Rh(II)-carbenoid mediated 2H-azirine ring-expansion as a convenient route to non-fused photo- and thermochromic 2H-1,4-oxazines

Article abstract of DOI:10.1016/j.tet.2013.03.106

The Rh₂(OAc)₄-catalyzed domino reaction of 2H-azirines with 2-acyl-2-diazoacetates provides a unique synthetic approach to non-fused 2H-1,4-oxazines. The reaction proceeds via sequential formation of a rhodium carbenoid, an azirinium

Full text of DOI:10.1016/j.tet.2013.03.106

Tetrahedron 69 (2013) 4292e4301
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Rh(II)-carbenoid mediated 2H-azirine ring-expansion
as a convenient route to non-fused photo- and thermochromic
2H-1,4-oxazines
*
Nikolai V. Rostovskii, Mikhail S. Novikov , Alexander F. Khlebnikov,
Vsevolod A. Khlebnikov, Sergei M. Korneev
Department of Chemistry, Saint-Petersburg State University, Universitetskii pr. 26, 198504 St. Petersburg, Russia
a r t i c l e i n f o
a b s t r a c t
Article history:
The Rh2(OAc)4-catalyzed domino reaction of 2H-azirines with 2-acyl-2-diazoacetates provides a unique
synthetic approach to non-fused 2H-1,4-oxazines. The reaction proceeds via sequential formation of
a rhodium carbenoid, an azirinium ylide, and a 1-acyl-1-(alkoxycarbonyl)-2-azabuta-1,3-diene to give,
Received 12 December 2012
Received in revised form 27 February 2013
Accepted 18 March 2013
after 1,6-p-electrocyclization, a 2H-1,4-oxazine derivative in good yield. The observed stereoselectivity of
Available online 2 April 2013
2-azadiene formation is consistent with DFT calculations of the azirinium ylidee2-azadiene isomeriza-
tion, providing evidence for the ylide mechanism of the reaction. The substitution pattern and config-
uration of the carbonecarbon double bond in 2-azadienes has a dramatic influence on their cyclization to
oxazines: the CO2R group on C4 stabilizes an open-chain form and, as the result of this, a new class of
stable 2-azadienes, 1-acyl-2-azadiene-1,4-dicarboxylates, could be isolated. The 1,4-oxazines obtained by
this method are the first representatives of monocyclic 2H-1,4-oxazine derivatives, which exhibit photo-
and thermochromic activity.
Keywords:
Azirines
Carbenoids
Diazo compounds
Electrocyclic reactions
Photochromism
Ó 2013 Elsevier Ltd. All rights reserved.
1. Introduction
Photochromism is a phenomenon involving a photoinduced
reversible transformation between two molecular states whose
absorption spectra are significantly different. Organic photochro-
mic compounds have been the subject of intense investigations
as to their potential applications. These include erasable optical
disks,1 lenses,2 light filters and photo-switching devices,3 three-
dimensional memory,4 photochromic liquid crystals,3 photochro-
mic plastics,4 and photoswitchable biomaterials.5
One of the promising classes of organic photochromic materials
having excellent fatigue resistance are spirooxazines.6 These mol-
ecules contain a fused ring-substituted 2H-1,4-oxazine moiety in
which the C2 atom is involved in a spiro linkage. Under UV irradi-
ation these colorless compounds undergo oxazine ring opening by
CeN bond cleavage to give the colored merocyanine open-chain
isomer, which cyclizes back to the oxazine in the dark. In the case
of non-fused 2H-1,4-oxazines the open-chained valence isomer
would be 1-acyl-2-azabuta-1,3-diene (Scheme 1).
Scheme 1. Valence isomerism of spiro benzoxazines and non-fused oxazines.
a few simple and efficient methods for the preparation of ortho-
fused spirooxazines from o-hydroxynitroso compounds, 1-amino-
2-naphthols and several other compounds have been elabo-
rated.6a,c A few examples of the preparation of photochromic non-
spiro ortho-fused 2H-1,4-oxazines are also known.7 To date, there
are no general methods of preparation of non-fused 2H-1,4-
oxazines. Attempts to synthesize them by standard protocols
have failed.8 6-Alkoxy- or 6-acetoxy-2H-1,4-oxazines were isolated
as byproducts of alkylation or acylation of the corresponding oxa-
zinones.9 3,5-Diphenyl-2H-1,4-oxazine, which was synthesized
The structural diversity of the known 2H-1,4-oxazines is limited
to ortho-fused derivatives because of their synthetic availability:
* Corresponding author. Tel.: þ7 812 428 4021; fax: þ7 812 428 6939; e-mail
address: m.s.novikov@chem.spbu.ru (M.S. Novikov).
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.03.106

N.V. Rostovskii et al. / Tetrahedron 69 (2013) 4292e4301
4293
from diphenacyl ether and ammonia is the only stable non-fused
1,4-oxazine prepared in reasonable yield.10 Meanwhile, it is
known that aryl-substituted 2H-azirines react with diazo esters,
such as dimethyl diazomalonate and methyl 2-diazo-2-
phenylacetate in the presence of rhodium catalyst to give
substituted 2-azadienes in good yields (Scheme 2).11
reaction of ethyl 2-diazoacetoacetate 2a with 2,3-diphenyl-2H-
azirine 1a. It is known that diazo compound 2a in benzene or flu-
orobenzene decomposes in the presence of Rh2(OAc)4 or Cu(hfa-
cac)2 at temperatures over 70 ꢀC.13a,14
Slow addition of the solution of diazoacetoacetate 2a to a mix-
ture of azirine 1a and Rh2(OAc)4 in benzene at 80 ꢀC (method A)
gave rise to 2H-1,4-oxazine 3a, which was isolated in 37% yield
(Scheme 3, Table 1).
In this case no 2-azadiene 4a was observed in the reaction
mixture. Analogously, oxazines 3b,c,e,g were synthesized in
11e45% yield from 1aec and ethyl 2-acyl-2-diazoacetates 2aec
(Table 1, entries 2, 3, 5, 7).12
The yields of the products obtained according to the described
procedure proved to be very sensitive to variation of the sub-
stituents in both the azirine and diazo compound. The nitrogen
atom of some substituted azirines is expected to coordinate to the
rhodium catalyst, substantially reducing its efficiency. Besides, the
substituent R4 in the rhodium carbenoid affects its reactivity not
only toward azirines but also the initial diazo compound. The latter
reactions result in the formation of side products, ‘carbene di-
mers’,15 and the products of insertion to CH-bonds.16 To achieve
Scheme 2. The reaction of azirines with diazo esters.
It is not hard to notice that when X¼acyl (Scheme 2) the aza-
dienes, which could be expected to be formed in this reaction are
valence isomers of the target non-fused oxazines (see Scheme 1).
The first examples of preparative synthesis of non-fused 2H-1,4-
Scheme 3. The reaction of azirines 1aep with 2-acyl-2-diazoacetates 2aed.
oxazines, using the Rh2(OAc)4-catalyzed reaction of 2-acyl-2-
diazoacetates with aryl-substituted 2H-azirines, have already
been reported in our preliminary publication.12
acceptable yields of oxazines for the majority of the reactions the
preparation procedure needs to be modified. Experiments to opti-
mize the procedure showed that the yields of oxazines 3a,e,g (en-
tries 1, 5, 7) derived from ethyl 2-diazoacetoacetate 2a could be
substantially improved by changing the solvent from benzene to
1,2-dichloroethane (DCE) as well as modifying the rate of addition
of the diazo compound: three equivalents of diazo compound were
added, one equivalent every 5 min (method B).12 According to the
1H NMR data the reaction in 1,2-dichloroethane gave lower
amounts of byproducts. The decrease in product yield over pro-
longed reaction time was attributed to the lability of the starting
azirines and the oxazines formed under the reaction conditions. By
use of this modified procedure oxazines 3a,e,g,iep were synthe-
sized from 3-mono-, 2,3-di- and 2,2,3-trisubstituted azirines 1aek
and diazo compound 2a in good yields (entries 1, 5, 7, 9e16). The
shortening of the reaction time is especially important for prepa-
ration of the thermally unstable oxazines, such as compound 3v,
whose half-life in boiling DCE is about 15 min.
In order to determine the scope and limitations of this reaction,
the examination of reactions of a wide range of substituted azirines
and 2-acyl-2-diazoacetates have been carried out in the work re-
ported herein. The influence on product yield by the reaction
conditions and the method of carrying out the reactions was also
investigated. Quantum chemical calculations were performed to
verify the mechanism of the reaction and rationalize the influence
of the structure of starting compounds on the outcome of the
process. The ability of the products to display photo- and thermo-
chromic activity was demonstrated.
2. Results and discussion
2.1. Rh2(OAc)4-catalyzed reaction of 2H-azirines with diazo
keto esters
2,2-Dimethyl-3-phenyl-2H-azirine 1m failed to react with diazo
compound 2a under conditions either of procedure A or procedure
B. However, when during the addition of the diazo compound ad-
ditional portions of Rh2(OAc)4 were introduced into the reaction
mixture (method C), the corresponding oxazine 3t was obtained in
43% yield (entry 21).
The common procedure for carrying out the catalytic reaction of
heteroatomic compounds13 including azirines11 with diazo esters
involves very slow addition of a solution of diazo compound to
a boiling solution of nitrogen substrate and catalyst in an appro-
priate solvent. Such reaction conditions usually prevent the com-
peting reaction of the intermediate Rh(II)-carbenoid with the diazo
compound. For the investigation of the reactivity of rhodium car-
benoids, derived from the diazo keto ester, toward azirines under
these conditions we started with the Rh2(OAc)4-catalyzed test
According to TLC- and 1H NMR-analysis two products (oxazines
3 and 2-azadienes 4) were formed in the reactions of 2,2-
disubstituted and 2,2,3-trisubstituted azirines 1a,hej,l,n,o (en-
tries 1, 13e15, 17e18, 22e24) when carried out using a fast addition

4294
N.V. Rostovskii et al. / Tetrahedron 69 (2013) 4292e4301
Table 1
Rh2(OAc)4-catalyzed reaction of azirines 1aep with diazo compounds 2aed
Entry
Azirine 1
R1
R2
R3
Diazo ester 2
R4
R5
Isolated yields of oxazines 3 and azadienes
4 by method B (by method A), %
1
2
3
4
5
6
7
8
1a
1a
1a
1a
1b
1b
1c
1c
1d
1e
1f
1g
1h
1i
1j
1k
1l
1l
1l
1l
1m
1n
1n
1o
1p
Ph
Ph
Ph
Ph
Ph
Ph
4-MeC6H4
4-MeC6H4
4-O2NC6H4
4-MeOC6H4
2-BrC6H4
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Me
Me
Ph
Ph
Ph
Ph
H
H
H
H
H
H
H
Me
H
H
H
H
H
H
H
H
H
H
H
H
H
H
Ph
2a
2b
2c
2d
2a
2c
2a
2c
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2b
2c
2a
2a
2a
2a
2a
Me
Ph
Et
Et
Et
Me
Et
Et
Et
Et
Et
Et
Et
Et
Et
Et
Et
Et
Et
Et
Et
Et
Et
Et
Et
Et
Et
75 (37) 3a
39 (45) 3b
(83)a 3c
CF3
4-NCC6H4
Me
CF3
Me
CF3
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Ph
79 3d
73 (11) 3e
(62)a 3f
81 (16) 3g
(52)a 3h
79 3i
66 3j
65 3k
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
72 3l
N-Phthalimido
Benzotriazol-1-yl
Ph
2,20-Carbonylbisphenyl
2,20-Biphenylene
2,20-Biphenylene
2,20-Biphenylene
2,20-Biphenylene
Me
CO2Et
CO2Et
Ph
CO2Et
40b 3m
79 3n
75 3o
74 3p
59 3q, 21 4q
75c (43) 3q
(33) 3r, (20) 4r
(82)a 3s
CF3
Me
Me
Me
Me
Me
Me
H
H
H
H
43d 3t
10 3u, 70 4u
35e 3u, 29e 4u
40 3v, 17 Z-4v
38 E-4w, 17 Z-4w
a
The compound was synthesized according to method A using the increased concentration of azirine (see Experimental Part, method A0).
Analytical yield based on 1H NMR data with CHBr2CHBr2 as internal standard is 79%.
After reflux of the mixture of oxazine and azadiene for 5 h in ethanol.
Was synthesized by method C.
After reflux of the mixture of oxazine and azadiene for 2.5 h in 1,2-dichloroethane.
b
c
d
e
Table 2
rate of diazo compound 2a and, as a result, under short-term
heating of reaction mixture (Scheme 3). In most cases azadienes
4 could be smoothly converted into oxazines 3 by short heating in
DCE. To remove traces of azadienes the reaction mixtures, derived
from azirines 1a,hej (entries 1, 13e15), were refluxed for an addi-
tional 5 min: azadienes formed in these reactions are too labile to
be separated from 1,4-2H-oxazines, the products of its cyclization.
In the case of azirine 1l, however, the product mixture could be
separated by chromatography to give compounds 3q and 4q in 59
and 21% yields, respectively (entry 17). Oxazine 3q can be prepared
in 75% yield by reflux of the mixture of compounds 3q and 4q in
ethanol for 5 h (entry 18). In the reactions of azirines 1n,o along
with oxazines 3u,v Z- and E-azadienes 4u,v were formed (entries
22e24). The configuration of the C]C bond in 4u,v was verified by
1H 2D NOESY NMR spectroscopy (see Supplementary data). It is
noticeable that only E-isomer of 4u derived from the azirine 1n
turns to oxazine 3u when heated in DCE. Thus, the analytical yields
of 3u/E-4u/Z-4u after the completion of the reaction (10 min) of the
azirine 1n with diazo compound 2a, measured by 1H NMR with
CHBr2CHBr2 as internal standard, were 11, 33, 38%, while after ad-
ditional refluxing for 2.5 h in DCE the yields became 36, 2, 37%. The
cyclization of Z-4u to oxazine 3u was observed in boiling toluene
only, but was accompanied by the formation of decomposition
products.
In the reaction of ethyl benzoyldiazoacetate 2b with 2,3-
diphenylazirine 1a (method B) along with oxazine 3b the corre-
sponding azadiene was also formed but its cyclization rate proved
to be lower than that in the similar reaction of acetyl analog 2a
(Table 2). Azadiene 4r formed from fluorene-spiro-azirine 1l is
stable enough to be isolated easily (entry 19).
The reaction of diazo compound 2a with ethyl 3-methyl-2H-
azirine-2-carboxylate 1p in the presence of Rh2(OAc)4 gave only
isomeric azadienes E- and Z-4w (entry 25). Configurations of the
C]C bonds in compounds 4w were determined by NOESY-
experiments (see Supplementary data). According to 1H NMR
The half reaction times of dark cyclization of azadienes 4a,b,d,n,p,q,t (0.02 M so-
lution, 20 ꢀC in CDCl3)
Oxazine
t1/2, h
% of azadiene 4 after
irradiation of 3
Duration of
irradiation, min
3a
3b
3d
3n
3q
3p
3t
24.5a
29
9.5
8
9.5
1
81
100
94
67
77
70
90
70
70
70
35
35
68
34
0.5
a
The half reaction time in C6D6 at 20 ꢀC is 80 h.
spectrum of the reaction mixture E- and Z-isomers 4w are formed
in 2.3:1 ratio and the formation of oxazine 3w, under conditions of
method B, was not observed. Thus the introduction of alkox-
ycarbonyl substituents at C2 of azirine ring results in a decrease of
the ability of the azadiene formed to undergo 1,6-cyclization. The
rate of cyclization of azadienes 4 decreases as R2 changes from H to
Ar to CO2Et.
In contrast to diazo compounds 2a,b, ethyl 2-diazo-4,4,4-
trifluoroacetoacetate 2c is rarely utilized in catalytic reactions.17
A
major obstacle to its use is the number of side reactions both of the
diazo compound itself and the intermediate carbenoid.13b,17a The
known reactions of this diazo compound usually failed to proceed
in solution of an inert solvent, but provide good results when the
substrate is used as a solvent. All our attempts to prepare the cor-
responding trifluoromethyl-substituted oxazines 3c,f using pro-
cedure B were unsuccessful. Nevertheless, using procedure A, we
succeeded in obtaining compounds 3c,f,h,s in good yields. It was
found that the yields are dramatically reduced with the decrease of
azirine concentration. Thus, the reduction of the initial concentra-
tion of azirine 1a from 0.33 M to 0.25 M as well as the increase of
the concentration of diazo compound 2c from 0.67 M to 1.0 M and

N.V. Rostovskii et al. / Tetrahedron 69 (2013) 4292e4301
4295
the rate of addition of diazo compound from 0.35 mL hꢁ1 to
1.0 mL hꢁ1 causes a decrease in the yield of oxazine 3c from ca. 80 to
ca. 30%. In contrast to reactions of diazo compounds 2a and 2b
(entries 1, 2), when diazo compound 2c (entry 3) is used no traces
of azadiene 4c were observed. Therefore, the ability of the sub-
stituents R4 in the acyl fragment of azadienes 4 to facilitate 1,6-
cyclization to oxazine are placed in the order: CF3>CH3>Ph.
As follows from Table 1, once the aryl substituent in position 3 in
azirine is substituted with a methyl group, the barrier to cyclization
of azadiene to oxazine rises so much that in some cases (Table 1,
entry 25) no cyclization occurs under the reaction conditions. For
example, azadiene E-4w begins to cyclize to oxazine 3w when
refluxed in toluene solution only. Oxazine 3w is not a very stable
compound but was detected by the appearance of the signal of
Besides, we hoped that computations of the possible trans-
formations of ylides 6aec with such substitution patterns would
allow the determination of the stereochemistry of intermediate
azadienes, since because of their high reactivity an experimental
solution to the problem would be difficult.
The geometries of ylides 6aec, azadienes E,E-, E,Z-, Z,E- and Z,Z-
7aec (differing one from another by the configurations of C]N and
C]C bonds), 1,4-oxazines 8aec,80a, as well as the transition states
of ring opening of ylides 6aec (TS1eTS4), 1,6-cyclizations of aza-
dienes 7aec in oxazines 8aec,80a (TS5, TS6, TS10, TS11), E,Z-isom-
erization of ylides 6aec (TS7) and E,Z-isomerization of azadienes
7aec (TS8, TS9) were optimized at the DFT B3LYP/6-31G(d) level
using the PCM solvent model for 1,2-dichloroethane. In designa-
tions of azadiene configurations the first descriptor denotes the
configuration of the C]N bond and coincides with the configura-
tion of its ylide precursor, while the second descriptor indicates the
configuration of the C]C bond (Scheme 5).
proton HeC2 at 5.01
d (see Supplementary data). Even in harsh
conditions azadiene Z-4w is not transformed into the cyclic form.
2.2. Theoretical calculations
As it follows from 1H NMR and TLC azadienes 4 and oxazines 3 in
the reaction are formed in succession. Azadienes 4, as was stated
above, are in many cases very reactive compounds and the rates of
their conversion to oxazines 3 are influenced by the nature of
substituents R1, R2, R3. We supposed that the reaction sequence
leading to oxazines 3 involves the generation of a Rh(II)-carbenoid,
whose interaction with azirine 1 gives azirinium ylides 5, ring
opening of azirine ring with the formation of azadienes 4, followed
by 1,6-electrocyclization (Scheme 3). To prove this reaction se-
quence, as well as to elucidate the influence of the azirine structure
on product distribution and stereoselectivity of azadiene formation,
quantum-chemical calculations of transformations of model ylides
6aec (Scheme 4) were carried out at the DFT B3LYP/6-31G(d) level
by using the Gaussian 0918 suite of quantum chemical programs.
Geometry optimizations of intermediates, transition states, re-
actants, and products in 1,2-dichloroethane solutions were per-
formed using PCM model (see Supplementary data). Stationary
points on the respective potential-energy surfaces were charac-
terized at the same level of theory by evaluating the corresponding
Hessian indices. Careful verification of the unique imaginary fre-
quencies for transition states was carried out to check whether the
frequency indeed pertains to the desired reaction coordinate. In-
trinsic reaction coordinates (IRC) were calculated to authenticate all
transition states.
Scheme 5. The transformation of ylides E-6aec and Z-6aec into oxazines 8aec.
A transition states search was carried out for the most stable W-
conformations of the ylides and a number of cisoid-conformations
(relative to the single CeN bond) of azadienes. These conformations
differed from one another by angles of rotation of the acyl and
methoxycarbonyl groups. Geometry optimization of azadienes
showed that cisoid-conformations for azadienes 7a,b with a phenyl
substituent R1 (dihedral angle in the range from 56 to 76ꢀ) are
preferable, while the most stable azadienes 7c with a methyl sub-
stituent R1 can have both a cisoid- and transoid-conformation. The
most favorable transition state and most stable azadiene were
used for calculations of the activation free energies of each reaction
(Figs. 1e3).
Computations show small differences in the free energies be-
tween E- and Z-isomers of 6aec (Scheme 4) and this gives grounds
to assume that both stereoisomers are formed in the reaction. It is
known that E,Z-isomerization of azomethine ylides, realized via
rotation around the CeN bond, has a sufficiently high activation
barrier and is often not able to compete with some intermolecular
processes such as 1,3-dipolar cycloaddition.19 For all of the calcu-
lated azirinium ylides the activation barriers of E,Z-isomerization
exceed the activation barriers of ring opening. From Figs. 1e3
Scheme 4. Relative free energies (kcal molꢁ1) of E- and Z-isomers of ylides 6aec in W-
conformations.
The calculations were carried out both for E-ylides E-6aec and
their Z-isomers Z-6aec. Me, Ph and CO2Me substituents at C2 and
C3 of the azirine ring were included in the calculations because of
their dramatic influence on the above stated product distribution.

4296
N.V. Rostovskii et al. / Tetrahedron 69 (2013) 4292e4301
the Z-isomer intermediate Z,E- and Z,Z-azadienes have to isomerize
to E,E- and E,Z-azadienes, respectively. Computed activation bar-
riers of N-inversions of Z,E- and Z,Z-azadienes 7a to E,E- and E,Z-
isomers proved to be slightly lower than the barriers of 1,6-
cyclization of the latter to oxazine 8a (Fig. 1). On changing R2¼Me
for CO2Me in 7 only slightly affects the N-inversion barriers of
azadienes 7 (Figs. 2 and 3). Computed N-inversion barriers
(
D
Gs¼9.7e17.5 kcal molꢁ1) are in good agreement with the pub-
lished values of topomerization barriers of imine systems.
According to these results, C]N-containing systems with un-
saturated substituents, such as phenyl, cyano, methoxycarbonyl at
the nitrogen atom undergo syn,anti-isomerization with rather low
activation barriers 12e16 kcal molꢁ1 20
.
Formally Z,E- and Z,Z-azadienes 7aec can produce oxazines 80
(isomers of oxazines 8aec) via 1,6-electrocyclization with partici-
pation of the ester carbonyl. The calculations for the cyclization of
azadienes Z,E- and Z,Z-7a gave the barriers for the formation of
oxazine 80a as 5.8e6.9 kcal molꢁ1 higher than those for cyclizations
with participation of ketonic carbonyl (Fig. 1). The cyclizations of
Z,E- and Z,Z-azadienes 7a to oxazine 80a are also thermodynami-
Fig. 1. B3LYP/6-31G(d) free energy profiles (kcal molꢁ1
formations of ylides E-, Z-6a to oxazines 8a, 80a in 1,2-dichloroethane.
, 298.15 K) for the trans-
cally unfavorable (
D
G¼1.0e1.6 kcal molꢁ1). These results are in
good agreement with the experimental observations that 6-alkoxy-
substituted oxazines were never formed.
Changing R2¼Me for CO2Me in azadiene 7 leads to an increase of
the cyclization barriers to oxazine by a value of 5e9 kcal molꢁ1
,
which makes azadienes with alkoxycarbonyl groups at the both
ends of azadiene system kinetically much more stable than the
alkyl- and aryl-substituted analogs. This result, which can be ra-
tionalized by push-pull stabilization of the iminoacrylate system of
the molecule, is in good agreement with the distinctive outcome of
the reaction of ethyl azirinecarboxylate 1p with ethyl diazo-
acetoacetate (Table 1, entry 25). This change in substitution pattern
in the azadiene system results in a decrease of energy difference
between cyclic and open chain forms from 13 kcal molꢁ1 for the
couple 7a/8a to 4.7e8.1 kcal molꢁ1 for 7b/8b, and to 2.9e4.3 for 7c/
8c. Fairly high sensitivity of the equilibrium constant [between
colored (yellow or orange) azadiene and colorless (or slightly col-
ored) oxazine forms] to structural changes suggests the possibility
of thermochromism for some oxazine/azadiene pairs. In fact, we
disclose thermal interconversion of azadiene 3r to oxazine 4r (vide
infra).
Fig. 2. B3LYP/6-31G(d) free energy profiles (kcal molꢁ1
formations of ylides E-, Z-6b to oxazines 8b in 1,2-dichloroethane.
, 298.15 K) for the trans-
For ylide 6a, with a Me substituent as R2, the calculations predict
a selective ring opening with preferable formation of azadiene E,E-
and Z,E-7a with the C]C bond in E-configuration (Fig. 1). Sub-
stitution at the C]C bond with the electron withdrawing group
CO2Me causes a decrease in selectivity of the ring opening (Figs. 2
and 3). It was experimentally shown that in the reaction of azir-
ine 1p with diazo compound 2a, which stops after the formation of
azadienes E-4w and Z-4w, the stereoisomeric products, according
to the 1H NMR spectrum, are formed in 2.3:1 ratio (Table 1, entry
25). A little less ratio (1.2:1) of azadienes E-4u and Z-4u in the
analogous reaction of azirine 1n was observed with the assumption
that oxazine 3u is the product of cyclization of azadiene E-4u. The
appropriateness of this statement is confirmed by a large difference
in calculated values DG
s of cyclization of azadienes E,E-7b and E,Z-
Fig. 3. B3LYP/6-31G(d) free energy profiles (kcal molꢁ1
, 298.15 K) for the trans-
formations of ylides E-, Z-6c to oxazines 8c in 1,2-dichloroethane.
7b to oxazine 8b (5.8 kcal molꢁ1 in favor of the former one). There
is, therefore, every reason to believe that both stereoisomeric
azadienes E,E-7b and E,Z-7b are formed in the reaction with low
selectivity (both through ylide E-6b and ylide Z-6b), the first one of
which rapidly cyclizes under reaction conditions. Much longer
heating is required for the cyclization of isomeric azadiene E,Z-7b to
oxazine 8b.
follows that all the ylides 6 are unstable intermediates that can
easily undergo cleavage of the NeC2 bond of the azirine ring
(D
Gs¼8.5e12.0 kcal molꢁ1) to give 2-azadienes 7.
Because of the absence of interconversion between E- and Z-
ylides it follows that the formation of oxazine 8aec from these
isomers proceeds through independent pathways. It is obvious that
only the E-ylide can be transformed into oxazine 8 in two stages via
E,E- or E,Z-azadienes 7, while for the formation of this oxazine from
Oxazines 3aev are the result of the isomerization of both E- and
Z-isomeric forms of ylides 5aev via their azadiene intermediate.
Depending on the nature of the substituent at C4 the latter can be
formed either as a single E-isomer or a E,Z-azadiene mixture.

N.V. Rostovskii et al. / Tetrahedron 69 (2013) 4292e4301
4297
2.3. Photo- and thermochromism of oxazines 3
Half-life times (t1/2
)
of the dark cyclization of azadienes
4a,b,d,n,q,p,t to oxazines 3a,b,d,n,q,p,t were measured by 1H NMR
(Table 2). Predictably, the rate of cyclization depends upon the
nature of the solvent. Thus, the half reaction time of azadiene 4a
bleaching in C6D6 is three times greater than that in CDCl3. The rise
in temperature accelerates the process: the bleaching of azadiene
4a is completed in 20 min under reflux in C6D6.
With the exception of the methyl derivative 3v the synthesized
oxazines 3 are thermally stable compounds both in the solid phase
and in solution and do not undergo ring opening in the dark. Their
electronic spectra have a long-wave absorption maximum in the
region of 315e360 nm, while the open-chained isomers 4 absorb
more long-wave radiation at 380e455 nm. Thus the transformation
of 3 to 4 may be detected by the change of the color of solution from
colorless to bright yellow or orange.
We failed to evaluate the stability of azadienes 4eek, derived
from oxazines 3eek, bearing no substituents at C2 due to the ex-
tremely low concentration of compounds 4eek in the irradiated
solutions.
UV irradiation of CDCl3 solutions of oxazines 3q,t, containing
two identical substituents at C2 produces azadienes 4q,t as a single
isomer (Scheme 6). Broadened signals of some carbon atoms in the
13C NMR spectrum of compound 4q show that N-inversion takes
place at room temperature and this is in good agreement with the
According to the calculations the difference in energies of cyclic
form 8 and open chain form 7 strongly depends upon the nature of
the substituent at C2 of the oxazine ring. Thus on going from the
system 8a/7a to system 8c/7c this difference falls from 13.0 to
2.9 kcal molꢁ1 (Figs. 1 and 3). So for oxazines with the appropriate
substitution pattern the equilibrium between these two forms is
possible at reasonable temperatures. Such equilibria were found for
the spirofluorene derivatives 3qes, which along with their photo-
chromic properties, showed thermochromic activity as well: the
intensity of the color of their solutions is changed with temperature
variation. Equilibrium constants of thermal ring opening of oxa-
zines 3qes, measured in CDCl3 solutions by 1H NMR, decrease in
the sequence Ph>CH3>CF3 and increase in all cases with the in-
crease of temperature (Table 3). It is noticeable that the equilibrium
is most rapidly attained with the trifluoromethyl derivative 3s.
D
Gs values for N-inversion of azadienes 7aec (vide supra).
According to the 1H NMR spectrum the content of unreacted oxa-
zine 3q in the photolysate obtained after irradiation of the solution
for 2 h at 20 ꢀC is 19%. In contrast to this, the maximal degree of
conversion of the 2,2-dimethyl-substituted analog 3t, which could
be achieved under these conditions was only 48% because of the
high rate of reverse dark reaction.
Table 3
Equilibrium constants of thermal ring opening of oxazines 3qes
Oxazine
R
Keq (25 ꢀC)
Keq (95 ꢀC)
3q
3r
3s
CH3
Ph
CF3
0.02
0.11
d
0.14
0.39
0.02
3. Conclusions
The Rh2(OAc)4-catalyzed domino reaction of 2H-azirines with 2-
acyl-2-diazoacetates provides the first synthetic approach to non-
fused 2H-1,4-oxazines. Several modifications of the general pro-
cedure are presented, allowing the use of a wide range of diazo keto
esters and azirines. The formation of 2H-1,4-oxazines may be rea-
sonably interpreted in terms of the generation of azirinium ylide, its
ring opening to 1-acyl-1-(alkoxycarbonyl)-2-azabuta-1,3-diene
followed by 1,6-electrocyclization. The last stage can be realized
only with the participation of the ketonic carbonyl group of the
azadiene having the E-configuration of the C]N bond. According to
DFT-calculations Z- and E-isomers of azirinium ylides are more
rapidly transformed into the corresponding azadienes than in-
terconvert. Transformation of Z-ylide to azadiene with E-configu-
ration of the C]N bond proceeds via N-inversion in azadienes,
which has a lower activation barrier than the 1,6-cyclization and
occurs at ambient temperatures. Ring opening of azirinium ylides
with alkyl and aryl substituents on the azirine ring proceeds ster-
eoselectively to give azadienes with C]C bond of E-configuration,
while ylides with an alkoxycarbonyl group at the same position
isomerize to the azadiene unselectively. The substitution pattern of
the carbonecarbon double bond in azadienes, as well as its con-
figuration, influences dramatically on their cyclization to oxazines.
Azadienes nonsubstituted at C4 and azadienes with alkyl and aryl
groups at this position undergo 1,6-cyclization very easily, while an
alkoxycarbonyl group stabilizes an open-chained form and in some
cases a new class of stable 2-azadienes, 1-acyl-2-azabuta-1,3-
diene-1,4-dicarboxylates, could be isolated. The 1,4-oxazines ob-
tained by this method are the first representatives of monocyclic
Scheme 6. Photochromism of 2-mono- and 2,2-disubstituted oxazines 3aed,n,q,t,u.
Irradiation of 2-monosubstituted oxazines 3b,d for 1.5 h at 20 ꢀC
in CDCl3 results in the quantitative formation of the mixture of two
isomeric azadienes 4b,d (Scheme 6). Monitoring of the photolytic
ring opening of oxazine 3d and back reaction of cyclization
(bleaching) by 1H NMR shows that the ratio of the isomeric aza-
dienes remains constant in the course of both reactions.
The 1H NMR spectra of the photolysates obtained after UV ir-
radiation of oxazines 3a,c,n,u for 1 h show, apart from a signal of
starting oxazine, only signals corresponding to the Z-azadiene
4a,c,n,u. Of the oxazines 3a,c,n,u irradiated the complete conver-
sion of only compound 3u has been achieved. Irradiation of the
trifluoromethyl-substituted oxazine 3c for 6.5 h produced 55% of
opened chain isomer Z-4c only. Only oxazine 3u can, therefore, be
considered to undergo ring opening with full stereoselectivity,
giving exclusively Z-isomer. In the remaining cases the formation of
some amounts of E-isomer should not be excluded since the oxa-
zines 3a,c,n observed in photolysates may be the products of rapid
cyclization of the E-isomers, which according to computations cy-
clize much faster than Z-isomers.

4298
N.V. Rostovskii et al. / Tetrahedron 69 (2013) 4292e4301
2H-1,4-oxazine derivatives, which exhibit photo- and thermo-
chromic activity.
4.2.1. Ethyl 2,3,6-triphenyl-2H-1,4-oxazine-5-carboxylate (3b). Com-
pound 3b was prepared according to the procedure A from azirine
1a (97 mg, 0.5 mmol) and diazo compound 2b (327 mg,1.5 mmol) in
anhydrous benzene to afford 89 mg (45%) of oxazine 3b. Yellowish
solid, mp 122e124 ꢀC (hexane/Et2O); [Found: C, 78.19; H, 5.44; N,
3.55. C25H21NO3 requires C, 78.31; H, 5.52; N, 3.65]; Rf (20% EtOAc/
4. Experimental section
4.1. General methods
hexane) 0.27; lmax (EtOH,
(13,660); nmax (CHCl3) 3020, 1710 (C]O), 1575, 1500, 1455, 1385,
1340, 1200, 1105 cmꢁ1
dH (300 MHz, CDCl3) 1.09 (3H, t, J 7.1 Hz),
4.06e4.24 (2H, m), 6.53 (1H, s), 7.33e7.56 (13H, m), 7.92e8.00 (2H,
m); dC (75 MHz, CDCl3) 13.8, 60.5, 72.9, 120.9, 127.1, 127.7, 128.3,
128.7 (2C), 129.0, 129.6, 129.7, 130.6, 131.5, 132.7, 134.1, 135.2, 150.1,
151.7, 165.5. Compound 3b (77 mg, 39%) was also prepared
according to the procedure B from azirine 1a (100 mg, 0.51 mmol)
and diazo compound 2b (339 mg, 1.53 mmol).
3
Melting points were determined on a hot stage microscope and
are uncorrected. 1H (300 MHz) and 13C (75 MHz) NMR spectra were
measured in CDCl3 on Bruker DPX 300 spectrometer. Chemical
;
shifts (d) are reported in parts per million downfield from tetra-
methylsilane. Physical constants and spectral data for compounds
3a,g, 4a presented in preliminary report.12 Electrospray ionization
mass spectra were measured on a Bruker micrOTOF mass spec-
trometer. Elemental analysis was performed on a HewlettePackard
185B CHN-analyser. IR spectra were recorded on an SPECORD M80
spectrometer for solutions in CHCl3∙ UV spectra were measured on
an SHIMADZU UV-1800 spectrophotometer for solutions in EtOH.
Silica gel Merck 60 was used for column chromatography. Thin-
layer chromatography (TLC) was conducted on aluminia sheets
precoated with SiO2 ALUGRAM SIL G/UV254. Photochemical exper-
iments were carried out with a mercury lamp Tungsram HGOK 400
(main radiation bands 310, 360, 365 nm). Azirines were prepared
according to published procedures: 1a,21 1b, 1c, and 1e,22 1d,23 1f,24
1g,25 1h,26 1k,27 1l,28 1m,29 1n,30 1o,31 1p.32 Diazo keto esters 2
were synthesized according to published procedures: 2a and 2b,33
2c.34
4.2.2. Ethyl 2,3-diphenyl-6-trifluoromethyl-2H-1,4-oxazine-5-carboxy
late (3c). Compound 3c was prepared according to the procedure
A0 from azirine 1a (97 mg, 0.5 mmol) and diazo compound 2c
(130 mg, 0.62 mmol) in anhydrous benzene to afford 156 mg (83%) of
oxazine 3c. White solid, mp 87e88 ꢀC (hexane/Et2O); [Found: C,
63.99; H, 4.23; N, 3.64. C20H16F3NO3 requires C, 64.00; H, 4.30; N,
3.73]; Rf (20% EtOAc/hexane) 0.36; lmax (EtOH,
(10,850), 322 nm (10,980); nmax (CHCl3) 3045, 2995, 1735 (C]O),
1595, 1580, 1460, 1380, 1320, 1200, 1165, 1130, 1070 cmꢁ1
dH
3
;
(300 MHz, CDCl3) 1.34 (3H, t, J 7.1 Hz), 4.25e4.42 (2H, m), 6.49 (1H, s),
7.39e7.55 (8H, m), 7.93e7.97 (2H, m); dC (75 MHz, CDCl3) 13.8, 61.8,
72.2, 119.7 (q, J 273.7 Hz), 124.9 (q, J 2.6 Hz), 127.6, 127.9, 128.86,
128.93, 130.0, 132.0, 132.6, 134.2, 136.8 (q, J 38.6 Hz), 154.6 (q, J
1.1 Hz), 163.2.
4.2. General procedures for preparation of oxazines 3aev and
azadienes 4uew
Method A (for reactions of acetyl- and benzoyldiazoacetates). A
1.0 M solution of diazo compound 2a,b in anhydrous benzene was
added dropwise with a syringe at a rate of 1.0 mL hꢁ1 to a stirred
0.25 M solution of azirine 1aec,l and Rh2(OAc)4 (5 mol % on azirine)
in anhydrous benzene at reflux under argon until the azirine was
consumed completely (control by TLC). The solvent was removed
under vacuum and the residue was purified by column chromatog-
raphy on silica gel (eluent hexane/EtOAc) to give, after crystallization
from the solvent indicated below, compounds 3a,b,e,g q,r,4r.
Method A0 (for reactions of trifluoroacetyldiazoacetate). A 0.67 M
solution of ethyl 2-diazo-4,4,4-trifluoro-3-oxobutanoate 2c in an-
hydrous benzene was added dropwise with a syringe at a rate
0.35 mL hꢁ1 to a stirred 0.33 M solution of azirine 1aec,l (0.5 mmol)
and Rh2(OAc)4 (5 mol % on azirine) in anhydrous benzene at reflux
under argon until the azirine was consumed completely (control by
TLC). The reaction solution was diluted with a mixture hexane/
EtOAc (15:1) and filtered through a pad of neutral Al2O3 (15 g)
eluting the product using the same mixture. Compounds 3c,f,h,s
were obtained as colorless solids after recrystallization from the
solvent indicated below.
Method B. Stoichiometric amounts of azirine 1ael,nep and di-
azo compound 2a,b,d in anhydrous 1,2-dichloroethane (DCE)
(0.25 M solution of each component) were heated to reflux under
an argon atmosphere and then Rh2(OAc)4 (5 mol %) was added. The
mixture was stirred under reflux until nitrogen evolution stopped
(from 5 min for diazo compound 2a,d to 15 min for diazo com-
pound 2b), and then the next equivalents of diazo compound (1.0 M
solution in anhydrous DCE) were added consecutively every 5 min
(diazo compound 2a,d) or 15 min (diazo compound 2b) until the
azirine was consumed completely (control by TLC). The resulting
mixture was evaporated under reduced pressure and the residue
was purified by column chromatography on silica gel (eluent hex-
ane/EtOAc) to give after recrystallization from the appropriate
solvent oxazines 3a,b,d,e,g,ieq,u,v.
4.2.3. Methyl 6-(4-cyanophenyl)-2,3-diphenyl-2H-1,4-oxazine-5-car
boxylate (3d). Compound 3d was prepared according to the pro-
cedure B from azirine 1a (60 mg, 0.31 mmol) and diazo compound
2d (216 mg, 0.93 mmol) in anhydrous DCE to afford 96 mg (79%) of
oxazine 3d. Yellowish solid, mp 151e164 ꢀC (dec) (Et2O); [Found: C,
76.17; H, 4.36; N, 7.17. C25H18N2O3 requires C, 76.13; H, 4.60; N, 7.10];
Rf (20% EtOAc/hexane) 0.16; lmax (EtOH,
363 nm (15,020); nmax (CHCl3) 2230 (C^N), 1715 (C]O), 1600, 1580,
1500, 1450, 1435, 1330, 1205, 1195, 1095 cmꢁ1
dH (300 MHz, CDCl3)
3
;
3.75 (3H, s), 6.53 (1H, s), 7.41e7.51 (10H, m), 7.63e7.66 (2H, m),
7.93e7.96 (2H, m); dC (75 MHz, CDCl3) 52.0, 72.9, 113.6, 118.3, 121.6,
127.2, 128.2, 128.8, 129.2, 130.0, 130.3, 131.3, 131.5, 133.5, 134.7, 136.9,
149.6, 151.5, 165.2.
4.2.4. Ethyl 6-methyl-3-phenyl-2H-1,4-oxazine-5-carboxylate
(3e). Compound 3e was prepared according to the procedure B
from azirine 1b (117 mg, 1 mmol) and diazo compound 2a (468 mg,
3 mmol) in anhydrous DCE to afford 178 mg (73%) of oxazine 3e. The
preparation according to the procedure A yielded 27 mg (11%) of
oxazine 3e. Colorless solid, mp 45e47 ꢀC (hexane/Et2O); nmax (CHCl3)
3050, 1715 (C]O), 1590, 1475, 1395, 1330, 1235, 1110 cmꢁ1
; dH
(300 MHz, CDCl3) 1.40 (3H, t, J 7.3 Hz), 2.39 (3H, s), 4.35 (2H, q, J
7.3 Hz), 4.80 (2H, s), 7.35e7.50 (3H, m), 7.80e7.91 (2H, m); dC
(75 MHz, CDCl3) 14.3, 17.8, 60.5, 61.9, 120.5, 126.5, 128.6, 130.5, 134.9,
148.2,157.5, 165.7; HRMS (ESI-TOF): MHþ, found 246.1130. C14H16NO3
requires 246.1125.
4.2.5. Ethyl 3-phenyl-6-trifluoromethyl-2H-1,4-oxazine-5-carboxylate
(3f). Compound 3f was prepared according to the procedure A0
from azirine 1b (62 mg, 0.53 mmol) and diazo compound 2c (147 mg,
0.7 mmol) in anhydrous benzene to afford 99 mg (62%) of oxazine 3f.
Colorless solid, mp 78e79 ꢀC (hexane/Et2O); [Found: C, 56.25; H,
4.06; N, 4.69. C14H12F3NO3 requires C, 56.19; H, 4.04; N, 4.68]; Rf (20%
EtOAc/hexane) 0.34; lmax (EtOH,
3
Oxazine 3t was prepared according to method C (vide infra).
322 nm (8770); nmax (CHCl3) 3050, 2995, 1735 (C]O), 1595, 1570,

N.V. Rostovskii et al. / Tetrahedron 69 (2013) 4292e4301
4299
1460, 1385, 1330, 1325, 1290, 1200, 1160, 1130 cmꢁ1
;
dH (300 MHz,
(3H, d, J 6.9 Hz), 1.42 (3H, t, J 7.2 Hz), 2.39 (3H, s), 4.36 (2H, q, J
7.2 Hz), 5.48 (1H, q, J 6.9 Hz), 7.41e7.48 (3H, m), 7.86e7.89 (2H, m);
dC (75 MHz, CDCl3) 14.4, 15.3, 18.6, 60.5, 67.6, 118.6, 126.4, 128.6,
130.4, 134.7, 151.5, 154.8, 165.9; HRMS (ESI-TOF): MHþ, found
260.1301. C15H18NO3 requires 260.1281.
CDCl3) 1.40 (3H, t, J 7.1 Hz), 4.40 (2H, q, J 7.1 Hz), 4.92 (2H, s),
7.46e7.58 (3H, m), 7.90e7.97 (2H, m); dC (75 MHz, CDCl3) 13.9, 61.9,
62.4, 119.6 (q, J 273.7 Hz), 125.8 (q, J 2.5 Hz), 127.5, 128.9, 132.1, 133.5,
139.6 (q, J 38.4 Hz), 153.2 (q, J 1.2 Hz), 163.3.
4.2.6. Ethyl 3-(4-methylphenyl)-6-trifluoromethyl-2H-1,4-oxazine-5-
carboxylate (3h). Compound 3h was prepared according to the
procedure A0 from azirine 1b (66 mg, 0.5 mmol) and diazo com-
pound 2c (130 mg, 0.62 mmol) in anhydrous benzene to afford
82 mg (52%) of oxazine 3h. Colorless solid, mp 78e79 ꢀC (hexane);
[Found: C, 57.24; H, 4.52; N, 4.47. C15H14F3NO3 requires C, 57.51; H,
4.2.11. Ethyl 6-methyl-3-phenyl-2-phthalimido-2H-1,4-oxazine-5-
carboxylate (3m). Compound 3m was prepared according to the
procedure B from azirine 1h (37 mg, 0.14 mmol) and diazo com-
pound 2a (175 mg, 1.12 mmol) in anhydrous DCE to afford 50 mg
(72%) of oxazine 3m, contaminated with products of diazo com-
pound decomposition. After double crystallization from Et2O/hex-
ane mixture 22 mg (40%) of compound 3m was obtained as
a yellowish solid. Mp 117e119 ꢀC; [Found: C, 67.48; H, 4.66; N, 7.24.
C22H18N2O5 requires C, 67.69; H, 4.65; N, 7.18]; Rf (20% EtOAc/hex-
4.50; N, 4.47]; Rf (20% EtOAc/hexane) 0.37; lmax (EtOH, ) 232
3
(10,180), 239sh, 252 (9040), 326 nm (12,620); nmax (CHCl3) 3040,
3000, 1730 (C]O), 1590, 1570, 1325, 1315, 1290, 1205, 1160, 1140,
1120 cmꢁ1
;
dH (300 MHz, CDCl3) 1.39 (3H, t, J 7.3 Hz), 2.43 (3H, s),
ane) 0.14; lmax (EtOH,
(10,540); nmax (CHCl3) 3030, 2985, 1780, 1730 (C]O), 1705 (C]O),
1600, 1470, 1450, 1370, 1350, 1325, 1115, 1090 cmꢁ1
dH (300 MHz,
3
4.40 (2H, q, J 7.3 Hz), 4.90 (2H, s), 7.29 (2H, d, J 8.7 Hz), 7.84 (2H, d, J
8.7 Hz); dC (75 MHz, CDCl3) 13.9, 21.6, 61.9, 62.4, 120.1 (q, J
273.5 Hz), 126.3 (q, J 2.7 Hz), 127.6, 129.7, 130.8, 142.9, 139.8 (q, J
38.3 Hz), 153.6 (q, J 1.1 Hz), 163.4.
;
CDCl3) 1.46 (3H, t, J 7.2 Hz), 2.42 (3H, s), 4.41 (2H, q, J 7.2 Hz), 7.26
(1H, s), 7.35e7.41 (3H, m), 7.73e7.80 (2H, m), 7.84e7.95 (4H, m); dC
(75 MHz, CDCl3) 14.4, 18.4, 60.7, 68.4, 118.4, 124.1 (2C), 126.2, 128.7,
130.7, 131.3, 134.2, 134.8, 143.9, 154.3, 165.6, 166.2.
4.2.7. Ethyl 6-methyl-3-(4-nitrophenyl)-2H-1,4-oxazine-5-carboxylate
(3i). Compound 3i was prepared according to the procedure B from
azirine 1d (60 mg, 0.37 mmol) and diazo compound 2a (174 mg,
1.11 mmol) in anhydrous DCE to afford 85 mg (79%) of oxazine 3i.
Light-yellow solid, mp 143e146 ꢀC (Et2O); [Found: C, 58.05; H, 4.91;
N, 9.63. C14H14N2O5 requires C, 57.93; H, 4.86; N, 9.65]; Rf (20% EtOAc/
4.2.12. Ethyl 2-(benzotriazol-1-yl)-6-methyl-3-phenyl-2H-1,4-oxazine-
5-carboxylate (3n). Compound 3n was prepared according to the
procedure B from azirine 1i (50 mg, 0.214 mmol) and diazo
compound 2a (200 mg, 1.28 mmol) in anhydrous DCE to afford
61 mg (79%) of oxazine 3n. Colorless solid, mp 101e102 ꢀC (hex-
ane); [Found: C, 66.28; H, 5.06; N, 15.44. C20H18N4O3 requires C,
66.29; H, 5.01; N, 15.46]; Rf (20% EtOAc/hexane) 0.19; lmax (EtOH,
hexane) 0.18; lmax (EtOH,
3
nmax (CHCl3) 3008, 2850,1708 (C]O),1566,1526 cmꢁ1
;
CDCl3) 1.42 (3H, t, J 7.3 Hz), 2.44 (3H, s), 4.38 (2H, q, J 7.3 Hz), 4.86
(2H, s), 8.04 (2H, d, J 8.7 Hz), 8.31 (2H, d, J 8.7 Hz); dC (75 MHz, CDCl3)
14.4, 18.0, 60.8, 61.7, 121.1, 123.9, 127.4, 140.5, 145.3, 148.6, 158.8,
165.2.
3
nmax (CHCl3) 3004, 2940, 2876, 1708 (C]O), 1612, 1590 cmꢁ1
; dH
(300 MHz, CDCl3) 1.45 (3H, t, J 7.1 Hz), 2.36 (3H, s), 4.43 (2H, q, J
7.1 Hz), 7.33e7.55 (6H, m), 7.86 (1H, s), 7.83e7.90 (2H, m), 8.10 (1H,
d, J 8.0 Hz); dC (75 MHz, CDCl3) 14.4, 18.2, 61.0, 75.4, 110.1, 119.4,
120.4, 124.7, 126.5, 128.8, 129.0, 131.2, 131.3, 133.7, 143.4, 146.6,
153.9, 165.0.
4.2.8. Ethyl 3-(4-methoxyphenyl)-6-methyl-2H-1,4-oxazine-5-
carboxylate (3j). Compound 3j was prepared according to the pro-
cedure B from azirine 1e (60 mg, 0.41 mmol) and diazo compound 2a
(192 mg, 1.23 mmol) in anhydrous DCE to afford 74 mg (66%) of
oxazine 3j as a yellowish oil. nmax (CHCl3) 2984, 2940, 2844, 1704
4.2.13. Ethyl 6-methyl-2,2,3-triphenyl-2H-1,4-oxazine-5-carboxylate
(3o). Compound 3o was prepared according to the procedure B
from azirine 1j (135 mg, 0.5 mmol) and diazo compound 2a
(468 mg, 3 mmol) in anhydrous DCE to afford 149 mg (75%) of
oxazine 3o. Colorless solid, mp 122e126 ꢀC (Et2O); [Found: C,
78.60; H, 5.90; N, 3.60. C26H23NO3 requires C, 78.57; H, 5.83; N,
(C]O), 1600, 1516 cmꢁ1
; dH (300 MHz, CDCl3) 1.40 (3H, t, J 7.3 Hz),
2.38 (3H, s), 3.85 (3H, s), 4.34 (2H, q, J 7.3 Hz), 4.77 (2H, s), 6.95 (2H, d,
J 8.7 Hz), 7.82 (2H, d, J 8.7 Hz); dC (75 MHz, CDCl3) 14.4, 17.9, 55.3,
60.5, 61.8, 114.0, 120.4, 127.6, 128.2, 148.0, 157.0, 161.5, 165.9; HRMS
(ESI-TOF): MNaþ, found 298.1085. C15H17NNaO4 requires 298.1050.
3.52]; Rf (20% EtOAc/hexane) 0.34; lmax (EtOH,
321 nm (7050); nmax (CHCl3) 3065, 3035, 3010, 2930, 1700 (C]O),
1600, 1580, 1495, 1450, 1375, 1330, 1180, 1095 cmꢁ1
dH (300 MHz,
CDCl3) 1.35 (3H, t, J 7.2 Hz), 2.38 (3H, s), 4.29 (2H, q, J 7.2 Hz),
7.10e7.23 (3H, m), 7.26e7.36 (10H, m), 7.45e7.38 (2H, m); dC
(75 MHz, CDCl3) 14.4, 18.5, 60.5, 83.3, 120.8, 127.5, 128.0, 128.7,
128.9, 129.0, 129.3, 137.3, 140.2, 152.5, 155.9, 165.4.
) 245 (12,050),
4.2.9. Ethyl 3-(2-bromophenyl)-6-methyl-2H-1,4-oxazine-5-carboxy
late (3k). Compound 3k was prepared according to the procedure
B from azirine 1f (80 mg, 0.41 mmol) and diazo compound 2a
(256 mg, 1.64 mmol) in anhydrous DCE to afford 86 mg (65%) of
oxazine 3k. Colorless solid, mp 81e83 ꢀC (hexane/Et2O); [Found: C,
51.93; H, 4.36; N, 4.45. C14H14BrNO3 requires C, 51.87; H, 4.35; N,
4.32]; Rf (20% EtOAc/hexane) 0.27; lmax (EtOH,
(5990); vmax (CHCl3) 3030, 2990, 2850, 1705 (C]O),1575, 1440, 1390,
1370, 1325, 1295, 1100, 1070, 1025 cmꢁ1
dH (300 MHz, CDCl3) 1.38
(3H, t, J 7.2 Hz), 2.42 (3H, s), 4.37 (2H, q, J 7.2 Hz), 4.76 (2H, s),
7.25e7.31 (1H, m), 7.35e7.41 (1H, m), 7.57e7.63 (2H, m); dC (75 MHz,
CDCl3) 14.5,17.8, 60.7, 64.2,121.3, 121.5,127.6,131.1, 131.8,132.8,138.1,
149.4, 158.4, 165.4.
3
4.2.14. Ethyl 60-methyl-10-oxo-30-phenyl-9H-spiro[anthracene-9,20-
[1,4]-oxazine]-50-carboxylate (3p). Compound 3p was prepared
according to the procedure B (instead of chromatographic purifi-
cation recrystallization from ethanol was used) from azirine 1k
(148 mg, 0.5 mmol) and diazo compound 2a (468 mg, 2 mmol) in
anhydrous DCE to afford 156 mg (74%) of oxazine 3p. Colorless
solid, mp 185e190 ꢀC (dec) (hexane/CH2Cl2); [Found: C, 76.51; H,
4.96; N, 3.46. C27H21NO4 requires C, 76.58; H, 5.00; N 3.31]; Rf (20%
;
4.2.10. Ethyl 2,6-dimethyl-3-phenyl-2H-1,4-oxazine-5-carboxylate
(3l). Compound 3l was prepared according to the procedure B
from azirine 1g (70 mg, 0.53 mmol) and diazo compound 2a
(284 mg, 1.82 mmol) in anhydrous DCE to afford 99 mg (72%) of
oxazine 3l as a yellowish oil, which solidified on cooling. Mp
39e42 ꢀC; nmax (CHCl3) 3030, 2990, 2930, 1700 (C]O), 1585, 1450,
EtOAc/hexane) 0.25; lmax (EtOH,
(8340); nmax (CHCl3) 3020, 2990, 1700 (C]O), 1670, 1600, 1590,
1460,1375, 1320,1256,1094 cmꢁ1
dH (300 MHz, CDCl3) 1.47 (3H, t, J
3
;
7.3 Hz), 2.30 (3H, s), 4.43 (2H, q, J 7.3 Hz), 6.96e7.17 (3H, m),
7.24e7.34 (2H, m), 7.50e7.65 (6H, m), 8.40 (2H, d, J 6.5 Hz); dC
(75 MHz, CDCl3) 14.5, 19.0, 60.7, 75.7, 114.9, 127.8, 127.89, 127.93,
1370, 1320, 1305, 1110, 1090, 1075 cmꢁ1
; dH (300 MHz, CDCl3) 1.39

4300
N.V. Rostovskii et al. / Tetrahedron 69 (2013) 4292e4301
129.2, 129.6, 129.8, 130.0, 134.5, 135.3, 140.9, 151.1, 154.9, 165.9,
182.4.
328 nm (7060); nmax (CHCl3) 3050, 2950, 1730 (C]O), 1595, 1580,
1465, 1385, 1355, 1320, 1290, 1200, 1175, 1040 cmꢁ1
dH (300 MHz,
;
CDCl3) 1.45 (3H, t, J 7.2 Hz), 4.47 (2H, q, J 7.2 Hz), 7.09 (2H, t, J 7.6 Hz),
7.21e7.30 (5H, m), 7.41 (2H, d, J 7.6 Hz), 7.49 (2H, t, J 7.6 Hz), 7.76 (2H,
d, J 7.6 Hz); dC (75 MHz, CDCl3) 13.9, 62.1, 83.2, 119.5 (q, J 274.1 Hz),
120.7, 124.5 (q, J 2.5 Hz), 125.8, 127.9, 128.1, 128.9, 130.9, 131.1, 134.4,
139.0 (q, J 38.7 Hz), 140.2, 142.9, 158.8 (q, J 0.8 Hz), 163.6.
4.2.15. Ethyl 60-methyl-30-phenyl-2H0,90H-spiro[fluorene-2,90-[1,4]-
oxazine]-50-carboxylate (3q) and ethyl 2-[fluoren-9-ylidene(phenyl)
methylimino]-3-oxobutanoate (4q). From azirine 1l (133 mg,
0.5 mmol) and diazo compound 2a (312 mg, 2 mmol) using anhy-
drous DCE as a solvent according to the procedure B 117 mg (59%) of
oxazine 3q and 42 mg (21%) of compound 4q were obtained. When
a mixture of compounds 3q and 4q was further refluxed in ethanol
for 5 h 147 mg (75%) of oxazine 3q was obtained after crystalliza-
tion from hexane/Et2O.
4.2.18. Ethyl 2,2,6-trimethyl-3-phenyl-2H-1,4-oxazine-5-carboxylate
(3t). Method C: A solution of azirine 1m (40 mg, 0.28 mmol)
and diazo compound 2a (196 mg, 1.26 mmol) in anhydrous DCE
(3 mL) was heated to reflux under argon and then Rh2(OAc)4
(1.8 mg, 1.5 mol %) was added. The mixture was refluxed for
10 min after what a solution of diazo compound 2a (47 mg,
0.3 mmol) in DCE (1.5 mL) and Rh2(OAc)4 (1.8 mg, 1.5 mol %) were
sequentially added. After accomplishing of this operation one
time else the azirine vanished (according to monitoring by TLC).
The isolation of oxazine 3t was carried out according to the
procedure A. White solid, mp 101e103 ꢀC (hexane); [Found: C,
70.26; H, 7.15; N, 5.09. C16H19NO3 requires C, 70.31; H, 7.01; N,
Compound 3q. Colorless solid, mp 133e134 ꢀC (hexane/Et2O);
[Found: C, 78.72; H, 5.36; N, 3.31. C26H21NO3 requires C, 78.97; H,
5.35; N, 3.54]; Rf (20% EtOAc/hexane) 0.29; lmax (EtOH, ) 232
3
(26,970), 252sh, 278infl, 293infl, 336 nm (5680); nmax (CHCl3) 3030,
3000, 1710 (C]O), 1610, 1590, 1460, 1380, 1340, 1300, 1280, 1290,
1270, 1185, 1170, 1105 cmꢁ1
; dH (300 MHz, CDCl3) 1.47 (3H, t, J
7.3 Hz), 2.38 (3H, s), 4.44 (2H, q, J 7.3 Hz), 7.02e7.07 (2H, m),
7.14e7.24 (5H, m), 7.41e7.47 (4H, m), 7.74 (2H, d, J 7.5 Hz); dC
(75 MHz, CDCl3) 14.5,18.8, 60.7, 83.2, 119.0,120.5,125.8,127.6,127.7,
128.7, 129.6, 130.5, 135.6, 140.0, 144.6, 152.4, 157.8, 165.9.
Compound 4q was also obtained with 19% impurity of oxazine
3q after UV irradiation of 3q for 2 h at 20 ꢀC in CDCl3 (it cyclzes into
oxazine 3q during recording of 13C NMR spectrum). Its 1H and 13C
NMR spectra are identical with those of azadiene obtained from
azirine 1l and diazo compound 2a.
5.12]; Rf (20% EtOAc/hexane) 0.29; lmax (EtOH,
312 nm (6360); nmax (CHCl3) 3390, 2985, 1700 (C]O), 1580, 1460,
1445, 1370, 1330, 1290, 1275, 1125, 1090 cmꢁ1
dH (300 MHz,
3
;
CDCl3) 1.37 (3H, t, J 7.2 Hz), 1.55 (6H, s), 2.37 (3H, s), 4.34 (2H, q, J
7.2 Hz), 7.35e7.42 (3H, m), 7.52e7.58 (2H, m); dC (75 MHz, CDCl3)
14.4, 18.7, 24.5, 60.4, 75.0, 119.1, 128.0, 128.1, 129.3, 136.8, 156.27,
156.31, 165.8.
Compound 4q. Orange oil; Rf (20% EtOAc/hexane) 0.36; lmax
(EtOH,
3
4.2.19. Diethyl 6-methyl-3-phenyl-2H-1,4-oxazine-2,5-dicarboxylate
(3u), ethyl (E)-3-{[1-(ethoxycarbonyl)-2-oxopropylidene]amino}-3-
phenyl-2-propenoate (E-4u), and ethyl (Z)-3-{[1-(ethoxycarbonyl)-2-
oxopropylidene]amino}-3-phenyl-2-propenoate (Z-4u). According to
the procedure B from azirine 1n (95 mg, 0.5 mmol) and diazo
compound 2a (195 mg, 1.26 mmol) using anhydrous DCE as a solvent
16 mg (10%) of oxazine 3u and 111 mg (70%) of unseparated mixture
of azadienes E-4u J Z-4u were obtained. When the reaction mixture
was additionally refluxed under inert atmosphere for 2.5 h the
chromatography (hexane/EtOAc, 10:1) produced 55 mg (35%) of
compound 3u and 46 mg (29%) of compound Z-4u.
(3H, s), 3.71e3.86 (2H, m), 6.26 (1H, d, J 8.0 Hz), 6.84e6.90 (1H, m),
7.19e7.26 (1H, m) 7.29e7.53 (5H, m), 7.65e7.75 (2H, m), 8.06e8.10
(1H, m); dC (75 MHz, CDCl3) 13.5, 25.8, 61.8, 119.47, 119.52, 124.9,
126.7,127.2, 127.9, 128.5, 128.8, 130.6,131.3,134.3,136.1, 137.3,140.4,
141.1, 144.8, 156.4, 163.5, 197.0.
4.2.16. Ethyl 30,60-diphenyl-2H0,90H-spiro[fluorene-2,90-[1,4]-oxazine]-
50-carboxylate (3r) and ethyl 2-[fluoren-9-ylidene(phenyl)methyl-
imino]-3-oxo-3-phenylpropanoate (4r). Oxazine 3r (75 mg, 33%) and
azadiene 4r (47 mg, 20%) were prepared according to the procedure
A from azirine 1l (135 mg, 0.5 mmol) and diazo compound 2b
(327 mg, 1.5 mmol) in anhydrous benzene.
Compound 3u. Pale yellow oil; lmax (EtOH,
(9300), 327 nm (6100); nmax (CHCl3) 3030, 2990, 1750 (C]O), 1705
(C]O), 1585, 1450, 1370, 1330, 1210, 1170, 1100, 1020 cmꢁ1
dH
3
Compound 3r. Light yellow solid; mp 120e142 ꢀC (dec) (Et2O);
[Found: C, 81.62; H, 5.08; N, 3.20. C31H23NO3 requires C, 81.38; H,
5.07; N, 3.06]; Rf (20% EtOAc/hexane) 0.23; lmax (EtOH, ) 225
;
(300 MHz, CDCl3) 1.18 (3H, t, J 7.2 Hz),1.39 (3H, t, J 7.2 Hz), 2.49 (3H, s),
4.06e4.28 (2H, m), 4.34 (2H, q, J 7.2 Hz), 5.87 (1H, s), 7.40e7.50 (3H,
m), 7.96e8.04 (2H, m); dC (75 MHz, CDCl3) 13.8, 14.3, 18.1, 60.6, 62.2,
69.5, 120.1, 127.4, 128.4, 130.6, 134.8,145.8, 156.5, 165.2, 166.3; HRMS
(ESI-TOF): MHþ, found 318.1332. C17H20NO5 requires 318.1336.
(32,650), 232sh, 259 (23,940), 359 nm (9810); nmax (CHCl3) 3068,
2980, 1720 (C]O), 1610, 1560, 1540, 1488, 1450, 1368, 1336, 1292,
1260, 1228, 1208, 1184, 1112, 1096, 1060 cmꢁ1
; dH (300 MHz, CDCl3)
1.21 (3H, t, J 7.2 Hz), 4.29 (2H, q, J 7.2 Hz), 7.06e7.11 (2H, m),
7.16e7.24 (3H, m), 7.26e7.34 (4H, m), 7.35e7.42 (3H, m), 7.44e7.50
(4H, m), 7.79 (2H, d, J¼7.3 Hz); dC (75 MHz, CDCl3) 13.9, 60.8, 83.4,
120.5, 120.8, 126.0, 127.7, 127.8, 128.7, 129.5, 129.8, 130.3, 130.5,
132.5, 135.4, 140.2, 144.2, 154.0, 154.2, 165.7.
Compound Z-4u. Yellow oil; lmax (EtOH, ) 220 (12,100), 248
3
(11,200), 273 (13,300), 340 (1000), 400 nm (250); nmax (CHCl3)
3035, 2990, 1745 (C]O), 1710 (C]O), 1605, 1575, 1448, 1370, 1340,
1230, 1175, 1065, 1020 cmꢁ1
; dH (300 MHz, CDCl3) 1.19 (3H, t, J
7.2 Hz), 1.28 (3H, t, J 7.2 Hz), 2.64 (3H, s), 4.16 (2H, q, J 7.2 Hz), 4.23
(2H, q, J 7.2 Hz), 5.63 (1H, s), 7.37e7.46 (3H, m), 7.48e7.54 (2H, m);
dC (75 MHz, CDCl3) 13.8,14.1, 25.7, 60.1, 62.1, 98.0,126.4,128.7,130.6,
134.0, 156.2, 158.4, 160.7, 165.1, 195.9; HRMS (ESI-TOF): MHþ, found
318.1356. C17O20NO5 requires 318.1336.
Azadiene 4r. Orange solid; mp 108e111 ꢀC (Et2O/hexane); Rf
(20% EtOAc/hexane) 0.32; lmax (EtOH,
3
(300 MHz, CDCl3) 1.15e1.35 (3H, m, CH3), 4.30e4.50 (2H, m, CH2),
6.10e6.26 (2H, m), 6.75e6.86 (2H, m), 6.88e7.65 (13H, m),
8.05e6.26 (1H, m).
Compound E-4u (not separated from Z-4u): dH (300 MHz, CDCl3)
d
1.14 (3H, t, J 7.2 Hz), 1.34 (3H, t, J 7.2 Hz), 2.49 (3H, s), 4.07 (2H, q, J
4.2.17. Ethyl 30-phenyl-60-trifluoromethyl-2H0,90H-spiro[fluorene-2,90-
[1,4]-oxazine]-50-carboxylate (3s). Compound 3s was prepared
according to the procedure A0 from azirine 1l (144 mg, 0.54 mmol)
and diazo compound 2c (220 mg, 1.05 mmol) in anhydrous benzene
to afford 199 mg (82%) of oxazine 3s. Colorless solid, mp 130e132 ꢀC
(hexane/Et2O); [Found: C, 69.53; H, 4.20; N, 2.78. C26H18F3NO3 re-
quires C, 69.48; H, 4.04; N, 3.12]; Rf (20% EtOAc/hexane) 0.34; lmax
7.2 Hz), 4.38 (2H, q, J 7.2 Hz), 5.40 (1H, s), 7.37e7.54 (5H, m); dC
(75 MHz, CDCl3) 13.9, 14.0, 24.7, 60.2, 62.4, 103.0, 127.9, 128.5, 129.8,
133.1, 154.3, 161.0, 161.7, 165.0, 196.0.
4.2.20. Ethyl 3,6-dimethyl-2-phenyl-2H-1,4-oxazine-5-carboxylate
3v and ethyl 2-[(1-methyl-2-phenylvinyl)imino]-3-oxobutanoate
Z-4v. According to the procedure B from azirine 1o (66 mg,
0.5 mmol) and diazo compound 2a (156 mg, 1 mmol) using
(EtOH, ) 225 (29,420), 232 (26,600), 258 (20,550), 273infl, 288infl,
3

N.V. Rostovskii et al. / Tetrahedron 69 (2013) 4292e4301
4301
3. (a) Hobley, J.; Fukumura, H.; Goto, M. Appl. Phys. A 1999, 69, 945e948; (b) Levy,
D. Mol. Cryst. Liq. Cryst. Sci. Technol., Sect. A 1997, 297, 31e39; (c) Molecular
Switches; Feringa, B. L., Ed.; WileyeVCH: Weinhein, Germany, 2001; (d) Irie, M.
Chem. Rev. 2000, 100, 1685e1716; (e) Raymo, F. M.; Tomasulo, M. Chem. Soc. Rev.
2005, 34, 327e336; (f) Raymo, F. M.; Tomasulo, M. J. Phys. Chem. A 2005, 109,
7343e7352; (g) Delaire, J. A.; Nakatani, K. Chem. Rev. 2000, 100, 1817e1845.
4. Kawata, S.; Kawata, Y. Chem. Rev. 2000, 100, 1777e1788.
anhydrous DCE as a solvent 52 mg (40%) of oxazine 3v and 22 mg
(17%) of compound Z-4v were obtained.
Compound 3v. Pale yellow oil; lmax (EtOH,
(3600); nmax (CHCl3) 3030, 2985, 2930, 1710 (C]O), 1595, 1495,
1455, 1380, 1370, 1310, 1150 cmꢁ1
dH (300 MHz, CDCl3) 1.36 (3H, t, J
3
;
7.1 Hz), 2.02 (3H, s), 2.27 (3H, s), 4.32 (2H, q, J 7.1 Hz), 5.28 (1H, s),
7.30e7.42 (5H, m); dC (75 MHz, CDCl3) 14.4, 18.3, 23.3, 60.5, 76.1,
118.2, 127.6, 128.8, 129.2, 135.1, 153.7, 155.9, 165.6. HRMS (ESI-TOF):
MHþ, found 260.1264. C15H18NO3 requires 260.1281.
5. (a) Willner, I. Acc. Chem. Res. 1997, 30, 347e356; (b) Zahavy, E.; Rubin, S.; Willner,
I. J. Chem. Soc., Chem. Commun. 1993, 1753e1755; (c) Zahavy, E.; Rubin, S.; Willner,
I. Mol. Cryst. Liq. Cryst. 1994, 246, 195e199.
€
6. (a) Chu, N. Y. C. In Photochromism. Molecules and Systems; Durr, H., Bouas-
Laurent, H., Eds.; Elsevier: Amsterdam, The Netherlands, 1990; pp 493e509;
879e882; (b) Maeda, S. In Organic Photochromic and Thermochromic Compounds
(Topics in Applied Chemistry); Crano, J. C., Guglielmetti, R. J., Eds.; Plenum: New
York, NY, 1999; Vol. 1, pp 85e110; (c) Lokshin, V.; Samat, A.; Metelitsa, A. V.
Russ. Chem. Rev. Engl. Ed. 2002, 71, 893e916; (d) Minkin, V. I. Chem. Rev. 2004,
104, 2751e2776.
Compound Z-4v. Orange oil; lmax (EtOH,
(1700), 421 nm (700); nmax (CHCl3) 3030, 3010, 2990, 2930, 1736
(C]O), 1710 (C]O), 1495, 1445, 1370, 1360, 1300, 1058 cmꢁ1
dH
3
;
(300 MHz; CDCl3; Me4Si) dH (300 MHz, CDCl3) 1.19 (3H, t, J 7.2 Hz),
2.10 (3H, d, J 1.1 Hz), 2.56 (3H, s), 4.23 (2H, q, J 7.2 Hz), 5.95 (1H, q, J
1.1 Hz), 7.16e7.24 (1H, m), 7.26e7.33 (4H, m); dC (75 MHz, CDCl3)
13.8, 21.9, 25.0, 61.9, 118.0, 126.8, 128.1, 129.1, 135.6, 142.0, 155.8,
163.8, 197.0; HRMS (ESI-TOF): MNaþ, found 282.1109. C15H17NNaO3
requires 282.1101.
€
7. Grummt, U.-W.; Reichenbacher, M.; Paetzold, R. Tetrahedron Lett. 1981, 22,
3945e3948.
ꢀ
8. Christie, R. M.; Agyako, C.; Mitchell, K.; Lyeka, A. Dyes Pigm. 1996, 31, 155e170.
9. (a) El Achqar, A.; Boumzebra, M.; Roumestant, M.-L.; Viallefont, P. Tetrahedron
1988, 44, 5319e5332; (b) Solladie-Cavallo, A.; Sedy, O.; Salisova, M.; Schmitt, M.
Eur. J. Org. Chem. 2002, 3042e3049.
10. Bartsch, H. Arch. Pharmacol. 1982, 315, 684e691.
11. (a) Khlebnikov, A. F.; Novikov, M. S.; Amer, A. A. Tetrahedron Lett. 2004, 45,
6003e6006; (b) Khlebnikov, A. F.; Novikov, M. S.; Amer, A. A.; Kostikov, R. R.;
Magull, J.; Vidovic, D. Russ. J. Org. Chem. 2006, 42, 515e526; (c) Khlebnikov, A. F.;
Novikov, M. S. Tetrahedron 2013, 69, 3363e3401.
4.2.21. Ethyl (E)-3-{[1-(ethoxycarbonyl)-2-oxopropylidene]amino}-
2-butenoate (E-4w) and ethyl (Z)-3-{[1-(ethoxycarbonyl)-2-
oxopropylidene]amino}-2-butenoate (Z-4w). According to the pro
cedure B from azirine 1p (87 mg, 0.69 mmol) and diazo compound
2a (265 mg, 1.7 mmol) using anhydrous DCE as a solvent 67 mg
(38%) of compound E-4w and 29 mg (17%) of compound Z-4w were
obtained.
12. Khlebnikov, V. A.; Novikov, M. S.; Khlebnikov, A. F.; Rostovskii, N. V. Tetrahedron
Lett. 2009, 50, 6509e6511.
13. (a) Shi, B.; Blake, A. J.; Lewis, W.; Campbell, I. B.; Judkins, B. D.; Moody, C. J. J.
Org. Chem. 2010, 75, 152e161; (b) Wang, Y.; Chu, S. J. Fluorine Chem. 2000, 103,
139e144.
14. (a) Brooks, G.; Howarth, T. T.; Hunt, E. J. Chem. Soc., Chem. Commun. 1981,
642e643; (b) Maryanoff, B. E. J. Org. Chem. 1982, 47, 3000e3002; (c) Maryanoff,
B. E. J. Org. Chem. 1979, 44, 4410e4419; (d) Alonso, M. E.; Morales, A.; Chitty, A.
W. J. Org. Chem. 1982, 47, 3747e3754.
Compound E-4w. Yellow oil; Rf (20% EtOAc/hexane) 0.38; lmax
(EtOH,
2985, 2940, 1745 (C]O), 1710 (C]O), 1630, 1450, 1370, 1340, 1300,
1145, 1095, 1060 cmꢁ1
dH (300 MHz, CDCl3) 1.28 (3H, t, J 7.2 Hz),
3
15. (a) Adams, J.; Spero, D. M. Tetrahedron 1991, 47, 1765e1808; (b) Maas, G. Top.
Curr. Chem. 1987, 137, 75e253.
;
16. (a) Lall, M. S.; Ramtohul, Y. K.; James, M. N. G.; Vederas, J. C. J. Org. Chem. 2002,
67, 1536e1547; (b) Box, V. G. S.; Marinovic, N.; Yiannikouros, G. P. Heterocycles
1991, 32, 245e251; (c) Lee, E.; Jung, K. W.; Kim, Y. S. Tetrahedron Lett. 1990, 31,
1023e1026; (d) Balaji, B. S.; Chanda, B. M. Tetrahedron Lett. 1998, 39,
6381e6382.
1.30 (3H, t, J 7.2 Hz), 2.38 (3H, d, J 1.1 Hz), 2.47 (3H, s), 4.17 (2H, q, J
7.2 Hz), 4.32 (2H, q, J 7.2 Hz), 5.14 (1H, br s); dC (75 MHz, CDCl3) 14.0,
14.2, 17.2, 24.6, 60.0, 62.2, 101.4, 154.5, 161.6, 162.1, 166.0, 196.0;
HRMS (ESI-TOF): MNaþ, found 278.1018; C12H17NNaO3 requires
278.0999.
17. (a) Hoffmann, M. G.; Wenkert, E. Tetrahedron 1993, 49, 1057e1062; (b) Honey,
M. A.; Pasceri, R.; Lewis, W.; Moody, C. J. J. Org. Chem. 2012, 77, 1396e1405.
18. Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheese-
man, J. R.; Scalmani, G.; Barone, V.; Mennucci, B.; Petersson, G. A.; Nakatsuji, H.;
Caricato, M.; Li, X.; Hratchian, H. P.; Izmaylov, A. F.; Bloino, J.; Zheng, G.; Son-
nenberg, J. L.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida,
M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Vreven, T.; Montgomery, J. A.;
Peralta, J. E.; Ogliaro, F.; Bearpark, M.; Heyd, J. J.; Brothers, E.; Kudin, K. N.;
Staroverov, V. N.; Kobayashi, R.; Normand, J.; Raghavachari, K.; Rendell, A.;
Burant, J. C.; Iyengar, S. S.; Tomasi, J.; Cossi, M.; Rega, N.; Millam, N. J.; Klene, M.;
Knox, J. E.; Cross, J. B.; Bakken, V.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Strat-
mann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.;
Martin, R. L.; Morokuma, K.; Zakrzewski, V. G.; Voth, G. A.; Salvador, P.; Dan-
Compound Z-4w. Yellow oil; Rf (20% EtOAc/hexane) 0.33; lmax
(EtOH,
2985, 1740 (C]O), 1710 (C]O), 1625, 1445, 1370, 1300, 1140,
1060 cmꢁ1
dH (300 MHz, CDCl3) 1.23 (3H, t, J 7.2 Hz), 1.30 (3H, t, J
3
;
7.2 Hz), 2.08 (3H, d, J 1.1 Hz), 2.54 (3H, s), 4.08 (2H, q, J 7.2 Hz), 4.30
(2H, q, J 7.2 Hz), 5.05 (1H, d, J 1.1 Hz); dC (75 MHz, CDCl3) 14.0, 14.1,
18.9, 22.1, 59.8, 62.2, 98.8, 154.2, 158.7, 161.1, 164.9, 196.2; HRMS
(ESI-TOF): MHþ, found 256.1182. C12H18NO5 requires 256.1179.
}
nenberg, J. J.; Dapprich, S.; Daniels, A. D.; Farkas, O.; Foresman, J. B.; Ortiz, J. V.;
Cioslowski, J.; Fox, D. J. Gaussian 09, Revision C.01; Gaussian: Wallingford CT,
2010.
Acknowledgements
19. Khlebnikov, A. F.; Novikov, M. S.; Petrovskii, P. P.; Konev, A. S.; Yufit, D. S.; Se-
livanov, S. I.; Frauendorf, H. J. Org. Chem. 2010, 75, 5211e5215.
20. Galvez, J.; Guirado, A. J. Comput. Chem. 2009, 31, 520e530.
21. Fowler, F.; Hassner, A.; Levy, L. J. Am. Chem. Soc. 1967, 89, 2077e2082.
22. Hortmann, A.; Robertson, D.; Gillard, B. J. Org. Chem. 1972, 37, 322e324.
23. Broun, D.; Brown, G. A.; Andrews, M.; Large, J. M.; Urban, D.; Butts, C. P.; Hales, N. J.;
Gallagher, T. J. Chem. Soc., Perkin Trans. 1 2002, 2014e2021.
24. Khlebnikov, A. F.; Novikov, M. S.; Petrovskii, P. P.; Stoeckli-Evans, H. J. Org. Chem.
2011, 76, 5384e5391.
25. Bader, H.; Hansen, H.-J. Helv. Chim. Acta 1978, 61, 286e304.
26. Katritzky, A. R.; Wang, M.; Wilkerson, C. R.; Yang, H. J. Org. Chem. 2003, 68,
9105e9108.
27. Hirakawa, K.; Ogiue, E.; Motoyoshiya, J.; Kakurai, T. J. Org. Chem. 1986, 51,
1083e1087.
28. Schulthess, A. H.; Hansen, H.-J. Helv. Chim. Acta 1981, 64, 1322e1336.
29. Leonard, N. J.; Zwanenburg, B. J. Am. Chem. Soc. 1967, 89, 4456e4465.
30. Hassner, A.; Fowler, F. W. J. Am. Chem. Soc. 1968, 90, 2869e2875.
31. Isomura, K.; Kobayashi, S.; Taniguchi, H. Tetrahedron Lett. 1968, 9, 3499e3502.
32. Verstappen, M. M. H.; Ariaans, G. J. A.; Zwanenburg, B. J. Am. Chem. Soc. 1996,
118, 8491e8492.
We gratefully acknowledge the financial support of the Russian
Foundation for Basic Research (project 11-03-00186) and Saint-
ꢀ
Petersburg State University for a research grant (N 12.38.78.2012).
Supplementary data
1H, 13C NMR spectra of all new compounds, 1H 2D NOESY NMR
spectra of compounds 4u, Z-4v and Cartesian coordinates of opti-
mized structures can be found online. Supplementary data related
to this article can be found at http://dx.doi.org/10.1016/
j.tet.2013.03.106. These data include MOL files and InChiKeys of the
most important compounds described in this article.
References and notes
1. Berkovic, G.; Krongauz, V.; Weiss, V. Chem. Rev. 2000, 100, 1741e1753.
2. Iwamoto, K.; Tanaka, T.; Imura, S.; Okazaki, S.; Tanaka, S. Eur. Patent 449669,
1991; Chem. Abstr. 1992, 116, 21065d.
33. Davies, J. R.; Kane, P. D.; Moody, C. J. Tetrahedron 2004, 60, 3967e3977.
34. Guillaume, M.; Janousek, Z.; Viehe, H. G.; Wynants, C.; Declercq, J.-P.; Tinant, B.
J. Fluorine Chem. 1994, 69, 253e256.