Thermal transformations of alk-1-enyl-N-phthalimidoaziridines

Article abstract of DOI:10.1134/S1070428013010156

Thermolysis of alk-1-enyl-N-phthalimidoaziridines leads to products of 1,5-electrocyclization of intermediate azomethine ylides with participation of C=C bonds. If acyl or alkoxycarbonyl substituent is present in the aziridine ring, the C=O bond is also i

Full text of DOI:10.1134/S1070428013010156

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2013, Vol. 49, No. 1, pp. 83–94. © Pleiades Publishing, Ltd., 2013.
Original Russian Text © M.A. Kuznetsov, V.V. Voronin, 2013, published in Zhurnal Organicheskoi Khimii, 2013, Vol. 49, No. 1, pp. 91–100.
Dedicated to Full Member of the Russian Academy of Sciences
G.A. Tolstikov on his 80th anniversary
Thermal Transformations of Alk-1-enyl-N-phthalimidoaziridines
M. A. Kuznetsov and V. V. Voronin
St. Petersburg State University, Universitetskii pr. 26, St. Petersburg, 198504 Russia
e-mail: mak@mail.wplus.net
Received February 7, 2012
Abstract—Thermolysis of alk-1-enyl-N-phthalimidoaziridines leads to products of 1,5-electrocyclization of
intermediate azomethine ylides with participation of C=C bonds. If acyl or alkoxycarbonyl substituent is
present in the aziridine ring, the C=O bond is also involved. Thermolysis of the title compounds in the presence
of N-phenylmaleimide or dimethyl acetylenedicarboxylate under analogous conditions gives products of
1,3-dipolar cycloaddition of azomethine ylides to the double or triple bond of the dipolarophile.
DOI: 10.1134/S1070428013010156
Thermally or photochemically induced cleavage of
C–C bond in a strained aziridine ring generates so-
called azomethine ylides (1,3-dipoles) [1] whose
further transformations may follow several pathways.
From the synthetic viewpoint, the most interesting is
1,3-dipolar cycloaddition of azomethine ylides at
multiple bonds of dipolarophiles, which leads to the
formation of various nitrogen-containing heterocycles
[1, 2]. Furthermore, azomethine ylides conjugated to
C=O, C=N, and C=C bonds are capable of undergoing
intramolecular 1,5-electrocyclization to form other
five-membered nitrogen-containing heterocycles [3–8].
uents with a C=O bond, taking into account that the
latter can also be involved in 1,5-electrocyclization of
intermediate azomethine ylides. N-Phenylmaleimide
(PMI) and dimethyl acetylenedicarboxylate (DMAD)
were taken as dipolarophiles.
Aziridines Ia–Ie were synthesized from the corre-
sponding 1,3-dienes IIa–IId according to the opti-
mized standard procedure for oxidative addition of
N-aminophthalimide to unsaturated compounds [12]
(Scheme 1). As a rule, mixtures of mono- and bis-
adducts were obtained, from which pure monoaziri-
dines were isolated.
Analogous transformations of N-aminoaziridine
derivatives provide synthetic routes to difficultly
accessible N-amino heterocycles. For example, we
recently demonstrated the possibility for thermal
generation of azomethine ylides from 2,3-disubstituted
N-phthalimidoaziridines and their participation in
subsequent 1,3-dipolar cycloadditions [9–11]. On the
other hand, 2-acyl-N-phthalimidoaziridines on heating
are readily converted into oxazoles, which may be
regarded as the result of 1,5-electrocyclization of inter-
mediate azomethine ylides accompanied by elimina-
tion of phthalimide and aromatization [6–8].
The goal of the present work was to find out
whether 1,5-electrocyclization of alk-1-enyl azo-
methine ylides generated by thermolysis of the corre-
sponding N-phthalimidoaziridine derivatives is pos-
sible and estimate prospects in their use in 1,3-dipolar
cycloaddition reactions. As substrates we selected
vinylaziridines Ia–If, some of which contain substit-
Scheme 1.
NPhth
N
PhthNNH2
Pb(OAc)4
R2
R1
R2
R1
IIa–IIc
Ia–Ic
O
b
a
c
PhthN =
.
N
O
I, II, R1 = R2 = Ph (a); R1 = Ph, R2 = PhC(O) (b); R1 = Me,
R2 = MeOC(O) (c).
The reactions with unsymmetric 1,4-disubstituted
dienes IIb and IIc afforded only addition products at
the C=C bond neighboring to the carbonyl group;
however, 1,1,4-trisubstituted compound IId gave
rise to a mixture of regioisomeric aziridines Id and Ie
83

KUZNETSOV, VORONIN
84
Scheme 2.
NPhth
NPhth
N
COOMe
COOMe
PhthNNH2, Pb(OAc)4
COOMe
COOMe
N
Ph
+
COOMe
Ph
Ph
COOMe
Ie, 7%
IId
Id, 18%
Scheme 3.
NPhth
N
NPhth
Ph3P=CHC(O)OMe
40°C, 3 h
N
Ph
CHO
Ph
COOMe
Ig
If, 82%
(Scheme 2) which were separated by column chroma-
tography. Aziridine If was synthesized by the Wittig
reaction of aldehyde Ig (Scheme 3) prepared as de-
scribed in [12]. The vicinal coupling constant for
the protons at the exocyclic double bond in If (3J =
15.5 Hz) indicated (E) configuration of that bond.
slow (on the NMR time scale) inversion of the endo-
cyclic nitrogen atom at room temperature [13, 14]. The
ratio of invertomers of If was 10:1, whereas the
fraction of the minor invertomer of Ie was so small
that it cannot be detected by NMR spectroscopy. On
the basis of steric considerations we presumed that the
phthalimido group in the only spectrally detectable
invertomer of Ie occupies syn position with respect to
the proton in the aziridine ring, and in the major
invertomer of If, anti position with respect to the
phenyl group as the bulkier substituent. Aziridines Ia–
Id were equilibrium mixtures of two invertomers in
comparable amounts, which suggests similar effective
volumes of the corresponding substituents.
N-Phthalimidoaziridines Ia–Ig were isolated as
colorless, yellow, or greenish–yellow crystalline sub-
stances. Compounds Ib–If were not reported previ-
ously and were characterized by elemental analyses,
13
1H and C NMR spectra, and exact weights of quasi-
molecular ions determined from the high-resolution
ESI mass spectra. We failed to obtain satisfactory
elemental analysis data for aziridine Ie due to its
instability under the isolation and purification condi-
tions. trans Orientation of protons at the double bond
in initial unsaturated compounds IIb–IId was retained
in aziridines Ib–Id, as followed from the low values
of the corresponding vicinal coupling constants (3J =
4.4–5.8 Hz).
The structure of adducts Ic–Ie unambiguously
follows from the multiplicity of signals from the
1
aziridine proton in the H NMR spectra; however,
regioisomeric aziridination products of diene IIb can-
not be distinguished in such a way. For this purpose,
1
2D H NOESY experiment was performed. The
N-Aminoaziridine derivatives often display in the
NOESY spectrum contained cross peaks for readily
NMR spectra signals from two invertomers due to
identifiable ortho-protons in the benzoyl group (down-
Scheme 4.
NPhth
N
NPhth
COOMe
Ph
N
COOMe
OMe
60°C, 5 h
Ie
or
COOMe
O
Ph
–PhthNH
NPhth
COOMe
OMe
N
COOMe
COOMe
N
+
Ph
O
Ph
III, 27%
IV, 31%
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 1 2013

THERMAL TRANSFORMATIONS OF ALK-1-ENYL-N-PHTHALIMIDOAZIRIDINES
85
Scheme 5.
NPhth
PhthN
N
N
100°C, 2 h
Ib
Ph
O
O
Ph
Ph
Ph
–PhthNH
~1,3-PhthNH
NPhth
N
N
+
Ph
O
O
Ph
Ph
rel-(2R,5R)-VI, rel-(2R,5S)-VI
Ph
V
field signals) and aziridine ring proton (doublet) for
both invertomers, which reliably proved structure Ib.
1H and 13C NMR spectra of VI was consistent only
with structures where the phthalimido group is
attached to C5. The NOESY spectrum of stereoisomer
mixture VI showed that the styryl and phenyl substit-
uents in the major isomer [rel-(2R,5S)-VI] are oriented
cis, and in the minor isomer [rel-(2R,5R)-VI], trans.
1,5-Electrocyclization of N-phthalimidoaziridines
Ia–If with participation of the double carbon–carbon
bond was studied by heating these compounds in the
absence of dipolarophiles. Thermolysis of Ie gave
expected dihydropyrrole III and oxazole IV, the latter
being formed via 1,5-electrocyclization involving the
C=O bond (Scheme 4).
By heating aziridine Ib we obtained only 1,5-elec-
trocyclization products at the carbonyl group,
5-phenyl-2-styryloxazole (V) and two diastereoisomers
of dihydrooxazole VI at a ratio of 4:1 (Scheme 5).
This cyclization could be expected to produce 2,3-di-
hydrooxazole having a phthalimido group on the nitro-
gen atom; however, the position of some signals in the
The thermolysis of aziridines Ia, Ic, Id, and If was
accompanied by appreciable tarring. In each case, the
conversion of the initial compound was complete, but
chromatographic separation of the reaction mixtures
gave only fractions containing mixtures of products
and phthalimide. A new compound was detected by
TLC in the reaction mixture obtained by thermolysis of
Id; however, we succeeded in isolating only phthal-
imide, benzaldehyde, and tarry fractions with intrac-
table 1H NMR spectra.
Scheme 6.
R1
O
(2 equiv)
O
O
N
PhthN
N
N
Ph
Ph
O
R2
NPhth
N
90–110°C, 3 h
VIIa, VIIc, VIIf
Ia, Ic, If
R2
R1
R1
MeO
O
O
COOMe
(3 equiv)
PhthN
N
OMe
COOMe
R2
VIIIa, VIIIc, VIIIf
R1 = R2 = Ph (a); R1 = MeOC(O), R2 = Me (c); R1 = Ph, R2 = MeOC(O) (f).
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KUZNETSOV, VORONIN
86
Heating of aziridines Ia, Ic, and If under analogous
products in the presence of dipolarophiles. Only in the
reaction of Ib with PMI we succeeded in isolating
cycloadduct VIIb in a poor yield (Scheme 7).
conditions but with addition of N-phenylmaleimide or
dimethyl acetylenedicarboxylate smoothly afforded the
corresponding 1,3-dipolar cycloaddition products
whose spatial structure was determined on the basis of
the NOESY data. The reactions with PMI gave ex-
pected (cf. [8–10]) bicyclic exo-adducts VIIa, VIIc,
and VIIf with cis orientation of the substituents in the
former aziridine ring. The thermolysis in the presence
of DMAD produced 2,5-dihydro-1H-pyrrole deriva-
tives VIIIa, VIIIc, and VIIIf with cis orientation of
the same substituents as well (Scheme 6). The struc-
ture of adducts VII and VIII is very consistent with
the generally accepted reaction mechanism [1, 2, 8–11]
including allowed (by the Woodward–Hoffmann or-
bital symmetry rules) conrotatory opening of the trans-
2,3-disubstituted aziridine ring to form W-ylide and
concerted addition of the latter to the dipolarophile
(see below).
Quite unexpected results were obtained in the reac-
tions of dipolarophiles with aziridine Id (Scheme 8). In
both cases, mixtures of stereoisomeric cycloadducts
with both cis and trans configuration of the substit-
uents in the former aziridine ring were formed. The
steric structure of the products was determined using
NOESY experiments. The major product of the reac-
tion with PMI, rel-(1R,3R,3aR,6aS)-VIId, was isolated
as individual substance and completely characterized.
The second stereoisomer was not isolated pure, but the
NMR spectra of a 2:1 mixture of rel-(1R,3S,3aS,6aR)-
VIId and rel-(1R,3R,3aR,6aS)-VIId were fully consis-
tent with the assumed structures, and the elemental
analysis data for that mixture and its mass spectrum
corresponded to the general formula. The adducts
formed by aziridine Id with DMAD were separated
neither by chromatography nor by recrystallization;
therefore, only their mixture was analyzed and charac-
terized by spectral data; the ratio rel-(2R,5S)-VIIId–
By contrast, aziridines Ib and Ie which underwent
1,5-electrocyclization on heating in the absence of
dipolarophiles were generally converted into the same
Scheme 7.
Ph
O
O
PhthN
N
N
Ph
100°C, 2 h
O
O
Ib
+
2
+
V
+
VI
N
O
Ph
Ph
VIIb
Scheme 8.
COOMe
COOMe
MeOC(O)
O
MeOC(O)
O
80°C, 2 h
O
O
Id
+
+
N
Ph
N
N
NPhth
Ph
N
N
NPhth
Ph
O
Ph
O
Ph
rel-(1R,3R,3aR,6aS)-VIId
rel-(1R,3S,3aS,6aR)-VIId
COOMe
COOMe
MeOC(O)
MeOC(O)
O
80°C, 2 h
MeOC(O)
MeOC(O)
OMe
Id
+
+
MeO
N
NPhth
N
NPhth
MeOC(O)
MeOC(O)
O
Ph
Ph
rel-(2R,5S)-VIIId
rel-(2R,5R)-VIIId
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THERMAL TRANSFORMATIONS OF ALK-1-ENYL-N-PHTHALIMIDOAZIRIDINES
87
Scheme 9.
Id
NPhth
NPhth
N
Ph
N
NPhth
N
COOMe
COOMe
Ph
COOMe
COOMe
COOMe
COOMe
Ph
S1
W
S2
O
O
O
O
N
N
Ph
Ph
O
O
N
O
N
O
O
COOMe
Ph
N
O
N
N
O
Ph
N
MeOOC
COOMe
O
CO2Me
MeOC(O)
MeO2C
O
Ph
N
N
NPhth
O
Ph
rel-(2R,5R)-VIIId was 7 :1. Adducts VII and VIII
specifically featured slow (on the NMR time scale)
rotation about the N–N bond in the hydrazine frag-
ment. As a result, their 13C NMR spectra displayed
broadening or doubling of signals from carbon atoms
in the phthalimide fragment. The same factor is re-
sponsible for symmetry distortion of the multiplet
signal from protons in the phthaloyl group in the
1H NMR spectra of some adducts.
The results obtained in the present work are some-
what surprising. In all cases studied previously, ther-
mally induced 1,3-dipolar cycloaddition of disubsti-
tuted N-phthalimidoaziridines was stereospecific, and
only adducts arising from conrotatory opening of the
three-membered ring were formed [8–10]. Here, we
were the first to obtain mixtures of stereoisomeric
products. As before, their major components corre-
spond to conrotatory opening of the aziridine ring to
generate W-dipole and subsequent concerted cycload-
dition, while the formation of minor stereoisomers may
be due to partial isomerization of W-ylide into S-ylide.
On the other hand, stepwise addition of intermediate
ylide to dipolarophile cannot be ruled out, which
should lead to violation of stereospecificity.
Theoretically, adducts with trans orientation of the
substituents in the former aziridine ring may be formed
from S-dipoles S1 and S2. As shown in Scheme 9, the
formation of trans-adduct rel-(1R,3S,3aS,6aR)-VIId
from N-phenylmaleimide and S2 implies approach of
the dipolarophile from the side of the bulky phthal-
imide group, whereas the interaction of PMI with S1
does not involve appreciable steric hindrances. There-
fore, it is more probable that trans-adducts are formed
via rearrangement of W-ylide into S1.
Presumably, the presence of two electron-withdraw-
ing groups in the NCHCH=C(CO2Me)2 fragment of
intermediate ylide favors charge delocalization in such
a way that the order of the C–N bond in the above
fragment decreases, which reduces the barrier to rota-
tion about the C–N bond. As a result, the rate of iso-
merization of W-dipole into S1 becomes comparable to
the rate of cycloaddition, and mixtures of stereoiso-
meric products are formed.
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KUZNETSOV, VORONIN
88
1
To conclude, it should be noted that alkenyl deriva-
8:2; the H NMR spectrum was very consistent with
that given in [17].
tives of N-phthalimidoaziridine undergo intramolecular
transformations and react with dipolarophiles at a con-
siderably lower temperature (60–110°C) than do analo-
gous derivatives with acyl, alkoxycarbonyl, aryl, and
cyano groups (130–220°C [7–11]). This fact indicates
efficient stabilization of intermediate azomethine
ylides by alkenyl groups.
rel-(2R,3S)-2-Benzoyl-3-styryl-1-phthalimido-
aziridine (Ib) was synthesized from (2E,4E)-1,5-di-
phenylpenta-2,4-dien-1-one (IIb) [18] at –20°C. After
removal of the solvent, the residue was subjected to
chromatography on 40 g of silica gel using ethyl
acetate–hexane (1:6 to 1:3) as eluent. Yield 627 mg
1
(53%), greenish–yellow crystals, mp 146°C. H NMR
EXPERIMENTAL
spectrum (a mixture of two invertomers at a ratio of
8:2), δ, ppm: 3.83 d.d (3-H, minor, J = 8.0, 5.1 Hz)
and 4.34 d.d (3-H, major, J = 7.3, 5.1 Hz) (1H); 4.28 d
(2-H, major, J = 5.1 Hz) and 4.87 d (2-H, minor, J =
5.1 Hz) (1H); 6.05 d.d (HC=CHPh, minor, J = 16.0,
8.0 Hz) and 6.19 d.d (HC=CHPh, major, J = 16.0,
7.3 Hz) (1H); 6.92 d (HC=CHPh, minor, J = 16.0 Hz)
and 7.01 d (HC=CHPh, major, J = 16.0 Hz) (1H);
7.25–7.81 m (12H, Harom); 8.06–8.09 m (o-H in COPh,
major) and 8.23–8.26 m (o-H in COPh, minor) (2H).
13C NMR spectrum, δC, ppm: major invertomer: 47.92
and 50.56 (C2, C3), 123.25 and 123.46 (Cb,
HC=CHPh); 126.74, 128.76, 128.83, 128.90 (Cm, Co);
128.39 and 129.02 (Cp), 130.38 (Ca), 133.71
(HC=CHPh), 134.09 (Cc), 135.83 and 137.50 (Ci),
164.47 (NCO), 190.85 (CO). Found, %: C 76.06;
H 4.47; N 7.10. m/z 417.1191 [M + Na]+. C21H18N2O3.
Calculated, %: C 76.13; H 4.60; N 7.10. (M + Na)
417.1210.
1
The H and 13C NMR spectra were measured on
a Bruker DPX-300 spectrometer (300 and 75 MHz,
respectively) from solutions in CDCl3 using the
residual proton (δ 7.26 ppm) and carbon signals
(δC 77.16 ppm) of the solvent as reference [15]. The
elemental compositions were determined on an HP-
185B automatic CHN analyzer. The high-resolution
mass spectra (electrospray ionization) were obtained
on a Bruker micrOTOF instrument. The composition
of the reaction mixtures and fractions obtained after
their separation, as well as the purity of the isolated
compounds, were monitored by TLC on Polygram SIL
G/UV254 and Alugram SIL G/UV254 plates (Macherey-
Nagel). N-Aminophthalimide was synthesized accord-
ing to the procedure described in [16].
N-Phthalimidoaziridines Ia–Ie and Ig (general
procedure). Anhydrous potassium carbonate, 1.863 g
(13.5 mmol), was dispersed in a solution of 3.0 mmol
of the corresponding 1,3-diene in 30 ml of anhydrous
methylene chloride, and N-aminophthalimide and lead
tetraacetate were added one by one in 7–15-mg
portions (4.5 mmol each in the synthesis of Ia–Ie and
3 mmol each in the synthesis of Ig) under stirring over
a period of 20 min. The mixture was then stirred for
20–30 min more at room temperature and filtered
through a 1.5-cm layer of silica gel, the precipitate was
washed with 40–150 ml of methylene chloride, the
filtrate was combined with the washings and evaporat-
ed under reduced pressure at room temperature (18–
23°C), and the residue was subjected to column chro-
matography on silica gel.
Methyl rel-(2R,3S)-3-[(E)-prop-1-en-1-yl]-1-
phthalimidoaziridine-2-carboxylate (Ic) was syn-
thesized from methyl (2E,4E)-hexa-2,4-dienoate (IIc)
[19] at –20°C. After removal of the solvent, the residue
was subjected to chromatography on 30 g of silica gel
using ethyl acetate–hexane (1:6) as eluent. Yield
345 mg (40%), light yellow crystals, mp 95–96°C.
1H NMR spectrum (a mixture of two invertomers at
a ratio of 7:3), δ, ppm: 1.68 d.d (CH3, minor, J = 6.6,
1.5 Hz) and 1.79 d.d (CH3, major, J = 6.6, 1.5 Hz)
(3H); 3.23 d (2-H, major, J = 5.0 Hz), 3.45 d.d (3-H,
minor, J = 7.7, 5.1 Hz), and 3.78–3.81 m (3-H, major
and 2-H, minor) (2H); 3.70 s (OCH3, major) and 3.84 s
(OCH3, minor) (3H); 5.28 d.d.d (HC=CHCH3, minor,
J = 15.2, 7.7, 1.5 Hz) and 5.39 d.d.d (HC=CHCH3,
major, J = 15.4, 7.4, 1.5 Hz) (1H); 5.97–6.17 m (1H,
HC=CHCH3); 7.65–7.80 m (4H, PhthN). 13C NMR
spectrum, δC, ppm: 18.14 and 18.33 (CH3); 44.15,
44.97, 48.87, 49.29 (C2, C3); 52.87 and 52.97 (OCH3),
121.31 (HC=CHCH3); 123.19, 123.36, 124.97 (Cb,
HC=CHCH3); 130.36 (Ca), 133.40 and 136.02
(HC=CHCH3), 134.09 and 134.33 (Cc), 164.81 and
165.22 (NCO), 167.14 and 168.37 (COO); signals
rel-(2R,3R)-2-Phenyl-3-styryl-1-phthalimido-
aziridine (Ia) was synthesized from (1E,3E)-1,4-di-
phenylbuta-1,3-diene IIa at –20°C. After removal of
the solvent, the residue was subjected to chromatog-
raphy on 40 g of silica gel using ethyl acetate–hexane
(1:8 to 1:4) as eluent. Yield 538 mg (49%), greenish–
yellow crystals, mp 138°C; published data [13]:
1
mp 138–139°C. According to the H NMR data, the
product was a mixture of two invertomers at a ratio of
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THERMAL TRANSFORMATIONS OF ALK-1-ENYL-N-PHTHALIMIDOAZIRIDINES
89
from Ca in the phthalimido group of both invertomers
coincided. Found, %: C 63.16; H 5.02; N 9.64.
m/z 287.1006 [M + H]+. C15H14N2O4. Calculated, %:
C 62.93; H 4.93; N 9.79. (M + H) 287.1026.
tals, mp 172–174°C; published data [21]: mp 176°C.
The H NMR spectrum of Ig was very consistent with
that given in [21].
1
Methyl (2E)-3-[rel-(2R,3R)-3-phenyl-1-phthal-
imidoaziridin-2-yl]acrylate (If). A solution of 585 mg
(2 mmol) of compound Ig and 0.8 g (2.4 mmol) of
methyl (triphenyl-λ5-phosphanylidene)acetate [22] in
5 ml of methylene chloride was heated for 4 h under
reflux, the progress of the reaction being monitored by
TLC. The resulting solution (without evaporation) was
applied to a column charged with 20 g of silica gel,
and the column was eluted with ethyl acetate–hexane
(1:4) to isolate 573 mg (82%) of If as greenish–yellow
Aziridines Id and Ie were synthesized from di-
methyl 2-(3-phenylprop-2-en-1-ylidene)malonate (IId)
[20] at 13°C. After removal of the solvent, the residue
was subjected to chromatography on 40 g of silica gel
using ethyl acetate–hexane (1:4 to 1:0) as eluent to
isolate 450 mg (37%) of a mixture of Id and Ie at
a ratio of 2:1 (1H NMR). Repeated chromatography on
50 g of silica gel (ethyl acetate–hexane, 1:8 to 1:1)
gave fractions enriched in aziridines Id and Ie due to
their close Rf values.
1
crystals with mp 130–132°C. H NMR spectrum
(a mixture of two invertomers at a ratio of 10:1), δ,
ppm: 3.46 d.d (2-H, major, J = 9.5, 5.1 Hz) and
4.76 d.d (2-H, minor, J = 8.7, 5.4 Hz) (1H); 3.70 s
(OCH3, major) and 3.77 s (OCH3, minor) (3H); 4.04 d
(3-H, minor, J = 5.4 Hz) and 4.19 d (3-H, major, J =
5.4 Hz) (1H); 6.28 d (CH=CHCO2CH3, major, J =
15.5 Hz) and 6.38 d (CH=CHCO2CH3, minor, J =
15.7 Hz) (1H); 6.68 d.d (CH=CHCO2CH3, major, J =
15.5, 9.5 Hz) and 6.99 d.d (CH=CHCO2CH3, minor,
J = 15.7, 8.7 Hz) (1H); 7.33–7.54 m (5H, Ph), 7.61–
7.62 m (PhthN, minor) and 7.69–7.82 m (PhthN,
major) (4H). 13C NMR spectrum, δC, ppm: major in-
vertomer: 50.24, 50.58, 51.89 (C2, C3, OCH3); 123.46
(Cb), 125.66 (CH=CHCO2CH3), 127.07 and 128.79
(Cm, Co), 128.50 (Cp), 130.84 (Ca), 134.43 (Cc), 135.41
(Ci), 140.53 (CH=CHCO2CH3), 165.49 and 165.92
(NCO, COO). Found, %: C 69.09; H 4.55; N 8.16.
m/z 349.1188 [M + H]+. C20H16N2O4. Calculated, %:
C 68.96; H 4.63; N 8.04. (M + H) 349.1183.
Dimethyl {[rel-(2R,3R)-3-phenyl-1-phthalimido-
aziridin-2-yl]methylidene}malonate (Id). Yield
219 mg (18%), colorless crystals, mp 103–104°C.
1H NMR spectrum (a mixture of two invertomers at
a ratio of 3:1), δ, ppm: 3.74 s (OCH3, major), 3.82–
3.88 m (OCH3, major; OCH3, minor, 2-H, major, 3-H,
minor), 4.15 d (3-H, major, J = 5.1 Hz), 5.09 d.d (2-H,
minor, J = 8.0, 5.8 Hz) (8H); 6.75 d (CH=C, major, J =
10.2 Hz) and 6.79 d (CH=C, minor, J = 8.0 Hz) (1H);
7.24–7.49 m (5H, Ph), 7.60–7.61 (PhthN, minor) and
13
7.71–7.83 (PhthN, major) (4H). C NMR spectrum,
δC, ppm: major invertomer: 47.35, 51.10, 52.77 (C2,
C3, OCH3); 123.57 (Cb), 128.42 and 128.79 (Cm, Co),
128.65 (Cp), 130.31 (CH=C), 130.47 (Ca), 134.12 (Cc),
134.57 (Ci), 142.85 (CH=C); 163.92, 164.76, 165.44
(NCO, COO). Found, %: C 65.41; H 4.24; N 6.83.
m/z 429.1020 [M + Na]+. C22H18N2O6. Calculated, %:
C 65.02; H 4.46; N 6.89. (M + Na) 429.1057.
Dimethyl 1-phthalimido-3-styrylaziridine-2,2-
dicarboxylate (Ie). Yield 85 mg (7%), yellow crystals,
mp 120–121°C. 1H NMR spectrum, δ, ppm: 3.77 s and
3.88 s (3H each, OCH3), 4.39 d (1H, 3-H, J = 6.2 Hz),
5.97 d.d (1H, HC=CHPh, J = 16.0, 6.2 Hz), 7.05 d
(1H, HC=CHPh, J = 16.0 Hz), 7.26–7.38 m (5H, Ph),
7.70–7.85 m (4H, PhthN). 13C NMR spectrum, δC,
ppm: 53.49, 53.90, 54.10 (C3, OCH3); 119.38
(HC=CHPh), 123.45 (Cb), 126.94 and 128.74 (Cm, Co),
128.62 (Cp), 130.22 (Ca), 134.36 (Cc), 135.89 (Ci),
137.63 (HC=CHPh); 163.43, 163.82, 164.30 (NCO,
COO). Found: m/z 407.1213 [M + H]+. Calculated:
(M + H) 407.1238.
Thermolysis of aziridines Ib and Ie in the ab-
sence of dipolarophiles (general procedure). A solu-
tion of aziridine Ib or Ie in 10 ml of anhydrous toluene
in a thick-walled glass reactor was heated on a silicone
bath. When the initial compound disappeared (TLC),
the mixture was cooled, the solvent was distilled off
under reduced pressure, and the residue was treated as
described below.
a. Aziridine Ib, 394 mg (1 mmol), was heated for
2 h at 100°C. The residue was subjected to chromatog-
raphy on 20 g of silica gel using hexane–ethyl acetate
(8:1 to 2:1) as eluent. Fractions containing dihydro-
oxazole VI and contaminated with phthalimide were
combined and evaporated, and the residue was sub-
jected to repeated chromatography on silica gel using
methylene chloride as eluent. We isolated 96 mg (39%)
of V and 158 mg (40%) of a 1:4 mixture of diastereo-
isomers rel-(2R,5R)-VI and rel-(2R,5S)-VI.
rel-(2R,3S)-3-Phenyl-1-phthalimidoaziridine-
2-carbaldehyde (Ig) was synthesized from cinnamal-
dehyde at 0°C. The residue was subjected to chroma-
tography on 20 g of silica gel using methylene chloride
as eluent. Yield 745 mg (85%), greenish–yellow crys-
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KUZNETSOV, VORONIN
90
5-Phenyl-2-styryloxazole (V). Yellow crystals,
added dropwise until crystallization started. After 1 h,
the precipitate was filtered off and dried in air. We
isolated 55 mg (27%) of III and 40 mg (31%) of IV.
mp 101–103°C; published data [23]: mp 102–104°C.
1
The H and 13C NMR spectra of the product were in
good agreement with published data [23, 24].
Dimethyl 3-phenyl-1-phthalimido-2,3-dihydro-
Stereoisomer mixture VI was dissolved in 10 ml of
ethyl acetate, 40 ml of hexane was added, and the
mixture was evaporated under reduced pressure until
crystallization started. After 2 h, the precipitate was
filtered off and dried in air. We thus isolated 110 mg
(28%) of pure isomer rel-(2R,5S)-VI. The mother
liquor was evaporated under reduced pressure to obtain
42 mg of a 3:1 mixture of rel-(2R,5R)-VI and rel-
(2R,5S)-VI as colorless crystals.
1H-pyrrole-2,2-dicarboxylate (III). Yellow crystals,
mp 135°C. H NMR spectrum, δ, ppm: 3.07 s and
1
3.69 s (3H each, OCH3), 5.09 d.d (1H, 3-H, J = 4.1,
2.2 Hz), 5.13 d.d (1H, 4-H, J = 4.1, 4.1 Hz), 6.20 d.d
(1H, 5-H, J = 4.1, 2.2 Hz), 7.21–7.33 m (3H, m-H,
p-H), 7.39–7.42 m (2H, o-H), 7.75–7.88 m (4H,
PhthN). 13C NMR spectrum, δC, ppm: 51.92 and 53.56
(OCH3), 55.46 (C3), 79.75 (C2), 105.18 (C4), 123.79
(Cb), 127.80 (Cp), 128.30 and 129.41 (Cm, Co), 130.03
(Ca), 134.65 (Cc), 136.14 (C5), 138.52 (Ci); 166.43,
166.68, 167.26 (COO, NCO). Found, %: C 65.21;
H 4.56; N 6.73. m/z 407.1189 [M + H]+. C22H18N2O6.
Calculated, %: C 65.02; H 4.46; N 6.89. (M + H)
407.1238.
rel-(2R,5S)-5-Phenyl-5-phthalimido-2-styryl-2,5-
dihydrooxazole (VI). Colorless needles, mp 176–
1
178°C. H NMR spectrum, δ, ppm: 6.32 d.d (1H,
HC=CHPh, J = 15.9, 6.4 Hz), 6.55 d.d (1H, 2-H, J =
6.4, 2.5 Hz), 6.92 d (1H, HC=CHPh, J = 15.9 Hz),
7.29–7.53 m (10H, Ph), 7.75–7.87 m (4H, PhthN),
Methyl (E)-5-methoxy-2-styryloxazole-4-carbox-
13
1
8.14 d (1H, 4-H, J = 2.5 Hz). C NMR spectrum, δC,
ylate (IV). Yellow oily substance. H NMR spectrum,
ppm: 98.50 (C5), 107.58 (C2), 123.84 (Cb), 124.91
(HC=CHPh); 125.39, 127.11, 128.76, 129.06 (Cm, Co);
128.53 and 128.93 (Cp), 131.82 (Ca), 134.67 (Cc),
134.92 (HC=CHPh), 136.06 and 137.59 (Ci), 159.70
(C4), 167.31 (NCO). Found, %: C 76.14; H 4.50;
N 7.23. m/z 417.1228 [M + Na]+. C25H18N2O3. Calcu-
lated, %: C 76.13; H 4.60; N 7.10. (M + Na) 417.1210.
δ, ppm: 3.89 s (3H, OCH3), 4.25 s (3H, OCH3), 6.78 d
(1H, HC=CHPh, J = 16.4 Hz), 7.32–7.39 m (4H, m-H,
p-H, HC=CHPh), 7.46–7.50 m (2H, o-H). 13C NMR
spectrum, δC, ppm: 51.92 (CO2CH3), 59.93 (OCH3),
113.04 (HC=CHPh), 127.18 and 129.03 (Cm, Co, C4),
129.45 (Cp), 135.24 (Ci), 135.90 (HC=CHPh), 150.90
(C5), 161.54 and 161.91 (C2, C=O). Found:
m/z 260.0904 [M + H]+. Calculated: (M + H) 260.0917.
Diastereoisomer mixture rel-(2R,5R)-VI/rel-
(2R,5S)-VI (3:1). Found, %: C 76.44; H 4.42; N 7.03.
m/z 417.1179 [M + Na]+. C25H18N2O3. Calculated, %:
C 76.13; H 4.60; N 7.10. (M + Na) 417.1210. Analysis
of the NMR spectra of the mixture allowed us to iden-
tify the following spectral parameters of rel-(2R,5R)-
5-phenyl-5-phthalimido-2-styryl-2,5-dihydrooxazole
Reactions of aziridines Ia–Id and If with
N-phenylmaleimide (general procedure). A solution
of 0.5 mmol of aziridine Ia–Id or If and 173 mg
(1 mmol) of N-phenylmaleimide in 10 ml of anhydrous
toluene was heated in a thick-walled glass reactor at
a required temperature on a silicone bath. When the
initial compound disappeared (TLC), the mixture was
cooled, the solvent was distilled off under reduced
pressure, and the residue was subjected to column
chromatography on silica gel.
1
(VI). H NMR spectrum, δ, ppm: 6.18 d.d (1H,
HC=CHPh, J = 16.0, 6.5 Hz), 6.58 d.d (1H, 2-H, J =
6.5, 2.0 Hz), 6.81 d (1H, HC=CHPh, J = 16.0 Hz),
7.24–7.51 m (10H, Ph), 7.72–7.85 m (4H, PhthN),
13
8.11 d (1H, 4-H, J = 2.0 Hz). C NMR spectrum, δC,
a. The residue obtained after heating a mixture of
aziridine Ia and PMI for 3 h at 90°C was separated
using hexane–ethyl acetate (6:1 to 3:1) as eluent to
isolate 175 mg (65%) of rel-(3aR,4S,6S,6aS)-2,4-di-
phenyl-5-phthalimido-6-[(E)-styryl]tetrahydropyrrolo-
[3,4-c]pyrrole-1,3(2H,3aH)-dione (VIIa) as colorless
ppm: 97.78 (C5), 108.16 (C2), 123.90 (Cb); 125.01,
127.06, 128.60, 129.16 (Cm, Co); 125.29 (HC=CHPh),
128.37 and 128.99 (Cp), 131.78 (Ca), 134.02
(HC=CHPh), 134.68 (Cc), 135.97 and 137.42 (Ci),
159.21 (C4), 167.18 (NCO).
1
b. Aziridine Ie, 203 mg (0.5 mmol), was heated for
5 h at 60°C. The residue was subjected to chromatog-
raphy on 15 g of silica gel using hexane–ethyl acetate
(6:1 to 2:1) as eluent. Fractions containing compound
III were combined and evaporated, the residue was
dissolved in 3 ml of diethyl ether, and hexane was
crystals with mp 245°C. H NMR spectrum, δ, ppm:
3.49–3.62 m (2H, 3a-H, 6a-H), 4.80 d.d (1H, 6-H, J =
8.2, 8.2 Hz), 5.36 d (1H, 4-H, J = 7.2 Hz), 6.39 d.d
(1H, HC=CHPh, J = 15.8, 8.2 Hz), 6.72 d (1H,
HC=CHPh, J = 15.8 Hz), 7.21–7.72 m (19H, Ph,
PhthN). 13C NMR spectrum, δC, ppm: 47.85 and 50.33
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THERMAL TRANSFORMATIONS OF ALK-1-ENYL-N-PHTHALIMIDOAZIRIDINES
91
(C3a, C6a), 67.18 and 67.31 (C4, C6), 123.19 and 124.01
(Cb); 125.99, 128.38, 128.82, 128.91 (HC=CHPh, Cp);
126.64, 127.02, 127.83, 128.65, 128.99, 129.33 (Cm,
Co); 129.45 and 129.75 (Ca); 131.66, 135.93, 137.72
(Ci); 134.42 and 134.61 (Cc), 136.39 (HC=CHPh),
165.86 and 168.11 (NCO), 174.85 and 175.10 (C1, C3).
Due to restricted rotation about the N–N bond, all
carbon nuclei in the phthalimide fragment are non-
equivalent, and they give 8 signals. Found, %:
C 75.65; H 4.69; N 7.60. m/z 540.1896 [M + H]+.
C34H25N3O4. Calculated, %: C 75.68; H 4.67; N 7.79.
(M + H) 540.1918.
J = 15.1, 9.0, 1.3 Hz), 5.74 d.q (1H, HC=CHCH3, J =
15.1, 5.8 Hz), 7.36–7.53 m (5H, Ph), 7.75–7.87 m (4H,
PhthN). 13C NMR spectrum, δC, ppm: 17.98 (CH3),
45.14 and 47.63 (C3a, C6a), 53.24 (OCH3), 63.14 and
68.64 (C1, C3), 123.79 (Cb), 126.59 and 129.33 (Cm,
Co), 127.11 and 128.94 (HC=CHCH3, Cp), 129.77 (Ca),
131.58 (Ci), 134.00 and 134.75 (HC=CHCH3, Cc);
169.35, 174.28, 175.03 (C4, C6, COO). Signals from
the NCO carbon atoms in the phthalimide group were
not identified because of strong broadening. Found, %:
C 65.32; H 4.54; N 8.88. m/z 460.1483 [M + H]+.
C25H21N3O6. Calculated, %: C 65.35; H 4.61; N 9.15.
(M + H) 460.1503.
b. The residue obtained after heating a mixture of
Ib with PMI for 2 h at 100°C was separated by chro-
matography on silica gel using hexane–ethyl acetate
(8:1 to 2:1) as eluent to isolate 28 mg (10%) of adduct
VIIb, 32% of V, and 34% of VI.
d. The residue obtained after heating a mixture of
aziridine Id and PMI for 2 h at 80°C was subjected to
chromatographic separation using hexane–ethyl acetate
(3:1) as eluent to isolate 252 mg (87%) of a mixture of
rel-(1R,3R,3aR,6aS)-VIId and rel-(1R,3S,3aS,6aR)-
VIId. Repeated chromatography on silica gel using
hexane–ethyl acetate (4 :1) as eluent gave 148 mg
(51%) of pure isomer (1R,3R,3aR,6aS)-VIId and
75 mg (26%) of a 2:1 mixture of rel-(1R,3R,3aR,6aS)-
VIId and rel-(1R,3S,3aS,6aR)-VIId.
rel-(3aR,4R,6R,6aS)-4-Benzoyl-2-phenyl-5-
phthalimido-6-[(E)-styryl]tetrahydropyrrolo[3,4-c]-
pyrrole-1,3(2H,3aH)-dione (VIIb). Colorless crys-
1
tals, mp 247–248°C. H NMR spectrum, δ, ppm:
3.64 d.d (1H, 6a-H, J = 8.7, 8.7 Hz), 4.20 d.d (1H,
3a-H, J = 8.7, 5.3 Hz), 4.76 d.d (1H, 6-H, J = 8.7,
8.7 Hz), 5.80 d (1H, 4-H, J = 5.3 Hz), 6.33 d.d (1H,
HC=CHPh, J = 15.8, 8.7 Hz), 6.64 d (1H, HC=CHPh,
J = 15.8 Hz), 7.19–7.68 m (13H, Ph, m-H, p-H in
COPh), 7.64–7.70 m (4H, PhthN), 7.98 d (2H, o-H in
Dimethyl {[rel-(1R,3R,3aR,6aS)-4,6-dioxo-3,5-di-
phenyl-2-phthalimidooctahydropyrrolo[3,4-c]pyr-
rol-1-yl]methylidene}malonate (VIId). Colorless
1
crystals, mp 138–140°C. H NMR spectrum, δ, ppm:
13
COPh). C NMR spectrum, δC, ppm: 40.50 and 48.75
3.49–3.60 m (2H, 3a-H, 6a-H), 3.67 s and 3.77 s (3H
each, OCH3), 5.07 d.d (1H, 1-H, J = 9.9, 6.6 Hz),
5.39 d (1H, 3-H, J = 7.1 Hz), 7.16 d (1H, CH=C, J =
9.9 Hz), 7.29–7.55 m (8H, NPh, m-H, p-H in NCHPh),
7.60 d (2H, o-H in NCHPh, J = 6.8 Hz), 7.66–7.78 m
(C3a, C6a), 65.31 and 66.63 (C4, C6), 132.72 (Cb);
125.26, 128.43, 129.08 (HC=CHPh, Cp in Ph); 126.70,
127.07, 128.63, 128.76, 129.03, 129.45 (Cm, Co);
131.69, 135.89, 135.77 (Ci); 133.77, 134.68, 136.40
(HC=CHPh, Cc, Cp in COPh), 174.28 and 175.78 (C1,
C3), 194.54 (CO); signals from Ca and NCO in the
phthalimide fragment were not identified because of
strong broadening. Found, %: C 74.42; H 4.33; N 7.29.
m/z 568.1830 [M + H]+. C35H25N3O5. Calculated, %:
C 74.06; H 4.44; N 7.40. (M + H) 568.1867.
13
(4H, PhthN). C NMR spectrum, δC, ppm: 47.86 and
50.73 (C3a, C6a), 52.76 and 52.78 (OCH3), 62.02 and
67.88 (C1, C3), 123.07 and 124.14 (Cb); 126.54,
127.68, 128.97, 129.04, 129.35 (Cm, Co, Cp); 129.67
and 129.77 (Ca); 131.57, 133.00, 137.14 (CH=C, Ci);
134.50 and 134.62 (Cc), 143.26 (CH=C), 163.28 and
164.34 (COO), 165.38 and 167.72 (NCO), 173.88 and
174.41 (C4, C6). Due to restricted rotation about the
N–N bond, all carbon nuclei in the phthalimide frag-
ment are nonequivalent, and they give 8 signals; two
signals in the region δC 126.54–129.35 overlapped
each other. Found, %: C 66.09; H 4.46; N 7.10.
m/z 580.1720 [M + H]+. C32H25N3O8. Calculated, %:
C 66.32; H 4.35; N 7.25. (M + H) 580.1714.
c. The residue obtained after heating a mixture of Ic
and PMI for 3 h at 130°C was separated by chromatog-
raphy on silica gel using hexane–ethyl acetate (4:1 to
1:2) as eluent to isolate 143 mg (62%) of methyl rel-
(1R,3R,3aS,6aR)-4,6-dioxo-5-phenyl-2-phthalimido-3-
[(E)-prop-1-en-1-yl]octahydropyrrolo[3,4-c]pyrrole-1-
carboxylate (VIIc) as colorless crystals with mp 149–
150°C. 1H NMR spectrum, δ, ppm: 1.62 d.d (3H, CH3,
J = 5.8, 1.3 Hz), 3.44 d.d (1H, 3a-H, J = 9.0, 9.0 Hz),
3.72 s (3H, OCH3), 4.07 d.d (1H, 6a-H, J = 9.0,
5.7 Hz), 4.47 d.d (1H, 3-H, J = 9.0, 9.0 Hz), 4.78 d
(1H, 1-H, J = 5.7 Hz), 5.58 d.d.q (1H, HC=CHCH3,
Mixture (1R,3S,3aS,6aR)-VIId/(1R,3R,3aR,6aS)-
VIId (2:1). Found: m/z 580.1683 [M + H]+. Calcu-
lated: (M + H) 580.1714. Analysis of the NMR spectra
of that mixture allowed us to identify signals belonging
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KUZNETSOV, VORONIN
92
to dimethyl {[rel-(1R,3S,3aS,6aR)-4,6-dioxo-3,5-di-
phenyl-2-phthalimidooctahydropyrrolo[3,4-c]pyrrol-1-
yl]methylidene}malonate (VIId). H NMR spectrum,
reactor on a silicone bath. When the initial aziridine
disappeared (TLC), the mixture was cooled, the sol-
vent was distilled off under reduced pressure, and the
residue was subjected to column chromatography on
silica gel.
1
δ, ppm: 3.66 d.d (1H, 3a-H, J = 9.1, 5.7 Hz), 3.70 s
and 3.76 s (3H each, OCH3), 4.13 d.d (1H, 6a-H, J =
9.1, 9.1 Hz), 5.36 d.d (1H, 1-H, J = 11.1, 9.1 Hz),
5.64 d (1H, 3-H, J = 5.7 Hz), 7.11 d (1H, CH=C, J =
11.1 Hz), 7.29–7.55 m (8H, NPh, m-H, p-H in
NCHPh), 7.60 d (2H, o-H in NCHPh, J = 6.9 Hz),
7.64–7.74 m (4H, PhthN). 13C NMR spectrum, δC,
ppm: 46.36 and 50.47 (C3a, C6a), 52.78 and 52.90
(OCH3), 60.46 and 65.05 (C1, C3), 123.41 and 123.59
(Cb), 126.56 and 127.69 (Cp); 126.66, 127.71, 129.18,
129.46 (Cm, Co); 129.60 and 129.69 (Ca); 131.59,
132.61, 137.35 (CH=C, Ci); 134.51 and 134.53 (Cc),
140.63 (CH=C), 163.34 and 164.34 (COO), 166.15
and 167.52 (NCO), 173.13 and 175.31 (C4, C6). Due to
restricted rotation about the N–N bond, all carbon
nuclei in the phthalimide fragment are nonequivalent,
and they give 8 signals.
a. A mixture of aziridine Ia and DMAD was heated
for 3 h at 90°C, and the product was isolated by chro-
matography on silica gel using hexane–ethyl acetate
(6:1 to 4:1) as eluent. Yield of dimethyl rel-(2R,5S)-
2-phenyl-1-phthalimido-5-(E)-styryl-2,5-dihydro-1H-
pyrrole-3,4-dicarboxylate (VIIIa) 97 mg (38%), color-
1
less crystals, mp 179–181°C. H NMR spectrum, δ,
ppm: 3.60 s and 3.77 s (3H each, OCH3), 5.48 d.d (1H,
5-H, J = 7.9, 5.5 Hz), 5.89 d (1H, 2-H, J = 5.5 Hz),
6.40 d.d (1H, HC=CHPh, J = 15.8, 7.9 Hz), 6.37 d
(1H, HC=CHPh, J = 15.8 Hz), 7.22–7.40 m (8H,
HC=CHPh, m-H, p-H in 5-Ph), 7.56 d (2H, o-H in
5-Ph, J = 7.1 Hz), 7.67–7.79 m (4H, PhthN). 13C NMR
spectrum, δC, ppm: 52.33 and 52.57 (OCH3), 70.74 and
71.90 (C2, C5); 126.32, 127.06, 128.09, 128.35,
128.62, 128.75 (HC=CHPh, Cm, Co, Cp); 129.89 (Ca),
134.45 (Cc), 134.53 (HC=CHPh); 136.41, 136.75,
137.38, 138.95 (C3, C4, Ci); 164.32 and 163.39 (COO);
signals from Ca and Cc were strongly broadened, while
signals from Cb and NCO were not identified; two
signals in the region δC 127.06–128.75 overlapped
each other. Found, %: C 70.90; H 4.75; N 5.70.
m/z 547.1296 [M + K]+. C30H24N2O6. Calculated, %:
C 70.86; H 4.76; N 5.51. (M + K) 547.1266.
e. The residue obtained after heating a mixture of If
and PMI for 3 h at 110°C was subjected to chromato-
graphic separation on silica gel using hexane–ethyl
acetate (4:1 to 2:1) as eluent to isolate 212 mg (81%)
of methyl (E)-[rel-(1R,3R,3aR,6aS)-4,6-dioxo-3,5-di-
phenyl-2-phthalimidooctahydropyrrolo[3,4-c]pyrrol-1-
yl]acrylate (VIIf) as colorless crystals with mp 222–
1
224°C. H NMR spectrum, δ, ppm: 3.50–3.56 m (2H,
3a-H, 6a-H), 3.70 s (3H, OCH3), 4.84 d.d (1H, 1-H,
J = 7.5, 7.5 Hz), 5.30 d (1H, 3-H, J = 6.9 Hz), 6.29 d
(1H, CH=CHCO2CH3, J = 15.6 Hz), 7.09 d.d (1H,
CH=CHCO2CH3, J = 15.6, 7.5 Hz), 7.19–7.68 m (8H,
NPh, m-H, p-H in NCHPh), 7.60 d (2H, o-H in 3-Ph,
J = 7.5 Hz), 7.65–7.75 m (4H, PhthN). 13C NMR spec-
trum, δC, ppm: 47.77, 50.37, 51.95 (C3a, C6a, OCH3);
65.16 and 67.95 (C1, C3); 123.38, 124.14, 126.00,
128.98 (Cb, CH=CHCO2CH3, Cp); 126.59, 127.82,
129.00, 129.37 (Cm, Co); 129.61 (Ca), 131.50 and
137.16 (Ci), 134.59 and 134.79 (Cc), 143.61
(CH=CHCO2CH3); 165.29, 165.89, 167.76 (NCO,
COO); 174.48 and 174.66 (C4, C6). Due to restricted
rotation about the N–N bond, the Cc carbon nuclei in
the phthalimide fragment are nonequivalent, and they
give two signals. Found, %: C 69.25; H 4.42; N 8.06.
m/z 544.1452 [M + Na]+. C30H23N3O6. Calculated, %:
C 69.09; H 4.45; N 8.06. (M + Na) 544.1479.
b. A mixture of aziridine Ic and DMAD was heated
for 3 h at 130°C, and the residue was subjected to
chromatography on silica gel using hexane–ethyl
acetate (6:1 to 3:1) as eluent. Fractions containing
compound VIIIc were combined and concentrated
under reduced pressure until a viscous oily material
was obtained, 1 ml of diethyl ether and 3 ml of hexane
were added, and the resulting emulsion was left to
stand in a refrigerator. After 12 h, the precipitate was
filtered off and dried in air. Yield of trimethyl
rel-(2R,5R)-1-phthalimido-5-[(E)-prop-1-en-1-yl]-2,5-
dihydro-1H-pyrrole-2,3,4-tricarboxylate (VIIIc)
107 mg (50%), light yellow crystals, mp 110°C.
1H NMR spectrum, δ, ppm: 1.62 d (3H, CH3, J =
6.0 Hz), 3.72 s (3H, OCH3), 3.76 s (3H, OCH3), 3.82 s
(3H, OCH3), 5.14 d (1H, 2-H, J = 4.5 Hz), 5.20 d.d
(1H, 5-H, J = 7.6, 4.5 Hz), 5.55 d.d (1H, HC=CHCH3,
J = 15.2, 7.6 Hz), 5.63–5.75 m (1H, HC=CHCH3),
7.75–7.86 m (4H, PhthN). 13C NMR spectrum, δC,
ppm: 17.76 (CH3); 52.62, 52.67, 52.92 (OCH3); 70.06
and 73.57 (C2, C5), 123.81 (Cb), 126.98 (HC=CHCH3),
128.82 and 143.76 (C3, C4), 129.98 (Ca), 132.24
Thermal reactions of aziridines Ia, Ic, Id, and
If with dimethyl acetylenedicarboxylate (general
procedure). A solution of 0.5 mmol of aziridine Ia, Ic,
Id, or If and 213 mg (1.5 mmol) of DMAD in 10 ml of
anhydrous toluene was heated in a thick-walled glass
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THERMAL TRANSFORMATIONS OF ALK-1-ENYL-N-PHTHALIMIDOAZIRIDINES
93
(HC=CHCH3), 134.70 (Cc); 161.91, 163.64, 169.10
(COO). Signals from the carbonyl carbon atoms in the
phthalimide group were not identified because of
strong broadening. Found, %: C 65.35; H 4.83; N 9.00.
m/z 429.1302 [M + H]+. C25H21N3O6. Calculated, %:
C 65.35; H 4.61; N 9.15. (M + H) 429.1292.
spectrum, δ, ppm: 3.59 s (3H, OCH3), 3.73 s (3H,
OCH3), 3.79 s (3H, OCH3), 5.50 d.d (1H, 2-H, J = 5.5,
5.5 Hz), 5.84 d (1H, 5-H, J = 5.5 Hz), 6.49 d (1H,
CH=CHCO2CH3, J = 15.5 Hz), 7.14 d.d (1H,
CH=CHCO2CH3, J = 15.5, 5.5 Hz), 7.28–7.30 m (3H,
m-H, p-H), 7.47 d (2H, o-H, J = 7.4 Hz), 7.71–7.75 m
(4H, PhthN). 13C NMR spectrum, δC, ppm: 51.86,
52.48, 52.70 (OCH3); 69.00 and 73.42 (C2, C5), 123.80
(Cb), 124.37 (CH=CHCO2CH3), 128.50 and 128.54
(Cm, Co), 128.98 (Cp), 129.77 (Ca); 132.40, 136.63,
1 4 2 . 0 5 ( C 3 , C 4 , C i ) ; 1 3 4 . 6 6 ( C c ) , 1 4 3 . 7 5
(CH=CHCO2CH3); 162.27, 163.41, 166.60 (COO);
signals from the Cb atoms were strongly broadened,
while those corresponding to the carbonyl groups in
the phthalimide fragment were not identified. Found,
%: C 63.62; H 4.56; N 5.72. m/z 513.1251 [M + Na]+.
C26H22N2O8. Calculated, %: C 63.67; H 4.52; N 5.71.
(M + Na) 513.1268.
c. A mixture of aziridine Id and DMAD was heated
for 2 h at 80°C, and the residue was subjected to
chromatography on silica gel using hexane–ethyl ace-
tate (4:1) to isolate a mixture of rel-(2R,5R) and rel-
(2R,5S) isomers of dimethyl 2-[2,2-bis(methoxycar-
bonyl)ethenyl]-5-phenyl-1-phthalimido-2,5-dihydro-
1H-pyrrole-3,4-dicarboxylate (VIIId) at a ratio of 1:7
(according to the 1H NMR data). Yield 110 mg (40%),
light yellow crystals, mp 71–78°C. 1H NMR spectrum,
δ, ppm: 3.52 (OCH3, major), 3.60 (OCH3, major), 3.61
(OCH3, minor), 3.69 (OCH3, minor), 3.748 (OCH3,
minor), 3.754 (OCH3, major), 3.78 (OCH3, major),
3.84 (OCH3, minor) (12H); 5.67 d.d (2-H, minor, J =
10.8, 5.8 Hz), 5.68 d.d (2-H, major, J = 10.4, 5.1 Hz)
(2H); 5.98 d (5-H, major, J = 5.1 Hz), 6.38 d (5-H,
minor, J = 5.8 Hz) (2H); 7.10 d (CH=C, major, J =
10.4 Hz), 7.12 d (CH=C, minor, J = 10.8 Hz) (2H);
7.25–7.35 m (3H, m-H, p-H), 7.42 d.d (o-H, minor, J =
8.0, 2.0 Hz), 7.51 d.d (o-H, major, J = 8.0, 1.6 Hz)
This study was performed under financial support
by the St. Petersburg State University (project
no. 12.38.16.2011).
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