Domino reactions of 2H-azirines with acylketenes from furan-2,3-diones: Competition between the formation of ortho-fused and bridged heterocyclic systems

Article abstract of DOI:10.3762/bjoc.10.74

3-Aryl-2H-azirines react with acylketenes, generated by thermolysis of 5-arylfuran-2,3-diones, to give bridged 5,7-dioxa-1-azabicyclo[ 4.4.1]undeca-3,8-diene-2,10-diones and/or ortho-fused 6,6a,12,12a- tetrahydrobis[1,3]oxazino[3,2-a:3′,2′-d]pyrazine-4,10

Full text of DOI:10.3762/bjoc.10.74

Domino reactions of 2H-azirines with acylketenes
from furan-2,3-diones: Competition between
the formation of ortho-fused and bridged
heterocyclic systems
Alexander F. Khlebnikov*1, Mikhail S. Novikov1, Viktoriia V. Pakalnis1,
Roman O. Iakovenko1 and Dmitry S. Yufit2
Full Research Paper
Open Access
Address:
Beilstein J. Org. Chem. 2014, 10, 784–793.
1Department of Chemistry, Saint-Petersburg State University,
Universitetskii pr. 26, 198504 St. Petersburg, Russia and
2Department of Chemistry, University of Durham, Durham, South Rd.,
DH1 3LE, UK
doi:10.3762/bjoc.10.74
Received: 20 January 2014
Accepted: 14 March 2014
Published: 04 April 2014
Email:
Alexander F. Khlebnikov* - alexander.khlebnikov@pobox.spbu.ru
This article is dedicated to Professor Armin de Meijere on the occasion of
his 75th birthday.
* Corresponding author
Associate Editor: J. A. Murphy
Keywords:
acylketene; azirine; domino reaction; furandione
© 2014 Khlebnikov et al; licensee Beilstein-Institut.
License and terms: see end of document.
Abstract
3-Aryl-2H-azirines react with acylketenes, generated by thermolysis of 5-arylfuran-2,3-diones, to give bridged 5,7-dioxa-1-azabi-
cyclo[4.4.1]undeca-3,8-diene-2,10-diones and/or ortho-fused 6,6a,12,12a-tetrahydrobis[1,3]oxazino[3,2-a:3′,2′-d]pyrazine-4,10-
diones. The latter compounds, with a new heterocyclic skeleton, are the result of the coupling of two molecules of azirine and two
molecules of acylketene and can be prepared only from 3-aryl-2H-azirines having no electron-withdrawing groups in the aryl
substituent. Calculations at the DFT B3LYP/6-31G(d) level for the various routes of bis[1,3]oxazino[3,2-a:3′,2′-d]pyrazine skeleton
formation revealed a new domino reaction of 3-aryl-2H-azirines occurring in the presence of furandiones: acid-catalyzed dimeriza-
tion to dihydropyrazine followed by consecutive cycloaddition of the latter to two molecules of acylketenes.
Introduction
2H-Azirines, the most strained nitrogen unsaturated hetero- the three-membered ring can be preserved in some reactions,
cyclic systems, are versatile building blocks for the construc- 2H-azirines mostly undergo ring cleavage to relieve the strain
tion of various heterocyclic nitrogen-containing compounds. [1-21].
Because 2H-azirines contain an activated C=N double bond and
a lone pair of electrons on the nitrogen atom they are extremely 2H-Azirines can react with ketenes both with cleavage and
reactive towards both electrophiles and nucleophiles. Though preservation of the three-membered ring [22-26]. It was found
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that acylketenes, which are generated in situ from diazo different solvents (benzene, toluene, cyclohexane, THF,
ketones, undergo cycloaddition with 3-mono- and 2,3-disubsti- nitromethane) monitoring the reaction by 1H NMR using
tuted-2H-azirines to afford 2:1 or 1:1 adducts: 5,7-dioxa-1- 1-methylnaphthalene as internal standard. 1H NMR spectra of
azabicyclo[4.4.1]undeca-3,8-diene or 5-oxa-1-aza- the new compounds 4a and 5a have clearly distinguishable
bicyclo[4.1.0]hept-3-ene derivatives. From the results of DFT signals for the methylene protons. Thus, in cis-diastereomer 4а
B3LYP/6-31G(d) computations a step-wise mechanism appears the chemical shifts of the doublet signals for the protons of the
likely for the formation of [4 + 2]-monoadducts [22]. The main CH2-groups differ by more than 2 ppm (3.26, 5.62 ppm),
limitation for the synthetic application of the reaction is the whereas in trans-diastereomer (5а) they represent an
nonselective mode of the Wolff rearrangement of the unsym- AB-system (4.56, 4.68 ppm). Attempts to initiate the reaction
metrical diazo compounds. This generates a mixture of isomeric by UV-irradiation (at 20 or 50 °C) or catalysis by compounds of
oxoketenes [27-29] and, as a result, a complex mixture of prod- transition metals (Cu(acac)2, Fe(acac)3, Pd(bzac)2, Rh2(AcO)4,
ucts is formed [22]. Moreover not all diazo compounds give Cu(OTf)2, Pd/C) at 20 or 40 °C failed. Benzene was found to be
oxoketenes easily [27-29]. In particular, unsubstituted a solvent of choice, and a 1:1 molar ratio of reagents results in
acylketenes, the reactivity of which towards azirines is until the highest yields of the products (Table 1).
now unknown, cannot be generated from diazo compounds. An
alternative source of acylketenes can be furan-2,3-diones, which
Table 1: Yields of products of the reaction of furan-2,3-dione 1a and
have been used in reactions with nucleophiles and various
cycloadditions [30-32]. Aiming to broaden the scope of the
reaction of acylketenes with 2H-azirines we tried to use furan-
2,3-diones instead of diazo compounds as the source of ketenes.
azirine 2a in boiling benzene solution for 0.5 h according to 1H NMR.
Ratio
Conversion
Yieldsa of 3a, Overall yieldsa of
2a:1a
of 2a (%)
4a, 5a, %
3a–5a, %
1:2
100
89
42
57
43
2, 16, 9
27
44
71
32
37
1:1.5
1:1
5, 22, 17
19, 37, 15
2, 19, 11
4, 20, 13
Results and Discussion
Unexpectedly, with a new source of acylketenes in addition to
predictable products (derivatives of 5,7-dioxa-1-aza-
bicyclo[4.4.1]undeca-3,8-diene) derivatives of 4,11-dioxa-1,8-
diazatricyclo[8.4.0.03,8]tetradeca-5,12-diene, a new hetero-
cyclic system, were formed. Boiling a benzene solution of
furan-2,3-dione 1a and azirine 2a (1:1) for 0.5 h gave a mixture
1.5:1
2:1
aYield based on consumed azirine 2a.
of compounds 3a–5a, which were isolated by column chroma- Reactions of azirines 2a–c and furandiones 1a–c, containing
tography (Scheme 1).
electron-donating and electron-withdrawing groups in the aryl
rings, were studied to determine an influence of substituents
To find the optimal reaction conditions a series of experiments with different electronic effects on the product distribution. The
was performed with furan-2,3-dione 1a and azirine 2a in analytical and isolated yields of the reaction products are listed
Scheme 1: Reactions of furan-2,3-diones 1 and azirines 2.
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Beilstein J. Org. Chem. 2014, 10, 784–793.
in Table 2. Compounds 3–5 were fully characterized using stan- The formation of compounds 3 proceeds in the same way as for
dard spectral methods. The structures of compounds 3а, 4b similar compounds obtained by reaction of azirines with
were confirmed by X-ray analysis (Figure 1).
acylketenes from diazo compounds (Scheme 2) [22]. According
to the calculation at the DFT B3LYP/6-31G(d) level with PCM
Furandiones 1a–c react with 3-(4-nitrophenyl)-2H-azirine (2c) solvation model for benzene (Figure 2) the formation of the
to give only 1:2 adducts 3. These were easily isolated from the monoadducts 8a,c proceeds via the formation of zwitterionic
reaction mixtures by crystallization. In reactions of 1a with 2b, intermediates 7a,c by nucleophilic attack of the azirine nitrogen
1b with 2b, and 1c with 2a only 2:2 adducts 4 and 5 are formed lone pair on the C=O group of the ketene fragment of inter-
and were isolated by chromatography. Thermolysis of furan- mediate 6a. Interaction of monoadducts 8a,c with ketene 6a
dione 1c in the presence of azirine 2b led to tarring. Analysis of leads to the formation of the unstable zwitterionic intermedi-
the data obtained (Table 2) shows that the ratio of the products ates 9a,c which further cyclize to bisadducts 3a,c. The barriers
3–5 is determined by the electronic effects of the substituents in for addition of the azirine and aziridine nitrogen lone pair of
the benzene rings both in arylazirine 2 and arylfurandione 1. An 1a,c, and 8a,c to ketene 6a increase in passing from com-
increase of the electron-withdrawing effect of substituents in the pounds 1a, 8a to compounds 1c, 8c, because of a decrease in
benzene rings of 3-aryl-2H-azirine leads to an increase of yield the nucleophilicity of the latter due to the electron withdrawing
of 1:2 adduct 3, and in the case of 3-(4-nitrophenyl)-2H-azirine effect of the nitro group.
(2c) it becomes the only product, while from 3-(4-
methoxyphenyl)-2H-azirine (2b) only 2:2 adducts 4 and 5 were As for possible routes for the formation of adducts 4 and 5, the
formed. It is also worth noting that in all cases the proportion of first (Scheme 2, (a)) involves cleavage of the aziridine ring of
cis-isomer 4 was larger than that of trans-isomer 5.
intermediate 8 to generate azomethine ylide 10, and further
Table 2: Products of the reactions of azirines 2a–c and furandiones 1a–c.
Ar1
Ar2
Conversion of 2, %
Analytical yieldsa of 3, 4, 5, %
Yieldsa of isolated 3, 4, 5, %
Ph
Ph
2a, 71
2b, 74
2c, 50
2a, 70
2b, 72
2c, 50
2a, 87
2b, –
3a, 19
3b, 0
3c, 89
3d, 77
3e, 0
4a, 37
4b, 45
4c, 0
5a, 15
5b, 23
5c, 0
5d, 9
5e, 23
5f, 0
3a, 15
–
4a, 34
5a, 13
5b, 20
–
Ph
4-MeOC6H4
4-NO2C6H4
Ph
4b, 24
Ph
3c, 79
3d, 42
–
–
4-MeOC6H4
4-MeOC6H4
4-MeOC6H4
4-NO2C6H4
4-NO2C6H4
4-NO2C6H4
4d, 14
4e, 41
4f, 0
4d + 5d, 18
4-MeOC6H4
4-NO2C6H4
Ph
4e + 5e, 51
3f, 92
3g, 0
3h, 0
3i, 62
3f, 85
–
–
–
4g, 58
4h, 0
4i, 0
5g, 29
5h, 0
5i, 0
4g + 5g, 80
4-MeOC6H4
4-NO2C6H4
–
–
–
–
–
2c, 50
3i, 56
aYield based on consumed azirine.
Figure 1: Molecular structures of compounds 3а, 4b.
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Beilstein J. Org. Chem. 2014, 10, 784–793.
Scheme 2: The route of formation of compounds 3 and possible intermediates in route to compounds 4 and 5.
Another route to compounds 4 and 5 could, therefore, involve
interaction of dihydropyrazine 11 with ketene 6, leading to the
monoadduct 12, which further reacts with a second molecule of
6 to give 2:2 adducts 4 and 5 (Scheme 3, (b)).
To evaluate the free energy barriers for the interaction of 2,5-
dihydropyrazine with acylketenes the calculations of the reac-
tion of dihydropyrazine 11a with ketene 6a, leading to adduct
12a, and the reaction of the latter with ketene 6a, leading to
adducts 4a and 5a, were performed at the DFT B3LYP/6-
31G(d) level (Figure 3).
According to the calculation (Figure 3) the formation of
monoadduct 12a proceeds via the formation of the zwitterionic
intermediate 12a' by nucleophilic attack of the dihydropyrazine
nitrogen lone pair on the C=O group of ketene 6a. Intermediate
12a' further easily undergoes cyclization to give monoadduct
12a. Interaction of the latter with ketene 6a leads to unsymmet-
Figure 2: Energy profiles for the reactions of azirines 2a,c and
acylketene 6a, as well as acylketene 6a with monoadducts 8a,c. Rela-
tive free energies [kcal·mol−1, 353 K, benzene (PCM)] computed at the
DFT B3LYP/6-31G(d) level.
“dimerization” of the latter. Examples of compounds that can be rical cis-isomer 4a' with the piperazine ring in a chair con-
considered as dimers of azomethine ylides have been published, formation. The isomer 4a' transforms through a low barrier to a
though concerted thermal dimerization of azomethine ylides is a much more stable isomer 4a of C2 symmetry with the piper-
forbidden process [33]. According to our calculations the free azine ring in a boat conformation (see Supporting Information
energy barriers to formation of the azomethine ylides 10a–c File 1). No intermediate structure was located on the way to the
from compounds 8a–c are 34.1, 34.7, 32.2 kcal·mol−1 (353 K, most stable conformation of trans-isomer 5a with the piper-
benzene (PCM)), respectively, that far exceed the barriers to azine ring in a boat conformation. The free energies of the
reactions leading to compound 3. These do not allow the possi- highest transition states on the pathways from 12a to cis-isomer
bility that azomethine ylide 10 can be a probable intermediate in 4a and trans-isomer 5a are practically equal, but 4a is much
the formation of adducts 4 and 5.
more stable than 5a. Therefore, one can consider the experi-
mental 4a:5a isomer ratio of 37:15 to result from the thermody-
It has been known that imines react with acylketenes, generated namic control, since the barrier to the back transformation of 5a
from furandiones, to give derivatives of 1,3-oxazines [34-36]. to 12a + 6a is as low as 22.7 kcal·mol−1. Calculations also show
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Beilstein J. Org. Chem. 2014, 10, 784–793.
Scheme 3: Possible intermediates in routes to compounds 4 and 5.
Figure 3: Energy profiles for the reactions of dihydropyrazine 11a with acylketene 6a, as well as acylketene 6a with monoadduct 12a. Relative free
energies [kcal·mol−1, 353 K, benzene (PCM)] computed at the DFT B3LYP/6-31G(d) level.
(Figure 2 and Figure 3) that the reaction involving dihydropy- with unsubstituted and an electron-donor substituted benzene
razines 11 on the way to 4 and 5 could be quite competitive ring, fast transform into pyrazines, even when stored in a fridge.
with the reaction leading to 3, provided that a source of dihy-
dropyrazines 11 is available. Formation of ‘dimer azirines’, Different mechanisms of dimerization were assumed, such as
dihydropyrazines [37-41], or products of their dehydrogenation, formation and dimerization of nitrile ylides [37,40], hydrolysis
pyrazines [37-49] under different conditions is quite common. to α-aminoketenes followed by condensation [37,41], inter-
Moreover, everybody who works with 3-aryl-2H-azirines faces mediate formation of metal complexes in the reaction mediated
the problem of their storage, because these compounds, both by metals [41,43,46]. It was found that water [37], Brønsted
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Beilstein J. Org. Chem. 2014, 10, 784–793.
[44,48] and Lewis acids [40,41,43] facilitate the formation of dioxobutanoic acids, which can protonate basic azirines 2a,b.
pyrazine derivatives. 2H-Azirines undergo ring opening on The concentration of protonated azirine 2c have to be negli-
electronic excitation to give nitrile ylides [50]. Nitrile ylide for- gible due to low basicity of this azirine, as one can see from
mation under thermal conditions even from such strained com- isodesmic equation (Scheme 4).
pounds as 2H-azirines needs to overcome a quite high energy
barrier. According to calculations at the DFT B3LYP/6-31G(d) Thus, the absence of 4c,f,i and 5c,f,i in the reaction of furan-
level the free energy barriers to formation of nitrile ylides 13a–c diones 1a–c with azirine 2c can most probably be explained by
from azirines 2a–c are 48.4, 47.6, 47.9 kcal·mol−1 (353 K, the low basicity of the latter, and this prevents the formation of
benzene (PCM)), respectively. Therefore the process of the for- 11c in any significant concentration.
mation of dihydropyrazines 11 via azirine–nitrile ylide isomer-
ization cannot compete with reaction of azirines with We also decided to implement this theoretical conclusion into
acylketenes (Figure 2). Dimerization of azirine 2a via nucleo- an approach to storing 3-aryl-2H-azirines. It was found that a
philic attack of the nitrogen lone pair of one azirine molecule on sample of azirine 2a upon storage over anhydrous K2CO3 at
the C=N bond of another is also energetically unfavourable room temperature for 2 months underwent no changes, whereas
(ΔG# = 53.6 kcal·mol−1, 353 K, benzene (PCM)). In contrast to a sample stored under the same conditions but without addition
this, the nucleophilic attack of the nitrogen lone pair of azirine 2 of K2CO3 completely transformed into 2,5-diphenylpyrazine.
on the C=N bond of protonated azirine 14 and consequent
cyclization to dihydropyrazine 15 proceeds via quite low The reaction of 2-phenyl-substituted azirine 2d with furandione
barriers (Figure 4).
1a leads, obviously due to steric reasons, to formation of only
the exo-monoadduct 17 (Scheme 5). The structure of com-
pound 17 was confirmed by X-ray analysis (Figure 5). In the
case of the reaction of the azirine 2d “dimeric” products of type
3, 4 and 5 were not detected, most probably due to steric
hindrance both for the reaction of monoadduct 17 with
acylketene 3a and the “dimerization” of 2d to tetraphenyldihy-
dropyrazole.
Figure 4: Energy profiles for the reactions of azirines 2a,c with proto-
nated azirines 14a,c. Relative free energies [kcal·mol−1, 353 K,
benzene (PCM)] computed at the DFT B3LYP/6-31G(d) level.
Scheme 5: Reaction of furandione 1a with azirine 2d.
4,5-Diphenylfuran-2,3-dione (1d) is the source of benzoyl-
phenylketene 6d. Reaction of ketene 6d, generated from
2-diazo-1,3-diphenylpropane-1,3-dione, with azirine 2a was
studied earlier [22]. Higher temperatures are needed to generate
benzoylphenylketene 6d from furanedione 1d, than from the
By comparison of the data presented on Figures 2–4 one can
conclude that competitive formation of compounds 3, 4 and 5
can proceed under acidic catalysis. Probably traces of water
cause hydrolysis of the furandiones 1a–c to give 4-aryl-2,4-
Scheme 4: Isodesmic equation for evaluation of relative basicity of azirines 2c,a.
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Beilstein J. Org. Chem. 2014, 10, 784–793.
Figure 5: Molecular structure of compound 17.
Scheme 7: Reactions of compounds 3d and 18a with methanol.
diazo compound. Boiling an o-xylene solution of furanedione
1d and azirine 2a (1:1 ratio) gave bisadduct 18 in 34% yield
(Scheme 6). This is less than when using the diazo compound as
a source of acylketene, probably due to dimerization of ketene
6d under higher temperature.
methoxyphenyl)-2H-azirine (2b) only 2:2 adducts 4 and 5 were
formed. Calculations at the DFT B3LYP/6-31G(d) level for
various routes of bis[1,3]oxazino[3,2-a:3′,2′-d]pyrazine
skeleton formation revealed a new reaction of 3-aryl-2H-
Compounds 3 and 17, stable at room temperature, react with azirines in the presence of acylketenes from furandiones, i.e.
methanol under mild conditions. Thus the boiling of methanol/ acid-catalyzed dimerization to dihydropyrazines followed by
CH2Cl2 (1:2) solutions of compound 3d and 17 leads to the for- consecutive double cycloaddition of the latter to acylketenes.
mation of the corresponding derivatives of 3,4-dihydro-1,4- According to the calculations the larger proportion of cis-isomer
oxazepin-5(2H)-one 19 and 20 (Scheme 7).
4 than of trans-isomer 5 is a result of thermodynamic control.
We also recommend storing liquid 3-aryl-2H-azirines, both with
unsubstituted and an electron-donor substituted benzene ring,
Conclusion
2-Unsubstituted 3-aryl-2H-azirines 2 react with acylketenes, over anhydrous K2CO3.
generated by thermolysis of 5-arylfuran-2,3-diones 1, to give
Experimental
5,7-dioxa-1-azabicyclo[4.4.1]undeca-3,8-diene-2,10-diones 3
and/or cis- and trans-6,6a,12,12a-tetrahydrobis[1,3]oxa- General methods
zino[3,2-a:3′,2′-d]pyrazine-4,10-diones 4 and 5. The latter com- Melting points were determined on a hot stage microscope and
pounds are the products of coupling of two molecules of azirine are uncorrected. 1H (300 MHz) and 13C (75 MHz) NMR spectra
with two molecules of acylketene. The ratio of the adducts 3–5 were determined in CDCl3 with a Bruker DPX 300 spectrom-
is determined by electronic effects of the substituents in the eter. Chemical shifts (δ) are reported in parts per million down-
benzene rings both in arylazirine 2 and arylfurandione 1. The field from tetramethylsilane. Electrospray ionization mass
increase of the electron-withdrawing effect of the substituents in spectra were measured on MS Q-TOF and micrOTOF 10223
the benzene rings of the arylazirine leads to an increase in the mass spectrometers. IR spectra were recorded on a Bruker
yield of 1:2 adduct 3, and in the case of 3-(4-nitrophenyl)-2H- TENSOR 27 spectrometer for tablets in KBr. Single-crystal
azirine (2c) it becomes the only product, while from 3-(4- X-ray data for 3a were collected at 100 K on a Bruker Proteum
Scheme 6: Reaction of furandione 1d with azirine 2a.
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Beilstein J. Org. Chem. 2014, 10, 784–793.
R diffractometer (FR-591 rotating anode generator, Pt-135 CCD 131.3, 131.5, 138.4, 161.5, 163.2; IR (KBr, cm−1) ν 1674
detector) equipped with Cobra (Oxford Cryosystems) open-flow (C=O); HRMS–ESI: [M + H]+ calcd for C34H27N2O4+,
cryostat. Data for 4b and 17 were collected on an Agilent XCal- 527.1965; found, 527.1937.
ibur diffractometer at the temperature 120 K maintained by
Cryostream (Oxford Cryosystems) cryostat. The structures were (6aRS,12aSR)-2,6a,8,12a-Tetraphenyl-6,6a,1,2,12a-tetrahy-
solved by direct method and refined by full-matrix least squares drobis[1,3]oxazino[3,2-a:3′,2′-d]pyrazine-4,10-dione (5a).
on F2 for all data using Olex2 [51] and SHELXTL [52] soft- White solid; mp 171–173 °C (EtOAc/hexane); yield 13% (on
ware. All non-hydrogen atoms were refined anisotropically, consumed azirine); 1H NMR (CDCl3) δ 4.56 (d, J = 14.5 Hz,
hydrogen atoms in the structure 3a were placed in the calcu- 2H), 4.68 (d, J = 14.5 Hz, 2H), 5.73 (s, 2H), 7.29–7.31 (m, 2H),
lated positions and refined in riding mode. The hydrogen atoms 7.39–7.52 (m, 9H), 7.63–7.71 (m, 9H); 13C NMR (CDCl3) δ
in the structures 4b and 17 were located in the difference 47.5, 93.2, 97.6, 125.1, 126.3, 128.6, 129.0, 129.7, 131.3, 138.0,
Fourier maps and refined isotropically. Crystallographic data 162.3, 163.1; IR (KBr, cm−1) ν: 2930, 1661 (C=O);
for the structure have been deposited with the Cambridge Crys- HRMS–ESI: [M + K]+ calcd for C34H26N2KO4+, 565.1524;
tallographic Data Centre as supplementary publication CCDC- found, 565.1496.
974303-974305. Compounds 1a [53], 1b,c [32], 1d [54], and
2a,b [55], 2c [56], 2d [57] were prepared by the reported pro- (6aRS,12aRS)-6a,12a-Bis(4-methoxyphenyl)-2,8-diphenyl-
cedures.
6,6a,12,12a-tetrahydrobis[1,3]oxazino[3,2-a:3′,2′-
d]pyrazine-4,10-dione (4b). White solid; mp 186–186.5 °C
General procedures for reactions of acylketenes from (EtOAc/hexane); yield 24% (on consumed azirine); 1H NMR
5-arylfuran-2,3-diones 2a–c and 3-aryl-2H-azirines 1a–c. A (CDCl3) δ 3.22 (d, J = 14.9 Hz, 2H), 3.76 (s, 6H), 5.59 (d, J =
mixture of azirine 1 (1 mmol) and furane-2,3-dione 2 (1 mmol) 14.9 Hz, 2H), 5.89 (s, 2H), 6.87 (d, J = 8 Hz, 4H), 7.34–7.45
in anhydrous benzene (5 mL) was refluxed for 0.5–1 h. The (m, 10H), 7.69 (d, J = 8 Hz, 4H); 13C NMR (CDCl3) δ 47.6,
solvent was removed in vacuum, and the residue was purified 55.2, 93.1, 97.5, 114.2, 126.3, 126.5, 128.5, 129.8, 131.2, 131.4,
by flash chromatography on silica (eluent petroleum ether/ethyl 160.5, 162.1, 163.1; IR (KBr, cm−1) ν: 1731 (C=O);
acetate, 1:1).
HRMS–ESI: [M + H]+ calcd for C36H31N2O6+, 587.2177;
found, 587.2183; Crystal data for 4b: C36H30N2O6, M =
4,6,8-Triphenyl-5,7-dioxa-1-azabicyclo[4.4.1]undeca-3,8- 586.62, monoclinic, space group P 21/c, a = 12.1236(5), b =
diene-2,10-dione (3a). White solid; mp 214–215 °C (benzene); 18.2526(7), c = 13.4793(5) Å, β = 103.738(4)°, U =
yield 15% (on consumed azirine); 1H NMR (CDCl3) δ 4.70 (s, 2897.46(19) Å3, F(000) = 1232, Z = 4, Dc = 1.345 mg m−3, μ =
2H), 6.28 (s, 2H), 7.35–7.48 (m, 9H), 7.60–7.63 (m, 6H); 13C 0.092 mm−1. 16575 reflections were collected yielding 6654
NMR (CDCl3) δ 49.1, 104.5, 113.6, 125.0, 127.0, 128.7, 129.0, unique data (Rmerg = 0.0596). Final wR2(F2) = 0.1284 for all
130.3, 131.1, 134.5, 137.4, 160.2, 164.9; IR (KBr, cm−1) ν: data (517 refined parameters), conventional R1(F) = 0.0567 for
1721 (C=O); HRMS–ESI: [M + Na]+ calcd for C26H19NNaO4+, 4337 reflections with I ≥ 2σ, GOF = 1.043.
432.1206; found, 432.1192; Anal. calcd for C26H19NO4: C,
76.27; H, 4.68; N, 3.42; found: C, 76.57; H, 4.47; N, 3.66; (6aRS,12aSR)-6a,12a-Bis(4-methoxyphenyl)-2,8-diphenyl-
Crystal data for 3a: C26H19NO4, M = 409.42, monoclinic, space 6,6a,12,12a-tetrahydrobis[1,3]oxazino[3,2-a:3′,2′-
group P 21/n, a = 14.5600(5), b = 17.9642(6), c = 17.1799(6) Å, d]pyrazine-4,10-dione (5b). White solid; mp 123–124 °C
β = 105.850(10)°, U = 4322.7(3) Å3, F(000) = 1712, Z = 8, Dc = (EtOAc/hexane); yield 20% (on consumed azirine); 1H NMR
1.258 mg m−3, μ = 0.692 mm−1. 21195 reflections were (CDCl3) δ 3.71 (s, 6H), 4.53 (d, J = 14.2 Hz, 2H), 4.62 (d, J =
collected yielding 5904 unique data (Rmerg = 0.0506). Final 14.2 Hz, 2H), 5.74 (s, 2H), 6.75–6.78 (m, 4H), 7.40–7.48 (m,
wR2(F2) = 0.1073 for all data (559 refined parameters), conven- 6H), 7.53–7.56 (m, 4H), 7.67–7.69 (m, 4H); 13C NMR (CDCl3)
tional R1(F) = 0.0440 for 4157 reflections with I ≥ 2σ, GOF = δ 47.9, 55.1, 91.6, 98.6, 113.7, 126.3, 127.4, 128.7, 130.2,
0.991.
131.36, 131.42, 160.3, 161.3, 163.3; IR (KBr, cm−1) ν: 1733
(C=O); HRMS–ESI: [M + H]+ calcd for C36H31N2O6+,
(6aRS,12aRS)-2,6a,8,12a-Tetraphenyl-6,6a,1,2,12a-tetrahy- 587.2177; found, 587.2196.
drobis[1,3]oxazino[3,2-a:3’,2’-d]pyrazine-4,10-dione (4a).
White solid; mp 154–156 °C (EtOAc/hexane); yield 34% (on Calculations. All calculations were carried out at the DFT
consumed azirine); 1H NMR (CDCl3) δ 3.26 (d, J = 15.3 Hz, B3LYP/6-31G(d) level [58-60] by using the Gaussian 09 suite
2H), 5.62 (d, J = 15.3 Hz, 2H), 5.90 (s, 2H), 7.36–7.44 (m, of quantum chemical programs [61] at Resource center
12H), 7.51–7.54 (m, 4H), 7.70–7.74 (m, 4H); 13C NMR ‘Computer center of Saint Petersburg State University’. Geom-
(CDCl3) δ 47.9, 91.7, 98.7, 126.0, 126.3, 128.4, 128.7, 129.6, etry optimizations of intermediates, transition states, reactants,
791

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Intrinsic reaction coordinates were calculated to authenticate all
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Supporting Information
Detailed experimental procedures including
characterization data for all synthesized compounds, 1H
and 13C NMR spectra for all new compounds.
Computational details: energies of molecules, transition
states and their Cartesian coordinates of atoms.
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Detailed experimental procedures and computational
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[http://www.beilstein-journals.org/bjoc/content/
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[http://www.beilstein-journals.org/bjoc/content/
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Supporting Information File 4
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Chemical information file of compound 17.
[http://www.beilstein-journals.org/bjoc/content/
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Acknowledgements
We gratefully acknowledge the financial support of the Russian
Foundation for Basic Research (Grant No. 14-03-00187) and
Saint Petersburg State University (Grant No. 12.38.78.2012).
This research used resources of the resource center ‘Computer
Center’ and ‘Center for Chemical Analysis and Material
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