Efficient conversion of nitronate into nitrile oxide using cyanuric chloride. One-pot synthesis of bicyclic isoxazolines and isoxazoles from nitroalkenes

Article abstract of DOI:10.1039/b606717d

Bicyclic isoxazolines and isoxazoles are obtained in good yields by proceeding through a convenient one-pot, two-step procedure utilizing 2,4,6-trichloro-1,3,5-triazine (TCT) as a dehydrating agent. The Royal Society of Chemistry 2006.

Full text of DOI:10.1039/b606717d

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www.rsc.org/obc | Organic & Biomolecular Chemistry
Efficient conversion of nitronate into nitrile oxide using cyanuric chloride.
One-pot synthesis of bicyclic isoxazolines and isoxazoles from nitroalkenes†
Shijay Gao, Zhijay Tu, Chun-Wei Kuo, Ju-Tsung Liu, Cheng-Ming Chu and Ching-Fa Yao*
Received 12th May 2006, Accepted 5th June 2006
First published as an Advance Article on the web 28th June 2006
DOI: 10.1039/b606717d
Bicyclic isoxazolines and isoxazoles are obtained in good yields by proceeding through a convenient
one-pot, two-step procedure utilizing 2,4,6-trichloro-1,3,5-triazine (TCT) as a dehydrating agent.
Introduction
nucleophiles to generate nitroalkanes, halooximes, nitrile oxides,
and/or polycyclic compounds under different reaction conditions
or workup procedures. As part of our incessant research efforts
with nitroalkene chemistry, we now report a new, economic and
efficient dehydrating agent, TCT, for the one-pot synthesis of
bicyclic isoxazolines and isoxazoles.
Isoxazolines and isoxazoles are often encountered in molecules
of medicinal interest. There are numerous examples of these N,O-
heterocycles being used as key building blocks in the total synthesis
of several natural and unnatural compounds such as b-lactam
antibiotics, quinolizidine and indolizine tricycles, testosterone,
7
1
sarkomycin, and biotin. The isoxazolines or isoxazoles can also
be transformed into a variety of other 1,3-bifunctional organic
Results and discussion
compounds, whether cyclic or acyclic, such as b-hydroxy ketones,
a,b-unsaturated ketones and c-amino alcohols. Intramolecu-
The methodology is to convert a nitroalkene into the correspond-
ing nitronate by reaction with the allylmalonate anion in THF
2
lar 1,3-cycloaddition provides a useful tool for the synthesis
of a variety of the above-mentioned heterocyclic compounds,
particularly for the construction of merged cyclic ring systems
such as bicyclic isoxazolines or isoxazoles. Conventional 1,3-
cycloaddition involves a two-step process such as dipolarphile
◦
solution at −78 C for 30 minutes. Thus, the generated nitronate
is transformed into the corresponding nitrile oxide by adding
TCT, as the dehydrating agent, directly to the mixture without
isolation. The nitrile oxide generated in situ undergoes a tandem
1
,3-dipolar cycloaddition with the dipolarphile, furnishing the
bicyclic isoxazoline within 15 minutes at the same temperature
Scheme 1).
3
introduction followed by cycloaddition.
The one-pot synthesis of bicyclic isoxazolines proved futile,
presumably due to poor conversion of the nitronate into nitrile
oxide in the presence of phenyl isocyanate and triethylamine under
(
4
the conditions usually employed for nitroalkanes. Treatment of
the nitronate with di-tert-butyl dicarbonate in the presence of
catalytic amounts of DMAP led to low to medium yields (24–67%)
of the desired isoxazoline in a one-pot procedure, or in separated
5
steps via the isolated nitroalkane. A highly stereoselective one-
pot synthesis of bicyclic compounds developed by Hassner et al.
suffers from several drawbacks, such as longer reaction times (15–
4
8 hours), the use of toxic solvent (HMPA), and lower yields (18%)
5
with aliphatic substrates. By adopting a similar procedure, Cheng
et al. reported that the same reaction with different nucleophiles
also suffers from longer reaction times (13 hours). In this context,
Scheme 1 One-pot and two-step synthesis of isoxazolines.
5
exploring efficient reagents and the development of simple and
mild procedures for the preparation of isoxazolines and isoxazoles
is still an interesting topic for organic chemists. Over the past
few years, 2,4,6-trichloro-1,3,5-triazine (TCT), also referred as
cyanuric chloride, has emerged as an activator or activating agent
of carboxylic acids for various organic transformations to afford
Preliminary efforts were mainly focused on the evaluation of the
optimum amount of TCT at different temperatures. The yields of
nitroalkane1 and isoxazoline2 obtainedbyreacting b-nitrostyrene
1.0 eq.) with the potassium dimethyl allylmalonate (1.2 eq.)
generated from dimethyl allylmalonate and potassium t-butoxide,
and subsequent treatment with TCT under different conditions at
different temperatures are shown in Table 1.
(
6
the corresponding products in good to excellent yields. Our
previous study found that nitroalkenes can react with different
Initially, the treatment of nitronate solution with 1 eq. of TCT at
0 C for 15 min afforded nitroalkane 1 and bicyclic isoxazoline 2
◦
Department of Chemistry, National Taiwan Normal University 88, Sec.
4
, Tingchow Road, Taipei, 116, Taiwan, ROC. E-mail: cheyaocf@scc.
in 8% and 61% yields respectively (entry 1). In order to restrict
the formation of nitroalkane, we endeavoured to improve the
conversion of the nitronate into nitrile oxide by varying the
amounts of TCT and/or dimethylaminopyridine (DMAP) in the
ntnu.edu.tw; Fax: +886 2 29309092
†
Electronic supplementary information (ESI) available: General experi-
mental details, characterization data and NMR spectra for all compounds.
See DOI: 10.1039/b606717d
This journal is © The Royal Society of Chemistry 2006
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Table 1 Reaction of b-nitrostryene with dimethyl allylmalonate and t-BuOK, and then with TCT, under different conditions
◦
a
a
b
Entry
TCT (eq.)
Additives
Temp ( C)
Yield of 1 (%)
Yield of 2 (%)
cis : trans
1
2
3
4
5
6
1
5
1
1
3
1
—
—
0
0
0
8
5
11
18
—
—
61
54
64
81
99
96
3.2 : 1
3.2 : 1
4.0 : 1
4.0 : 1
4.3 : 1
3.9 : 1
c
DMAP(1 eq.)
—
—
−78
−78
−78
d
2
ZnCl (0.2 eq.)
a
b
c
d
NMR yield. The cis : trans ratios were measured by NMR. TCT was initially added to the nitronate solution followed by DMAP. TCT and ZnCl
2
were added simultaneously.
reaction system (entries 2 and 3). The product yields were not
significantly improved, either by increasing or decreasing the
amounts of TCT or DMAP. However, the effect of temperature
Table 2 The preparation of isoxazoline from nitroalkenes and dimethyl
allylmalonate
c
d
%
Yield (cis : trans)
◦
was apparent. When the reaction was carried out at −78 C, a
a
b
Entry Nitroalkene
1
Isoxazoline
Method A Method B
mixture of nitroalkane and bicyclic isoxazoline were obtained in
◦
quantitative yield (entry 4). The increased product yields at −78 C
2a 97(4.3 : 1) 94 (3.9 : 1)
2b 88(4.3 : 1) 93 (4.5 : 1)
imply that the addition of the allylmalonate anion to nitroalkenes
should be performed at a lower temperature in order to prevent
unwanted reactions such as dimerization of nitrile oxide or the
formation of other side products. Although the yield of bicyclic
isoxazoline was increased, the reaction still afforded nitroalkane
in 18% yield. After considerable experimentation, we were pleased
to find that when nitronate was treated with 3 equivalents of
2
3
4
◦
TCT at −78 C, isoxazoline was generated in quantitative yield
2c 85(3.4 : 1) 80 (3.8 : 1)
2d 83(3.7 : 1) 88 (3.4 : 1)
without any trace of nitroalkane. This result clearly suggests that
the use of one eq. of TCT is not enough to completely convert
the nitronate into nitrile oxide under these conditions (entry 5).
Literature studies revealed that mild Lewis acids such as ZnCl
can improve the reactivity of TCT. Based on these results, we
2
8
next investigated the effect of ZnCl as an additive. The mild
2
Lewis acidity of zinc chloride dramatically improved the activity
of TCT and thus, one eq. of TCT in combination with 0.2 eq.
of ZnCl
2
was sufficient to afford the nitrile oxide in excellent
system
5
6
2e 94(4.5 : 1) 86 (4.8 : 1)
2f 84(4.1 : 1) 70 (5.0 : 1)
yield (entry 6). The generality of the TCT or TCT–ZnCl
2
for the one-pot conversion of nitroalkenes into nitrile oxides has
been verified using a wide variety of nitroalkenes (Table 2). The
bicyclic isoxazolines thus formed (70–97% yield) can be obtained
in pure form by simple filtration, followed by passing the crude
mixture through a short plug of silica. In some cases the cis
and trans isomers could be further separated by flash column
chromatography. In order to extend the scope of this one-pot
conversion, dimethylallylmalonate was replaced either with prop-
a
Method A: the reaction was carried out in the presence of 3 eq. of TCT.
Method B: the reaction was carried out in the presence of 1 eq. of TCT
2
-ynylmalonates or prop-2-ynylmalononitriles. In both cases the
b
bicyclic products were formed in 62–96% isolated yields. Not only
aromatic nitroalkenes, but also aliphatic nitroalkenes in a reaction
with these nucleophiles afforded bicyclic products in relatively
high yield (73–91%) (Table 3). It is noteworthy to observe that
the corresponding aliphatic products were obtained in excellent
c
d
and 0.2 eq. of ZnCl . Isolated yields. The cis : trans ratios were measured
by the crude NMR results.
2
the product yields obtained by reacting nitroalkenes with ally-
malonate are higher than those using prop-2-ynylmalonate due to
the higher reactivity of the double bond compared to the triple
bond (compare entries 1 and 5 of Table 2 to entries 1 and 2 of
Table 3). Similarly, the rate of cycloaddition of nitroalkenes with
yield compared to the known methods existing in the literature
5
(
entries 6 and 12). The scope of this transformation has been
demonstrated by using a wide range of nitroalkenes in which the
phenyl group was substituted with different groups. Generally,
2
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Table 3 Isoxazoles prepared from nitroalkenes and prop-2-ynylmalonate or prop-2-ynylmalononitrile
c
c
Yield (%)
Yield (%)
a
b
a
b
Entry
1
Isoxazole
Method A
96
Method B
89
Entry
7
Isoxazole
Method A
89
Method B
3a
3g
81
2
3
3b
3c
88
89
82
82
8
9
3h
3i
73
78
63
73
4
5
3d
3e
74
91
80
84
10
11
3j
71
74
66
66
3k
6
3f
91
84
12
3l
86
73
a
b
Method A: the reaction was carried out in the presence of 3 eq. of TCT. Method B: the reaction was carried out in the presence of 1 eq. of TCT and
.2 eq. of ZnCl . Isolated yield relative to nitroalkene.
2
c
0
prop-2-ynylmalonate is faster than with prop-2-ynylmalononitrile,
because the presence of the bulky dimethoxycarbonyl groups
enables the dipolarphile to be closer to the nitrile oxide to
more easily undergo the intramolecular cycloaddition. That is
the reason why the product yields of prop-2-ynylmalonate are
always higher than those of prop-2-ynylmalononitrile in a reaction
with nitroalkenes (Table 3, compare entries 1–7 to entries 8–
Scheme
2
Tricyclic isoxazoline prepared from b-nitrostryene and
1
2). The same reaction system has been extended efficiently for
dimethyl-(3-cyclohexyl)malonate.
the construction of a tricyclic ring system. Thus, reaction of
b-nitrostyrene with dimethyl 3-cyclohexylmalonate afforded the
tricyclic product 4 in 60% isolated yield (Scheme 2).
encountered in molecules of medicinal interest. The procedures
described here are simple and efficient. The use of TCT as a
dehydrating agent has the advantages of being economically viable
and more efficient for the conversion of nitronate into nitrile oxide.
The reaction system can be successfully applied to a variety of
nitroalkenes as well as nucleophiles to synthesize various bicyclic
isoxazolines and isoxazoles, and tricyclic products.
Conclusions
In conclusion, we have developed a novel procedure for the one-
pot synthesis of isoxazolines and isoxazoles, which are often
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Experimental
tration in vacuo to give a colorless oil; IR (CHCl ) mmax 2950,
3
1
731, 1610, 1514, 1434, 1369, 1278, 1250, 1207, 1179, 1102, 1077,
General
−1
1
1
031, 836, 788 cm ; H NMR (400 MHz, CDCl ) d 7.16–7.12
3
(
m, 2H), 6.83–6.79 (m, 2H), 4.96 (d, J = 1.32 Hz, 1H), 4.67 (dd,
All reactions were performed in oven-dried glassware under a
positive pressure of nitrogen when the reactions were sensitive to
J = 9.6, 7.7 Hz, 1H), 4.63–4.52 (m, 1H), 3.88 (s, 3H), 3.77 (s,
3
1
1
5
H), 3.12 (s, 3H), 2.85 (dd, J = 12.9, 7.6 Hz, 1H), 1.79 (dd, J =
2.8, 11.1 Hz, 1H); C NMR (100 MHz, CDCl ) d 171.29, 171.01,
70.02, 159.26, 129.99, 128.80, 113.89, 75.34, 71.60, 55.50, 55.48,
˚
moisture or oxygen. Solvents were dried over 4 A molecular sieves.
1
3
3
All other commercially available reagents were used as received
without purification. Analytical thin layer chromatography was
performed with E. Merck silica gel 60F glass plates and flash
chromatography with E. Merck silica gel 60 (230–400 mesh). MS
or HRMS were measured by JEOL JMS-D300 or JEOL JMS-
3.35, 52.49, 45.53, 36.61; HRMS (EI) m/z calcd for C17
M ) 333.1212, found 333.1215.
H
19NO
6
+
(
cis-5,5-Dimethoxycarbonyl-6-(4-fluorophenyl)-3a,4-dihydro-
1
13
HX110 spectrometer. H and C NMR spectra were recorded
with a Varian Gemini-200 or Bruker Avance EX 400 or 500 FT
NMR. Elemental analyses were carried out with a HERAEUS
3H,6H-cyclopenta[c]isoxazole (cis-2c). Purified by column chro-
matography (ethyl acetate–hexanes 1 : 5) after concentration in
vacuo to give a colorless oil; IR (CHCl ) m 3445, 2955, 1730,
3
max
1
−1
VarioEL-III (for CHN). H NMR data are reported with the
1606, 1510, 1435, 1365, 1275, 1216, 1161, 1100, 1075, 842 cm ;
1
solvent resonance as the internal standard relative to CDCl
3
–TMS
H NMR (400 MHz, CDCl ) d 7.33–7.24 (m, 2H), 7.02–6.96 (m,
3
(
(
d = 0.00) as follows: chemical shift (d), integration, multiplicity
2H), 5.01 (s, 1H), 4.65 (dd, J = 9.7, 8.2 Hz, 1H), 4.10 (dd, J =
s = singlet, d = doublet, t = triplet, q = quartet, br = broadened,
12.2, 8.2 Hz, 1H), 4.13–4.08 (m, 1H), 3.82 (s, 3H), 3.18 (s, 3H), 2.67
1
3
13
m = multiplet), coupling constants (J, given in Hz). C NMR
(dd, J = 13.7, 11.0 Hz, 1H), 2.54 (dd, J = 13.7, 8.5 Hz, 1H); C
chemical shifts (d) are recorded in parts per million (ppm) relative
NMR (100 MHz, CDCl ) d 171.47, 170.30, 168.72, 162.58 (d, J =
3
to CDCl
3
(d = 77.23) as internal standard. High-resolution mass
246 Hz), 131.84 (d, J = 8 Hz), 131.15 (d, J = 3 Hz), 115.28 (d,
spectra (HRMS) are reported as m/z.
J = 21 Hz), 75.50, 70.10, 53.70, 52.61, 51.91, 46.26, 35.25; HRMS
+
(
EI) m/z calcd for C16
H
16FNO
5
(M ) 321.1013, found 321.1014.
Typical experimental procedure
trans-5,5-Dimethoxycarbonyl-6-(4-fluorophenyl)-3a,4-dihydro-
To a stirred solution of t-BuOK (168 mg, 1.5 mmol) in 3 mL THF
3H,6H-cyclopenta[c]isoxazole (trans-2c). Purified by column
was added a THF solution of dimethyl allylmalonate (159 mg,
chromatography (ethyl acetate–hexanes 1 : 5) after concentration
in vacuo to give a white solid with a melting point of 140–141 C;
◦
◦
◦
1
.2 mmol) at −78 C. After stirring the mixture at −78 C for 10
minutes, b-nitrostyrene (149 mg, 1.0 mmol) in 5 mL of THF was
added dropwise and the mixture stirred for an additional 30 min
at the same temperature to generate the nitronate. Then, TCT
IR (CHCl
1259, 1207, 1174, 1099, 1077, 1012, 849 cm ; H NMR (400 MHz,
CDCl
3
) mmax 2994, 2950, 2868, 1731, 1605, 1509, 1435, 1279,
−
1 1
3
) d 7.25–7.19(m, 2H), 7.01–6.95(m, 2H), 4.99(d, J = 1.2 Hz,
(
0
564 mg, 3 mmol), or TCT (188 mg, 1 mmol) and ZnCl
.2 mmol) were added sequentially at −78 C over 15 min. After
2
(27 mg,
1H), 4.68 (dd, J = 9.6, 7.8 Hz, 1H), 4.63–4.49 (m, 1H), 3.92 (dd,
◦
J = 12.7, 7.8 Hz, 1H) 3.81 (s, 3H), 3.12 (s, 3H), 2.85 (dd, J = 12.8,
1
3
the addition was complete the reaction mixture was poured into
ice cold dilute HCl(aq) solution and then extracted with CH Cl
3 × 25 mL). The combined CH Cl layers were washed with
brine and distilled H O and dried over anhydrous MgSO . After
7.6 Hz, 1H), 1.81 (dd, J = 12.8, 11.3 Hz, 1H); C NMR (100 MHz,
3
CDCl
) d 170.91, 170.84, 169.82, 162.43 (d, J = 246 Hz), 132.59
2
2
(
2
2
(d, J = 3 Hz), 130.62 (d, J = 8 Hz), 115.42 (d, J = 21 Hz), 75.39,
71.63, 55.42, 53.43, 52.48, 45.44, 36.67; HRMS (EI) m/z calcd for
2
4
+
evaporation of the organic solvent, the crude product was purified
by flash column chromatography using silica gel (eluent; ethyl
acetate–hexane; 1 : 5) to obtain bicyclic isoxazoline (2a) (294 mg,
C
16
H
16FNO
5
(M ) 321.1013, found 321.1014.
cis-5,5-Dimethoxycarbonyl-6-(4-chlorophenyl)-3a,4-dihydro-
H,6H-cyclopenta[c]isoxazole (cis-2d). Purified by column chro-
matography (ethyl acetate–hexanes 1 : 10) after concentration in
vacuo to give a colorless oil; IR (CHCl ) mmax 3460, 3001, 2954,
1731, 1646, 1596, 1494, 1435, 1415, 1362, 1273, 1213, 1167, 1092,
3
9
7% combined yield).
cis-5,5-Dimethoxycarbonyl-6-(4-methoxylphenyl)-3a,4-dihydro-
H,6H-cyclopenta[c]isoxazole (cis-2b). Purified by column chro-
3
3
−
1
1
matography (ethyl acetate–hexanes 1 : 5) after concentration in
vacuo to give a colorless oil; IR (CHCl ) mmax 3462, 3001, 2954,
840, 2252, 2053, 1731, 1612, 1583, 1515, 1460, 1435, 1362, 1251,
1016, 942, 908, 838 cm ; H NMR (400 MHz, CDCl ) d 7.29–
3
3
7.24 (m, 4H), 4.99 (d, J = 1.04 Hz, 1H), 4.65 (dd, J = 9.7, 8.2 Hz,
1H), 4.10 (dd, J = 12.2, 8.2 Hz, 1H), 3.92–3.82 (m, 1H), 3.82 (s,
3H), 3.19 (s, 3H), 2.67 (dd, J = 13.7, 10.9 Hz, 1H), 2.55 (dd, J =
2
1
−
1
1
213, 1180, 1100, 1032, 945, 908, 891, 868, 838 cm ; H NMR
) d 7.23–7.20 (m, 2H), 6.84–6.80 (m, 2H), 4.97
1
3
(400 MHz, CDCl
3
13.7, 8.5 Hz, 1H); C NMR (100 MHz, CDCl ) d 171.40, 170.03,
3
(
s, 1H), 4.63 (dd, J = 9.5, 8.2 Hz, 1H), 4.08 (dd, J = 12.3, 8.2 Hz,
168.66, 134.19, 133.90, 131.49, 128.54, 75.52, 70.09, 53.74, 52.68,
+
1
2
H), 3.90–3.81 (s, 1H), 3.80 (s, 3H), 3.77 (s, 3H), 3.18 (s, 3H),
51.91, 46.37, 35.28; HRMS(EI) m/z calcd for C16
H
16ClNO (M )
5
.67 (dd, J = 13.6, 11.1 Hz, 1H), 2.54 (dd, J = 13.6, 8.4 Hz, 1H);
337.0717, found 337.0716.
1
3
C NMR (100 MHz, CDCl ) d 171.57, 170.86, 168.79, 159.33,
3
trans-5,5-Dimethoxycarbonyl-6-(4-chlorophenyl)-3a,4-dihydro-
H,6H-cyclopenta[c]isoxazole (trans-2d). Purified by column
1
4
31.13, 127.40, 113.69, 75.33, 70.17, 55.38, 53.56, 52.53, 51.95,
3
+
6.27, 35.16; HRMS (EI) m/z calcd for C17
H
19NO (M ) 333.1212,
6
chromatography (ethyl acetate–hexanes 1 : 5) after concentration
in vacuo to give a colorless oil; IR (CHCl ) mmax 3463, 3000,
2953, 2869, 1732, 1647, 1595, 1492, 1435, 1412, 1362, 1275, 1258,
found 333.1215.
3
trans-5,5-Dimethoxycarbonyl-6-(4-methoxylphenyl)-3a,4-di-
hydro-3H,6H-cyclopenta[c]isoxazole (trans-2b). Purified by col-
umn chromatography (ethyl acetate–hexanes 1 : 5) after concen-
−
1
1
1208, 1175, 1090, 1015, 930, 908, 889, 868, 842 cm ; H NMR
(400 MHz, CDCl ) d 7.28–7.23 (m, 2H), 7.20–7.16 (m, 2H), 4.98
3
2
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(
1
d, J = 1.7 Hz, 1H), 4.68 (dd, J = 9.6, 7.8 Hz, 1H), 4.63–4.52 (m,
H), 3.92 (dd, J = 12.3, 7.9 Hz, 1H), 3.81 (s, 3H), 3.13 (s, 3H), 2.85
ddd, J = 8.2, 7.6, 0.4 Hz, 1H), 1.81 (dd, J = 12.8, 11.2 Hz, 1H);
C NMR (100 MHz, CDCl ) d 170.78, 170.64, 169.72, 135.30,
33.89, 130.26, 128.65, 75.40, 71.60, 55.41, 53.47, 52.51, 45.53,
8.2 Hz, 1H), 7.60–7.55 (m, 1H), 7.51–7.47 (m, 1H), 7.36 (t, J =
7.7 Hz, 1H), 7.09 (d, J = 7.2 Hz, 1H), 5.83 (s, 1H), 4.74 (dd, J =
9.7, 8.0 Hz, 1H), 4.69–4.58 (m, 1H), 4.00 (dd, J = 11.7, 8.0 Hz,
1H), 3.81 (s, 3H), 3.03 (dd, J = 12.7, 7.8 Hz, 1H), 2.61 (s, 3H),
(
1
3
3
1
3
1
3
1.85 (dd, J = 12.7, 11.0 Hz, 1 H); C NMR (100 MHz, CDCl
3
)
+
6.69; HRMS (EI) m/z calcd for C16
H
16ClNO
5
(M ) 337.0717,
d 171.78, 171.08, 169.79, 134.71, 133.75, 132.54, 128.78, 128.65,
found 337.0716.
126.74, 126.24, 126.08, 125.13, 124.67, 75.40, 71.60, 56.01, 53.53,
+
5
3
1.89, 41.94, 37.64; HRMS (EI) m/z calcd for C20
53.1263, found 353.1263.
H
19NO
5
(M )
cis-5,5-Dimethoxycarbonyl-6-(2-thienyl)-3a,4-dihydro-3H,6H-
cyclopenta[c]isoxazole (cis-2e). Purified by column chromatog-
raphy (ethyl acetate–hexanes 1 : 5) after concentration in vacuo to
5,5-Dimethoxycarbonyl-6-phenyl-4-dihydro-6H-cyclopenta[c]-
give a colorless oil; IR (CHCl
3
) mmax 3108, 3000, 2953, 2879, 1731,
isoxazole (3a). Purified by column chromatography (ethyl
1
7
1
1
3
1
434, 1361, 1279, 1246, 1208, 1175, 1077, 1042, 943, 905, 886, 864,
acetate–hexanes 1 : 5) after concentration in vacuo to give a white
−
1
1
◦
11 cm ; H NMR (400 MHz, CDCl
3
) d 7.23 (dd, J = 5.1, 0.8 Hz,
solid with a melting point of 135–136 C; IR (CHCl
3
) mmax 3583,
H), 7.09 (d, J = 3.5 Hz, 1H), 6.95 (dd, J = 5.1, 3.5 Hz, 1H), 5.28 (s,
H), 4.65 (dd, J = 9.7, 8.2 Hz, 1H), 4.12 (dd, J = 12.4, 8.1 Hz, 1H),
.91–3.82 (m, 1H), 3.82 (s, 3H), 3.32 (s, 3H), 2.64 (dd, J = 13.7,
3461, 3127, 2954, 1753, 1731, 1621, 1497, 1434, 1400, 1281, 1261,
−
1
1
1214, 1162, 1144, 1074, 1048, 941, 898, 863, 819 cm ; H NMR
(400 MHz, CDCl ) d 8.10 (s, 1H), 7.30–7.20 (m, 3H), 7.19–7.16
(m, 2H), 5.32 (s, 1H), 3.80 (s, 3H), 3.72 (dd, J = 16.6, 1.4 Hz, 1H),
3.21 (s, 3H), 3.14 (dd, J = 16.6, 1.4 Hz, 1H); C NMR (100 MHz,
CDCl ) d 172.02, 171.13, 168.81, 150.43, 136.16, 129.06, 128.56,
128.21, 121.39, 73.01, 53.51, 52.53, 48.72, 29.70; HRMS (EI) m/z
3
1
3
0.1 Hz, 1H), 2.52 (dd, J = 13.7, 8.8 Hz, 1H); C NMR (100 MHz,
1
3
CDCl
3
) d 171.14, 169.88, 168.66, 136.30, 128.52, 126.64, 125.90,
7
5.83, 70.05, 52.62, 52.81, 51.29, 42.42, 34.56; HRMS (EI) m/z
3
+
calcd for C14
H
15NO S (M ) 309.0671, found 309.0670.
5
+
calcd for C16
H
15NO (M ) 301.0950, found 301.0955.
5
trans-5,5-Dimethoxycarbonyl-6-(2-thienyl)-3a,4-dihydro-3H,6H-
cyclopenta[c]isoxazole (trans-2e). Purified by column chromato-
graphy (ethyl acetate–hexanes 1 : 5) after concentration in vacuo
5,5-Dimethoxycarbonyl-6-(2-thienyl)-4-dihydro-6H-cyclopenta-
[c]isoxazole (3b). Purified by column chromatography (ethyl
to give a colorless oil; IR (CHCl
3
) mmax 3583, 3000, 2953, 2857,
acetate–hexanes 1 : 5) after concentration in vacuo to give a white
◦
1
8
4
731, 1434, 1281, 1266, 1208, 1175, 1100, 1077, 1009, 886, 852,
21, 788, 706 cm ; H NMR (400 MHz, CDCl
.9, 1.4 Hz, 1H), 6.94–6.91 (m, 2H), 5.19 (d, J = 1.6 Hz, 1H), 4.68
solid with a melting point of 129–130 C; IR (CHCl
3
) mmax 3439,
−
1
1
3
) d 7.21 (dd, J =
3109, 2954, 2785, 1732, 1626, 1433, 1409, 1271, 1214, 1174, 1116,
−
1
1
1065, 941, 888, 853, 823, 705 cm ; H NMR (400 MHz, CDCl )
3
(
7
dd, J = 9.7, 7.8 Hz, 1H), 4.63–4.53 (m, 1H), 3.92 (dd, J = 12.2,
d 8.09 (s, 1H), 7.23–7.21 (m, 1H), 6.94–6.91 (m, 2H), 5.53 (s,
.8 Hz, 1H), 3.82 (s, 3H), 3.29 (s, 3H), 2.91 (dd, J = 13.1, 7.9 Hz,
H), 1.86 (dd, J = 13.1, 10.5 Hz, 1H); C NMR (100 MHz,
) d 170.66, 170.01, 169.51, 138.86, 127.21, 126.93, 125.59,
5.71, 71.20, 54.11, 53.49, 52.83, 41.82, 36.05; HRMS (EI) m/z
1H), 3.81 (s, 3H), 3.68 (dd, J = 16.5, 1.2 Hz, 1H), 3.41 (s, 3H),
1
3
13
1
3.14 (dd, J = 16.5, 1.2 Hz, 1H); C NMR (100 MHz, CDCl
3
)
CDCl
7
3
d 171.51, 170.71, 168.55, 150.62, 137.44, 127.55, 126.82, 125.89,
120.66, 72.88, 53.54, 52.84, 44.07, 29.26; HRMS (EI) m/z calcd
+
+
calcd for C14
H
15NO
5
S (M ) 309.0671, found 309.0670.
for C14
H
13NO
5
S (M ) 307.0514, found 307.0513.
cis-5,5-Dimethoxycarbonyl-6-(naphthalen-1-yl)-3a,4-dihydro-
H,6H-cyclopenta[c]isoxazole (cis-2f). Purified by column chro-
5,5-Dimethoxycarbonyl-6-(2-furyl)-4-dihydro-6H-cyclopenta-
[c]isoxazole (3c). Purified by column chromatography (ethyl
3
matography (ethyl acetate–hexanes 1 : 5) after concentration in
vacuo to give a white solid, which decomposed at 190 C; IR
acetate–hexanes 1 : 10) after concentration in vacuo to give a white
◦
◦
solid which decompose at 134 C; IR (CHCl
3
) mmax 3126, 2956,
(
1
CHCl
3
) mmax 3043, 2994, 2939, 2846, 1750, 1723, 1508, 1448, 1432,
2774, 1732, 1624, 1499, 1448, 1434, 1400, 1274, 1257, 1216, 1163,
−
1
1
−1
1
283, 1247, 1204, 1174, 1166, 1152, 887 cm ; H NMR (400 MHz,
1144, 1069, 1045, 1013, 931, 885, 816 cm ; H NMR (400 MHz,
CDCl ) d 8.07 (s, 1H), 7.33–7.32 (m, 1H), 6.30–6.29 (m, 1H), 6.21
CDCl
(
(
3
) d 8.28 (d, J = 8.4 Hz, 1H), 7.82 (d, J = 7.9 Hz, 1H), 7.76
3
d, J = 8.1 Hz, 1H), 7.57–7.53 (m, 1H), 7.49–7.45 (m, 1H), 7.42
t, J = 7.6 Hz, 1H), 7.38–7.37 (m, 1H), 6.06 (s, 1H), 4.69 (dd,
(d, J = 3.2 Hz, 1H), 5.38 (s, 1H), 3.80 (s, 3H), 3.73 (dd, J =
16.4, 1.1 Hz, 1H), 3.49 (s, 3H), 3.15 (dd, J = 16.4, 1.1 Hz, 1H);
1
3
J = 9.5, 8.4 Hz, 1H), 4.14 (dd, J = 12.3, 8.2 Hz, 1H), 4.03–
.81 (m, 1H), 3.85 (s, 3H), 2.82 (t, J = 13.0 Hz, 1H), 2.66 (dd,
J = 13.3, 7.4 Hz, 1H), 2.58 (s, 3H); C NMR (100 MHz, CDCl
d 172.16, 171.88, 168.15, 133.73, 132.78, 128.78, 128.74, 128.09,
C NMR (100 MHz, CDCl ) d 170.54, 169.89, 168.51, 150.55,
3
3
149.25, 143.02, 120.92, 110.69, 109.22, 71.57, 53.63, 53.12, 42.74,
1
3
+
3
)
29.54; HRMS (EI) m/z calcd for C14
H
13NO (M ) 291.0743, found
6
291.0746.
1
4
26.50, 125.81, 125.27, 123.81, 75.04, 71.28, 53.88, 52.72, 51.83,
5
,5-Dimethoxycarbonyl-6-(2-nitrophenyl)-4-dihydro-6H-cyclo-
+
1.12, 36.06; HRMS (EI) m/z calcd for C20
H
19NO (M ) 353.1263,
5
penta[c]isoxazole (3d). Purified by column chromatography
ethyl acetate–hexanes 1 : 5) after concentration in vacuo to give
a white solid with a melting point of 134–135 C; IR (CHCl
3126, 2957, 1736, 1627, 1531, 1435, 1408, 1356, 1274, 1214, 1168,
1067, 944, 900, 864, 848, 824, 786 cm ; H NMR (400 MHz,
CDCl
found 353.1263.
(
◦
trans-5,5-Dimethoxycarbonyl-6-(naphthalen-1-yl)-3a,4-dihydro-
H,6H-cyclopenta[c]isoxazole (trans-2f). Purified by column
3
)
3
−
1
1
chromatography (ethyl acetate–hexanes 1 : 5) after concentration
in vacuo to give a white solid with a melting point of 146–148 C;
IR (CHCl
◦
3
) d 8.16 (s, 1H), 7.89 (dd, J = 7.9, 1.4 Hz, 1H), 7.50–7.41
3
) mmax 3463, 3049, 3002, 2953, 2872, 1732, 1639, 1597,
(m, 2H), 7.02 (d, J = 7.5 Hz, 1H), 6.26 (s, 1H), 3.78 (s, 3H),
1
1
8
511, 1435, 1398, 1361, 1300, 1276, 1255, 1221, 1205, 1103, 1073,
016, 924, 904, 887, 791 cm ; H NMR (400 MHz, CDCl
.46 (d, J = 8.6 Hz, 1H), 7.82 (d, J = 7.9 Hz, 1H), 7.75 (d, J =
3.76 (d, J = 16.8 Hz, 1H), 3.28 (s, 3H), 3.21 (dd, J = 16.8,
−
1
1
13
3
) d
1.0 Hz, 1H); C NMR (100 MHz, CDCl
3
) d 171.56, 170.32,
168.47, 150.95, 150.38, 132.83, 131.02, 130.65, 129.15, 125.12,
This journal is © The Royal Society of Chemistry 2006
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1
21.55, 72.92, 53.80, 52.94, 42.49, 29.97; HRMS (EI) m/z calcd
1446, 1405, 1362, 1296, 1260, 1224, 1112, 1092, 1071, 1016, 950,
+
−1
1
for C16
H
14
N
2
O
7
(M ) 346.0800, found 346.0813.
903, 867, 833, 806, 745 cm ; H NMR (400 MHz, CDCl ) d 8.34
3
(
3
s, 1H), 7.43–7.49 (m, 4H), 5.02 (s, 1H), 3.71 (d, J = 15.7 Hz, 1H),
5
,5-Dimethoxycarbonyl-6-(1,3-benzodioxol-5-yl)-4-dihydro-6H-
13
.58 (dd, J = 15.7, 1.3 Hz, 1H); C NMR (100 MHz, CDCl
3
)
cyclopenta[c]isoxazole (3e). Purified by column chromatography
ethyl acetate–hexanes 1 : 5) after concentration in vacuo to give
a white solid with a melting point of 93–94 C; IR (CHCl
115, 2955, 2780, 1732, 1627, 1504, 1489, 1444, 1408, 1364, 1267,
d 167.09, 152.85, 136.63, 130.25, 129.94, 129.42, 118.47, 114.21,
1
(
(
13.22, 52.99, 48.24, 34.50; HRMS (EI) m/z calcd for C14
M ) 269.0356, found 269.0357.
H
8
ClN O
3
◦
3
) mmax
+
3
1
−
1
1
216, 1066, 1038, 931, 881, 825, 785 cm ; H NMR (400 MHz,
) d 8.09 (s, 1H), 6.72–6.66 (m, 3H), 5.91–5.90 (m, 2H),
.23 (s, 1H), 3.79 (s, 3H), 3.66 (dd, J = 18.1, 1.0 Hz, 1H), 3.33
5,5-Dinitrile-6-(2-thienyl)-4-dihydro-6H-cyclopenta[c]isoxazole
CDCl
3
(3j). Purified by column chromatography (ethyl acetate–hexanes
1 : 10) after concentration in vacuo to give a white solid with a
melting point of 129–130 C; IR (CHCl
2774, 2252, 1728, 1709, 1630, 1509, 1444, 1408, 1365, 1296, 1237,
5
(
1
3
◦
s, 3H), 3.11 (dd, J = 16.5, 1.0 Hz, 1H); C NMR (100 MHz,
3
) mmax 3583, 3115, 2923,
CDCl
3
) d 171.91, 170.96, 168.70, 150.45, 147.69, 147.37, 129.49,
−
1 1
1
2
3
22.49, 121.16, 109.38, 108.15, 101.22, 72.74, 53.38, 52.58, 48.31,
9.46; HRMS (EI) m/z calcd for C17
45.0847.
1120, 1070, 1043, 947, 856, 795 cm ; H NMR (400 MHz, CDCl )
3
+
H
15NO
7
(M ) 345.0849, found
d 8.32 (s, 1H), 7.44 (dd, J = 5.1, 0.7 Hz, 1H), 7.33 (d, J = 3.7 Hz,
1H), 7.12 (dd, J = 5.1, 3.7 Hz, 1H), 5.31 (s, 1H), 3.71 (d, J = 15.7,
1
3
1
H), 3.57 (dd, J = 15.7, 1.1 Hz, 1H); C NMR (100 MHz, CDCl
3
)
5
,5-Dimethoxycarbonyl-6-(n-butyl)-4-dihydro-6H-cyclopenta-
d 167.49, 152.86, 132.36, 129.25, 128.03, 127.94, 118.01, 114.28,
1
(
[
c]isoxazole (3f). Purified by column chromatography (ethyl
acetate–hexanes 1 : 10) after concentration in vacuo to give a white
solid with a melting point of 63–64 C; IR (CHCl
13.03, 49.18, 48.78, 34.23; HRMS (EI) m/z calcd for C12
M ) 241.0310, found 241.0313.
H
7
3
N OS
+
◦
3
) mmax 3583, 3461,
2
956, 2863, 1735, 1629, 1454, 1435, 1401, 1268, 1215, 1163, 1119,
5,5-Dinitrile-6-(naphthalen-1-yl)-4-dihydro-6H-cyclopenta[c]-
isoxazole (3k). Purified by column chromatography (ethyl
−
1 1
1
066, 954, 938, 872, 835, 820, 792, 665 cm ; H NMR (400 MHz,
) d 7.95 (s, 1H), 3.86 (dd, J = 11.3, 3.9 Hz, 1H), 3.762 (s,
H), 3.760 (s, 3H) 3.48 (dd, J = 16.4, 1.3 Hz, 1H), 3.09 (dd, J =
CDCl
3
acetate–hexanes 1 : 5) after concentration in vacuo to give a white
◦
3
1
solid with the melting point of 180–181 C; IR (CHCl
3
) mmax 3583,
1
3
6.4, 1.3 Hz, 1H), 1.69–1.25 (m, 6H), 0.91 (t, J = 7.3 Hz, 3H);
C
3137, 3054, 2939, 1709, 1630, 1598, 1514, 1443, 1409, 1360, 1293,
−
1
1
NMR (100 MHz, CDCl
3
) d 172.51, 171.20, 169.65, 149.54, 120.06,
1223, 1071, 949, 803, 781 cm ; H NMR (400 MHz, CDCl ) d
3
7
0.40, 53.37, 52.92, 43.43, 29.56, 29.45, 28.98, 22.63, 12.06; HRMS
8.39 (s, 1H), 8.24 (d, J = 8.6 Hz, 1H), 7.96 (dd, J = 8.1, 2.5 Hz,
+
(
EI) m/z calcd for C14
H
19NO (M ) 281.1263, found 281.1258.
5
2H) 7.72–7.68 (m, 1H), 7.63–7.59 (m, 1H), 7.50 (t, J = 7.8 Hz,
1
H), 7.36 (d, J = 7.1 Hz, 1H), 5.98 (s, 1H), 3.78–3.69 (m, 2H);
3
1
3
5,5-Dimethoxycarbonyl-6-(4-diethylaminophenyl)-4-dihydro-6H-
C NMR (100 MHz, CDCl ) d 169.04, 152.72, 134.24, 131.73,
cyclopenta[c]isoxazole (3g). Purified by column chromatography
131.04, 129.67, 128.03, 127.72, 127.52, 126.83, 125.51, 122.45,
(
methanol–chloroform 1 : 50) after concentration in vacuo to give
118.96, 115.22, 113.21, 48.81, 47.26, 35.18; HRMS (EI) m/z calcd
◦
+
a white solid with a melting point of 104–106 C; IR (CHCl
3
) mmax
for C H N O (M ) 285.0902, found 285.0902.
1
8
11
3
3
1
1
3
3
668, 3451, 2953, 2291, 1793, 1733, 1613, 1521, 1457, 1435, 1372,
1
5
,5-Dinitrile-6-(iso-butyl)-4-dihydro-6H-cyclopenta[c]isoxazole
3l). Purified by column chromatography (ethyl acetate–hexanes
: 5) after concentration in vacuo to give a colorless oil; IR (CHCl
max 2960, 2923, 2873, 2247, 1706, 1630, 1506, 1469, 1445, 1403,
269, 1163, 1147, 1096; H NMR (400 MHz, CDCl ) d 8.07 (s,
3
(
1
m
H), 7.05–6.95 (m, 2H), 6.62–6.57 (m, 2H), 5.21 (s, 1H), 3.79 (s,
H), 3.69 (dd, J = 16.5, 1.3 Hz, 1H), 3.35–3.27 (m, 4H), 3.29 (s,
H), 3.10 (dd, J = 16.5, 1.3 Hz, 1H), 1.11 (t, J = 7.1 Hz, 6H);
3
)
−
1
1
1
3
1
370, 1305, 1278, 1220, 1168, 1069, 943, 829 cm ; H NMR
400 MHz, CDCl
C NMR (100 MHz, CDCl ) d 172.42, 171.19, 168.86, 149.95,
3
(
3
) d 8.19 (s, 1H), 3.82 (dd, J = 9.4, 6.4 Hz,
1
4
3
47.39, 129.63, 122.03, 121.67, 111.69, 72.71, 53.16, 52.37, 47.96,
4.30, 29.29, 12.44; HRMS (EI) m/z calcd for C20
72.1685, found 372.1691.
+
1
1
1
H), 3.59 (dd, J = 15.7, 0.6 Hz, 1H), 3.48 (dd, J = 15.7, 1.4 Hz,
H), 2.08–2.18 (m, 1H), 1.97 (ddd, J = 13.7, 9.3, 6.2 Hz, 1H),
.84 (ddd, J = 13.7, 8.3, 6.2 Hz, 1H), 1.09 (d, J = 6.4 Hz, 3H),
H
24
N
2
O (M )
5
1
3
5
,5-Dinitrile-6-phenyl-4-dihydro-6H-cyclopenta[c]isoxazole (3h).
1.07 (d, J = 6.4 Hz, 3H); C NMR (100 MHz, CDCl ) d 169.02,
3
Purified by column chromatography (ethyl acetate–hexanes 1 : 5)
after concentration in vacuo to give a white solid with a melting
point of 143–144 C; IR (CHCl
151.68, 117.52, 114.79, 113.49, 46.07, 44.91, 38.45, 34.73, 25.79,
+
22.91, 22.02; HRMS (EI) m/z calcd for C H N O (M ) 215.1059,
found 215.1060.
1
2
13
3
◦
3
) mmax 3583, 3137, 2923, 1708,
−
1
1
1630,1499, 1455, 1406, 1261, 1070,950, 847, 805 cm ; H NMR
cis-4,4-Dimethoxycarbonyl-3-phenyl-4a,5,6,7,7a,7b-hexahydro-
3H-indeno[1,7-cd]isoxazole (cis-4). Purified by column chro-
matography (ethyl acetate–hexanes 1 : 5) after concentration in
(
3
400 MHz, CDCl
.70 (d, J = 15.7 Hz, 1H), 3.58 (dd, J = 15.7, 1.4 Hz, 1H);
3
) d 8.32 (s, 1H), 7.48 (s, 5H), 5.04 (s, 1H),
1
3
C
NMR (100 MHz, CDCl ) d 167.48, 152.65, 131.05, 130.36, 129.65,
1
m/z calcd for C14
3
◦
vacuo to give a white solid with the melting point of 189–190 C;
28.86, 118.56, 114.51, 113.33, 53.59, 48.30, 34.53; HRMS (EI)
+
IR (CHCl ) m 3032, 2952, 2864, 1729, 1645, 1497, 1455, 1435,
H
9
N
3
O (M ) 235.0746, found 235.0746.
3
max
−
1
1
1
355, 1313, 1280, 1254, 1205, 1180, 1079, 1044 cm . H NMR
5
,5-Dinitrile-6-(4-chlorophenyl)-4-dihydro-6H -cyclopenta[c]-
(400 MHz, CDCl ) d 7.38–7.23 (m, 5H), 5.02 (s, 1H), 4.81 (dd,
3
isoxazole (3i). Purified by column chromatography (ethyl
J = 17.2, 8.8 Hz, 1H), 3.84 (s, 3H), 3.77 (dd, J = 9.2, 8.2 Hz, 1H),
3.26 (s, 3H), 2.99–2.92 (m, 1H), 2.27–2.24 (m, 1H), 2.18–2.13 (m,
1H), 1.74–1.70 (m, 1H), 1.61–1.41 (m, 2H), 1.02–0.92 (m, 1H);
acetate–hexanes 1 : 5) after concentration in vacuo to give a white
◦
solid with a melting point of 108–109 C; IR (CHCl
3
) mmax 3479,
1
3
3139, 3003, 2920, 2252, 2126, 1911, 1710, 1630, 1597, 1577, 1494,
C NMR (100 MHz, CDCl
3
) d 171.91, 169.77, 166.70, 135.65,
2
856 | Org. Biomol. Chem., 2006, 4, 2851–2857
This journal is © The Royal Society of Chemistry 2006

View Article Online
1
4
29.94, 127.99, 127.57, 75.66, 74.20, 54.22, 53.48, 51.54, 46.57,
2 (a) A. A. Fuller, B. Chen, A. R. Minter and A. K. Mapp, J. Am. Chem.
Soc., 2005, 127, 5376; (b) J. W. Bode and E. M. Carreira, Org. Lett.,
1.90, 29.02, 25.43, 19.78; HRMS (EI) m/z calcd for C19
H
21NO
5
2
1
001, 3, 1587; (c) A. P. Kozikowski and P. D. Stein, J. Am. Chem. Soc.,
982, 104, 4023; (d) D. P. Curran, J. Am. Chem. Soc., 1983, 105, 5826;
+
(
M ) 343.1420, found 303.1109; Elemental analysis calculated for
C
19
H
21NO
5
: C, 66.46; H, 6.16: N, 4.08. Found: C, 66.40; H, 6.15;
(e) S. H. Andersen, K. K. Sharma and K. B. G. Torsell, Tetrahedron,
1983, 39, 2241; (f) P. G. Baraldi, A. Barco, S. Benetti, S. Manfredini and
D. Simoni, Synthesis, 1987, 276.
N, 3.93%.
3
A. Padwa and W. H. Pearson, in Synthetic Applications of 1,3-Dipolar
Cycloaddition Chemistry Toward Heterocycles and Natural Products,
John Wiley & Sons, Inc., New Jersey, 2003, pp. 437–461.
trans-4,4-Dimethoxycarbonyl-3-phenyl-4a,5,6,7,7a,7b-hexa-
hydro-3H-indeno[1,7-cd]isoxazole (trans-4). Purified by column
chromatography (ethyl acetate–hexanes 1 : 5) after concentration
in vacuo to give a white solid with a melting point of 154–155 C;
IR (CHCl ) mmax 3032, 2954, 1730, 1644, 1601, 1497, 1456, 1435,
4 T. Mukaiyama and T. Hoshino, J. Am. Chem. Soc., 1960, 82, 5339.
5 (a) Y. Basel and A. Hassner, Synthesis, 1997, 309; (b) I. N. N.
Namboothiri and A. Hassner, J. Org. Chem., 1997, 62, 485; (c) Q. Cheng,
T. Oritani, T. Horiguchi and Q. Shi, Eur. J. Org. Chem., 1999, 2689.
◦
3
−
1 1
1
7
1
2
1
1
5
280, 1254, 1207, 1078 cm . H NMR (400 MHz, CDCl ) d 7.29–
3
6
(a) M. Falorni, A. Porcheddu and M. Taddei, Tetrahedron Lett., 1999, 40,
4395; (b) M. Falorni, G. Giacomelli, A. Porcheddu and M. Taddei, J. Org.
Chem., 1999, 64, 8962;(c) A. Falchi, G. Giacomelli, A. Porcheddu and M.
Taddei, Synlett, 2000, 275; (d) L. De Luca, G. Giacomelli and M. Taddei,
J. Org. Chem., 2001, 66, 2534; (e) L. De Luca, G. Giacomelli and A.
Porcheddu, Org. Lett., 2001, 3, 1519; (f) L. De Luca, G. Giacomelli and
A. Porcheddu, Org. Lett., 2001, 3, 3041; (g) L. De Luca, G. Giacomelli
and A. Porcheddu, Org. Lett., 2002, 4, 553; (h) L. De Luca, G. Giacomelli
and A. Porcheddu, J. Org. Chem., 2002, 67, 5152; (i) L. De Luca, G.
Giacomelli and A. Porcheddu, J. Org. Chem., 2002, 67, 6272; (j) L.
De Luca, G. Giacomelli, S. Masala and A. Porcheddu, J. Org. Chem.,
.21 (m, 5H), 5.05 (d, J = 2.0 Hz, 1H), 4.85 (dd, J = 17.2, 8.8 Hz,
H), 4.60 (dd, J = 8.6, 8.2 Hz, 1H), 3.79 (s, 3H), 3.00 (s, 3H), 2.95–
.90 (m, 1H), 2.11–2.06 (m, 1H), 1.69–1.63 (m, 2H), 1.39–1.29 (m,
H), 1.08–0.90 (m, 2H); C NMR (100 MHz, CDCl ) d 171.24,
69.81, 169.41, 135.63, 128.75, 128.28, 127.64, 77.02, 56.99, 52.64,
1
3
3
2.01, 44.71, 40.51, 28.49, 24.28, 20.28; HRMS (EI) m/z calcd for
+
C
19
H
21NO
5
(M ) 343.1420, found 303.1109; Elemental analysis
calculated for C19
H
21NO : C, 66.46; H, 6.16: N, 4.08. Found: C,
5
2
003, 68, 4999–5001; (k) G. Giacomelli, L. De Luca and A. Porcheddu,
66.41; H, 6.15; N, 3.93%.
Tetrahedron Lett., 2003, 59, 5437; (l) Z. J. Kaminski, P. Paneth and
J. Rudzinski, J. Org. Chem., 1998, 63, 4248; (m) D. C. Forbes, E. J.
Barrett, D. L. Lewis and M. C. Smith, Tetrahedron Lett., 2000, 41, 9943;
Acknowledgements
(
(
n) B. P. Bandgar and S. S. Pandit, Tetrahedron Lett., 2002, 43, 3413;
o) Z. J. Kaminski, B. Kolesinska, J. Kolesinska, G. Sabatino, M. Chelli,
Financial support of this work by the National Science Council
of the Republic of China is gratefully acknowledged.
P. Rovero, M. Blaszczyk, M. L. Glowka and A. M. Papini, J. Am. Chem.
Soc., 2005, 127, 16912.
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