Nonconcerted cycloaddition of 2H-azirines to acylketenes: A route to N-bridgehead heterocycles

Article abstract of DOI:10.1021/jo201563b

Reactions of acylketenes, generated from diazo diketones, with 2-unsubstituted and 2-monosubstituted 3-aryl-2H-azirines lead to 1:1 or 2:1 adducts, which are derivatives of 5-oxa-1-azabicyclo[4.1.0]hept-3-ene or 5,7-dioxa-1-azabicyclo[4.4.1]undeca-3,8-diene. According to DFT B3LYP/6-31G(d) computations, the formation of (4+2)-monoadducts proceeds via a stepwise non-pericyclic mechanism. Reaction with methanol transforms quantitatively both 1:1 and 2:1 adducts into 1,4-oxazepine derivatives.

Full text of DOI:10.1021/jo201563b

Article
pubs.acs.org/joc
Nonconcerted Cycloaddition of 2H-Azirines to Acylketenes: A Route
to N-Bridgehead Heterocycles
Alexander F. Khlebnikov,*,† Mikhail S. Novikov,† Viktoriia V. Pakalnis,† and Dmitry S. Yufit‡
†Department of Chemistry, Saint-Petersburg State University, Universitetskii pr. 26, 198504 St. Petersburg, Russia
‡Department of Chemistry, University of Durham, Durham, South Rd., DH1 3LE, U.K.
S
* Supporting Information
ABSTRACT: Reactions of acylketenes, generated from diazo diketones, with
2-unsubstituted and 2-monosubstituted 3-aryl-2H-azirines lead to 1:1 or 2:1 adducts,
which are derivatives of 5-oxa-1-azabicyclo[4.1.0]hept-3-ene or 5,7-dioxa-1-
azabicyclo[4.4.1]undeca-3,8-diene. According to DFT B3LYP/6-31G(d) computa-
tions, the formation of (4+2)-monoadducts proceeds via a stepwise non-pericyclic
mechanism. Reaction with methanol transforms quantitatively both 1:1 and 2:1
adducts into 1,4-oxazepine derivatives.
Scheme 1
INTRODUCTION
■
Ketenes have found wide application in organic synthesis
because of their high reactivity and availability via Wolff
rearrangement.1 They react even with such weak nucleophiles
as 2H-azirines.2 Hassner has shown that reactions of
3-arylazirines with diphenyl- and tert-butylcyanoketenes lead
to the formation of 1:1 adducts, 3,3-diphenyl-1,3-dihydropyr-
rol-2-ones, or 1:2 adducts, 6-phenyl-2,4-bis(diphenylmethylen)-
1-azabicyclo[4.1.0]heptane-3,5-diones, depending on the sub-
stitution in position 2 of the azirine.3 Derivatives of pyrrolin-2-
ones are the products of reaction of 2-(2-formylvinyl)-3-phenyl-
2-methyl-2H-azirines with diphenylketene.4 Reactions of
ketenes with 2-(dimethylamino)-2H-azirines can lead to the
formation of 5-(dimethylamino)pyrrolin-2-ones, 1,3-oxazolines,
benzazepines, and ketene imines.5
Scheme 2
Acylketenes are highly reactive intermediates that can be
trapped by different nucleophiles and dienophiles.1,6 Their
reactions give rise to products of formal [4+2]-cycloaddition. In
particular, reactions of acylketenes with the CN double bond
of imines and heterocycles lead to derivatives of 1,3-oxazines.7
Reactions of acylketenes with azirines that can serve as both a
nucleophile and dipolarophile are, to the best of our knowledge,
still unknown.
Because of our research interest concerning the chemistry of
azirines8 and the synthesis of nitrogenated heterocycles via
reactions of diazo compounds with imines,8c,d,f,g,9 we
envisioned the possibility of assembling a new heterocyclic
system, 5-oxa-1-azabicyclo[4.1.0]hept-3-ene 1, by the reaction
of azirines 2 with acylketenes 3, according to the retrosynthetic
sequence described in Scheme 1.
RESULTS AND DISCUSSION
■
1
The structures of compounds 5 were verified by H and 13C
Heating a toluene solution of azirines 2a−c and diazo diketone
4a (in 1:1.1 ratio), as precursor of acylketene 3a via Wolff
rearrangement,1b led unexpectedly to the formation of unusual
bridged heterocycles 5a−c, which are formed from one azirine
and two acylketene units (Scheme 2).
NMR, IR spectroscopy, and elemental analysis and the
Received: August 1, 2011
Published: October 10, 2011
© 2011 American Chemical Society
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structure of 5c was confirmed by X-ray analysis (Figure 1, the
nitro group is disordered over two positions).
mechanism, the calculations were performed at the DFT
B3LYP/6-31G(d) level of the energy profiles of the interaction
of acylketene 3a with azirine 2a and monoadduct 1a, as well as
the two model reactions of azirine 2a with acrolein 8 and buta-
2,3-dienal 9 (Scheme 3).
Scheme 3
According to the calculations, the transition states for the
reactions of heterodienes 8, 9 with azirine 2a are typical for
asynchronous hetero-Diels−Alder cycloaddition11 (Figure 2)
Figure 1. X-ray crystal structure of 5c.
A change in the 2a−c/4a ratio from 1:1.1 to 1:2.2 led to
improved yields of compounds 5, whereas using microwave
irradiation as a heat source led to a decrease in yields, although
the reaction occurred much faster (Table 1).
Figure 2. Structures of transition states for the reactions of
heterodienes 8, 9 with azirine 2a computed at the DFT B3LYP/6-
31G(d) level. Hydrogen atoms on the Ph-ring are omitted for clarity.
with the activation barriers (ΔG#) of 30.8 and 27.4 kcal·mol−1,
respectively.
Table 1. Reaction of Azirines 2a−c with Diazo Diketone 4a
ratio
2:4a
solvent/temperature
(°C)/time (h)
yield of 5
a
In contrast to these model reactions, no similar four-center
transition state was found for the formation of the monoadduct
1a from azirine 2a and acylketene 3a. Instead of this, the
intermediate 6a (Scheme 2) was located, which then cyclizes
via transition state TS2 to the monoadduct 1a (Figures 3 and
4). That the reaction proceeds via route b rather than routes
Ar
(%)
Ph
Ph
Ph
Ph
1:1.1
1:2.2
1:2.2
1:2.2
1:1.1
1:2.2
1:1.1
1:2.2
toluene/90/2
toluene/90/2
55
70
25
6
b
toluene/mw /0.17
b
neat/mw /0.17
4-MeOC6H4
4-MeOC6H4
4-O2NC6H4
4-O2NC6H4
toluene/90/2
toluene/90/2
toluene/90/2
48
69
49
55
toluene/90/2
a
b
Isolated yield based on starting azirine. Microwave irradiation at
160 W.
The formation of bisadducts 5 proceeds obviously via
monoadduct 1. The latter may be the product of the hetero-
Diels−Alder cycloaddition of acylketene 3a to the CN
double bond of azirine 2 (Scheme 2, route a). The alternative
route (Scheme 2, route b) to monoadduct 1 could involve the
formation of zwitterionic intermediate 6 by nucleophilic attack
of the azirine nitrogen lone pair on the ketene, which then
cyclizes to monoadduct 1. Earlier, Regits and Michels10
proposed a nonconcerted mechanism for the formation of
5-oxa-2-azatricyclo[5.2.0.02,4]nona-6,8-diens by the reaction of
tert-butyl 2,3,4-tri-tert-butylcyclobutadienecarboxylate with
2H-azirines, which involved the nucleophilic addition of the
carbonyl oxygen atom across the azirine CN bond to form a
stabilized zwitterion and subsequent ring closure in the latter.
However, in our case the analogous route c (Scheme 2) is the
least probable in the absence of the specific stabilization of
zwitterions 6′, which is characteristic of the zwitterion described
in the work.10 The formation of bisadducts 5 proceeds most
probably via the formation of zwitterionic intermediate 7
by nucleophilic attack of the aziridine nitrogen lone pair on
the ketene CO group (Scheme 2). To verify the reaction
Figure 3. Energy profiles for the reactions of azirine 2a and acylketene
3a (route b), as well as acylketene 3a with monoadduct 1a. Relative
free energies (kcal·mol−1, 298 K, toluene) computed at the DFT
B3LYP/6-31G(d) level.
a and c is most probably because of the extremely high elec-
trophilicity of the ketene carbonyl group.
Formally, the nitrogen atom in the monoadducts 1 is amidic
and consequently should have low nucleophilicity. But because
of the specific geometry of the amidic fragment of the
monoadducts 1, in which the nitrogen atom is included into a
three-membered ring, conjugation between the carbonyl group
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Figure 4. Structures of intermediates 6a, 7a and transition states TS2
and TS4 computed at the DFT B3LYP/6-31G(d) level. Hydrogen
atoms are omitted for clarity.
and the nitrogen lone pair is ineffective. Thus, according to
the DFT B3LYP/6-31G(d) computations, the amidic C−N
bond in 1a is much longer than that in the related molecule,
3-methyl-2,5,6-triphenyl-2H-1,3-oxazin-4(3H)-one, which con-
tains no three-membered ring: 1.421 and 1.385 Å, respectively.
The nitrogen atom in monoadducts 1 has then sufficiently high
nucleophilicity that it can attack the ketene CO group of 3a.
According to the calculations, the interaction of 1a with 3a
leads to the formation of an unstable zwitterionic intermediate
7a with an activation barrier similar to the barrier for formation
of the intermediate 6a (Figure 3). The intermediate 7a further
cyclizes to bisadduct 5a through a low energy barrier (TS4)
due to opening of the strained aziridine ring (Figures 3 and 4),
which undergoes the bridge C−N bond cleavage in the
transition state (Figure 4).
Figure 5. X-ray crystal structure of exo-14.
methyl-substituted azirine 12 with acylketene 3a leads to the
formation of both exo-monoadduct exo-14 and endo-mono-
adduct endo-14, but, because of steric reasons, only the endo-
monoadduct endo-14 reacts further with the second molecule
3a, giving bisadduct 15. (2) The reaction of phenyl-substituted
azirine 13 with acylketene 3a leads, because of steric reasons, to
the formation of only the exo-monoadduct exo-16, which is
unreactive toward acylketene 3a (Scheme 5). To verify this
hypothesis, the DFT B3LYP/6-31G(d) computations of the
interaction of acylketene 3a with 3-aryl-2H-azirines 12, 13 were
performed (Figure 6).
The calculations support the above hypothesis. Thus, in the
case of the reaction of the methyl-substituted azirine 12, both
the free energy of the transition states TS5 and TS6 leading to
the intermediates syn-17, anti-17 and the free energy of the
transition states TS7 and TS8 leading to endo-monoadduct
endo-14 and exo-monoadduct exo-14 are close to one another.
This means that both monoadducts (exo- and endo-14) have to
be formed in the reaction of azirine 12 with acylketene 3a.
Further reaction of isomers 14 with a second molecule of 3a is
possible only for the endo-monoadduct endo-14. This is because
the formation of an intermediate of type 7 from the exo-
monoadduct exo-14 is hindered by the exo-methyl group. This
is evident from the fact that even the distance between the exo-
hydrogen of the aziridine ring and the enolate oxygen in the
intermediate 7a is only 2.22 Å. Unlike in the case of azirine 12,
with azirine 13 the free energy of the transition states TS11
leading to endo-monoadduct endo-16 is much higher (by 3.5
kcal·mol−1) than the free energy of the transition state TS12
leading to exo-monoadduct exo-16. This makes the first route
noncompetitive. The exo-monoadduct exo-16 is unreactive
toward acylketene 3a for the reasons mentioned above for the
exo-monoadduct exo-14.
Further evidence for the proposed reaction route was found
by studying the reactions of acylketene 3a with 2-methyl-
3-phenyl-2H-azirine 12 and 2,3-diphenyl-2H-azirine 13
(Scheme 4).
Scheme 4
Heating a toluene solution of azirine 12 and diazo diketone
4a (in 1:1.1 ratio), as precursor of acylketene 3a, for 2 h gave
rise to the exo-monoadduct exo-14 and bisadduct 15 in 7 and
40% yield, respectively. exo-Monoadduct exo-16 was obtained
as a sole product in 47% yield from azirine 13 and diazo
diketone 4a under the same reaction conditions. The structures
1
of compounds exo-14, 15, and exo-16 were verified by H and
13C NMR, IR spectroscopy, and elemental analysis and the
structure of exo-14 was confirmed by X-ray analysis (Figure 5).
The stereochemistry of exo-monoadduct exo-16 was confirmed
by X-ray analysis of the product of methanolysis of compound
exo-16 (vide infra).
The 13C NMR spectrum of bisadduct 5a shows only one
signal for the imidic carbonyl groups at 169.3 ppm, and the IR
spectrum in KBr pellet shows a single CO vibration band υ =
1717 cm−1. This is due to actual equivalence of the carbonyl
groups both in solution and in solid. Thus according to X-ray
analysis, the lengths of the NCO/CO bonds in compound
5c are in fact equal (1.401(2)/1.212(2) and 1.393(2)/1.206(2)
Å), and, according to the calculations, the conformations of
Heating the monoadducts exo-14, exo-16 with excess of
diazo diketone 4a gave no bisadducts. We believe that the
substituent at position 2 of the 3-aryl-2H-azirine determines the
pathway (Scheme 5) of the reaction: (1) The reaction of the
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Scheme 5
Scheme 6
116.1 ppm corresponding to 25 C3 and 26 C3,9 and one
quartet signal at 159.0 ppm corresponding to 25 C8 in the 13C
NMR spectrum indicate the formation of isomer 26 rather
than 24.
Figure 6. Energy profiles for the reaction of azirines 12 and 13 with
acylketene 3a. Relative free energies (kcal·mol−1, 298 K, toluene)
computed at the DFT B3LYP/6-31G(d) level.
This result implies that both acylketenes 20 and 21 were
formed (Scheme 6) and that they further reacted with azirine
2a to give monoadducts 22 and 23. Bisadduct 26 can be
formed only by reaction of monoadduct 23 with acylketene 21,
whereas bisadduct 25 could be a product of the interaction of
monoadduct 22 with acylketene 21 and of monoadducts 23
with acylketene 20. The absence of the bisadduct 24 in the
reaction mixture indicates that acetylphenylketene 20 is less
reactive toward monoadducts. Xu and Chen found that
N-benzylidenanilines are much more reactive to ketene 20
than to ketene 21.7e We can suppose, therefore, that the
formation of monoadduct 22 prevails over the formation of
monoadduct 23. All this allows us to conclude that the
formation of bisadducts proceeds mostly by reaction of both
monoadducts with acylketene 21.
The reaction of acylketene 3a with azirine 27, containing the
fluorene moiety, proves to be more complicated because the
primary intermediate 28 is more crowded and especially because
of the specific stabilization by the aromatic fluorenyl anion
fragment of the products of the transformations of the primary
intermediate 28. Heating of a toluene solution of azirine 27 and
diazo diketone 4a (in 1:1.1 ratio) gave compounds 29 (7%), 30
(31%), and 31 (6%) (Scheme 7). The structures of compounds
29−31 were verified by 1H and 13C NMR, IR spectroscopy, and
elemental analysis and the structures of 29 and 30 were
confirmed by X-ray analysis (Figure 7).
compound 5a (see the Supporting Information) have close
energies and a low barrier to interconversion, resulting in a Cs
average molecular symmetry (on the NMR time scale at rt).
Unlike bisadducts 5, bisadduct 15, because of the steric
influence of the 11-Me-group, has a conformation in which the
carbonyl groups have rather different structural characteristics.
As follows from the calculations, one carbonyl group in
compound 15 is conjugated with the nitrogen lone pair (N
CO/CO bond lengths 1.389/1.223 Å), whereas the second
is not (NCO/CO bond lengths 1.462/1.206 Å). In
accordance with this, the 13C NMR spectrum of bisadduct 15
shows two imidic carbonyl signals at 166.6 and 169.0 ppm,
and the IR spectrum shows two vibration bands υ = 1716 and
1718 cm−1.
It is known that thermal decomposition of 2-diazo-1-
phenylbutane-1,3-dione 19 leads to two acylketenes 20 and
21.7d,12 In particular, when a xylene solution of diazo diketone
19 was heated at 100 °C for 0.25 h and methanol was used
as a trap for the ketenes, compounds 20 and 21 were formed in
the ratio of 1.3:1.7d We could therefore expect the formation
of the three isomeric bisadducts 24−26 in the reaction of
azirine 2a with diazo diketone 19. Heating a toluene solution of
azirine 2a and diazo diketone 19 (in 1:1.1 ratio) led, however,
to a mixture of only compounds 25 and 26 in a 2:1 ratio
(Scheme 6). The structure of bisadducts 25 and 26 was
An attack of azirine 27 on the ketene carbonyl group of
acylketene 3a leads to intermediate 28, which, unlike
intermediate 6, cannot cyclize with the formation of an oxazine
ring as the fluorene fragment shields the aziridine carbon atom.
Intermediate 28 in fact undergoes aziridine ring-opening to
the zwitterion 32, which further cyclizes to monoadduct 29.
Though the compound 30 can be considered as the product of
(2+4)-cycloaddition of acylketene 3a to pyrrolinone 29, these
1
elucidated by H and 13C NMR spectroscopy. The proton AB
system of C11H2 proves the presence of isomer 25 of
C1-symmetry, whereas the singlet of C11H2 corresponds to
one of isomers 24 or 26 of Cs-symmetry. The 13C NMR
spectrum (without proton decoupling) allows us to distinguish
between 24 and 26. The two quartet signals at 115.6 and
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Scheme 7
Figure 7. X-ray crystal structures of 29, 30.
compounds were not found to react with each other under the
reaction conditions. We suppose, therefore, that zwitterion 32
interacts with a second molecule of 3a to give finally bisadduct
30. The formation of product 31 most probably proceeds via a
quite different pathway. Earlier, we found that 1,4-oxazine
derivatives can be prepared by the reaction of azirines with Rh-
carbenoids generated from diazo keto esters. This reaction
proceeds via formation of azirinium ylide, which undergoes
ring-opening to oxazatriene, followed by 6π-cyclization of the
latter.8f According to this, the carbene, derived from diazo
compound 4a, would be expected to react with azirine 27 to
give ylide 34, which is then further transformed to compound
31 via 6π-cyclization of oxazatriene 35.
Scheme 8
Scheme 9
To prove the role of the aromatic fluorenyl anion fragment in
the aforementioned transformations, the reaction between
diazo compound 4a with 2,2,3-triphenyl-2H-azirine 36,
containing a crowded CN bond like in 27, was investigated.
In accordance with the discussed hypotheses, the only
product of this reaction was oxazine 37, which was obvi-
ously formed analogously to oxazine 31 via carbene 33
and ylide 38 (Scheme 8). The low yields of oxazines 31,
37 is due to easiness of the Wolff rearrangement of diazo
compound 4a.1
oxazepines 40a,b (Scheme 9). Analogously, when a solution of
compound exo-16 in a mixture of CH2Cl2/MeOH was boiled
for 2 h, it was transformed stereoselectively into oxazepine 41
(Scheme 9). The structures of compounds 40a,b and 41 were
Compounds 5 isolated as solids are fairly stable and can be
stored indefinitely at rt. However, when solutions of com-
pounds 5a,c in a mixture of CH2Cl2/MeOH (1:2) were kept at
room temperature, they were quantitatively transformed into
1
verified by H and 13C NMR, IR spectroscopy, and elemental
analysis and the structures of 40a and 41 were confirmed by
X-ray analysis (see the Supporting Information).
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128.7 (2CH), 129.1 (2CH), 129.9 (4CH), 130.1 (CH), 131.1
(4CH), 135.1 (2C), 135.4 (2C), 137.2 (C), 157.4 (2C), 166.3
(2C); IR (KBr, cm−1) ν 3060, 1717, 1637, 1616, 1445, 1391,
1357, 1223, 1096, 1040, 974, 754, 694, 614, 486, 474. Anal.
Calcd for C38H27NO4: C 81.27, H 4.85, N 2.49. Found: C
81.43, H 4.87, N 2.70.
6-(4-Methoxyphenyl)-3,4,8,9-tetraphenyl-5,7-dioxa-1-
azabicylo[4.4.1]undeca-3,8-diene-2,10-dione, 5b. White
solid: mp 193−195 °C (hexane−CH2Cl2); yield, 69%; 1H
NMR (CDCl3) δ 3.81 s (3H, OCH3), 5.03 s (2H, CH2), 6.81−
6.85 m (2H, arom), 6.94−6.97 m (4H, arom), 7.01−7.06 m
(4H, arom), 7.11−7.16 m (2H, arom), 7.21−7.24 m (6H,
arom), 7.32−7.35 m (4H, arom), 7.51−7.54 m (2H, arom);
13C NMR (CDCl3) δ 47.6 (CH2), 55.3 (OCH3), 113.9 (2CH),
114.0 (C, C), 121.6 (C), 126.9 (2CH), 127.5 (2CH), 127.6
(4CH), 128.1 (4CH), 129.1 (2CH), 129.5 (C), 129.9 (4CH),
131.2 (4CH), 135.2 (2C), 135.5 (2C), 157.5 (2C), 160.6 (C),
166.4 (2C); IR (KBr, cm−1) ν 3062, 1718, 1637, 1616, 1351,
618, 475. Anal. Calcd for C39H29NO5: C 79.17, H 4.94, N 2.37.
Found: C 79.19, H 4.92, N 2.14.
CONCLUSION
■
Acylketenes, generated from diazo diketones, react with 2-
unsubstituted and 2-monosubstituted 2H-azirines with
formation of 2:1 or 1:1 adducts, derivatives of 5,7-dioxa-1-
azabicyclo[4.4.1]undeca-3,8-diene or 5-oxa-1-azabicyclo[4.1.0]-
hept-3-ene. The composition and the stereochemistry of the
products, as well as the DFT B3LYP/6-31G(d) calculations,
prove a stepwise non-pericyclic mechanism for the formation of
5-oxa-1-azabicyclo[4.1.0]hept-3-ene derivatives. This is due, on
the one hand, to the extremely high electrophilicity of the
ketene carbonyl group and, on the other hand, due to the
sufficiently high nucleophilicity of the nitrogen atom in the
monoadducts 1 because of the specific geometry of the amidic
fragment in the bicycle 1. The reaction of 2-diazo-1,3-
diphenylpropane-1,3-dione with the 2,2-disubstituted azirine,
3-phenylspiro[2H-azirine-2,9′-fluorene], proceeds via quite
different routes for steric reasons and because of the
stabilization of the intermediates by the aromatic fluorenyl
anion fragment. Both the 1:1 and 2:1 adducts are quantitatively
transformed under mild conditions with methanol into 1,4-
oxazepine derivatives.
6-(4-Nitrophenyl)-3,4,8,9-tetraphenyl-5,7-dioxa-1-
azabicylo[4.4.1]undeca-3,8-diene-2,10-dione, 5c. White
solid: mp 220−222 °C (toluene); yield, 55%; 1H NMR
(CDCl3) δ 5.11 s (2H, CH2), 6.95−6.99 m (4H, arom), 7.02−
7.07 m (4H, arom), 7.12−7.17 m (2H, arom), 7.22−7.30 m
(10H, arom), 7.66−7.70 m (2H, arom), 8.04−8.08 m (2H,
arom); 13C NMR (CDCl3) δ 47.1 (CH2), 112.5 (C, C), 122.9
(C), 123.6 (2CH), 126.7 (2CH), 127.8 (4CH), 127.9 (2CH),
128.2 (2CH), 128.3 (4CH), 129.5 (4CH), 131.0 (4CH), 134.8
(2C), 134.9 (2C), 143.5 (C), 148.3 (C), 156.7 (2C), 166.0
(2C); IR (KBr, cm−1) ν 3057, 1730, 1609, 1527, 1445, 1349,
1222, 1041, 963, 697. Anal. Calcd for C38H26N2O6: C 75.24, H
4.32, N 4.62. Found: C 75.43, H 4.26, N 4.71. Crystal data:
C38H26N2O6, M = 606.61, monoclinic, space group P21/n (No.
14), a = 9.5212(3), b = 10.8122(4), c = 28.4537(11) Å, β =
94.39(1)°, U = 2920.56(18) Å3, Z = 4; F(000) = 1264, Dc =
1.380 mg/m3, μ = 0.094 mm−3. 39887 reflections were
measured yielding 7747 unique data (Rint = 0.0325). The
final wR(F2) was 0.1482 (all data), conventional R1(F) =
0.0530 for 6152 reflections with I ≥ 2σ, GOF = 1.062.
Reaction of 2-Methyl-3-phenyl-2H-azirine 12 and 2-
Diazo-1,3-diphenylpropane-1,3-dione 4a. A mixture of
azirine 12 (65.5 mg, 0.5 mmol) and diazo diketone 4a (137.5
mg, 0.55 mmol) in dry toluene (4 mL) was heated with stirring
at 90 °C for 2 h. The reaction was monitored by TLC (eluent
hexane/ethyl acetate, 5:1). The crystalline compound 15 (115
mg, 40%) obtained on cooling the reaction mixture was filtered
off and washed with diethyl ether. The solvent was removed in
vacuum, and the residue was purified by recrystallization from
hexane/CH2Cl2 mixture (3:1) to give compound exo-14 (12.4
mg, 7%).
EXPERIMENTAL SECTION
■
General Methods. Melting points were determined on a
hot stage microscope and are uncorrected. H (300 MHz) and
1
13C (75 or 150 MHz) NMR spectra were determined in
CDCl3. Chemical shifts (δ) are reported in ppm downfield
from tetramethylsilane. Single crystal X-ray data for all
compounds were collected at 120 K on a SMART-6000
diffractometer (graphite-monochromated Mo−Kα radiation, λ
= 0.71073 Å) equipped with open-flow nitrogen cryostat. All
structures were solved by direct method and refined by full-
matrix least-squares on F2 for all data using OLEX213 and
SHELXTL14 software. All non-disordered non-hydrogen atoms
were refined with anisotropic displacement parameters; H-
atoms were located on the difference map and refined
isotropically in all structures except 30, where they were placed
into calculated positions and refined in the riding mode. The
reactions under microwave irradiation at 160 W were carried
out in a sealed flask in Minotavr-2 microwave oven for
laboratory experiments. Compounds 2a,b,15 2c,16 4a, 19,17
12,18 13,19 and 2720 were prepared by the reported procedures.
General Procedures for Reactions of Azirines 2a−c
and 2-Diazo-1,3-diphenylpropane-1,3-dione 4a. A mix-
ture of compound 2a−c (0.5 mmol) and 4a (275 mg, 1.1
mmol) in dry toluene (4 mL) was heated at the reaction
temperature and reaction time indicated in Table 1. The
reaction was monitored by TLC (eluent hexane/ethyl acetate,
5:1). The crystalline substance obtained after cooling the
reaction mixture to rt was filtered off and washed with diethyl
ether. An additional amount of the product was isolated from
the filtrate by removing the solvent in vacuum, followed by
recrystallization of the residue from hexane/CH2Cl2 mixture
(5:1).
(6RS,7RS)-7-Methyl-3,4,6-triphenyl-5-oxa-1-
azabicyclo[4.1.0]hept-3-en-2-one, exo-14. Colorless crys-
1
tals: mp 59−60 °C (hexane−CH2Cl2); H NMR (CDCl3) δ
1.21 d (3H, J = 5.5 Hz, CH3), 3.31 q (1H, J = 5.8 Hz, CH),
7.18−7.27 m (8H, arom), 7.49−7.53 m (5H, arom), 7.72−7.75
m (2H, arom); 13C NMR (CDCl3) δ 13.7 (CH3), 42.8 (CH),
78.5 (C), 110.2 (C), 127.28 (2CH), 127.32 (CH), 127.8
(2CH), 128.1 (2CH), 128.2 (2CH), 129.1 (CH), 129.4
(2CH), 130.2 (CH), 131.0 (2CH), 132.6 (2C), 134.0 (C),
162.2 (C), 173.5 (C); IR (KBr, cm−1) ν 3060, 1619, 1612,
1597, 1446, 982, 996, 716, 697. Anal. Calcd for C24H19NO2: C
81.56, H 5.42, N 3.96. Found: C 81.46, H 5.48, N 3.84. Crystal
3,4,6,8,9-Pentaphenyl-5,7-dioxa-1-azabicyclo[4.4.1]-
undeca-3,8-diene-2,10-dione, 5a. White solid: mp 221−
223 °C (hexane−CH2Cl2); yield, 70%; H NMR (CDCl3) δ
5.07 s (2H, CH2), 6.93−6.99 m (4H, arom), 7.00−7.04 m (4H,
arom), 7.10−7.15 m (2H, arom), 7.19−7.23 m (6H, arom),
7.30−7.38 m (7H, arom), 7.60 dd (2H, J = 7.8 Hz, J = 1.4 Hz,
arom); 13C NMR (CDCl3) δ 47.4 (CH2), 113.9 (C, C), 121.8
(C), 125.3 (2CH), 127.5 (4CH), 127.6 (2CH), 128.1 (4CH),
1
9349
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Article
data: C24H19NO2, M = 353.40, monoclinic, space group C2/c
(No. 15), a = 9.6834(2), b = 19.3806(4), c = 19.9584(4) Å, β =
98.46(1)°, U = 3704.80(13) Å3, Z = 8; F(000) = 1488, Dc =
1.267 mg/mm3, μ = 0.080 mm−1. 30608 reflections were
measured yielding 4933 unique data (Rint = 0.0430). The final
wR(F2) was 0.1176 (all data), conventional R1(F) = 0.0431 for
3619 reflections with I ≥ 2σ, GOF = 1.030.
arom), 7.29−7.41 m (13H, arom), 7.51−7.53 m (2H, arom);
13C NMR (CDCl3) δ 16.36, 16.42 (2CH3 minor, CH3 major),
22.1 (CH3 major), 47.3 (CH2 minor), 47.5 (CH2 major), 112.7
(C), 113.7 (C), 115.6, 116.1 (2C minor, C major), 120.2 (C),
125.0 (CH), 125.2 (CH), 127.7 (CH), 127.89 (CH), 127.94
(CH), 128.2 (CH), 128.3 (CH), 128.6 (CH), 128.67 (CH),
128.70 (CH), 129.1 (CH), 129.2 (CH), 129.6 (CH), 129.9
(CH), 130.3 (CH), 135.69 (C), 135.71 (C), 137.5 (C), 137.9
(C), 156.16 (C), 156.24 (C), 159.0 (C major), 165.3 (C
major), 167.65 (C), 167.69 (C); IR (KBr, cm−1) ν 3056, 1725,
1620, 1450, 1443, 1381, 1358, 1230, 1152, 1053, 1030, 779,
775, 760, 697. Anal. Calcd for C28H23NO4: C 76.87, H 5.30, N
3.20. Found: C 76.63, H 5.14, N 3.37.
Reaction of 3-Phenylspiro[2H-azirine-2,9′-fluorene]
27 and 2-Diazo-1,3-diphenyl-propane-1,3-dione 4a. A
mixture of azirine 27 (267 mg, 1 mmol) and diazo diketone 4a
(275 mg, 1.1 mmol) in dry toluene (5.5 mL) was heated with
stirring at 90 °C for 2 h. The reaction was monitored by TLC
(eluent hexane/ethyl acetate, 4:1). The solvent was removed in
vacuum, the residue was purified by flash chromatography
on silica (hexane/ethyl acetate, 10:1) to give compounds 29
(34 mg, 7%), 30 (123 mg, 17%), and 31 (30 mg, 6%).
4′-Benzoyl-2′,4′-diphenylspiro[fluorene-9,3′-pyrrol]-
5′(4′H)-one, 29. Colorless crystals: mp 194−195 °C (Et2O);
1H NMR (CDCl3) δ 6.76 t (2H, J = 7.6 Hz, arom), 6.89 t (1H,
J = 7.3 Hz, arom), 7.08−7.25 m (8H, arom), 7.30−7.35 m (2H,
arom), 7.40−7.56 m (6H, arom), 7.62−7.65 m (3H, arom),
7.89 d (1H, J = 8.0 Hz, arom); 13C NMR (CDCl3) δ 75.1 (C),
84.0 (C), 119.99 (CH), 120.05 (CH), 124.4 (CH), 127.0
(2CH), 127.2 (CH), 127.3 (CH), 127.5 (2CH), 127.9 (CH),
128.4 (2CH), 128.5 (2CH), 129.0 (CH), 129.1 (CH), 129.3
(CH), 130.0 (2CH), 130.4 (2CH), 130.8 (C), 132.0 (CH),
133.9 (C), 134.0 (CH), 136.7 (C), 139.6 (C), 142.2 (C), 143.1
(C), 143.2 (C), 185.9 (C), 194.6 (C), 197.8 (C); IR (KBr,
cm−1) ν 3062, 1739, 1672, 1670, 1599, 1534, 1532, 1446, 1324,
1229, 1137, 988, 962, 756, 750, 737, 707, 694, 651, 581. Anal.
Calcd for C35H23NO2: C 85.87, H 4.74, N 2.86. Found: C
85.80, H 4.80, N 2.99. Crystal data: C35H23NO2, M = 489.54,
orthorhombic, space group P212121 (No. 19), a = 10.5934(2), b
= 12.6294(3), c = 18.7414(4) Å, U = 2507.38(9) Å3, Z = 4;
F(000) = 1024, Dc = 1.297 mg/mm−3, μ = 0.080 mm−1. 44620
11-Methyl-3,4,6,8,9-pentaphenyl-5,7-dioxa-1-
azabicyclo[4.4.1]undeca-3,8-diene-2,10-dione, 15.
1
White solid: mp 190−192 °C (toluene); H NMR (CDCl3)
δ 1.81 d (3H, J = 7.3 Hz, CH3), 5.16 q (1H, J = 7.3 Hz, C11H),
6.68−6.70 m (2H, arom), 6.88−6.93 m (2H, arom), 7.04−7.09
m (1H, arom), 7.15−7.19 m (3H, arom), 7.22−7.27 m (8H,
arom), 7.31−7.34 (2H, arom), 7.38−7.41 m (2H, arom), 7.50−
7.52 m (3H, arom), 7.82−7.85 m (2H, arom); 13C NMR
(CDCl3) δ 13.4 (CH3), 54.8 (CH), 111.2 (C), 117.1 (C),
122.0 (C), 125.2 (2CH), 126.9 (CH), 127.4 (2CH), 127.7
(2CH, CH), 127.8 (2CH), 128.2 (2CH), 128.9 (CH), 129.2
(2CH), 129.5 (2CH), 129.6 (CH), 130.3 (CH), 130.8 (2CH),
131.3 (2CH), 131.7 (2CH), 135.0 (C), 135.4 (C), 136.3 (C),
137.0 (2C), 155.0 (2C), 166.6 (C), 169.0 (C); IR (KBr, cm−1)
ν 3058, 1717, 1716, 1600, 1445, 1331, 1322, 1235, 1144, 987,
742, 696. Anal. Calcd for C39H29NO4: C 81.37, H 5.08, N 2.43.
Found: C 81.30, H 4.96, N 2.17.
(6RS,7RS)-3,4,6,7-Tetraphenyl-5-oxa-1-azabicyclo-
[4.1.0]hept-3-en-2-one, exo-16. A mixture of azirine 13
(96.5 mg, 0.5 mmol) and diazo diketone 4a (137.5 mg, 0.55
mmol) in dry toluene (7 mL) was heated with stirring at 90 °C
for 2 h. The reaction was monitored by TLC (eluent hexane/
ethyl acetate, 5:1). The solvent was removed in vacuum, and
the residue was crystallized from petroleum ether/ethyl acetate
mixture (4:1) to give compound exo-16 (97.5 mg, 47%).
Yellowish solid: mp 149−150 °C (petroleum ether−ethyl
acetate, 4:1); 1H NMR (CDCl3) δ 4.36 s (1H, CH), 7.16−7.39
m (18H, arom), 7.59−7.62 m (2H, arom); 13C NMR (CDCl3)
δ 48.2 (CH), 79.5 (C), 110.4 (C), 127.4 (CH), 127.47 (2CH),
127.49 (2CH), 127.8 (CH), 127.9 (2CH), 128.0 (2CH),
128.17 (2CH), 128.23 (2CH), 129.0 (CH), 129.5 (2CH),
130.3 (CH), 131.0 (2CH), 132.4 (2C), 132.5 (C), 133.0 (C),
162.5 (C), 172.7 (C); IR (KBr, cm−1) ν 3061, 1690, 1681,
1608, 1595, 1571, 1497, 1448, 1356, 1231, 1223, 1014, 767,
751, 695. Anal. Calcd for C29H21NO2: C 83.83, H 5.09, N 3.37.
Found: C 83.76, H 5.10, N 3.28.
3,8-Dimethyl-4,6,9-triphenyl-5,7-dioxa-1-azabicyclo-
[4.4.1]undeca-3,8-diene-2,10-dione, 25, 3,9-Dimethyl-
4,6,8-triphenyl-5,7-dioxa-1-azabicyclo[4.4.1]undeca-3,8-
diene-2,10-dione, 26. A mixture of 3-phenyl-2H-azirine 2a
(117 mg, 1 mmol) and 2-diazo-1-phenyl-butane-1,3-dione 19
(207 mg, 1.1 mmol) in dry toluene (4 mL) was heated with
stirring at 90 °C for 2 h. The reaction was monitored by TLC
(eluent hexane/ethyl acetate, 4:1). A solid mixture of
compounds 25 and 26 was obtained on cooling the reaction
mixture, and this was filtered off and washed with diethyl ether.
An additional amount of compounds 25 and 26 was isolated
from the filtrate by removing the solvent in vacuum, followed
by recrystallization of the residue from hexane/CH2Cl2 mixture
to give the 2:1 mixture of compounds 25 and 26 (131 mg, 30%
overall yield).
reflections were measured yielding 7312 unique data (Rint
=
0.0540). The final wR(F2) was 0.0981 (all data), conventional
R1(F) = 0.0391 for 6095 reflections with I ≥ 2σ, GOF = 1.036.
(7′RS,8a′SR)-7′-Benzoyl-2′,3′,7′,8a′-tetraphenylspiro-
[fluorene-9, 8′-pyrrolo[2, 1-b][1, 3]oxazine]-
4′,6′(7′H,8a′H)-dione, 30. Colorless crystals: mp 147−148
1
°C (CH2Cl2); H NMR (CDCl3) δ 6.24 br d (1H, J = 6.2 Hz,
arom), 6.57 d (1H, J = 8.0 Hz, arom), 6.78 br t (1H, J = 7.6 Hz,
arom), 6.84−6.87 m (3H, arom), 6.96 br t (1H, J = 7.6 Hz,
arom), 7.04−7.27 m (18H, arom), 7.30−7.38 m (5H, arom),
7.50 d (1H, J = 6.9 Hz, arom), 7.55 td (1H, J = 7.6 Hz, J = 0.7
Hz, arom), 7.77 d (1H, J = 7.3 Hz, arom); 13C NMR (CDCl3)
δ 65.5 (C), 75.4 (C), 97.3 (C), 115.4 (C), 119.8 (CH), 119.9
(CH), 123.2 (CH), 123.4 (CH), 125.5 (CH), 126.6 (CH),
126.9 (2CH), 127.0 (CH), 127.4 (CH), 127.7 (CH), 127.8
(CH), 127.9 (3CH), 128.0 (2CH), 128.3 (2CH), 128.7 (CH),
129.0 (CH), 129.1 (CH), 129.7 (2CH), 129.8 (2CH), 129.9
(2CH), 130.7 (CH), 130.8 (CH), 131.4 (2CH), 131.5 (CH),
132.26 (C), 132.30 (C), 134.0 (C), 134.5 (C), 137.8 (C), 138.4
(C), 140.7 (C), 144.1 (C), 146.2 (C), 160.2 (C), 163.4 (C),
171.5 (C), 196.4 (C); IR (KBr, cm−1) ν 3061, 1769, 1685,
1560, 1447, 1356, 1297, 1277, 1263, 1231, 1181, 782, 757, 739,
White solid: mp 168−173 °C (petroleum ether−CH2Cl2,
4:1); 1H NMR (CDCl3) δ 1.78 s (3H, CH3, major), 2.04 s (3H,
CH3), 2.05 s (3H, CH3), 4.73 d (1H, JAB = 16.3 Hz, CHAHB,
major), 4.74 s (2H, CH2, minor), 4.78 d (1H, JAB = 16.3 Hz,
CHAHB, major), 7.13−7.19 m (4H, arom), 7.22−7.27 m (3H,
9350
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Article
697, 624. Anal. Calcd for C50H33NO4: C 84.37, H 4.67, N 1.97.
Found: C 84.43, H 4.62, N 2.02. Crystal data: C50H33NO4 ×
CH2Cl2, M = 769.70, monoclinic, space group Cc (No. 9), a =
14.3216(5), b = 14.1401(5), c = 20.2005(7) Å, β = 93.068(10)°,
U = 4084.9(2) Å3, Z = 4; F(000) = 1656, Dc = 1.295 mg/mm−3,
μ = 0.207 mm−1. 38350 reflections were measured yielding
9858 unique data (Rint = 0.0686). The final wR(F2) was 0.1322
(all data), conventional R1(F) = 0.0529 for 6802 reflections with
I ≥ 2σ, GOF = 0.987.
(2CH), 127.9 (2CH), 128.0 (2CH), 128.1 (CH), 128.6 (CH),
128.8 (CH), 129.7 (2CH), 129.9 (2CH), 130.4 (2CH), 130.9
(2CH), 133.8 (C), 135.1 (C), 135.8 (C), 136.5 (C), 137.4 (C),
155.6 (C), 156.9 (C), 168.5 (C), 170.2 (C); IR (KBr, cm−1) ν
3410, 3186, 3058, 2948, 1717, 1713, 1662, 1631, 1491, 1446,
1325, 1258, 1220, 1099, 1089, 1068, 1001, 970, 774, 696. Anal.
Calcd for C39H31NO5: C 78.90, H 5.26, N 2.36. Found: C
79.03, H 5.21, N 2.29. Crystal data: C39H31NO5 × EtOH, M =
639.72, triclinic, space group P1 (No. 2), a = 10.1297(3), b =
̅
12.8314(4), c = 14.6074(4) Å, α = 96.969(10), β =
104.944(10), γ = 106.416(10)°, U = 1720.58(9) Å3, F(000)
= 676, Dc = 1.235 mg/mm−3, μ = 0.082 mm−1. 26722 reflec-
tions were measured yielding 9595 unique data (Rint = 0.0657).
The final wR(F2) was 0.0996 (all data), conventional R1(F) =
0.0441 for 5796 reflections with I ≥ 2σ, GOF = 0.921.
(3′,6′-Diphenylspiro[fluorene-9,2′-[1,4]oxazine]-5′-yl)-
(phenyl)methanone, 31. Yellow solid: mp 249−251 °C
1
(hexane−ethyl acetate); H NMR (CDCl3) δ 7.05 t (2H, J =
7.3 Hz, arom), 7.12−7.17 m (1H, arom), 7.22−7.27 m (5H,
arom), 7.30−7.36 m (4H, arom), 7.48−7.53 m (4H, arom),
7.56−7.60 m (3H, arom), 7.82 d (2H, J = 7.3 Hz, arom), 8.11−
8.14 m (2H, arom); 13C NMR (CDCl3) δ 98.1 (C), 110.0 (C),
121.0 (2CH), 124.9 (2CH), 126.7 (CH), 128.27 (2CH),
128.35 (2CH), 128.4 (2CH), 128.6 (2CH), 128.7 (2CH),
128.9 (2CH), 129.8 (2CH), 130.7 (2CH), 132.0 (CH), 132.5
(CH), 134.8 (C), 139.8 (C), 140.5 (2C), 142.3 (2C), 164.3
(C), 172.3 (C), 196.4 (C); IR (KBr, cm−1) ν 3057, 1667, 1636,
1536, 1448, 1218, 1002, 757, 733, 686. Anal. Calcd for
C35H23NO2: C 85.87, H 4.74, N 2.86. Found: C 85.74, H 4.87,
N 2.81.
(Z)-Methyl 3-(2-(4-Nitrophenyl)-5-oxo-6,7-diphenyl-
2,3,4,5-tetrahydro-1,4-oxazepin-2-yloxy)-2,3-diphenyla-
crylate, 40b. Colorless crystals: mp 204−205 °C (methanol);
1H NMR (CDCl3) δ 3.81 s (3H, OCH3), 4.19 dd (1H, JAB
=
15.4 Hz, JBX = 6.5 Hz, CHBHA), 4.50 dd (1H, JAB = 15.4 Hz, JAX
= 6.5 Hz, CHAHB), 6.25 br d (2H, J = 7.6 Hz, arom), 6.35 br
(1H, NH), 6.69−6.76 m (4H, arom), 6.97−7.08 m (4H, arom),
7.09−7.13 m (2H, arom), 7.18−7.27 m (3H, arom), 7.32−7.37
m (5H, arom), 7.70−7.74 m (2H, arom), 8.00−8.05 m (2H,
arom); 13C NMR (CDCl3) δ 49.7 (CH2), 52.2 (OCH3), 110.5
(2C), 121.8 (C), 122.8 (2CH), 126.9 (2CH), 127.1 (CH),
127.4 (CH), 127.9 (2CH), 128.0 (2CH), 128.1 (2CH), 128.6
(2CH), 128.7 (CH), 129.0 (CH), 129.6 (2CH), 129.7 (2CH),
130.5 (2CH), 130.7 (2CH), 133.1 (C), 134.6 (C), 135.2 (C),
136.0 (C), 144.4 (C), 147.9 (C), 155.2 (C), 155.7 (C), 168.5
(C), 170.1 (C); IR (KBr, cm−1) ν 3417, 3057, 2946, 1722,
1693, 1675, 1614, 1523, 1444, 1404, 1346, 1327, 1212, 1097,
1067, 1038, 1017, 1002, 972, 853, 766, 696. Anal. Calcd for
C39H30N2O7: C 73.34, H 4.73, N 4.39. Found: C 73.41, H 4.59,
N 4.50.
(2RS,3SR)-2-Methoxy-2,3,6,7-tetraphenyl-3,4-dihydro-
1,4-oxazepin-5(2H)-one, 41. Compound 16 (60 mg, 0.1445
mmol) in dry methanol/CH2Cl2 mixture (2:1, 3 mL) was
refluxed with stirring for 2.5 h. The reaction mixture was
cooled, and the solid product was filtered and washed with
methanol. An additional amount of compound 41 (overall yield
56 mg, 86%) was isolated from the filtrate by removing the
solvent in vacuum, followed by recrystallization of the residue
from a mixture of hexane−CH2Cl2.
Phenyl(2,5,6,6-tetraphenyl-6H-[1,4]oxazin-3-yl)-
methanone, 37. A mixture of 2,2,3-triphenyl-2H-azirine 36
(128 mg, 0.475 mmol) and diazo diketone 4a (131 mg, 0.52
mmol) in dry toluene (3 mL) was heated with stirring at 90 °C
for 2 h. The reaction was monitored by TLC (eluent petroleum
ether/ethyl acetate, 5:1). The solvent was removed in vacuum,
and the residue was purified by flash chromatography on silica
(petroleum ether/ethyl acetate, 10:1) to give compound 37
(15 mg, 6%).
1
Yellow solid: mp 172−173 °C (Et2O); H NMR (CDCl3) δ
7.18−7.23 m (4H, arom), 7.27−7.32 m (3H, arom), 7.40−7.41
m (10H, arom), 7.51−7.63 m (6H, arom), 8.02−8.05 m (2H,
arom); 13C NMR (CDCl3) δ 99.1, 109.7, 126.560, 126.564,
126.57, 128.21, 128.24, 128.26, 128.34, 128.456, 128.460,
128.6, 128.9, 129.7, 129.95, 129.96, 130.9, 131.7, 132.3, 134.8,
138.4, 139.7, 163.0, 173.2, 196.4; IR (KBr, cm−1) ν 2961, 2925,
1634, 1617, 1446, 1359, 1262, 1219, 1180, 1100, 986, 760, 693,
615; HRMS-ESI calcd for C35H26NO2 [M + H]+, 492.1964,
+
found 492.1940.
General Procedure for Reactions of 5a,c with
Methanol. Solutions of 5a,c (0.036 mmol) in methanol/
CH2Cl2 mixture (2:1) were kept at rt until the reaction was
completed (24 h for 5a, 2 weeks for 5c). The reaction was
monitored by TLC (eluent hexane/ethyl acetate 2:1). The
solvent was removed in vacuum, and the residue was
recrystallized from methanol to give compounds 40a (20 mg,
95%) and 40b (21.5 mg, 93%).
Colorless crystals: mp >260 °C (ethanol); 1H NMR (CDCl3)
δ 2.79 s (3H, OCH3), 5.27 d (1H, J = 6.2 Hz, C3H), 6.31 br d
(1H, J = 5.8 Hz, NH), 6.76 d (2H, J = 7.6 Hz, arom), 7.07 br
(2H, arom), 7.17−7.29 m (13H, arom), 7.31−7.37 m (1H,
arom), 7.40−7.43 m (2H, arom); 13C NMR (CDCl3) δ 51.4
(OCH3), 64.1 (CH), 115.0 (C), 125.4 (C), 127.3 (2CH), 127.6
(CH), 127.8 (2CH), 127.9 (2CH), 128.2 (CH), 128.3 (4CH),
128.77 (CH), 128.85 (CH), 129.0 (2CH), 129.2 (2CH), 130.7
(2CH), 134.1 (C), 134.7 (C), 135.1 (C), 136.0 (C), 155.1 (C),
170.9 (C); IR (KBr, cm−1) ν 3425, 3199, 3058, 1658, 1446,
1395, 1325, 1223, 1122, 980, 719, 698. Anal. Calcd for
C30H25NO3: C 80.51, H 5.63, N 3.13. Found: C 80.53, H
5.54, N 3.09. Crystal data: C30H25NO3, M = 447.51, monoclinic,
space group C2/c (No. 15), a = 24.4292(6), b = 10.2810(3), c =
21.1739(5) Å, β = 117.263(10)°, U = 4727.2(2) Å3, Z = 8;
F(000) = 1888, Dc = 1.258 mg/mm−3, μ = 0.081 mm−1. 26620
(Z)-Methyl 3-(5-Oxo-2,6,7-triphenyl-2,3,4,5-tetrahy-
dro-1,4-oxazepin-2-yloxy)-2,3-diphenylacrylate, 40a.
1
Colorless crystals: mp 175−180 °C (methanol); H NMR
(CDCl3) δ 3.82 s (3H, OCH3), 4.19 dd (1H, JAB = 15.3 Hz, JBX
= 6.9 Hz, CHBHA), 4.48 dd (1H, JAB = 15.3 Hz, JAX = 6.9 Hz,
CHAHB), 6.02 br (1H, NH), 6.24 d (2H, J = 7.7 Hz, arom),
6.68−6.73 m (2H, arom), 6.74−6.78 m (2H, arom), 6.93−6.98
m (1H, arom), 7.00−7.03 m (3H, arom), 7.11−7.14 m (2H,
arom), 7.17−7.24 m (6H, arom), 7.29−7.49 m (5H, arom),
7.49−7.51 m (2H, arom); 13C NMR (CDCl3) δ 50.1 (CH2),
52.0 (OCH3), 111.4 (2C), 121.0 (C), 126.6 (2CH), 126.8
(CH), 127.15 (CH), 127.23 (2CH), 127.7 (2CH), 127.8
reflections were measured yielding 6588 unique data (Rint
=
0.0233). The final wR(F2) was 0.1217 (all data), conventional
R1(F) = 0.0411 for 5481 reflections with I ≥ 2σ, GOF = 1.049.
9351
dx.doi.org/10.1021/jo201563b|J. Org. Chem. 2011, 76, 9344−9352

The Journal of Organic Chemistry
Article
L; Li, Y; Dong, Y.; Gong, M.; Zhao, X.; Zhang, Y.; Wang, J. J. Am.
Chem. Soc. 2011, 133, 4330. (i) Presset, M.; Mohanan, K.; Hamann,
M.; Coquerel, Y.; Rodriguez, J. Org. Lett. 2011, 13, 4124.
Computational Details. All calculations were performed
with the B3LYP density functional method21 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 DFT B3LYP/
6-31G(d) level using Gaussian 03.22 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. The energies of the stationary
points were corrected by single-point calculations using
polarizable continuum solvent model for toluene.
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ASSOCIATED CONTENT
* Supporting Information
■
S
1H and 13C NMR spectra for all new compounds and
crystallographic data for compounds 5c, exo-14, 29, 30, 40a,
and 41 (CIF format). Computational details: energies of the
reactants, transition states, their Cartesian coordinates. This
material is available free of charge via the Internet at http://
pubs.acs.org.
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AUTHOR INFORMATION
Corresponding Author
*E-mail: alexander.khlebnikov@pobox.spbu.ru.
■
ACKNOWLEDGMENTS
■
We gratefully acknowledge the financial support of the Russian
Foundation for Basic Research (Project 11-03-00186) and the
Federal Grant-in-Aid Program “Human Capital for Science and
Education in Innovative Russia” (Governmental Contract No.
16.740.11.0442).
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