The study of reaction mechanism for the transformation of nitronate into nitrile by phosphorus trichloride

Article abstract of DOI:10.1016/j.tet.2005.08.041

Nitronate was generated using β-nitrostyrene and the anion of dimethyl malonate in THF at 0°C. Subsequent treatment with PCl₃ in the presence/absence of DMAP either in THF or pyridine afforded nitroalkane, chloroxime, and nitrile. Pyridine, THF, and THF-pyridine co-solvent as solvents were investigated under different conditions. With different anions of malonates containing dipolarphiles, cyclic compounds were obtained as major products indicating nitrile oxides were generated during the reaction. Based on the results, compared to that of the one reported in literature, a plausible mechanism involving nitrile oxide intermediate was proposed.

Full text of DOI:10.1016/j.tet.2005.08.041

Tetrahedron 61 (2005) 10541–10551
The study of reaction mechanism for the transformation of
nitronate into nitrile by phosphorus trichloride
Zhijay Tu, Yaochung Jang, Chunchi Lin, Ju-Tsung Liu, Jianming Hsu, M. N. V. Sastry
*
and Ching-Fa Yao
Department of Chemistry, National Taiwan Normal University, 88, Sec. 4, Tingchow Road, Taipei, Taiwan 116, ROC
Received 19 April 2005; revised 8 August 2005; accepted 10 August 2005
Available online 9 September 2005
Abstract—Nitronate was generated using b-nitrostyrene and the anion of dimethyl malonate in THF at 0 8C. Subsequent treatment with PCl
3
in the presence/absence of DMAP either in THF or pyridine afforded nitroalkane, chloroxime, and nitrile. Pyridine, THF, and THF–pyridine
co-solvent as solvents were investigated under different conditions. With different anions of malonates containing dipolarphiles, cyclic
compounds were obtained as major products indicating nitrile oxides were generated during the reaction. Based on the results, compared to
that of the one reported in literature, a plausible mechanism involving nitrile oxide intermediate was proposed.
q 2005 Elsevier Ltd. All rights reserved.
1
. Introduction
of the products with hindered primary and secondary
alcohols. Recently, Iranpoor et al. have reported that
alcohols, thiols, and trimethylsilyl ethers can be converted
Nitrile oxides are the most important intermediates in the
synthesis of heterocyclic compounds via 1,3-dipolar
into their corresponding nitriles by using PPh /DDQ/
3
1
cycloaddition. Two widely used methods to produce nitrile
oxides are (i) reaction of aldoximes with oxidizing agents or
16e
n-Bu
NCN in acetonitrile solution at rt.
Usually, a,b-
4
unsaturated nitriles can be obtained through a Wittig
reaction of aldehyde with cyanoalkyl phosphonates.
However, it always results in an unbiased form of E- and
2
halogenating species and (ii) reaction of primary nitro-
3
alkanes with dehydrating agents such as PhNCO and Et N,
3
4
5
POCl , diketene and Na, H SO , Me SiCl and Et N,
6
7
17
Z-isomeric nitriles. Preparation of nitrile by means of
3
2
4
3
3
8
Ac O and AcONa, AcCl and MeONa, p-TsOH, PhSO2-
9
10
dehydration of amides or aldoximes with an appropriate
nonmetal dehydrating agent is an alternative method, which
also suffers from disadvantages, such as inconvenient
preparation of the reagents, limited substrate scope or
incompatibility of sensitive groups to the reaction con-
2
1
Cl or ClCOOEt and Et N, SOCl and Et N, (BOC) O
1
12
3
2
3
2
1
and DMAP, BURGESS and DAST or (COCl)2.
3
14
Nitrile is also a valuable synthetic intermediate for organic
chemistry including pharmaceuticals, agricultural chemi-
cals, dyes and material science and is also a key constituent
in many natural products. Some of the useful methods for
the preparation of alkylnitrile includes (i) the direct
nucleophilic substitution of alkyl halides with inorganic
1
8
dition. Several main or transition metal complexes were
also used as dehydrating agents to affect this transform-
1
9
1
5
ation. The conversion of primary nitro compounds into
nitrile were also reported by different electrophilic
2
0a–c
phosphorus derivatives
PCl , sulfur compounds
such as (EtO) PCl, P I , and
2 2 4
2
1a–d
1
6a,b
such as SO , Me SiSSSiMe ,
2 3 3
cyanides;
either by using HCN or acetone cyanohydrins under
(ii) the exchange of alcohols into cyanides
3
2
and CS , silyl derivatives such as Me SiI, radical
2
2
3
2
3
24
chemistry, or isocyanides. Wehrli et al. used PCl in
1
6c
Mitsunobu conditions and (iii) the use of n-Bu P/KCN/
3
3
pyridine to generate nitriles from primary nitro compounds
in moderate yields and the following reaction mechanism
1
nitriles.
8-crown-6 for the conversion of only primary alcohols to
1
6d
However, these reactions are frequently
2
0c
(
Scheme 1) has been proposed.
accompanied by elimination of hydrogen halides especially
when bulky alkyl halides were used and gives lower yields
Our previous studies established that b-nitrostyrenes react
with different nucleophiles to generate nitroalkanes,
halooximes, nitrile oxides, and polycyclic compounds
Keywords: Reaction mechanism; Nitrile; b-Nitrostyrene; Malonate ester;
PCl ; Nitrile oxide intermediate; Cyclic compounds.
3
Corresponding author. Tel.: C886 2 29309092; fax: C886 2 29324249;
e-mail: cheyaocf@scc.ntnu.edu.tw
2
5
*
under different reaction conditions. As part of our
incessant research efforts with nitroolefin chemistry, we
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.08.041

10542
Z. Tu et al. / Tetrahedron 61 (2005) 10541–10551
Scheme 1.
wish to report the reaction of trans-b-nitrostyrene 1 with
different anions of malonate esters to generate nitronates
and subsequent treatment with PCl in the absence/presence
3
Literature studies revealed that DMAP is one of the most
effective reagents to convert the nitronate into the final
products. A careful observation has led to identify two
different reaction conditions during the addition of DMAP.
Addition of 0.5 equiv of DMAP initially to the nitronate
2
1
of DMAP to afford nitroalkane 4 or 7, chlorooxime 5, nitrile
6
, 9 or 12, and cyclic products 8 or 11 under different
conditions and also to propose a plausible reaction
mechanism.
solution, followed by PCl resulted in the formation of
3
products 4a (32%) with increased yield and 5a (23%) and 6a
(25%) with decreased yield. In another variation, addition of
PCl followed by DMAP resulted in the increased yield of
3
2
. Results and discussion
nitrile 6a (38%) with reduced yields of 4a (13%) and 5a
(15%). The decrease in the yields of 4a and 5a and the
trans-b-Nitrostyrene 1a reacts with the anion of dimethyl
malonate to afford nitronate 3a, and subsequent treatment
with 3 equiv of PCl for 1.5 h at rt afforded nitroalkane 4a
increase in the yield of 6a clearly support the assumption
that, DMAP plays an important role during reaction. Based
on the above observation, increasing the amount of DMAP
to 5 equiv afforded the nitrile product 6a in 49% yield.
Similarly, with further increase in the amount of DMAP to
3
(
(
28%), chlorooxime 5a (26%), and nitrile 6a (23%)
Scheme 2).
10 equiv the yield of 6a increased to 62%. These results
clearly signify that the increase in the amount of DMAP
increases the formation of nitrile product 6a efficiently.
The compounds 4a, 5a and 6a were characterized
thoroughly using H, C NMR spectrums and the data is
1
13
2
in consistent with the reported literature data. Although
1
1
parts of the H NMR pattern of 5a are similar to 6a, these
two products can be distinguished by the following
characteristics. For example, the coupling constant of the
vicinal proton of chlorooxime 5a is 12.0 Hz and that of
The effect of solvents and temperature were also investi-
gated by employing different reaction conditions at different
reaction times and proved that all the parameters play
important roles and may have different effects to the same
reaction. After observing the results of entries 1–7 in THF
solution, pyridine was used as solvent for similar reactions
by modifying the literature procedures and conditions. Only
13% of 4a and 29% of 6a were obtained and no product 5a
was observed when the reaction was carried out in pyridine
at 95 8C for 2 h (entry 8). However, only 34% of 6a was
isolated when the same solution was stirred at rt for 9 h
(entry 9). These results indicate that 4a can be converted
into 6a slowly in pyridine solution and also consist with
nitrile 6a is only 9.6 Hz. In addition to this, the D O
2
exchangeable proton of ClC]NOH was observed in
product 5a. Besides this, different IR absorptions were
K1
also observed for compound 5a [3410 cm
(OH, broad)
and 1639 cm (C]N stretch, weak)] and 6a [2248 cm
K1
K1
1
CN stretch, weak)]. In the C NMR spectrums of these
3
(
compounds absorption at d 141.24 ppm corresponds to
ClC]NOH in 5a and at d 118.40 ppm to CN in 6a and are
also useful to distinguish between the two products.
2
1c
literature report.
Similar reactions were also conducted in different solvents
with varying amounts of DMAP under different reaction
conditions and all the experimental results were shown in
Table 1. The result of entry 1 indicates that nitronate 3a can
be converted into 4a, 5a and 6a by reacting with PCl in
3
THF solution. The increase in the amount of PCl from 5 to
3
Although the use of pyridine as solvent afforded the product
6a only, the longer reaction times and formation of insoluble
materials made the workup very difficult. In addition to this,
lower yield of products, tedious workup procedures and
longer reaction times limited the use of pyridine as a choice
of solvent. In order to attain better yields of the nitrile, a
1
0 equiv did not improve the yields of 4a, 5a and 6a.
Scheme 2.

Z. Tu et al. / Tetrahedron 61 (2005) 10541–10551
Table 1. Reaction of 1a with anion of 2a in presence of PCl in different solvents to generate 4a, 5a, 6a
10543
3
a
a
a
Entry
PCl
3
(equiv)
Solvent
DMAP
equiv)
Condition
Time (h)
4a (%)
5a (%)
6a (%)
(
1
2
3
4
5
6
7
8
9
3
5
10
5
5
5
5
5
5
THF
THF
THF
THF
THF
THF
THF
Pyridine
Pyridine
—
—
—
rt
rt
rt
rt
rt
rt
rt
95 8C
rt
1.5
1.5
1.5
1.5
48
48
48
2
28
10
12
32
13
10
10
13
—
26
29
29
23
15
15
—
—
—
23
24
29
25
38
49
62
29
34
b
c
0.5
0.5
c
5
c
10
—
—
9
a
All compounds were purified by silica gel column chromatography and yields are for pure isolated products, relative to 1a.
b
c
DMAP was initially added to the nitronate solution followed by PCl
3
.
PCl was initially added to the nitronate solution followed by DMAP.
3
Scheme 3.
combination of THF and pyridine were used as solvent.
After the generation of nitronate in THF, pyridine was
added to form the co-solvent of THF–pyridine solution
6b–f in 17–59% yield under identical reaction conditions
(Table 2).
(
Scheme 3).
The use of THF–pyridine as co-solvent though yielded 6
only in most cases, similar disadvantages were observed due
to formation of insoluble materials. The reaction at higher
temperature (95 8C) in the presence of 1 equiv of DMAP
under similar conditions resulted the product 6a in 62% with
27% of 4a (Scheme 4).
To our surprise, only 7% of 4a and 43% of 6a were
isolated and no 5a was detected by the crude H NMR
and GCMS analysis. Increasing the reaction time from
7
1
.5 to 48 h dramatically increased the yield of nitrile 6a
to 60%, without accompanying any other products. To
prove the efficiency of the reaction we have subjected
various substituted nitroolefins to obtain the products
The increase in the amount of DMAP neither improved
reaction rate nor the nitrile product formation. In the
3
Table 2. Reaction of 1 with anion of 2a PCl in the co-solvent of THF–pyridine solution
a
b
b
Entry
1
Solvent
Condition
Time (h)
4 (%)
6 (%)
1
2
3
4
5
6
7
1a
1a
1b
1c
1d
1e
1f
THF–pyridine
THF–pyridine
THF–pyridine
THF–pyridine
THF–pyridine
THF–pyridine
THF–pyridine
rt
rt
rt
rt
rt
rt
rt
7.5
48
48
48
48
48
48
4a (7)
—
—
4c (10)
—
—
6a (43)
6a (60)
6b (59)
6c (31)
6d (51)
6e (34)
6f (17)
—
a
After adding PCl
3
to the nitronate in 5 mL THF solution, 10 mL of pyridine was added to form the co-solvent of THF–pyridine solution.
All compounds were purified by using silica gel column chromatography and yields are for pure isolated products, relative to 1.
b
Scheme 4.

10544
Z. Tu et al. / Tetrahedron 61 (2005) 10541–10551
Table 3. Reaction of 1 with anion of 2a in presence of PCl
3
and DMAP in THF under refluxing condition
a
b
b
Entry
1
Solvent
DMAP
Time (h)
4 (%)
6 (%)
1
2
3
4
5
6
7
8
9
1a
1a
1a
1a
1a
1b
1c
1d
1e
1f
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
—
1
2
10
10
1
1
1
1
1
2
2
2
2
48
2
2
2
2
2
4a (7)
6a (44)
6a (62)
6a (61)
6a (57)
6a (62)
6b (59)
6c (58)
6d (55)
6e (41)
6f (33)
4a (27)
4a (10)
4a (11)
4a (11)
4b (31)
4c (19)
4d (27)
4e (35)
4f (26)
10
a
After adding 5 equiv of PCl
3
to the nitronate solution, different amounts of DMAP were added and then the solution was refluxed for 2 h.
All compounds were purified by silica gel column chromatography and yields are for pure isolated products, relative to 1.
b
presence of 10 equiv of DMAP under refluxing conditions
for 48 h yielded 11% of 4a and 62% of 6a. Similarly,
substituted nitroolefins afforded products 4b–f and 6b–f by
subjecting 1b–f as substrates (Table 3).
hand, traces of 4a and 24% of 6a were isolated when 4a was
treated with t-BuOK followed by PCl3 under similar
conditions (Scheme 5). These results signify that t-BuOK
can efficiently acts as a base rather than DMAP to
deprotonate 4a to generate nitronate and to convert it into
the final products.
These results clearly indicate that using 1 equiv of DMAP
under refluxing conditions for a time period of 2 h not only
facilitates the reaction efficiently, but also increased the
yield of 6a. It is also revealed that 4a is always present in the
solution even when excess amounts of DMAP were used
under refluxing conditions. To verify this observation, 4a
was first treated with 2 equiv of DMAP and subsequently
treated with 5 equiv of PCl3 in THF solution and the
solution was refluxed for 2 h. To our surprise, 76% of
unreacted 4a was recovered and only traces of unidentified
products were observed in the crude NMR. On the other
Other than dimethyl malonate 2a, dimethyl allylmalonate
2b was also used to react with 1a and PCl under similar
3
conditions. A trace of nitroalkane 7 along with low to
medium yields of bicyclic product 8 and nitrile 9 were
obtained (Scheme 6).
It is interesting to find that higher yields (50–58%) of cis-8
and trans-8 (the NMR ratio is from 4.0:1.0 to 4.5:1.0) with
better selectivity were observed, when the reaction was
Scheme 5.
Scheme 6.

Z. Tu et al. / Tetrahedron 61 (2005) 10541–10551
10545
Table 4. Reaction of 1a with anion of 2b in presence of PCl
3
and DMAP to generate 7, 8, and 9
a
a
b
a
Entry
PCl
3
(equiv)
DMAP
equiv)
Temperature
Time (h)
7
8 (%)
Cis/trans
9 (%)
(
1
2
3
4
5
6
7
8
9
1.5
2
2
5
5
5
5
5
5
—
—
0.5
—
—
K78 8C
K78 8C
K78 8C
rt
K0 8C
K0 8C
K10 8C
K78 8C
K78 8C
K78 8C
2
2
2
2
2
2
2
2
2
2
tr
tr
tr
3
7
6
50
56
35
31
32
42
39
45
53
58
4.0:1.0
4.5:1.0
3.5:1.0
1.0:1.1
2.0:1.0
1.6:1.0
3.2:1.0
4.2:1.0
3.7:1.0
3.8:1.0
27
16
19
16
13
18
25
22
20
26
c
c
1
—
—
8
tr
tr
tr
c
1
d
1
10
5
a
b
c
d
All compounds were purified by silica gel column chromatography and yields are for pure isolated products relative to 1.
The cis/trans ratio was measured by H NMR.
1
3
PCl was added to the nitronate solution followed by DMAP.
DMAP was added initially to the nitronate solution followed by PCl
3
.
carried out at K78 8C using different equivalents of PCl3.
On the other hand, it was observed that either increase in the
products always favors the former at lower temperature and
the later at higher temperature (Table 4).
amount of PCl or DMAP have no effect on the product
3
yields as well as on the stereoselectivity of 8. A decrease in
the temperature from 25 to 0 8C, and further to K78 8C,
reduced the nitroalkane 7 yields and increased the formation
of 8 and 9. A trace of the nitronate was observed at little
elevated temperatures (i.e., at 25, 0, K10 8C) and in most
In order to explore further, a different malonate ester such as
dimethyl 3-(cyclohexen-1-yl)malonate 2c also used to react
with 1a, under similar reaction conditions using PCl at
3
K78 8C. As expected, only 49% of tricyclic product 11 (cis/
trans Z3.8:1) and 9% of nitrile 12 were isolated without a
small amount of nitroalkane 10. The increase in the amount
cases the nitronate reacts readily with PCl to generate 8 and
3
9
at K78 8C. Possible explanation is that the presence of the
dimethoxycarbonyl group increases the steric hindrance of
of PCl from 2 to 5 equiv considerably increased the yield of
3
the tricyclic product 11 (cis/transZ3.3:1) to 55%, along
with nitrile product 12 (8%). A further increase in the
amount of PCl (10 equiv) did not improve the formation of
nitronate (A), which facilitates to react with PCl to generate
3
nitrile oxide. This undergoes intramolecular 1,3-dipolar
cycloaddition with the vinyl group to produce 8 and little
3
tricyclic product (Table 5). Based on the steric effect in the
1,4-adduct (B) one can explain the formation of the products
11 and 12 from 1a and 2c. Compared to the results obtained
with dimethyl allylmalonate 2b (Table 4) the complete
absence of nitroalkane product 10 implies the role of steric
hindrance associated with the intermediate nitronate. The
higher steric hindrance of the intermediate nitronate (B)
amount of nitrile oxide further reacts with PCl to undergo
3
deoxygenation reaction to yield 9. Two diastereomers of
bicyclic product were isolated and assigned to be cis-8 and
trans-8. Compound cis-8 has been proposed as kinetically
controlled product and trans-8 to be thermodynamically
controlled product, because the formation of these two
Table 5. Reaction of 1a with anion of 2c in presence of PCl
3
to generate 11 and 12
a
11
b
a
Entry
PCl
3
(equiv)
Temperature (8C)
Time (h)
Cis/trans
12 (%)
1
2
3
2
5
10
K78
K78
K78
2
2
2
49
55
45
3.8:1.0
3.3:1.0
3.7:1.0
9
8
8
a
All compounds were purified by silica gel column chromatography and yields are for pure isolated products, relative to 1a.
The cis/trans ratio was measured by H NMR.
b
1
Scheme 7.

10546
Z. Tu et al. / Tetrahedron 61 (2005) 10541–10551
over (A) facilitates the formation of 11 and 12 from (B) than
the formation of 8 and 9 from (A) at the same temperature
(K78 8C) and the results obtained were also consistent with
this assumption (Scheme 7).
compounds. With different anions of malonates containing
dipolarphiles, cyclic compounds were obtained as major
products indicating, nitrile oxides were generated during the
reaction. A plausible reaction mechanism has been proposed
involving a nitrile oxide intermediate for the formation of
nitrile compounds, which is little different from the one
reported in the literature.
The generation of different products can be controlled by
changing several parameters such as, use of different solvent
systems, conducting the reaction at different temperatures,
varying the amounts of reagents and substrates and by using
different nucleophiles. Based on these observations, we
proposed a stepwise mechanism (Scheme 8) for the
formation of different products involving nitronate and
nitrile oxide intermediates. The mechanism is different from
3. Experimental
3
.1. General
2
0c
those reported by Wehrli et al. in which the generation of
nitrile product exclusively proceeds through different steps.
The anion generated from malonate ester and t-BuOK reacts
with nitroolefin to form a nitronate intermediate C. The
nitronate C under mild acidic conditions furnishes the
product nitroalkane 4, from which the nitronate can be
regenerated using pyridine as a base. The reaction of PCl3
on the nitronate generates a nitroso intermediate E via D.
The nitroso compound either rearranges to form chloroxime
All reactions were performed in flame or oven-dried
glassware under a positive pressure of nitrogen. Analytical
thin-layer chromatography was performed with E. Merck
silica gel 60F glass plates and flash chromatography by use
of E. Merck silica gel 60 (230–400 mesh). THF was distilled
over sodium–benzophenone and pyridine was heated under
reflux over calcium hydride before use. All melting points
were determined on a MEL-TEMP II melting point
1
13
apparatus and were uncorrected. H and C NMR spectra
were recorded with a Bruker EX 400 FT NMR. All NMR
data were obtained in CDCl solution and chemical shift (d)
5
or to form nitrile oxide intermediate F. A clear evidence
for the formation of nitrile oxide F can be explained on the
basis of bicyclic product with dimethyl allylmalonate 2b
and the tricyclic product with 3-(cyclohexen-1-yl)malonate
3
were given in ppm relative to TMS. MS or HRMS were
measured by JEOL JMS-D300 or JEOL JMS-HX110
spectrometer. Elemental analyses were analyzed by
HERAEUS VarioEL-III (for CHN).
2c. We also concluded an important result that either from
chloroxime 5 or from nitrile oxide F, the nitrile product 6
can be obtained by the reaction of PCl3.
3
.2. Starting materials
In conclusion, we have successfully developed a method-
ology using PCl3 for the preparation of nitroalkanes,
chloroximes, and nitriles using nitronates. We have also
tested various parameters such as solvent, temperature and
additives to achieve maximum yields of the nitrile
trans-b-Nitrostyrene 1a and analogues 1b, 1c, trans-2-(2-
nitrovinyl)thiophene 1e, 2-(2-nitrovinyl)furan 1f, and other
starting materials such as dimethyl malonate 2a, dimethyl
allylmalonate 2b, t-BuOK, DMAP, pyridine, and PCl were
3
Scheme 8.

Z. Tu et al. / Tetrahedron 61 (2005) 10541–10551
10547
purchased from Aldrich Chemical Co., and other com-
mercially available reagents were used with or without
further purification. The compounds such as trans-4-chloro-
1738 (C]O stretch, strong), 1604, 1558 (N]O stretch,
strong), 1497, 1456, 1436, 1380, 1292, 1259, 1199, 1158,
K1
1020 cm . HRMS (CI) m/z calcd for C H NO (M )
C
1
3
15
6
2
6
b-nitrostyrene 1d and dimethyl 3-(cyclohexen-1-yl)malo-
nate 2c were prepared according to literature procedures
with slight modifications.
281.0899, found 281.0905. Anal. Calcd for C H NO C,
13 15 6
55.51; H, 5.38; N, 4.98. Found C, 55.08; H, 5.26; N, 5.26.
2
7
3
.4.2. 3,3-Dimethoxycarbonyl-1-nitro-2-(4-methyl-
phenyl)propane (4b). H NMR (400 MHz, CDCl ) d 7.11
1
3.3. Typical experimental procedures for the synthesis of
nitroalkane 4a, chloroxime 5a, and nitrile 6a using PCl3
at 0 8C in THF
3
(s, 4H), 6.83 (dt, JZ8.8, 2.0 Hz, 2H), 4.90 (dd, JZ13.0,
5.2 Hz, 1H), 4.84 (dd, JZ13.0, 9.0 Hz, 1H), 4.20 (td, JZ
9
.0, 5.2 Hz, 1H), 3.84 (d, JZ9.2 Hz, 1H), 3.75 (s, 3H), 3.56
13
(s, 3H), 2.30 (s, 3H). C NMR (100 MHz, CDCl ) d 167.8,
167.2, 138.1, 133.0, 130.0, 127.6, 77.5, 54.7, 52.9, 52.7,
Typical experimental procedure of entry 1 in Table 1 is
representative.
3
42.5, 21.0. IR (CHCl ) n 3028, 2956 (CH stretch, strong),
1737 (C]O stretch, strong), 1614, 1556 (N]O stretch,
3
To a 3 mL THF solution of t-BuOK (168 mg, 1.5 mmol)
added a THF solution of dimethyl malonate 2a (159 mg,
strong), 1516, 1436, 1380, 1291, 1259, 1198, 1159,
K1
C
1
.2 mmol) slowly at 0 8C. After stirring the reaction mixture
1022 cm . HRMS (CI) m/z calcd for C H NO (M )
14 17 6
at the same temperature for 30 min, a 5 mL solution of
trans-b-nitrostyrene 1a (149 mg, 1.0 mmol) in THF was
added dropwise, and stirred for another 30 min. Followed by
295.1056, found 295.1056. Anal. Calcd for C H NO C,
14 17 6
56.94; H, 5.80; N, 4.74. Found C, 57.02; H, 5.93; N, 4.69.
the addition of PCl (0.26 mL, 3.0 mmol) to the nitronate
3
3.4.3. 3,3-Dimethoxycarbonyl-1-nitro-2-(4-methoxy-
phenyl)propane (4c). Mp 100 8C. H NMR (400 MHz,
1
solution at 0 8C and allowed to stir at rt for 1.5 h. The
reaction mixture was poured into the ice cold dil HCl and
extracted with CH Cl (3!25 mL). The combined CH Cl
CDCl ) d 6.98 (dt, JZ8.8, 2.0 Hz, 2H), 6.83 (dt, JZ8.8,
3
2
2
2
2
2.0 Hz, 2H), 4.89 (dd, JZ13.0, 5.0 Hz, 1H), 4.82 (dd, JZ
13.0, 9.2 Hz, 1H), 4.19 (td, JZ9.2, 5.0 Hz, 1H), 3.83 (d, JZ
layers were washed with brine, distilled H O and dried over
2
MgSO . Evaporation of the organic solvent, the crude
4
product was purified by flash column chromatography using
silica gel (eluent; hexane/ethylacetate; 100:1) to yield
nitroalkane 4a (79 mg, 28% Y), chloroxime 5a (78 mg,
1
3
9.2 Hz, 1H), 3.77 (s, 3H), 3.75 (s, 3H), 3.56 (s, 3H).
NMR (100 MHz, CDCl ) d 167.9, 167.3, 159.5, 129.0,
C
3
127.9, 114.4, 77.7, 55.2, 54.9, 53.0, 52.8, 42.3. IR (CHCl ) n
3
3006, 2957 (CH stretch, strong), 2841, 1737 (C]O stretch,
strong), 1612, 1556 (N]O stretch, strong), 1516, 1436,
2
6% Y), and nitrile 6a (57 mg, 23% Y).
K1
380, 1296, 1255, 1182, 1032 cm . HRMS (CI) m/z calcd
1
C
3.4. Typical experimental procedure for the synthesis of
nitrile 6 in a co-solvent of THF–pyridine
for C14
Calcd for C14
3.89; H, 5.44; N, 4.54.
H17NO
7
(M ) 311.1005, found 311.1000. Anal.
H17NO : C, 54.02; H, 5.50; N, 4.50. Found C,
6
5
Typical experimental procedure of entry 1 in Table 2 is
representative.
3.4.4. 3,3-Dimethoxycarbonyl-1-nitro-2-(4-chloro-
phenyl)propane (4d). H NMR (400 MHz, CDCl ) d 7.30
1
3
To a stirred solution of t-BuOK (168 mg, 1.5 mmol) in THF
(dt, JZ8.4, 2.0 Hz, 2H), 7.17 (dt, JZ8.4, 2.0 Hz, 2H), 4.90
(dd, JZ13.2, 5.0 Hz, 1H), 4.82 (dd, JZ13.2, 9.0 Hz, 1H),
4.23 (td, JZ9.0, 5.0 Hz, 1H), 3.82 (d, JZ9.0 Hz, 1H), 3.77
(
0
5 mL) added dimethyl malonate 2a (159 mg, 1.2 mmol) at
8C. After stirring the reaction mixture at the same
temperature for 30 min, trans-b-nitrostyrene 1a (149 mg,
.0 mmol) was added to obtain a orange color nitronate 3a
1
3
(s, 3H), 3.59 (s, 3H). C NMR (100 MHz, CDCl ) d 167.6,
167.1, 134.7, 134.5, 129.4, 129.3, 77.2, 54.6, 53.1, 53.0,
42.4. IR (CHCl ) n 3028, 3006, 2957 (CH stretch, strong),
3
1
solution. To this, PCl (0.43 mL, 5 mmol) was added and
3
3
stirred for another 30 min followed by the addition of 10 mL
of pyridine to form THF–pyridine co-solvent system. The
obtained reaction mixture was further stirred at rt for 7.5 h,
and poured the contents into the ice cold dil HCl. The
insoluble materials were filtered through a Celite pad and
the aq layer was extracted with CH Cl (3!25 mL). The
1737 (C]O stretch, strong), 1557 (N]O stretch, strong),
1493, 1436, 1379, 1259, 1199, 1159, 1015 cm . HRMS
K1
C
(CI) m/z calcd for C H ClNO (M ) 315.0510, found
1
3
14
6
315.0510. Anal. Calcd for C H ClNO C, 49.46; H, 4.47;
1
3
14
6
N, 4.44. Found C, 49.35; H, 4.49; N, 4.58.
2
2
combined CH Cl layers were washed with ice cold brine
2
solution, distilled water and dried over anhyd MgSO . After
4
3.4.5. 3,3-Dimethoxycarbonyl-1-nitro-2-thienylpropane
2
1
(4e). H NMR (400 MHz, CDCl ) d 7.23 (dd, JZ4.8,
3
evaporation of the solvent, the crude mixture was purified
by flash column chromatography using silica gel (eluent;
hexane/ethylacetate; 100:1) to obtain 4a (20 mg, 7% Y) and
1.2 Hz, 1H), 6.95 (dd, JZ3.6, 1.2 Hz, 1H), 6.93 (dd, JZ4.8,
3.6 Hz, 1H), 4.95 (dd, JZ13.6, 5.4 Hz, 1H), 4.90 (dd, JZ
13.6, 8.0 Hz, 1H), 4.24 (td, JZ8.0, 5.4 Hz, 1H), 3.92 (d, JZ
1
3
6
a (106 mg, 43% Y).
7.8 Hz, 1H), 3.77 (s, 3H), 3.67 (s, 3H). C NMR (100 MHz,
CDCl ) d 167.6, 167.1, 138.5, 127.1, 126.8, 125.7, 77.9,
3
3
(
4
1
1
.4.1. 3,3-Dimethoxycarbonyl-1-nitro-2-phenylpropane
4a). H NMR (400 MHz, CDCl ) d 7.34–7.21 (m, 5H),
.93 (dd, JZ13.2, 5.3 Hz, 1H), 4.86 (dd, JZ13.2, 8.8 Hz,
55.3, 53.2, 53.1, 38.4. IR (CHCl ) n 3113, 3010, 2957 (CH
3
1
stretch, strong), 1732 (C]O stretch, strong), 1604, 1557
3
K1
(N]O stretch, strong), 1436, 1380, 1265, 1162, 1018 cm
HRMS (CI) m/z calcd for C H NO S (M ) 287.0464,
.
C
H), 4.24 (ddd, JZ9.2, 8.8, 5.3 Hz, 1H), 3.86 (d, JZ9.2 Hz,
H), 3.76 (s, 3H), 3.56 (s, 3H). C NMR (100 MHz, CDCl3)
1
1
13
6
1
3
found 287.0462. Anal. Calcd for C H NO S: C, 45.99; H,
11 13 6
d 167.8, 167.2, 136.1, 129.0, 128.4, 127.8, 77.4, 54.7, 53.0,
2.8, 42.9. IR (CHCl ) n 3034, 2957 (CH stretch, strong),
4.56; N, 4.88; S, 11.16. Found C, 45.78; H, 4.29; N, 4.71; S,
10.52.
5
3

10548
Z. Tu et al. / Tetrahedron 61 (2005) 10541–10551
3
.4.6. 3,3-Dimethoxycarbonyl-1-nitro-2-furylpropane
NMR (100 MHz, CDCl ) d 167.4, 167.2, 140.4, 134.5,
3
133.5, 129.7, 129.1, 55.5, 53.2, 52.9, 51.7. IR (CHCl ) n
3
1
(
4f). H NMR (400 MHz, CDCl ) d 7.35 (dd, JZ1.8,
3
0
1
1
8
.8 Hz, 1H), 6.29 (dd, JZ3.2, 1.8 Hz, 1H), 6.22 (dd, JZ3.2,
.8 Hz, 1H), 4.92 (dd, JZ13.6, 8.2 Hz, 1H), 4.89 (dd, JZ
3.6, 5.0 Hz, 1H), 4.39 (td, JZ8.0, 5.2 Hz, 1H), 3.94 (d, JZ
3402 (OH, broad), 2956 (CH stretch, weak), 1743 (C]O
stretch, strong), 1639 (C]N stretch, weak), 1595, 1492,
1436, 1361, 1281, 1199, 1156, 1093, 1016 cm . HRMS
K1
1
3
C
.0 Hz, 1H), 3.77 (s, 3H), 3.69 (s, 3H). C NMR (100 MHz,
(CI) m/z calcd for C H Cl NO (M ) 333.0171, found
1
3
13
2
5
CDCl ) d 167.5, 167.3, 149.4, 142.9, 110.6, 108.5, 75.3,
3
333.0175. Anal. Calcd for C H Cl NO C, 46.73; H, 3.92;
13 13 2 5
5
3.1, 53.0, 52.7, 36.9. IR (CHCl ) n 3154, 3121, 3011, 2958
3
N, 4.19. Found C, 47.02; H, 3.89; N, 4.04.
(
CH stretch, strong), 2852, 1739 (C]O stretch, strong),
1
1
559 (N]O stretch, strong), 1505, 1437, 1379, 1343, 1293,
264, 1242, 1197, 1163, 1014 cm . HRMS (CI) m/z calcd
3.4.11. 3,3-Dimethoxycarbonyl-2-thienylpropano-
hydroximoyl chloride (5e). Mp 157 8C. H NMR
K1
1
C
for C H NO (M ) 271.0692, found 271.0693. Anal.
7
(400 MHz, CDCl ) d 7.81 (br, 1H), 7.27 (dd, JZ4.8,
1
1
13
3
Calcd for C H NO C, 48.71; H, 4.83; N, 5.16. Found C,
1
1.0 Hz, 1H), 7.01 (dd, JZ2.4, 1.0 Hz, 1H), 6.95 (dd, JZ4.8,
2.4 Hz, 1H), 4.83 (d, JZ12.0 Hz, 1H), 4.30 (d, JZ12.0 Hz,
1
d 167.1, 167.0, 140.6, 137.4, 127.6, 127.0, 126.2, 56.4,
1
13
7
4
8.92; H, 4.71; N, 5.06.
1
H), 3.78 (s, 3H), 3.57 (s, 3H). C NMR (100 MHz, CDCl3)
3
3
.4.7. 3,3-Dimethoxycarbonyl-2-phenylpropanohydroxi-
1
moyl chloride (5a). Mp 149 8C. H NMR (400 MHz,
CDCl ) d 7.61 (br, 1H, D O exchangeable), 7.34–7.27 (m,
53.10, 52.91, 47.50. IR (CHCl ) n 3305 (OH, broad), 2956
3
(CH stretch, weak), 1752 (C]O stretch, strong), 1639
(C]N stretch, weak), 1435, 1315, 1267, 1210, 1177, 1118,
3
2
5
3
1
5
H), 4.50 (d, JZ12.0 Hz, 1H), 4.27 (d, JZ12.0 Hz, 1H),
13
.78 (s, 3H), 3.44 (s, 3H). C NMR (100 MHz, CDCl ) d
K1
C
1027 cm . HRMS (CI) m/z calcd for C H ClNO S (M )
11 12 5
3
67.6, 167.2, 141.2, 134.9, 128.8, 128.6, 128.5, 55.7, 53.0,
2.6, 52.5. IR (CHCl ) n 3410 (OH, broad), 2956 (CH
305.0125, found 305.0122. Anal. Calcd for C H ClNO S
11 12 5
C, 43.21; H, 3.96; N, 4.58; S, 10.49. Found C, 43.22; H,
3.76; N, 4.53; S, 9.78.
3
stretch, weak), 1743 (C]O stretch, strong), 1639 (C]N
stretch, weak), 1496, 1456, 1436, 1281, 1199, 1156, 1120,
K1 C
025 cm . HRMS (CI) m/z calcd for C H ClNO (M )
1
3.4.12. 3,3-Dimethoxycarbonyl-2-furylpropanohydroxi-
moyl chloride (5f). Mp 113–114 8C. H NMR (400 MHz,
1
3
14
5
1
2
C, 52.10; H, 4.71; N, 4.67. Found C, 52.18; H, 4.67; N, 4.65.
99.0561, found 299.0570. Anal. Calcd for C H ClNO
5
1
3
14
CDCl ) d 8.03 (br, 1H), 7.37 (dd, JZ1.6, 1.0 Hz, 1H), 6.33
3
(dd, JZ3.2, 1.8 Hz, 1H), 6.22 (dd, JZ3.2, 1.8 Hz, 1H), 4.70
3.4.8. 3,3-Dimethoxycarbonyl-2-(4-methylphenyl)pro-
panohydroximoyl chloride (5b). Mp 144–144.5 8C. H
(d, JZ12.0 Hz, 1H), 4.32 (d, JZ12.0 Hz, 1H), 3.77 (s, 3H),
1
13
3.61 (s, 3H). C NMR (100 MHz, CDCl ) d 167.2, 148.1,
3
NMR (400 MHz, CDCl ) d 8.35 (br, 1H), 7.17 (d, JZ
143.2, 138.5, 110.6, 109.5, 53.6, 53.1, 53.0, 46.1. IR
(CHCl ) n 3410 (OH, broad), 2958 (CH stretch, weak), 1743
3
8
1
2
1
2
.2 Hz, 2H), 7.12 (d, JZ8.2 Hz, 2H), 4.83 (d, JZ12.0 Hz,
3
H), 4.32 (d, JZ12.0 Hz, 1H), 3.78 (s, 3H), 3.47 (s, 3H),
(C]O stretch, strong), 1639 (C]N stretch, weak), 1563,
1503, 1437, 1272, 1209, 1151, 1118, 1075, 1014 cm
1
3
.32 (s, 3H). C NMR (100 MHz, CDCl ) d 167.7, 167.5,
K1
.
3
3
7
C
40.9, 138.2, 131.8, 129.5, 128.4, 55.7, 53.1, 52.7, 52.0,
1.1. IR (CHCl ) n 3410 (OH, broad), 2956 (CH stretch,
HRMS (CI) m/z calcd for C H ClNO ((MC2) )
11 12 6
C
291.0318, found 291.0309; (M ) 289.0348, found
289.0344. Anal. Calcd for C H ClNO C, 45.61; H,
4.18; N, 4.84. Found C, 45.78; H, 4.20; N, 4.70.
3
weak), 1744 (C]O stretch, strong), 1639 (C]N stretch,
1
1
12
6
K1
weak), 1514, 1436, 1280, 1246, 1156, 1120, 1027 cm
HRMS (CI) m/z calcd for C H ClNO ((MC2) )
.
3
7
16
C
1
4
5
C
3
3
5
15.0682, found 315.0675; (M ) 313.0712, found
13.0690. Anal. Calcd for C H ClNO C, 53.60; H,
.14; N, 4.46. Found C, 53.90; H, 5.17; N, 4.36.
3.4.13. 2,2-Dimethoxycarbonyl-1-cyano-1-phenylethane
(6a). H NMR (400 MHz, CDCl ) d 7.37 (s, 5H), 4.53 (d,
1
1
4
16
5
3
JZ9.6 Hz, 1H), 3.92 (d, JZ9.6 Hz, 1H), 3.82 (s, 3H), 3.61
1
s, 3H). C NMR (100 MHz, CDCl ) d 166.1, 165.8, 132.0,
3
(
129.2, 129.1, 128.1, 118.4, 56.3, 53.3, 53.1, 36.7. IR
3
3.4.9. 3,3-Dimethoxycarbonyl-2-(4-methoxyphenyl)pro-
panohydroximoyl chloride (5c). Mp 113–114 8C. H NMR
1
(CHCl ) n 2957 (CH stretch, medium), 2248 (CN stretch,
3
(
400 MHz, CDCl ) d 8.53 (br, 1H), 7.21 (dt, JZ8.8, 2.0 Hz,
H), 6.85 (dt, JZ8.8, 2.0 Hz, 2H), 4.44 (d, JZ12.0 Hz, 1H),
weak), 1740 (C]O stretch, strong), 1497, 1436, 1273,
1199, 1158, 1022 cm . HRMS (CI) m/z calcd for
3
K1
2
4
3
1
C
C H NO (M ) 247.0845, found 247.0847. Anal. Calcd
.31 (d, JZ12.0 Hz, 1H), 3.79 (s, 3H), 3.77 (s, 3H), 3.47 (s,
1
3
13
4
1
H). C NMR (100 MHz, CDCl ) d 167.7, 167.6, 159.5,
3
for C H NO C, 63.15; H, 5.30; N, 5.67. Found C, 63.19;
13 13 4
H, 5.32; N, 5.60.
3
40.9, 129.7, 126.8, 114.2, 55.8, 55.2, 53.0, 52.7, 51.7. IR
(
(
CHCl ) n 3400 (OH, broad), 2957 (CH stretch, weak), 1742
3
C]O stretch, strong), 1638 (C]N stretch, weak), 1611,
3.4.14. 2,2-Dimethoxycarbonyl-1-cyano-1-(4-methyl-
phenyl)ethane (6b). H NMR (400 MHz, CDCl ) d 7.24
K1
1
1
HRMS (CI) m/z calcd for C H ClNO ((MC2) )
3
3
4
513, 1437, 1305, 1256, 1199, 1179, 1119, 1031 cm
.
3
37
16
C
1
4
6
(d, JZ8.0 Hz, 2H), 7.17 (d, JZ8.0 Hz, 2H), 4.49 (d, JZ
9.6 Hz, 1H), 3.90 (d, JZ9.6 Hz, 1H), 3.82 (s, 3H), 3.62 (s,
C
31.0631, found 331.0635; (M ) 329.0661, found
29.0662. Anal. Calcd for C H ClNO C, 51.00; H,
.89; N, 4.25. Found C, 51.06; H, 4.84; N, 4.10.
1
3H), 2.34 (s, 3H). C NMR (100 MHz, CDCl ) d 166.2,
3
1
4
16
6
3
165.9, 139.1, 129.9, 129.0, 128.0, 118.6, 56.4, 53.5, 53.1,
3
(CN stretch, weak), 1739 (C]O stretch, strong), 1436,
6.4, 21.1. IR (CHCl ) n 2957 (CH stretch, medium), 2247
3
3.4.10. 3,3-Dimethoxycarbonyl-2-(4-chlorophenyl)pro-
panohydroximoyl chloride (5d). Mp 129 8C. H NMR
1
K1
1260, 1198, 1159, 1023 cm . HRMS (CI) m/z calcd for
C
C H NO (M ) 261.1001, found 261.1009. Anal. Calcd
(
400 MHz, CDCl ) d 7.86 (br, 1H), 7.31 (dt, JZ8.4, 2.0 Hz,
3
14 15
4
2
4
H), 7.23 (dt, JZ8.4, 2.0 Hz, 2H), 4.49 (d, JZ11.8 Hz, 1H),
for C H NO C, 64.36; H, 5.79; N, 5.36. Found C, 64.27;
14 15 4
H, 5.83; N, 5.39.
1
3
.26 (d, JZ11.8 Hz, 1H), 3.77 (s, 3H), 3.49 (s, 3H).
C

Z. Tu et al. / Tetrahedron 61 (2005) 10541–10551
10549
3.4.15. 2,2-Dimethoxycarbonyl-1-cyano-1-(4-methoxy-
phenyl)ethane (6c). H NMR (400 MHz, CDCl ) d 7.27
nitronate 3a solution. To this, PCl3 (0.43 mL, 5 mmol)
followed by DMAP (122 mg, 1.0 mmol) were added
sequentially at 0 8C and the resultant solution was refluxed
for 30 min. The reaction mixture was then poured into ice
cold dil HCl and extracted with CH Cl (3!25 mL). The
1
3
(
d, JZ8.4 Hz, 2H), 6.88 (d, JZ8.4 Hz, 2H), 4.48 (d, JZ
9
3
1
5
.6 Hz, 1H), 3.89 (d, JZ9.6 Hz, 1H), 3.82 (s, 3H), 3.80 (s,
13
H), 3.62 (s, 3H). C NMR (100 MHz, CDCl ) d 166.1,
3
2
2
65.8, 159.9, 129.3, 123.7, 118.6, 114.5, 56.4, 55.3, 53.3,
3.1, 35.9. IR (CHCl ) n 2958 (CH stretch, medium), 2247
combined CH Cl layers were washed with brine, distilled
2 2
H O and dried over anhyd MgSO . After evaporation of the
2 4
3
(
CN stretch, weak), 1739 (C]O stretch, strong), 1436,
organic solvent, the crude mixture as purified by flash
column chromatography using silica gel (eluent; hexane/
ethyl acetate; 100:1) to obtain nitroalkane 4a (76 mg, 27%
Y) and nitrile 6a (153 mg, 62% Y).
K1
255, 1200, 1182, 1158, 1032 cm . HRMS (CI) m/z calcd
1
for C H NO (M ) 277.0945, found 277.0948. Anal.
Calcd for C H NO C, 60.64; H, 5.45; N, 5.05. Found C,
1
C
1
4
14
5
4
14
5
6
0.82; H, 5.35; N, 5.17.
3.5.1. 3,3-Dimethoxycarbonyl-1-nitro-2-phenylhex-5-ene
(7). H NMR (400 MHz, CDCl ) d 7.34–7.29 (m, 3H), 7.13–
7.10 (m, 2H), 5.79–5.70 (m, 1H), 5.15–4.96 (m, 4H), 4.20
(dd, JZ10.8, 7.4 Hz, 1H), 3.81 (s, 3H), 3.75 (s, 3H), 2.58
1
3.4.16. 2,2-Dimethoxycarbonyl-1-cyano-1-(4-chloro-
phenyl)ethane (6d). H NMR (400 MHz, CDCl ) d 7.36
3
1
3
(
(
3
1
dt, JZ8.8, 2.2 Hz, 2H), 7.32 (dt, JZ8.8, 2.2 Hz, 2H), 4.52
d, JZ9.6 Hz, 1H), 3.89 (d, JZ9.6 Hz, 1H), 3.83 (s, 3H),
(dd, JZ14.4, 6.7 Hz, 1H), 2.28 (dd, JZ14.4, 8.0 Hz, 1H).
1
3
.64 (s, 3H). C NMR (100 MHz, CDCl ) d 165.9, 165.6,
13
C NMR (100 MHz, CDCl ) d 170.1, 169.9, 134.8, 131.8,
128.8, 128.5, 119.8, 78.3, 60.8, 52.8, 52.7, 46.8, 38.5. IR
(CHCl ) n 3034, 2955 (CH stretch, weak), 1735 (C]O
3
3
35.3, 130.5, 129.6, 129.5, 118.0, 56.1, 53.4, 53.3, 36.1. IR
(
weak), 1743 (C]O stretch, strong), 1494, 1436, 1271,
CHCl ) n 2957 (CH stretch, medium), 2249 (CN stretch,
3
3
stretch, strong), 1640 (C]C stretch, weak), 1556 (N]O
stretch, strong), 1497, 1456, 1436, 1379, 1297, 1285, 1222,
K1
199, 1155, 1094, 1017 cm . HRMS (CI) m/z calcd for
1
C H ClNO (M ) 281.0455, found 281.0456. Anal.
C
K1
1140, 1088 cm . HRMS (CI) m/z calcd for C H NO
6
1
3
12
4
16 19
C
Calcd for C H ClNO C, 46.73; H, 3.92; N, 4.19. Found
1
(M ) 321.1212, found 321.1205. Anal. Calcd for
C H NO C, 59.81; H, 5.96; N, 4.36. Found C, 59.70;
H, 5.86; N, 4.46.
3
12
4
C, 46.55; H, 3.98; N, 4.16.
1
6
17
5
3
.4.17. 2,2-Dimethoxycarbonyl-1-cyano-1-thienylethane
1
(
6e). H NMR (400 MHz, CDCl ) d 7.32 (dd, JZ5.2,
3.5.2. cis-5,5-Dimethoxycarbonyl-6-phenyl-3a,4-di-
hydro-3H,6H-cyclopenta[c]isoxazole (cis-8). H NMR
3
1
1
3
1
.2 Hz, 1H), 7.12 (dd, JZ3.6, 1.2 Hz, 1H), 6.98 (dd, JZ5.2,
.6 Hz, 1H), 4.84 (d, JZ9.2 Hz, 1H), 3.97 (d, JZ9.2 Hz,
H), 3.84 (s, 3H), 3.71 (s, 3H). C NMR (100 MHz, CDCl3)
(400 MHz, CDCl ): d 7.29–7.24 (m, 5H), 5.02 (d, JZ
3
1
3
1.2 Hz, 1H), 4.64 (dd, JZ9.7, 8.2 Hz, 1H), 4.10 (dd, JZ
12.3, 8.2 Hz, 1H), 3.81 (s, 3H), 2.70 (dd, JZ13.6, 11.2 Hz,
d 165.8, 165.6, 133.3, 128.2, 127.3, 126.9, 117.5, 56.6, 53.5,
3.4, 31.9. IR (CHCl ) n 2957 (CH stretch, medium), 2249
1
3
5
1H), 2.56 (dd, JZ13.6, 8.3 Hz, 1H). C NMR (100 MHz,
3
(
CN stretch, weak), 1741 (C]O stretch, strong), 1436,
CDCl ): d 171.3, 170.5, 168.4, 135.4, 129.8, 128.1, 127.9,
75.1, 70.2, 53.4, 52.2, 51.9, 46.7, 35.1. IR (CHCl ) n 3033,
3
K1
266, 1161, 1021 cm . HRMS (CI) m/z calcd for C H -
1
ClNO S (M ) 305.0125, found 305.0122. Anal. Calcd for
C H ClNO S C, 43.21; H, 3.96; N, 4.58. Found C, 43.43;
1
1
1
12
3
C
2954 (CH stretch, medium), 2873, 1732 (C]O stretch,
strong), 1648 (C]N stretch, weak), 1603, 1497, 1456,
1435, 1274, 1212, 1167, 1100, 1080, 1010 cm . HRMS
5
1
12
5
K1
H, 3.89; N, 4.55.
C
(CI) m/z calcd for C H NO (M ) 303.1107, found
303.1109. Anal. Calcd for C16
1
6
17
5
3
.4.18. 2,2-Dimethoxycarbonyl-1-cyano-1-furylethane
H
17NO C, 63.36; H, 5.65; N,
5
1
(
6f). H NMR (400 MHz, CDCl ) d 7.42 (dd, JZ1.8,
4.62. Found C, 63.16; H, 5.49; N, 4.22.
3
1
1
1
.0 Hz, 1H), 6.33 (dd, JZ3.2, 1.8 Hz, 1H), 6.22 (dd, JZ3.2,
.8 Hz, 1H), 4.70 (d, JZ9.0 Hz, 1H), 4.06 (d, JZ9.0 Hz,
H), 3.84 (s, 3H), 3.73 (s, 3H). C NMR (100 MHz, CDCl3)
3.5.3. trans-5,5-Dimethoxycarbonyl-6-phenyl-3a,4-di-
hydro-3H,6H-cyclopenta[c]isoxazole (trans-8). H NMR
1
3
1
d 165.8, 165.6, 144.1, 143.7, 116.0, 110.9, 109.7, 53.5, 53.4,
3.3, 30.7. IR (CHCl ) n 2958 (CH stretch, medium), 2249
(400 MHz, CDCl ) d 7.30–7.20 (m, 5H), 5.01 (d, JZ1.4 Hz,
1H), 4.68 (dd, JZ9.6, 7.7 Hz, 1H), 4.62–4.56 (m, 1H), 3.91
(dd, JZ12.0, 7.7 Hz, 1H), 3.81 (s, 3H), 3.04 (s, 3H), 2.87
3
5
3
(
CN stretch, weak), 1742 (C]O stretch, strong), 1503,
K1
437, 1267, 1208, 1162, 1015 cm . HRMS (CI) m/z calcd
1
for C H NO (M ) 237.0632, found 237.0641. Anal.
(dd, JZ12.8, 7.6 Hz, 1H), 1.80 (dd, JZ12.8, 11.0 Hz, 1H).
C
13
C NMR (100 MHz, CDCl ) d 170.8, 170.7, 169.6, 135.6,
128.7, 128.2, 127.6, 75.7, 71.4, 55.3, 53.1, 52.1, 45.9, 36.5.
IR (CHCl ) n 3004, 2954 (CH stretch, medium), 2870, 1732
1
1
11
5
3
Calcd for C H NO C, 55.70; H, 4.67; N, 5.90. Found C,
1
1
11
5
5
5.94; H, 4.56; N, 5.83.
3
(C]O stretch, strong), 1649 (C]N stretch, weak), 1604,
1497, 1455, 1435, 1280, 1259, 1208, 1176, 1102, 1078,
3
.5. Typical experimental procedures for the synthesis of
nitroalkane 4 and nitrile 6 using PCl and DMAP in THF
K1
1009 cm . HRMS (CI) m/z calcd for C16
C
H17NO (M )
5
3
303.1107, found 303.1111. Anal. Calcd for C H NO C,
63.36; H, 5.65; N, 4.62. Found C, 63.16; H, 5.14; N, 4.06.
1
6
17
5
Typical experimental procedure of entry 2 in Table 3 is
representative.
3.5.4. 2,2-Dimethoxycarbonyl-1-cyano-1-phenylpent-4-
ene (9). H NMR (400 MHz, CDCl ) d 7.37–7.33 (m,
1
To a stirred solution of t-BuOK (168 mg, 1.5 mmol) in 3 mL
THF was added a THF solution of dimethyl malonate 2a
3
3H), 7.31–7.28 (m, 2H), 5.82–5.71 (m, 1H), 5.23–5.19 (m,
2H), 4.49 (s, 1H), 3.82 (s, 3H), 3.73 (s, 3H), 2.78 (dd, JZ
(
159 mg, 1.2 mmol) at 0 8C. After stirring the reaction
mixture at 0 8C for 30 min, trans-b-nitrostyrene 1a (149 mg,
.0 mmol) in 5 mL of THF was added dropwise to generate
1
3
14.8, 6.9 Hz, 1H), 2.57 (dd, JZ14.8, 7.6 Hz, 1H). C NMR
1
(100 MHz, CDCl ) d 168.5, 168.3, 131.1, 131.0, 129.2,
3

10550
Z. Tu et al. / Tetrahedron 61 (2005) 10541–10551
1
29.1, 128.9, 120.6, 118.8, 61.1, 52.9, 52.8, 40.5, 36.9. IR
CHCl ) n 3034, 2955 (CH stretch, medium), 2246 (CN
Taiwan Normal University (ORD93-C) is gratefully
acknowledged.
(
stretch, weak), 1739 (C]O stretch, strong), 1640 (C]C
3
stretch, weak), 1602, 1495, 1456, 1436, 1300, 1255, 1218,
1
K1
141, 1083 cm . HRMS (CI) m/z calcd for C H NO
16 17 4
C
M ) 287.1158, found 287.1162. Anal. Calcd for
(
C H NO C, 66.89; H, 5.96; N, 4.88. Found C, 66.81;
H, 5.79; N, 4.76.
Supplementary data
1
6
17
4
Supplementary data associated with this article can be
found, in the online version, at doi:10.1016/j.tet.2005.08.
3
7
1
5
3
.5.5. cis-4,4-Dimethoxycarbonyl-3-phenyl-4a,5,6,7,7a,
b-hexahydro-3H-indeno[1,7-cd]isoxazole (cis-11). Mp
1
13
41. The spectrums including H, C NMR and IR for all
0
important compounds and for some compounds XRD
information are available.
1
89–190 8C. H NMR (400 MHz, CDCl ) d 7.38–7.23 (m,
3
H), 5.02 (s, 1H), 4.81 (dd, JZ17.2, 8.8 Hz, 1H), 3.84 (s,
H), 3.77 (dd, JZ9.2, 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). C NMR
100 MHz, CDCl ) d 171.9, 169.8, 166.7, 135.7, 129.9,
3
1
3
1
2
2
28.0, 127.6, 78.7, 74.2, 54.2, 53.5, 51.5, 46.6, 41.9, 29.0,
5.4, 19.8. IR (CHCl ) n 3032, 2952 (CH stretch, medium),
864, 1729 (C]O stretch, strong), 1645 (C]N stretch,
References and notes
3
1. (a) Caramella, P.; Gr u¨ nanger, P. In Padwa, A., Ed.; 1,3-
Dipolar Cycloaddition Chemistry; Wiley: New York, 1984;
Vol. 1, p 291. (b) Torsell, K. B. G. Nitrile Oxides, Nitrones and
Nitronates in Organic Synthesis; VCH: New York, 1988.
(c) Mulzer, J. Organic Synthesis Highlights; VCH: Weinheim,
1991; p 77. (d) Wade, P. A. In Trost, B. M., Ed.;
Comprehensive Organic Synthesis; Pergamon: Oxford, 1991;
Vol. 3, p 1111. (e) Padwa, A.; Pearson, W. H. Synthetic
Applications of 1,3-Dipolar Cycloaddition Chemistry Toward
Heterocycles and Natural Products; Wiley: New Jersey, 2003.
2. (a) Grundmann, C.; Richter, R. J. Org. Chem. 1968, 33, 476.
(b) Hassner, A.; Rai, K. M. L.; Linganna, N. Synthesis 1989,
57. (c) Kim, J. N.; Ryu, E. K. Synth. Commun. 1990, 20, 1373.
3. Mukaiyama, T.; Hoshino, T. J. Am. Chem. Soc. 1960, 82,
5339.
weak), 1497, 1455, 1435, 1355, 1313, 1280, 1254, 1205,
1
C H NO (M ) 343.1420, found 343.1429. Anal. Calcd
K1
180, 1079, 1044 cm . HRMS (CI) m/z calcd for
C
1
9
21
5
for C H NO C, 66.46; H, 6.16; N, 4.08. Found C, 66.40;
5
1
9
21
H, 6.15; N, 3.93.
3
7
.5.6. trans-4,4-Dimethoxycarbonyl-3-phenyl-4a,5,6,7,
a,7b-hexahydro-3H-indeno[1,7-cd]isoxazole (trans-11).
1
Mp 154 8C. H NMR (400 MHz, CDCl ) d 7.29–7.21 (m,
3
5
1
3
2
H), 5.05 (d, JZ2.0 Hz, 1H), 4.85 (dd, JZ17.2, 8.8 Hz,
H), 4.60 (dd, JZ8.6, 8.2 Hz, 1H), 3.79 (s, 3H), 3.00 (s,
H), 2.95–2.90 (m, 1H), 2.11–2.06 (m, 1H), 1.69–1.63 (m,
1
3
H), 1.39–1.29 (m, 1H), 1.08–0.90 (m, 2H). C NMR
(
100 MHz, CDCl ) d 171.2, 169.8, 169.4, 135.6, 128.8,
3
1
2
28.3, 127.6, 77.0, 57.0, 52.6, 52.0, 44.7, 40.5, 28.5, 24.3,
0.3. IR (CHCl ) n 3032, 2954 (CH stretch, medium), 1730
4. Tsushima, S.; Tsujikawa, T.; Aki, O. Japan Patent 24,902,
1968.
3
(
1
(
3
4
C]O stretch, strong), 1644 (C]N stretch, weak), 1601,
5. Vigalok, I. V.; Moisak, I. E.; Svetlakov, N. V. Khim.
Geterotsikl. Soedin. 1969, 175.
K1
497, 1456, 1435, 1280, 1254, 1207, 1078 cm . HRMS
C
CI) m/z calcd for C H NO (M ) 343.1420, found
1
9
21
5
6. (a) Torsell, K. B. G.; Zeuthen, O. Acta Chem. Scand. 1978,
B32, 118. (b) Colvin, E. W.; Beck, A. K.; Bastani, B.; Seebach,
D.; Kai, Y.; Dunitz, D. Helv. Chim. Acta 1980, 63, 697.
43.1428. Anal. Calcd for C H NO C, 66.46; H, 6.16; N,
19 21 5
.08. Found C, 66.41; H, 6.15; N, 3.93.
7
. Namboothiri, I. N. N.; Hassner, A.; Gottlieb, H. E. J. Org.
Chem. 1997, 62, 485.
3.5.7. 2,2-Dimethoxycarbonyl-2-(cyclohex-2-enyl)-1-
cyano-1-phenylethane (12). Mp 132 8C. H NMR
1
8. Mckillop, A.; Kobylecki, R. J. Tetrahedron 1974, 30, 1365.
9. (a) Harada, K.; Kaji, E.; Sen, S. Chem. Pharm. Bull. 1980, 28,
3296. (b) Harada, K.; Kaji, E.; Sen, S. Nippon Kagaku Kaishi
1981, 1195.
(
400 MHz, CDCl ) d 7.40–7.36 (m, 3H), 7.34–7.32 (m,
3
2
3
2
1
1
2
H), 5.78–5.75 (m, 1H), 5.60–5.56 (m, 1H), 4.93 (s, 1H),
.71 (s, 3H), 3.60 (s, 3H), 3.38–3.30 (m, 1H), 2.08–1.92 (m,
H), 1.87–1.18 (m, 1H), 1.68–1.55 (m, 1H), 1.36–1.26 (m,
10. (a) Shimizu, T.; Hayashi, Y.; Teramura, K. Bull. Chem. Soc.
Jpn. 1984, 57, 2531. (b) Duranleau, R. G.; Larin, J. M.;
Newman, R. R. U.S. Patent 4,089,867, 1978.
1
3
H). C NMR (100 MHz, CDCl ) d 168.0, 131.8, 129.3,
3
29.1, 128.8, 128.5, 126.5, 118.5, 65.6, 52.4, 40.9, 40.1,
4.7, 24.3, 22.0. IR (CHCl ) n 3030, 2952 (CH stretch,
3
11. Shimizu, T.; Hayashi, Y.; Shibafuchi, H.; Teramura, K. Bull.
Chem. Soc. Jpn. 1986, 59, 2827.
strong), 2240 (CN stretch, weak), 1736 (C]O stretch,
strong), 1638 (C]C stretch, weak), 1435, 1326, 1293,
12. Chen, Y.-J.; Li, C.-N. J. Chin. Chem. Soc. 1993, 40, 203.
13. Basel, Y.; Hassner, S. Synthesis 1997, 309.
14. Maugein, N.; Wagner, A.; Mioskowsi, C. Tetrahedron Lett.
1997, 38, 1547.
K1
246, 1230, 1152, 1092, 1047, 1022 cm . HRMS (CI) m/z
1
calcd for C H NO (M ) 327.1471, found 327.1479.
C
1
9
21
4
Anal. Calcd for C H NO C, 69.71; H, 6.47; N, 4.28.
4
1
9
21
Found C, 69.04; H, 6.33; N, 3.98.
15. (a) Fatiadi, A. J. In Preparation and Synthetic Applications of
Cyano Compounds; Patai, S., Rappaport, Z., Eds.; Wiley: New
York, 1983; p 1057. (b) Miller, J. S.; Manson, J. L. Acc. Chem.
Res. 2001, 34, 563.
Acknowledgements
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Chem. Rev. 1996, 156, 333. (b) Chiappe, C.; Pieraccini, D.;
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Financial support of this work was provided by the National
Science Council of the Republic of China and National

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