New way to methylene-2H-azirines and their use as powerful intermediates for the stereo- and regioselective synthesis of compounds with vinylamine substructure

Article abstract of DOI:10.1002/ejoc.200600302

New and relatively stable methylene-2H-azirines 1 have been prepared by photolysis of allenyl azides or from 2-halo-2H-azirines by elimination of HX (X = halogen). The reaction of these methylene-2H-azirines with nucleophiles led to the highly stereo- and

Full text of DOI:10.1002/ejoc.200600302

FULL PAPER
DOI: 10.1002/ejoc.200600302
New Way to Methylene-2H-azirines and Their Use as Powerful Intermediates
for the Stereo- and Regioselective Synthesis of Compounds with Vinylamine
Substructure[‡]
Joseph Rodolph Fotsing[a] and Klaus Banert*[a]
Keywords: Heterocycles / 1-Aminovinyl derivatives / Elimination / Ring opening / Nucleophilic addition
New and relatively stable methylene-2H-azirines 1 have
been prepared by photolysis of allenyl azides or from 2-halo-
2H-azirines by elimination of HX (X = halogen). The reaction
of these methylene-2H-azirines with nucleophiles led to the
highly stereo- and regio-selective formation of novel 1-ami-
novinyl derivatives with good to excellent yields. The trap-
ping reactions of the less stable methylene-2H-azirines gave
rise to similar results. Moreover, we were able to prove that
the previous report on 2-(phenylsulfonyl)acrylonitrile (9) was
based on incorrect data. For this reason, the latter compound
can be supposed to be firstly described in this paper.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2006)
is rather short (less than one hour for solutions at room
temperature). Therefore, our first challenge was to find out
how the stability of methylene-2H-azirines can be im-
proved. It is well known that compounds like cyclopro-
penones 2,[11–13] cyclopropenthiones 3,[11a,13] cyclopropen-
imines 4,[14] and methylenecyclopropenes 5,[12,15] which are
structurally similar to methylene-2H-azirines, can be stabi-
lized by donor substituents R1 and R2 at the cyclopropene
ring. Noteworthy, the stability of methylenecyclopropenes 5
can be improved by the introduction of donor substituents
R1 and R2 at the ring and acceptor substituents R3 and R4
at the methylene terminus.[16] Therefore, we assumed that
the introduction of both the acceptor substituents at the
methylene group and a donor substituent at the azirine ring
of the title compounds 1 might also increase their lifetime.
In this context, we describe here the generation and charac-
terization of some methylene-2H-azirines with improved
stabilities using a new, simple, and inexpensive method.
Moreover, the conversion of the latter compounds by nu-
cleophiles and the analogous trapping reactions of the less
stable azatriafulvenes 1 to form their 1-aminovinyl deriva-
tives are reported. In fact, due to their presence in a range
of naturally occurring compounds and synthetic biological
Introduction
2-Methylene-2H-azirines 1 form a long-sought[1–3] com-
pound class which was unknown[4–6] until 1990 when the
first examples were generated in our group by photolysis of
allenyl azides.[7,8] Thereby, the difficult access to consider-
able amounts of these first heterocyclic triafulvenes was at-
tributed to their thermal and photochemical sensitivity as
well as the difficult handling of the allenyl azides which
served as precursors. Fortunately, we recently developed a
new synthetic strategy that allows us to isolate some rela-
tively stable allenyl azides.[9] The photochemical transfor-
mation of the latter compounds is described in this paper.
Another method for the generation of methylene-2H-azir-
ines based on matrix photolysis of 1,3-diazidophenyl deriv-
atives, monitored by IR spectroscopy, has been reported by
Tomioka and co-workers in 2003.[10] However, the esti-
mated yields of the methylene-2H-azirines formed by this
method were very low (Ͻ10%).
In both methods mentioned above, the stability of the
obtained methylene-2H-azirines
1 proved to depend
strongly on the electronic nature of the substituent R1 at
the 3-position (Scheme 1). Thus, methylene-2H-azirines
with R1 = H are extremely unstable whereas those with R1
= ERG (ERG = electron releasing group) show better sta-
bilities. Nevertheless, the lifetime of the latter compounds
[‡] Reactions of Unsaturated Azides, 21. Part 20: K. Banert, S.
Grimme, R. Herges, K. Heß, F. Köhler, C. Mück-Lichtenfeld,
E.-U. Würthwein, Chem. Eur. J., manuscript accepted.
[a] Chemnitz University of Technology, Institute of Chemistry,
Organic Chemistry,
Strasse der Nationen 62, 09111 Chemnitz, Germany
Fax: +49-371-531-1839
E-mail: klaus.banert@chemie.tu-chemnitz.de
Scheme 1.
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J. R. Fotsing, K. Banert
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active ones, compounds with the title substructure, such as
α,β-dehydro amino acids and α,β-dehydro amino acid es-
ters,[17] peptides,[17f,18] and α,β-dehydro amino ketones,[19]
have received increased attention in the last decades.
Results and Discussion
Methylene-2H-azirines from Allenyl Azides
Photolysis of solutions of the recently synthesized allenyl
azides 6[9a] and 10[9a] in CD2Cl2 at –80 °C affords the
acrylonitrile derivatives 9 (56%) and 13[20] (E/Z, 17%),
respectively, instead of the expected methylene-2H-azirines
(Scheme 2). Compound 9 is also obtained by photolysis of
6 in CDCl3 at –55 °C or by the thermal decomposition of
6. The formations of 9 and 13 probably proceed via the
short-lived cumulenes 7, 8 and 11, 12, respectively. Analo-
gous intermediates were reported earlier.[21] However, in the
case of 7 and 11, direct 1,2-migration of the sulfonyl group
or the hydrogen atom, respectively, can also explain the for-
mation of the products 9 and 13.
Scheme 3.
In order to prove the structure of 9 generated from 6
(Scheme 2), 2-(phenylsulfanyl)acrylonitrile (17)[23] was
treated with two equivalents of m-chloroperbenzoic acid
(m-CPBA, Scheme 3). This reaction afforded a mixture of
1
compounds none of which gave rise to a H NMR signal
attributable to 9. When using three equivalents of m-CPBA,
only the oxirane 18 was identified. Fortunately, the Diels–
Alder reaction of 17 and cyclopentadiene forming 19[24] fol-
lowed by oxidation of the latter compound to produce 20
and its subsequent flash vacuum pyrolysis led to the desired
product 9 by retro-Diels–Alder reaction. However, the yield
of 9 was low (ca. 5%) since renewed [4+2] cycloaddition of
9 and cyclopentadiene could not be suppressed completely
even at low temperature because of the high reactivity of
both compounds. Our spectroscopic data of 9 and espe-
1
cially the H NMR spectroscopic data are compatible with
the structure of this acceptor-substituted alkene in contrast
to the data published by Bazavova[22] and co-workers.
Contrary to the photolysis of 6 and 10, irradiation of
21[9a] yielded a product mixture including the desired het-
1
erocycles E/Z-22 which were identified by their H NMR
Scheme 2.
spectroscopic data (14% yield based on 1H NMR,
Scheme 4). In fact, the observation of 22 is the consequence
According to Bazavova and co-workers,[22] compound 9 of its better stabilization, which can be rationalized as pos-
can also be obtained from the reaction of (phenylsulfonyl)- tulated in the introductive part and explained with the help
acetonitrile (14), piperidine, and paraformaldehyde via the of the mesomeric form 22Ј in consideration of the methyl
1
Mannich base 15 (Scheme 3). However, the H NMR spec- group (donor) at 3-position and the phenylsulfonyl group
troscopic data published for 9 (δ = 4.11 and 4.99 for the (acceptor) at the methylene terminus. In addition to 22, sig-
signals of the olefinic hydrogen atoms) were not compatible nals ascribable to (phenylsulfonyl)acetylene (23)[25] (6%)
with the structure of such acceptor substituted alkenes. and acetonitrile (24) (6%) were also detected in the product
Moreover, performing the reaction by analogy with the re- mixture. The formation of 23 and 24 can be rationalized by
ported procedure gave rise to 16 (Ͼ95% based on 14) in- the well-known photochemical fragmentation of methylene-
stead of 15.
2H-azirines.[7]
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New Way to Methylene-2H-azirines
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Scheme 4.
Although electron-withdrawing groups are necessary for
a better stabilization of both azido allenes[9] and methylene-
2H-azirines, the low yield of 22 generated by the photolysis
of the allenyl azide 21 and the non-formation of methylene-
2H-azirines by the photolysis of 6 and 10 provide an evi-
dence that compounds of type 1 bearing strong acceptor
substituents at the methylene terminus can undergo rapid
reactions if compared to other methylene-2H-azirines de-
scribed in the literature.[7,8]
Scheme 5. Generation of methylene-2H-azirines and subsequent re-
actions with nucleophiles.
Methylene-2H-azirines from 2-Halo-2H-azirines
In order to find an appropriate method for the pro- thesis of the ketones Z-29, Z-30, the imines 31, Z,Z-32, and
duction of stable methylene-2H-azirines, dry CDCl3 solu- the acetals Z-33, Z-34 by direct trapping of the produced
tions of the recently synthesized 2-bromo-2H-azirines 25[26] methylene-2H-azirines gave rise to similar results and over-
and 26[26] were treated with dry Et3N at room temperature all yields in the range of 85–96% (Scheme 6).
under nitrogen atmosphere (Scheme 5). The reaction was
When the 2-halo-2H-azirines 35,[26] 36,[26] 37,[26] and
1
monitored by H NMR spectroscopy. The formation of the 38[26] were treated with dry Et3N at room temperature un-
desired methylene-2H-azirines 27 (only one stereoisomer, der the conditions mentioned above, no signals of the corre-
50% yield based on 1H NMR) and E/Z-28 (75% yield sponding methylene-2H-azirines 39, 40, and 41 could be ob-
1
based on H NMR, ratio of isomers = 1:15) from 25 and served (Scheme 6). This was ascribed to the low kinetically
26, respectively, was observed. Compounds 27 and 28 could stabilizing character of the donor substituents at C-3 and
be detected in CDCl3 solutions at room temperature for 2 the relatively high reaction temperatures. However, per-
and 36 hours, respectively. Hitherto, the maximal lifetime forming the reactions at lower temperatures led only to
observed for a methylene-2H-azirine was one hour at room complex mixtures. Fortunately, the one-pot trapping reac-
temperature. At –18 °C, 28 could be conserved for several tions of compounds 39, 40, and 41 with water, p-anisidine
weeks without any remarkable decomposition. The stabiliz- or methanol as nucleophiles afforded the corresponding 1-
ing character of the bulky tert-butyl group in 28, which has aminovinyl ketones Z-42, Z-43, and Z-44, 3-amino-1-aza-
an +I effect accompanied with a strong kinetically stabiliz- buta-1,3-dienes E,Z-45, E,Z-46, and E,Z-47 as well as 2-
ing mode, is clearly more effective than that of the phenyl aminoacrolein acetal Z-48, respectively, with very good
group in 27. However, despite their relative long lifetime, 27 yields. Compound Z-44 had already been synthesized using
and 28 could not be isolated. This was attributed to their another method,[28] however, without any report on the
rapid succeeding reactions in contact with silica gel and the NMR spectroscopic data and the stereocontrol. Using the
difficulties on attempts of crystallization from the product one-pot procedure described above, the nucleophiles at-
mixtures.
tacked in the same way as in the two-step procedure selec-
The methylene-2H-azirines 27 and E/Z-28 proved to be tively at C-3 of the intermediate methylene-2H-azirine, and
powerful electrophiles. In fact, their treatment with water, the products were formed with complete stereoselectivity.
p-anisidine, and methanol led to the corresponding addition In all cases, the configuration of the vinylamine substruc-
reactions with subsequent ring-opening to form 1-amino- ture was proved to be Z whereas that of the imine double
vinyl ketones Z-29[27] and Z-30, 3-amino-1-azabuta-1,3- bond was found to depend on the steric interactions with
dienes 31 and Z,Z-32 as well as 2-aminoacrolein acetals Z- the substituent R1. For the bulky tert-butyl group, a Z con-
33 and Z-34, respectively, with very good yields (Scheme 5). figuration was found whereas the E configuration was
These reactions took place with complete site selectivity at adopted for R1 = methyl or n-pentyl. Except for Z-29, for
C-3. Except for 31, which was obtained as mixture of iso- which the stereochemistry was assigned by X-ray crystal
mers (ratio of isomers = 1:14, unknown assignment), only structure analysis,[27] the configurational assignments of all
one stereoisomer was formed in each case. The one-pot syn- compounds were supported by 1H NMR NOE experiments.
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J. R. Fotsing, K. Banert
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Scheme 6. One-pot synthesis of ketones, imines, and acetals including trapping of methylene-2H-azirines. [a] Yield of isolated compound.
[b] Mixture of isomers.
Both the generation of methylene-2H-azirines from 2-
halo-2H-azirines and the subsequent nucleophilic transfor-
mation into 1-aminovinyl derivatives by two-step or one-
pot procedures are new chemical transformations. Al-
though the nature of the halogen do not influence the yield
of the final product in the one-pot procedures, as shown for
43 and 46 (Scheme 6), it might be significantly relevant in
the two-step pathway because the elimination of HCl in the
first step to produce the short-lived methylene-2H-azirine is
relatively difficult, taking longer time, if compared to that
of HBr.
Scheme 7.
Mechanistic Aspects for the Formation of 1-Aminovinyl
Derivatives
For the reactions of nucleophiles with methylene-2H-
azirines, previous work in our group had predicted the re-
gioselective attack of the nucleophile at C-3 (Scheme 7).[8]
However, the only known example of such reactions (49 Ǟ
50)[7] afforded exclusively a normal 2H-azirine as product
of simple 1,4-addition.
The formation of the ring-opening products described in
this paper can be explained by the direct formation of inter-
mediates of type 54 from 52 or by the formation of the
azirines of type 53 and their rapid prototropic isomeriza-
tion[29] into 54 followed by ring opening to the thermody-
namically more stable final products of type 55 (Scheme 8).
The isomerization of 53 into 54 could be facilitated by
Scheme 8. Mechanism of the reaction of binucleophiles with meth-
the acceptor substituent (EWG), which increased the acid- ylene-2H-azirines.
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New Way to Methylene-2H-azirines
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(Elementar Analysensystem GmbH) was employed. Mariner 5229
from Applied Biosystems was used for mass spectra. The method
applied was the electrospray ionization.
ity of the α-EWG hydrogen. As far as the stereochemistry
is concerned, the highly favorable Z configuration might be
adopted via an enamine-imine tautomerism. In the case of
the formation of the acetals, NuH2 is replaced by two mole-
cules of methanol, and the reaction with 52 might produce
an intermediate of type 57, which is attacked by a second
molecule of methanol. The sequence is finished by the
above-mentioned enamine-imine tautomerism to afford the
final acetals Z-58 (Scheme 9).
The photolyses were performed with a 150-W Hg high-pressure
lamp (polychromatic) TQ 150 from Heraeus GmbH. Quartz equip-
ment was used for cooling the lamp with the help of an ethanol
cryostat (Lauda GmbH). Solutions of the substrates in normal
NMR sample tubes were cooled in the same way while being irradi-
ated. In order to get good yields of the 2H-azirines by preventing
succeeding photochemical reactions, solutions in CDCl3, which
1
function as UV filter, were used. Monitoring the photolyses by H
NMR spectroscopy means that spectra were recorded at low tem-
perature, e.g. –50 °C, after a definite time of irradiation at the same
temperature.
The known compounds 6,[9a] 10,[9a] 17,[23] 19,[24] 21,[9a] 25,[26] 26,[26]
and (35–38)[26] were synthesized according to the literature.
2-(Phenylsulfonyl)acrylonitrile (9): The allenyl azide 6[9a] (25.0 mg,
113 µmol) in CD2Cl2 (0.5 mL) was irradiated at –80 °C. The reac-
tion was monitored by 1H NMR spectroscopy at –50 °C. After 2 h,
the formation of 9 was observed with 56% yield based on 1H NMR
spectroscopy. Photolysis of 6 in CDCl3 at –55 °C led to similar
result. The formation of 9 was also observed during the thermal
decomposition of compound 6 at room temperature. Neat 9 poly-
merizes rapidly at room temperature. The assignments of the NMR
signals of 9 was performed with the help of 13C,1H NMR corre-
Scheme 9. Mechanism of the reaction of methanol with methylene-
2H-azirines.
lation spectroscopy. IR (CDCl ): ν = 1334 cm–1 (SO2), 1154 (SO2).
˜
3
2
1H NMR (CDCl3): δ = 6.71 (d, J = 1.1 Hz, 1 H, H2C=), 7.12 (d,
Conclusions
2J = 1.1 Hz, 1 H, H2C=), 7.62 (m, 3 H), 7.98 (m, 2 H, o-Ph).
The chemical shifts of the signals assigned to the olefinic protons
correspond well with δ values calculated using an empirical system
of increments[31] (δ = 6.93, 6.96). 13C NMR (CDCl3): δ = 111.7 (s,
C-1), 128.1 (s, C-2), 129.9 (d, 2 C), 129.8 (d, 2 C), 135.2 (d, p-Ph),
136.4 (s, i-Ph), 139.6 (t, C-3).
A new, simple, and efficient approach towards methyl-
ene-2H-azirines was developed. Some of these strained het-
erocycles proved to possess relatively high stabilities. The
latter compounds could be regio- and stereoselectively con-
verted to 1-aminovinyl derivatives with very good yields.
Both the generation and the transfer of methylene-2H-azir-
ines to 1-aminovinyl derivatives were combined in a one-
pot procedure starting from 2-halo-2H-azirines to afford
products with similar regio- and stereoselectivities and also
with high yields. Using the one-pot synthesis strategy, less
stable methylene-2H-azirines could be generated and
trapped directly with nucleophiles to form the correspond-
ing 1-aminovinyl derivatives likewise with high regio- and
stereoselectivities and very good yields. The synthesis of 1-
aminovinyl ketones and the analogous imines described in
this paper represents new aspects of the azirine chemistry.
3-(Phenylsulfinyl)acrylonitrile (E/Z-13): The allene 10[9a] (20.0 mg,
97.6 µmol) in CD2Cl2 (0.5 mL) was irradiated at –80 °C. The reac-
tion was monitored by 1H NMR spectroscopy at –50 °C. After
90 min, the formation of E/Z-13[20] was observed with a combined
1
yield of 17% based on H NMR spectroscopy. For E-13, only one
3
signal at δ = 6.41 (d, J = 15.0 Hz, 1 H) was clearly identified in
the 1H NMR spectrum of the reaction mixture whereas two signals
3
3
at δ = 5.89 (d, J = 10.3 Hz, 1 H) and 7.12 (d, J = 10.3 Hz, 1 H)
were identifiable for Z-13.
2-(Phenylsulfonyl)-1,3-dipiperidinopropane-2-carbonitrile
(16):
Treatment of the mixture of (phenylsulfonyl)acetonitrile 14 (6.13 g,
33.9 mmol), piperidine (32 mL) and 4.00 g of paraformaldehyde
[(CH2O)n] by analogy with the literature[22] led to 16 (12.07 g,
32.2 mmol, 95%), instead of 15 as reported by the authors. Com-
pound 16 was obtained as white solid, m.p. 86–88 °C (n-hexane).
1H NMR (CDCl3): δ = 1.33 (m, 4 H, NCH2CH2CH2), 1.39 (m, 8
H, NCH2CH2), 2.52 (br. t, J = 4.5 Hz, 8 H, NCH2CH2), 2.94 (d,
Experimental Section
1
General Remarks: H and 13C NMR spectra were recorded at 300
and 75 MHz, respectively, in CDCl3, unless otherwise noted.
Chemical shifts (δ) are reported in parts per million (ppm) down-
field from TMS. Coupling constants (J) are reported in Hertz (Hz)
and spin multiplicities are indicated by the following symbols: s
(singlet), d (doublet), t (triplet), q (quartet), m (multiplet). Assign-
ments of configuration were supported by homonuclear NOE ex-
periments except for 29[27] for which the configuration was ascer-
tained by X-ray crystal structure analysis. Infrared spectra were
recorded as solutions in CDCl3. TLC was performed on Macherey–
Nagel precoated silica gel Polygram Sil G/UV254 plates and viewed
by UV. Chromatography refers to flash chromatography,[30] carried
out on Fluka silica gel 60. For the elemental analyses, Vario El
2
2J = 14.1 Hz, 2 H, CH2CS), 3.04 (d, J = 14.1 Hz, 2 H, CH2CS),
7.57 (m, 2 H, m-Ph), 7.70 (m, 1 H, p-Ph), 8.05 (m, 2 H, o-Ph). 13C
NMR (CDCl3): δ = 23.7 (t, 2 C, NCH2CH2CH2), 25.9 (t, 4 C,
NCH2CH2), 55.8 (t, 4 C, NCH2CH2), 59.0 (t, 2 C, CH2CS), 67.3
(s, C-2), 117.6 (CN), 128.7 (d, 2 C), 130.5 (d, 2 C), 134.4 (d, p-
Ph), 136.9 (s, i-Ph). MS (ESI); m/z: 376.20 [M+H+]. C20H29N3O2S
(375.53): calcd. C 63.97, H 7.78, N 11.19, S 8.52; found C 63.70,
H 7.46, N 11.17, S 8.24.
1-(Phenylsulfonyl)oxirane-1-carbonitrile (18): Compound 17[23]
(600 mg, 3.73 mmol) in CH2Cl2 (15 mL) was treated dropwise at
0 °C with a solution of 70% m-CPBA (3.00 g, 12.15 mmol, remain-
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J. R. Fotsing, K. Banert
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der 3-chlorobenzoic acid) in CH2Cl2 (15 mL) and then allowed to
stay overnight at 6 °C. The reaction mixture was diluted with
CH2Cl2, washed three times with a saturated aqueous solution of
Na2CO3 and dried with MgSO4. The solvent was then removed,
and the residue was chromatographed on silica gel with Et2O/n-
hexane (1:1) to give 18 (450 mg, 2.15 mmol, 58%) as white solid,
3-Phenyl-2-[(phenylsulfonyl)methylene]-2H-azirine (27): Compound
25[26] (80 mg, 229 µmol) was dried for several hours at 10–3 Torr
and dissolved under nitrogen atmosphere in dry CDCl3 (0.6 mL).
The solution was treated in a NMR tube with 40 µL dry Et3N.
The reaction was monitored by 1H NMR, while the mixture was
occasionally shaken up. The complete transformation of the start-
1
2
m.p. 59–60 °C (Et2O/n-hexane). H NMR (CDCl3): δ = 3.57 (d, J ing material could be observed after 10 min. At that moment, the
2
= 5.7 Hz, 1 H, CH2), 3.86 (d, J = 5.7 Hz, 1 H, CH2), 7.69 (m, 2
desired product 27 (only one stereoisomer) was detected with 50%
H, m-Ph), 7.82 (m, 1 H, p-Ph), 8.02 (m, 2 H, o-Ph). 13C NMR yield based on 1H NMR spectroscopy. This compound 27 was
(CDCl3): δ = 52.1 (t, C-2), 60.0 (s, C-1), 112.0 (s, CN), 129.8 (d, 2 stable to be observed for ca. 2 h at room temperature, but it could
C), 129.9 (d, 2 C), 133.9 (s, i-Ph), 136.0 (d, p-Ph). C9H7NO3S
(209.22): calcd. C 51.67, H 3.37, N 6.69, S 15.33; found C 51.56,
H 3.38, N 6.51, S 15.40.
not be isolated due to the rapid decomposition on silica gel. IR
(CDCl , mixture): ν = 1869 cm–1 (C=N), 1309 (SO2), 1145 (SO2).
˜
3
1H NMR (CDCl3): δ = 5.94 (s, 1 H, HC–SO2), 7.35–7.86 (m, 8 H),
8.52 (m, 2 H). 13C NMR (CDCl3): δ = 87.8 (d, HC–SO2), 120.4 (s,
i-Ph at C-3), 126.5 (d, 2 C), 128.9 (d, 2 C), 129.7 (d, 2 C), 132.4
(d), 132.4 (d, 2 C), 137.0 (d), 143.1 (s), 143.7 (s) 180.4 (s, C-3).
2-(Phenylsulfonyl)bicyclo[2.2.1]hept-5-ene-2-carbonitrile (20): The
mixture endo/exo-19[24] (1.00 g, 4.41 mmol) was treated with two
equivalents of m-CPBA under similar reaction conditions as de-
scribed for 18. The reaction mixture was then chromatographed
over silica gel with Et2O/n-hexane (1:1) to give exo/endo-20
(690 mg, 2.66 mmol, 61%) as white solid, m.p. 110–113 °C (Et2O/
n-hexane, 7:4 mixture). C14H13NO2S (259.32): calcd. C 64.84, H
5.05, N 5.40, S 12.37; found C 64.20, H 5.09, N 5.22, S 12.60.
E/Z-3-tert-Butyl-2-[(phenylsulfonyl)methylene]-2H-azirine (E/Z-28):
Under similar conditions as described for 27, compound 26[26]
(40 mg, 229 µmol) was treated with 1.5 equivalents of Et3N to give
E/Z-28 with 75% yield based on 1H NMR, ratio of isomers = 1:15.
IR (CDCl , mixture): ν = 1868 cm–1 (C=N), 1314 (SO2), 1145
˜
3
(SO2).
Minor Isomer: 1H NMR (CDCl3): δ = 1.50–3.50 (m, 6 H), 6.24 (m,
1 H), 6.49 (m, 1 H), 7.13 (m, 2 H, m-Ph), 7.73 (m, 1 H, p-Ph), 8.04
(m, 2 H, o-Ph). 13C NMR (CDCl3): δ = 36.9 (t), 42.4 (d), 46.1 (t),
50.0 (d), 67.0 (s, C-2), 118.7 (s, CN), 129.6 (d, 2 C), 130.4 (d), 134.9
(d), 135.6 (s, i-Ph), 139.1 (d), 142.4 (d).
1
Minor Isomer: H NMR (CDCl3): δ = 1.28 (s, 9 H, H3C), 5.74 (s,
1 H, HC–SO2), 7.41 (m, 3 H, Ph), 7.86 (m, 2 H, o-Ph). 13C NMR
(CDCl3): δ = 25.1 (q, 3 C, H3C); other signals could not be de-
tected.
Major Isomer: 1H NMR (CDCl3): δ = 1.50–3.50 (m, 6 H), 6.17 (m,
1 H), 6.42 (m, 1 H), 7.13 (m, 2 H, m-Ph), 7.73 (m, 1 H, p-Ph), 7.96
(m, 2 H, o-Ph). 13C NMR (CDCl3): δ = 36.9 (t), 43.0 (d), 49.7 (t),
52.6 (d), 66.8 (s, C-2), 119.8 (s, CN), 129.3 (d, 2 C), 130.2 (d), 134.8
(d), 136.4 (s), 139.1 (d), 142.4 (d).
1
Major Isomer: H NMR (CDCl3): δ = 1.42 (s, 9 H, H3C), 5.77 (s,
1 H, HC–SO2), 7.41 (m, 3 H, Ph), 7.71 (m, 2 H, o-Ph). 13C NMR
(CDCl3): δ = 24.9 (q, 3 C, H3C), 34.6 (s, H3CC), 88.0 (d, HC–SO2),
126.1 (d, 2 C), 129.0 (d, 2 C), 132.3 (d, p-Ph), 142.8 (s), 145.8 (s)
193.4 (s, C-3).
After treating exo/endo-20 by flash vacuum pyrolysis at 550 °C and
10–5 Torr (for this technique, see ref.[32]), 9 is collected at low tem-
perature and identified by its NMR spectroscopic data, which were
identical with those of 9 generated by photolysis of 6.
Synthesis of 1-Aminovinyl Ketones Z-29, Z-30, Z-42, Z-43, and Z-
44. Two-Step Procedure: This procedure is only applicable to the
synthesis of Z-29, Z-30. Starting from 25 or 26, the methylene-2H-
azirines 27 and 28 were produced as shown above and treated with
excess of water to give after 5 min the 1-aminovinyl ketones Z-29
(97% with regard to 27) and Z-30 (95% with regard to 28), respec-
3-Methyl-2-[(phenylsulfonyl)methylene]-2H-azirine (E/Z-22): The
azido allene 21[9a] (8 mg, 34 µmol) in CDCl3 (0.5 mL) was irradi-
ated at –55 °C. The reaction was monitored by 1H NMR spec-
troscopy at –55 °C. After 45 min of irradiation, the methylene-2H-
1
tively. The yields were based on H NMR spectroscopy.
One-Pot Procedure: To a stirred emulsion of compounds 25, 26, 35,
36, 37, or 38 in a mixture of water and dichloromethane, Et3N was
added (Table 1). After stirring at room temperature for the time
given in Table 1, the reaction mixture was treated with dichloro-
methane, and the layers were separated. The aqueous phase was
extracted several times with small amount of dichloromethane. The
combined organic layers were dried with MgSO4 and chromato-
graphed on silica gel with Et2O/n-hexane to give the 1-aminovinyl
ketones Z-29, Z-30, Z-42, Z-43, and Z-44,[28] respectively.
1
azirines E/Z-22 were obtained in ca. 14% yield based on H NMR
(ratio of products: 3:2). (Phenylsulfonyl)acetylene (23),[25] acetoni-
trile (24), and the unreacted starting material were also observed
in the products mixture in each case with ca. 6% yield based on
1H NMR spectroscopy. The 13C NMR spectroscopic data of the
desired methylene-2H-azirines E/Z-22 could not be obtained.
1
Minor Isomer: H NMR (CDCl3, –55 °C): δ = 2.65 (s, 3 H, H3C),
5.88 (s, 1 H, HC–SO2), 7.90–8.60 (m, 5 H, Ph).
1
Major Isomer: H NMR (CDCl3, –55 °C): δ = 2.96 (s, 3 H, H3C), (Z)-2-Amino-1-phenyl-3-(phenylsulfonyl)prop-2-en-1-one
(Z-29):
5.90 (s, 1 H, HC–SO2), 7.90–8.60 (m, 5 H, Ph).
Yellow crystals (crystallization at –18 °C), m.p. 137–138 °C (ace-
Table 1. One-pot synthesis of 1-aminovinyl ketones.
Starting material
(mmol)
CH2Cl2/H2O
(mL/mL)
Et3N
(mmol)
Time
(min)
Et2O/n-hexane
Product
Yield[a]
(%)
(mmol)
25
26
35
36
37
38
0.428
0.454
0.581
0.410
0.410
0.661
5:1
1.287
0.891
1.089
1.188
1.188
1.287
60
60
40
50
60
45
1:1
2:3
1:4
1:1
1:1
1:2
Z-29
Z-30
Z-42
Z-43
Z-43
Z-44
0.334
0.378
0.505
0.346
0.346
0.496
78
83
87
85
85
75
1:0.5
1:0.5
5:1
5:1
2:0.5
[a] Yield of isolated product.
3622
www.eurjoc.org
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2006, 3617–3625

New Way to Methylene-2H-azirines
FULL PAPER
tone/Et O). IR (CDCl ): ν = 3492 cm–1 (NH), 3376 (NH), 1676
(C=O), 1610 (NH), 1304 (SO2), 1140 (SO2). H NMR (CDCl3): δ
applicable for the synthesis of 31 and Z,Z-32. Starting from 25 and
26, the methylene-2H-azirines 27 and 28 were produced as shown
˜
2
3
1
= 5.34 (s, 1 H, H-3), ca. 6.20 (br. s, 2 H, NH2), 7.40–7.61 (m, 6 H), above and treated with an excess of dry p-anisidine to give after
7.72 (m, 2 H), 7.91 (m, 2 H). 13C NMR (CDCl3): δ = 101.6 (d, C-
about 10 min the imines 31 (mixture) and Z,Z-32 both with 98%
3), 126.3 (d, 2 C), 128.6 (d, 2 C), 129.2 (d, 2 C), 129.7 (d, 2 C), yield based on H NMR and calculated with regard to the respec-
1
133.2 (d), 133.6 (d), 134.6 (s), 143.0 (s), 147.3 (s, C-2), 191.8 (s, C-
1). C15H13NO3S (287.33): calcd. C 62.70, H 4.56, N 4.87, S 11.16;
found C 62.39, H 4.61, N 4.79, S 11.63. The stereochemistry was
determined by X-ray structure analysis.[27]
tive methylene-2H-azirines 27 and 28.
One-Pot Procedure: To a stirred solution of compounds 25, 26, 35,
36, 37, or 38 in dry dichloromethane, dry p-anisidine and Et3N
were added successively (Table 2). After stirring at room tempera-
ture for the time given in Table 2, the reaction mixture was concen-
trated, and the residue was filtered through silica gel with Et2O.
Solvent was removed from the filtrate to give a solid, which was
washed three times with small amounts of Et2O. In some cases,
purification on silica gel with Et2O or Et2O/n-hexane was neces-
sary. The corresponding imine derivatives 31 (ratio of isomers =
1:14), Z,Z-32, E,Z-45, E,Z-46, and E,Z-47 were obtained, respec-
tively.
(Z)-2-Amino-4,4-dimethyl-1-(phenylsulfonyl)pent-1-en-3-one (Z-30):
White Powder, m.p. 108–110 °C (Et O/n-hexane). IR (CDCl ): ν =
˜
2
3
3489 cm–1 (NH), 3371 (NH), 1695 (C=O), 1610 (NH), 1301 (SO2),
1
1138 (SO2). H NMR (CDCl3): δ = 1.24 (s, 9 H, H3C), 5.39 (s, 1
H, H-1), 6.03 (br. s, 2 H, NH2), 7.55 (m, 3 H), 7.90 (m, 2 H, o-Ph).
13C NMR (CDCl3): δ = 27.7 (q, 3 C, H3C), 44.0 (s, C-4), 96.0 (d,
C-1), 126.0 (d, 2 C), 129.1 (d, 2 C), 132.9 (d, p-Ph), 143.3 (s, i-Ph),
148.0 (s, C-2), 203.2 (s, C-3). C13H17NO3S (264.34): calcd. C 58.40,
H 6.41, N 5.24, S 11.99; found C 58.45, H 6.18, N 5.16, S 12.02.
3-Amino-1-(4-methoxyphenyl)-2-phenyl-4-(phenylsulfonyl)-1-aza-
(Z)-2-Amino-1-(phenylsulfonyl)oct-1-en-3-one (Z-42): White pow-
buta-1,3-diene (31): Yellow solid (Et2O, mixture). IR (CDCl3, mix-
der, m.p. 69–71 °C (Et O/n-hexane). IR (CDCl ): ν = 3491 cm–1
ture): ν = 3479 cm–1 (NH), 3362 (NH), 1600 (NH), 1300 (SO2),
˜
2
3
˜
(NH), 3376 (NH), 1704 (C=O), 1613 (NH), 1304 (SO2), 1139 (SO2).
1137 (SO2). C22H20N2O3S (392.47): calcd. C 67.33, H 5.14, N 7.14,
S 8.17; found C 66.84, H 5.12, N 7.12, S 8.71.
3
1H NMR (CDCl3): δ = 0.84 (t, J = 7.2 Hz, 3 H, H-8), 1.25 (m, 4
H), 1.57 (quint, J = 7.5 Hz, 2 H), 2.61 (t, J = 7.5 Hz, 2 H, H-4),
5.61 (s, 1 H, H-1), ca. 6.10 (br. s, 2 H, NH2), 7.56 (m, 3 H, Ph),
7.91 (m, 2 H, o-Ph). 13C NMR (CDCl3): δ = 13.8 (q, C-8), 22.3 (t),
23.5 (t), 31.0 (t), 36.8 (t, C-4), 97.7 (d, C-1), 126.3 (d, 2 C), 129.2
(d, 2 C), 133.1 (d, p-Ph), 142.9 (s, i-Ph), 146.1 (s, C-2), 196.2 (s, C-
3). C14H19NO3S (281.37): calcd. C 59.76, H 6.80, N 4.98, S 11.39;
found C 59.25, H 6.96, N 4.97, S 11.23.
Minor Isomer: 1H NMR (CDCl3): δ = 3.77 (s, 3 H, H3CO), 4.76
(s, 1 H, H-4), 6.58 (d, J = 9.0 Hz, 2 H), 6.65 (d, J = 9.0 Hz, 2 H),
7.01 (m, 2 H, o-Ph at C-2) 7.27 (m, 3 H), 7.52 (m, 3 H), 7.89 (m,
2 H, o-Ph–SO2). The 13C NMR signals of this isomer could not be
observed.
Major Isomer: 1H NMR (CDCl3): δ = 3.70 (s, 3 H, H3CO), 4.96
(s, 1 H, H-4), 6.58 (d, J = 9.0 Hz, 2 H), 6.65 (d, J = 9.0 Hz, 2 H),
7.01 (m, 2 H, o-Ph at C-2), 7.27 (m, 3 H), 7.52 (m, 3 H), 7.89 (m,
2 H, o-Ph–SO2). The 1H NMR signal of NH2 could not be de-
tected. 13C NMR (CDCl3): δ = 55.3 (q, H3C), 99.5 (C-4), 113.7 (d,
2 C), 123.4 (d, 2 C), 126.1 (d, 2 C), 128.4 (d, 2 C), 129.0 (d, 2 C),
129.1 (d, 2 C), 129.3 (d), 132.6 (d), 132.9 (s), 141.0 (s), 143.7 (s),
151.0 (s), 157.2 (s), 160.7 (s).
(Z)-3-Amino-4-(phenylsulfonyl)but-3-en-2-one (Z-43): Yellow solid,
m.p. 73–75 °C (Et O/n-hexane). IR (CDCl ): ν = 3492 cm–1 (NH),
˜
2
3
1
3376 (NH), 1706 (C=O), 1614 (NH), 1305 (SO2), 1139 (SO2). H
NMR (CDCl3): δ = 2.33 (s, 3 H, H3C), 5.61 (s, 1 H, H-4), ca. 6.20
(br. s, 2 H, NH2), 7.53 (m, 2 H, m-Ph), 7.61 (m, 1 H, p-Ph), 7.92
(m, 2 H, o-Ph). 13C NMR (CDCl3): δ = 24.8 (q, H3C), 98.7 (d, C-
4), 126.3 (d, 2 C), 129.2 (d, 2 C), 133.2 (d, p-Ph), 142.8 (s), 146.1
(s), 193.7 (s, C-2). C10H11NO3S (225.26): calcd. C 53.32, H 4.92, N
6.22, S 14.23; found C 53.32, H 4.98, N 6.14, S 14.13.
(1Z,3Z)-3-Amino-2-(tert-butyl)-1-(4-methoxyphenyl)-4-(phenylsulfo-
nyl)-1-azabuta-1,3-diene (Z,Z-32): Yellow solid, m.p. 140–142 °C
(Et O). IR (CDCl ): ν = 3506 cm–1 (NH), 3363 (NH), 1609 (NH),
˜
(Z)-3-Amino-4-(methylsulfonyl)but-3-en-2-one (Z-44): This com-
pound 44 had already been synthesized using a different pro-
cedure.[28] However, neither the NMR spectroscopic data nor the
details on its stereochemistry were mentioned. Beige powder. IR
2
3
1295 (SO2), 1136 (SO2). 1H NMR (CDCl3): δ = 1.29 (s, 9 H,
H3CC), 3.73 (s, 3 H, H3CO), 4.49 (s, 1 H, H-4), ca. 5.80 (br. s, 2
H, NH2), 6.54 (s, 4 H), 7.36 (m, 2 H), 7.48 (m, 3 H). 13C NMR
(CDCl3): δ = 28.5 (q, 3 C, H3CC), 39.8 (s, H3CC), 55.1 (q, H3CO),
93.1 (d, C-4), 113.7 (d, 2 C), 120.0 (d, 2 C), 125.7 (d, 2 C), 128.7
(d, 2 C), 132.2 (d), 142.5 (s), 143.5 (s), 151.6 (s), 156.1 (s), 173.6
(s). C20H24N2O3S (372.48): calcd. C 64.49, H 6.49, N 7.52, S 8.61;
found C 64.15, H 6.39, N 7.47, S 8.84.
(CDCl ): ν = 3491 cm–1 (NH), 3377 (NH), 1708 (C=O), 1614 (NH),
˜
3
1307 (SO2), 1142 (SO2). 1H NMR (CDCl3): δ = 2.42 (s, 3 H,
H3CC), 3.04 (s, 3 H, H3CSO2), 5.60 (s, 1 H, H-4), ca. 6.00 (br. s, 2
H, NH2). 13C NMR (CDCl3): δ = 24.8 (q, H3CC), 44.3 (q,
H3CSO2), 97.4 (d, C-4), 146.9 (s, C-3), 193.6 (s, C-2).
Synthesis of 3-Amino-1-azabuta-1,3-dienes 31, Z,Z-32, E,Z-45,
E,Z-46, and E,Z-47. Two-Step Procedure: This procedure is only
(1E,3Z)-3-Amino-1-(4-methoxyphenyl)-2-pentyl-4-(phenylsulfonyl)-
1-azabuta-1,3-diene (E,Z-45): Yellow solid, m.p. 129–131 °C
Table 2. One-pot synthesis of 3-amino-1-azabuta-1,3-dienes.
Starting material
(mmol)
p-Anisidine
(mmol)
CH2Cl2
(mL)
Et3N
(mmol)
Time
(min)
Et2O/
Product
Yield[b]
(%)
n-hexane[a]
(mmol)
25
26
35
36
37
38
0.571
0.606
0.727
0.616
0.616
1.377
1.143
1.212
1.453
1.250
1.232
2.066
2
2
2
2
2
2
1.089
1.139
1.188
1.188
1.188
1.980
30
30
30
30
30
30
1:0
1:1
1:0
1:0
1:0
1:0
31[c]
0.487
0.462
0.697
0.586
0.585
1.263
85
76
96
95
95
92
Z,Z-32
E,Z-45
E,Z-46
E,Z-46
E,Z-47
[a] Purification by filtration through silica gel using Et2O or Et2O/n-hexane. [b] Yield of isolated product. [c] Mixture of isomers with
unknown stereochemistry.
Eur. J. Org. Chem. 2006, 3617–3625
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3623

J. R. Fotsing, K. Banert
Yield[b]
FULL PAPER
Table 3. One-pot synthesis of 2-aminoacrolein acetals.
Starting material
(mmol)
MeOH
(mL)
Et3N
(mmol)
Time
(min)
Et2O/n-hexane[a]
Product
(mmol)
(%)
25
26
38
0.229
0.364
0.386
1
1
1
0.289
0.693
0.772
30
30
30
1:0
1:1
1:0
Z-33
Z-34
Z-48
0.217
0.342
0.369
95
94
96
[a] Purification by chromatography on silica gel with Et2O or Et2O/n-hexane. [b] Yield of isolated product.
(Et O). IR (CDCl ): ν = 3476 cm–1 (NH), 3358 (NH), 1597 (NH), 3 H), 7.40–7.51 (m, 5 H), 7.80 (m, 2 H). 13C NMR (CDCl3): δ =
˜
2
3
1301 (SO2), 1137 (SO2). 1H NMR (CDCl3): δ = 0.74 (t, 3J = 6.9 Hz,
49.7 (q, 2 C, H3CO), 91.3 (d, C-2), 100.9 (s, COCH3), 125.6 (d, 2
3 H, H3CC), 1.09 (m, 4 H), 1.37 (m, 2 H), 2.32 (m, 2 H, H2CC-2),
C), 126.1 (d, 2 C), 128.3 (d, 2 C), 128.7 (d, 2 C), 128.8 (d), 132.1
3.79 (s, 3 H, H3CO), 5.41 (s, 1 H, H-4), ca. 6.60 (br. s, 2 H, NH2), (d), 138.2 (s, i-Ph), 144.5 (s, i-Ph), 157.0 (s, C-1). HRMS (ESI):
6.63 (d, J = 8.7 Hz, 2 H, H-2Ј), 6.88 (d, J = 8.7 Hz, 2 H, H-3Ј), m/z calcd. for C20H20NO4S [M+H+] 334.1110; found 334.1108.
7.54 (m, 3 H), 7.96 (m, 2 H, o-Ph–SO2). 13C NMR (CDCl3): δ =
(Z)-2,2-Dimethoxy-3,3-dimethyl-1-[(phenylsulfonyl)methylene]butyl-
13.7 (q, H3CC), 21.9 (t), 28.1 (t), 28.2 (t), 31.5 (t), 55.4 (q, H3CO),
amine (Z-34): Yellow oil. IR (CDCl ): ν = 3501 cm–1 (NH), 3373
˜
3
95.0 (d, C-4), 114.3 (d, 2 C), 120.1 (d, 2 C), 126.0 (d, 2 C), 129.0
(NH), 1612 (NH), 1290 (SO2), 1133 (SO2). 1H NMR (CDCl3): δ =
(d, 2 C), 132.6 (d), 142.1 (s), 143.8 (s), 149.6 (s), 156.6 (s), 164.4
0.89 (s, 9 H, H3CC), 3.26 (s, 6 H, H3CO), 4.87 [s, 1 H, C(H)SO2],
(s). C17H18N2O3S (386.51): calcd. C 65.26, H 6.78, N 7.25, S 8.30;
7.48 (m, 3 H, Ph), 7.87 (m, 2 H, o-Ph). The 1H NMR signal of
found C 64.92, H 6.75, N 7.22, S 8.53.
NH2 could not be detected.13C NMR (CDCl3): δ = 26.7 (q, 3 C,
(1E,3Z)-3-Amino-1-(4-methoxyphenyl)-2-methyl-4-(phenylsulfonyl)-
1-azabuta-1,3-diene (E,Z-46): Yellow solid, m.p. 128–130 °C (ace-
H3CC), 40.8 (s, C-3), 52.3 (q, H3CO), 92.2 [d, C(H)SO2], 105.6 (s,
C-2), 125.5 (d, 2 C), 128.8 (d, 2 C), 132.1 (d, p-Ph), 144.7 (s, i-Ph),
155.7 (s, C-1). HRMS (ESI): m/z calcd. for C15H24NO4S [M+H+]
314.1421; found 314.1421.
tone/Et O). IR (CDCl ): ν = 3478 cm–1 (NH), 3360 (NH), 1721
˜
2
3
1
(C=N), 1599 (NH), 1302 (SO2), 1137 (SO2). H NMR (CDCl3): δ
= 1.99 (s, 3 H, H3CC), 3.80 (s, 3 H, H3CO), 5.42 (s, 1 H, H-4), ca.
6.60 (br. s, 2 H, NH2), 6.69 (d, J = 8.7 Hz, 2 H, H-2Ј), 6.89 (d, J
= 8.7 Hz, 2 H, H-3Ј), 7.52 (m, 3 H), 7.97 (m, 2 H, o-PhSO2). 13C
NMR (CDCl3): δ = 15.4 (q, H3CC), 55.4 (q, H3CO), 95.2 (d, C-4),
114.3 (d, 2 C), 121.0 (d, 2 C), 126.2 (d, 2 C), 129.0 (d, 2 C), 132.7
(d), 141.8 (s), 143.8 (s), 150.6 (s), 157.0 (s), 159.7 (s). C17H18N2O3S
(314.40): calcd. C 61.80, H 5.49, N 8.48, S 9.71; found C 61.93 H
5.56, N 8.52, S 9.76.
(Z)-2,2-Dimethoxy-1-[(methylsulfonyl)methylene]propylamine
(Z-
48): Yellow oil. IR (CDCl ): ν = 3499 cm–1 (NH), 3376 (NH), 1620
˜
3
(NH), 1289 (SO2), 1117 (SO2). 1H NMR (CDCl3): δ = 1.45 (s, 3
H, H3CC), 2.93 (s, 3 H, H3CSO2), 3.19 (s, 6 H, H3CO), 5.03 [s, 1
H, C(H)SO2], ca. 5.80 (br. s, 2 H, NH2). 13C NMR (CDCl3): δ =
23.8 (q, H3CC), 44.6 (q, H3CSO2), 49.4 (q, 2 C, H3CO), 88.9 [d,
C(H)SO2], 100.0 (s, C-2), 158.5 (s, C-1). HRMS (ESI): m/z calcd.
for C7H16NO4S [M+H+] 210.0798; found 210.0795.
(1E,3Z)-3-Amino-1-(4-methoxyphenyl)-2-methyl-4-(methylsulfonyl)-
1-azabuta-1,3-diene (E,Z-47): Yellow solid, m.p. 151–153 °C
(Et O). IR (CDCl ): ν = 3476 cm–1 (NH), 3360 (NH), 1602 (NH),
Acknowledgments
˜
2
3
1297 (SO2), 1119 (SO2). 1H NMR (CDCl3): δ = 2.05 (s, 3 H,
H3CC), 3.05 (s, 3 H, H3CSO2), 3.81 (s, 3 H, H3CO), 5.40 (s, 1 H,
H-4), 6.44 (br. s, 2 H, NH2), 6.72 (d, J = 8.7 Hz, 2 H, H-2Ј), 6.91
(d, J = 8.7 Hz, 2 H, H-3Ј). 13C NMR (CDCl3): δ = 15.3 (q, H3CC),
44.2 (q, H3CSO2), 55.5 (q, H3CO), 94.4 (d, C-4), 114.3 (d, 2 C),
121.0 (d, 2 C), 141.7 (s), 151.3 (s), 157.0 (s), 159.6 (s). MS (ESI);
m/z: 269.07 [M+H+]. C12H16N2O3S (268.33): calcd. C 53.71, H
6.01, N 10.44, S 11.95; found C 53.75, H 6.07, N 10.25, S 11.59.
Joseph Rodolph Fotsing gratefully thanks the German Academic
Exchange Service (DAAD) for a generous fellowship. The research
was supported by the Fonds der Chemischen Industrie.
[1] G. L’abbé, M. Bollyon, G. Germain, G. Scheefer, Bull. Soc.
Chim. Belg. 1983, 92, 881–891.
[2] G. L’abbé, Bull. Soc. Chim. Belg. 1984, 93, 579–592.
[3] A. Hassner, J. Keogh, J. Org. Chem. 1986, 51, 2767–2770.
[4] An alleged 2-methylene-2H-azirine[5] proved to be a structur-
ally isomeric product.[6]
Synthesis of 2-Aminoacrolein Acetals Z-33, Z-34, and Z-48. Two-
Step Procedure: This procedure is only applicable for the synthesis
of 33 and 34. Starting from 25 and 26, the methylene-azirines 27
and 28 were produced as shown above and treated with an excess
of dry methanol to give after 5 to 10 min the acetals Z-33 and Z-
34 with 96% and 97% yield, respectively, based on NMR spec-
troscopy. The yields were calculated with regard to the correspond-
ing methyleneazirines.
[5] R. K. M. R. Kallury, P. S. U. Devi, Tetrahedron Lett. 1977, 18,
3655–3658.
[6] a) D. J. Anderson, J. Org. Chem. 1986, 51, 945–947; b) K.
Ashok, G. Sridevi, Y. Umadevi, Synthesis 1993, 623–626.
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One-Pot Procedure: To a stirred solution of compounds 25, 26, or
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room temperature for the time given in Table 3, the reaction mix-
ture was concentrated, and the residue was purified on silica gel
with Et2O or Et2O/n-hexane to give the acetals Z-33, Z-34, and Z-
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(Z)-1-[Dimethoxy(phenyl)methyl]-2-(phenylsulfonyl)vinylamine (Z-
33): Yellow oil. IR (CDCl ): ν = 3497 cm–1 (NH), 3374 (NH), 1618
˜
3
(NH), 1297 (SO2), 1134 (SO2). 1H NMR (CDCl3): δ = 3.10 (s, 6
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3624
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Received: April 6, 2006
Published Online: June 12, 2006
Eur. J. Org. Chem. 2006, 3617–3625
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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