The unusual thermal transformations of the dimethyl 2,2,3,3-tetramethyl-7a-R-1,2,3,7a-tetrahydroimidazo[1,2-b]isoxazole-6,7-dicarboxylate derivatives

Article abstract of DOI:10.1016/j.tet.2008.05.038

Dimethyl 2,2,3,3-tetramethyl-7a-R-1,2,3,7a-tetrahydroimidazo[1,2-b]-isoxazole-6,7-dicarboxylate derivatives were shown to undergo thermal rearrangement along two competing routes giving rise to dimethyl 2-(2-R-4,5-dihydro-1H-3λ-5-imidazol-3-ylidene)-3-oxosuccinate derivatives and (or) dimethyl-2-oxo-3-(1-R-imidazolidin-2-ylidene)succinates. The latter undergoes intramolecular cyclization producing, in case of N-unsubstituted derivatives, methyl 5,6-dioxo-1-R-2,3,5,6-tetrahydro-1H-pyrrolo[1,2-a]imidazol-7-carboxylates.

Full text of DOI:10.1016/j.tet.2008.05.038

Tetrahedron 64 (2008) 7432–7436
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Tetrahedron
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The unusual thermal transformations of the dimethyl 2,2,3,3-tetramethyl-7a-
R-1,2,3,7a-tetrahydroimidazo[1,2-b]isoxazole-6,7-dicarboxylate derivatives
,
b
c
b
Nikita V. Chukanov a , Sergey A. Popov , Galina V. Romanenko , Vladimir A. Reznikov
*
a Novosibirsk State University, Pirogova Street 2, 630090 Novosibirsk, Russia
b N.N. Vorozhtsov Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, Akad. Lavrent’ev Ave. 9, 630090 Novosibirsk, Russia
c International Tomography Center, Siberian Branch of Russian Academy of Sciences, Institutskaya Street 3a, 630090 Novosibirsk, Russia
a r t i c l e i n f o
a b s t r a c t
Article history:
Dimethyl 2,2,3,3-tetramethyl-7a-R-1,2,3,7a-tetrahydroimidazo[1,2-b]-isoxazole-6,7-dicarboxylate deri-
Received 11 December 2007
Received in revised form 21 April 2008
Accepted 8 May 2008
vatives were shown to undergo thermal rearrangement along two competing routes giving rise to dimethyl
2-(2-R-4,5-dihydro-1H-3l-5-imidazol-3-ylidene)-3-oxosuccinate derivatives and (or) dimethyl-2-oxo-3-
(1-R-imidazolidin-2-ylidene)succinates. The latter undergoes intramolecular cyclizationproducing, in case
of N-unsubstituted derivatives, methyl 5,6-dioxo-1-R-2,3,5,6-tetrahydro-1H-pyrrolo[1,2-a]imidazol-7-
carboxylates.
Available online 14 May 2008
Keywords:
Ó 2008 Elsevier Ltd. All rights reserved.
2,3-Dihydroisoxazole
Azomethine ylide
Rearrangement
1,2-Sigmatropic shift
1. Introduction
nitrogen N-1 (R1¼H) enaminones 4 undergo further cyclization
with the formation of methyl 2,2,3,3-tetramethyl-5,6-dioxo-
One of the most common approaches to the synthesis of 2,3-
dihydroisoxazole derivatives is a 1,3-dipolar cycloaddition reaction
of alkynes with nitrones. 2,3-Dihydroisoxazoles formed this way, as
a rule, undergo further thermal transformations. The most typical
route for these rearrangements is the initial cleavage of the N–O
bond with further cyclization to the corresponding acylaziridines.1
Sometimes, the cleavage of the N–O bond is accompanied by the
migration of the substituent from position 3 of the isoxazoline ring
to the nitrogen atom.2–5 Thus, the goal of this paper is to study
the thermal rearrangements of dimethyl 2,2,3,3-tetramethyl-
7a-R-1,2,3,7a-tetrahydroimidazo[1,2-b]isoxazole-6,7-dicarboxylate
derivatives 1,6 that are, in turn, the annelated derivatives of 2,3-
dihydroisoxazole.
1-aryl-2,3,5,6-tetrahydro-1H-pyrrolo[1,2-a]imidazol-7-carboxylate
derivatives 5.
O
O
O
CO2Me
CO2Me
R2
O
CO2Me
CO2Me
O
CO2Me
R2
4
N
I
N
N
N
7a
N
R2
N
1
R1
R1
R1
3a-e,g
2
R2
N
R2
N
CO2Me
CO2Me
O
O
O
4
1
R1 = H
- MeOH
N
II
CO2Me
O
7a
N
O
R2
N
N
CO2Me
R1
R1
4g-i
2. Results and discussion
O
1a-j
5d-f,j
Scheme 1.
It was shown that dimethyl 2,2,3,3-tetramethyl-7a-R-1,2,3,7a-
tetrahydroimidazo[1,2-b]isoxazole-6,7-dicarboxylate derivatives 1
undergo a rearrangement by at least two competing ways upon
heating (Scheme 1). One way is the formation of ylides 3 and an-
other one is the migration of the substituent R2 to the nitrogen N-4,
leading to enaminones 4. In the absence of the substituent at the
The structures of compounds 3, 4 and 5 were proved by 1H and
13C NMR, IR and UV spectroscopy as well as X-ray analysis (Fig. 1).
The reaction conditions and the ratio of the products 3 and 4 or
5, which are formed as the result of two competing rearrangements
are presented in Table 1.
The direction of the rearrangement is shown to depend on the
nature of the substituent R2. If R2 is alkyl (1a, 1b), the only path-
way I is present. It probably includes the initial formation of
* Corresponding author.
E-mail address: nikita@nioch.nsc.ru (N.V. Chukanov).
0040-4020/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.05.038

N.V. Chukanov et al. / Tetrahedron 64 (2008) 7432–7436
7433
It should be noted that the relative amount of the rearrange-
ment product 4 in case of N-methyl-substituted cycloadducts 1
(R1¼Me) is higher in comparison with corresponding N-unsub-
stituted derivatives (R1¼H).
O
O
O
O
O
O
O
O
O
N
N
2.1. Mechanism of the rearrangement
N
O
The migration of the aromatic substituent in 1 and 6 is most
likely a concerted 1,2-shift. This reaction proceeds through transi-
tion state (TS) 7 (Scheme 2). Such TS can be achieved only in case of
syn-position of the migrant R2 and a lone electron pair on nitrogen
N-4. In a number of cases, the syn-position of the substituent (es-
pecially hydrogen atom) relative to the lone electron pair leads to
unstable 2,3-dihydroisoxazole derivatives, which thereby cannot
be isolated.1,10,11 At the same time, 2,3-dihydroisoxazole derivative
6a, containing migrant and the lone electron pair in anti-position, is
stable for several hours even at 80 ꢀC.
N
4h
3d
O
O
O
#
R4
N
δ-
X
O
R4
R3
O
R1
N
O
O
N
R1
δ+
N
R3
H
O
O
H
N
R1
N
H
R4
O
N
X
O
R3
X
O
7
6a: 1=t-Bu, X=H, R3=COPh,R4=Ph
R
5d
5e
6b:R1= t-Bu, X=NMe ,
R
=
4=CO Me
3
R
2
2
8b
8c
Figure 1. Crystal structure of dimethyl 2-(2-phenyl-4,4,5,5-tetramethyl-4,5-dihydro-
1H-3 -5-imidazol-3-ylidene)-3-oxosuccinate 3d (CCDC 628084), dimethyl-2-oxo-3-
6c:R1=Ph, X=NMe2, R3=R4=CF3
2=C H -X
R
l
6
4
(3,4,4,5,5-pentamethyl-1-phenylimidazolidin-2-ylidene)succinate 4h (CCDC 628083),
methyl 2,2,3,3-tetramethyl-5,6-dioxo-1-phenyl-2,3,5,6-tetrahydro-1H-pyrrolo[1,2-a]-
imidazol-7-carboxylate 5d (CCDC 628086) and methyl 2,2,3,3-tetramethyl-5,6-dioxo-
1-(4-metoxyphenyl)-2,3,5,6-tetrahydro-1H-pyrrolo[1,2-a]imidazol-7-carboxylate 5e
(CCDC 628085).
Scheme 2.
Upon heating, 2,3-dihydroisoxazole derivative 6b is shown to
undergo the rearrangement with migration of the aryl substituent,
but not the hydrogen atom. The same result was found by
Kobayashi et al. for 2,3-dihydroisoxazole 6c.4 This is apparently due
to much higher thermodynamic stability of the conformer in which
the para-dimethylaminophenyl group and lone electron pair are
situated on the same side of the isoxazoline ring plane. These ex-
amples unambiguously show the stereoselectivity of the reaction,
which is typical for the 1,2-sigmatropic shifts.
acylaziridine 27,8 with subsequent cleavage of the azyridine ring
leading to ylide 3 formation.9 The other way (II) is predominant in
the case of substituents bearing conjugated
p
-system (R2¼Ar,
–CH]CH–Ph), being sometimes the only path observed (cf.
Table 1). It should be noted that the migration occurs only to ni-
trogen N-4, but not to N-1. The evidence for this is the formation of
enaminones 4g–i from cycloadducts 1g–i, where methyl group is
attached to N-1 (R1¼Me).
3. Conclusion
The data presented in Table 1 demonstrate that the relative
content of R2 migration product 4 or 5 substantially increases with
Thus, upon heating, dimethyl 2,2,3,3-tetramethyl-7a-R-1,2,3,7a-
tetrahydroimidazo[1,2-b]isoxazole-6,7-dicarboxylate derivatives 1
undergo a rearrangement by two competing ways with the
formation of either dimethyl 2-(2-R-4,4,5,5-tetramethyl-4,5-dihy-
the enhance of
p
-donor character of substituent R2. Thus, in the
case of compound 1c (R2¼4-NO2–C6H4) product 4 or 5 is not
observed, whereas the reaction of 1d (R2¼C6H5) and especially 1e
(R2¼4-OMe-C6H4) results in formation of appreciable amount of
aryl migration product 5. For the 1f (R2¼4-NMe2–C6H4) rear-
rangement leads exclusively to product 5 (Table 1).
dro-1H-3l-5-imidazol-3-ylidene)-3-oxosuccinate derivatives 3 or
dimethyl-2-oxo-3-(4,4,5,5-tetramethyl-1-R-imidazolidin-2-ylidene)-
succinates 4, the latter, in the case of N-unsubstituted derivatives,
undergo further cyclization into methyl 2,2,3,3-tetramethyl-5,6-
dioxo-1-R-2,3,5,6-tetrahydro-1H-pyrrolo[1,2-a]imidazol-7-carbox-
ylate derivatives 5; the ratio of the products being dependent on
the nature of the substituents R1 and R2.
Table 1
The reaction conditions (in toluene) and the ratio of products 3 and 4 or 5 by 1H NMR
Compound
R1
R2
Reaction condition
Ratio (%)
Temp (ꢀC)
Time (h)
3
4
5
4. Experimental section
4.1. General
1a
1b
1c
1d
1e
1f
1g
1h
1i
H
H
H
H
H
H
Me
Me
Me
H
Me
t-Bu
105
105
131
131
131
80
131
105
105
105
150
55
11
6
100
100
100
85
25
0
55
5
0
d
d
d
d
d
d
45
95
100
d
0
0
0
15
75
100
d
d
d
100
4-NO2–C6H4
Ph
4-MeO–C6H4
4-NMe2–C6H4
4-NO2–C6H4
Ph
2.5
1H and 13C NMR (200 and 50 MHz, respectively) spectra were
recorded on Bruker AC-200, AV-300, AM-400 and WP-200 spec-
trometers; solvents were used as internal standards. IR spectra
were recorded with a Bruker IFS 66 spectrometer for KBr pellets
(concentration 0.25%, pellet thickness 1 mm). Melting points were
1
17
21
2
4-MeO–C6H4
–CH]CH–Ph
1j
12.5
0
The overall conversion equals to or more than 95%.
measured in a sealed capillary. Thin layer chromatography

7434
N.V. Chukanov et al. / Tetrahedron 64 (2008) 7432–7436
monitoring was carried out on aluminium oxide plates (Fluka) and
silica gel 60 F254 plates with chloroform and chloroform/MeOH
mixtures (from 50:1 to 120:1) as eluents. The solutions were
evaporated in vacuo in all cases.
4.3.1. Dimethyl 2-oxo-3-(2,4,4,5,5-pentamethyl-4,5-dihydro-1H-
1l-5-imidazol-1-ylidene)succinate 3a
Starting from 1a, following the general procedure and using
CHCl3/MeOH (50:1) as eluent for the chromatography on alumina,
the product was obtained as a white powder (0.014 g, 25%). Mp
222.5–227 ꢀC (with decomposition). IR (KBr) 3179, 2988, 2926,
2766, 2720, 1736, 1687, 1589, 1521, 1432, 1364, 1336, 1276, 1242,
4.2. X-ray diffraction
Single crystal diffraction data for the compounds 3d, 4h, 5d and
5e were collected on a SMART APEX CCD (Bruker AXS) automatic
1189, 1174, 1158, 1132, 1065 cmꢁ1
. dH (CDCl3): 1.13 (s, 3H, 4-CH3 or
5-CH3), 1.18 (s, 3H, 4-CH3 or 5-CH3), 1.25 (s, 3H, 4-CH3 or 5-CH3),
1.26 (s, 3H, 4-CH3 or 5-CH3), 1.97 (s, 3H, 2-CH3), 3.59 (s, 3H,
CO2CH3), 3.81 (s, 3H, CO2CH3), 10.40 (br s, 1H, NH); dC (CDCl3): 12.2,
20.1, 20.6, 22.1, 23.3, 50.3, 51.7, 64.7, 72.9, 91.6, 166.3, 167.4, 169.6,
174.1. Anal. Calcd for C14H22N2O5: C, 56.36; H, 7.43; N, 9.39. Found:
C, 56.61; H, 7.40; N, 9.22%.
diffractometer (Mo K
a
,
l¼0.71073 Å, T¼240 K). The structures were
solved by direct methods and refined by the full-matrix least-
squares method in an anisotropic approximation for non-hydrogen
atoms. The H atoms’ positions were calculated and refined together
with non-hydrogen atoms in an isotropic approximation. All
structure solution and refinement calculations were carried out
with SHELX-97 and Bruker SHELXTL Version 6.14 program pack-
ages. Atomic coordinates, thermal parameters, bond lengths and
bond angles have been deposited at the Cambridge Crystallo-
graphic Data Centre; CCDC’s contain the supplementary crystallo-
graphic data for this paper. These data can be obtained free of
charge at www.ccdc.cam.ac.uk/conts/retrieving.html [or from the
Cambridge Crystallographic Data Centre,12 Union Road, Cambridge
CB2 1EZ, UK; fax: (internat.) þ44 1223 336033; e-mail:
deposit@ccdc.cam.ac.uk].
4.3.2. Dimethyl 2-oxo-3-(2-tert-butyl-4,4,5,5-pentamethyl-4,5-
dihydro-1H-1l-5-imidazol-1-ylidene)succinate 3b
Starting from 1b, following the general procedure and using
CHCl3/MeOH (50:1) as eluent for the chromatography on alumina,
the product was obtained as a white powder (0.043 g, 80%). Mp
275–277 ꢀC (with decomposition). IR (KBr) 3148, 3000, 2944, 2881,
1734, 1675, 1536, 1518, 1437, 1397, 1373, 1335, 1271, 1223, 1191, 1177,
1157, 1064 cmꢁ1
. dH (CD3OH): 1.20 (s, 3H, 4-CH3 or 5-CH3), 1.23 (s,
3H, 4-CH3 or 5-CH3), 1.32 (s, 3H, 4-CH3 or 5-CH3), 1.37 (s, 3H, 4-CH3
or 5-CH3), 1.29 (s, 9H, C(CH3)3), 3.59 (s, 3H, CO2CH3), 3.78 (s, 3H,
CO2CH3); dC (CD3OH): 21.5, 22.0, 23.3, 23.9, 28.6, 36.7, 51.5, 53.0,
66.1, 76.1, 170.4, 171.9, 176.9, 177.0. Anal. Calcd for C17H28N2O5: C,
59.98; H, 8.29; N 8.23. Found: C, 60.02; H, 8.47; N, 8.22%.
4.2.1. Crystallographic data for 3d
C
19H24N2O5, FW¼360.40, orthorhombic, Pna21 a¼13.027(3),
b¼14.603(3), c¼10.617(2) Å, V¼2019.7(7) Å3, Z¼4, Dc¼1.185 g/cm3,
m
¼0.086 mmꢁ1
,
2.09<
q
<29.50ꢀ, reflections collected/unique¼
22,408/5209, Rint¼0.1463, 277 parameters, Goof¼0.999, R indices
4.3.3. Dimethyl 2-oxo-3-(2-(4-nitrophenyl)-4,4,5,5-pentamethyl-
4,5-dihydro-1H-1l-5-imidazol-1-ylidene)succinate 3c
(I>2
s
(I)): R1¼0.0879, wR2¼0.1477, R indices (all data): R1¼0.1659,
wR2¼0.746.
Starting from 1c, following the general procedure and using
CHCl3/MeOH (50:1) as eluent for the chromatography on alumina,
the product was obtained as a white powder, which was recrys-
tallized from toluene/CHCl3 (0.016 g, 50%). Mp 222.5–224.5 ꢀC
(with decomposition). IR (KBr) 2980, 2948, 2846, 2721, 1739, 1676,
4.2.2. Crystallographic data for 4h
C
20H26N2O5, FW¼374.43, orthorhombic, Pna21, a¼15.856(4),
b¼9.165(2), c¼13.510(3) Å, V¼1963.2(8) Å3, Z¼4, Dc¼1.267 g/cm3,
m
¼0.091 mmꢁ1
,
2.57<
q
<23.33ꢀ, reflections collected/unique¼
1612,1556,1521,1436,1340,1238,1167,1122,1057 cmꢁ1
. dH (CDCl3):
7901/2786, Rint¼0.0322, 349 parameters, Goof¼0.942, R indices
1.08 (s, 3H, 4-CH3 or 5-CH3), 1.23 (s, 3H, 4-CH3 or 5-CH3), 1.25 (s, 3H,
4-CH3 or 5-CH3), 1.38 (s, 3H, 4-CH3 or 5-CH3), 3.51 (s, 3H, CO2CH3),
3.60 (s, 3H, CO2CH3), 7.72 (d, 3J¼8.7 Hz, 2H, Ar), 8.07 (d, 3J¼8.7 Hz,
2H, Ar), 11.18 (br s, 1H, NH); dC (CDCl3): 20.0, 20.7, 21.8, 23.1, 50.5,
51.5, 65.7, 73.8, 93.4, 123.0, 129.6, 130.6, 149.9, 163.6, 168.6, 166.9,
173.6. Anal. Calcd for C19H23N3O7: C, 56.29; H, 5.72; N, 10.37. Found:
C, 56.43; H, 5.92; N, 10.24%.
(I>2
s
(I)): R1¼0.0326, wR2¼0.0911, R indices (all data): R1¼0.0335,
wR2¼0.0919.
4.2.3. Crystallographic data for 5d
C
36H40N4O8, FW¼218.91, monoclinic, P21/c, a¼10.422(2),
b¼9.556(2), c¼16.783(4) Å,
b
¼106.557(4)ꢀ, V¼1602.3(6) Å3, Z¼4,
Dc¼1.361 g/cm3,
m
q
¼0.097 mmꢁ1, 2.04< <23.33ꢀ, reflections col-
lected/unique¼6779/2319, Rint¼0.0742, 298 parameters, Goof¼
4.3.4. Dimethyl 2-oxo-3-(2-phenyl-4,4,5,5-pentamethyl-4,5-
dihydro-1H-1l-5-imidazol-1-ylidene)succinate 3d
0.938, R indices (I>2
s
(I)): R1¼0.0412, wR2¼0.0863, R indices (all
data): R1¼0.0571, wR2¼0.0925.
Starting from 1d, following the general procedure, the product
was obtained as a white powder, which was recrystallized from
hexane/acetone (0.006 g, 20%). Mp 238–240 ꢀC. IR (KBr) 3165, 2992,
2948, 2907, 2844, 2726, 1742, 1674, 1610, 1592, 1540, 1521, 1436,
4.2.4. Crystallographic data for 5e
C
40H44N4O10
,
FW¼238.92, monoclinic, P21/c, a¼10.383(3),
b¼12.011(4), c¼15.037(5) Å,
b
¼105.912(6)ꢀ, V¼1803.5(10) Å3, Z¼4,
1398, 1373, 1351, 1272, 1237, 1199, 1129, 1058 cmꢁ1
. dH (CDCl3): 1.07
Dc¼1.320 g/cm3,
m
¼0.096 mmꢁ1, 2.20<
q
<23.39ꢀ, reflections col-
(s, 3H, 4-CH3 or 5-CH3), 1.15 (s, 6H, 4-CH3 or 5-CH3), 1.21 (s, 3H,
4-CH3 or 5-CH3), 3.39 (s, 3H, CO2CH3), 3.51 (s, 3H, CO2CH3), 7.11–
7.47 (m, 5H, Ph), 10.55 (br s, 1H, NH); dC (CDCl3): 20.0, 20.8, 21.8,
23.0, 50.1, 51.3, 64.8, 73.3, 93.3,124.7, 128.1, 128.1, 132.3, 165.0,167.5,
169.1, 174.0. Anal. Calcd for C19H24N2O5: C, 63.32; H, 6.71; N, 7.77.
Found: C, 63.13; H, 6.66; N, 7.62%.
lected/unique¼7604/2590, Rint¼0.0769, 324 parameters, Goof¼
0.973, R indices (I>2
s
(I)): R1¼0.0425, wR2¼0.0958, R indices (all
data): R1¼0.0541, wR2¼0.1012.
4.3. General experimental procedure
The solution of 0.1–0.2 mmol of 1 in 1–2 ml of toluene, unless
otherwise stated was heated (the conditions are shown in Table 1).
In the cases when the temperature was 131 ꢀC, the reaction was
carried out in a sealed tube. After evaporation of a reaction mixture
the products of rearrangement 3 and/or 4 (5) were separated by
chromatographing on silica gel or alumina with CHCl3/MeOH
mixture as eluent.
4.3.5. Dimethyl 2-oxo-3-(2-(4-methoxyphenyl)-4,4,5,5-penta-
methyl-4,5-dihydro-1H-1l-5-imidazol-1-ylidene)succinate 3e
Starting from 1e, following the general procedure and using
CHCl3/MeOH (50:1) as eluent for the chromatography on silica gel,
the product was obtained as a yellowish oil (0.039 g, 22%), which
was crystallized in hexane at ꢁ95 ꢀC and recrystallized from hep-
tane/EtOAc to give colourless crystals. Mp 183–185 ꢀC. IR (KBr)

N.V. Chukanov et al. / Tetrahedron 64 (2008) 7432–7436
7435
3104, 2947, 2852, 1736, 1677, 1612, 1586, 1506, 1435, 1397, 1373,
1339, 138, 1263, 1171, 1121, 1055 cmꢁ1
dH (CDCl3): 1.12 (s, 3H, 4-CH3
3J¼8.8 Hz, 2H, Ar); dC (CDCl3): 19.4, 20.4, 20.6, 21.7, 28.7, 49.8, 51.4,
55.2, 68.2, 68.7, 81.0, 113.9, 127.8, 129.1, 159.4, 165.5, 165.7, 168.0,
178.7. Anal. Calcd for C21H28N2O6: C, 62.36; H, 6.98; N, 6.93. Found:
C, 62.66; H, 7.06; N, 6.80%.
.
or 5-CH3), 1.18 (s, 3H, 4-CH3 or 5-CH3), 1.22 (s, 3H, 4-CH3 or 5-CH3),
1.24 (s, 3H, 4-CH3 or 5-CH3), 3.47 (s, 3H, CO2CH3), 3.64 (s, 3H,
CO2CH3), 3.70 (s, 3H, OCH3), 6.68 (d, 3J¼8.8 Hz, 2H, Ar), 7.50 (d,
3J¼8.8 Hz, 2H, Ar), 10.28 (br s, 1H, NH); dC (CDCl3): 20.0, 21.1, 21.7,
23.1, 50.1, 51.3, 55.1, 64.4, 73.0, 93.6, 113.6, 116.7, 130.5, 162.8, 164.2,
167.6, 161.2, 174.2. Anal. Calcd for C20H26N2O6: C, 61.53; H, 6.71; N
7.18. Found: C, 61.29; H, 6.96; N, 7.01%.
4.3.10. Methyl 2,2,3,3-tetramethyl-5,6-dioxo-1-phenyl-2,3,5,6-
tetrahydro-1H-pyrrolo[1,2-a]imidazole-7-carboxylate 5d
A solution of 1d in 1 ml of DMSO was kept at 130 ꢀC for 5 h. The
resulting mixture was poured into 10 ml of CHCl3 and extracted
four times with 5 ml of water. The organic solution was dried
with MgSO4 and then evaporated. The crude product was purified
chromatographically on silica gel, with CHCl3/MeOH (100:1) and
recrystallized from hexane/toluene (0.017 g, 25%). Mp 209–
210.5 ꢀC. IR (KBr) 3052, 2987, 2954, 1757, 1683, 1602, 1578, 1498,
4.3.6. Dimethyl 2-(2-(4-nitrophenyl)-3,4,4,5,5-pentamethyl-4,5-
dihydro-1H-1l-5-3l-5-imidazol-1-ylidene)-3-oxosuccinate 3g
Starting from 1g, following the general procedure and using
CHCl3/MeOH (120:1) as eluent for the chromatography on silica gel,
the product was obtained as a yellow powder, which was recrys-
tallized from hexane/EtOAc (0.022 g, 29%). Mp 131.5–133.5 ꢀC. IR
(KBr) 3055, 2984, 2945, 1737, 1672, 1573, 1534, 1436, 1349, 1297,
1465, 1449, 1401, 1378, 1310, 1257, 1213, 1124 cmꢁ1
. dH (CDCl3): 1.30
(s, 6H, 2-CH3 or 3-CH3), 1.57 (s, 6H, 2-CH3 or 3-CH3), 3.26 (s, 3H,
CO2CH3), 7.20–7.23 (m, 2H, Ph), 7.44–7.48 (m, 3H, Ph); dC (CDCl3):
21.1, 22.2, 50.6, 63.8, 77.1, 86.6, 127.6, 129.1, 129.4, 135.2,159.9, 161.0,
165.1, 177.5. Anal. Calcd for C18H20N2O4: C, 65.84; H, 6.14; N, 8.53.
Found: C, 65.63; H, 6.12; N, 8.42%.
1208, 1186, 1146, 1113, 1082, 1036 cmꢁ1
. dH (CDCl3): 1.35 (s, 3H, 4-
CH3 or 5-CH3), 1.36 (s, 3H, 4-CH3 or 5-CH3), 1.43 (s, 3H, 4-CH3 or 5-
CH3), 1.48 (s, 3H, 4-CH3 or 5-CH3), 2.89 (s, 3H, NCH3), 3.47 (s, 3H,
CO2CH3), 3.61 (s, 3H, CO2CH3), 7.65 (br s, 2H, Ar), 8.26 (d, 3J¼9.0 Hz,
2H, Ar); dC (CDCl3): 19.7, 20.0, 20.5, 20.5, 23.3, 50.2, 51.4, 70.8, 72.5,
91.9, 123.6, 129.0, 130.3, 149.7, 165.0, 166.8, 168.7, 174.9. Anal. Calcd
for C20H25N3O7: C, 57.27; H, 6.01; N, 10.02. Found: C, 57.25; H, 6.03;
N, 10.24%.
4.3.11. Methyl 1-(4-methoxyphenyl)-2,2,3,3-tetramethyl-5,6-dioxo-
2,3,5,6-tetrahydro-1H-pyrrolo[1,2-a]imidazole-7-carboxylate 5e
Starting from 1e, following the general procedure and using
CHCl3/MeOH (80:1) as eluent for the chromatography on silica gel,
the product was obtained as a yellow powder (0.105 g, 60%), which
was recrystallized from EtOAc. Mp 204–205 ꢀC. IR (KBr) 3076, 2982,
2946, 2846, 1754, 1729, 1696, 1578, 1513, 1466, 1377, 1306, 1254,
4.3.7. Dimethyl 2-(1-(4-nitrophenyl)-3,4,4,5,5-pentamethyl-
imidazolidin-2-ylidene)-3-oxosuccinate 4g
Starting from 1g, following the general procedure and using
CHCl3/MeOH (120:1) as eluent for the column chromatography on
silica gel, the product was obtained as a yellow powder, which was
recrystallized from hexane/EtOAc (0.005 g, 7%). Mp 168–169.5 ꢀC.
IR (KBr) 3088, 2990, 2951, 1732, 1681, 1592, 1544, 1523, 1499, 1449,
1175, 1128, 1030 cmꢁ1
. dH (CDCl3): 1.24 (s, 6H, 2-CH3 or 3-CH3), 1.50
(s, 6H, 2-CH3 or 3-CH3), 3.20 (s, 3H, CO2CH3), 3.79 (s, 3H, OCH3),
6.90 (d, J¼8.8 Hz, 2H, Ar), 7.10 (d, J¼8.8 Hz, 2H, Ar); dC (CDCl3): 20.9,
21.9, 50.4, 55.3, 63.5, 77.0, 86.3, 114.0, 127.4, 128.7, 159.8, 159.8,
160.9, 164.9, 177.3. Anal. Calcd for C19H22N2O5: C, 63.67; H, 6.19; N,
7.82. Found: C, 64.04; H, 6.25; N, 7.89%.
1341, 1298, 1231, 1200, 1154, 1134, 1080, 1021 cmꢁ1
. dH (CDCl3): 1.25
(s, 3H, 4-CH3 or 5-CH3), 1.35 (s, 3H, 4-CH3 or 5-CH3), 1.38 (s, 3H, 4-
CH3 or 5-CH3), 1.39 (s, 3H, 4-CH3 or 5-CH3), 3.05 (s, 3H, NCH3), 3.38
(s, 3H, CO2CH3), 3.72 (s, 3H, CO2CH3), 7.36 (d, 3J¼8.7 Hz, 2H, Ar),
8.21 (d, 3J¼8.7 Hz, 2H, Ar); dC (CDCl3): 19.4, 20.6, 20.7, 22.0, 28.9,
50.2, 51.6, 69.0, 69.1, 81.5, 124.2, 127.5, 142.2, 146.7, 165.0, 165.4,
167.5, 179.4. Anal. Calcd for C20H25N3O7: C, 57.27; H, 6.01; N, 10.02.
Found: C, 57.31; H, 6.12; N, 9.97%.
4.3.12. Methyl 1-(4-(dimethylamino)phenyl)-2,2,3,3-tetramethyl-
5,6-dioxo-2,3,5,6-tetrahydro-1H-pyrrolo[1,2-a]imidazole-7-
carboxylate 5f
Startingfrom1f, followingthegeneralprocedure(4 mlofbenzene
was a solvent, reaction time 2 h), the product was obtained as a yel-
low powder, which was recrystallized from hexane/EtOAc (0.122 g,
88%). Mp 189–191 ꢀC. IR (KBr) 2982, 2923, 2810, 1755, 1688, 1586,
4.3.8. Dimethyl 2-(1-phenyl-3,4,4,5,5-pentamethylimidazolidin-2-
ylidene)-3-oxosuccinate 4h
1523,1458,1359,1254,1215,1193,1122,1020 cm .
ꢁ1 dH (CDCl3):1.26(s,
6H, 2-CH3 or3-CH3),1.53(s, 6H, 2-CH3 or3-CH3), 2.99(s,3H,N(CH3)2),
3.29 (s, 3H, CO2CH3), 6.66 (d, J¼8.8 Hz, 2H, Ar), 7.01 (d, J¼8.8 Hz,
2H, Ar); dC (CDCl3): 20.9, 21.8, 40.0, 50.4, 63.4, 77.0, 86.4, 111.3, 122.8,
127.9, 150.2, 160.1, 160.9, 164.6, 177.3. Anal. Calcd for C20H25N3O4: C,
64.67; H, 6.78; N, 11.31. Found: C, 64.34; H, 6.80; N, 11.10%.
Starting from 1h, following the general procedure, the product
was obtained as a white powder, which was recrystallized from
heptane (0.035 g, 78%). Mp 171–172 ꢀC. IR (KBr) 2988, 2951, 1735,
1673, 1579, 1539, 1506, 1431, 1396, 1376, 1350, 1297, 1209, 1152,
1133, 1071, 1022 cmꢁ1
. dH (CDCl3): 1.16 (s, 3H, 4-CH3 or 5-CH3), 1.34
(s, 3H, 4-CH3 or 5-CH3), 1.36 (s, 6H, 4-CH3 or 5-CH3), 3.02 (s, 3H,
NCH3), 3.34 (s, 3H, CO2CH3), 3.70 (s, 3H, CO2CH3), 7.15–7.17 (m, 2H),
7.30–7.35 (m, 3H); dC (CDCl3): 19.4, 20.6, 22.0, 28.9, 49.8, 51.4, 68.4,
68.7, 127.7, 128.5, 128.8, 135.6, 165.4, 165.7, 168.0, 179.0. Anal. Calcd
for C20H26N2O5: C, 64.15; H, 7.00; N, 7.48. Found: C, 64.47; H, 7.07;
N, 7.47%.
4.3.13. Methyl 2,2,3,3-tetramethyl-5,6-dioxo-1-[(E)-2-phenylvinyl]-
2,3,5,6-tetrahydro-1H-pyrrolo[1,2-a]imidazole-7-carboxylate 5j
Starting from 1j, following the general procedure (4 ml of benzene
was a solvent, reaction time 37 h), the product was obtained as a yel-
low powder, which was recrystallized from EtOAc (0.024 g, 53%). Mp
202.5–204 ꢀC. IR (KBr) 3068, 2986, 2946,1758,1678,1562,1456,1402,
1379, 1256, 1225, 1189, 1157, 1129 cmꢁ1
. dH (CDCl3): 1.47 (s, 6H, 2-CH3
4.3.9. Dimethyl 2-(1-(4-methoxyphenyl)-3,4,4,5,5-pentamethyl-
imidazolidin-2-ylidene)-3-oxosuccinate 4i
or 3-CH3), 1.48 (s, 6H, 2-CH3 or 3-CH3), 3.68 (s, 3H, CO2CH3), 6.52 (d,
J¼14.7 Hz, 1H, CH), 7.26–7.43 (m, 5H, Ph), 7.50 (d, J¼14.7 Hz, 1H, CH);
dC (CDCl3): 20.5, 21.9, 51.3, 63.8, 76.6, 87.3, 122.3, 126.4, 128.8, 126.6,
128.5, 134.0, 159.2, 162.2, 163.9, 177.2. Anal. Calcd for C20H22N2O4:
C, 67.78; H, 6.26; N, 7.90. Found: C, 67.30; H, 6.10; N, 7.75%.
Starting from 1i, following the general procedure, the product
was obtained as a white powder, which was recrystallized from
hexane/EtOAc (0.030 g, 46%). Mp 144–145.5 ꢀC. IR (KBr) 2982, 2951,
2839,1732, 1673,1582,1515,1435, 1397, 1374,1350, 1295,1251, 1197,
1154, 1133, 1079,1022 cmꢁ1
.
dH (CDCl3): 1.12 (s, 3H, 4-CH3 or 5-CH3),
4.3.14. Dimethyl 2-tert-butyl-3-[4-(dimethylamino)phenyl]-2,3-
dihydroisoxazole-4,5-dicarboxylate 6b
The solution of 0.36 g (1.63 mmol) N-(4-{[tert-butyl(oxido)-
imino]methyl}phenyl)-N,N-dimethylamine and 0.24 ml (1.96 mmol)
1.29 (s, 3H, 4-CH3 or 5-CH3), 1.31 (s, 3H, 4-CH3 or 5-CH3), 1.32 (s, 3H,
4-CH3 or 5-CH3), 2.98 (s, 3H, NCH3), 3.35 (s, 3H, CO2CH3), 3.68 (s,
3H, CO2CH3), 3.74 (s, 3H, OCH3), 6.80 (d, 3J¼8.8 Hz, 2H, Ar), 7.05 (d,

7436
N.V. Chukanov et al. / Tetrahedron 64 (2008) 7432–7436
dimethyl but-2-ynedioate in 5 ml CHCl3 was kept for 36 h at 20 8C.
After evaporation of the reaction mixture the product was sepa-
rated by chromatographing on alumina with hexane/EtOAc (4:1) as
eluent. Compound 6b was obtained as white powder, which was
recrystallized from hexane (0.144 g, 24%). Mp 74–75 ꢀC. IR (KBr)
2984, 2947, 2808, 1748, 1706, 1661, 1615, 1526, 1439, 1341, 1247,
CO2CH3), 6.58 (d, J¼9.0 Hz, 2H, Ar), 6.86 (d, J¼9.0 Hz, 2H, Ar), 8.34
(s, 1H, CH); dC (CDCl3): 29.9, 40.2, 51.3, 52.0, 62.7, 67.1, 111.3, 129.2,
128.0, 149.8, 152.7, 165.0, 166.8. Anal. Calcd for C19H26N2O5: C,
62.97; H, 7.23; N, 7.73. Found: C, 62.99; H, 7.20; N, 7.49%.
References and notes
1207,1121, 1064,1034 cmꢁ1
. dH (CDCl3): 1.15 (s, 9H, C(CH3)3), 2.92 (s,
6H, N(CH3)2), 3.56 (s, 3H, CO2CH3), 3.86 (s, 3H, CO2CH3), 5.22 (s, 1H,
CH), 6.59 (d, J¼8.8 Hz, 2H, Ar), 7.13 (d, J¼8.8 Hz, 2H, Ar); dC (CDCl3):
24.6, 40.3, 51.4, 52.3, 61.6, 67.1, 109.7, 112.2, 128.0, 129.3, 150.0, 151.6,
159.6, 162.5. Anal. Calcd for C19H26N2O5: C, 62.97; H, 7.23; N, 7.73.
Found: C, 62.62; H, 7.33; N, 7.73%.
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4.3.15. Dimethyl 2-({tert-butyl[4-(dimethylamino)phenyl]amino}-
methylene)-3-oxosuccinate 8b
The solution of 0.10 g (0.28 mmol) 6b in 1 ml toluene was
heated for 14 h at 105 8C. After evaporation of the reaction mixture
the product was separated by chromatographing on silica gel, using
CHCl3/MeOH as eluent (0.024 g, 24%). Mp 117–178 ꢀC. IR (KBr) 3050,
2952, 2858, 2817, 1724, 1691, 1649, 1609, 1541, 1516, 1443, 1394,
1368, 1340, 1251, 1229, 1180, 1150, 1023 cmꢁ1
9H, C(CH3)3), 2.92 (s, 6H, N(CH3)2), 3.14 (s, 3H, CO2CH3), 3.72 (s, 6H,
. dH (CDCl3): 1.35 (s,