 7.52–7.37 (m, 6H, Ar-H), 6.12
(s, 1H, CH=), 4.26 (d, J=17.7 Hz, 1H, one proton of CH2),
3.80 (s, 3H, CO2CH3), 3.58 (d, J=18.0 Hz, 1H, one proton
of CH2); 13C NMR (100 MHz, CDCl3): d=194.7, 173.7,
167.7, 155.0, 146.5, 139.5, 134.3, 130.2, 129.0, 128.72, 128.70,
128.4, 127.6, 127.3, 127.2, 125.2, 102.8, 57.2, 53.6, 43.4; MS
(ESI): m/z=467 (M+Na+ +MeOH), 445 (M+H+ +
MeOH), 435 (M+Na+), 413 (M+H+); IR (neat): n=1801,
2(3H)-furanone (3ae)
The reaction of NaI (3 mg, 0.02 mmol), 2-methoxyfuran 1a
(46 mg, 0.20 mmol), and organic iodide 2e (44 mg,
0.24 mmol) in 2 mL of THF afforded 3ae (eluent: petroleum
ether/ethyl acetate=5/1) as an oil; yield: 45 mg (83%).
1H NMR (300 MHz, CDCl3): d=7.66–7.60 (m, 2H, Ar-H),
7.44–7.38 (m, 3H, Ar-H), 6.02 (s, 1H, CH=), 3.74 (s, 3H,
CO2CH3), 3.58 (d, J=18.3 Hz, 1H, one proton of CH2), 2.99
(d, J=18.0 Hz, 1H, one proton of CH2), 2.20 (s, 3H, CH3);
13C NMR (75 MHz, CDCl3): d=203.6, 173.3, 167.4, 154.8,
130.2, 128.7, 127.5, 125.1, 102.5, 56.9, 53.5, 47.2, 29.7; MS
(EI): m/z=274 (M+, 4.81), 43 (100); IR (neat): n=1800,
1738, 1720, 1651, 1495, 1449, 1434, 1401, 1363, 1225, 1176,
1120, 1076, 1120, 1075, 1045,0 1031, 1011 cmÀ1; HR-MS
(EI): m/z=274.0845, calcd for C15H14O5 (M+): 274.0841.
1738, 1681, 1603, 1494, 1449, 1403, 1351, 1231, 1117 cmÀ1
;
HR-MS (ESI): m/z=435.1218, calcd. for C26H20O5Na+ (M+
Na+): 435.1203.
3-(Methoxycarbonyl)-3-(2-oxo-2-phenylethyl)-5-
phenyl-2(3H)-furanone (3af)
3-(Methoxycarbonyl)-3-allyl-5-butyl-2(3H)-furanone
(3bi)
The reaction of NaI (3 mg, 0.02 mmol), 2-methoxyfuran 1a
(46 mg, 0.20 mmol), and organic iodide 2f (59 mg,
0.24 mmol) in 2 mL of THF afforded 3af (eluent: petroleum
ether/ethyl acetate=10/1) as a solid; yield: 57 mg (86%);
mp 148–1498C (petroleum ether/ethyl acetate) [lit.: 148–
The reaction of NaI (3 mg, 0.02 mmol), 2-methoxyfuran 1b
(41 mg, 0.19 mmol), and organic iodide 2i (41 mg,
0.24 mmol) in 2 mL of THF afforded 3bi[12] (eluent: petrole-
um ether/ethyl acetate=20/1) as an oil; yield: 35 mg (76%).
1H NMR (400 MHz, CDCl3): d=5.68–5.56 (m, 1H, one ole-
finic proton), 5.20–5.10 (m, 3H, three olefinic protons), 3.74
(s, 3H, CO2CH3), 2.79 (dd, J=13.6, 6.8 Hz, 1H, one proton
of CH2), 2.68 (dd, J=13.6, 7.6 Hz, 1H, one proton of CH2),
2.32 (td, J=7.5, 1.0 Hz, 2H, CH2), 1.59–1.49 (m, 2H, CH2),
1.41–1.30 (m, 2H, CH2), 0.92 (t, J=7.2 Hz, 3H, CH3);
13C NMR (100 MHz, CDCl3): d=174.2, 168.4, 157.9, 130.8,
120.2, 103.2, 59.5, 53.1, 38.2, 27.64, 27.58, 21.9, 13.6; MS
(EI): m/z=238 (M+, 7.46), 197 (100); IR (neat): n=2958,
2934, 2874, 1804, 1744, 1676, 1642, 1435, 1381, 1239, 1168,
1110, 1014 cmÀ1.
1
1518C (petroleum ether/ethyl acetate)]. H NMR (400 MHz,
CDCl3): d=7.96 (d, J=7.6 Hz, 2H, Ar-H), 7.68–7.64 (m,
2H, Ar-H), 7.59 (t, J=7.4 Hz, 1H, Ar-H), 7.50–7.40 (m, 5H,
Ar-H), 6.09 (s, 1H, CH=), 4.22 (d, J=18.0 Hz, 1H, one
proton of CH2), 3.78 (s, 3H, CO2CH3), 3.54 (d, J=18.4 Hz,
1H, one proton of CH2); 13C NMR (100 MHz, CDCl3): d=
195.1, 173.6, 167.7, 155.0, 135.6, 133.8, 130.1, 128.72, 128.67,
128.1, 127.6, 125.1, 102.7, 57.1, 53.6, 43.4; MS (ESI): m/z=
+
359 (M+Na+), 354 (M+NH4 ), 337 (M+H+); IR (neat):
n=1798, 1744, 1678, 1596, 1493, 1448, 1357, 1281, 1257,
Adv. Synth. Catal. 2012, 354, 1114 – 1128
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
1121

Jie Chen et al.
FULL PAPERS
ether/ethyl acetate=20/1): as an oil; yield: 61 mg (92%).
1H NMR (400 MHz, CDCl3): d=7.65–7.58 (m, 2H, Ar-H),
7.44–7.37 (m, 3H, Ar-H), 7.31–7.16 (m, 5H, Ar-H), 6.54 (d,
J=15.6 Hz, 1H, one olefinic proton), 6.14–6.04 (m, 1H, one
olefinic proton), 5.89 (s, 1H, one olefinic proton), 3.77 (s,
3H, CO2CH3), 3.11 (ddd, J=13.9, 6.7, 1.3 Hz, 1H, one
proton of CH2), 2.94 (ddd, J=14.0, 8.2, 1.0 Hz, 1H, one
proton of CH2); 13C NMR (100 MHz, CDCl3): d=173.3,
167.9, 154.3, 136.5, 135.3, 130.2, 128.7, 128.5, 127.6, 127.4,
126.3, 125.1, 121.9, 102.0, 60.4, 53.3, 38.1; MS (ESI): m/z=
3-(Methoxycarbonyl)-3-(2-phenylallyl)-5-butyl-2(3H)-
furanone (3bj)
The reaction of NaI (3 mg, 0.02 mmol), 2-methoxyfuran 1b
(42 mg, 0.20 mmol), and organic iodide 2j (98 mg,
0.40 mmol) in 2 mL of THF afforded 3bj as an oil; yield:
1
41 mg (66%). H NMR (300 MHz, CDCl3): d=7.33–7.20 (m,
5H, Ar-H), 5.31 (d, J=1.2 Hz, 1H, one olefinic proton),
5.18 (s, 1H, one olefinic proton), 4.78 (t, J=1.2 Hz, 1H, one
olefinic proton), 3.67 (s, 3H, CO2CH3), 3.46 (d, J=13.8 Hz,
1H, one proton of CH2), 3.14 (d, J=13.8 Hz, 1H, one
proton of CH2), 2.18–1.98 (m, 2H, CH2), 1.40–1.15 (m, 4H,
2ꢂCH2), 0.85 (t, J=7.1 Hz, 3H, CH3); 13C NMR (75 MHz,
CDCl3): d=174.2, 168.4, 157.2, 143.1, 141.0, 128.2, 127.7,
126.4, 118.1, 103.5, 60.1, 53.1, 39.4, 27.4, 27.1, 21.9, 13.6; MS
(EI): m/z=314 (M+, 12.66), 41 (100); IR (neat): n=1800,
+
357 (M+Na+), 352 (M+NH4 ), 335 (M+H+); IR (neat):
n=1803, 1740, 1650, 1495, 1449, 1434, 1233 cmÀ1; HR-MS
(ESI): m/z=357.1089, calcd. for C21H18O4Na+ (M+Na+):
357.1097.
3-(Methoxycarbonyl)-3-(2-phenylallyl)-5-phenyl-
2(3H)-furanone (3aj)
1739, 1677, 1627, 1494, 1434, 1233, 1134, 1107, 1016 cmÀ1
;
+
HR-MS (EI): m/z=314.1511, calcd. for C19H22O4 (M+):
314.1518.
The reaction of NaI (3 mg, 0.02 mmol), 2-methoxyfuran 1a
(46 mg, 0.20 mmol), and organic iodide 2j (98 mg,
0.40 mmol) in 2 mL of THF afforded 3aj as an oil; yield:
3-(Methoxycarbonyl)-3-(2-methylallyl)-5-butyl-2(3H)-
furanone (3bk)
1
40 mg (60%). H NMR (300 MHz, CDCl3): d=7.38–7.25 (m,
5H, Ar-H), 7.24–7.20 (m, 5H, Ar-H), 5.37 (s, 1H, one ole-
finic proton), 5.27 (s, 1H, one olefinic proton), 5.23 (s, 1H,
one olefinic proton), 3.69 (s, 3H, CO2CH3), 3.57 (d, J=
13.8 Hz, 1H, one proton of CH2), 3.26 (d, J=13.5 Hz, 1H,
one proton of CH2); 13C NMR (100 MHz, CDCl3): d=173.5,
168.0, 153.3, 143.2, 141.1, 130.0, 128.5, 128.2, 127.6, 127.5,
126.6, 125.0, 118.2, 102.7, 60.8, 53.3, 40.3; MS (EI): m/z=334
(M+, 22.84), 217 (100); IR (neat): n=1804, 1741, 1651, 1628,
1600, 1575, 1494, 1448, 1435, 1283, 1232, 1135, 1097, 1045,
The reaction of NaI (3 mg, 0.02 mmol), 2-methoxyfuran 1b
(42 mg, 0.20 mmol), and organic iodide 2k (73 mg,
0.40 mmol) in 2 mL of THF afforded 3bk (eluent: petroleum
ether/ethyl acetate=30/1) as an oil; yield: 40 mg (80%).
1H NMR (400 MHz, CDCl3): d=5.20 (s, 1H, one olefinic
proton), 4.84 (t, J=1.2 Hz, 1H, one olefinic proton), 4.76 (s,
1H, one olefinic proton), 3.74 (s, 3H, CO2CH3), 2.82 (d, J=
13.6 Hz, 1H, one proton of CH2), 2.72 (d, J=13.6 Hz, 1H,
one proton of CH2), 2.32 (td, J=7.4, 1.2 Hz, 2H, CH2), 1.68
(s, 3H, CH3), 1.58–1.49 (m, 2H, CH2), 1.41–1.31 (m, 2H,
CH2), 0.91 (t, J=7.4 Hz, 3H, CH3); 13C NMR (100 MHz,
CDCl3): d=174.6, 168.6, 157.6, 139.5, 115.7, 103.7, 59.7, 53.2,
41.7, 27.7, 27.6, 23.6, 21.9, 13.6; MS (EI): m/z=252 (M+,
2.64), 84 (100); IR (neat): n=1800, 1741, 1676, 1648, 1434,
1378, 1229, 1122, 1065, 1025 cmÀ1; HR-MS (EI): m/z=
1001 cmÀ1
;
HR-MS (EI): m/z=334.1204, calcd. for
+
+
C21H18O4 (M ): 334.1205.
3-(Methoxycarbonyl)-3-(3-methylbut-2-en-1-yl)-5-
phenyl-2(3H)-furanone (3am)
The reaction of NaI (3 mg, 0.02 mmol), 2-methoxyfuran 1a
(46 mg, 0.20 mmol), and organic iodide 2m (78 mg,
0.40 mmol) in 2 mL of THF afforded 3am (eluent: petrole-
um ether/ethyl acetate=20/1) as an oil; yield: 49 mg (86%).
1H NMR (300 MHz, CDCl3): d=7.66–7.59 (m, 2H, Ar-H),
7.47–7.39 (m, 3H, Ar-H), 5.83 (s, 1H, CH=), 5.04 (tm, J=
7.5 Hz, 1H, CH2CH=), 3.77 (s, 3H, CO2CH3), 2.84 (d, J=
7.5 Hz, 2H, CH2), 1.66 (s, 3H, CH3), 1.65 (s, 3H, CH3);
13C NMR (75 MHz, CDCl3): d=173.7, 168.2, 153.9, 137.5,
130.1, 128.7, 127.6, 125.0, 115.9, 102.4, 60.4, 53.2, 33.3, 25.9,
18.0; MS (ESI): m/z=341 (M+MeOH+Na+), 309 (M+
Na+), 287 (M+H+); IR (neat): n=1803, 1740, 1650, 1495,
1449, 1435, 1378, 1282, 1228, 1125, 1111, 1047 cmÀ1; HR-MS
+
+
252.1364, calcd. for C14H20O4 (M ): 252.1362.
3-(Methoxycarbonyl)-3-allyl-5-phenyl-2(3H)-furanone
(3ai)
The reaction of NaI (3 mg, 0.02 mmol), 2-methoxyfuran 1a
(46 mg, 0.20 mmol), and organic iodide 2i (40 mg,
0.24 mmol) in 2 mL of THF afforded 3ai[12] as an oil; yield:
1
42 mg (82%). H NMR (300 MHz, CDCl3): d=7.66–7.59 (m,
2H, Ar-H), 7.46–7.39 (m, 3H, Ar-H), 5.84 (s, 1H, one ole-
finic proton), 5.78–5.61 (m, 1H, one olefinic proton), 5.25–
5.11 (m, 2H, two olefinic protons), 3.77 (s, 3H, CO2CH3),
2.94 (dd, J=13.8, 6.6 Hz, 1H, one proton of CH2), 2.80 (dd,
J=13.7, 8.0 Hz, 1H, one proton of CH2); 13C NMR
(75 MHz, CDCl3): d=173.3, 167.9, 154.1, 130.6, 130.2, 128.7,
127.5, 125.1, 120.6, 101.9, 60.2, 53.3, 38.6; MS (EI): m/z=258
(M+, 8.96), 217 (100); IR (neat): n=1804, 1740, 1646, 1495,
1449, 1435, 1229, 1184, 1121, 1095, 1074, 1044 cmÀ1.
+
(EI): m/z=286.1208, calcd. for C17H18O4 (M+): 286.1205.
3-(Phenylsulfonyl)-3-allyl-5-phenyl-2(3H)-furanone
(3ci)
The reaction of NaI (7 mg, 0.05 mmol), Na2CO3 (5 mg,
0.05 mmol), 2-methoxyfuran 1c (141 mg, 0.45 mmol), and or-
ganic iodide 2i (152 mg, 0.90 mmol) in 2 mL of THF afford-
ed 3ci[12] (eluent: petroleum ether/ethyl acetate=10/1) as
a solid; yield: 35 mg (23%); mp 108–1108C (petroleum
ether/ethyl acetate) [lit.: 102.5–1048C (petroleum ether/
3-(Methoxycarbonyl)-3-cinnamyl-5-phenyl-2(3H)-
furanone (3al)
The reaction of NaI (3 mg, 0.02 mmol), 2-methoxyfuran 1a
(46 mg, 0.20 mmol), and organic iodide 2l (98 mg,
0.40 mmol) in 2 mL of THF afforded 3al (eluent: petroleum
1
ethyl acetate)]. H NMR (400 MHz, CDCl3): d=7.89 (d, J=
7.6 Hz, 2H, Ar-H), 7.66 (t, J=7.6 Hz, 1H, Ar-H), 7.55–7.48
1122
asc.wiley-vch.de
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2012, 354, 1114 – 1128

Tuning of Regioselectivity in Inorganic Iodide-Catalyzed Alkylation of 2-Methoxyfurans
(m, 4H, Ar-H), 7.46–7.36 (m, 3H, Ar-H), 5.90 (s, 1H, one
olefinic proton), 5.62–5.51 (m, 1H, one olefinic proton),
5.23–5.11 (m, 2H, two olefinic protons), 3.07 (dd, J=13.6,
6.8 Hz, 1H, one proton of CH2), 2.96 (dd, J=13.6, 8.0 Hz,
1H, one proton of CH2); 13C NMR (100 MHz, CDCl3): d=
170.0, 156.8, 134.8, 134.4, 130.9, 130.5, 129.1, 128.9, 128.8,
126.6, 125.4, 121.6, 97.1, 77.7, 34.9; MS (ESI): m/z=363
CH3), 2.81 (dd, J=13.8, 7.2 Hz, 1H, one proton of CH2),
2.62 (dd, J=14.1, 7.8 Hz, 1H, one proton of CH2), 2.29 (t,
J=7.4 Hz, 2H, CH2), 1.56–1.46 (m, 2H, CH2), 1.42–1.29 (m,
2H, CH2), 0.90 (t, J=7.1 Hz, 3H, CH3); 13C NMR
(100 MHz, CDCl3): d=175.0, 168.3, 157.6, 131.1, 120.0,
102.5, 60.4, 57.7, 38.4, 33.0, 27.8, 27.7, 22.0, 13.6; MS (EI):
m/z=267 (M+, 29.37), 179 (100); IR (neat): n=3080, 2959,
2937, 2874, 1794, 1676, 1460, 1433, 1412, 1375, 1263, 1195,
1170, 1107 cmÀ1; HR-MS (EI): m/z=267.1473, calcd. for
+
(M+Na+), 358 (M+NH4 ), 231 (M+ +MeOHÀSO2Ph), 199
(M+ÀSO2Ph); IR (neat): n=1801, 1643, 1494, 1448, 1313,
1146, 1126, 1081, 1040 cmÀ1.
C14H21NO4 (M+): 267.1471.
+
3-(Methoxycarbonyl)-3-[2-(ethoxycarbonyl)allyl]-5-
butyl-2(3H)-furanone (3bn) and 3-(Methoxycar-
bonyl)-5-[2-(ethoxycarbonyl)allyl]-5-butyl-2(5H)-
furanone (4bn)
3-(Allyloxycarbonyl)-3-allyl-5-butyl-2(3H)-furanone
(3di)
The reaction of NaI (3 mg, 0.02 mmol), 2-methoxyfuran 1d
(40 mg, 0.20 mmol), and organic iodide 2i (68 mg,
0.40 mmol) in 2 mL of THF afforded 3di (eluent: petroleum
ether/ethyl acetate=50/1 to 5/1) as an oil; yield: 10 mg
The reaction of NaI (3 mg, 0.02 mmol), 2-methoxyfuran 1b
(42 mg, 0.20 mmol), and organic iodide 2n (97 mg,
0.40 mmol) in 2 mL of THF afforded 3bn (eluent: petroleum
ether/ethyl acetate=10/1); yield: 7 mg (11%) and 4bn
(eluent: petroleum ether/ethyl acetate=5/1); yield: 40 mg
(65%).
1
(19%). H NMR (300 MHz, CDCl3): d=5.94–5.81 (m, 1H,
one olefinic proton), 5.71–5.57 (m, 1H, one olefinic proton),
5.35–5.23 (m, 2H, two olefinic protons), 5.23–5.12 (m, 3H,
three olefinic protons), 4.64 (d, J=5.4 Hz, 2H, OCH2), 2.81
(dd, J=13.5, 6.6 Hz, 1H, one proton of CH2), 2.70 (dd, J=
13.5, 7.5 Hz, 1H, one proton of CH2), 2.34 (t, J=7.2 Hz,
2H, CH2), 1.59–1.50 (m, 2H, CH2), 1.43–1.31 (m, 2H, CH2),
0.92 (t, J=7.2 Hz, 3H, CH3); 13C NMR (100 MHz, CDCl3):
d=174.1, 167.6, 158.0, 131.1, 130.8, 120.3, 118.7, 103.2, 66.4,
59.6, 38.1, 27.7, 27.6, 21.9, 13.6; MS (EI): m/z=264 (M+,
9.94), 179 (100); IR (neat): n=3083, 2959, 2932, 2874, 1803,
1
3bn: oil; H NMR (300 MHz, CDCl3): d=6.24 (s, 1H, one
olefinic proton), 5.67 (s, 1H, one olefinic proton), 5.12 (s,
1H, one olefinic proton), 4.18 (q, J=6.9 Hz, 2H, CO2CH2),
3.75 (s, 3H, CO2CH3), 3.36 (d, J=13.2 Hz, 1H, one proton
of CH2), 2.88 (d, J=13.5 Hz, 1H, one proton of CH2), 2.26
(t, J=7.4 Hz, 2H, CH2), 1.53–1.41 (m, 2H, CH2), 1.39–1.23
(m, 5H, CH2 and CH3), 0.89 (t, J=7.4 Hz, 3H, CH3);
13C NMR (100 MHz, CDCl3): d=174.3, 168.2, 166.5, 157.8,
134.8, 129.6, 103.1, 61.0, 60.3, 53.3, 34.8, 27.6, 21.9, 14.1, 13.7;
MS (ESI): m/z=333 (M+Na+), 311 (M+H+); IR (neat):
n=1802, 1744, 1717, 1676, 1630, 1436, 1239, 1177, 1115,
1743, 1676, 1644, 1457, 1436, 1270, 1221, 1168, 1109 cmÀ1
;
+
HR-MS (EI): m/z=264.1367, calcd. for C15H20O4 (M+):
264.1362.
1025 cmÀ1
;
HR-MS (ESI): m/z=333.1298, calcd. for
3-Acetyl-3-allyl-5-butyl-2(3H)-furanone (3ei)
C16H22O6Na+ (M+Na+): 333.1309.
4bn: oil; 1H NMR (300 MHz, CDCl3): d=8.02 (s, 1H,
CH=), 6.29 (s, 1H, one olefinic proton), 5.72 (s, 1H, one ole-
finic proton), 4.20–4.05 (m, 2H, CO2CH2), 3.81 (s, 3H,
CO2CH3), 3.00 (d, J=13.8 Hz, 1H, one proton of CH2), 2.74
(d, J=13.8 Hz, 1H, one proton of CH2), 1.95–1.76 (m, 2H,
CH2), 1.35–1.10 (m, 7H, 2ꢂCH2 and CH3), 0.86 (t, J=
6.8 Hz, 3H, CH3); 13C NMR (100 MHz, CDCl3): d=166.9,
166.6, 165.7, 160.3, 132.6, 131.7, 124.9, 87.2, 61.2, 52.4, 38.5,
36.9, 25.5, 22.6, 14.0, 13.7; MS (ESI): m/z=333 (M+Na+),
311 (M+H+); IR (neat): n=1778, 1711, 1632, 1465, 1437,
1370, 1338, 1308, 1267, 1184, 1149, 1053, 1018 cmÀ1; HR-MS
(ESI): m/z=333.1300, calcd. for C16H22O6Na+ (M+Na+):
333.1309.
The reaction of MgI2 (6 mg, 0.02 mmol), 2-methoxyfuran
1b (42 mg, 0.20 mmol), and organic iodide 2n (96 mg,
0.40 mmol) in 2 mL of THF afforded 4bn (eluent: petroleum
ether/ethyl acetate=6/1) as an oil; yield: 38 mg (62%).
1H NMR (300 MHz, CDCl3): d=8.01 (s, 1H, CH=), 6.28 (s,
1H, one olefinic proton), 5.71 (s, 1H, one olefinic proton),
4.20–4.06 (m, 2H, CO2CH2), 3.80 (s, 3H, CO2CH3), 2.99 (d,
J=13.8 Hz, 1H, one proton of CH2), 2.73 (d, J=13.8 Hz,
1H, one proton of CH2), 1.95–1.76 (m, 2H, CH2), 1.33–1.11
(m, 7H, 2ꢂCH2 and CH3), 0.84 (t, J=6.6 Hz, 3H, CH3).
The reaction of NaI (3 mg, 0.02 mmol), 2-methoxyfuran 1e
(40 mg, 0.20 mmol), and organic iodide 2i (67 mg,
0.40 mmol) in 2 mL of THF afforded 3ei (eluent: petroleum
ether/ethyl acetate=20/1) as an oil; yield: 20 mg (45%).
1H NMR (300 MHz, CDCl3): d=5.66–5.52 (m, 1H, one ole-
finic proton), 5.18–5.10 (m, 3H, three olefinic protons), 2.74
(J=13.8, 7.2 Hz, 1H, one proton of CH2), 2.63 (J=13.8,
7.8 Hz, 1H, one proton of CH2), 2.36 (t, J=7.5 Hz, 2H,
CH2), 2.23 (s, 3H, CH3), 1.62–1.52 (m, 2H, CH2), 1.45–1.32
(m, 2H, CH2), 0.94 (t, J=7.2 Hz, 3H, CH3); 13C NMR
(75 MHz, CDCl3): d=200.1, 175.2, 158.2, 131.0, 120.1, 103.2,
66.5, 37.8, 29.7, 27.7, 26.4, 22.0, 13.7; MS (ESI) m/z 245
+
(M+Na+),
240
(M+NH4 ),
223
(M+H+),
179
(M+ÀCH3CO); IR (neat): n=3081, 2958, 2927, 2856, 1798,
1722, 1671, 1642, 1465, 1434, 1378, 1358, 1321, 1263, 1185,
1108, 1084, 1044 cmÀ1; HR-MS (EI): m/z=222.1257, calcd.
for C13H18O3 (M+): 222.1256.
+
3-{[N-methoxyACHTUNGTRENNUNG(N-methyl)amino]carbonyl}-3-allyl-5-
butyl-2(3H)-furanone (3fi)
The reaction of NaI (3 mg, 0.02 mmol), 2-methoxyfuran 1f
(49 mg, 0.20 mmol), and organic iodide 2i (68 mg,
0.40 mmol) in 2 mL of THF afforded 3fi (eluent: petroleum
ether/ethyl acetate=5/1) as an oil; yield: 43 mg (79%).
1H NMR (300 MHz, CDCl3): d=5.69–5.55 (m, 1H, one ole-
finic proton), 5.14–5.07 (m, 2H, one olefinic proton), 4.97 (s,
1H, one olefinic proton), 3.55 (s, 3H, CH3), 3.16 (s, 3H,
Adv. Synth. Catal. 2012, 354, 1114 – 1128
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
1123

Jie Chen et al.
FULL PAPERS
d=174.4, 167.9, 158.7, 145.4, 138.5, 133.8, 129.4, 128.4, 127.9,
102.9, 59.6, 53.5, 32.0, 27.7, 27.5, 22.0, 13.7; MS (EI): m/z=
378 (M+, 1.96), 197 (100); IR (neat): n=2958, 2933, 2873,
1799, 1741, 1676, 1447, 1435, 1307, 1236, 1144, 1114, 1082,
3-(Methoxycarbonyl)-3-(2-cyanoallyl)-5-butyl-2(3H)-
furanone (3bo) and 3-(Methoxycarbonyl)-5-(2-cyano-
allyl)-5-butyl-2(5H)-furanone (4bo)
1016 cmÀ1
;
HR-MS (EI): m/z=378.1142, calcd. for
The reaction of NaI (3 mg, 0.02 mmol), 2-methoxyfuran 1b
(42 mg, 0.20 mmol), and organic iodide 2o (77 mg,
0.40 mmol) in 2 mL of THF afforded 3bo (eluent: petroleum
ether/ethyl acetate=10/1); yield: 4 mg (8%) and 4bo
(eluent: petroleum ether/ethyl acetate=2/1); yield: 33 mg
(63%).
+
C19H22O6S+ (M ): 378.1137.
4bp: oil; 1H NMR (300 MHz, CDCl3): d=7.97 (s, 1H,
CH=), 7.84–7.78 (m, 2H, Ar-H), 7.69–7.62 (m, 1H, Ar-H),
7.60–7.52 (m, 2H, Ar-H), 6.33 (s, 1H, one olefinic proton),
6.02 (s, 1H, one olefinic proton), 3.87 (s, 3H, CO2CH3), 2.87
(d, J=15.6 Hz, 1H, one proton of CH2), 2.76 (d, J=15.3 Hz,
1H, one proton of CH2), 1.93–1.70 (m, 2H, CH2), 1.33–1.05
(m, 4H, 2ꢂCH2), 0.85 (t, J=6.9 Hz, 3H, CH3); 13C NMR
(75 MHz, CDCl3): d=166.7, 165.0, 160.1, 143.3, 137.9, 134.0,
129.51, 129.46, 128.4, 125.6, 86.7, 52.5, 37.0, 35.3, 25.4 22.5,
13.7; MS (EI): m/z=379 (M+, 10.98), 197 (100); IR (neat):
n=2956, 1780, 1730, 1630, 1584, 1468, 1448, 1438, 1347,
1
3bo: oil; H NMR (300 MHz, CDCl3): d=6.00 (s, 1H, one
olefinic proton), 5.87 (s, 1H, one olefinic proton), 5.33 (s,
1H, one olefinic proton), 3.77 (s, 3H, CO2CH3), 3.07 (d, J=
13.8 Hz, 1H, one proton of CH2), 2.90 (d, J=13.8 Hz, 1H,
one proton of CH2), 2.38 (t, J=7.7 Hz, 2H, CH2), 1.65–1.52
(m, 2H, CH2), 1.45–1.32 (m, 2H, CH2), 0.93 (t, J=7.2 Hz,
3H, CH3); 13C NMR (100 MHz, CDCl3): d=173.4, 167.4,
159.8, 136.1, 118.2, 116.9, 102.0, 59.7, 53.5, 37.8, 27.7, 27.4,
1293, 1262, 1228, 1167, 1145, 1127, 1090, 1060, 1024 cmÀ1
;
22.0, 13.6; MS (GC-MS): m/z=263 (M+ 6.19), 57 (100); IR
,
HR-MS (EI): m/z=378.1139, calcd. for C19H22O6S+ (M+):
(neat): n=2959, 2225, 1803, 1744, 1675, 1436, 1245, 1121,
378.1137.
1021 cmÀ1
;
HR-MS (EI): m/z=263.1166, calcd. for
+
C14H17NO4 (M+): 263.1158.
3-(Methoxycarbonyl)-5-(2-benzoylallyl)-5-butyl-
4bo: oil; 1H NMR (300 MHz, CDCl3): d=8.14 (s, 1H,
CH=), 6.07 (s, 1H, one olefinic proton), 5.90 (s, 1H, one ole-
finic proton), 3.88 (s, 3H, CO2CH3), 2.84 (d, J=14.4 Hz,
1H, one proton of CH2), 2.73 (d, J=14.4 Hz, 1H, one
proton of CH2), 1.99–1.78 (m, 2H, CH2), 1.40–1.10 (m, 4H,
2ꢂCH2), 0.88 (t, J=7.1 Hz, 3H, CH3); 13C NMR (100 MHz,
CDCl3): d=166.2, 163.8, 159.9, 137.2, 126.6, 118.2, 115.0,
86.4, 52.6, 41.6, 36.4, 25.3, 22.4, 13.6; MS (ESI): m/z=286
(M+Na+), 264 (M+H+); IR (neat): n=2224, 1775, 1728,
1640, 1437, 1342, 1260, 1054, 1019 cmÀ1; HR-MS (ESI): m/
z=286.1047, calcd. for C14H17NO4Na+ (M+Na+): 286.1050.
The reaction of MgI2 (6 mg, 0.02 mmol), 2-methoxyfuran
1b (42 mg, 0.20 mmol), and organic iodide 2o (77 mg,
0.40 mmol) in 2 mL of THF afforded 4bo (eluent: petroleum
ether/ethyl acetate=3/1) as an oil; yield: 30 mg (58%).
1H NMR (300 MHz, CDCl3): d=8.14 (s, 1H, CH=), 6.06 (s,
1H, one olefinic proton), 5.89 (s, 1H, one olefinic proton),
3.87 (s, 3H, CO2CH3), 2.84 (d, J=14.4 Hz, 1H, one proton
of CH2), 2.73 (d, J=14.1 Hz, 1H, one proton of CH2), 1.95–
1.78 (m, 2H, CH2), 1.40–1.08 (m, 4H, 2ꢂCH2), 0.87 (t, J=
6.9 Hz, 3H, CH3).
2(5H)-furanone (4bq)
The reaction of NaI (3 mg, 0.02 mmol), 2-methoxyfuran 1b
(42 mg, 0.20 mmol), and organic iodide 2q (82 mg,
0.30 mmol) in 2 mL of THF afforded 3bq (eluent: petroleum
ether/ethyl acetate=10/1); yield: 4 mg (6%) and 4bq
(eluent: petroleum ether/ethyl acetate=5/1); yield: 46 mg
(68%).
3bq: oil; 1H NMR (300 MHz, CDCl3): d=7.70 (d, J=
7.8 Hz, 2H, Ar-H), 7.55 (t, J=7.4 Hz, 1H, Ar-H), 7.43 (t,
J=7.4 Hz, 2H, Ar-H), 6.02 (s, 1H, one olefinic proton), 5.73
(s, 1H, one olefinic proton), 5.03 (s, 1H, one olefinic
proton), 3.76 (s, 3H, CO2CH3), 3.71 (d, J=13.2 Hz, 1H, one
proton of CH2), 2.97 (d, J=13.5 Hz, 1H, one proton of
CH2), 2.19–1.88 (m, 2H, CH2), 1.37–1.08 (m, 4H, 2ꢂCH2),
0.75 (t, J=6.9 Hz, 3H, CH3); 13C NMR (100 MHz, CDCl3):
d=196.5, 174.1, 168.0, 158.0, 141.7, 136.7, 132.6, 130.9, 129.6,
128.2, 103.8, 60.1, 53.3, 35.9, 27.5, 27.0, 21.9, 13.5; MS (EI):
m/z=342 (M+, 4.27), 105 (100); IR (neat): n=2957, 2932,
2873, 1803, 1745, 1658, 1598, 1448, 1435, 1337, 1239, 1197,
1177, 1117, 1019, 1001 cmÀ1; HR-MS (EI): m/z=342.1471,
+
+
calcd. for C20H22O5 (M ): 342.1467.
4bq: oil; 1H NMR (300 MHz, CDCl3): d=7.95 (s, 1H,
CH=), 7.58–7.47 (m, 3H, Ar-H), 7.42–7.35 (m, 2H, Ar-H),
6.11 (s, 1H, one olefinic proton), 5.86 (s, 1H, one olefinic
proton), 3.66 (s, 3H, CO2CH3), 3.27 (d, J=13.8 Hz, 1H, one
proton of CH2), 2.86 (d, J=13.8 Hz, 1H, one proton of
CH2), 2.00–1.82 (m, 2H, CH2), 1.40–1.10 (m, 4H, 2ꢂCH2),
0.87 (t, J=6.9 Hz, 3H, CH3); 13C NMR (100 MHz, CDCl3):
d=197.2, 167.0, 165.7, 160.0, 139.8, 136.7, 133.8, 132.4, 129.2,
128.2, 125.1, 87.7, 52.2, 38.6, 37.0, 25.5, 22.6, 13.7; MS (EI):
m/z=342 (M+, 18.75), 197 (100); IR (neat): n=2957, 2932,
2872, 1777, 1729, 1653, 1597, 1578, 1436, 1339, 1263, 1122,
1100, 1053, 1018 cmÀ1; HR-MS (EI): m/z=342.1466, calcd.
3-(Methoxycarbonyl)-3-(2-(phenylsulfonyl))-5-butyl-
2(3H)-furanone (3bp) and 3-(Methoxycarbonyl)-5-(2-
(phenylsulfonyl))-5-butyl-2(5H)-furanone (4bp)
The reaction of NaI (3 mg, 0.02 mmol), 2-methoxyfuran 1b
(42 mg, 0.20 mmol), and organic iodide 2p (91 mg,
0.30 mmol) in 2 mL of THF afforded 3bp (eluent: petroleum
ether/ethyl acetate=10/1); yield: 16 mg (21%) and 4bp
(eluent: petroleum ether/ethyl acetate=5/1); yield: 34 mg
(45%).
3bp: oil; 1H NMR (300 MHz, CDCl3): d=7.88–7.83 (m,
2H, Ar-H), 7.68–7.60 (m, 1H, Ar-H), 7.59–7.52 (m, 2H, Ar-
H), 6.45 (s, 1H, one olefinic proton), 5.86 (s, 1H, one olefin-
ic proton), 5.15 (s, 1H, one olefinic proton), 3.73 (s, 3H,
CO2CH3), 3.17 (d, J=15.6 Hz, 1H, one proton of CH2), 2.86
(d, J=15.3 Hz, 1H, one proton of CH2), 2.30 (t, J=7.5 Hz,
2H, CH2), 1.60–1.47 (m, 2H, CH2), 1.43–1.24 (m, 2H, CH2),
0.93 (t, J=7.4 Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3):
+
for C20H22O5 (M+): 342.1467.
1124
asc.wiley-vch.de
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2012, 354, 1114 – 1128

Tuning of Regioselectivity in Inorganic Iodide-Catalyzed Alkylation of 2-Methoxyfurans
proton), 5.81 (s, 1H, one olefinic proton), 4.22–4.08 (m, 2H,
3-(Methoxycarbonyl)-3-[2-(methoxycarbonyl)allyl]-5-
phenyl-2(3H)-furanone (3ar) and 3-(Methoxycar-
bonyl)-5-[2-(methoxycarbonyl)allyl]-5-phenyl-2(5H)-
furanone (4ar)
CO2CH2), 3.82 (s, 3H, CO2CH3), 3.37 (d, J=13.8 Hz, 1H,
one proton of CH2), 2.99 (d, J=13.8 Hz, 1H, one proton of
CH2), 1.27 (t, J=7.1 Hz, 3H, CH3); 13C NMR (100 MHz,
CDCl3): d=166.6, 166.4, 164.9, 160.2, 137.3, 132.4, 132.2,
129.0, 128.7, 124.9, 123.5, 87.3, 61.2, 52.4, 41.5, 14.0; MS
(EI): m/z=330 (M+, 1.77), 217 (100); IR (neat): n=1782,
1709, 1632, 1436, 1317, 1181, 1001 cmÀ1; HR-MS (EI): m/z=
The reaction of NaI (3 mg, 0.02 mmol), 2-methoxyfuran 1a
(46 mg, 0.20 mmol), and organic iodide 2r (90 mg,
0.40 mmol) in 2 mL of THF afforded 3ar (eluent: petroleum
ether/ethyl acetate=10/1); yield: 6 mg (10%) and 4ar[12]
(eluent: petroleum ether/ethyl acetate=5/1); yield: 49 mg
(78%, purity 98% with mesitylene as internal standard).
3ar: oil; 1H NMR (300 MHz, CDCl3): d=7.59–7.53 (m,
2H, Ar-H), 7.42–7.37 (m, 3H, Ar-H), 6.23 (s, 1H, one ole-
finic proton), 5.79 (s, 1H, one olefinic proton), 5.75 (s, 1H,
one olefinic proton), 3.77 (s, 3H, CO2CH3), 3.65 (s, 3H,
CO2CH3), 3.48 (d, J=13.8 Hz, 1H, one proton of CH2), 3.01
(d, J=13.5 Hz, 1H, one proton of CH2); 13C NMR
(75.4 MHz, CDCl3): d=173.5, 167.8, 167.1, 153.9, 134.4,
130.3, 130.1, 128.7, 127.4, 125.1, 102.1, 60.9, 53.5, 52.0, 35.5;
MS (ESI): m/z=339 (M+Na+); IR (neat): n=2954, 1804,
1742, 1722, 1650, 1631, 1495, 1438, 1235, 1196, 1166, 1115,
1047, 1002 cmÀ1; HR-MS (ESI): m/z=339.0839, calcd. for
C17H16O6Na+ (M+Na+): 339.0839.
+
330.1106, calcd. for C18H18O6 (M+): 330.1103.
3-(Methoxycarbonyl)-3-[2-(butoxycarbonyl)allyl]-5-
phenyl-2(3H)-furanone (3as) and 3-(Methoxycar-
bonyl)-5-[2-(butoxycarbonyl)allyl]-5-phenyl-2(5H)-
furanone (4as)
The reaction of NaI (3 mg, 0.02 mmol), 2-methoxyfuran 1a
(46 mg, 0.20 mmol), and organic iodide 2s (107 mg,
0.40 mmol) in 2 mL of THF afforded 3as (eluent: petroleum
ether/ethyl acetate=10/1); yield: 9 mg (13%) and 4as
(eluent: petroleum ether/ethyl acetate=5/1); yield: 58 mg
(82%).
3as: oil; 1H NMR (300 MHz, CDCl3): d=7.58–7.53 (m,
2H, Ar-H), 7.45–7.33 (m, 3H, Ar-H), 6.21 (s, 1H, one ole-
finic proton), 5.79 (s, 1H, one olefinic proton), 5.73 (s, 1H,
one olefinic proton), 4.03 (t, J=6.8 Hz, 2H, CO2CH2), 3.77
(s, 3H, CO2CH3), 3.49 (d, J=13.8 Hz, 1H, one proton of
CH2), 2.99 (d, J=13.2 Hz, 1H, one proton of CH2), 1.52–
1.40 (m, 2H, CH2), 1.26–1.17 (m, 2H, CH2), 0.79 (t, J=
7.4 Hz, 3H, CH3); 13C NMR (75.4 MHz, CDCl3): d=173.5,
167.8, 166.7, 153.8, 134.7, 130.2, 129.7, 128.7, 127.4, 125.0,
102.1, 64.9, 61.0, 53.5, 35.5, 30.5, 19.0, 13.6; MS (ESI): m/z=
381 (M+Na+); IR (neat): n=2959, 1807, 1746, 1715, 1650,
1630, 1495, 1450, 1435, 1238, 1174, 1116, 1048 cmÀ1; HR-MS
(ESI): m/z=381.1302, calcd. for C20H22O6Na+ (M+Na+):
381.1309.
4ar: solid; mp 82–848C (petroleum ether/ethyl acetate)
1
[lit.: 81–838C (petroleum ether/ether)]; H NMR (400 MHz,
CDCl3): d=8.34 (s, 1H, CH=), 7.48–7.30 (m, 5H, Ar-H),
6.35 (d, J=0.8 Hz, 1H, one olefinic proton), 5.80 (d, J=
0.8 Hz, 1H, one olefinic proton), 3.82 (s, 3H, CO2CH3), 3.71
(s, 3H, CO2CH3), 3.34 (d, J=14.0 Hz, 1H, one proton of
CH2), 3.00 (d, J=13.2 Hz, 1H, one proton of CH2);
13C NMR (100 MHz, CDCl3): d=167.1, 166.4, 164.8, 160.2,
137.2, 132.4, 132.1, 129.0, 128.8, 124.9, 123.5, 87.3, 52.5, 52.2,
41.5; IR (neat): n=1779, 1717, 1633, 1601, 1494, 1438, 1345,
1315, 1258, 1197, 1174, 1147, 1068, 1025, 1001 cmÀ1; MS
(EI): m/z=316 (M+, 1.88), 217 (100).
4as: oil; 1H NMR (300 MHz, CDCl3): d=8.35 (s, 1H,
CH=), 7.49–7.32 (m, 5H, Ar-H), 6.36 (s, 1H, one olefinic
proton), 5.81 (s, 1H, one olefinic proton), 4.18–4.05 (m, 2H,
CO2CH2), 3.82 (s, 3H, CO2CH3), 3.37 (d, J=13.8 Hz, 1H,
one proton of CH2), 2.99 (d, J=14.1 Hz, 1H, one proton of
CH2), 1.69–1.55 (m, 2H, CH2), 1.45–1.30 (m, 2H, CH2), 0.94
(t, J=7.4 Hz, 3H, CH3); 13C NMR (100 MHz, CDCl3): d=
166.7, 166.4, 164.8, 160.1, 137.2, 132.3, 132.0, 129.0, 128.7,
124.9, 123.4, 87.3, 65.0, 52.4, 41.4, 30.4, 19.0, 13.6; MS (EI):
m/z=358 (M+, 1.76), 217 (100); IR (neat): n=2960, 1785,
1711, 1632, 1437, 1317, 1257, 1179, 1146, 1067, 1025,
3-(Methoxycarbonyl)-3-[2-(ethoxycarbonyl)allyl]-5-
phenyl-2(3H)-furanone (3an) and 3-(Methoxycar-
bonyl)-5-[2-(ethoxycarbonyl)allyl]-5-phenyl-2(5H)-
furanone (4an)
The reaction of NaI (3 mg, 0.02 mmol), 2-methoxyfuran 1a
(46 mg, 0.20 mmol), and organic iodide 2n (98 mg,
0.40 mmol) in 2 mL of THF afforded 3an (eluent: petroleum
ether/ethyl acetate=10/1); yield: 11 mg (17%) and 4an
(eluent: petroleum ether/ethyl acetate=5/1); yield: 50 mg
(76%).
1001 cmÀ1
;
HR-MS (EI): m/z=358.1422, calcd. for
+
C20H22O6 (M+): 358.1416.
3an: oil; 1H NMR (300 MHz, CDCl3): d=7.58–7.53 (m,
2H, Ar-H), 7.42–7.37 (m, 3H, Ar-H), 6.22 (s, 1H, one ole-
finic proton), 5.79 (s, 1H, one olefinic proton), 5.73 (s, 1H,
one olefinic proton), 4.14–4.05 (m, 2H, CO2CH2), 3.77 (s,
3H, CO2CH3), 3.48 (d, J=13.8 Hz, 1H, one proton of CH2),
3.00 (d, J=13.8 Hz, 1H, one proton of CH2), 1.13 (t, J=
7.2 Hz, 3H, CH3); 13C NMR (100 MHz, CDCl3): d=173.5,
167.8, 166.6, 153.9, 134.8, 130.2, 129.7, 128.7, 127.4, 125.1,
102.2, 61.0, 60.9, 53.4, 35.5, 14.0; MS (ESI): m/z=353 (M+
3-(Methoxycarbonyl)-3-(2-cyanoallyl)-5-phenyl-
2(3H)-furanone (3ao) and 3-(methoxycarbonyl)-5-(2-
cyanoallyl)-5-phenyl-2(5H)-furanone (4ao)
The reaction of NaI (3 mg, 0.02 mmol), 2-methoxyfuran 1a
(46 mg, 0.20 mmol), and organic iodide 2o (77 mg,
0.40 mmol) in 2 mL of THF afforded 3ao (eluent: petroleum
ether/ethyl acetate=10/1); yield: 6 mg (11%) and 4ao
(eluent: petroleum ether/ethyl acetate=2/1); yield: 40 mg
(71%).
+
Na+), 348 (M+NH4 ), 331 (M+H+); IR (neat): n=1804,
1743, 1713, 1650, 1630, 1495, 1449, 1435, 1235, 1177,
1113 cmÀ1
;
HR-MS (ESI): m/z=353.0990, calcd. for
C18H18O6Na+ (M+Na+): 353.0996.
3ao: oil; 1H NMR (300 MHz, CDCl3): d=7.69–7.63 (m,
2H, Ar-H), 7.47–7.40 (m, 3H, Ar-H), 6.00 (s, 1H, one ole-
finic proton), 5.96 (s, 1H, one olefinic proton), 5.92 (s, 1H,
4an: oil; 1H NMR (300 MHz, CDCl3): d=8.35 (s, 1H,
CH=), 7.48–7.31 (m, 5H, Ar-H), 6.36 (s, 1H, one olefinic
Adv. Synth. Catal. 2012, 354, 1114 – 1128
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
1125

Jie Chen et al.
FULL PAPERS
one olefinic proton), 3.80 (s, 3H, CO2CH3), 3.21 (d, J=
14.1 Hz, 1H, one proton of CH2), 3.01 (d, J=14.1 Hz, 1H,
one proton of CH2); 13C NMR (100 MHz, CDCl3): d=172.6,
167.0, 155.5, 136.3, 130.7, 128.9, 127.0, 125.5, 118.1, 116.7,
100.5, 60.3, 53.7, 38.3; MS (EI): m/z=283 (M+, 22.81), 105
(100); IR (neat): n=2223, 1796, 1745, 1495, 1439, 1407,
1321, 1283, 1230, 1116, 1069, 1048 cmÀ1; HR-MS (EI): m/z=
1.08 (m, 8H, CH of cyclohexyl and 2ꢂCH2 and CH3);
13C NMR (100 MHz, CDCl3): d=174.4, 168.3, 166.6, 161.8,
134.8, 129.5, 101.3, 61.0, 60.1, 53.2, 36.6, 35.0, 29.5, 29.1, 25.9,
25.31, 25.28, 14.2; MS (EI): m/z=336 (M+, 0.91), 223 (100);
IR (neat): n=2928, 2854, 1707, 1603, 1471, 1451, 1406, 1264,
1232, 1191, 1143, 1082 cmÀ1; HR-MS (EI): m/z=336.1571,
+
calcd. for C18H24O6 (M+): 336.1573.
283.0844, calcd. for C16H13NO4 (M+): 283.0845.
4gn: oil; 1H NMR (300 MHz, CDCl3): d=8.06 (s, 1H,
CH=), 6.28 (s, 1H, one olefinic proton), 5.70 (s, 1H, one ole-
finic proton), 4.21–4.05 (m, 2H, CO2CH2), 3.81 (s, 3H,
CO2CH3), 3.08 (d, J=13.8 Hz, 1H, one proton of CH2), 2.75
(d, J=13.8 Hz, 1H, one proton of CH2), 1.86–1.60 (m, 6H,
2ꢂCH of cyclohexyl and 2ꢂCH2), 1.30–0.99 (m, 8H, CH of
cyclohexyl and 2ꢂCH2 and CH3).
+
4ao: solid; mp 146–1488C (petroleum ether/ethyl acetate);
1H NMR (300 MHz, CDCl3): d=8.46 (s, 1H, CH=), 7.48–
7.35 (m, 5H, Ar-H), 6.07 (s, 1H, one olefinic proton), 5.89
(s, 1H, one olefinic proton), 3.88 (s, 3H, CO2CH3), 3.11 (d,
J=15.0 Hz, 1H, one proton of CH2), 3.01 (d, J=14.4 Hz,
1H, one proton of CH2); 13C NMR (100 MHz, CDCl3): d=
165.7, 163.1, 159.9, 137.7, 135.8, 129.3, 125.2, 125.0, 118.0,
114.8, 86.5, 52.7, 44.3; MS (ESI): m/z=306 (M+Na+); IR
(neat): n=2224, 1789, 1729, 1437, 1349, 1330, 1259, 1070,
1024, 1001 cmÀ1; HR-MS (ESI): m/z=306.0731, calcd. for
C16H13NO4Na+ (M+Na+): 306.0737; anal. calcd. for
C16H13NO4: C 67.84, N 4.94, H 4.63; found: C 67.65, N 4.88,
H 4.73.
The reaction of MgI2 (6 mg, 0.02 mmol), 2-methoxyfuran
1g (48 mg, 0.20 mmol), and organic iodide 2n (96 mg,
0.40 mmol) in 2 mL of THF afforded 4gn (eluent: petroleum
ether/ethyl acetate=6/1) as an with 20:1 regioselectivity ac-
1
cording to H NMR analysis of the crude reaction mixture:
oil; yield: (6 mg (68%): 1H NMR (300 MHz, CDCl3): d=
8.05 (s, 1H, CH=), 6.26 (s, 1H, one olefinic proton), 5.69 (s,
1H, one olefinic proton), 4.21–4.03 (m, 2H, CO2CH2), 3.80
(s, 3H, CO2CH3), 3.06 (d, J=13.5 Hz, 1H, one proton of
CH2), 2.74 (d, J=13.8 Hz, 1H, one proton of CH2), 1.86–
1.60 (m, 6H, 2ꢂCH of cyclohexyl and 2ꢂCH2), 1.28–0.97
(m, 8H, CH of cyclohexyl and 2ꢂCH2 and CH3); 13C NMR
(100 MHz, CDCl3): d=167.0, 166.7, 165.6, 160.3, 132.7,
131.6, 125.1, 89.7, 61.1, 52.3, 45.0, 35.9, 28.0, 27.1, 26.1, 26.0,
25.8, 14.0; MS (EI): m/z=337 (M+ +1, 28.83), 336 (M+,
3.11), 223 (100); IR (neat): n=2931, 2855, 1778, 1711, 1632,
1436, 1370, 1335, 1315, 1265, 1233, 1179, 1147, 1100, 1073,
3-(Phenylsulfonyl)-5-[2-(ethoxycarbonyl)allyl]-5-
butyl-2(5H)-furanone (4cn)
The reaction of NaI (3 mg, 0.02 mmol), 2-methoxyfuran 1c
(59 mg, 0.20 mmol), and organic iodide 2n (96 mg,
0.40 mmol) in 2 mL of THF afforded 4cn (eluent: petroleum
ether/ethyl acetate=7/1) as an oil; yield: 39 mg (50%).
1H NMR (300 MHz, CDCl3): d=8.10 (s, 1H, CH=), 8.03–
7.97 (m, 2H, Ar-H), 7.70–7.62 (m, 1H, Ar-H), 7.54 (t, J=
7.7 Hz, 2H, Ar-H), 6.15 (s, 1H, one olefinic proton), 5.62 (s,
1H, one olefinic proton), 4.28–4.08 (m, 2H, CO2CH2), 3.00
(d, J=13.8 Hz, 1H, one proton of CH2), 2.74 (d, J=14.1 Hz,
1H, one proton of CH2), 1.96–1.77 (m, 2H, CH2), 1.35–1.05
(m, 7H, 2ꢂCH2 and CH3), 0.84 (t, J=6.8 Hz, 3H, CH3);
13C NMR (75 MHz, CDCl3): d=166.4, 164.0, 163.8, 138.3,
135.8, 134.4, 132.3, 131.7, 129.1, 128.6, 88.1, 61.5, 38.4, 36.9,
25.4, 22.5, 14.1, 13.7; MS (EI): m/z=393 (M+, 15.58), 125
(100); IR (neat): n=2958, 2932, 2872, 1770, 1705, 1630,
1614, 1412, 1329, 1310, 1285, 1194, 1165, 1151, 1118,
1021 cmÀ1
;
HR-MS (ESI): m/z=336.1574, calcd. for
+
C18H24O6 (M+): 336.1573.
3-(Methoxycarbonyl)-3-[2-(ethoxycarbonyl)allyl]-5-
tert-butyl-2(3H)-furanone (3hn) and 3-(Methoxy-
carbonyl)-5-[2-(ethoxycarbonyl)allyl]-5-tert-butyl-
2(5H)-furanone (4hn)
The reaction of NaI (3 mg, 0.02 mmol), 2-methoxyfuran 1h
(42 mg, 0.20 mmol), and organic iodide 2n (96 mg,
0.40 mmol) in 2 mL of THF afforded 3hn (eluent: petroleum
ether/ethyl acetate=10/1); yield: 36 mg (59%) and 4hn
(eluent: petroleum ether/ethyl acetate=5/1); yield: 13 mg
(21%).
1023 cmÀ1
;
HR-MS (ESI): m/z=392.1299, calcd. for
C20H24O6S+ (M+): 392.1294.
3-(Methoxycarbonyl)-3-[2-(ethoxycarbonyl)allyl]-5-
cyclohexyl-2(3H)-furanone (3gn) and 3-(Methoxy-
carbonyl)-5-[2-(ethoxycarbonyl)allyl]-5-cyclohexyl-
2(5H)-furanone (4gn)
1
3hn: oil; H NMR (300 MHz, CDCl3): d=6.21 (s, 1H, one
olefinic proton), 5.64 (s, 1H, one olefinic proton), 5.05 (s,
1H, one olefinic proton), 4.16 (q, J=7.1 Hz, 2H, CO2CH2),
3.74 (s, 3H, CO2CH3), 3.37 (d, J=13.5 Hz, 1H, one proton
of CH2), 2.86 (d, J=13.5 Hz, 1H, one proton of CH2), 1.28
The reaction of NaI (3 mg, 0.02 mmol), 2-methoxyfuran 1g
(48 mg, 0.20 mmol), and organic iodide 2n (96 mg,
0.40 mmol) in 2 mL of THF afforded 3gn (eluent: petroleum
ether/ethyl acetate=10/1); yield: 19 mg (28%) and 4gn
(eluent: petroleum ether/ethyl acetate=6/1); yield: 34 mg
(50%).
(t, J=7.2 Hz, 3H, CH3), 1.10 [s, 9H, CACTHNUTRGNEUNG
(CH3)3]; 13C NMR
(100 MHz, CDCl3): d=174.5, 168.2, 166.6, 165.2, 134.7,
129.5, 100.3, 61.0, 60.4, 53.2, 35.0, 32.3, 26.8, 14.2; MS (EI):
m/z=310 (M+, 3.39), 123 (100); IR (neat): n=2974, 1797,
1743, 1701, 1663, 1626, 1482, 1370, 1235, 1175, 1024,
1
3gn: oil; H NMR (300 MHz, CDCl3): d=6.22 (s, 1H, one
1007 cmÀ1
;
HR-MS (EI): m/z=310.1415, calcd. for
+
olefinic proton), 5.65 (d, J=0.6 Hz, 1H, one olefinic
proton), 5.06 (d, J=0.9 Hz, 1H, one olefinic proton), 4.17
(q, J=7.1 Hz, 2H, CO2CH2), 3.74 (s, 3H, CO2CH3), 3.37 (d,
J=13.5 Hz, 1H, one proton of CH2), 2.87 (d, J=13.5 Hz,
1H, one proton of CH2), 2.29–2.18 (m, 1H, CH of cyclohex-
yl), 1.89–1.61 (m, 5H, CH of cyclohexyl and 2ꢂCH2), 1.33–
C16H22O6 (M+): 310.1416.
4hn: oil; 1H NMR (300 MHz, CDCl3): d=8.11 (s, 1H,
CH=), 6.27 (s, 1H, one olefinic proton), 5.69 (s, 1H, one ole-
finic proton), 4.22–4.05 (m, 2H, CO2CH2), 3.82 (s, 3H,
CO2CH3), 3.16 (d, J=13.5 Hz, 1H, one proton of CH2), 2.78
(d, J=13.5 Hz, 1H, one proton of CH2), 1.24 (t, J=7.1 Hz,
1126
asc.wiley-vch.de
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2012, 354, 1114 – 1128

Tuning of Regioselectivity in Inorganic Iodide-Catalyzed Alkylation of 2-Methoxyfurans
3H, CH3), 1.06 [s, 9H, C
G
3-(Methoxycarbonyl)-5-[2-(methoxycarbonyl)allyl]-5-
butyl-2(5H)-furanone (4br): To a Schlenk reaction tube with
a screw cap, evacuated and backfilled with argon, were
CDCl3): d=167.3, 166.8, 165.2, 160.2, 133.0, 131.8, 125.6,
91.9, 61.2, 52.4, 37.7, 33.7, 25.6, 14.0; MS (EI): m/z=310
(M+, 1.60), 155 (100); IR (neat): n=1771, 1720, 1632, 1371,
1284, 1221, 1184, 1149, 1094, 1053, 1022 cmÀ1; HR-MS (EI):
added sequentially RuCl2ACHTNUTRGNE(UNG PPh3)3 (5 mg, 0.005 mmol), cyclo-
propenyl dicarboxylate 6 (42 mg, 0.20 mmol), and 2 mL of
THF. The resulting mixture was stirred at room temperature
and after 10 h the reaction was over as monitored by TLC.
Then to the same tube were added sequentially MgI2 (6 mg,
0.02 mmol) and organic idodide 2r (90 mg, 0.40 mmol). The
resulting mixture was stirred at 608C and after 23.5 h the re-
action was over as monitored by TLC. Evaporation and
column chromatography on silica gel (eluent: petroleum
ether/ethyl acetate=5/1) afforded the desired product 4br
m/z=310.1419, calcd. for C16H22O6 (M+): 310.1416.
3-(Methoxycarbonyl)-5-[2-(methoxycarbonyl)allyl]-5-
butyl-2(5H)-furanone (4br)
The reaction of MgI2 (6 mg, 0.02 mmol), 2-methoxyfuran 1b
(42 mg, 0.20 mmol), and organic iodide 2r (91 mg,
0.40 mmol) in 2 mL of THF afforded 4br (eluent: petroleum
ether/ethyl acetate=6/1) as an oil; yield: 42 mg (72%).
1H NMR (300 MHz, CDCl3): d=8.01 (s, 1H, CH=), 6.29 (s,
1H, one olefinic proton), 5.74 (s, 1H, one olefinic proton),
3.82 (s, 3H, CO2CH3), 3.69 (s, 3H, CO2CH3), 2.99 (d, J=
13.5 Hz, 1H, one proton of CH2), 2.76 (d, J=13.8 Hz, 1H,
one proton of CH2), 1.93–1.75 (m, 2H, CH2), 1.38–1.10 (m,
4H, 2ꢂCH2), 0.86 (t, J=7.1 Hz, 3H, CH3).
1
with 26:1 regioselectivity according to H NMR analysis of
the crude reaction mixture as an oil; yield: 43 mg (72%).
1H NMR (300 MHz, CDCl3): d=8.01 (s, 1H, CH=), 6.29 (s,
1H, one olefinic proton), 5.74 (s, 1H, one olefinic proton),
3.82 (s, 3H, CO2CH3), 3.69 (s, 3H, CO2CH3), 2.99 (d, J=
13.8 Hz, 1H, one proton of CH2), 2.76 (d, J=13.8 Hz, 1H,
one proton of CH2), 1.94–1.75 (m, 2H, CH2), 1.34–1.10 (m,
4H, 2ꢂCH2), 0.86 (t, J=7.1 Hz, 3H, CH3); 13C NMR
(100 MHz, CDCl3): d=167.1, 166.9, 165.6, 160.3, 132.3,
131.9, 125.0, 87.3, 52.4, 52.2, 38.5, 36.9, 25.5, 22.6, 13.7; MS
(EI): m/z=297 (M+ +1, 15.38), 296 (M+, 1.63), 197 (100);
IR (neat): n=2956, 1777, 1718, 1633, 1437, 1349, 1308, 1250,
1198, 1150, 1052, 1018 cmÀ1; HR-MS (EI): m/z=296.1268,
3-(Methoxycarbonyl)-5-[2-(butoxycarbonyl)allyl]-5-
butyl-2(5H)-furanone (4bs)
The reaction of MgI2 (6 mg, 0.022 mmol), 2-methoxyfuran
1b (42 mg, 0.20 mmol), and organic iodide 2s (107 mg,
0.40 mmol) in 2 mL of THF afforded 4bs (eluent: petroleum
ether/ethyl acetate=6/1) with 27:1 regioselectivity according
+
calcd. for C15H20O6 (M+): 296.1260.
1
to H NMR analysis of the crude reaction mixture as an oil;
1
yield: 48 mg (72%). H NMR (300 MHz, CDCl3): d=8.01 (s,
1H, CH=), 6.28 (s, 1H, one olefinic proton), 5.72 (s, 1H,
one olefinic proton), 4.16–4.00 (m, 2H, CO2CH2), 3.81 (s,
3H, CO2CH3), 3.00 (d, J=13.8 Hz, 1H, one proton of CH2),
2.74 (d, J=13.8 Hz, 1H, one proton of CH2), 1.95–1.78 (m,
2H, CH2), 1.64–1.52 (m, 2H, CH2), 1.40–1.05 (m, 6H, 3ꢂ
CH2), 0.90 (t, J=7.4 Hz, 3H, CH3), 0.86 (t, J=6.9 Hz, 3H,
CH3); 13C NMR (75 MHz, CDCl3): d=166.9, 166.7, 165.7,
160.3, 132.6, 131.6, 125.0, 87.3, 65.0, 52.3, 38.4, 36.9, 30.4,
25.5, 22.6, 19.0, 13.7, 13.6; MS (EI): m/z=339 (M + +1,
10.21), 197 (100); IR (neat): n=2958, 2935, 2873, 1779, 1712,
1632, 1460, 1436, 1339, 1308, 1266, 1183, 1149, 1121, 1053,
Acknowledgements
Financial support from the National Basic Research Program
of China (2009CB825300) and NSF of China (20732005) is
greatly appreciated. We thank Wangqing Kong in this group
for reproducing the preparation of 3ae in Table 1, 3ai in
Table 2, 3dn and 4dn in Table 3, and 4dn in Scheme 2.
References
1018 cmÀ1
;
HR-MS (EI): m/z=338.1729, calcd. for
+
+
[1] a) F. S. de Guzman, F. J. Schmitz, J. Nat. Prod. 1990, 53,
926; b) R. Estevez-Reyes, A. Estevez-Braun, A. G.
Gonzalez, J. Nat. Prod. 1993, 56, 1177; c) A. Evidente,
L. Sparapano, J. Nat. Prod. 1994, 57, 1720.
C18H26O6 (M ): 338.1729.
One-Pot Syntheses of 3bb and 4br
3-(Methoxycarbonyl)-3-methyl-5-butyl-2(3H)-furanone
(3bb): To a Schlenk reaction tube with a screw cap, evacuat-
ed and backfilled with argon, were added sequentially
[2] For a review on the synthesis of butenolides, see: E.
Negishi, M. Kotora, Tetrahedron 1997, 53, 6707.
[3] a) G. Casiraghi, G. Rassu, Synthesis 1995, 607; b) S. K.
Bur, S. F. Martin, Tetrahedron 2001, 57, 3221; c) C.
Cho, M. J. Krische, Angew. Chem. 2004, 116, 6857;
Angew. Chem. Int. Ed. 2004, 43, 6689; d) C. Cho, J.
Kong, M. J. Krische, Org. Lett. 2004, 6, 1337; e) P. K.
Koech, M. J. Krische, J. Am. Chem. Soc. 2004, 126,
5350; f) Y. Jiang, Y. Shi, M. Shi, J. Am. Chem. Soc.
2008, 130, 7202.
RuCl2ACHTUNGTRENNUNG(PPh3)3 (5 mg, 0.005 mmol), cyclopropenyl dicarboxy-
late 6 (42 mg, 0.20 mmol), and 2 mL of THF. The resulting
mixture was stirred at room temperature and after 12 h the
reaction was over as monitored by TLC. Then to the same
tube were added sequentially NaI (3 mg, 0.02 mmol) and
MeI 2b (30 mL, d=2.28 gmLÀ1, 68 mg, 0.48 mmol). The re-
sulting mixture was stirred at 808C and after 47 h the reac-
tion was over as monitored by TLC. Evaporation and
column chromatography on silica gel (eluent: petroleum
ether/ethyl acetate=20/1) afforded the desired product 3bb
[4] K. Takahashi, K. Nishijima, N. Makino, K. Takase, S.
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1
as an oil; yield: 31 mg (74%). H NMR (300 MHz, CDCl3):
d=5.20 (s, 1H, CH=), 3.73 (s, 3H, CO2CH3), 2.32 (td, J=
7.5, 1.2 Hz, 2H, CH2), 1.63–1.48 (m, 2H, CH2), 1.52 (s, 3H,
CH3), 1.43–1.29 (m, 2H, CH2), 0.92 (t, J=7.2 Hz, 3H).
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Adv. Synth. Catal. 2012, 354, 1114 – 1128
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Jie Chen et al.
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final R indices [I>2s(I)], R1=0.0397, wR2=0.0838, R
indices (all data), R1=0.0629, wR2=0.0962, a=6.9445
(15) ꢃ, b=11.372 (3) ꢃ, c=17.438 (4) ꢃ, a=908, b=
90 (2)8, g=908, V=1377.2 (5) ꢃ3, T=173 (2) K, Z=4,
reflections collected/unique: 14489/2415 (RACHTUNGTRENNUNG(int)=
[9] S. Ma, L. Lu, J. Zhang, J. Am. Chem. Soc. 2004, 126,
9645.
0.1059), number of observations [>2s(I)] 1905; param-
eters: 198. Supplementary crystallographic data have
been deposited at the Cambridge Crystallographic
Data Center under CCDC 806134. These data can be
obtained free of charge from The Cambridge Crystallo-
graphic Data Centre via www.ccdc.cam.ac.uk/data_re-
quest/cif.
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structures of products except 3ae in this report should
be read as the 3-arylation products instead of the 5-ary-
lation products.
[13] Crystal data for compound 3aa: 2C20H15BrO5 +
CH3CO2Et, MW=918.56, monoclinic, space group
P2(1)/c, final R indices [I>2s(I)], R1=0.0290, wR2=
0.0697, R indices (all data), R1=0.0313, wR2=0.0708,
a=14.1862 (5) ꢃ, b=5.6007 (2) ꢃ, c=25.5496 (8) ꢃ,
a=908, b=96.5170 (10)8, g=908, V=2016.87 (12) ꢃ3,
T=173 (2) K, Z=2, reflections collected/unique:
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Greif, Monatsh. Chem. 2001, 132, 929.
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79, 393.
23436/7065 (RACHTUNTRGNEUNG(int)=0.0216), number of observations
[>2s(I)] 6717; parameters: 524. Supplementary crystal-
lographic data have been deposited at the Cambridge
Crystallographic Data Center under CCDC 806133.
These data can be obtained free of charge from The
Cambridge
Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
[21] J. C. S. Woo, E. Fenster, G. R. Dake, J. Org. Chem.
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[14] Crystal data for compound 4ao: C16H13O4N, MW =
283.27, orthorhombic, space group P2(1)2(1)2(1)/c,
1128
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ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2012, 354, 1114 – 1128