Thermolysis of dimethyl Cis- and Trans-1 pthalimidoaziridine-2,3- dicarboxylates in the presence of dipolarophiles

Article abstract of DOI:10.1134/S1070428009080144

Thermolysis of dimethyl esters of stereoisomeric phthalimidoaziridine-2,3- dicarboxylic acids in the presence of dimethyl fumarate, dimethyl maleate, and N-phenylmaleimide occurred stereo-specifically and stereoselectively led to the formation of derivati

Full text of DOI:10.1134/S1070428009080144

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2009, Vol. 45, No. 8, pp. 1200−1207. © Pleiades Publishing, Ltd., 2009.
Original Russian Text © M.A. Kuznetsov, A.V. Ushkov, S.I. Selivanov, A.S. Pan’kova, A. Linden, 2009, published in Zhurnal Organicheskoi Khimii,
2009, Vol. 45, No. 8, pp. 1209−1216.
Thermolysis of Dimethyl cis-
and trans-1 Pthalimidoaziridine-2,3-dicarboxylates
in the Presence of Dipolarophiles
M. A. Kuznetsova, A. V. Ushkova, S. I. Selivanova, A. S. Pan’kovaa, andA.Lindenb
aSt. Petersburg State University, St. Petersburg, 198504 Russia
e-mail: mak@mail.wplus.net
.. ..
bOrganisch-chemisches Institut der Universitat Zurich
Received September 24, 2008
Abstract—Thermolysis of dimethyl esters of stereoisomeric phthalimidoaziridine-2,3-dicarboxylic acids in the
presence of dimethyl fumarate, dimethyl maleate, and N-phenylmaleimide occurred stereo-specifically and
stereoselectively led to the formation of derivatives of 1-phthalimidopyrrolidine, products of 1,3-dipolar additrion
of intermediately arising azomethine ylides. In keeping with the rules of the conservation of orbital symmetry the
thermal opening of the 2,3-disubstituted 1-phthalimidoaziridines into azomethine ylides occurred conrotatory.
The relative positions of the substituents in the dipolarophiles is retained in the reaction products indicating the
concerted addition mechanism.
DOI: 10.1134/S1070428009080144
We recently showed that the thermolysis of trans-
2,3-disubstituted N-phthalimidoaziridines with nitrile
substituents in the presence of various dipolarophiles
proceeded stereospecifically, stereoselectively, and
afforded in good yields the corresponding derivatives of
N-aminopyrrolidine and therefore might underlie a general
preparation method of these unavailable compounds [1].
The target of this study was the extension of the approach
to 2,3-disubstituted N-phthalimidoaziridines I and II with
methoxycarbonyl substituents that far weaker activated
the cleavage of the C–C bond than the cyano group (cf.
[1] and references therein). Besides we aimed to reveal
the spatial relationships of this process not only by the
example of trans- I, but also cis-2,3-disubstituted aziridine
II in combination with dipolarophiles IIIa–IIIc with
electron-deficient double carbon-carbon bonds differing
in activity and spatial arrangement.
ture. It turned out however that at –15...–18°C the
reaction with dimethylfumarate gave aziridine I in only
13–20% yield. Yet at the room temperature (18–23°C)
its yield grew to 85%. Aziridine II was obtained at 0°C.
The characteristics of N-phthalimidoaziridines I and
II are well consistent with the published data [3–5]. The
inversion of the endocyclic nitrogen atom slow in the
NMR time scale [6] is degenerate for aziridine I, and in
its 1H NMR spectrum in the region δ 4.8–4.9 ppm two
characteristic doublets are present of AX system from
the protons of the aziridine ring existing in a single form.
Aziridine II, in keeping with the NMR data, at room
temperature existed as an only invertomer, evidently, with
Aziridines I and II were obtained from N-amino-
phthalimide and the appropriate unsaturated esters by
oxidative aminoaziridination [2]. Inasmuch as the strained
three-membered ring possesses a low stability the
oxidative addition of the N-aminophthalimide to unsaturat-
ed compounds is commonly performed at low tempera-
1200

THERMOLYSIS OF DIMETHYL cis- AND trans-1 PTHALIMIDOAZIRIDINE
1201
the syn-orientation of the aziridine proton and the
phthalimide group.
formation. On workup of the reaction mixtures in all cases
we obtained from aziridines I and II the products of 1,3-
dipolar cycloaddition: previously unknown N-phthal-
imidopyrrolidines IVa–IVc and Va–Vc respectively nearly
always as a single stereoisomer. The reaction of aziridine
II with dimethyl fumarate IIIa was an exception for it
gave a mixture of diastereomers Va1 and Va2 and also
oxazole VII formed apparently through an intramolecular
cyclization of the intermediate azomethine ylide followed
by aromatization of oxazoline VI by elimination of
a phthalimide molecule (Scheme 2).
The thermolysis of aziridines I and II was carried out
in sealed ampoules and/or in an air-tight glass reactor in
the presence of a 50% excess of the dipolarophile.
Benzene or chlorobenzene served as solvents. The
reaction of aziridines I and II with dipolarophiles IIIa–
IIIc started with appreciable velocity only at heating to
220°C. TLC monitoring showed that under these
conditions in about 3 h aziridines I and II completely
converted into the thermolysis products (Scheme 1).
The formation of 5-alkoxyoxazoles from alkoxy-
carbonyl-substituted N-phthalimidoaziridines was already
described [7], but here we report on the first example of
this conversion of 2,3-disubstituted N-phthalimido-
aziridines.
Similarly to the previous reaction series [1] we
observed in the process a strong tarring and phthalimide
Scheme 1.
R
The formation in the thermolysis only of the above
listed compounds was confirmed by 1H NMR spectra of
the reaction mixtures taken just after their cooling.
Compound Vb is a viscous oily fluid, all other products of
these reactions are crystalline substances. The
composition of N-phthalimidopyrrolidines IV and V was
proved by elemental analysis, and the structure was in
total agreement with the 1H, 13C NMR, and mass spectra
where the same regularities were observed as in the
spectra of compounds with the cyano substituents [1]. In
particular, the rotation of phthalimide group slow in the
NMR time scale is characteristic of these compounds;
therefore at the lack of axial symmetry of the molecule
the 13C signals of the imide carbon atoms (δ 164–
165ppm) are strongly broadened or totally absent, and
the other signals from the phthalimide fragment are also
broadened.
R'
3 h
220oC
+ IIIа_IIIc
Pi N+
I, II
_
H
MeOOC
R'
R
N
R''
R''
Pi
MeOOC
IVа_IVc (29_48%),
Vа_Vc (22_88%)
O
N
COOMe
COOMe
Ph
MeOOC
IIIa
COOMe
O
IIIc
IIIb
The spatial arrangement of compounds obtained was
established mostly in the same way that we had applied
before [1]. Obviously for pyrrolidines IV and V with
identical in pairs substituents at α- and β-carbon atoms 6
diastereomeric structures are theoretically possible: two
with a symmetry plane σ (symmetry Cs), two with the
second order symmetry axis C2, and two without
symmetry elements. Therewith in adducts IVa and Vb,
Vc all four protons of the pyrrolidine ring are aniso-
chronous and form ABXY system. Consequently in their
1H NMR spectra the signals of H3 and H4 appear as
doublets of doublets or triplets indicating that pyrrolidines
IVa and Vb, Vc lack any symmetry elements. In contrast,
in compounds IVb, IVc, and Va1,2 the four ring protons
appear as only two signals of AA'XX' system
demonstrating the symmetry of their molecules. These
Scheme 2.
MeOOC
Pi N+
220oC
O
O
II
_
COOMe
O
Pi
MeOOC
O
N
O
O
_PiH
N
VII
VI
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 8 2009

KUZNETSOV et al.
1202
Scheme 3.
small NOE
H3
small NOE
MeOOC
H5
H2
H4
COOMe
MeOOC
COOMe
small NOE
N
Pi
large NOE
Pi
N
MeOOC
COOMe
H4
MeOOC
COOMe
H3
H5
H2
large NOE
large NOE
Vb
IVa
data are in agreement with the presence in the 13C NMR
spectra of four carbon signals of pyrrolidine ring for
adduct IVa, three for adducts Vb, Vc (signals of atoms
C3 and C4 coincide), and only two for compounds IVb,
IVc, and Va1,2.
of compound IVa the relative NOE value for the pair of
the cis-located vicinal protons H2–H3 is essentially larger
than for the other two pairs of the trans-located protons
H3–H4 and H4–H5 (Scheme 3).
For the three symmetrical stereoisomeric adducts IVb
and Va1,2 the choice should be made from four theoretical-
ly possible structures: IVb1, IVb2 with a mirror plane
and protons enantiotopic in pairs, and Va1, Va2 with the
second order rotation axis and protons equivalent in pairs
(Scheme 4).
The assignment of structures of two unsymmetrical
stereoisomeric compounds IVa and Vb was performed
owing to 2D NOESY spectra. In the spectrum 2D
NOESY of compound Vb obviously the relative NOE
value for the pair of protons H2–H3 is considerably smaller
that for the pairs H3–H4 and H4–H5 leading at once just
to the assumed structure. Besides a cross-peak appears
for the protons pair H3–H5 indicating their location on
the same side of the pyrrolidine ring plane; this additionally
confirms the validity of the assignment.
To distinguish the symmetry type of these compounds
molecules we registered their 13C NMR spectra at low
temperature. At reduced temperature the sterically
hampered rotation around the N–N bond became even
slower; then the spectra of molecules lacking the axial
symmetry (C2 axis) should reveal the nonequivalence of
two halves of the phthalimide fragment (cf. [1]). Thus in
the 13C NMR spectrum of compound IVb already at
–10°C two signals of N–C=O appeared that at room
temperature coincided with the base line, split in two the
signal of atom Cb, and the signals of atoms Ca and Cc
Inasmuch as with the given set of substituents only
two structures without symmetry elements are possible
the assignment to the second unsymmetrical adduct
structure IVa with a pair of cis- and two pairs of trans-
vicinal protons would be possible simply by exclusion. In
full agreement with the above in 2D 1H NOESY spectrum
Scheme 4.
MeOOC
MeOOC
COOMe
COOMe
COOMe
s
Pi
N
Pi
N
COOMe
MeOOC
MeOOC
MeOOC
MeOOC
IVb1
IVb2
COOMe
COOMe
COOMe
COOMe
Pi
N
Pi
N
C2
MeOOC
MeOOC
Va1
Va2
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 8 2009

THERMOLYSIS OF DIMETHYL cis- AND trans-1 PTHALIMIDOAZIRIDINE
1203
Fig. 1. 2D NOESY spectrum of the mixture of compounds Va1, Va2, 1 : 1.
turned out for the mixture IVb and Va1 that the NOE
values for proton pairs H2,5-H3,4 were nearly identical in
both compounds. It shows their trans-position also in
compound IVb that therefore has the structure IVb1,
expectedly, for the formation under the severe thermolysis
conditions the sterically strained structure IVb2 as the
sole product seems highly improbable.
significantly broadened.At –40°C all the four signals were
split in two unambiguously indicating that in the molecules
of adduct IVb the mirror plane and not the symmetry
axis was present. On the contrary, the spectra of com-
pounds Va1 and Va2 remained virtually unchanged on
cooling to –40°C. Therefore their molecules possess
a symmetry axis C2.
For the final assignment of structures of compounds
IVb and Va1,2 we registered the NOESY spectra of mix-
tures of equal amounts of compounds Va1, Va2 (Fig. 1)
and IVb,Va1.
In the spectrum of the pair of compounds Va1, Va2
whose molecules have the axial symmetry it is well seen
that the relative NOE value for proton pairs H2,5-H3,4 for
compound Va2 is essentially larger than in compound Va1
that unambiguously indicates the cis-position of proton
pairs H2,5-H3,4 in compound Va2 and their more favorable
trans-location in the main product, compound Va1. It
In the analysis of the spatial structure of bicyclic
compounds IVc and Vc we excluded from the con-
sideration the versions with very unfavorable trans-junc-
tion of two five-membered rings. Under this restriction
the structure of compound Vc unambiguously follows
directly from the lack of symmetry elements in its
molecule, and for adduct IVc only structures of the type
IVb1 or IVb2 can be regarded having a symmetry plane
and distinguished by the position of methoxy-carbonyl
groups and N phenylmaleimide fragment with respect to
the plane of the pyrrolidine ring. Evidently the exo-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 8 2009

KUZNETSOV et al.
1204
NC
N
structure is more probable, and it was assigned to
compound IVc.
CN
CN
COOMe
COOMe
C6H5Cl, 220oC
+ IIIb
Pi
N
Pi
This assignment is well consistent with the already
proved spatial structure of adduct IVb obtained from
aziridine I with dimethyl maleate (IIIb). An additional
argument to its validity are the results of XRD analysis
of compound IX (Fig. 2) that we have obtained formerly
[1] from (Ε)-1-phthalimidoaziridine-2,3-dinitrile (VIII) and
dimethyl maleate (IIIb).
NC
VIII
IX
(IIIa), both possible stereo-isomers, Va1 and Va2, are
present in the reaction mixture, but even here significantly
prevails the less strained “all-trans” adduct Va1.
It is clear from Fig. 2, that in total agreement with the
above stated the cyano and methoxycarbonyl groups in
adduct IX are removed from each other. We can add to
this statement that in no cases up till now (see [1]) we
have detected the formation in such reactions of “all-
cis” adducts (adducts of endo-type) having all four
substituents on one side of the pyrrolidine ring.
The limiting stage of the whole process is apparently
the opening of the aziridine ring into the azomethine ylide
whose rate should mainly be governed by the substituents
in the three-membered ring. In this connection it is curious
that the temperature of the start of the reaction with
dipolarophiles of 1-phthalimidoaziridines I, II containing
two methoxycarbonyl substituents is practically the same
(220°C) as for the previously studied dinitrile [1], although
it is assumed that CN group activates this process far
stronger. The complete stereospecificity of both stages
also should be stressed for it does not always occur with
aziridines having other substituents at the nitrogen. It may
be stated in conclusion that disregarding the severe
reaction conditions the thermolysis of 2,3-disubstituted
N phthalimidoaziridines in the presence of dipolarophile
can really serve as a general stereospecific and highly
stereoselective method of synthesis of N-aminopyrrolidine
derivatives.
The results obtained completely correspond to the two-
stage mechanism we had previously suggested [1]: The
beginning of the process was the permitted in the
thermolysis by the rules of orbital symmetry conservation
conrotatory opening, probably, reversible, of 2,3-
disubstituted 1-phthal-imidoaziridines I, II into the
corresponding azomethine ylides. Then the concerted
cycloaddition of these 1,3-dipoles occurred to the multiple
bonds of dipolarophiles IIIa–IIIc, and both stages
proceeded completely stereo-specifically, and the
cycloaddition was highly stereoselective. Thus in the
reactions of trans-disubstituted aziridine I with dimethyl
maleate (IIIb) and N-phenylmaleimide (IIIc) formed only
the less sterically strained adducts IVb, IVc of exo-type.
When the cycloaddition products are of comparable stability,
like in the reaction of cis-aziridine II with dimethyl fumarate
EXPERIMENTAL
1H and 13C NMR spectra were registered on a spec-
trometer Bruker DPX-300 (300 MHz), as internal
reference served the signals of residual protons (δ 7.26
and 2.50 ppm) and carbon atoms (δ 77.16 and 39.50 ppm
respectively) of solvents. Mass spectra were obtained
on an instrument MKh-1303, the energy of ionizing
electrons 70 eV. Elemental analysis was carried out on
an automatic CHN-analyzer HP-185B. The composition
of reaction mixtures and the fractions obtained at their
separation, and also the purity of isolated products were
checked by TLC on Polygram sil G/UV254 and Alugram
sil G/UV254 plates purchased from Macherey-Nagel.
Melting points were measured on a device Buchi Melting
point B-540. N-Aminophthalimide was obtained by
procedure [8].
Dimethyl trans-1-phthalimidoaziridine-2,3-
dicarboxylate I. To a dispersion of 1.3 g (9.4 mmol) of
anhydrous potassium carbonate in solution of 432 mg
Fig. 2. Structure of compound IX according to XRD analysis.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 8 2009

THERMOLYSIS OF DIMETHYL cis- AND trans-1 PTHALIMIDOAZIRIDINE
1205
CH2Cl2–THF, from 1:0 to 20:1 v/v). We obtained 100 mg
(33%) of initial N-phthalimidoaziridine I(Rf 0.65, CH2Cl2),
40 mg (27%) of phthalimide (Rf 0.25, CH2Cl2), and
130 mg (29%) of compound IVa (Rf 0.1, CH2Cl2), mp
136–138°C. 1H NMR spectrum (CDCl3), δ, ppm: 3.68 s
(3H, MeO), 3.70 s (6H, 2MeO), 3.79 s (3H, MeO),
4.06 t (1H, H4, J 8.4 Hz), 4.14 t (1H, H3, J 8.4 Hz),
4.50 d (2H, H2,5, J 8.4 Hz), 7.50–7.90 m (4H, Pi).
13C NMR spectrum (CDCl3), δ, ppm: 46.82 and 47.17
(C3,4); 52.66, 52.72, 52.91, 52.96 (4MeO); 66.39 and
66.67 (C2,5); 123.87 (Cb), 129.97 (Ca), 134.75 (Cc),
169.00, 169.51, 169.64, 170.92 (4COO). Signal of NC=O
was not seen due to slow rotation of phthalimide fragment.
Mass spectrum, m/z (Irel, %): 448 (1) [M]+, 357 (31), 302
(34), 297 (100), 270 (41), 59 (25). Found, %: C 53.33;
H 4.49; N 6.21. C20H20N2O10. Calculated, %: C 53.57;
H 4.50; N 6.25.
(3 mmol) of dimethyl fumarate (IIIa) in 40 ml of
dichloromethane at room temperature (18–23°C) within
40 min was added by portions of 10–15 mg by turns 486
mg (3 mmol) of N-aminophthalimide and 1.33 g (3 mmol)
of lead tetraacetate. The reaction mixture was stirred
for 1 h more, filtered through a thin bed of silica gel, and
the solution was distilled off on a rotary evaporator. Yield
775 mg (85%), mp 158°C (149–150°C [3], 151°C [4,
1
5]). H NMR spectrum (CDCl3), δ, ppm: 3.60 d (1H,
CH, J 4.8 Hz), 3.74 s (3H, MeO), 3.86 s (3H, MeO),
3.96 d (1H, CH, J 4.8 Hz), 7.65–7.79 m (4H, Pi).
13C NMR spectrum (CDCl3), δ, ppm: 42.65 and 44.65
(2CH), 53.13 and 53.27 (2MeO), 123.33 (Cb), 129.90
(Ca), 134.21 (Cc), 164.01 (CON), 165.25 and 166.52
(2COO). Mass spectrum, m/z (Irel, %): 304 (30) [M]+,
245 (100), 201 (40), 132 (38), 130 (38), 113 (60), 105
(92), 76 (100). Found, %: C 55.42; H 3.99; N 9.21.
C14H12N2O6. Calculated, %: C 56.27; H 3.98; N 9.21.
Tetramethyl rel-(2R,3R,4S,5S)-1-phthalimidopyr-
rolidine-2,3,4,5-tetracarboxylate (IVb). A solution of
304 mg (1 mmol) of aziridine I and 0.19 ml (216 mg,
1.5 mmol) of dimethyl maleate (IIIb) in 10 ml of
anhydrous chlorobenzene was heated for 3 h in a thick-
walled glass reactor at 220°C. On completion of the
reaction the solvent was distilled off in a vacuum on
a rotary evaporator. The obtained dry residue was
subjected to chromatography on a column packed with
45 g of silica gel (gradient elution with a mixture CH2Cl2–
Et2O, from 1:0 to 9:1 v/v). We obtained 35 mg (20%) of
phthalimide (Rf 0.25, CH2Cl2), and 170 mg (38%) of com-
pound IVb (Rf 0.15, CH2Cl2), mp 121–124°C. 1H NMR
spectrum (CDCl3), δ, ppm: 3.68 s (6H, 2MeO), 3.78 s
(6H, 2MeO), 3.86 m (2H, H3,4), 4.64 m (2H, H2,5), 7.70–
7.90 m (4H, Pi). 13C NMR spectrum (CDCl3, 20–25°C),
δ, ppm: 45.64 (C3,4), 52.72 (2MeO), 53.02 (2MeO), 65.81
(C2,5), 123.80 (Cb), 129.95 (Ca), 134.70 (Cc), 169.51
(2COO), 170.39 (2COO). Signal of NC=O was not seen
due to slow rotation of phthalimide fragment. 13C NMR
spectrum (CDCl3, –40°C), δ, ppm: 45.04 (C3,4), 53.10
(2MeO), 53.46 (2MeO), 65.46 (C2,5), 123.60 and 124.22
(Cb,b'), 129.07 and 129.28 (Ca,a'), 134.81 and 135.02 (Cc,c'),
165.29 and 166.49 (CON and C'ON), 169.58 (2COO),
170.53 (2COO). Mass spectrum, m/z (Irel, %): 448 (1)
[M]+, 302 (100), 297 (86), 270 (15), 239 (25), 130 (11), 104
(19), 76 (15), 59 (27). Found, %: C 53.63; H 4.46; N 6.28.
C20H20N2O10. Calculated, %: C 53.57; H 4.50; N 6.25.
Dimethyl cis-1-phthalimidoaziridine-2,3-di-
carboxylate II. To a dispersion of 1.3 g (9.4 mmol) of
anhydrous potassium carbonate in cooled to 0°C solution
of 1.13 ml (1.3 g, 9 mmol) of dimethyl -maleate (IIIb) in
40 ml of dichloromethane at room temperature (18–23°C)
within 40 min was added by portions of 10–15 mg by
turns 486 mg (3 mmol) of N-aminophthalimide and 1.33 g
(3 mmol) of lead tetraacetate. The reaction mixture was
stirred for 1 h more, filtered through a thin bed of silica
gel, and the solution was distilled off on a rotary
evaporator. The oily residue was dissolved in 5 ml of
ethyl ether and was left overnight in a refrigerator. On
the next day the separated precipitate was recrystallized
from methanol. Yield 310 mg (34%), mp 140°C (137°C
[4, 5]). 1H NMR spectrum (CDCl3), δ, ppm: 3.64 s (2H,
2CH), 3.86 s (6H, 2MeO), 7.70–7.85 m (4H, Pi).
13C NMR spectrum (CDCl3), δ, ppm: 44.93 (CH), 53.05
(MeO), 123.52 (Cb), 129.72 (Ca), 134.53 (Cc), 163.98
(CON), 165.45 (COO). Mass spectrum, m/z (Irel, %):
304 (5) [M]+, 245 (60), 213 (12), 113 (20), 104 (100), 76
(80). Found, %: C 55.26; H 4.03; N 9.10. C14H12N2O6.
Calculated, %: C 56.27; H 3.98; N 9.21.
Tetramethyl rel-(2R,3S,4S,5S)-1-phthalimidopyr-
rolidine-2,3,4,5-tetra-carboxylate (IVa). A solution of
304 mg (1 mmol) of aziridine I and 216 mg (1.5 mmol) of
dimethyl fumarate (IIIa) in 10 ml of anhydrous benzene
in a sealed ampule was heated at 220°C for 3 h. On
completion of the reaction the solvent was distilled off in
a vacuum on a rotary evaporator. The obtained dry residue
was subjected to chromatography on a column packed
with 45 g of silica gel (gradient elution with a mixture
Dimethyl rel-(1R,2R,4S,5S)-6,8-dioxo-7-phenyl-
3-phthalimido-3,7-diazabicyclo-[3.3.0]octane-2,4-
dicarboxylate (IVc). A solution of 304 mg (1 mmol) of
aziridine I and 260 mg (1.5 mmol) of phenylmaleimide
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 8 2009

KUZNETSOV et al.
1206
[M]+, 389 (12), 357 (43), 302 (57), 297 (100), 270 (62),
239 (23), 210 (12), 166 (12), 130 (14), 104 (18), 76 (16),
59 (25). Found, %: C 53.62; H 4.54; N 6.15.
C20H20N2O10. Calculated, %: C 53.57; H 4.50; N 6.25.
Pyrrolidine Va2 in the mixture with compound Va1.
1H NMR spectrum (CDCl3), δ, ppm: 3.62 s (6H, 2MeO),
3.71 s (6H, 2MeO), 4.15 m (2H, H3,4), 4.82 m (2H, H2,5),
7.70–7.90 m (4H, Pi). 13C NMR spectrum (CDCl3), δ,
ppm: 45.80 (C3,4), 52.69 (4MeO), 63.46 (C2,5), 123.82
(Cb), 129.91 (Ca), 134.77 (Cc), 166.24 (CON), 169.35
(2COO), 170.27 (2COO).
(IIIc) in 10 ml of anhydrous benzene was heated for 3 h
in a sealed ampoule at 220°C. On completion of the
reaction the solvent was distilled off in a vacuum on
a rotary evaporator. The obtained dry residue was
subjected to chromatography on a column packed with
45 g of silica gel (eluent a mixture CH2Cl2–dioxane, 70 :
3 v/v). We obtained 30 mg (20%) of phthalimide (Rf 0.25,
CH2Cl2) and 230 mg (48%) of compound IVc (Rf 0.20,
1
CH2Cl2), mp 237–239°C. H NMR spectrum (CDCl3),
δ, ppm: 3.76 s (6H, 2MeO), 4.18 m (2H, H1,5), 4.57 m
(2H, H2,4), 7.40–7.48 m (3H, Hm,p), 7.48–7.55 m (2H,
HO), 7.75–7.95 m (4H, Pi). 13C NMR spectrum (CDCl3),
δ, ppm: 46.38 (C1,5), 53.35 (2MeO), 67.61 (C2,4), 124.03
(Cb), 126.78 and 129.42 (Co,m), 129.11 (Cp), 129.70 (Ca),
131.72 (Ci), 134.92 (Cc), 169.07 (COO), 174.86 (CON).
Signal of NC=O was not seen due to slow rotation of
phthalimide fragment. Mass spectrum, m/z (Irel, %): 477
(4) [M]+, 447 (62), 445 (74), 419 (21), 418 (79), 390 (100),
389 (52), 333 (58), 239 (100), 152 (33), 119 (25), 104
(42), 76 (35), 59 (31). Found, %: C 60.25; H 4.03; N 8.67.
C24H19N3O8. Calculated, %: C 60.38; H 4.01; N 8.80.
1
Oxazole (VII). H NMR spectrum (CDCl3), δ, ppm:
3.96 s (3H, MeO), 4.00 s (3H, MeO), 6.35 s (1H, CH).
13C NMR spectrum (CDCl3), δ, ppm: 53.02 (MeO), 59.00
(MeO), 102.0 (CH), 143.12 (C=N), 155.79 (COO), 162.11
(COO). Mass spectrum, m/z (Irel, %): 157 (38) [M]+, 126
(15), 68 (28), 59 (89), 55 (23), 54 (38), 43 (100). Found,
%: C 46.20; H 4.70; N 8.81. C6H7NO4. Calculated, %:
C 45.86; H 4.46; N 8.92.
Tetramethyl rel-(2R,3R,4S,5R)-1-phthalimido-
pyrrolidine-2,3,4,5-tetracarboxylate (Vb). A solution
of 304 mg (1 mmol) of aziridine II and 0.19 ml (216 mg,
1.5 mmol) of dimethyl maleate (IIIb) in 10 ml of
anhydrous chlorobenzene was heated for 3 h in a thick-
walled glass reactor at 220°C. On completion of the
reaction the solvent was distilled off in a vacuum on
a rotary evaporator. The obtained dry residue was
subjected to chromatography on a column packed with
40 g of silica gel (gradient elution with a mixture CH2Cl2–
Et2O, from 1:0 to 9:1 v/v). We obtained 30 mg (10%) of
initial aziridine II (Rf 0.27, CH2Cl2), 60 mg (41%) of
phthalimide (Rf 0.25, CH2Cl2), and 154 mg (34%) of oily
product Vb (Rf 0.15, CH2Cl2). 1H NMR spectrum
(CDCl3), δ, ppm: 3.57 s (3H, MeO), 3.68 s (3H, MeO),
3.74 s (3H, MeO), 3.76 s (3H, MeO), 3.86 d.d (1H, H4,
J 8.0, 6.5 Hz), 4.05 d.d (1H, H3, J 8.0, 8.0 Hz), 4.89 d
(1H, H5, J 6.5 Hz), 5.08 d (1H, H2, J 8.0 Hz). 7.70–7.90
m (4H, Pi). 13C NMR spectrum (CDCl3, 20–25°C), δ,
ppm: 45.43 (C3,4), 52.38, 52.65, 52.94 (4MeO), 62.84 and
64.71 (C2,5), 123.67 (Cb), 129.94 (Ca), 134.61 (Cc),
166.51 (CON), 168.90 (COO), 169.51 (COO), 169.55
(COO), 169.81 (COO). Mass spectrum, m/z (Irel, %):
448 (3) [M]+, 389 (51), 313 (12), 302 (100), 297 (73), 270
(27), 242 (17), 239 (46), 236 (17), 198 (15), 166 (12), 130
(22), 104 (29). Found, %: C 52.09; H 4.55; N 5.92.
C20H20N2O10. Calculated, %: C 53.57; H 4.50; N 6.25.
Reactions of dimethyl cis-1-phthalimidoaziridine-
2,3-dicarboxylate II with dimethyl fumarate. A solu-
tion of 304 mg (1 mmol) of aziridine II and 216 mg
(1.5 mmol) of dimethyl fumarate (IIIa) in 10 ml of
anhydrous benzene in a sealed ampule was heated at
220°C for 3 h. On completion of the reaction the solvent
was distilled off in a vacuum on a rotary evaporator. The
obtained dry residue was subjected to chromatography
on a column packed with 45 g of silica gel (gradient elution
with a mixture CH2Cl2–Et2O, from 1 : 0 to 9 : 1 v/v). We
obtained 35 mg (22%) of methyl 5-methoxy-1,3-
oxazole-2-carboxylate (VII) (Rf 0.35, CH2Cl2), 55 mg
(37%) of phthalimide (Rf 0.25, CH2Cl2), 50 mg (11%)
tetramethyl rel-(2R,3R,4R,5R)-1-phthalimidopyr-
rolidine-2,3,4,5-tetra-carboxylate (Va1) (Rf 0.15,
CH2Cl2), and 50 mg (11%) of a mixture of compound
Va1 and tetramethyl rel-(2R,3S,4S,5R)-1-phthal-
imidopyrrolidine-2,3,4,5-tetracarboxylate (Va2)
(Rf 0.13, CH2Cl2) in a ratio 7:4 (according to 1H NMR
data). Overall yield of adduct Va1 18%, of its stereoisomer
Va2 4%.
Pyrrolidine Va1. mp 115–117°C. 1H NMR spectrum
(CDCl3), δ, ppm: 3.63 s (6H, 2MeO), 3.82 s (6H, 2MeO),
4.00 m (2H, H3,4), 4.87 m (2H, H2,5), 7.70–7.90 m (4H,
Pi). 13C NMR spectrum (CDCl3), δ, ppm: 46.93 (C3,4),
52.92 (2MeO), 53.09 (2MeO), 64.37 (C2,5); 123.74 (Cb),
130.01 (Ca), 134.67 (Cc), 166.49 (CON), 169.32 (2COO),
171.02 (2COO). Mass spectrum, m/z (Irel, %): 448 (2)
Dimethyl rel-(1R,2R,4R,5S)-6,8-dioxo-7-phenyl-
3-phthalimido-3,7-diazabicyclo-[3.3.0]octane-2,4-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 8 2009

THERMOLYSIS OF DIMETHYL cis- AND trans-1 PTHALIMIDOAZIRIDINE
1207
dicarboxylate (Vc). A solution of 304 mg (1 mmol) of
aziridine II and 260 mg (1.5 mmol) of phenylmaleimide
(IIIc) in 10 ml of anhydrous chlorobenzene was heated
for 3 h in a thick-walled glass reactor at 220°C. On
completion of the reaction the solvent was distilled off in
a vacuum on a rotary evaporator. The obtained dry residue
was subjected to chromatography on a column packed
with 40 g of silica gel (gradient elution with a mixture
CH2Cl2–Et2O, from 1 : 0 to 3 : 1 v/v).Yield 420 mg (88%),
mp 215–216°C, Rf 0.3 (CH2Cl2–Et2O, 10 : 1 v/v).
1H NMR spectrum (CDCl3), δ, ppm: 3.67 s (3H, MeO),
3.72 s (3H, MeO), 3.84 d.d (1H, H1, J 8.7, 1.6 Hz),
3.93 d.d (1H, H5, J 8.5, 8.0 Hz), 4.62 d (1H, H2,
J 1.5 Hz), 5.31 d (1H, H4, J8.0 Hz), 7.23–7.55 m (5H,
168.68, 174.43, 175.00 (2COO and 2CON). Mass
spectrum, m/z (Irel, %): 477 (5) [M]+, 418 (63), 330 (77),
239 (100), 152 (20), 104 (26), 80 (17), 76 (20). Found, %:
C 59.98; H 4.10; N 8.62. C24H19N3O8. Calculated, %:
C 60.38; H 4.01; N 8.80.
REFERENCES
1. Kuznetsov, M.A., Pan’kova, A.S., Ushkov, A.V., and
Selivanov, S.I., Zh. Org. Khim., 2008, vol. 44, p. 1807.
2. Gladstone, W.A.F., Norman, R.O.C. J. Chem. Soc. C, 1966,
p. 1536.
3. Siu, T.,Yudin,A.K., J. Am. Chem. Soc., 2002, vol. 124, p. 530.
4. Loznevaya, Yu.G., Belov, V.N., and Kuznetsov, M.A.,
Abstracts of Papers, IV Vsesoyuzn. konf. po khimii
karbenov (4th All-Union Conf. on Carbene Chemistry),
Moscow: Nauka, 1987, p. 56.
5. Semenovskii, V.V., Cand. Sci. (Chem.) Dissertation,
Leningrad, 1991.
6. Atkinson, R.S. and Malpass, J.R., J. Chem. Soc., Perkin
Trans. 1, 1977, p. 2242.
1
Ph), 7.70–7.85 m (4H, Pi). H NMR spectrum (CD3CN),
δ, ppm: 3.57 s (3H, MeO), 3.62 s (3H, MeO), 3.84 d.d
(1H, H1, J 8.7, 1.5 Hz), 4.04 d.d (1H, H5, J 8.7, 8.0 Hz),
4.41 d (1H, H2, J 1.5 Hz), 5.25 d (1H, H4, J 8.0 Hz),
7.20–7.30 m (2H, Hm), 7.40–7.60 m (3H, Ho,p), 7.91 C
(4H, Pi). 13C NMR spectrum (CDCl3), δ, ppm: 44.81
(C1,5), 52.73 (MeO), 53.32 (MeO), 61.66 and 64.66 (C2,4),
123.78 (Cb), 126.92 (Co), 129.25 (Cp), 129.50 (Cm),
129.90 (Ca), 131.75 (Ci), 134.76 (Cc), 166.18 (CON Pi);
7. Person, H., Luanglath, K., Baudru, M., and Foucaud, A.,
Bull. Soc. Chim., 1976, p. 1989.
8. Drew, N.D.K. and Hatt, N.H., J. Chem. Soc., 1937, p. 16.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 8 2009