α-Nitro carbonyl compounds in the synthesis of 2,3-dihydrofurans

Article abstract of DOI:10.1016/j.tet.2008.05.122

A new method for the synthesis of 2,3-dihydrofurans from readily available starting enones and α-nitro carbonyl compounds has been developed. This protocol can provide a novel and effective methodology for the preparation of 2,3-dihydrofurans in a stereoselective fashion. With 1,4-dien-3-ones, 2,3-dihydrofurans and cyclohexenecarboxylates were produced and high chemoselectivity was observed in different solvents.

Full text of DOI:10.1016/j.tet.2008.05.122

Tetrahedron 64 (2008) 7511–7516
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
a-Nitro carbonyl compounds in the synthesis of 2,3-dihydrofurans
*
Che-Ping Chuang , Kuang-Po Chen, Yu-Lin Hsu, An-I. Tsai, Shui-Te Liu
Department of Chemistry, National Cheng Kung University, Tainan 70101, Taiwan
a r t i c l e i n f o
a b s t r a c t
Article history:
A new method for the synthesis of 2,3-dihydrofurans from readily available starting enones and a-nitro
Received 15 March 2008
Received in revised form 19 May 2008
Accepted 30 May 2008
carbonyl compounds has been developed. This protocol can provide a novel and effective methodology
for the preparation of 2,3-dihydrofurans in a stereoselective fashion. With 1,4-dien-3-ones, 2,3-dihy-
drofurans and cyclohexenecarboxylates were produced and high chemoselectivity was observed in
different solvents.
Available online 3 June 2008
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords:
a
-Nitro carbonyl compounds
2,3-Dihydrofuran
Michael addition
O-Cyclization
1. Introduction
O
O
O
O
O
O
O
R3
O2N
R1
R2
O2N
R
R2
2
5
R1
R2
R
Dihydrofurans are the most important heterocycles commonly
found in a large variety of naturally occurring substances.1 The
development of new and efficient methods for their synthesis re-
mains an area of current interest and a whole series of new syn-
thetic methods have appeared in literature.2–5 Among synthetic
methodologies toward dihydrofurans, non-ionic as well as ionic
procedures have been exploited. Radical2 or carbenoid3 additions
to olefins have been utilized as non-ionic procedures. Among ionic
reaction conditions, dihydrofuran syntheses via tandem nucleo-
philic reaction of 1,3-dicarbonyl compounds4 or ylides5 with
enones have been reported. Aliphatic nitro compounds can be
considered as versatile building blocks in organic synthesis, both
the activating effect of the nitro group and its facile transformation
into various functionalities have extended the importance of nitro
compounds in the preparation of complex molecules.6 Although
a number of methods are available as cited above, the search for
newer methods for dihydrofuran synthesis is continuously being
pursued. In this paper, we report a new method for the synthesis of
2,3-dihydrofuran via nitronate anions.
H
H
base
base
R1
O
3
R3
R3
4
1
R
O
O
O
O
R
O
O
O2N
1
+
R
R1
R2 path b
R1
R3
R2
7
R3
RCO
O
H
9
H
O
O
6
NO2
R1
R2
O
4 +
8
R1
O
O
R3
R2
R2
path a
H
H
R3
H
RCO
R1
O
R
H
NO2 10
3 O
Scheme 1.
2,3-dihydrofuran 3a as the only product in 93% yield (Table 1, entry
1). The structure of 3a is clearly assigned as trans compounds by the
analysis of the vicinal coupling constant of the two methine protons
(J2,3¼4.7 Hz) and by the analogy with earlier reported paper.2g,4c,5b–d
On the basis of this finding, a plausible reaction mechanism is
shown in Scheme 1. Deprotonation of 2a forms nitronate anion 7a
and then a Michael addition of 7a to enone 1a affords the enolate
anion 10a. Finally, the intramolecular nucleophilic O-alkylation7
of 10a gave the cycloadduct 3a (path a). In this reaction, no
cyclopropane 6a derived from the intramolecular nucleophilic
2. Results and discussion
The reaction between 3-benzylidene-2,4-pentanedione (1a)
and ethyl nitroacetate (2a) was first examined (Scheme 1). Treat-
ment of 1a with triethylamine and 2a in acetonitrile at 60 ꢀC gave
* Corresponding author. Fax: þ886 6 2740552.
E-mail address: cpchuang@mail.ncku.edu.tw (C.-P. Chuang).
0040-4020/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.05.122

7512
C.-P. Chuang et al. / Tetrahedron 64 (2008) 7511–7516
Table 1
5). The reaction worked well and 2,3-dihydrofurans 3c and 3e were
formed in 96% and 99% yields, respectively. With -nitro-
acetophenone (2b), the corresponding 2,3-dihydrofuran 3 was also
Reaction between 3-benzylidene-2,4-pentanedione (1a) and ethyl nitroacetate (2a)
a
Entry
Solvent
Base
Reaction time (h)
Product (yield (%))a
produced in good yield (entries 2, 4, and 6). This method proved to
be of general applicability on enone 1 and a-nitro carbonyl com-
pound 2. In all cases, 2,3-dihydrofuran 3 was obtained in good to
excellent yield.
1
2
3
4
5
6
7
CH3CN
EtOH
CH3NO2
CHCl3
C6H6
Et3N
Et3N
Et3N
Et3N
Et3N
K2CO3
DABCO
2
2
2
17
23
2
3a (93)
3a (92)
3a (92)
3a (89)
3a (87)
3a (94)
3a (95)
According to the proposed reaction mechanism shown above,
we believe that enolate 10 can also be formed via the Michael ad-
dition of enolate 8 (generated by the deprotonation of 5) to enone 4
and subsequently 2,3-dihydrofuran 3 can be produced. We then
studied the reaction between 4 and 5 for the synthesis of 2,3-
dihydrofuran 3. In agreement with this expectation, when 4a was
heated with 5a and triethylamine in acetonitrile, 3a was obtained
in 92% yield (Table 2, entry 7). Other examples are also summarized
in Table 2 (entries 8–10) and 2,3-dihydrofurans were obtained
effectively.
CH3CN
CH3CN
2
a
Isolated yield.
C-alkylation8 of 9a could be found (path b). During the ring closure,
the two large neighboring groups preferably formed trans confor-
mation for the sake of stereohindrance. In attempt to investigate
the range of solvents compatible with this reaction, enone 1a and
ethyl nitroacetate (2a) were chosen as model compounds and this
reaction was performed in various solvents. The results are sum-
marized in Table 1 (entries 2–5). The change of solvent to ethanol,
nitromethane, chloroform, or benzene gave similar result. In chlo-
roform and benzene, it proceeds in a much slower reaction rate. We
also used different bases for this reaction. In acetonitrile, re-
placement of triethylamine with other bases also led to a similar
reaction yield (entries 6 and 7). On the basis of these results, by
choosing acetonitrile as solvent and triethylamine as base, we ap-
plied this method to other enones 1b and 1c (Table 2, entries 3 and
Next, we investigate this reaction with 1,4-dien-3-ones 12. The
starting 2E,4E-dienones were prepared effectively by the reaction
of methyl acetoacetate (5d) with appropriate aromatic aldehydes
11 under Knoevenagel conditions followed by the recrystallization
of the product mixture (Scheme 2). The reaction yields of dienones
12 are listed in Table 3. This dienone 12 was formed presumably via
the Knoevenagel condensation of 5d with 11 followed by the aldol
condensation of the resulting Knoevenagel condensation product
with another 11. The structure of 12 was revealed by 1H and 13C
NMR analyses. In addition, the stereochemistry of 12b was further
assigned by single crystal X-ray diffraction analysis (Fig. 1).9 When
dienone 12a was reacted with ethyl nitroacetate (2a) and tri-
ethylamine in acetonitrile, in addition to the expected 2,3-dihy-
drofuran 13a (25%), cyclohexenecarboxylates 14a and 15a were also
produced in 42% and 19% yield, respectively (Table 4, entry 1). 2,3-
Dihydrofuran 13a was formed via the O-alkylation of 16a similar to
that for 3a (Scheme 2, path a). Cyclohexenecarboxylates 14a and
15a were produced via the intramolecular Michael addition of
nitronate anion 17a, generated by the proton shift of 16a (Scheme 2,
path b). It is well known that the O-alkylation of an enolate anion is
usually favored by the use of polar aprotic solvents.10 We believed
that 13a could be obtained in a higher selectivity when this reaction
was performed in DMF or DMSO. Indeed, when 12a was reacted
with 2a and triethylamine in DMF, the 13a/14aþ15a ratio rose to
71:16 (entry 2). In DMSO, a similar result was obtained (entry 3).
Table 2
Synthesis of 2,3-dihydrofuransa
Entry Enone
Carbonyl compound Reaction Product
time (h) (yield (%))b
1
2
3
4
5
6
7
8
9
10
1a: R1¼Me, R2¼Me, R3¼Ph
2a: R¼OEt
2b: R¼Ph
2
5
2
5
4
4
4
4
4
4
3a (93)
3b (88)
3c (96)
3d (89)
3e (99)
3f (89)
3a (92)
3e (97)
3f (84)
3b (82)
1a: R1¼Me, R2¼Me, R3¼Ph
1b: R1¼Me, R2¼OMe, R3¼p-Tol 2a: R¼OEt
1b: R1¼Me, R2¼OMe, R3¼p-Tol 2b: R¼Ph
1c: R1¼Ph, R2¼OEt, R3¼Ph
1c: R1¼Ph, R2¼OEt, R3¼Ph
4a: R3¼Ph, R¼OEt
2a: R¼OEt
2b: R¼Ph
5a: R1¼Me, R2¼Me
5b: R1¼Ph, R2¼OEt
5b: R1¼Ph, R2¼OEt
5a: R1¼Me, R2¼Me
4a: R3¼Ph, R¼OEt
4b: R3¼Ph, R¼Ph
4b: R3¼Ph, R¼Ph
a
All reactions were performed at 60 ꢀC in CH3CN with Et3N as base.
Isolated yield.
b
O
O
O
O
R4
H
O2N
O
O
R
11
OMe
2
OMe
O
piperidine
AcOH
R4 R4
base
5d
12
O
OH
O
OH
O
R4
MeO
R4
OMe
R4
H
OMe
+
+
H
R4
O2N
R4
O2N
R4
R
R
COR
15
COR
14
13
O
O
O
H
R4
R4
NO2
H
O
MeO
R4
MeO
path a
H
12
+
O2N
H
COR
O
13
O
16
R
7
O
R4
path b
O
O
OMe
14 + 15
R4
R4
O2N
COR
17
Scheme 2.

C.-P. Chuang et al. / Tetrahedron 64 (2008) 7511–7516
7513
by the 1H NMR, 13C NMR, and X-ray analyses (Figs. 2 and 3).9 Under
Et3N/CHCl3 conditions, with dienones 12b and 12c, cyclo-
hexenecarboxylate derivatives were obtained in good yields and
the results are listed in Table 4 (entries 13 and 14).
In conclusion, we have developed a new reaction for the syn-
thesis of 2,3-dihydrofurans from readily available starting enones
Table 3
Synthesis of 1,4-dien-3-ones 12
Entry
Benzaldehyde
Product (yield (%))a
1
2
3
11a: R1¼p-ClC6H4
12a (46)
12b (55)
12c (52)
11b: R1¼Ph
11c: R1¼p-Tol
a
and a-nitro carbonyl compounds. This protocol can provide a novel
Isolated yield.
and effective methodology for the preparation of 2,3-dihydrofurans
in a stereoselective fashion. The reaction is applicable to a range of
enones and a-nitro carbonyl compounds with a variety of versatile
functional groups. With 1,4-dien-3-ones, 2,3-dihydrofurans and
cyclohexenecarboxylates were produced and high chemo-
selectivity was observed in different solvents.
3. Experimental
3.1. General
Melting points are uncorrected. The NMR spectra were recor-
ded on a Brucker AVANCE 300, AMX-400, or AVANCE 500 spec-
trometer. Chemical shifts are reported in parts per million relative
to TMS as internal reference. Elemental analyses were performed
with Heraeus CHN-Rapid Analyzer. HRMS were recorded on
a JEOL JMS-SX 102A mass spectrometer. X-ray diffraction struc-
ture analyses were performed with a Nonius Kappa CCD diffrac-
tometer. Structure analysis was made by using SHELXTL program
on a personal computer. Analytical thin-layer chromatography
was performed with precoated silica gel 60 F-254 plates
(0.25 mm thick) and visualized by UV light. The reaction mixture
was purified by column chromatography over silica gel (70–230
mesh).
Figure 1. The molecular structure of 12b.
With potassium carbonate, 13a was obtained as the only product in
83% yield (entry 4). Since K2CO3/DMF is the most effective condi-
tion for the formation of 13a, so the scope of this reaction was
explored with a variety of dienone 12 and a-nitro carbonyl com-
pound 2 using K2CO3/DMF conditions and a series of 2,3-dihy-
drofuran derivatives were synthesized in good yields. All of these
results are summarized in Table 4 (entries 5–9). We have continued
to study the reaction between 12 and ethyl nitroacetate (2a) in non-
polar solvent. Reaction of dienone 12a with ethyl nitroacetate (2a)
and triethylamine in benzene only resulted in the formation of
cyclohexenecarboxylates 14a and 15a in 55% and 13% yield, re-
spectively, and no 2,3-dihydrofuran 13a could be found (entry 10).
In chloroform, the reaction yield for 14a and 15a are 69% and 11%,
respectively (entry 11). This high chemoselectivity is presumably
due to the stronger coordination of triethylammonium cation with
the oxygen atom of nitronate anion 16a in chloroform than that in
DMFdthe intramolecular O-alkylation rate of 16a is retarded (path
a) and the Michael addition of nitronate anion 17a becomes the
major route (path b). In protic solvent (EtOH), this reaction also
gave only the cyclohexenecarboxylate products but in a lower 14a/
15a ratio (entry 12). The structures of 14a and 15a were established
3.2. Typical procedure for the reactions between enones 1
and a-nitro carbonyl compounds 2 to produce 2,3-
dihydrofurans 3
A solution of 3-benzylidene-2,4-pentanedione (1a, 167 mg,
0.89 mmol), ethyl nitroacetate (2a, 177 mg, 1.33 mmol), and tri-
ethylamine (134 mg, 1.33 mmol) in CH3CN (6 mL) was heated at
60 ꢀC for 2 h. The reaction mixture was diluted with EtOAc
(100 mL), washed with H2O (3ꢁ50 mL), dried (Na2SO4), and con-
centrated in vacuo. The residue was chromatographed over silica
gel (20 g, eluted with 8:1 hexane/EtOAc) followed by crystallization
(hexane/EtOAc) to give 3a (226 mg, 93%).
Table 4
Reactions of 1,4-dien-3-ones 12
Entry
Dienone
Nitro carbonyl
compound
Solvent
Base
Reaction
time (h)
Product
(yield (%))a
1
2
3
4
5
6
7
8
12a: R1¼p-ClC6H4
12a: R1¼p-ClC6H4
12a: R1¼p-ClC6H4
12a: R1¼p-ClC6H4
12b: R1¼Ph
2a: R¼OEt
2a: R¼OEt
2a: R¼OEt
2a: R¼OEt
2a: R¼OEt
2a: R¼OEt
2b: R¼Ph
CH3CN
DMF
DMSO
DMF
DMF
DMF
DMF
DMF
DMF
C6H6
CHCl3
EtOH
CHCl3
CHCl3
Et3N
Et3N
Et3N
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
Et3N
4
2
2
2
2
2
2
2
2
14
14
14
14
14
13a (25)b
13a (71)b
13a (67)b
13a (83)
13b (79)
13c (87)
13d (89)
13e (91)
13f (81)
14a (42)
14a (12)
14a (12)
15a (19)b
15a (4)b
15a (5)b
12c: R1¼p-Tol
12b: R1¼Ph
12b: R1¼Ph
2c: R¼(CH2)2Ph
2d: R¼N(Et)2
2a: R¼OEt
2a: R¼OEt
2a: R¼OEt
2a: R¼OEt
2a: R¼OEt
9
12b: R1¼Ph
10
11
12
13
14
12a: R1¼p-ClC6H4
12a: R1¼p-ClC6H4
12a: R1¼p-ClC6H4
12b: R1¼Ph
14a (55)
14a (69)
14a (57)
14b (66)c
14c (72)c
15a (13)
15a (11)
15a (24)
15b (15)c
15c (13)c
Et3N
Et3N
Et3N
Et3N
12c: R1¼p-Tol
a
Isolated yield.
Deduced from the NMR integration of the product mixture of 13a and 15a.11
Deduced from the NMR integration of the product mixture of 14 and 15.12
b
c

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C.-P. Chuang et al. / Tetrahedron 64 (2008) 7511–7516
3.2.4. trans-5-Benzoyl-2-methyl-4-(p-tolyl)-4,5-dihydrofuran-3-
carboxylic acid methyl ester 3d
White needles; mp 108–109 ꢀC; IR (CHCl3) 2955, 1690, 1650,
1440, 1180 cmꢂ1; 1H NMR (500 MHz, CDCl3)
d 2.37 (s, 3H, CH3), 2.45
(s, 3H, CH3), 3.53 (s, 3H, OCH3), 4.36–4.39 (m, 1H, CH), 5.69 (d,
J¼4.4 Hz, 1H, OCH), 7.15 (d, J¼8.2 Hz, 2H, ArH), 7.17 (d, J¼8.2 Hz, 2H,
ArH), 7.46 (t, J¼7.5 Hz, 2H, ArH), 7.61 (t, J¼7.5 Hz, 1H, ArH), 7.85 (d,
J¼7.5 Hz, 2H, ArH); 13C NMR (125.7 MHz, CDCl3)
d 14.1 (q), 21.1 (q),
50.8 (q), 51.3 (d), 89.5 (d), 106.7 (s), 127.3 (2ꢁd), 128.8 (2ꢁd), 129.0
(2ꢁd), 129.5 (2ꢁd), 133.4 (s), 133.9 (d), 137.0 (s), 139.4 (s), 165.3 (s),
168.5 (s), 193.5 (s). Anal. Calcd for C21H20O4: C, 74.98; H, 5.99.
Found: C, 74.98; H, 6.07.
3.2.5. trans-3,5-Diphenyl-2,3-dihydrofuran-2,4-dicarboxylic acid
diethyl ester 3e
Colorless oil; IR (CHCl3) 2985, 1740, 1690, 1450, 1190 cmꢂ1 1H
;
Figure 2. The molecular structure of 14a.
NMR (400 MHz, CDCl3)
d
1.02 (t, J¼7.1 Hz, 3H, CH3), 1.36 (t, J¼7.2 Hz,
3H, CH3), 3.99 (q, J¼7.1 Hz, 2H, OCH2), 4.26–4.37 (m, 2H, OCH2), 4.61
(d, J¼4.1 Hz, 1H, CH), 4.96 (d, J¼4.1 Hz, 1H, OCH), 7.24–7.39 (m, 5H,
ArH), 7.39–7.52 (m, 3H, ArH), 7.92–7.99 (m, 2H, ArH); 13C NMR
3.2.1. trans-4-Acetyl-5-methyl-3-phenyl-2,3-dihydrofuran-2-
carboxylic acid ethyl ester 3a
White crystals; mp 65–66 ꢀC; IR (CHCl3) 2990, 1740, 1670, 1495,
(100.6 MHz, CDCl3) d 13.8 (q),14.2 (q), 54.0 (d), 59.9 (t), 61.8 (t), 84.9
1180 cmꢂ1; 1H NMR (300 MHz, CDCl3)
d
1.34 (t, J¼7.3 Hz, 3H, CH3),
(d), 106.6 (s), 127.1 (2ꢁd), 127.4 (d), 127.7 (2ꢁd), 128.8 (2ꢁd), 129.1
(s), 129.8 (2ꢁd), 130.9 (d), 142.5 (s), 164.0 (s), 165.4 (s), 170.2 (s);
HRMS calcd for C22H22O5: m/e 366.1467; found: m/e 366.1477.
1.96 (s, 3H, CH3), 2.44 (d, J¼1.2 Hz, 3H, CH3), 4.23–4.35 (m, 2H,
OCH2), 4.45–4.51 (m, 1H, CH), 4.78 (d, J¼5.0 Hz, 1H, OCH), 7.21–7.38
(m, 5H, ArH); 13C NMR (74.5 MHz, CDCl3)
d 14.1 (q), 14.9 (q), 29.6
(q), 53.2 (d), 61.9 (t), 86.0 (d), 115.1 (s), 127.2 (2ꢁd), 127.6 (d),
3.2.6. trans-5-Benzoyl-2,4-diphenyl-4,5-dihydrofuran-3-carboxylic
acid ethyl ester 3f
129.1(2ꢁd), 142.2 (s), 168.6 (s), 169.9 (s), 194.3 (s). Anal. Calcd for
C
16H18O4: C, 70.06; H, 6.61. Found: C, 70.01; H, 6.59.
White crystals; mp 115–116 ꢀC; IR (CHCl3) 2990,1680,1630,1450,
1230 cmꢂ1; 1H NMR (400 MHz, CDCl3)
3.89–3.97 (m, 2H, OCH2), 4.65 (d, J¼4.3 Hz,1H, CH), 5.82 (d, J¼4.3 Hz,
1H, OCH), 7.29–7.50 (m, 10H, ArH), 7.59–7.65 (m, 1H, ArH), 7.89–7.94
(m, 2H, ArH), 7.95–8.01 (m, 2H, ArH); 13C NMR (100.6 MHz, CDCl3)
d
0.98 (t, J¼7.1 Hz, 3H, CH3),
3.2.2. trans-1-(5-Benzoyl-2-methyl-4-phenyl-4,5-dihydrofuran-3-
yl)ethanone 3b
White crystals; mp 139–140 ꢀC; IR (CHCl3) 3005, 1670, 1600,
1450, 1220 cmꢂ1; 1H NMR (300 MHz, CDCl3)
d 1.94 (s, 3H, CH3), 2.47
d
13.8 (q), 53.0 (d), 59.8 (t), 88.5 (d), 107.0 (s), 127.5 (d), 127.6 (2ꢁd),
(s, 3H, CH3), 4.54 (d, J¼4.7 Hz, 1H, CH), 5.65 (d, J¼4.7 Hz, 1H, OCH),
127.7 (2ꢁd), 128.8 (2ꢁd), 128.9 (2ꢁd), 129.0 (2ꢁd), 129.3 (s), 129.9
(2ꢁd),130.8 (d),133.4 (s),133.9 (d),142.4 (s),164.0 (s),165.5 (s),193.5
(s). Anal. CalcdforC26H22O4:C, 78.37;H, 5.57. Found:C, 78.41;H, 5.56.
7.25 (d, J¼7.8 Hz, 2H, ArH), 7.29–7.42 (m, 3H, ArH), 7.47 (t, J¼7.6 Hz,
2H, ArH), 7.62 (t, J¼7.6 Hz, 1H, ArH), 7.88 (d, J¼7.6 Hz, 2H, ArH); 13
C
NMR (75.4 MHz, CDCl3)
d 14.9 (q), 29.6 (q), 51.9 (d), 89.4 (d), 115.8
(s), 127.6 (2ꢁd), 127.7 (d), 128.8 (2ꢁd), 129.09 (2ꢁd), 129.13 (2ꢁd),
133.4 (s), 134.0 (d), 142.2 (s), 168.4(s), 193.3 (s), 194.2 (s). Anal. Calcd
for C20H18O3: C, 78.41; H, 5.92. Found: C, 78.36; H, 5.92.
3.3. Typical procedure for the synthesis of 1,4-dien-3-ones 12
A solution of methyl acetoacetate (5d, 1.03 g, 8.88 mmol), benz-
aldehyde (11a, 4.97 g, 35.5 mmol), piperidine (305 mg, 3.59 mmol),
and 306 mg (5.1 mmol) of acetic acid (306 mg, 5.1 mmol) in benzene
(20 mL) was heated under reflux for 24 h with azotropic removal of
water using a Dean–Stark trap. The reaction mixture was diluted
with EtOAc (300 mL), washed with H2O (3ꢁ100 mL), aqueous sat-
urated sodium bicarbonate (3ꢁ100 mL), dried (Na2SO4), and con-
centrated in vacuo. The residue was chromatographed over silica gel
(40 g, eluted with 10:1 hexane/EtOAc) followed by recrystallization
(hexane/EtOAc) to give 12a (1.46 g, 46%).
3.2.3. trans-5-Methyl-3-(p-tolyl)-2,3-dihydrofuran-2,4-
dicarboxylic acid 2-ethyl ester 4-methyl ester 3c
Colorless oil; IR (CHCl3) 2990, 1745, 1690, 1650, 1325 cmꢂ1 1H
;
NMR (400 MHz, CDCl3)
d
1.32 (t, J¼7.1 Hz, 3H, CH3), 2.33 (s, 3H,
CH3), 2.40 (d, J¼1.2 Hz, 3H, CH3), 3.57 (s, 3H, OCH3), 4.22–4.31 (m,
2H, OCH2), 4.35–4.40 (m, 1H, CH), 4.79 (d, J¼4.7 Hz, 1H, OCH), 7.06–
7.18 (m, 4H, ArH); 13C NMR (100.6 MHz, CDCl3)
d 14.1 (q), 21.1 (q),
50.9 (q), 52.2 (d), 61.7 (t), 85.9 (d), 106.1 (s), 126.8 (2ꢁd), 129.4
(2ꢁd), 136.9 (s), 139.5 (s), 165.4 (s), 168.6 (s), 170.0 (s); HRMS calcd
for C17H20O5: m/e 304.1311; found: m/e 304.1320.
3.3.1. (2E,4E)-2-(4-Chlorobenzylidene)-5-(4-chlorophenyl)-3-oxo-
4-pentenoic acid methyl ester 12a
White powder; mp 126–127 ꢀC; IR (KBr) 1715, 1640, 1255, 1195,
825 cmꢂ1 1H NMR (400 MHz, CDCl3)
; d 3.82 (s, 3H, OCH3), 6.80 (d,
J¼16.8 Hz, 1H, CH), 7.29 (d, J¼8.6 Hz, 2H, ArH), 7.34 (d, J¼8.6 Hz, 2H,
ArH), 7.36 (d, J¼8.6 Hz, 2H, ArH), 7.41 (d, J¼8.6 Hz, 2H, ArH), 7.42 (d,
J¼16.8 Hz, 1H, CH), 7.86 (s, 1H, CH); 13C NMR (75.4 MHz, CDCl3)
d
52.7 (q), 127.0 (d), 129.1 (2ꢁd), 129.2 (2ꢁd), 129.7 (2ꢁd), 131.2 (s),
131.3 (2ꢁd), 131.6 (s), 132.4 (s), 136.7 (s), 137.1 (s), 141.2 (d), 145.0
(d), 165.1 (s), 194.9 (s). Anal. Calcd for C19H14Cl2O3: C, 63.18; H, 3.91.
Found: C, 62.84; H, 3.87.
3.3.2. (2E,4E)-2-Benzylidene-3-oxo-5-phenyl-4-pentenoic acid
methyl ester 12b
White powder; mp 102–103 ꢀC; IR (KBr) 1715, 1645, 1255, 1200,
690 cmꢂ1 1H NMR (400 MHz, CDCl3)
; d 3.82 (s, 3H, OCH3), 6.84 (d,
Figure 3. The molecular structure of 15a.

C.-P. Chuang et al. / Tetrahedron 64 (2008) 7511–7516
7515
J¼16.3 Hz,1H, CH), 7.28–7.51 (m,11H, ArHþCH), 7.92 (s,1H, CH); 13
C
2H, ArH), 7.42 (d, J¼16.2 Hz, 1H, CH), 7.48 (d, J¼8.1 Hz, 2H, ArH),
NMR (75.4 MHz, CDCl3)
d
52.4 (q), 126.7 (d), 128.4 (2ꢁd), 128.7
7.64 (d, J¼16.2 Hz, 1H, CH); 13C NMR (75.4 MHz, CDCl3)
d 14.2 (q),
(2ꢁd), 128.8 (2ꢁd), 130.0 (2ꢁd), 130.3 (d), 130.8 (d), 131.0 (s), 132.6
21.1 (q), 21.4 (q), 51.1 (q), 52.7 (d), 61.7 (t), 85.5 (d), 106.9 (s), 114.5
(d), 127.0 (2ꢁd), 127.8 (2ꢁd), 129.45 (2ꢁd), 129.51 (2ꢁd), 133.1 (s),
136.9 (s), 138.2 (d), 139.5 (s), 139.7 (s), 164.0 (s), 165.1 (s), 170.2 (s).
Anal. Calcd for C25H26O5: C, 73.87; H, 6.45. Found: C, 73.91; H, 6.44.
(s), 133.8 (s), 142.4 (d), 146.4 (d), 165.3 (s), 195.4 (s). Anal. Calcd for
C
19H16O3: C, 78.06; H, 5.52. Found: C, 78.01; H, 5.51.
3.3.3. (2E,4E)-2-(4-Methylbenzylidene)-5-(4-methylphenyl)-3-
oxo-4-pentenoic acid methyl ester 12c
3.4.4. trans-5-Benzoyl-4-phenyl-2-[(E)-styryl]-4,5-dihydrofuran-3-
carboxylic acid methyl ester 13d
White crystals; mp 119–120 ꢀC; IR (KBr) 1715, 1640, 1260, 1200,
815 cmꢂ1; 1H NMR (400 MHz, CDCl3)
d
2.30 (s, 3H, CH3), 2.35 (s, 3H,
White needles; mp 180–181 ꢀC; IR (KBr) 1695, 1635, 1215, 1040,
CH3), 3.81 (s, 3H, OCH3), 6.81 (d, J¼16.2 Hz, 1H, CH), 7.10 (d,
J¼8.1 Hz, 2H, ArH), 7.16 (d, J¼8.1 Hz, 2H, ArH), 7.34 (d, J¼8.1 Hz, 2H,
ArH), 7.37 (d, J¼8.1 Hz, 2H, ArH), 7.46 (d, J¼16.2 Hz, 1H, CH), 7.88 (s,
695 cmꢂ1 1H NMR (500 MHz, CDCl3)
; d 3.58 (s, 3H, OCH3), 4.56 (d,
J¼4.3 Hz, 1H, CH), 5.78 (d, J¼4.3 Hz, 1H, CH), 7.27–7.40 (m, 8H, ArH),
7.46 (d, J¼16.4 Hz, 1H, CH), 7.48 (d, J¼7.8 Hz, 2H, ArH), 7.58 (d,
J¼7.2 Hz, 2H, ArH), 7.62 (d, J¼7.2 Hz,1H, ArH), 7.71 (d, J¼16.4 Hz,1H,
1H, CH); 13C NMR (75.4 MHz, CDCl3)
d 21.4 (q), 21.5 (q), 52.5 (q),
126.0 (d), 128.6 (2ꢁd), 129.5 (2ꢁd), 129.6 (2ꢁd), 130.0 (s), 130.1 (s),
130.3 (2ꢁd), 131.4 (s), 141.0 (s), 141.6 (s), 142.5 (d), 146.5 (d), 165.7
(s), 196.0 (s). Anal. Calcd for C21H20O3: C, 78.73; H, 6.29. Found: C,
78.69; H, 6.29.
CH), 7.91 (d, J¼7.2 Hz, 2H, ArH); 13C NMR (125.7 MHz, CDCl3)
d 51.1
(q), 52.0 (d), 89.0 (d), 107.9 (s), 115.5 (d), 127.5 (3ꢁd), 127.8 (2ꢁd),
128.7 (2ꢁd), 128.8 (2ꢁd), 128.9 (2ꢁd), 129.0 (2ꢁd), 129.4 (d), 133.6
(s), 133.9 (d), 135.8 (s), 138.3 (d), 142.3 (s), 163.7 (s), 164.9 (s), 193.7
(s). Anal. Calcd for C27H22O4: C, 79.01; H, 5.40. Found: C, 78.98; H,
5.41.
3.4. Typical procedure for the reactions between dienones 12
and a-nitro carbonyl compounds 2 in DMF to produce 2,3-
dihydrofurans 13
3.4.5. trans-4-Phenyl-5-(3-phenylpropanoyl)-2-[(E)-styryl]-4,5-
dihydrofuran-3-carboxylic acid methyl ester 13e
A mixture of dienone (12a, 127 mg, 0.35 mmol), ethyl nitro-
acetate (2a, 92 mg, 0.69 mmol), and potassium carbonate (114 mg,
0.83 mmol) in DMF (6 mL) was heated at 60 ꢀC for 2 h. The reaction
mixture was diluted with EtOAc (100 mL), washed with H2O
(3ꢁ50 mL), dried (Na2SO4), and concentrated in vacuo. The residue
was chromatographed over silica gel (20 g, eluted with 15:1 hex-
ane/EtOAc) followed by crystallization (hexane/EtOAc) to give 13a
(130 mg, 83%).
White needles; mp 116–117 ꢀC; IR (KBr) 1700, 1635, 1225, 1045,
695 cmꢂ1
;
1H NMR (400 MHz, CDCl3)
d
2.85–3.06 (m, 4H, 2ꢁCH2),
3.60 (s, 3H, OCH3), 4.41 (d, J¼4.3 Hz, 1H, CH), 4.80 (d, J¼4.3 Hz, 1H,
CH), 7.16–7.43 (m, 14H, ArHþCH), 7.56–7.61 (m, 2H, ArH), 7.71 (d,
J¼16.3 Hz, 1H, CH); 13C NMR (100.6 MHz, CDCl3)
d 29.2 (t), 40.1 (t),
51.2 (q), 51.7 (d), 91.9 (d), 107.8 (s), 115.5 (d), 126.3 (d), 127.2 (2ꢁd),
127.3 (d), 127.8 (2ꢁd), 128.4 (2ꢁd), 128.6 (2ꢁd), 128.79 (2ꢁd),
128.82 (2ꢁd), 129.6 (d), 135.6 (s), 138.0 (d), 140.6 (s), 142.4 (s), 163.2
(s), 164.9 (s), 207.7 (s). Anal. Calcd for C29H26O4: C, 79.43; H, 5.98.
Found: C, 79.37; H, 5.95.
3.4.1. trans-5-[(E)-4-Chlorostyryl]-3-(4-chlorophenyl)-2,3-
dihydrofuran-2,4-dicarboxylic acid 2-ethyl 4-methyl ester 13a
White crystals; mp 132–133 ꢀC; IR (KBr) 1695, 1635, 1205, 1045,
3.4.6. trans-5-(Diethylcarbamoyl)-4-phenyl-2-[(E)-styryl]-4,5-
dihydrofuran-3-carboxylic acid methyl ester 13f
820 cmꢂ1
;
1H NMR (400 MHz, CDCl3)
d
1.33 (t, J¼7.2 Hz, 3H, CH3),
3.63 (s, 3H, OCH3), 4.24–4.36 (m, 2H, OCH2), 4.50 (d, J¼4.4 Hz, 1H,
CH), 4.86 (d, J¼4.4 Hz, 1H, CH), 7.20 (d, J¼8.5 Hz, 2H, ArH), 7.31 (d,
J¼8.5 Hz, 2H, ArH), 7.35 (d, J¼8.4 Hz, 2H, ArH), 7.40 (d, J¼16.3 Hz,
White needles; mp 154–155 ꢀC; IR (KBr) 1695, 1635, 1215, 1045,
695 cmꢂ1; 1H NMR (400 MHz, CDCl3)
d
1.17 (t, J¼7.0 Hz, 6H, 2ꢁCH3),
3.23–3.41 (m, 3H, NCH2þNCH), 3.53 (dq, J¼13.9, 7.0 Hz, 1H, NCH),
3.59 (s, 3H, OCH3), 4.77 (d, J¼5.1 Hz, 1H, CH), 5.15 (d, J¼5.1 Hz, 1H,
CH), 7.23–7.36 (m, 7H, ArHþCH), 7.38 (d, J¼8.0 Hz, 2H, ArH), 7.56 (d,
J¼8.0 Hz, 2H, ArH), 7.69 (d, J¼16.3 Hz, 1H, CH); 13C NMR
1H, CH), 7.51 (d, J¼8.4 Hz, 2H, ArH), 7.64 (d, J¼16.3 Hz, 1H, CH); 13
C
NMR (75.4 MHz, CDCl3) d 14.1 (q), 51.2 (q), 52.4 (d), 61.9 (t), 85.2 (d),
107.3 (s), 115.7 (d), 128.5 (2ꢁd), 128.94 (2ꢁd), 128.97 (2ꢁd), 129.04
(2ꢁd), 133.2 (s), 134.2 (s), 135.3 (s), 137.1 (d), 140.7 (s), 163.7 (s),
164.7 (s), 169.7 (s). Anal. Calcd for C23H20Cl2O5: C, 61.76; H, 4.51.
Found: C, 61.57; H, 4.53.
(100.6 MHz, CDCl3) d 12.8 (q), 14.4 (q), 40.5 (t), 41.4 (t), 51.0 (q), 52.3
(d), 85.5 (d), 108.6 (s), 115.8 (d), 127.2 (d), 127.5 (2ꢁd), 127.7 (2ꢁd),
128.7 (4ꢁd), 129.2 (d), 135.9 (s), 137.5 (d), 142.8 (s), 163.1 (s), 165.1
(s), 167.5 (s). Anal. Calcd for C25H27NO4: C, 74.05; H, 6.71; N, 3.45.
Found: C, 73.97; H, 6.75; N, 3.38.
3.4.2. trans-3-Phenyl-5-[(E)-styryl]-2,3-dihydrofuran-2,4-
dicarboxylic acid 2-ethyl 4-methyl ester 13b
White needles; mp 126–127 ꢀC; IR (KBr) 1695, 1630, 1205, 1040,
3.5. Typical procedure for the reactions between dienones 12
and ethyl nitroacetate (2a) in CHCl3 to produce
cyclohexenecarboxylates 14 and 1512
695 cmꢂ1
;
1H NMR (400 MHz, CDCl3)
d
1.33 (t, J¼7.1 Hz, 3H, CH3),
3.62 (s, 3H, OCH3), 4.26–4.36 (m, 2H, OCH2), 4.52 (d, J¼4.3 Hz, 1H,
CH), 4.92 (d, J¼4.3 Hz, 1H, CH), 7.23–7.41 (m, 8H, ArH), 7.46 (d,
J¼16.2 Hz, 1H, CH), 7.59 (d, J¼7.0 Hz, 2H, ArH), 7.69 (d, J¼16.2 Hz,
A solution of dienone 12a (130 mg, 0.36 mmol), ethyl nitro-
acetate (2a, 74 mg, 0.56 mmol), and triethylamine (75 mg,
0.74 mmol) in CHCl3 (6 mL) was heated at 60 ꢀC for 14 h. The re-
action mixture was diluted with EtOAc (100 mL), washed with H2O
(3ꢁ50 mL), dried (Na2SO4), and concentrated in vacuo. The residue
was chromatographed over silica gel (20 g, eluted with 15:1 hex-
ane/EtOAc) to give 14a (123 mg, 69%) and 15a (20 mg, 11%).
1H, CH); 13C NMR (75.4 MHz, CDCl3)
d 14.2 (q), 51.2 (q), 53.0 (d),
61.8 (t), 85.4 (d), 107.2 (s), 115.4 (d), 127.1 (2ꢁd), 127.4 (d), 127.8
(2ꢁd), 128.77 (2ꢁd), 128.79 (2ꢁd), 129.4 (d), 135.8 (s), 138.3 (d),
142.3 (s), 163.9 (s), 165.0 (s), 170.1 (s). Anal. Calcd for C23H22O5: C,
73.00; H, 5.86. Found: C, 72.88; H, 5.87.
3.4.3. trans-5-[(E)-4-Methylstyryl]-3-(4-methylphenyl)-2,3-
dihydrofuran-2,4-dicarboxylic acid 2-ethyl 4-methyl ester 13c
White needles; mp 120–121 ꢀC; IR (KBr) 1695, 1630, 1205, 1045,
3.5.1. rel-(1S,2S,6R)-2,6-Bis(4-chlorophenyl)-4-hydroxy-1-
nitrocyclohex-3-ene-1,3-dicarboxylic acid 1-ethyl 3-
methyl ester 14a
810 cmꢂ1
;
1H NMR (400 MHz, CDCl3)
d
1.32 (t, J¼7.1 Hz, 3H, CH3),
2.33 (s, 3H, CH3), 2.37 (s, 3H, CH3), 3.62 (s, 3H, OCH3), 4.24–4.33 (m,
2H, OCH2), 4.48 (d, J¼4.3 Hz, 1H, CH), 4.88 (d, J¼4.3 Hz, 1H, CH), 7.13
(d, J¼8.5 Hz, 2H, ArH), 7.17 (d, J¼8.5 Hz, 2H, ArH), 7.18 (d, J¼8.1 Hz,
White crystals; mp 191–192 ꢀC; IR (KBr) 1750, 1660, 1220, 1095,
820 cmꢂ1
;
1H NMR (400 MHz, CDCl3)
d
1.01 (t, J¼7.1 Hz, 3H, CH3),
2.78 (dd, J¼19.6, 7.8 Hz, 1H, CH), 2.83 (d, J¼19.6, 11.2 Hz, 1H, CH),

7516
C.-P. Chuang et al. / Tetrahedron 64 (2008) 7511–7516
3.60 (s, 3H, OCH3), 3.80 (q, J¼7.1 Hz, 2H, OCH2), 3.98 (dd, J¼11.2,
7.8 Hz, 1H, CH), 4.85 (s, 1H, CH), 7.15 (d, J¼8.3 Hz, 2H, ArH), 7.17 (d,
J¼8.3 Hz, 2H, ArH), 7.23 (d, J¼8.3 Hz, 2H, ArH), 7.32 (d, J¼8.3 Hz,
References and notes
1. (a) Dean, F. M.; Sargent, M. V. Comprehensive Heterocyclic Chemistry; Bird, C. W.,
Cheeseman, G. W. H., Eds.; Pergamon: New York, NY, 1984; Vol. 4, Part 3, p 531;
(b) Lipshutz, B. H. Chem. Rev. 1986, 86, 795.
2H, ArH), 12.31 (s, 1H, OH); 13C NMR (75.4 MHz, CDCl3)
d 13.3 (q),
32.5 (t), 39.5 (d), 46.4 (d), 51.9 (q), 62.6 (t), 97.4 (s), 98.1 (s), 127.8
(2ꢁd), 128.6 (2ꢁd), 130.6 (2ꢁd), 131.7 (2ꢁd), 134.0 (s), 134.1 (s),
134.6 (s), 136.8 (s), 163.8 (s), 169.1 (s), 170.9 (s). Anal. Calcd for
2. (a) Heiba, E. I.; Dessau, R. M. J. Org. Chem. 1974, 39, 3456; (b) Baciocchi, E.;
Ruzziconi, R. Synth. Commun. 1988, 18, 1841; (c) Nair, V.; Mathew, J.; Radhak-
rishnan, K. V. J. Chem. Soc., Perkin Trans. 1 1996, 1487; (d) Nair, V.; Mathew, J.;
Nair, L. G. Synth. Commun. 1996, 26, 4531; (e) Roy, S. C.; Mandal, P. K. Tetrahe-
dron 1996, 52, 2193; (f) Roy, S. C.; Mandal, P. K. Tetrahedron 1996, 52, 12495; (g)
Lee, Y. R.; Kim, N. S.; Kim, B. S. Tetrahedron Lett. 1997, 38, 5671; (h) Lee, Y. R.;
Kim, B. S.; Wang, H. C. Tetrahedron 1998, 54, 12215; (i) Bar, G.; Parson, A. F.;
Thomas, C. B. Tetrahedron Lett. 2000, 41, 7751; (j) Zhang, Y.; Raines, A. J.;
Flowers, R. A., II. Org. Lett. 2003, 5, 2363.
3. (a) Pirrung, M. C.; Zhang, J.; McPhail, A. T. J. Org. Chem. 1991, 56, 6269; (b)
Davies, H. M. L.; Ahmed, G.; Calvo, R. L.; Churchill, M. R.; Churchill, D. G. J. Org.
Chem. 1998, 63, 2641; (c) Pirrung, M. C.; Blume, F. J. Org. Chem. 1999, 64, 3642;
(d) Lee, Y. R.; Suk, J. Y.; Kim, B. S. Tetrahedron Lett. 1999, 40, 6603; (e) Mu¨ller, P.;
Allenbach, Y. F.; Bernardinelli, G. Helv. Chim. Acta 2003, 86, 3164.
4. (a) Jaxa-Chamiec, A. A.; Sammes, P. G. J. Chem. Soc., Perkin Trans. 1 1980, 170; (b)
Hagiwara, H.; Sato, K.; Suzuki, T.; Ando, M. Tetrahedron Lett. 1997, 38, 2103; (c)
Arai, S.; Nakayama, K.; Suzuki, Y.; Hatano, K.; Shioiri, T. Tetrahedron Lett. 1998,
39, 9739.
5. (a) Jiang, Y.; Ma, D. Tetrahedron: Asymmetry 2002, 13, 1033; (b) Cao, W.; Ding,
W.; Chen, J.; Chen, Y.; Zang, Q.; Chen, G. Synth. Commun. 2004, 34, 1599; (c)
Yang, Z.; Fan, M.; Mu, R.; Liu, W.; Liang, Y. Tetrahedron 2005, 61, 9140; (d)
Chuang, C.-P.; Tsai, A.-I. Synthesis 2006, 675.
C
23H21Cl2NO7: C, 55.88; H, 4.28; N, 2.83. Found: C, 55.70; H, 4.28;
N, 2.74.
3.5.2. rel-(1S,2S,6R)-4-Hydroxy-1-nitro-2,6-diphenylcyclohex-3-
ene-1,3-dicarboxylic acid 1-ethyl 3-methyl ester 14b
White crystals; mp 145–146 ꢀC; IR (KBr) 1755, 1670, 1220, 1035,
835 cmꢂ1
;
1H NMR (400 MHz, CDCl3)
d
0.93 (t, J¼7.1 Hz, 3H, CH3),
2.82 (dd, J¼19.3, 7.0 Hz, 1H, CH), 2.89 (dd, J¼19.3, 11.9 Hz, 1H, CH),
3.59 (s, 3H, OCH3), 3.64–3.80 (m, 2H, OCH2), 4.10 (dd, J¼11.9,
7.0 Hz, 1H, CH), 4.88 (s, 1H, CH), 7.18–7.27 (m, 7H, ArH), 7.30–7.39
(m, 3H, ArH), 12.32 (s, 1H, OH); 13C NMR (75.4 MHz, CDCl3)
d 13.2
(q), 32.9 (t), 40.1 (d), 47.2 (d), 51.8 (q), 62.3 (t), 98.0 (s), 98.5 (s),
127.7 (2ꢁd), 128.0 (d), 128.1 (d), 128.4 (2ꢁd), 129.4 (2ꢁd), 130.4
(2ꢁd), 136.5 (s), 138.4 (s), 164.2 (s), 169.3 (s), 171.2 (s). Anal. Calcd
for C23H23NO7: C, 64.93; H, 5.45; N, 3.29. Found: C, 64.78; H, 5.43;
N, 3.23.
6. (a) Rosini, G.; Ballini, R. Synthesis 1988, 833; (b) Ballini, R. Synlett 1999, 1009; (c)
In, Y. J.; Lee, K. Y.; Kim, T. H.; Kim, J. N. Tetrahedron Lett. 2002, 43, 4675; (d)
Ballini, R.; Barboni, L.; Giarlo, G. J. Org. Chem. 2003, 68, 9173.
7. Similar O-alkylation with a nitro group as leaving group has been reported. See:
(a) Niwas, S.; Kumar, S.; Bhaduri, A. P. Synthesis 1983, 1027; (b) Ono, N.; Yanai,
3.5.3. rel-(1S,2S,6R)-4-Hydroxy-2,6-bis(4-methylphenyl)-1-
nitrocyclohex-3-ene-1,3-dicarboxylic acid 1-ethyl 3-
methyl ester 14c
´
T.; Hamamoto, I.; Kamimura, A.; Kaji, A. J. Org. Chem. 1985, 50, 2806; (c) Melot,
J.-M.; Texier-Boullet, F.; Foucaud, A. Synthesis 1988, 588; (d) Chatterjee, A.; Jha,
S. C.; Joshi, N. N. Tetrahedron Lett. 2002, 43, 5287.
8. Similar three-membered ring C-alkylation has been reported. See: (a) Moorh-
off, C. M. Tetrahedron Lett. 1996, 37, 9349; (b) Vo, N. H.; Eyermann, C. J.; Hodge,
C. N. Tetrahedron Lett. 1997, 38, 7951; (c) Papageorgiou, C. D.; Ley, S. V.; Gaunt,
M. J. Angew. Chem., Int. Ed 2003, 42, 828.
White crystals; mp 158–159 ꢀC; IR (KBr) 1745, 1645, 1220, 1040,
815 cmꢂ1
;
1H NMR (400 MHz, CDCl3)
d
0.98 (t, J¼7.2 Hz, 3H, CH3),
2.30 (s, 3H, CH3), 2.34 (s, 3H, CH3), 2.77 (dd, J¼19.2, 6.9 Hz, 1H, CH),
2.85 (dd, J¼19.2, 12.0 Hz, 1H, CH), 3.59 (s, 3H, OCH3), 3.75 (q,
J¼7.2 Hz, 2H, OCH2), 4.06 (dd, J¼12.0, 6.9 Hz, 1H, CH), 4.81 (s, 1H,
CH), 7.04 (d, J¼8.4 Hz, 2H, ArH), 7.09 (d, J¼8.4 Hz, 2H, ArH), 7.10 (d,
9. Crystal data for 12b: C19H16O3, M¼292.32, T¼200(2) K, ¼0.71073 Å, triclinic,
l
space group P1, a¼8.8923(2) Å, b¼9.3625(2) Å, c¼10.0929(3) Å,
a
¼112.
8270(10)ꢀ,
b
¼92.8430(10)ꢀ,
g
¼100.4750(10)ꢀ, V¼754.84(3) Å3, Z¼2, Dc¼1.
286 mg/m3,
m
¼0.086 mmꢂ1
,
F(000)¼308, crystal size 0.75ꢁ0.65ꢁ0.35 mm3,
J¼8.4 Hz, 2H, ArH), 7.13 (d, J¼8.4 Hz, 2H, ArH), 12.29 (s, 1H, OH); 13
C
reflections collected 10,206, independent reflections 2759 [R (int)¼0.0732],
refinement method, full-matrix least-squares on F2, goodness-of-fit on F2 0.983,
NMR (75.4 MHz, CDCl3) d 13.3 (q), 21.0 (q), 21.1 (q), 32.9 (t), 39.6 (d),
final R indices [I>2
s
(I)] R1¼0.0505, wR2¼0.1453, R indices (all data) R1¼0.0611,
wR2¼0.1693, largest diff. peak and hole 0.368 and ꢂ0.420 e Åꢂ3. Crystallo-
graphic data for the structure in this paper have been deposited with the
Cambridge Crystallographic Data Centre as supplementary publication no.
CCDC 679631.
46.8 (d), 51.8 (q), 62.2 (t), 98.0 (s), 98.6 (s), 128.3 (2ꢁd), 129.0 (2ꢁd),
129.3 (2ꢁd),130.2 (2ꢁd),133.4 (s),135.3 (s),137.7 (s),137.8 (s),164.1
(s), 169.2 (s), 171.3 (s). Anal. Calcd for C25H27NO7: C, 66.21; H, 6.00;
N, 3.09. Found: C, 66.14; H, 6.01; N, 3.11.
Crystal data for 14a: C23H21Cl2NO7, M¼494.31, T¼296(2) K, ¼0.71073 Å, tri-
l
clinic, space group P1, a¼9.577(2) Å, b¼10.459(3) Å, c¼13.331(3) Å,
a
¼92.
318(7)ꢀ,
b
¼109.428(6)ꢀ,
g
¼114.004(6)ꢀ, V¼1126.3(5) Å3, Z¼2, Dc¼1.458 mg/m3,
3.5.4. rel-(1R,2S,6R)-2,6-Bis(4-chlorophenyl)-4-hydroxy-1-
nitrocyclohex-3-ene-1,3-dicarboxylic acid 1-ethyl 3-
methyl ester 15a
m
¼0.334 mmꢂ1, F(000)¼512, crystal size 0.46ꢁ0.32ꢁ0.12 mm3, reflections col-
lected 7857, independent reflections 3846 [R (int)¼0.0270], refinement
method, full-matrix least-squares on F2, goodness-of-fit on F2 0.661, final R
White crystals; mp 214–215 ꢀC; IR (KBr) 1755, 1660, 1225, 1070,
indices [I>2
s
(I)] R1¼0.0440, wR2¼0.1262,
R
indices (all data) R1¼0.0677,
wR2¼0.1741, largest diff. peak and hole 0.676 and ꢂ0.422 e Åꢂ3. Crystallo-
graphic data for the structure in this paper have been deposited with the
Cambridge Crystallographic Data Centre as supplementary publication no.
CCDC 679632.
820 cmꢂ1
;
1H NMR (400 MHz, CDCl3)
d
1.22 (t, J¼7.1 Hz, 3H, CH3),
2.85 (dd, J¼19.5, 11.1 Hz, 1H, CH), 2.88 (dd, J¼19.5, 7.9 Hz, 1H, CH),
3.61 (s, 3H, OCH3), 4.00 (dd, J¼11.1, 7.9 Hz, 1H, CH), 4.21 (dq, J¼10.8,
7.1 Hz, 1H, OCH), 4.37 (dq, J¼10.8, 7.1 Hz, 1H, OCH), 4.80 (s, 1H, CH),
7.11 (d, J¼8.6 Hz, 2H, ArH), 7.18 (d, J¼8.6 Hz, 2H, ArH), 7.22 (d,
Crystal data for 15a:
C
23H21Cl2NO7, M¼494.31, T¼296(2) K,
l
¼0.71073 Å,
monoclinic, space group P21/n, a¼13.0209(15) Å, b¼9.5917(10) Å, c¼19.
436(2) Å,
m
a
¼90ꢀ,
b
¼105.880(1)ꢀ,
g
¼90ꢀ, V¼2334.7(4) Å3, Z¼4, Dc¼1.406 mg/m3,
J¼8.6 Hz, 2H, ArH), 7.30 (d, J¼8.6 Hz, 2H, ArH), 12.33 (s, 1H, OH); 13
C
¼0.322 mmꢂ1
,
F(000)¼1024, crystal size 0.72ꢁ0.26ꢁ0.20 mm3, reflections
collected 15,546, independent reflections 4127 [R (int)¼0.0446], refinement
NMR (75.4 MHz, CDCl3)
d 13.6 (q), 34.3 (t), 39.3 (d), 46.8 (d), 52.1
method, full-matrix least-squares on F2, goodness-of-fit on F2 0.979, final R
(q), 63.1 (t), 97.9 (s), 98.8 (s), 127.8 (2ꢁd), 128.8 (2ꢁd), 130.4 (2ꢁd),
132.1 (2ꢁd), 134.0 (s), 134.1 (s), 134.5 (s), 136.1 (s), 164.8 (s), 169.1
(s), 170.9 (s). Anal. Calcd for C23H21Cl2NO7: C, 55.88; H, 4.28; N, 2.83.
Found: C, 55.76; H, 4.24; N, 2.78.
indices [I>2
s
(I)] R1¼0.0547, wR2¼0.1480, R indices (all data) R1¼0.0919, wR2¼0.
1807, largest diff. peak and hole 0.529 and ꢂ0.308 e Åꢂ3. Crystallographic data
for the structure in this paper have been deposited with the Cambridge Crys-
tallographic Data Centre as supplementary publication no. CCDC 679633.
Copies of the data can be obtained, free of charge, on application to CCDC, 12
Union Road, Cambridge CB2 1EZ, UK (fax: þ44 (0)1223 336033 or e-mail:
deposit@ccdc.cam.ac.uk).
10. leNoble, W. J.; Morris, H. F. J. Org. Chem. 1969, 34, 1969.
11. Dihydrofuran 13a and cyclohexenecarboxylate 15a are inseparable on column
chromatography.
Acknowledgements
12. Cyclohexenecarboxylates 14b/15b and 14c/15c cannot be separated by column
chromatography; however, the major product 14b or 14c can be obtained in
pure form by crystallization from the isomeric product mixture.
We are grateful to the National Science Council of ROC for
financial support (Grant No. NSC-95-2113-M-006-010-MY3).