An efficient approach to azirino and pyrrolo-fused dibenzazepines. Conformations of substituted dibenzo[c,f]pyrrolo[1,2-a]azepines

Article abstract of DOI:10.1039/c1ob05081h

An effective approach to azepino-fused heterocycles is described. trans-1-Aryl-7,11b-dihydro-1H-azirino[1,2-a]dibenzo[c,f]azepines were synthesised via a domino sequence: isomerization of gem-dichloroaziridine- intramolecular Friedel-Crafts acylation of t

Full text of DOI:10.1039/c1ob05081h

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PAPER
An efficient approach to azirino and pyrrolo-fused dibenzazepines.
Conformations of substituted dibenzo[c,f ]pyrrolo[1,2-a]azepines†‡
Alexander F. Khlebnikov,*a Mikhail S. Novikov,a Maria V. Golovkina,a Petr P. Petrovskii,a
Alexander S. Konev,a Dmitry S. Yufitb and Helen Stoeckli-Evansc
Received 16th January 2011, Accepted 24th February 2011
DOI: 10.1039/c1ob05081h
An effective approach to azepino-fused heterocycles is described.
trans-1-Aryl-7,11b-dihydro-1H-azirino[1,2-a]dibenzo[c,f ]azepines were synthesised via a domino
sequence: isomerization of gem-dichloroaziridine–intramolecular Friedel–Crafts acylation of the
tethered benzene ring catalysed by SnCl4 and subsequent hydride induced intramolecular cyclization.
Cycloaddition of dibenzazepinium ylides, generated by heating these aziridines, to activated C C,
C
C dipolarophiles and fullerene C60, leads to derivatives of dibenzo[c,f ]pyrrolo[1,2-a]azepine. The
reaction proceeds with complete stereoselectivity via cycloaddition of only W-ylide, which due to the
high barrier does not undergo E,Z-isomerization under the reaction conditions. It was found that
2,3,9,13b-tetrahydro-1H-dibenzo[c,f ]pyrrolo[1,2-a]azepine systems can exist in conformations of two
types depending on the substituents at the pyrrolidine carbons in b-position with respect to nitrogen.
Details of cycloaddition reactions and the conformational behavior of cycloadducts were studied by
DFT calculations at the B3LYP/6-31G(d) level.
sedative, and antidepressive properties,9 but have been much less
Introduction
investigated than other ortho-fused dibenzo[b,e]azepines, probably
because of the lack of simple methods for their preparation. The
known methods of synthesis of tetrahydrodibenzo[c,f ]pyrrolo[1,2-
a]azepines that involved formation of a pyrrole ring via cyclization
of precursors with preformed dibenzo[b,e]azepine system9 or
formation of dibenzo[c,f ]pyrrolo[1,2-a]azepine moiety via
cyclization of precursors with preformed pyrrole ring10 or
multistage transformation of pyrroloisoxazoles11 did not provide
a wide range of heterocycles of this type.
In the framework of our research concerning the synthesis
of heterocycles via N-ylide reactions,12 we have recently pre-
sented an effective approach to 1-aryl-1,11b-dihydroazirino[1,2-
d]dibenz[b,f ][1,4]oxazepines13 which are excellent precursors of
corresponding azomethine ylides. They easily undergo com-
pletely stereoselective 1,3-dipolar cycloaddition to C C dipo-
larophiles with the formation of a great variety of derivatives
of dibenzo[b,f ]pyrrolo[1,2-d][1,4]oxazepine. In this study we have
extended our investigations to the replacement of the oxazepine
moiety with azepine.
Compounds with nitrogen heterocycles ortho-fused to
dibenzo[b,e]azepine demonstrate various bioactivities: derivatives
of dibenzo[c,f ]imidazo[1,5-a]azepine have specific binding
to histamine-1 and histamine-2 receptors1 and can be used
as antiallergics and antithrombotics,2 sedative and antiulcer
agents;3 derivatives of dibenzo[c,f ]pyrimido[1,6-a]azepine
show antidepressive and anxiolytic activity;4 derivatives of
dibenzo[c,f ]pyrido[1,2-a]azepine are highly specific for the
glucocorticoid receptor,5 partial agonists or antagonists of the
progesterone receptor;6 derivatives of dibenzo[c,f ]pyrazino[1,2-
a]azepine show anti-allergic and anti-asthmatic activities7 and
anxiolytic properties.8 Derivatives of dibenzo[c,f ]pyrrolo[1,2-
a]azepine were patented as having valuable antihistamine,
aDepartment of Chemistry, Saint Petersburg State University, Universitetskii
pr. 26, 198504, St. Petersburg, Russia. E-mail: alexander.khlebnikov@
pobox.spbu.ru; Fax: +7 812 4286939; Tel: +7 812 4284021
bDepartment of Chemistry, University of Durham, South Rd., Durham,
UK DH1 3L. E-mail: d.s.yufit@durham.ac.uk; Fax: +44 191-334-2051;
Tel: +44 191-334-2004
cInstitute of Physics, University of Neuchaˆtel, rue Emile-Argand 11,
CH-2000, Neuchaˆtel, Switzerland. E-mail: helen.stoeckli-evans@unine.ch;
Fax: +41 32 7182511; Tel: +41 32 7182426
Results and discussion
Preparation of derivatives of 9H-dibenzo[c,f ]pyrrolo[1,2-a]aze-
pine 1 via 7,11b-dihydro-1H-azirino[1,2-a]dibenzo[c,f ]azepines 2
according to retrosynthetic Scheme 1 seemed to be an attractive
idea. The synthesis of compounds 5a,b was performed by reaction
of imines 6a,b with dichlorocarbene generated from CHCl3
and solid KOH in the presence of TEBA as phase-transfer
† Dedicated to Professor Oleg Nefedov on the occasion of his 80th
birthday.
‡ Electronic supplementary information (ESI) available: X-Ray diffraction
data, refinement information and Cartesian coordinates. CCDC reference
numbers 809443, 809444, 809445, 809446, and 809447 for 2b, 13, 16, 18
& 20, respectively. For ESI and crystallographic data in CIF or other
electronic format see DOI: 10.1039/c1ob05081h
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The structure of compound 2b was confirmed by X-ray analysis
(Fig. 1). In the solid state aziridine 2b is in the most stable
conformation (cf . Fig. 3) with anti-oriented three-membered ring
and the methylene group of the dibenzazepine fragment.
Fig. 1 X-Ray crystal structure of 2b.
◦
Heating aziridines 2a,b in anhydrous toluene at 105 C led to
Scheme
pyrrolo[1,2-a]azepine 1.
1
Retrosynthetic approach to derivatives of dibenzo[c,f ]-
aziridine ring opening with formation of ylides 7 which in the
presence of dipolarophiles 8–12 containing an activated C
C
catalyst at 19–21 ◦C (Scheme 2). However when we tried to
synthesize compound 3 by making use of the domino sequence:
isomerization of gem-dichloroaziridine 5–intramolecular Friedel–
Crafts acylation of the tethered benzene ring in 4 under the con-
ditions used previously for preparation of the corresponding O-
analogs13a (AlCl3/MeNO2/50 ◦C) the only isolated product from
the complex reaction mixture was triphenylmethane. Probably, it
is the product of disproportionation which is characteristic for
alkylbenzenes in the presence of strong Lewis acids.14 Therefore,
we tested weaker Lewis acids (SnCl4, BF3·Et2O, TiCl4) as catalysts.
It was found that with BF3·Et2O or TiCl4 as catalyst the reaction
of aziridine 5b proceeded very slowly at 35 ◦C, while long heating
at this or higher temperature led to tarring and low yield of the
target compound (less then 10%). The Lewis acid of choice for
the realization of the target domino reaction proved to be SnCl4,
giving azepines 3a,b in reasonable yields.
double bond gave rise to 1,3-dipolar adducts 13–20 in good yields
(Table 1).
When the reactions were performed under solvent free condi-
tions at 140 ◦C they proceeded much faster yielding the same
products. The structures of compounds 13–20 were verified by
1
1H, 13C, H 2D NOESY NMR, IR spectroscopy, and elemental
analysis. Structures of 13, 16, 18 and 20 were confirmed by X-ray
analysis (Fig. 2).
Scheme 2 Synthesis of azirinodibenzazepines 2a,b.
Compounds 3a,b are very unstable and therefore they were
immediately introduced into the next step after workup of the
reaction mixtures without further purification. The preparation
of azirinodibenzazepines 2a,b was performed by reduction of
3a,b with LiAlH4 in 55–56% yields based on the starting
dichloroaziridines 5a,b. The 1H NMR spectra of compounds 2a,b
exhibited the characteristic coupling constant value for trans-
aziridines of ~3 Hz (J for cis- and trans-aziridines are 6–7 and
2.5–3.5 Hz, respectively15).
Fig. 2 X-Ray crystal structures of 13, 16, 18 and 20.
The main feature of all the products of the cycloaddition is cis-
configuration of pyrrolidine hydrogen at carbons in the a-position
to the nitrogen. This means that the ylide which cycloadds to the
C
C double bond of dipolarophiles has U- or W-configuration.16
According to DFT B3LYP/6-31G(d) calculations (Fig. 3) the
ring opening of aziridine trans-2a occurs conrotatory with the
formation either of the W-ylide 21 or the U-ylide 22. Formation of
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Table 1 Reaction of aziridines 2a,b with C C dipolarophiles 8–12
Entry
Aziridine 2
Dipolarophile
Product
Methoda
Time (h)
Yield (%)
1
2
a
A
B
16
4.5
70
70
3
4
5
b
a
a
8
A
A
B
15
16
3.5
67
68
72
6
a
B
5
89
7
8
a
b
A
A
17
18
73
78
12
a A: toluene, 105 ◦C; B: melt, 140 ◦C.
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Fig. 3 Reaction profiles for transformations of aziridines and ylides. Relative free energies [kcal mol-1] computed at the B3LYP/6-31G(d) level. Hydrogen
atoms on aromatic rings are omitted for clarity.
the latter involves transformation of the most stable conformation
of aziridine trans-2a to the less stable conformation trans-2a¢ via
inversion of azepine ring.
lowest barriers to cycloaddition are 9.0, 9.5, 13.6 and 10.7 kcal
mol-1, respectively, that is much less then the estimated barrier to
Z,E-isomerization of ylide 21.
The W-ylide 21 is more stable than the U-ylide 22 by 18.3
kcal mol-1 and the barrier to formation of the former is 8.5 kcal
mol-1 lower than that of the latter. Ylide 21 can be transformed
to the even more stable S-ylide 23 by rotating the PhCH group
around the C–N bond of the ylide. We were unable to find the
transition state for the transformation of ylides 21→23 because
of the extraordinary complexity of the potential energy surface.
Evaluation of a barrier to isomerization of ylides 21→23 was based
on the barriers to Z,E-isomerization of the iminium ylide: -CH2–
N+H CH2 (24), -CH2–N+Ph CH2 (25), -CHPh–N+H CH2
(26), and 1,4-oxazepiniomethanide (27) which were calculated
earlier13b and the corresponding barrier for azepiniomethanide
28 (DG# 29.6 kcal mol-1) calculated in this work. By using both
restricted and unrestricted B3LYP/6-31G(d) calculations, it was
found that the barriers to Z,E-isomerization change only a little
in the row of model ylidic structures 24–28. Hence, the value of the
barrier to transformation of ylides 21→23 is about 30 kcal mol-1.
The stereochemistry of cycloadducts 13–20 and calculated energy
parameters testify to the participation of only W-ylide 21 in the
cycloaddition.
The cycloaddition of cis-dipolarophiles proceeds via the exo-
transition state, which is in agreement with the results obtained
by DFT B3LYP/6-31G(d) computations: the minimal barriers
for exo-approach of maleonitrile, dimethyl maleate and N-
phenymaleimide to ylide 21 are less than those for endo-approach
by 2.2, 1.0, and 4.1 kcal mol-1, respectively.
We also performed stereoselective cycloaddition of ylide 7b
to fullerene C60. Heating aziridine 2b and fullerene C60 in o-
dichlorobenzene (o-DCB) at 100 ◦C led to the exclusive formation
of fulleropyrrolidine 29 (Scheme 3), with cis-orientation of pyrroli-
dine hydrogens. The composition of the product 29 was confirmed
by the exact mass experiments. The structure of the product is
in agreement with 1H-NMR and 13C-NMR data. cis-Orientation
of the pyrrolidine protons was confirmed by the presence of a
through-space interaction between them (2D 1H-NOESY).
One can also conclude from the results obtained that the
observed stereoselectivity is due to the lower barrier to cycload-
dition of ylide 21, compared with the barrier to transformation
of ylides 21→23. The results of the calculations of transition
states of cycloaddition of ylide 21 to fumaronitrile, maleonitrile,
dimethyl maleate and N-phenylmaleimide do not contradict
this conclusion. Four possible transition states were found (See
Supporting Information) for each of these dipolarophiles. The
Scheme 3 Synthesis of fulleropyrrolidine 29.
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Heating aziridine 2a and DMAD at 140 ◦C for 4.5 h gave rise to
adduct 30 (Scheme 4) which was isolated in 76% yield. Obviously
pyrrole 30 was formed via cycloaddition of ylide 7a to the triple
bond of DMAD and subsequent dehydrogenation of primarily
pyrrolidine cycloadduct 31.
Scheme 4 Synthesis of pyrrolodibenzazepine 30.
The conformation and conformational dynamics of biolog-
ically relevant molecules is the key to understanding their
functions.17 Taking into account the bioactivity demonstrated
by some derivatives, dibenzo[c,f ]pyrrolo[1,2-a]azepines9 and
dibenzo[b,f ]pyrrolo[1,2-d][1,4]oxazepines,9 we examined factors
which have an influence on conformations of cycloadducts syn-
thesised in this and previous works.13
Fig. 4 Conformers of compounds 35, 36, the relative free energies, bond
lengths, and H–H-distances computed at the B3LYP/6-31G(d) level.
Earlier it has been established13a by X-ray analysis that
dibenzo[c,f ]pyrrolo[1,2-a]oxazepines 33, 34, the adducts of ylide
32 (O-analog of ylide 7a) to dimethyl maleate 9 and fumaronitrile
10, have quite different conformations (Scheme 5). In compound
33 O-9 is cis-oriented to H-3 and H-13b and the pyrrolidine ring
has a half-chair conformation in which H-3 is in the equatorial
and H-13b is in the axial position (conformation A see Fig. 4). In
contrast, in compound 34 O-9 is trans-oriented to H-3 and H-13b
and pyrrolidine ring has an envelop conformation in which H-3
and H-13b are in axial positions (conformation B, see Fig. 4).
According to calculations,13b the adduct 35 of ylide 32 to fullerene
C60 has a conformation similar to conformation B. Experimentally
the structure of this adduct was confirmed by the presence of a
strong through-space interaction between the pyrrolidine protons
in 2D 1H-NOESY spectrum, taking into account that the distance
tween conformations of type A and B (See Fig. 4). Namely,
in conformation A the interaction of H-9 and H-13b has to
be present, while the interaction of H-3 and H-13b has to be
absent; in conformation B the contrary has to be true, that is the
interaction H-3 and H-13b has to be present, while the interaction
H-9 and H-13b has to be absent. The analysis of X-ray data
of compounds 13, 16, 18, 20 and 2D 1H-NOESY spectra of
compounds 13, 15–18, 29 shows that compounds 13, 15 have
conformation of type A and compounds 16–18, 20 and 29 have
conformation of type B. Thus, the adducts of the ylides with
fullerene C60 and N-arylmaleimides have conformation of type
B that can be determined by the rigidity of the fullerene and
maleimide skeletons. But utterly unexpectedly the adducts with
methoxycarbonyl-substituents have conformation of type A, while
the adducts with cyano-substituents have conformation of type B
irrespective of cis- or trans-arrangement of these substituents.
To ascertain the reasons of the conformational preference of
2,3,9,13b-tetrahydro-1H-dibenzo[c,f ]pyrrolo[1,2-a]azepine (36)
and 1,2,3,13b-tetrahydrodibenzo[b,f ]pyrrolo[1,2-d][1,4]oxazepine
(37) systems we performed DFT calculations of the conformations
of parent compounds 36, 37. Two conformations of type A and
B with close energy were found for each of compounds (Fig. 4).
The barriers to transformations of conformations A, B via ring
inversion according to computations are low (Fig. 4) and therefore
the existence of compounds in one or the other of conformations
is dependent on their relative free energies rather than on kinetic
factors of their formation.
˚
between these protons in the conformation like B is 2.428 A and
13b
˚
in the conformation like A is 3.617 A.
The results of these calculations are consistent with the sugges-
tion that the conformational preference of adducts of fullerene
and maleimides is due to the structural features of these fragments
in compounds 20, 29, 35. Namely, only in conformations 36B and
37B (Fig. 4) is there a possibility for fusion of bond C1–C2 with
the practically planar maleimide pentagon and fullerene hexagons.
The characteristic feature of the conformations of compounds
36, 37 is the difference of the C1–C2 bond lengths in the pyrrolidine
Scheme 5 Cycloaddition of ylide 32.
There are two possible characteristic through-space interac-
tions in 2D 1H-NOESY spectra of compounds containing a
dibenzazepine moiety that can be used for distinguishing be-
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Table 2 The experimental and calculated bond lengths in
1H-dibenzo[c,f ]pyrrolo[1,2-a]azepine systems can exist in confor-
mations of two types: A, in which C-9 is cis-oriented to H-3 and
H-13b and the pyrrolidine ring has a half-chair conformation with
H-3 in the equatorial and H-13b in the axial position, and B, in
which C-9 is trans-oriented to H-3 and H-13b and the pyrrolidine
ring has an envelop conformation with H-3 and H-13b in axial
positions. The conformation B is characteristic of compounds with
the pyrrolidine ring fused with a planar ring (maleimide pentagon
and fullerene hexagons) as well as cyano-substituted compounds,
and the conformation A is characteristic of methoxycarbonyl-
substituted compounds. It was suggested that the dependence on
the substituents (CO2Me/CN) is at least partly due to the influence
of these substituents on simple bond lengths.
methoxycarbonyl- and cyano-substituted molecules
a
b
˚
˚
˚
lC–C [A]
Adduct
lC1–C2 [A]
Compound
lC–C [A]
13-A
16-B
18-B
33-A
34-B
1.515(2)
1.557(4)
1.551(4)
1.543(3)
1.562(3)
CH3CH3
EtCN
ap-Succinonitrile
sc-Succinonitrile
EtCO2Me
ap-Dimethyl succinate
sc-Dimethyl succinate
1.531
1.540
1.551
1.550
1.527
1.527
1.526
1.535118
1.5479(15)19
1.561(6)20
—
—
1.509(5)21
—
a The CH2–CH2bond lengths computed at the B3LYP/6-31G(d) level.
b The experimental CH2–CH2bond lengths.
ring: in conformations A it is much shorter than in conformations
B.
Experimental section
The comparison of the C1–C2 bond lengths in compounds 13,
16, 18, 33, 34 determined by X-ray analysis (Table 2) disclose the
same tendency. Therefore we have hypothesized that the influence
of methoxycarbonyl- and cyano-substituents in the adducts on
conformational preferences can be related to the influence of these
substituents on single C–C bond length.
In fact, analysis of experimentally determined RH2C–CH2R¢
bond lengths in ethane, propanenitrile, dimethyl ester and dinitrile
of butanedioic acid shows that introduction of methoxycarbonyl-
substituents on the ethane C–C bond shortens this bond, while
introduction of cyano-substituents lengthens it (Table 2). DFT
B3LYP/6-31G(d) computations of the same molecules disclose
the same tendency. In the case of disubstituted derivatives this
influence weakly depends on the conformation (Table 2). These
findings allow us to conclude that dependence of conformational
preferences on methoxycarbonyl- and cyano-substituted adducts
is at least partly related to the influence of these substituents
on equilibrium bond lengths, as a deviation from these values
destabilizes the corresponding conformation.
General experimental details
Melting points were determined on a hot stage microscope
(Boetius) and are uncorrected. IR spectra were recorded on a
Specord M80 spectrometer. H (300 MHz) and 13C (75 MHz)
1
NMR spectra were determined in CDCl3 or DMSO-d6 with a
Bruker DPX 300 spectrometer. Chemical shifts (d) are reported
in ppm downfield from tetramethylsilane. Elemental analysis was
performed on a Hewlett-Packard 185B CHN-analyser. The X-
ray intensity data for 2b were collected at 173 K on a Stoe
Mark II-Image Plate Diffraction System equipped with a two-
circle goniometer and using Mo-Ka graphite monochromated
radiation. The structure was solved using direct methods and
refined by full-matrix least-squares on F2 for all data.22 The H-
atoms were included in calculated positions and treated as riding
atoms using SHELXL23 default parameters. The single crystal X-
ray data for the compounds 13 and 16 were collected at 120 K
on a Bruker SMART CCD 6000 diffractometer equipped with a
Cryostream (Oxford Cryosystems) open flow nitrogen cryostat
and using graphite monochromated lMo-Ka radiation (l =
◦
˚
0.71073 A, w-scan, -0.3 /frame). The data for compounds 18
and 20 were collected an a Bruker Microstar rotating anode
diffractometer with APEXII CCD detector using mirror-focused
Conclusions
In summary, a novel effective approach to azepino-fused hete-
rocycles is described. trans-1-Aryl-7,11b-dihydro-1H-azirino[1,2-
a]dibenzo[c,f ]azepines were synthesised via domino sequence:
isomerization of gem-dichloroaziridine–intramolecular Friedel–
Crafts acylation of the tethered benzene ring catalysed by SnCl4
and subsequent hydride induced intramolecular cyclization. These
aziridines are excellent precursors of heterocyclic azomethine
ylides which easily undergo completely stereospecific and stere-
oselective 1,3-dipolar cycloadditions to C C dipolarophiles with
the formation of dibenzo[c,f ]pyrrolo[1,2-a]azepine derivatives.22
1,3-Dipolar cycloaddition of the heterocyclic azomethine ylides
was also easily performed with DMAD and fullerene C60 as
dipolarophiles. Solvent free conditions allow the reactions to be
performed much faster. The reaction proceeds via cycloaddition
of W-ylide only, which does not undergo E,Z-isomerization under
the reaction conditions due to the high activation barrier. This
gives rise to cycloadducts with cis-configuration of pyrrolidine
hydrogen at carbons in a-position with respect to nitrogen. The
cycloaddition of cis-dipolarophiles proceeds via the exo-transition
state that is in agreement with the results of DFT B3LYP/6-
31G(d) computations. It was disclosed that 2,3,9,13b-tetrahydro-
◦
˚
lCu-Ka radiation (l = 1.54188 A, w-scan, -0.3 /frame) and
equipped with a Cobra (Oxford Cryosystems) cooling device at
120 and 100 K respectively. The structures were solved by a direct
method and refined by full-matrix least squares on F2 for all data
using OLEX2 software.24 Mass-spectrometry data were obtained
using a micrOTOF 10223 equipped with an electrospray ion source
or Accurate-Mass Q-TOF LC-MS G530. Flash chromatography
was performed using Merck silica (0.040–0.063 mm). TLC analysis
was performed on glass backed plates (Merck) coated with
0.2 mm silica layer with UV-indicator 60F254. Compound 6a was
prepared by the reported procedure.25
N-(4-Chlorobenzylidene)-2-benzylaniline (6b)
4-Chlorobenzaldehyde (2.21 g, 15.7 mmol) was added to a stirred
solution of 2-benzylaniline (2.88 g, 15.7 mmol) in ethanol (15 mL)
◦
at 30–40 C and then the reaction mixture was stirred for 4 h at
rt. The formed precipitate was separated and recrystallized from
ethano◦l to give 4.38 g (94%) of imine 6b as a yellowish solid, mp
55–57 C (from EtOH) (Found: C, 78.65; H, 5.25; N, 4.5. Calc.
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for C20H16ClN: C, 78.55; H, 5.3; N, 4.6%); nmax(CHCl3)/cm-1 1632
(N CH); dH (300 MHz; CDCl3; Me4Si) 4.16 (2H, s, CH2), 6.99 (1
H, m, Harom), 7.09–7.33 (8 H, m, Harom), 7.47 (2 H, m, Harom), 7.84
(2 H, m, Harom), 8.29 (1 H, s, N CH). dC (75 MHz; CDCl3; Me4Si)
37.5 (CH2), 117.7, 125.7, 126.2, 127.3, 128.2, 128.9, 129.0, 129.9,
130.0, 134.9, 135.2, 137.2, 141.3, 150.2 (Carom), 158.2 (N CH).
ether (70 mL), and then the reaction mixture was refluxed for 3 h.
The mixture was cooled, treated with a saturated aq solution of
Na2SO4 and filtered. The filtrate was concentrated under reduced
pressure and the residue was crystallized from hexane to give 1.82 g
(56% based on starting 5a) of compound 2a as a colorless solid,
mp 115–117 ◦C (from hexane) (Found: C, 89.1; H, 6.1; N, 5.0.
Calc. for C21H17N: C, 89.0; H, 6.1; N, 4.9%); nmax(CHCl3)/cm-1
1232, 1452, 1488, 3068; dH (300 MHz; CDCl3; Me4Si): 3.28 (1 H,
d, J 3.3, CH), 3.36 (1 H, d, J 13.2, CH2), 3.86 (1 H, d, J 3.3, CH),
4.92 (1 H, d, J 13.2, CH2), 6.82–6.84 (1 H, m, Harom), 6.99–7.24 (12
H, m, Harom); dC (75 MHz; CDCl3; Me4Si) 38.4 (CH2), 47.0 (CH),
48.9 (CH), 121.9, 122.0, 126.1, 127.1, 127.3, 127.5, 127.9, 127.9,
128.0, 128.6, 129.9, 133.1, 133.3, 139.3, 142.5, 148.4 (Carom).
1-(2-Benzylphenyl)-2,2-dichloro-3-phenylaziridine (5a)
Powdered KOH (3.35 g, 59.7 mmol) was added in small portions
to a vigorously stirred solution of imine 6a (2.70 g, 9.94 mmol) and
benzyltriethylammonium chloride (TEBA) (0.451 g, 1.98 mmol)
in chloroform (30 mL) at 19–21 ◦C, and then the reaction mixture
was stirred for 3 h. After addition of hexane (100 mL) the reaction
mixture was stirred for 0.5 h, then passed through a basic alumina
plug, which was subsequently washed with hexane. The solvent
was removed under reduced pressure, and the residue crystallized
from hexane to give 2.62 g (74%) of aziridine 5a as a colorless
solid, mp 60–62 ◦C (from hexane) (Found: C, 71.1; H, 4.8; N, 4.1.
Calc. for C21H17Cl2N: C, 71.2; H, 4.8; N, 3.95%); nmax(CHCl3)/cm-1
1264, 1400, 1454, 1492, 1600, 3064; dH (300 MHz; CDCl3; Me4Si):
3.86 (1 H, s, CH), 4.17 (1 H, d, J 16, CH2), 4.45 (1 H, d, J 16,
CH2), 6.88 (1 H, m, Harom), 7.11–7.39 (13 H, m, Harom); dC (75 MHz;
CDCl3; Me4Si) 37.6 (CH2), 52.9 (CH), 76.5 (CCl2), 118.3, 124.9,
126.2, 126.9, 127.9, 128.3, 128.4, 128.9, 129.4, 129.5, 130.3, 132.7,
135.2, 140.0, 143.0 (Carom).
trans-1-(4-Chlorophenyl)-7,11b-dihydro-1H-azirino[1,2-
a]dibenzo[c,f ]azepine (2b)
Compound 2b was prepared, analogously to 2a from aziridine 5b
(1.50 g, 3.85 mmol), SnCl4 (3.01 g, 11.55 mmol), and then LiAlH4
(0.146 g, 3.85 mmol) to afford 0.67 g (55% based on starting
5a) of compound 2b as a colorless solid, mp 175–177 ◦C (from
benzene) (Found: C, 79.5; H, 5.1; N, 4.4. Calc. for C21H16ClN: C,
79.4; H, 5.1; N, 4.4%); nmax(CHCl3)/cm-1 1312, 1454, 1490, 3068;
dH (300 MHz; CDCl3; Me4Si): 3.23 (1 H, d, J 2.9, CH), 3.35 (1
H, d, J 14, CH2), 3.79 (1 H, d, J 2.9, CH), 4.87 (1 H, d, J 14,
CH2), 6.79–6.83 (1 H, m, Harom), 6.93–6.96(1 H, m, Harom), 7.05–
7.10 (2 H, m, Harom), 7.13–7.31 (6 H, m, Harom), 7.37–7.49 (3 H, m,
Harom); dC (75 MHz; CDCl3; Me4Si) 38.3 (CH2), 46.3 (CH), 49.1
(CH), 121.8, 122.0, 127.1, 127.3, 127.4, 127.9, 128.0, 128.05, 128.7,
129.8, 132.9, 133.0, 133.2, 137.8, 142.4, 148.1 (Carom). Crystal data.
C21H16ClN, M = 317.80, monoclinic, a = 11.5596(6), b = 9.9041(5),
1-(2-Benzylphenyl)-2,2-dichloro-3-(4-chlorophenyl)aziridine (5b)
Compound 5b was prepared, analogously to 5a from imine
6b (3.78 g, 12.36 mmol), KOH (4.16 g, 74.16 mmol), and
benzyltriethylammonium chloride (TEBA) (0.563 g, 2.47 mmol)
to afford 3.67 g (76%) of aziridine 5b as a colorless solid, mp
49–51 ◦C (from hexane) (Found: C, 64.85; H, 4.3; N, 3.6. Calc.
for C21H16Cl3N: C, 64.9; H, 4.15; N, 3.6%); nmax(CCl4)/cm-1 1016,
1454, 1494, 1600, 3068; dH (300 MHz; CDCl3; Me4Si): 3.80 (1 H, s,
CH), 4.15 (1 H, d, J 16.2, CH2), 4.41 (1 H, d, J 16.2, CH2), 6.85
(1 H, m, Harom), 7.10–7.45 (12 H, m, Harom); dC (75 MHz; CDCl3;
Me4Si) 37.6 (CH2), 52.2 (CH), 76.3 (CCl2), 118.7, 125.5, 126.7,
127.4, 128.8, 129.0, 129.7, 129.9, 130.9, 131.7, 135.3, 135.4, 140.2,
143.0 (Carom).
◦
3
˚
˚
c = 13.9757(7) A, b = 91.254(4) , U = 1599.66(14) A , T = 173(2)
K, space group P 21/n (no. 14), Z = 4, 7700 reflections measured,
3392 unique (Rint = 0.0621) which were used in all calculations.
The final wR(F2) was 0.0957 (all data).
General procedures for cycloaddition of ylides from
trans-1-aryl-7,11b-dihydro-1H-azirino[1,2-a]dibenzo[c,f ]azepines
(2a,b) to dipolarophiles
A. A solution of compound 2a,b (100 mg, 0.353/0.315 mmol)
and dipolarophile in anhyd toluene (5 mL) was heated at 105 ◦C
(reaction time is indicated in Table 1). The reaction was monitored
by TLC. The solvent was removed in vacuo and the residue was
purified by crystallisation or flash chromatography.
trans-1-Phenyl-7,11b-dihydro-1H-azirino[1,2-
a]dibenzo[c,f ]azepine (2a)
A solution of SnCl4 (8.82 g, 33.87 mmol) in anhydrous ni-
tromethane (10 mL) was added to a vigorously stirred solution
of aziridine 5a (4.0 g, 11.29 mmol) in nitromethane (25 mL) at r.t.,
and then the reaction mixture was stirred for 1.5 h at 35 ◦C. The
reaction mixture was cooled, poured into cold water (100 mL) and
extracted with dichloromethane (50 mL). The organic layer was
separated and washed successively with water (2 ¥ 25 mL), diluted
solution of K2CO3, and then with water to neutral pH. The organic
solution was dried (Na2SO4) and the solvents were removed on
a rotary evaporator in vacuo (0.1 Torr/20 C bath temperature)
and the residue was immediately used for the next step without
purification.
A suspension of LiAlH4 (0.857 g, 22.58 mmol) in anhyd ether
(25 mL) was slowly added to a stirred solution of the crude
6-[chloro(phenyl)methyl]-11H-dibenzo[b,e]azepine in anhydrous
B. A mixture of compound 2a (100 mg, 0.353 mmol) and
dipolarophile was heated at 140 ◦C (reaction time is indicated in
Table 1). After cooling the product was purified by crystallisation
or flash chromatography.
Dimethyl (1RS,2RS,3SR,13bRS)-3-phenyl-2,3,9,13b-tetrahy-
dro-1H-dibenzo[c,f ]pyrrolo[1,2-a]azepine-1,2-dicarboxylate (13).
Compound 13 (0.105 g, 70%) was obtained from 2a (0.100 g, 0.353
mmol) and dimethyl fumarate 8 (0.101 g, 0.701 mmol) according
to the procedure A and B. A colorless solid, mp 178–180 ◦C
(from CH2Cl2–MeOH) (Found: C, 75.5; H 5.9; N, 3.5. Calc. for
C27H25NO4: C, 75.9; H, 5.9; N, 3.3%); nmax(CHCl3)/cm-1 1008,
1172, 1304, 1492, 1596, 1736 (C O), 3064; dH (300 MHz; CDCl3;
Me4Si): 3.41 (3 H, s, CH3), 3.72 (3 H, s, CH3), 3.95 (1 H, dd, J
10.0, 8.6, CH), 4.00 (1 H, d, J 14, CH2), 4.10 (1 H, dd, J 10.0, 10.6,
◦
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CH), 4.65 (1 H, d, J 14, CH2), 5.19 (1 H, d, J 8.6, CH), 5.60 (1 H,
d, J 10.6, CH), 6.32 (1 H, d, J 8, Harom), 6.63–6.68 (1 H, m, Harom),
6.84–6.89 (1 H, m, Harom), 7.05–7.08 (1 H, m, Harom), 7.17–7.34
(8 H, m, Harom), 7.50–7.53 (1 H, m, Harom); dC (75 MHz; CDCl3;
Me4Si) 40.3 (CH2), 47.4 (CH), 51.7 (CH3), 51.9 (CH3), 52.4 (CH),
64.7 (CH), 66.5 (CH), 116.8, 119.5, 125.7, 126.9, 127.0, 127.5,
127.8, 128.0, 128.3, 128.4, 128.5, 129.4, 135.1, 138.7, 139.8, 144.0
(Carom), 170.1 (C O), 172.7 (C O). Crystal data. C27H25NO4,
J 10.0, 7.7, CH), 3.63 (1 H, dd, J 10.0, 8.9, CH), 3.83 (1 H, d, J
13.8, CH2), 4.68 (1 H, d, J 13.8, CH2), 4.97 (1 H, d, J 8.9, CH),
4.99 (1 H, d, J 7.7, CH), 6.70 (1 H, d, J 7.3, Harom), 6.89–6.93 (1
H, m, Harom), 6.99–7.04 (1 H, m, Harom), 7.19–7.21 (1 H, m, Harom),
7.29–7.35 (8 H, m, Harom), 7.42–7.45 (1 H, m, Harom); dC (75 MHz;
CDCl3; Me4Si) 37.8 (CH2), 39.4 (CH), 39.7 (CH), 68.0 (CH), 68.2
(CH), 116.6 (C N), 117.1 (C N), 119.7, 123.8, 126.6, 127.36,
127.42, 127.5, 128.4, 128.7, 129.0, 129.4, 129.9, 133.9, 135.6,
136.6, 137.3, 141.9 (Carom); m/z (ESI) 362.168 (M + H+. C25H20N3
+
M = 427.48, monoclinic, a◦= 10.0710(2), b = 25.9843(5), c =
3
˚
˚
17.0032(3) A, b = 104.46(1) , U = 4308.58(14) A , T = 120 K,
space group P 21/n (no. 14), Z = 8, 52462 reflections measured,
11451 unique (Rint = 0.0702) were used in all calculations. The
final wR2(F2) was 0.0949 (all data).
requires 362.165). Crystal data. C25H19N3 ¥ 0.125 CH2Cl2, M =
366.74, monoclinic, 36.9379(14), b = 28.7704(11), c = 15.8020(6)
◦
3
˚
˚
A, b = 113.74(1) , U = 15372.1(10) A , T = 120 K, space group
C2/c (no. 15), Z = 32, 69184 reflections measured, 16751 unique
(Rint = 0.1100) were used in all calculations. The final wR2(F2) was
0.1546 (all data).
Dimethyl (1RS,2RS,3SR,13bRS)-3-(4-chlorophenyl)-2,3,9,13b-
tetrahydro-1H-dibenzo[c,f ]pyrrolo[1,2-a]azepine-1,2-dicarboxy-
late (14). Compound 14 (0.097 g, 67%) was obtained from 2b
(0.100 g, 0.315 mmol) and dimethyl fumarate 8 (0.089 g, 0.617
mmol) according to the procedure A. A colorless solid, mp 196–
198 ◦C (from CH2Cl2–MeOH) (Found: C, 69.85; H, 5.35; N, 3.3.
Calc. for C27H24ClNO4: C, 70.2; H, 5.2; N 3.0%); nmax(CHCl3)/cm-1
1014, 1176, 1304, 1492, 1598, 1736 (C O), 3068; dH (300 MHz;
CDCl3; Me4Si): 3.44 (3 H, s, CH3), 3.73 (3 H, s, CH3), 3.94 (1 H,
dd, J 10.0, 8.6, CH), 4.03 (1 H, d, J 14, CH2), 4.10 (1 H, dd, J
10.0, 10.2, CH), 4.60 (1 H, d, J 14, CH2), 5.19 (1 H, d, J 8.6, CH),
5.59 (1 H, d, J 10.2, CH), 6.29 (1 H, d, J 8.6, Harom), 6.61–6.71 (1
H, m, Harom), 6.86–6.91 (1 H, m, Harom), 7.06–7.14 (3 H, m, Harom),
7.16–7.33 (5 H, m, Harom), 7.42–7.51 (1 H, m, Harom); dC (75 MHz;
CDCl3; Me4Si) 40.2 (CH2), 47.6 (CH), 51.7 (CH3), 51.9 (CH3),
52.5 (CH), 64.8 (CH), 65.8 (CH), 116.8, 119.9, 125.7, 127.0, 127.5,
124.8, 125.0, 125.9, 127.5, 128.4, 128.6, 129.5, 133.6, 135.0, 137.3,
143.6 (Carom), 170.0 (C O), 172.6 (C O); m/z (ESI) 462.1465 (M
(1RS,2RS,3RS,13bSR)-3-Phenyl-2,3,9,13b-tetrahydro-1H-di-
benzo[c,f ]pyrrolo[1,2-a]azepine-1,2-dicarbonitrile (17) and (1RS,
2RS,3SR,13bRS)-3-phenyl-2,3,9,13b-tetrahydro-1H-dibenzo[c,f ]-
pyrrolo[1,2-a]azepine-1,2-dicarbonitrile (18). A mixture of com-
pounds 17 and 18 (0.112 g, 1.3 : 1, 89%) was obtained from 2a
(0.100 g, 0.353 mmol) and fumaronitrile 11 (0.082 g, 1.05 mm◦ol)
according to the procedure B. A colorless solid, mp 204–207 C
(from ethyl ether) (Found: C, 82.7, H, 5.1; N, 11.6. Calc. for
C25H19N3: C, 83.0; H, 5.3; N 11.6%); nmax(CHCl3)/cm-1 1030, 1132,
1296, 1494, 1596, 2248 (CN), 3072; dH (300 MHz; CDCl3; Me4Si):
3.35 (1 H, dd J 7.4, 3.3, CH) (18), 3.55 (1 H, d, J 13.6, CH2) (18),
3.63 (1.3 H, dd, J 8.7, 6.0, CH) (17), 3.74 (1 H, dd, J 5.8, 3.3, CH)
(18), 3.80 (1.3 H, d, J 13.9, CH2) (17), 3.84 (1.3 H, dd, J 7.2, 6.0,
CH) (17), 4.68 (1 H, d, J 5.8, CH) (18), 4.73 (1.3 H, d, J 8.7, CH)
(17), 4.83 (1.3 H, d, J 13.9, CH2) (17), 4.86 (1 H, d, J 7.4, CH) (18),
5.03 (1.3 H, d, J 7.2, CH) (17), 5.12 (1 H, d, J 13.6, CH2) (18), 6.65
(1.3 H, d, J 8.0, Harom) (17), 6.83 (1 H, d, J 8.0, Harom) (18), 6.91–7.07
(5.3 H, m, Harom), 7.21–7.49 (22.3 H, m, Harom); dC (75 MHz; CDCl3;
Me4Si) 38.8 (CH2), 39.26 (CH2), 39.3 (CH), 39.4 (CH), 40.0 (CH),
41.1 (CH), 65.6 (CH), 68.4 (CH), 68.5 (CH), 68.6 (CH), 116.9
(C N), 118.3 (C N), 119.8 (C N), 120.4 (C N), 124.0, 124.6,
126.8, 127.1, 127.2, 127.3, 127.4, 127.7, 128.0, 128.3, 128.6, 128.65,
128.7, 128.95, 129.0, 129.1, 129.4, 130.0, 130.1, 132.2, 133.9, 134.6,
136.2, 136.9, 138.6, 141.0, 142.0 (Carom); m/z (ESI) 362.168 (M +
+ H+. C27H25ClNO4 requires 462.1467).
+
Dimethyl (1RS,2SR,3SR,13bRS)-3-phenyl-2,3,9,13b-tetrahy-
dro-1H-dibenzo[c,f ]pyrrolo[1,2-a]azepine-1,2-dicarboxylate (15).
Compound 15 (0.100 g, 67%) was obtained from 2a (0.100 g,
0.353 mmol) and dimethyl maleate 9 (0.101 g, 0.701 mmo◦ l)
according to the procedure A. A colorless solid, mp 198–200 C
(from CH2Cl2–MeOH) (Found: C, 75.5; H 6.0; N, 3.35. Calc. for
C27H25NO4: C, 75.9; H, 5.9; N, 3.3%); nmax(CHCl3)/cm-1 1028,
1176, 1292, 1492, 1596, 1744 (C O), 3064; dH (300 MHz; CDCl3;
Me4Si): 3.45 (1 H, dd, J 8.0, 4.1, CH), 3.73 (3 H, s, CH3), 3.78
(3 H, s, CH3), 3.84 (1 H, dd, J 8.0, 8.5, CH), 4.00 (1 H, d, J 14,
CH2), 4.74 (1 H, d, J 14, CH2), 5.20 (1 H, d, J 4.1, CH), 5.85 (1 H,
d, J 8.5, CH), 6.32 (1 H, d, J 8, Harom), 6.63–6.67 (1 H, m, Harom),
6.86–6.90 (1 H, m, Harom), 7.06–7.09 (1 H, m, Harom), 7.15–7.26
(8 H, m, Harom), 7.50–7.53 (1 H, m, Harom); dC (75 MHz; CDCl3;
Me4Si) 40.6 (CH2), 47.7 (CH), 52.3 (CH3), 52.34 (CH3), 53.8
(CH), 62.7 (CH), 66.9 (CH), 116.8, 119.2, 124.3, 126.5, 126.9,
127.45, 127.5, 128.0, 128.7, 128.74, 129.5, 136.6, 139.4, 141.1,
144.3 (Carom), 171.67 (C O), 171.7 (C O).
H+. C25H20N3 requires 362.165). Crystal data. C25H19N3, M =
+
361.43, monoclinic, a = 12.6196(2), b = 5.85170(10), c = 12.6336(2)
◦
3
˚
˚
A, b = 99.290(1) , U = 920.71(3) A , T = 120 K, space group P
21 (no. 4), Z = 2, 3871 reflections measured, 2041 unique (Rint
=
0.0249) which were used in all calculations. The final wR2(F2) was
0.0822 (all data).
(3aRS,3bRS,14SR,14aSR)-2,14-Diphenyl-3b,8,14,14a-tetrahy-
drodibenzo[c,f ]pyrrolo[3¢,4¢:3,4]pyrrolo[1,2-a]azepine-1,3(2H,
3aH)-dione (19). Compound 19 (0.118 g, 73%) was obtained
from 2a (0.100 g, 0.353 mmol) and N-phenylmaleimide 12 (0.121 g,
0.70 mmol) according to the procedure A. A colorless solid, mp
214–217 ◦C (from CH2Cl2–MeOH) (Found: C, 81.6, H, 5.4, N, 5.9.
Calc. for C31H24N2O2: C, 81.6, H 5.3, N 6.1%); nmax(CHCl3)/cm-1
812, 1028, 1178, 1294, 1494, 1560, 1624, 1716, 3068; dH (300 MHz;
CDCl3; Me4Si): 3.53 (1 H, dd, J 9.5, 8.0, CH), 3.70 (1 H, d,
J 13.8, CH2), 3.80 (1 H, dd, J 9.5, 6.7, CH), 4.78 (1 H, d, J
6.7, CH), 4.85 (1 H, d, J 8.0, CH), 4.98 (1 H, d, J 13.8, CH2),
6.86–7.05 (3 H, m, Harom), 7.21–7.59 (14 H, m, Harom), 7.83 (1
H, d, J 7.3 Hz, Harom); dC (75 MHz; CDCl3; Me4Si) 40.4 (CH2),
(1RS,2SR,3SR,13bRS)-3-Phenyl-2,3,9,13b-tetrahydro-1H-di-
benzo[c,f ]pyrrolo[1,2-a]azepine-1,2-dicarbonitrile
(16). Com-
pound 16 (0.091 g, 72%) was obtained from 2a (0.100 g, 0.353
mmol) and maleonitrile 10 (0.055 g, 0.705 mmol) according
to the procedure B. A colorless solid, mp 189–191 ◦C (from
CH2Cl2–MeOH); nmax(CHCl3)/cm-1 1028, 1136, 1296, 1494, 1598,
2252 (CN), 3068; dH (300 MHz; CDCl3; Me4Si): 3.36 (1 H, dd,
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52.8 (CH), 53.0 (CH), 67.9 (CH), 68.5 (CH), 120.1, 124.3, 126.5,
126.9, 127.5, 127.6, 127.8, 128.45, 128.53, 129.17, 129.23, 129.57,
129.61, 129.94, 129.97, 132.1, 134.6, 136.8, 137.4, 138.0, 139.3,
144.0 (Carom), 175.6 (C O), 176.7 (C O); m/z (ESI) 457.1901
CDCl3; Me4Si): 3.71 (1H, d, J 13.2, CH2), 3.77 (3H, s, CH3), 3.85
(3H, s, CH3), 4.16 (1H, d, J 13.2, CH2), 6.60 (1H, d, J 8, Harom),
6.80–6.85 (1H, m, Harom), 7.08 (1H, m, Harom), 7.11–7.34 (9H, m,
Harom), 7.60 (1H, d, J 8, Harom); dC (75 MHz; CDCl3; Me4Si) 38.8
(CH2), 51.7 (CH3), 52.1 (CH3), 115.4 (CH), 115.46 (CH), 126.4
(CH), 126.5 (CH), 126.7, 127.4, 127.7, 127.8, 127.9, 128.2, 129.1,
130.4, 130.7, 130.8, 134.4, 135.0, 136.4, 138.7, 141.3 (Carom), 165.0
(M + H+. C31H25N2O2 requires 457.1911).
+
(3aRS,3bRS,14SR,14aSR)-14-(4-Chlorophenyl)-2-phenyl-3b,
8,14,14a-tetrahydro-dibenzo[c,f ]pyrrolo[3¢,4¢:3,4]pyrrolo[1,2-a]-
azepine-1,3(2H,3aH)-dione (20). Compound 20 (0.121 g, 78%)
was obtained from 2b (0.100 g, 0.353 mmol) and N-
phenylmaleimide 12 (0.107 g, 0.62 mmol) according to the
procedure A. A colorless solid, mp 220–223 ◦C (from CH2Cl2–
MeOH); nmax(CHCl3)/cm-1 1016, 1184, 1296, 1492, 1600, 1718,
3048; dH (300 MHz; CDCl3; Me4Si): 3.48 (1 H, dd, J 9.5, 7.9,
CH), 3.69 (1 H, d, J 13.8, CH2), 3.80 (1 H, dd, J 9.5, 6.7, CH),
4.77 (1 H, d, J 6.7, CH), 4.82 (1 H, d, J 7.9, CH), 4.95 (1 H,
d, J 13.8, CH2), 6.82–7.06 (3 H, m, Harom), 7.22–7.61 (14 H, m,
Harom), 7.79–7.83 (1 H, m, Harom); dC (75 MHz; CDCl3; Me4Si) 39.9
(CH2), 52.2 (CH), 52.5 (CH), 66.8 (CH), 68.0 (CH), 119.5, 124.1,
126.0, 126.4, 127.1, 127.2, 127.4, 128.2, 128.5, 128.8, 129.0, 129.1,
129.2, 129.5, 129.6, 131.5, 133.7, 136.2, 137.0, 137.4, 137.5, 143.2
(Carom), 175.0 (C O), 176.1 (C O). m/z (ESI) 491.1541 (M + H+.
(C O), 166.4 (C O); m/z (ESI) 424.157 (M + H+. C27H22NO4
+
requires 424.154).
Computational Details
All calculations were performed with the B3LYP density func-
tional method26 by using the Gaussian suite of quantum chemical
programs. Geometry optimizations of intermediates, transition
states, reactants, and products in the gas phase were performed at
the B3LYP/6-31G(d) level using Gaussian 03.27 Stationary points
on the respective potential-energy surfaces were characterized at
the same level of theory by evaluating the corresponding Hessian
indices. Careful verification of the unique imaginary frequencies
for transition states was carried out to check whether the frequency
indeed pertains to the desired reaction coordinate. Intrinsic
reaction coordinates (IRC) were calculated to authenticate all
transition states.28
+
C31H24N2ClO2 requires 491.1521). Crystal data. C31H23N2ClO2,
M = 490.96, mon◦oclinic, = 10.6905(2), b = 7.6706(1), c = 29.1159(4)
3
˚
˚
A, b = 90.142(1) , U = 2387.57(6) A , T = 100 K, space group P
21/n (no. 14), Z = 4, 8647 reflections measured, 2697 unique (Rint
=
Acknowledgements
0.0909) which were used in all calculations. The final wR2(F2) was
We gratefully acknowledge the financial support of the Russian
Foundation for Basic Research (project 11-03-00186), Council
for Grants of the President of Russian Federation (grant no.
MK-3112.2010.3), and Federal Grant-in-Aid Program «Human
Capital for Science and Education in Innovative Russia»
(Governmental Contract no. 16.740.11.0442).
0.1178 (all data).
Compound 29. Solution of aziridine 2b (11 mg, 0.035 mmol)
in o-DCB (2 ml) was added dropwise to the stirred solution of
C60 (72 mg, 0.1 mmol) in o-DCB (3 ml) at 100 ◦C over 30 min.
The reaction mixture was stirred at 100 ◦C for additional 6 h.
The solvent was evaporated in vacuo and the residue was dissolved
in benzene and purified by column chromatography (silica gel,
benzene – petroleum ether). The obtained crude product was
washed with ether and dried under high vacuum to give 8 mg (22%)
of the adduct 29 as brown solid. dH (300 MHz; CDCl3; Me4Si):
3.74 d (1H, CH2, J 12.9 Hz), 5.66 d (1H, CH2, J 12.9 Hz), 6.05 (1H,
CH), 6.28 (1H, CH–(C6H4Cl)), 7.02–7.10 m (2H, Harom), 7.10–7.25
m (4H, Harom), 7.35–7.42 m (3H, Harom), 7.45–7.50 m (1H, Harom),
7.60–7.65 m (1H, Harom), 7.75–7.80 m (1H, Harom); dC (75 MHz;
C6D6; Me4Si): 40.1 (CH2), 75.5 (Csp3), 76.5 (Csp3), 76.6 (Csp3), 79.2
(Csp3), 123.2, 124.7, 126.6, 127.4, the region between 127.5 and
129.1 is shadowed with the signal of C6D5H, 129.5, 130.2, 130.90,
130.92, 131.1, 133.6, 134.4, 135.3, 136.6, 136.9, 137.2, 137.4,
139.6, 139.7, 139.87, 139.90, 140.4, 140.5, 141.8, 141.9, 142.0,
142.2, 142.3, 142.40, 142.45, 142.46, 142.5, 142.95, 142.99, 143.06,
143.14, 143.45, 143.46, 144.80, 144.83, 144.88, 145.0, 145.52,
145.56, 145.58, 145.59, 145.63, 145.64, 145.79, 145.82, 145.9,
146.0, 146.17, 146.21, 146.25, 146.50, 146.55, 146.63, 146.68,
146.72, 146.8, 146.9, 147.2, 147.6, 147.9, 152.7, 153.1, 153.8; m/z
(ESI) 1037.0972 (M + e-. C81H16ClN- requires 1037.0977).
Notes and references
1 G. Walther, H. Daniel, W. D. Bechtel and K. Brandt, Arzneimittel
Forschung, 1990, 40, 440.
2 US Pat., 4 503 060, 1985.
3 Ger. Pat. 2 248 477, 1973.
4 Ger. Pat. 2 347 727, 1974.
5 Eur. Pat. 1 924 580, 2007.
6 Eur. Pat. 1 495 030, 2005.
7 US Pat., 5 362 725, 1994.
8 US Pat., 4 284 559, 1981.
9 (a) US Pat., 4 039 558, 1977; (b) Ger. Pat. 2 548 045, 1976.
10 J. Y. Lee, N. J. Baek, S. J. Lee, H. Y. S. Park and Lee, Heterocycles, 2001,
55, 1519; J. L. Garcia Ruano, J. Ignacio Andres Gil, A. Fraile, A. M.
Martin Castro and M. R. Martin, Tetrahedron Lett., 2004, 45, 4653.
11 J. L. Garcia Ruano, J. Ignacio Andres Gil, A. Fraile, A. M. Martin
Castro and M. R. Martin, Tetrahedron Lett., 2004, 45, 4653.
12 (a) A. F. Khlebnikov, M. S. Novikov and R. R. Kostikov, Russ. Chem.
Rev., 2005, 74, 171; (b) A. F. Khlebnikov, M. S. Novikov, R. R. Kostikov
and J. Kopf, Russ. J. Org. Chem., 2005, 41, 1341; (c) I. V. Voznyi, M. S.
Novikov and A. F. Khlebnikov, Synlett, 2005, 1006; (d) A. S. Konev,
M. S. Novikov and A. F. Khlebnikov, Tetrahedron Lett., 2005, 46, 8337;
(e) I. V. Voznyi, M. S. Novikov, A. F. Khlebnikov and R. R. Kostikov,
Russ. J. Org. Chem., 2006, 42, 689; (f) A. F. Khlebnikov, M. S. Novikov,
A. A. Amer, R. R. Kostikov, J. Magull and D. Vidovic, Russ. J. Org.
Chem., 2006, 42, 515; (g) M. S. Novikov, A. A. Amer and A. F.
Khlebnikov, Tetrahedron Lett., 2006, 47, 639; (h) E. Yu. Shinkevich,
M. S. Novikov and A. F. Khlebnikov, Synthesis, 2007, 2, 225; (i) A. S.
Konev, M. S. Novikov and A. F. Khlebnikov, Russ. J. Org. Chem., 2007,
43, 286; (j) A. P. Kadina, M. S. Novikov, A. F. Khlebnikov and J. Magull,
Chem. Heterocycl. Compd., 2008, 44, 576; (k) E. Yu. Shinkevich, K.
Abbaspour Tehrani, A. F. Khlebnikov and M. S. Novikov, Tetrahedron,
Dimethyl 3-phenyl-9H-dibenzo[c,f ]pyrrolo[1,2-a]azepine-1,2-
dicarboxylate (30). Compound 30 (0.113 g, 76%) was obtained
from 2a (0.100 g, 0.353 mmol) and DMAD (0.099 g, 0.70 mmol)
◦
according to the procedure B. A colorless solid, mp 224–226 C
(from CH2Cl2–MeOH); nmax(CHCl3)/cm-1 812, 1016, 1180, 1288,
1362, 1410, 1476, 1488, 1534, 1604, 1720, 3044; dH (300 MHz;
3894 | Org. Biomol. Chem., 2011, 9, 3886–3895
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©

View Article Online
2008, 64, 7524; (l) K. A. Khistiaev, M. S. Novikov, A. F. Khlebnikov and
J. Magull, Tetrahedron Lett., 2008, 49, 1237; (m) A. F. Khlebnikov, M. S.
Novikov, S. A. Dolgikh and J. Magull, ARKIVOC, 2008, 94; (n) A. S.
Konev and A. F. Khlebnikov, Collect. Czech. Chem. Commun., 2008,
1553; (o) V. A. Khlebnikov, M. S. Novikov, A. F. Khlebnikov and N. V.
Rostovskii, Tetrahedron Lett., 2009, 50, 6509; (p) A. F. Khlebnikov and
M. S. Novikov, Russ. J. Gen. Chem., 2010, 80, 1652.
Urbaniak, M. Domagała, A. Pfitzner, M. Zabel and H. Heimgartner,
Helv. Chim. Acta, 2009, 92, 2631.
23 G. M. Sheldrick, Acta Crystallogr., Sect. A: Found. Crystallogr., 2008,
A64, 112.
24 O. V. Dolomanov, L. J. Bourhis, R. J. Gildea, J. A. K. Howard and H.
Puschmann, J. Appl. Crystallogr., 2009, 42, 339.
25 E. C. Creencia, K. Taguchi and T. Horaguchi, J. Heterocycl. Chem.,
2008, 45, 837.
13 (a) A. F. Khlebnikov, M. S. Novikov, P. P. Petrovskii, J. Magull and
A. Ringe, Org. Lett., 2009, 11, 979; (b) A. F. Khlebnikov, M. S.
Novikov, P. P. Petrovskii, A. S. Konev, D. S. Yufit, S. I. Selivanov and
H. Frauendorf, J. Org. Chem., 2010, 75, 5211.
26 (a) A. D. Becke, J. Chem. Phys., 1993, 98, 5648; (b) A. D. Becke, Phys.
Rev. A: At., Mol., Opt. Phys., 1998, 38, 3098; (c) C. Lee, W. Yang and
R. G. Parr, Phys. Rev. B, 1998, 37, 785.
14 (a) H. C. Brown and C. R. Smoot, J. Am. Chem. Soc., 1956, 78, 2176;
(b) R. A. Moss, J.-M. Fede and S. Yan, J. Am. Chem. Soc., 2000, 122,
9878.
15 (a) N. De Kimpe, R. Verhe´, L. Buyck and N. Schamp, J. Org. Chem.,
1980, 45, 5319; (b) M. F. Mayer and M. M. Hossain, J. Org. Chem.,
1998, 63, 6839; (c) W. Xie, J. Fang, J. Li and P. G. Wang, Tetrahedron,
1999, 55, 12929.
16 O. Tsuge and S. Kanemasa, Adv. Heterocycl. Chem., 1989, 45, 231.
17 FOYE’s Principles of Medicinal Chemistry, ed. T. L. Lemke,
D. A. Williams and V. F. Roche, Lippincott Williams & Wilkins, 6th
edn, 2007.
18 CRC Handbook of Chemistry and Physics, ed. D. R. Lide and
H. P. R. Frederikse, Chemical Rubber, Boca Raton, 1994.
19 R. G. Lerner and B. P. Dailey, J. Chem. Phys., 1957, 26, 678.
20 L. Fernolt and K. Kveseth, Acta Chem. Scand., Ser. A, 1979, 33, 335.
21 G. P. Jones, B. A. Cornell, E. Horn and E. R. T. Tiekink, J. Crystallogr.
Spectrosc. Res., 1989, 19, 715.
27 M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A.
Robb, J. R. Cheeseman, J. A. Montgomery Jr., T. Vreven, K. N.
Kudin, J. C. Burant, J. M. Millam, S. S. Iyengar, J. Tomasi, V. Barone,
B. Mennucci, M. Cossi, G. Scalmani, N. Rega, G. A. Petersson, H.
Nakatsuji, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa,
M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai, M. Klene, X.
Li, J. E. Knox, H. P. Hratchian, J. B. Cross, C. Adamo, J. Jaramillo,
R. Gomperts, R. E. Stratmann, O. Yazyev, A. J. Austin, R. Cammi,
C. Pomelli, J. W. Ochterski, P. Y. Ayala, K. Morokuma, G. A. Voth,
P. Salvador, J. J. Dannenberg, V. G. Zakrzewski, S. Dapprich, A. D.
Daniels, M. C. Strain, O. Farkas, D. K. Malick, A. D. Rabuck, K.
Raghavachari, J. B. Foresman, J. V. Ortiz, Q. Cui, A. G. Baboul, S.
Clifford, J. Cioslowski, B. B. Stefanov, G. Liu, A. Liashenko, P. Piskorz,
I. Komaromi, R. L. Martin, D. J. Fox, T. Keith, M. A. Al-Laham, C. Y.
Peng, A. Nanayakkara, M. Challacombe, P. M. W. Gill, B. Johnson, W.
Chen, M. W. Wong, C. Gonzalez and J. A. Pople, Gaussian 03, Revision
B.05, Gaussian, Inc., Pittsburgh PA, 2003.
22 The example of non-stereospecific cycloaddition of azomethine ylides
derived from aziridines was recently published: G. Mloston´, K.
28 (a) C. Gonzalez and H. B. Schlegel, J. Chem. Phys., 1989, 90, 2154;
(b) C. Gonzalez and H. B. Schlegel, J. Phys. Chem., 1990, 94, 5523.
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