Generation of highly strained 2,3-bridged 2H-azirines via cycloaddition reactions of 2-azidobuta-1,3-dienes and photolysis of the resulting cyclic vinyl azides

Article abstract of DOI:10.1016/j.tet.2012.12.054

The 2-azidobuta-1,3-dienes 10a,b were treated with sulfur dioxide to prepare the 3-azido-3-sulfolenes 11a,b, and with electron-poor dienophiles to generate the Diels-Alder products 12a,b, 13a,b, 14a,b, 15a,b, and 16b. Both types of reactions provide an ac

Full text of DOI:10.1016/j.tet.2012.12.054

Tetrahedron 69 (2013) 2501e2508
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Generation of highly strained 2,3-bridged 2H-azirines via
cycloaddition reactions of 2-azidobuta-1,3-dienes and photolysis
of the resulting cyclic vinyl azidesq
,
a
a
a
a
Klaus Banert a , Andreas Ihle , Andrea Kuhtz , Enrico Penk , Biswajit Saha ,
*
b,
*
€
Ernst-Ulrich Wurthwein
a Institute of Chemistry, Chemnitz University of Technology, Strasse der Nationen 62, 09111 Chemnitz, Germany
b
€
€
Institute of Organic Chemistry, University of Munster, Corrensstrasse 40, 48149 Munster, Germany
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 28 August 2012
Received in revised form 10 December 2012
Accepted 21 December 2012
Available online 2 January 2013
The 2-azidobuta-1,3-dienes 10a,b were treated with sulfur dioxide to prepare the 3-azido-3-sulfolenes
11a,b, and with electron-poor dienophiles to generate the DielseAlder products 12a,b, 13a,b, 14a,b,
15a,b, and 16b. Both types of reactions provide an access to cyclic vinyl azides, which lead to short-lived
2,3-bridged 2H-azirines 18a,b and 20a,b on photolysis. Whereas the highly strained heterocycle 18b
could be characterized by low temperature NMR spectra, the bridgehead azirines 18a and 20a,b were
trapped with cyclopentadiene by stereoselective [4þ2]-cycloaddition or with hydrogen cyanide to give
bicyclic 2-cyanoaziridines. The latter transformation led to compound 22b that showed temperature-
dependent 1H NMR spectra because of rapid equilibration of the configuration at the aziridine N atom.
High-level quantum chemical studies, however, indicated that not only both invertomers of 22b (endo,
exo) but also two conformers of each (chair, boat) are involved.
Dedicated to Professor Paul Rademacher
Keywords:
Azides
Azirines
Cycloaddition
Quantum chemistry
Reactive intermediate
Ring strain
Ó 2012 Elsevier Ltd. All rights reserved.
1. Introduction
Vinyl azides are important intermediate compounds in the syn-
thesis of several nitrogen heterocycles, such as 2H-azirines, indoles,
triazoles, and many other products.2 These azides can be prepared by
different methods, but the Hassner reaction was the breakthrough
for the systematic investigation of their chemistry.3 By using this
synthetic procedure, explosive iodine azide was generated in situ
from iodine chloride and sodium azide, and reacted with nearly all
types of alkenes to get vicinal azidoeiodo addition products, which
led to alkenyl azides by base-induced elimination of hydrogen
iodide.4 The Hassner reaction can also be applied to the synthesis of
cyclic vinyl azides like 4d,e (Scheme 1).5,6 In the case of the addition
product 2c, however, treatment with the base potassium tert-but-
oxide gave a mixture of allyl azide 3c (25% yield) and vinyl azide 4c
(31%).6 Unfortunately, similar conversion of 2a,b resulted in exclusive
formation of 3a,b. Obviously, cleavage of hydrogen iodide is an anti
elimination, that excludes the process 2a,b/4a,b and dominates the
regiochemistry of the olefin generation in smaller carbocycles.5,6
Scheme 1.
Thus, vinyl azides fitted into a five- or six-membered ring, have to
be prepared by other methods, which often include multi-step syn-
thesis and lower yields.6,7 Cyclic vinyl azides, such as 4cee can be
transformed into the 2,3-bridged 2H-azirines 5cee by photolysis or
thermolysis. These fused heterocycles possess anti-Bredt structure,
and the more strained compounds are able to undergo addition and
cycloaddition reactions, that are not possible for simple 2H-azir-
ines.6,8 Bridgehead azirines with six-membered or five-membered
carbocycles are even more reactive and show surprising successive
reactions.6,9 Since the access to the corresponding precursors is
q
See Ref. 1.
* Corresponding authors. Tel.: þ49 371 531 31463; fax: þ49 371 531 21229;
e-mail address: klaus.banert@chemie.tu-chemnitz.de (K. Banert).
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2012.12.054

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K. Banert et al. / Tetrahedron 69 (2013) 2501e2508
limited, we looked for new methods to prepare cyclic vinyl azides
with five- or six-membered rings. Herein, we report the synthesis of
such azides by cycloaddition reactions of 2-azidobuta-1,3-dienes 10,
which are easily available from 2,3-butadienyl halides 9 (X¼Cl, Br) by
nucleophilic substitution followed by [3,3]-sigmatropic migration of
the azido group (Scheme 2).10 Furthermore, we present the photol-
ysis of the resulting cyclic vinyl azides, which leads to 2,3-bridged
2H-azirines or the corresponding trapping products.
with the dienophiles 4-phenyl-1,2,4-triazoline-3,5-dione or tetra-
cyanoethene gave the cycloadducts 12a,b and 13a,b, respectively, in
moderate yields (44e82% yields of isolated compounds). Excellent
NMR yields (95e100% based on an added standard) resulted
from the [4þ2]-cycloaddition of 10a,b and fumaryl chloride or
maleic anhydride. However, the corresponding products 14a,b
and 15a,b proved to be significantly less stable than 12a,b or
13a,b. Less reactive dienophiles, such as dimethyl fumarate or
N3
N3
O
S
O
O
O
O
ICl
NaN3
KOt-Bu
S
S
I
O
R
R
R
I
a R = H
b R = Me
6
8
7
N3
N3
R
SO2
O
O
NaN3
[3,3]
C
S
X
R
R
10
9
11
O
C
O
O
NC
NC
CN
CN
NC
CN
CN
NC
NC
N
N
Cl
N
Ph
O
N
Cl
C
O
NC
O
O
17b
O
ClC
O
O
NC
NC
NC
NC
NC
N3
R
N3
N3
R
N3
Me
N3
N
N
O
Ph N
NC
NC
R
ClC
O
R
O
O
12
13
15
14
16b
Scheme 2.
2. Results and discussion
2.1. Cycloaddition reactions of 2-azidobuta-1,3-dienes
2-chloroacrylonitrile are not able to undergo the DielseAlder
reaction with 10b. On the other hand, treatment of 10b with
tricyanoethene15 led in low yields to the cyclic vinyl azide 16b
(16%) and the side product 17b (3%). The structure of the
[4þ2]-cycloadduct and the regioselectivity of the reaction are
clarified with the help of NOE-NMR experiments. Similarly, the
constitution of 17b, which can be explained by regioselective
[2þ2]-cycloaddition and ring-enlargement, is confirmed. In a pre-
vious report, analogous azidocyclobutane derivatives and the cor-
responding successive dihydropyrrole products were described.13
After treatment of the sulfolene 6a with iodine chloride and so-
dium azide (Hassner’s procedure),3e5 we obtained the addition
product 7a, which selectively leads to the allyl azide 8a when reacted
with potassium tert-butoxide. Analogous generation of 7b from 6b11
directly resulted in the formation of 8b on work-up. In both cases, we
could not detect any trace of the desired vinyl azides 11a,b. We did
not determine the stereochemistry of the addition products 7a,b.
However, we assume that not only the supposed trans structure of
7 but also the acidity of the CH2 protons is responsible for the
regioselective conversion to furnish allyl compounds 8.
Organic azides are known to react with electrophiles mainly to
give products with loss of dinitrogen.12 Nevertheless, we found that
treatment of 2-azidobuta-1,3-dienes 10a,b with sulfur dioxide in
diethyl ether at 70e100 ꢀC in an autoclave afforded the heterocy-
cles 11a,b via [4þ1]-cycloaddition (cheletropic reaction). These
cyclic vinyl azides were isolated as light-yellow or white crystals in
30e32% yield.
The reactions of electron-deficient alkynes or ring-strained
alkenes or alkynes with compound 10a or 2,3-diazidobuta-1,3-
dienes were reported to lead to 1,2,3-triazole derivatives.10a,13 The
latter electron-rich diazides, however, are able to undergo [4þ2]-
cycloadditions in the presence of especially electron-poor dien-
ophiles.14 Thus, we thought that 1,3-dipolar cycloaddition can
also be avoided in the case of starting compounds 10a,b when
DielseAlder reactions are performed with reagents including par-
2.2. Photolysis of cyclic vinyl azides
2,3-Bridged 2H-azirines of type 5 with a six-16,17 or a five-
membered17 ring were produced only in situ until a few years ago.
The existence of such species was proved by trapping reactions, for
example, addition of nucleophiles at the C]N bond. However, the
bridgehead azirines of type 5 with n¼1 could be generated in
solution by irradiation of the corresponding cyclic vinyl azides at
low temperature and have recently been detected in high yield by
IR and NMR spectroscopic analysis even at ambient temperature.6
But isolation of these extremely strained heterocycles was not
possible, and the detection of 2,3-bridged 2H-azirines with a five-
membered carbocycle failed even upon irradiation of the azides
at ꢁ120 ꢀC and NMR spectroscopic investigations at the same
temperature.6 It was shown by quantum chemical calculations that
the latter azirines are located at the borderline of closed-shell
molecules and diradical triplet nitrenes.9,18
After photolysis of 12a or 12b in CDCl3 at ꢁ50 ꢀC and NMR
spectroscopic analysis at the same temperature, only the methyl-
ticularly electron-deficient
p-systems. Treatment of dienes 10a,b

K. Banert et al. / Tetrahedron 69 (2013) 2501e2508
2503
Scheme 3.
substituted azirine 18b can be detected and characterized by its
1
complete H and 13C NMR data (Scheme 3). It is known that a sub-
stituent like methyl at the bridgehead carbon of heterocyclic sub-
stances of type 5 (n¼1) increases the kinetic stability of the
compound significantly.6 Thus,18a should be less stable than 18b. On
the other hand, the absence of a methyl group in 18a will promote the
exo approach of a diene to perform a DielseAlder reaction. Whereas
alkyl- or aryl-substituted simple 2H-azirines do not react with
cyclopentadiene,8b the corresponding [4þ2]-cycloaddition or other
cycloaddition reactions of 2,3-bridged 2H-azirines were reported to
always occur under very mild conditions at the exo side of the folded
molecule.6 Irradiation of a chloroform solution of 12a in the presence
of cyclopentadiene at ꢁ50 ꢀC leads nearly quantitatively (94e100%)
to the stable trapping product 19a, which can be explained by exo
approach toward the intermediate 18a and endo orientation of
cyclopentadiene. Obviously, compounds 18 are less stable than
bridgehead azirines of type 5 (n¼1). We assume that the additional
urazole unit in 18 causes a more rigid tricyclic structure and thus an
increase of ring strain compared to bicyclic heterocycles 5.
The photolysis of azide 11a was also performed at ꢁ50 ꢀC in the
presence of cyclopentadiene to get in excellent yield (90e100%) the
interception product 21a with a stereochemistry, which is analogous
to that of 19a. The extremely strained intermediate 20a can be
captured as well by addition of hydrogen cyanide. Whereas this re-
agent does not react with simple 2H-azirines or 5e even after 7 days
at 90 ꢀC, the desired formation of bicyclic 2-cyanoaziridines takes
place with good yields at ꢁ50 ꢀC in the cases of 2,3-bridged 2H-
azirines 5b and 5c.6,19 However, we did not obtain the expected
trapping product of 20a after irradiation of 11a at ꢁ50 ꢀC in the
presence of hydrogen cyanide. Instead, the aminal 23a was isolated
in 82e86% yield. This surprising compound is easily explained by
generation of intermediate 20a and its interception product 22a,
which adds at the very reactive C]N bond of a second molecule
of 20a. In contrast to this, the analogous photolysis of 11b led in
excellent yield to the simple addition product 22b via bridgehead
azirine 20b. The 1H NMR spectra of compound 22b indicated a single
set of signals at higher temperatures (ꢂ60 ꢀC), while only broad
signals were observed at 20 or 0 ꢀC (Fig. 1). At ꢁ50 ꢀC, sharp signals
Fig. 1. 1H NMR spectra of 22b in DMF-d7 at different temperatures.
and the sets of two species in a 2:5 ratio were detected. We assume
that the temperature-dependent 1H NMR spectra of 22b result from
rapid equilibration of the configuration at the aziridine N atom, that
can bear its hydrogen atom in the exo or endo position.20 The exo
NeH structure is assigned to the main diastereomer with the help of
low temperature NOE experiments, which showed significant effects
between methyl and NH protons. On the other hand, similar in-
vestigations indicate increased signals of the endo-2 and endo-4
protons when irradiation at the frequency of the NeH signal of the
minor diastereomer was performed. Thus, the endo NeH structure is
1
attributed to this minor invertomer. In consideration of all their H
NMR data, we assume that both epimers of 22b adopt chair-like
conformations (Fig. 2). With the help of 1H NMR line-shape analy-
sis in the range of ꢁ40 to þ60 ꢀC, we kinetically investigated the

2504
K. Banert et al. / Tetrahedron 69 (2013) 2501e2508
Fig. 2. Calculational results for 22b including dimethylformamide as solvent (CPCM Polarizable Conductor Continuum Model); relative energies [kcal/mol] at three levels of theory
B3LYP/6-311þG(d,p), B3LYP/6-311þG(d,p)(G298), and SCS-MP2/B3LYP/6-311þG(d,p).
equilibration of the configuration at the aziridine
N
atom.21
azides with especially electron-poor dienophiles. Since the
products include five- or six-membered rings, the corresponding
2,3-bridged 2H-azirines, which were generated by photolysis of
the vinyl azides at low temperature, are extremely reactive. This
reactivity can be utilized in addition and cycloaddition reactions
that are not possible for simple monocyclic 2H-azirines.
This study leads to Ea¼(9.01ꢃ0.38) kcal molꢁ1, ln A¼20.89ꢃ0.69,
D
D
H╪¼(8.45ꢃ0.37) kcal molꢁ1
,
D
S╪¼(ꢁ18.89ꢃ1.35) cal molꢁ1 Kꢁ1, and
G╪ ¼(13.79ꢃ0.53) kcal molꢁ1. All these data correspond to the
283
transformation of the minor isomer into the major invertomer.
These NMR spectroscopic results are nicely supported by high-
level quantum chemical studies of the four possible isomers
(exo-chair, exo-boat, endo-chair and endo-boat) and their mutual
interconversions. The B3LYP/6-311þG(d,p) method was used for the
geometry optimizations, SCS-MP2-single point energies22 are re-
ported in the following discussion. All calculations were performed
by using the GAUSSIAN 09 package of programs.23 Interestingly, gas
phase calculations gave only two minima, a hydrogen-bridged
endo-boat-form and the exo-chair form. The former is calculated
to be about 0.6 kcal/mol lower in energy. The transition state for the
interconversion of these two isomers is related to the inversion at
the aziridine nitrogen atom with a calculated barrier of 17.8 kcal/
4. Experimental
4.1. General
Melting points were determined with a Pentakon Dresden
Boetius apparatus. FTIR spectra were recorded with a Bruker IFS 28
FTIR spectrophotometer. IR measurements were made on solutions
in KBr cuvettes or as KBr pellets. 1H NMR spectra were recorded
with Varian Gemini 2000 or Unity Inova 400 spectrometers oper-
ating at 300 and 400 MHz, respectively. By using the same spec-
trometers, 13C NMR data were recorded at 75 and 100 MHz. NMR
mol (the calculated DG-value at 298 K (B3LYP) amounts to 13.2 kcal/
mol). However, inclusion of a DMF-solvent sphere (CPCM-model,
Universal Force Field (UFF)) resulted in four minima for all possible
isomers and allowed the determination of the respective transitions
states (Fig. 2). According to these results, all four minima have very
similar energies within a range of 1.8 kcal/mol with barriers up to
2.0 kcal/mol for the chaireboat interconversions. The lowest energy
is attributed to the exo-boat-isomer (Erel¼0.0 kcal/mol]). Dominat-
ing again is the barrier for inversion at the aziridine nitrogen atom
signals were referenced to TMS (
d
¼0 ppm) or solvent signals and
recalculated relative to TMS. The multiplicities of 13C NMR signals
were determined with the aid of DEPT135 experiments. HRMS (ESI)
spectra were recorded with a Bruker micrOTOF-QII spectrometer.
Elemental analyses were performed with a Vario Micro Cube from
Elementar. Elemental analyses of explosive azides and highly un-
stable azirines could not be performed. TLC was carried out with
MachereyeNagel Polygram SIL G/UV254 polyester sheets. Flash
(17.5 kcal/mol) (the calculated DG-value at 298 K (B3LYP) amounts
column chromatography was performed with 32e63
For HPLC, a pump Maxi Star (Knauer), a UV detector (
m
m silica gel.
¼254 nm,
m) were
in DMF to 13.3 kcal/mol). Thus, here a very flexible system involving
four conformers is observed, with a major barrier related to the
exoeendo-interconversion at nitrogen.24,25
l
Knauer), and a column LiChrospher Si60 (20ꢄ2 cm, 5
m
applied.
Photochemical irradiation was conducted by using a high-
pressure mercury lamp (TQ150, Heraeus GmbH) supplied with
glass equipment and an ethanol cryostat (ꢁ50 ꢀC). Most of the
photoreactions were monitored by NMR spectroscopic analysis
utilizing anhydrous CDCl3 (ꢁ50 ꢀC). A solution of the appropriate
starting material was irradiated in an NMR tube. To exclude oxygen,
3. Conclusion
In summary, we have developed new methods to prepare cyclic
vinyl azides by cheletropic reactions of 2-azidobuta-1,3-dienes
with sulfur dioxide and by DielseAlder reactions of the same

K. Banert et al. / Tetrahedron 69 (2013) 2501e2508
2505
the solution was flushed with argon in an ultrasonic bath prior to
4.5. General procedure for the synthesis of 3-azido-3-
sulfolenes (11a,b)
irradiation. Dioxane, DMSO, or a signal of the solvent was used as
standard to determine yields based on 1H NMR spectroscopic data.
Caution! Care must be taken in handling azides, which are ex-
plosive. Especially, neat azides can lead to large explosions on
friction, impact, or heating.26
A precooled (<ꢁ20 ꢀC) mixture of 10a10a or 10b10b (1.0 mmol) in
anhydrous diethyl ether (20 mL), and liquid sulfur dioxide (10 g)
was transferred into an autoclave and heated at 70e100 ꢀC for 5 h.
After cooling and evaporation of the sulfur dioxide, the solvent was
removed under reduced pressure. The residue was purified by flash
chromatography (EtOAc/hexane 1:9) to give 11a,b as light-yellow
crystals or colorless solid.
4.2. Preparation of 3-azido-4-iodosulfolane (7a)
At ꢁ30 ꢀC, iodine monochloride (7.76 g, 47.8 mmol) was care-
fully dropped into a mixture of sodium azide (6.88 g, 106 mmol)
and acetonitrile (45 mL). After stirring for additional 15 min,
3-sulfolene (6a, 5.00 g, 42.3 mmol) was added in portions. There-
after, the mixture was stirred for 16 h while it was slowly warmed
to room temperature. Water (50 mL) was added, and the mixture
was extracted with dichloromethane (3ꢄ50 mL). The combined
layers were decolorized by washing with aqueous sodium thio-
sulfate (5%, 120 mL), dried with magnesium sulfate, and evaporated
under reduced pressure. The residue was purified by flash chro-
matography (Et2O) to give 7a (1.77 g, 15%) as colorless solid; mp
4.5.1. 3-Azido-3-sulfolene 11a. Yield 30e32% (from several experi-
ꢁ1
ꢀ
~
ments); mp ca. 62 C (decomp.); IR (CDCl3):
(SO2); 1H NMR (CDCl3):
¼3.76 (m, 2H, CH2), 3.95 (m, 2H, CH2), 5.54
(m,1H, CH); 13C NMR (CDCl3):
n
¼2116 (N3), 1329 cm
d
d
¼54.4 (t, CH2), 57.3 (t, CH2),105.5 (d,
CH), 133.8 (s, CeN3); HRMS (ESI) calcd for C4H5N3NaO2S
([MþNa]þ): 181.9995; found: 181.9968.
4.5.2. 3-Azido-4-methyl-3-sulfolene 11b. Yield 30e32% (from
several experiments); mp ca. 77 ꢀC (decomp.); IR (CDCl3):
106 C; IR (CDCl3):
d
¼2121 (N3), 1330 cmꢁ1 (SO2); 1H NMR (CDCl3):
n
¼2120 cmꢁ1 (N3), 1329 cmꢁ1 (SO2); 1H NMR (CDCl3):
d
¼1.78 (br s,
ꢀ
~
n
~
¼3.09 (ddd, 2J¼13.5 Hz, J¼8.2 Hz, J¼0.8 Hz, 1H, CH2), 3.48 (ddd,
3H, CH3), 3.85 (br s, 2H, CH2), 3.98 (br s, 2H, CH2); 13C NMR (CDCl3):
2J¼13.7 Hz, J¼10.2 Hz, J¼0.6 Hz, 1H, CH2), 3.54 (dd, 2J¼13.5 Hz,
J¼7.5 Hz, 1H, CH2), 3.80 (dd, 2J¼13.7 Hz, J¼7.4 Hz, 1H, CH2), 4.31
(ddd, J¼10.2 Hz, J¼8.8 Hz, J¼7.4 Hz, 1H, CH), 4.47 (ddd, J¼8.8 Hz,
d
¼13.3 (q, CH3), 54.4 (t, CH2), 61.1 (t, CH2), 117.4 (s), 123.8 (s); HRMS
(ESI) calcd for C5H7N3NaO2S ([MþNa]þ): 196.0151; found:
196.0126.
J¼8.2 Hz, J¼7.5 Hz,1H, CH); 13C NMR (CDCl3):
¼14.4 (d, CHeI), 55.2
d
(t, CH2), 61.1 (t, CH2), 65.4 (d, CHeN3); HRMS (ESI) calcd for
C4H6IN3NaO2S ([MþNa]þ): 309.9118; found: 309.9107.
4.6. General procedures for the DielseAlder reactions of 2-
azidobuta-1,3-dienes 10a,b
4.3. Preparation of 4-azido-2-sulfolene (8a)
Solutions of 10a or 10b were treated with the dienophiles at
room temperature for 1e5 days. In the case of 4-phenyl-1,2,4-
triazoline-3,5-dione, this reagent was reacted with a twofold
excess of 10a,b in a 1:1 mixture of CHCl3/Et2O (0.05 M) overnight.
Thereafter, addition of Et2O led to precipitation of the product,
which was purified by flash chromatography (EtOAc/hexane 1:1).
TCNE was treated with a 50% excess of 10a,b, which was
dissolved in acetone (0.2e0.3 M). After 24 h, the solvent was
removed under reduced pressure, and the product was recrys-
tallized from Et2O/acetone. In the case of fumaryl chloride (1.0 M
in chloroform), equimolar amounts of 10a,b and a reaction time
of 2 days were utilized, whereas maleic anhydride (1.0 M in
acetone) was reacted with equimolar amounts of 10a or 10b for
5 days.
At 0 ꢀC, potassium tert-butoxide (500 mg, 4.46 mmol) was
added in portions to a solution of 7a (1.01 g, 3.53 mmol) in anhy-
drous Et2O (50 mL). The mixture was slowly warmed to room
temperature and stirred for 3 days. Water (ca. 50 mL) was added,
and the aqueous phase was extracted with dichloromethane
(2ꢄ30 mL). The combined organic layers were dried with magne-
sium sulfate and evaporated under reduced pressure. The residue
was purified by flash chromatography (Et2O) to give 8a (98.5 mg,
ꢁ1
18%) as colorless oil; IR (CDCl3):
n
¼2110 (N3), 1318 cm (SO2); 1H
~
NMR (CDCl3):
d
¼3.19 (dd, 2J¼14.1 Hz, 3J¼3.9 Hz, 1H, CH2), 3.62 (dd,
2J¼14.1 Hz, 3J¼7.8 Hz, 1H, CH2), 4.81 (dddd, 3J¼7.8 Hz, 3J¼3.9 Hz,
3J¼2.9 Hz, 4J¼1.8 Hz, 1H, CHN3), 6.71 (dd, 3J¼6.6 Hz, 3J¼2.9 Hz, 1H,
CH), 6.83 (dd, 3J¼6.6 Hz, 4J¼1.8 Hz, 1H, CH); 13C NMR (CDCl3):
d
¼53.5 (t, CH2), 57.5 (d, CHN3), 134.9 (d, CH), 136.5 (d, CH).
4.6.1. 3-Azido-8-phenyl-1,6,8-triazabicyclo[4.3.0]non-3-ene-7,9-
4.4. Preparation of 4-azido-3-methyl-2-sulfolene (8b)
dione 12a. Yield 80e82%; white solꢁid1; mp 134e135 ꢀC (decomp.).
IR (CDCl3):
d
n
¼2123 (s, N3), 1721 cm (s, C]O); 1H NMR (CDCl3):
~
At ꢁ20 ꢀC, iodine monochloride (6.94 g, 42.7 mmol) was care-
fully dropped into a mixture of sodium azide (6.15 g, 94.6 mmol)
and acetonitrile (40 mL). After stirring for additional 15 min,
3-methyl-3-sulfolene11 (6b, 5.00 g, 37.8 mmol) was added in
portions. Thereafter, the mixture was slowly warmed to room
temperature and stirred for 7 days. Water (ca. 50 mL) was added,
and the mixture was extracted with dichloromethane (3ꢄca.
50 mL). The combined organic layers were decolorized with
aqueous sodium thiosulfate (5%, 120 mL), dried with magnesium
sulfate, and evaporated under reduced pressure. The residue was
purified by flash chromatography (Et2O) to give 8b (1.55 g, 24%) as
~
¼4.04 (dd, J¼2.5 Hz, J¼1.4 Hz, 2H, H-2), 4.26 (dd, J¼3.6 Hz,
J¼2.5 Hz, 2H, H-5), 5.57 (tt, J¼3.6 Hz, J¼1.4 Hz, 1H, H-4), 7.26e7.53
(m, 5H, Ph); 13C NMR (CDCl3):
d¼42.8 (t, C-2 or C-5), 43.9 (t, C-2 or
C-5),104.4 (d, C-4),125.3 (d, Ph),128.3 (d, Ph),129.2 (d, Ph),130.8 (s,
C-3 or Ph), 133.0 (s, C-3 or Ph), 152.2 (s, C-7 or C-9), 152.4 (s, C-7 or
C-9); HRMS (ESI) calcd for C12H10N6NaO2 ([MþNa]þ): 293.0757;
found: 293.0749. Anal. Calcd for C12H10N6O2: C 53.33, H 3.73, N
31.10, found: C 53.51, H 3.76, N 30.92.
4.6.2. 3-Azido-4-methyl-8-phenyl-1,6,8-triazabicyclo[4.3.0]non-3-
ene-7,9-dione 12b. Yield 79%; white needles; mp 132e133 ꢀC
~
slightly yellowish oil; IR (CDCl3):
n
¼2110 (N3), 1312 cmꢁ1 (SO2); 1H
(decomp.). IR (CDCl3):
n
¼2110 (s, N3), 1718 cmꢁ1 (s, C]O); 1H NMR
NMR (CDCl3):
d
¼1.98 (dd, 4J¼1.6 Hz, 4J¼0.9 Hz, 3H, CH3), 3.23
(CDCl3):
d
¼1.79 (s, 3H, Me), 4.07 (q, J¼2.1 Hz, 2H, H-2 or H-5), 4.29
(dd, 2J¼14.1 Hz, 3J¼3.7 Hz, 1H, CH2), 3.63 (dd, 2J¼14.1 Hz, 3J¼7.9 Hz,
1H, CH2), 4.55 (dddq, 3J¼7.9 Hz, 3J¼3.7 Hz, 4J¼1.4 Hz, 4J¼0.9 Hz, 1H,
CHN3), 6.42 (qd, 4J¼1.6 Hz, 4J¼1.4 Hz, 1H, CH); 13C NMR (CDCl3):
(q, J¼2.1 Hz, 2H, H-2 or H-5), 7.42e7.58 (m, 5H, Ph); 13C NMR
(CDCl3):
d
¼14.5 (q, Me), 42.7 (t, C-2 or C-5), 46.8 (t, C-2 or C-5),115.1
(s, C-3 or C-4), 122.1 (s, C-3 or C-4), 125.3 (d, Ph), 128.3 (d, Ph),
129.2 (d, Ph), 130.9 (s, Ph), 152.1 (s, C-7 or C-9), 152.2 (s, C-7 or
C-9); HRMS (ESI) calcd for C13H12N6NaO2 ([MþNa]þ): 307.0914;
d
¼15.7 (q, CH3), 54.7 (t, CH2), 60.7 (d, CHN3), 129.0 (d, CH), 148.9
(s, CeCH3).

2506
K. Banert et al. / Tetrahedron 69 (2013) 2501e2508
found: 307.0907. Anal. Calcd for C13H12N6O2: C 54.93, H 4.25, N
29.56, found: C 55.02, H 4.26, N 29.10.
and 17b in a 7:1 ratio. The reaction mixture was treated with
anhydrous Et2O, and the resulting precipitate was purified by flash
chromatography and then by HPLC (acetone/hexane 1:3) to give
two products (elution order: 16b 22 min, 17b 27 min).
4.6.3. 4-Azidocyclohex-4-ene-1,1,2,2-tetracarbonitrile
13a. Yieꢁld1
ꢀ
~
44%; light-brown solid; mp 73 C (decomp.). IR (KBr):
n
¼2109 cm
(s, N3); 1H NMR (acetone-d6):
H-5); 13C NMR (acetone-d6):
C-6), 38.6 (s, C-1 or C-2), 39.2 (s, C-1 or C-2), 105.3 (d, C-5), 111.1
d
¼3.61 (m, 4H, H-3, H-6), 5.71 (m, 1H,
4.7.1. 4-Azido-5-methylcyclohex-4-ene-1,1,2-tricarbonitrile
16b. Yield 56 mg; 16%; light-brown solid; mp 135 ꢀC (decomp.). IR
d
¼31.2 (t, C-3 or C-6), 31.8 (t, C-3 or
ꢁ1
(acetone-d6):
n
¼2114 cm (s, N3); 1H NMR (acetone-d6):
d
¼1.74
~
3
(s, C^N), 111.4 (s, C^N), 131.7 (s, C-4).
(br sept, J¼1.1 Hz, 3H, Me), 3.04 (ddq, 2J¼17.0 Hz, Jtrans,H-2/H-
¼8.8 Hz, J¼2.3 Hz, 1H, H-3), 3.17 (br m, 2H, H-6), 3.24
3
3
4.6.4. 4-Azido-5-methylcyclohex-4-ene-1,1,2,2-tetracarbonitrile
13b. Yield 50%; light-brown solid; mp 102 ꢀC (decomp.). IR (KBr):
(ddq, 2J¼17.0 Hz, Jcis,H-2/H-3¼5.5 Hz, J¼1.7 Hz, 1H, H-3), 4.36
3
3
(dd, Jtrans,H-2/H-3¼8.8 Hz, Jcis,H-2/H-3¼5.5 Hz, 1H, H-2); 13C NMR
ꢁ1
¼2120 cm (s, N3); 1H NMR (acetone-d6):
d
¼1.82 (t, J¼0.9 Hz,
(acetone-d6):
d
¼16.7 (q, Me), 26.2 (t, C-3 or C-6), 33.5 (d, C-2), 37.4
~
n
3H, Me), 3.48 (q, J¼1.8 Hz, 2H, H-3 or H-6), 3.88 (q, J¼1.8 Hz, 2H,
(t, C-3 or C-6), 113.9 (s), 114.4 (s), 115.4 (s), 117.1 (s), 125.2 (s). The
assignment of the 1H NMR signals was supported by homonuclear
shift correlation (2D NMR). The structure of the compound and
thus the regiochemistry of its formation by DielseAlder reaction
was also ascertained by NOE experiments that indicated an
interaction between H-2 and H-3, and between methyl protons
and H-6.
H-3 or H-6); 13C NMR (acetone-d6):
d
¼16.1 (q, Me), 30.7 (t, C-3 or
C-6), 35.6 (t, C-3 or C-6), 38.7 (s, C-1 or C-2), 39.2 (s, C-1 or C-2),
111.0 (s, C^N), 111.3 (s, C^N), 114.9 (s, C-4 or C-5), 122.6 (s, C-4
or C-5).
4.6.5. trans-4-Azidocyclohex-1-ene-1,2-dicarboxylic acid dichloride
14a. Yield 95% (1H NMR bꢁas1ed on an added standard); IR (CDCl3):
~
n
¼2115 (m, N3), 1728 cm
(s, C]O); 1H NMR (CDCl3):
d
¼2.28
4.7.2. 5-(1-Methylethenyl)-3,4-dihydro-2H-pyrrole-2,2,3-tricar-bo-
(m, 2H, H-3, H-6), 2.62 (dtt, 2J¼17.6 Hz, J¼5.5 Hz, J¼1.7 Hz, 1H, H-3
or H-6), 2.75 (dtt, 2J¼17.6 Hz, J¼5.5 Hz, J¼1.7 Hz, 1H, H-3 or H-6),
3.38 (dt, 3J¼9.3 Hz, J¼5.5 Hz, 1H, H-1 or H-2), 3.50 (dt, 3J¼9.3 Hz,
J¼5.5 Hz, 1H, H-1 or H-2), 5.36 (quint, J¼1.7 Hz, 1H, H-5), 13C NMR
nitrile 17b. Yield 8 mg; 3%; white solid; mp 151 ꢀC (decomp.). 1H
NMR (acetone):
d
¼2.03 (Me, partially covered by solvent signals),
3.75 (dd, 2J¼17.6 Hz, J¼7.2 Hz, 1H, H-4), 3.97 (dd, 2J¼17.6 Hz,
J¼9.8 Hz, 1H, H-4), 4.68 (dd, J¼9.8 Hz, J¼7.2 Hz, 1H, H-3), 5.95 (dq,
J¼1.5 Hz, J¼0.5 Hz, 1H, H-20), 5.97 (d, J¼0.5 Hz, 1H, H-20); 13C NMR
(CDCl3):
d
¼26.0 (t, C-3 or C-6), 27.6 (t, C-3 or C-6), 51.8 (d, C-1 or
C-2), 52.2 (d, C-1 or C-2), 107.8 (d, C-5), 133.5 (s, C-4), 174.2 (s, COCl),
174.7 (s, COCl). On attempts to isolate 14a or 14b and to perform
a purification as described for 13a,b, complete decomposition of
the cycloadducts 14a,b was observed.
(acetone-d6):
d¼18.7 (q, Me), 39.2 (d, C-3), 41.1 (t, C-4), 67.3 (s, C-2),
112.5 (s), 113.7 (s), 116.7 (s), 129.5 (t, C-20), 139.3 (s, C-10), 183.9
(s, C-5). The assignment of the NMR signals was supported
by double resonance experiments and by homonuclear and heter-
onuclear shift correlations (2D NMR). Furthermore, the spectro-
scopic data of 17b were compared with those of known13
3,4-dihydro-2H-pyrrole-2,2,3,3-tetracarbonitriles.
4.6.6. trans-4-Azido-5-methylcyclohex-1-ene-1,2-dicarboxylic acid
1
~
dichloride 14b. Yield ca. 100% ( H NMR); IR (CDCl3):
n
¼2105 (s, N3),
1725 cmꢁ1 (s, C]O); 1H NMR (CDCl3):
d
¼1.78 (quint, J¼1.1 Hz, 3H,
Me), 2.37 (m, 1H, H-3 or H-6), 2.56 (m, 2H, H-3 or H-6), 2.85
(ddt, 2J¼16.5 Hz, J¼5.8 Hz, J¼1.7 Hz, 1H, H-3 or H-6), 3.40
(dt, 3J¼9.7 Hz, J¼5.8 Hz,1H, H-1 or H-2), 3.52 (dt, 3J¼9.7 Hz, J¼5.8 Hz,
4.8. Generation of 9-methyl-5-phenyl-3,5,7,10-tetraazatri-cy-
clo[7.1.0.03,7]dec-1(10)-ene-4,6-dione 18b
1H, H-1 or H-2); 13C NMR (CDCl3):
d
¼17.0 (q, Me), 26.6 (t, C-3 or C-6),
A solution of 12b (50 mg, 0.18 mmol) in CDCl3 (0.7 mL) was
photolyzed in an NMR tube for 60 min at ꢁ50 ꢀC. The reaction was
monitored by NMR spectroscopic analysis at ꢁ50 ꢀC indicating
a maximum yield of 18b of 13%. Prolonged irradiation led to com-
plete conversion of 12b but also to excessive degradation of 18b.
The product 18b can only be handled in solution at low tempera-
31.9 (t, C-3 or C-6), 52.3 (d, C-1 or C-2), 52.6 (d, C-1 or C-2), 118.0
(s, C-4 or C-5), 123.6 (s, C-4 or C-5), 174.2 (s, COCl), 174.6 (s, COCl).
4.6.7. 3-Azido-8-oxabicyclo[4.3.0]non-3-ene-7,9-dione
15a. Yield
1
¼2117 (m, N3), 1733 cmꢁ1 (s, C]O);
~
nearly 100% ( H NMR); IR (KBr):
n
1H NMR (acetone-d6):
d
¼2.41e2.71 (m, 4H, H-2, H-5), 3.63 (m, 1H,
ture, such as ꢁ50 ꢀC. 1H NMR (CDCl3):
¼1.67 (s, 3H, CH3), 3.62 (d,
d
H-1 or H-6), 3.81 (m, 1H, H-1 or H-6), 5.77 (m, 1H, H-4); 13C NMR
(acetone-d6):
2J¼13.7 Hz, 1H, 8-H), 3.88 (d, 2J¼13.7 Hz, 1H, 8-H), 4.84 (d,
d
¼15.6 (t, C-2 or C-5), 16.8 (t, C-2 or C-5), 31.2 (d, C-1 or
2J¼12.1 Hz, 1H, 2-H), 5.43 (d, 2J¼12.1 Hz,1H, 2-H), 7.37e7.52 (m, 5H,
C-6), 32.2 (d, C-1 or C-6), 101.3 (d, C-4), 128.8 (s, C-3), 166.2 (s, C-7 or
C-9), 166.3 (s, C-7 or C-9). Compounds 15a and 15b proved to be
highly unstable on attempts of isolation and purification.
AreH); 13C NMR (CDCl3):
53.4 (t, C-2), 125.3 (d, AreC), 128.7 (d, AreC), 129.3 (d, AreC), 129.7
(s, AreC), 152.6 (s, C-4 or C-6), 154.1 (s, C-4 or C-6), 178.1 (s, C-1).
d
¼19.5 (q, CH3), 31.0 (s, C-9), 48.2 (t, C-8),
4.6.8. 3-Azido-4-methyl-8-oxabicyclo[4.3.0]non-3-ene-7,9-dione
4.9. Preparation of 7-phenyl-2,5,7,9-tetraazapentacyclo-
[10.2.1.02,1103,11.05,9]pentadec-13-ene-6,8-dione (19a)
15b. Yield nearly 100% (1H NMR); IR (KBr):
n
¼2111 (m, N3),
~
1712 cmꢁ1 (s, C]O); 1H NMR (acetone-d6):
(m, 2H, H-2 or H-5), 2.72 (m, 2H, H-2 or H-5), 3.64 (m, 1H, H-1, H-1
or H-6), 3.80 (m, 1H, H-1 or H-6); 13C NMR (acetone-d6):
d
¼1.67 (s, 3H, Me), 2.48
A solution of 12a (100 mg, 0.38 mmol) and freshly distilled
cyclopentadiene (120 mg, 1.8 mmol) in chloroform (5 mL) was
irradiated at ꢁ50 ꢀC for ca. 6 h until the azide was completely
consumed. Thereafter, the solvent was removed under reduced
pressure, and the residue was washed with ethyl acetate/hexane
(1:1) to get 19a (110e118 mg, 94e100%) as a ꢁco1 lorless solid; mp
d
¼8.6
(q, Me), 15.4 (t, C-2 or C-5), 21.8 (t, C-2 or C-5), 31.6 (d, C-1 or C-6),
32.5 (d, C-1 or C-6), 111.9 (s, C-3 or C-4), 118.4 (s, C-3 or C-4), 166.2
(s, C-7 or C-9), 166.4 (s, C-7 or C-9).
¼1713 cm (C]O); 1H NMR
ꢀ
~
183e188 C (decomp.); IR (CDCl3):
n
4.7. Reaction of 10b with tricyanoethene
(CDCl3):
d
¼1.81 (d, 2J¼8.1 Hz, 1H, 15-H), 1.95 (d, J¼3.7 Hz, 1H, 3-H),
To a solution of tricyanoethene15 (164 mg, 1.59 mmol) in
anhydrous acetone (5 mL) was added 10b (173 mg, 1.59 mmol) with
intensive stirring. The mixture was stirred for 5 days at room
temperature. Analysis of a sample indicated the formation of 16b
2.23 (d, 2J¼8.1 Hz, 1H, 15-H), 2.99 (s, 1H, 12-H), 3.72 (dd, 2J¼12.8 Hz,
J¼4.0 Hz, 1H, 4-H) 3.92 (d, 2J¼12.8 Hz, 1H, 4-H), 3.98 (d, 2J¼12.1 Hz,
1H, 10-H), 4.14 (d, 2J¼12.1 Hz, 1H, 10-H), 4.21 (s, 1H, 1-H),
5.80 (m, 1H, 13-H or 14-H), 6.19 (m, 1H, 13-H or 14-H), 7.32e7.48

K. Banert et al. / Tetrahedron 69 (2013) 2501e2508
2507
(m, 5H, AreH); 13C NMR (CDCl3):
d
¼41.3 (s, C-11), 43.1 (d, C-3 or
4.12. Preparation of 6-(60-aza-30-thiabicyclo[3.1.0]hexane-
30,30-dioxid-10-yl)-6-aza-3-thiabicyclo[3.1.0]hexane-1-carbo-
nitrile-3,3-dioxide (23a)
C-12), 44.1 (t, C-4 or C-10), 46.2 (t, C-4 or C-10), 47.8 (d, C-3 or C-12),
58.8 (t, C-15), 66.7 (d, C-1), 125.4 (d, eCH] or AreC), 128.07 (d,
eCH] or AreC), 128.11 (d, eCH] or AreC), 129.1 (d, eCH] or
AreC), 131.1 (s, AreC), 132.3 (d, eCH] or AreC), 152.6 (s, C-6 or C-
8), 152.6 (s, C-6 or C-8); HRMS (ESI) calcd for C17H17N4O2 ([MþH]þ):
309.1346; found: 309.1346. Anal. Calcd for C17H16N4O2: C 66.22, H
5.23, N 18.17, found: C 66.23, H 5.18, N 18.17.
A solution of 11a (100 mg, 0.63 mmol) and hydrogen cyanide
(ca. 65 mg, 2.4 mmol) in chloroform (4 mL) was irradiated at ꢁ50 ꢀC
for ca. 6 h. The product partially precipitated as a colorless solid.
After removal of the solvent under reduced pressure, the residue
was washed with chloroform to give 23a (74e78 mg, 82e86%) as
slightly yellow solid, which slowly decomposed on heating above
4.10. Preparation of 2-aza-5-thiatetracyclo[6.2.1.02,7.03,7]-un-
dec-9-ene-5,5-dioxide (21a)
50 C; IR (KBr):
d
¼2246 (CN), 1320 cmꢁ1 (SO2); 1H NMR (DMSO-d6):
ꢀ
~
n
¼2.77 (ddd, 3J¼6.2 Hz, J¼6.0 Hz, J¼1.4 Hz, 1H, 50-H), 3.00
3
(d, 3J¼6.2 Hz, 1H, NH), 3.03 (dd, 2J¼14.2 Hz, J¼1.4 Hz, 1H, 40-H), 3.21
A solution of 11a (100 mg, 0.63 mmol) and freshly distilled
cyclopentadiene (166 mg, 2.5 mmol) in chloroform (5 mL) was ir-
radiated at ꢁ50 ꢀC for ca. 6 h until the azide was completely con-
sumed. Thereafter, the solvent was removed under reduced
pressure, and the residue was washed with ethyl acetate/hexane
2
(d, 2J¼13.7 Hz, 1H, 4-H), 3.34 (d, J¼13.8 Hz, 1H, 20-H), 3.56
(d, J¼4.9 Hz, 1H, 5-H), 3.61 (ddd, 2J¼13.7 Hz, J¼4.9 Hz, J¼1.1 Hz, 1H,
4-H), 3.717 (d, 2J¼14.0 Hz, 1H, 2-H), 3.725 (ddd, 2J¼14.2 Hz,
3J¼6.0 Hz, J¼2.6 Hz, 1H, 40-H), 3.92 ( dd, 2J¼14.0 Hz, J¼1.1 Hz, 1H,
2-H), 4.12 (dd, 2J¼13.8 Hz, J¼2.6 Hz, 1H, 20-H); 13C NMR (DMSO-d6):
ꢁ1
~
(1:1) to get 21a (112e124 mg, 90e100%); IR (CDCl3):
n
¼1319 cm
d
¼32.4 (s, CeCN), 32.9 (d, CHeNH), 40.4 (d, CHeN), 53.1 (t, C-4),
(SO2); 1H NMR (CDCl3):
d
¼1.80 (d, 2J¼8.1 Hz, 1H, 11-H), 2.21 (d,
54.0 (t, C-40), 54.9 (t, C-2), 55.1 (s, CeNH), 55.7 (t, C-20),115.8 (s, CN);
HRMS (ESI) calcd for C9H12N3O4S2 ([MþH]þ): 290.0264; found:
290.0264. The assignment of the NMR signals was supported by
heteronuclear shift correlation (2D NMR) and by comparison of
experimental and simulated 1H NMR spectra.
2J¼8.1 Hz, 1H, 11-H), 2.30 (d, J¼5.2 Hz, 1H, 3-H), 3.09 (m, 1H, 8-H),
3.16 (d, 2J¼13.6 Hz, 1H, 4-H), 3.31 (dd, 2J¼13.6 Hz, J¼5.2 Hz, 1H,
4-H), 3.41 (d, 2J¼13.2 Hz,1H, 6-H), 3.49 (d, 2J¼13.2 Hz, 1H, 6-H), 4.19
(m, 1H, 1-H), 5.74 (m, 1H, 9-H or 10-H), 6.15 (m, 1H, 9-H or 10-H);
13C NMR (CDCl3):
d
¼46.5 (s, C-7), 46.7 (d, C-3 or C-8), 47.4 (d, C-3 or
C-8), 55.7 (t), 56.3 (t), 59.4 (t), 66.6 (d, C-1), 127.3 (d, C-9 or C-10),
132.2 (d, C-9 or C-10); HRMS (ESI) calcd for C9H12NO2S ([MþH]þ):
198.0583; found: 198.0574.
Acknowledgements
Financial support of the Alexander von Humboldt Foundation
and especially a fellowship for B.S. are gratefully acknowledged.
4.11. Preparation of 5-methyl-6-aza-3-thiabicyclo[3.1.0]-hex-
ane-1-carbonitrile-3,3-dioxide (22b)
Supplementary data
A solution of 11b (100 mg, 0.58 mmol) and hydrogen cyanide
(ca. 65 mg, 2.4 mmol) in chloroform (4 mL) was irradiated at ꢁ50 ꢀC
for ca. 6 h. The product partially precipitated. After removal of the
solvent under reduced pressure, the residue was washed with ethyl
acetate/hexane (1:1) to give 22b (94e98.6 mg, 95e100%) as slightly
yellow solid, which slowly decomposed on heating above 50 ꢀC; IR
Supplementary data associated with this article can be found in
the online version, at http://dx.doi.org/10.1016/j.tet.2012.12.054.
These data include MOL files and InChiKeys of the most important
compounds described in this article.
References and notes
ꢁ1
1
(KBr):
¼2246 (CN), 1320 cm (SO2); H NMR (DMSO-d6, 22 ꢀC):
~
n
d
¼1.57 (br s, 3H, CH3), 3.25 (d, 2J¼13.7 Hz, 1H, CH2), 3.35 (br s, 1H,
1. Part 31 of the series ‘Reactions of unsaturated azides’. For part 30, see: Banert,
K.; Arnold, R.; Hagedorn, M.; Thoss, P.; Auer, A. A. Angew. Chem. 2012, 124,
7633e7636; Angew. Chem., Int. Ed. 2012, 51, 7515e7518.
NH), 3.46 (d, 2J¼13.9 Hz, 1H, CH2), 3.58 (br s, 1H, CH2), 3.91 (br s, 1H,
CH2); 13C NMR (DMSO-d6, 22 ꢀC):
d¼18.8 (br q, CH3), 31.6 (s, CeCN),
2. For reviews on vinyl azides, see: (a) Banert, K. In Houben-Weyl; Kropf, H.,
Schaumann, E., Eds.; Thieme: Stuttgart, 1993; Vol. E15, pp 818e875; (b)
Hassner, A. In Azides and Nitrenes; Scriven, E. F. V., Ed.; Academic: Orlando,
1984; pp 35e76; (c) Banert, K. In Organic Azides: Syntheses and Applications;
45.3 (s, CeCH3), 55.3 (t, CH2), 56.7 (t, CH2), 117.5 (s, CN); 1H NMR
(DMF-d7, 60 ꢀC):
d
¼1.69 (s, 3H, CH3), 3.33 (d, 2J¼13.7 Hz, 1H, CH2),
3.54 (d, 2J¼13.9 Hz, 1H, CH2), 3.65 (dd, 2J¼13.7 Hz, J¼1.6 Hz, 1H,
€
Brase, S., Banert, K., Eds.; Wiley: Chichester, UK, 2010; pp 115e166; (d) Collier,
CH2), 3.94 (d, 2J¼13.9 Hz, 1H, CH2), 3.3e3.9 (very br s, NH); 13C NMR
S. J. In Science of Synthesis; Molander, G. A., Ed.; Thieme: Stuttgart, 2006; Vol.
33, pp 541e563; (e) Smolinsky, G.; Pryde, C. A. In The Chemistry of the Azido
Group; Patai, S., Ed.; Wiley: New York, NY, 1971; pp 555e585.
3. Hassner, A.; Levy, L. A. J. Am. Chem. Soc. 1965, 87, 4203e4204.
4. For a review, see: Hassner, A. Acc. Chem. Res. 1971, 4, 9e16.
5. (a) Hassner, A.; Fowler, F. W. J. Org. Chem. 1968, 33, 2686e2691; (b) Hassner, A.;
Fowler, F. W. Tetrahedron Lett. 1967, 8, 1545e1548; (c) Rose, B.; Schollmeyer, D.;
Meier, H. Liebigs Ann. 1997, 409e412.
6. Banert, K.; Meier, B. Angew. Chem. 2006, 118, 4120e4123; Angew. Chem., Int. Ed.
2006, 45, 4015e4019.
(DMF-d7, 60 ꢀC):
d¼19.5 (q, CH3), 33.0 (s, CeCN), 45.8 (s, CeCH3),
56.4 (t, CH2), 57.4 (t, CH2), 117.9 (s, CN); minor diastereomer: 1H
NMR (DMF-d7, e50 ꢀC):
d
¼1.57 (s, 3H, CH3), 3.43 (d, 2J¼14.0 Hz, 1H,
endo-4-H), 3.64 (d, 2J¼14.7 Hz, 1H, endo-2-H), 3.74 (s, 1H, NH), 3.94
(dd, 2J¼14.0 Hz, 4J¼2.9 Hz, 1H, exo-4-H), 4.39 (dd, 2J¼14.7 Hz,
4J¼2.9 Hz, 1H, exo-2-H); the assignments of the 1H NMR signals
were supported by the 4J coupling between exo-2-H and exo-4-H
(w coupling), and homonuclear NOE experiments, which were
performed at ꢁ67 ꢀC in a 5:2 mixture of DMF-d7 and acetone-d6.
These investigations made it possible to attribute all 1H NMR sig-
7. Schweng, J.; Zbiral, E. Liebigs Ann. Chem. 1978, 1089e1095.
8. Reviews on 2H-azirines: (a) Backes, J. In Houben-Weyl; Klamann, D., Ed.;
Thieme: Stuttgart, 1992; Vol. E16c, pp 321e369; (b) Nair, V. In The Chemistry of
Heterocyclic Compounds, Small-ring Heterocycles; Hassner, A., Ed.; Wiley: New
York, NY, 1983; Vol. 42, pp 215e332; (c) Pearson, W. H.; Lian, B. W.; Bergmeier,
S. C. In Comprehensive Heterocyclic Chemistry II; Padwa, A., Ed.; Pergamon: New
York, NY, 1996; Vol. 1A, pp 1e60; (d) Palacios, F.; Ochoa de Retana, A. N.;
Martinez de Marigorta, E.; de Los Santos, J. M. Eur. J. Org. Chem. 2001,
2401e2414; (e) Gilchrist, T. L. Aldrichimica Acta 2001, 34, 51e55; (f) Rai, K. M. L.;
Hassner, A. In Advances in Strained and Interesting Organic Molecules; Halton, B.,
Ed.; Jai: Greenwich, 2000; Vol. 8, pp 187e257.
nals of both invertomers of 22b; 13C NMR (DMF-d7, e50 ꢀC):
d¼20.6
(q, CH3), 32.6 (s, CeCN), 44.8 (s, CeCH3), 54.9 (t, CH2), 56.3 (t, CH2),
119.0 (s, CN); major diastereomer: 1H NMR (DMF-d7, e50 ꢀC):
d
¼1.71 (s, 3H, CH3), 3.44 (d, 2J¼13.5 Hz, 1H, endo-4-H), 3.70 (d, br,
2J¼13.5 Hz, 1H, exo-4-H), 3.71 (d, 2J¼13.5 Hz, 1H, endo-2-H), 4.03 (d,
br, 2J¼13.5 Hz, 1H, exo-2-H), 4.46 (s, 1H, NH); 13C NMR (DMF-d7,
€
€
9. Banert, K.; Meier, B.; Penk, E.; Saha, B.; Wurthwein, E.-U.; Grimme, S.; Ruffer, T.;
e50 ꢀC):
d¼18.8 (q, CH3), 32.9 (s, CeCN), 46.8 (s, CeCH3), 56.1
Schaarschmidt, D.; Lang, H. Chem.dEur. J. 2011, 17, 1128e1136.
10. (a) Priebe, H. Angew. Chem. 1984, 96, 728e729; Angew. Chem., Int. Ed. Engl. 1984,
23, 736e738; (b) Banert, K. Angew. Chem. 1985, 97, 231e232; Angew. Chem., Int.
Ed. Engl. 1985, 24, 216e217.
(t, CH2), 57.4 (t, CH2), 118.0 (s, CN); HRMS (ESI) calcd for C6H9N2O2S
([MþH]þ): 173.0379; found: 173.0368. Anal. Calcd for C6H8N2O2S:
C 41.85, H 4.68, found: C 41.73, H 4.69.
11. Frank, R. L.; Seven, R. P. Organic Syntheses; 1955; Collect. Vol. No. III, pp 499e500.

2508
K. Banert et al. / Tetrahedron 69 (2013) 2501e2508
12. Abramovitch, R. A.; Kyba, E. P. In The Chemistry of the Azido Group; Patai, S., Ed.;
Wiley: New York, NY, 1971; pp 221e329.
1986, 139, 315e325; (g) Rauk, A.; Allen, L. C.; Mislow, K. Angew. Chem. 1970, 82,
453e468; Angew. Chem., Int. Ed. Engl. 1970, 9, 400e414.
13. Banert, K. Chem. Ber. 1989, 122, 123e128.
21. For details, see also the Supplementary data.
14. Banert, K. Angew. Chem. 1987, 99, 932e934; Angew. Chem., Int. Ed. Engl. 1987, 26,
879e885.
15. Dickinson, C. L.; Wiley, D. W.; McKusick, B. C. J. Am. Chem. Soc. 1960, 82,
6132e6136.
22. Grimme, S. J. Chem. Phys. 2003, 118, 9095e9102.
23. Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.;
Cheeseman, J. R.; Montgomery, J. A.; Vreven, T., Jr.; Kudin, K. N.; Burant, J. C.;
Millam, J. M.; Iyengar, S. S.; Tomasi, J.; Barone, V.; Mennucci, B.; Cossi, M.;
Scalmani, G.; Rega, N.; Petersson, G. A.; Nakatsuji, H.; Hada, M.; Ehara, M.;
Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao,
O.; Nakai, H.; Klene, M.; Li, X.; Knox, J. E.; Hratchian, H. P.; Cross, J. B.; Bakken,
V.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A.
J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Ayala, P. Y.; Morokuma, K.; Voth, G.
A.; Salvador, P.; Dannenberg, J. J.; Zakrzewski, V. G.; Dapprich, S.; Daniels, A. D.;
Strain, M. C.; Farkas, O.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K.; Fores-
man, J. B.; Ortiz, J. V.; Cui, Q.; Baboul, A. G.; Clifford, S.; Cioslowski, J.; Stefanov,
B. B.; Liu, G.; Liashenko, A.; Piskorz, P.; Komaromi, I.; Martin, R. L.; Fox, D. J.;
Keith, T.; Al-Laham, M. A.; Peng, C. Y.; Nanayakkara, A.; Challacombe, M.; Gill, P.
M. W.; Johnson, B.; Chen, W.; Wong, M. W.; Gonzalez, C.; Pople, J. A. Gaussian
03, Revision C.01; Gaussian: Wallingford CT, 2004; Details of the quantum
chemical calculations (Gaussian archive entries) may be obtained from W., E.-U.
upon request.
16. (a) Rai, K. M. L.; Hassner, A. In Comprehensive Heterocyclic Chemistry II; Padwa,
A., Ed.; Elsevier: Oxford, 1996; Vol. 1A, pp 61e96; and references cited therein;
€
€
(b) Laue, J.; Seitz, G. Liebigs Ann. 1996, 645e648; (c) Drogemuller, M.; Jautelat,
R.; Winterfeldt, E. Angew. Chem. 1996, 108, 1669e1671; Angew. Chem., Int. Ed.
€
€
1996, 35, 1572e1574; (d) Drogemuller, M.; Flessner, T.; Jautelat, R.; Scholz, U.;
Winterfeldt, E. Eur. J. Org. Chem. 1998, 2811e2831; (e) Haak, E.; Winterfeldt, E.
Synlett 2004, 1414e1418; (f) Tamura, Y.; Yoshimura, Y.; Nishimura, T.; Kato, S.;
Kita, Y. Tetrahedron Lett. 1973, 14, 351e354; (g) Senda, S.; Hirota, K.; Asao, T.;
Maruhashi, K. J. Am. Chem. Soc. 1978, 100, 7661e7664; (h) Pearce, D. S.; Locke,
M. J.; Moore, H. W. J. Am. Chem. Soc. 1975, 97, 6181e6186; (i) Zaidlewicz, M.;
Uzarewicz, I. G. Heteroat. Chem. 1993, 4, 73e77; (j) Hassner, A.; Fowler, F. W. J.
Am. Chem. Soc. 1968, 90, 2869e2875.
17. Tamura, Y.; Kato, S.; Yoshimura, Y.; Nishimura, T.; Kita, Y. Chem. Pharm. Bull.
1974, 22, 1291e1296.
€
18. For a discussion on the ring strain in 2H-azirines, see: Wurthwein, E.-U.; Her-
24. Quantum chemical calculations on the exoeendo-interconversion at nitrogen
agree well with our experimental results for 22b; thus, we did not consider
tunneling processes25 in our discussion.
€
genrother, T.; Quast, H. Eur. J. Org. Chem. 2002, 1750e1755.
19. For the addition of exactly one equivalent of HCN to 2-methylene-2H-azirines,
€
€
see: Banert, K.; Hagedorn, M.; Knozinger, E.; Becker, A.; Wurthwein, E.-U. J. Am.
25. (a) Carter, R. E.; Drakenberg, T.; Bergman, N.-A. J. Am. Chem. Soc. 1975, 97,
ꢀ
Chem. Soc. 1994, 116, 60e62.
6990e6996; (b) Siebrand, W.; Smedarchina, Z.; Zgierski, M. Z.; Fernandez-Ra-
20. For the nitrogen inversion process of aziridines, see: (a) Martino, R.; Lopez, A.;
mos, A. Int. Rev. Phys. Chem. 1999, 18, 5e41; (c) Ley, D.; Gerbig, D.; Wagner, J. P.;
Reisenauer, H. P.; Schreiner, P. R. J. Am. Chem. Soc. 2011, 133, 13614e13621; (d)
Patureau, F. W. Angew. Chem. 2012, 124, 4866e4868; Angew. Chem., Int. Ed.
2012, 51, 4784e4786.
€
Lattes, A. Org. Magn. Reson. 1976, 8, 332e344; (b) Hofner, D.; Tamir, I.; Binsch, G.
Org. Magn. Reson. 1978, 11, 172e178; (c) Majchrzak, M. W.; Kote1ko, A.; Lambert,
J. B. Org. Magn. Reson. 1983, 21, 539e543; (d) Borchardt, D. B.; Bauer, S. H. J.
Chem. Phys. 1986, 85, 4980e4988; (e) Nielsen, I. M. B. J. Phys. Chem. A 1998, 102,
€
€
26. Keicher, T.; Lobbecke, S. In Organic Azides: Syntheses and Applications; Brase, S.,
Banert, K., Eds.; Wiley: Chichester, UK, 2010; pp 3e27.
€
3193e3201; (f) Rademacher, P.; Wurthwein, E.-U. J. Mol. Struct.: THEOCHEM