Formation of epoxides and N-arylaziridines via a simple Mg-Barbier reaction in DMF

Article abstract of DOI:10.1016/j.tet.2013.12.016

The Mg-activation of benzal bromide 2b in DMF in the presence of carbonyl compounds 1 or imines 4 leads to epoxides 3 and N-arylaziridines 5, respectively, with acceptable isolated yields. It was found that DMF is likely involved in this process to form a nucleophilic intermediate by reaction with a first generated electrophilic carbene. Results obtained in this chemical approach are compared to those obtained using electrochemical activation, also in DMF.

Full text of DOI:10.1016/j.tet.2013.12.016

Tetrahedron 70 (2014) 919e923
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Formation of epoxides and N-arylaziridines via a simple Mg-Barbier
reaction in DMF
Sylvain Oudeyer b, Eric L eꢀ onel a , Jean Paul Paugam , Jean-Yves Nedelec
a
,
,
a
ꢀ ꢀ
a
*
a
Electrochimie et Synth ꢁe se Organique, Institut de Chimie et des Mat ꢀe riaux Paris-Est, ICMPE, UMR 7182 CNRS e Universit ꢀe Paris-Est Cr ꢀe teil Val de
Marne, 2-8 rue Henri Dunant, 94320 Thiais, France
b
Normandie Univ, COBRA, UMR 6014 et FR 3038, Univ Rouen, INSA Rouen, CNRS, IRCOF, 1 rue Tesni ꢁe re, 76821 Mont Saint Aignan Cedex, France
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 11 October 2013
Received in revised form 29 November 2013
Accepted 6 December 2013
Available online 13 December 2013
The Mg-activation of benzal bromide 2b in DMF in the presence of carbonyl compounds 1 or imines 4
leads to epoxides 3 and N-arylaziridines 5, respectively, with acceptable isolated yields. It was found that
DMF is likely involved in this process to form a nucleophilic intermediate by reaction with a first gen-
erated electrophilic carbene. Results obtained in this chemical approach are compared to those obtained
using electrochemical activation, also in DMF.
Ó 2013 Published by Elsevier Ltd.
Keywords:
Benzal halides
Small ring cycles
Mg-Barbier reaction
Carbonyls
Imines
8
aed
1
. Introduction
a
-halogeno anions
(Aza-Darzens reactions) or 1,3-dipolar
9
additions
pounds
or nucleophilic additions of diazoic com-
are also involved.
b From olefins. The 1,3-dipolar addition of aryl azides and the
10aed
The formation of epoxides and aziridines has attracted a lot of
synthetic efforts because of their useful further transformations
into more complex structures. These small rings are also pre-
1
11aeb
subsequent photolysis or thermolysis of 1,2,3-triazolines
cursors of alcohol or amine functionalities by ring opening re-
actions. These rings are conventionally prepared by methods
mentioned below.
are more commonly described than the reactions via an aryl
12
nitrene. In CF
3 2
CO H, a diastereospecific addition of an aryl
13
nitrenium cation on nucleophilic olefins is also mentioned.
Epoxides are mainly prepared either by epoxidation of C]C
Regarding electrophilic olefins, N-arylaziridines are obtained
2
14a,b
bond with peracids or by nucleophilic addition of
a
-haloanions
from N-acyl-N-arylhydroxylamines (hydroxamic acids),
3
4
14c
(
Darzens reaction) or sulfonium ylides to carbonyl compounds.
and possibly in an enantioselective manner.
1
f
Unlike to epoxides, the synthesis of aziridines has attracted
c From epoxides. The ring opening by diethyl N-arylamidophos-
less synthetic efforts due to the presence of an additional valency
on the heteroatom thus rendering more complicated their further
transformations. Whereas the synthesis of aziridines bearing an
electron-withdrawing group at the nitrogen (i.e., sulfonyl, phos-
phoryl or carbonyl group) is well documented, the synthesis of N-
arylaziridines has received less attention. The principal methods for
the preparation of the latter compounds can be divided into four
categories depending on the starting materials:
phates in basic medium leads to oxazaphospholidines, which
15
are decomposed by heating in aziridines.
1
6a
d From N-(2-haloethyl)anilines
desylanilines, via the corresponding
for the preparation of 1,2,3-triaryllaziridines.
synthesis is the most used process: first reported by Whittaker
and more particularly from
b
-chloro secondary amines
16bei
This multistep
16b
et al. in 1938
and thereafter, frequently investigated to im-
prove the yields in N-arylaziridines (1,2,3-triphenylaziridine:
16f
40% overall yield, in five steps, from benzaldehyde).
5
aec
a From N-arylimines. Using diazo compounds
philic additions of sulfur
or by nucleo-
6
aeb
7
We have previously reported17,18 that small rings like cyclo-
propanes can be prepared in good yields via the magnesium acti-
or arsenic ylides. Addition of
1
7
vation of polyhalomethyl compounds (a,a,a-trichlorotoluene,
17,18
17
methyl trichloroacetate,
dichlorodiphenylmethane, and ben-
zal bromide ) in the presence of acyclic or cyclic activated olefins
*
Corresponding author. Tel.: þ33 (0)149781136; fax: þ33 (0)149781148; e-mail
17
addresses: leonel@icmpe.cnrs.fr, leonel@u-pec.fr (E. L eꢀ onel).
0
040-4020/$ e see front matter Ó 2013 Published by Elsevier Ltd.
http://dx.doi.org/10.1016/j.tet.2013.12.016

920
S. Oudeyer et al. / Tetrahedron 70 (2014) 919e923
in DMF. In this study, our aim has been to determine the scope and
limitations of such Mg-Barbier reaction for the access to epoxides
and aziridines starting from carbonyl compounds or N-arylimines,
respectively. Epoxide results obtained in this chemical approach are
compared to those obtained using electrochemical activation, also
in DMF.
It comes out that the Mg-Barbier reaction and the electro-
reductive coupling lead similarly to moderate isolated yields in
epoxides 3. Furthermore, in the two processes, the reaction is
prevented by an electron-withdrawing group at the para position in
benzaldehyde 1c (Table 1, entry 3) and the yields are lower with
cyclohexanone 1f than with the two aromatic ketones 1dee (Table
1, entries 6 vs 4e5). It is noteworthy that with ketones, the yields
are lower with this method as compared to electrochemical pro-
cess. Consequently, we did not extend the application of this Mg-
Barbier reaction to epoxide formation.
Our first investigations on the preparation of aziridines were
made from three commercially available imines (N-benzylidene-
methylamine 4a, N-benzylidenebenzylamine 4b, N-benzylidenea-
niline 4c) and benzal bromide 2b, using the same reaction
conditions as for epoxides formation (Scheme 2).
2
. Results and discussion
We initially applied the reaction conditions used for the cyclo-
propane formation17 as follows: 50e150 mesh-magnesium grits
(
30 mmol) are suspended in DMF (40 mL) in a three-neck flask
fitted with a dropping funnel and a thermometer, and cooled to
ꢁ
ꢀ
10 C; half of the solution containing benzaldehyde 1a (10 mmol),
benzal chloride 2a (12 mmol) and DMF (5 mL) was rapidly in-
troduced into the flask, and one hour later the remaining of the
reactants was added within 5 min. The expected epoxide 3a was
not detected, neither (E) nor (Z)-stilbenes (Scheme 1). The change
ꢁ
of either the reaction temperature (50 C), or the amount of DMF
(
20 mL), or even the solvent itself (DMAC), did not favour the
cyclocondensation. We then decided to replace benzal chloride by
the more reactive benzal bromide, and this allowed the formation
of 2,3-diphenyloxirane 3a in 53% yield in 1/1 cis/trans ratio along
with (E)- and (Z)-stilbenes as by-products (Scheme 1).
Scheme 2. Preliminary results for the aziridines 5 formation under Mg-Barbier con-
a
ditions. Incomplete conversion even when an extra amount of 2b (18 mmol) was
added.
Unfortunately, imines 4a and 4b bearing a methyl and a benzyl
group on the nitrogen, respectively, failed to furnish the expected
azidines, and only the stilbene by-products were obtained. When
the more electrophilic imine 4c was used, we were pleased to ob-
serve the formation of the aziridine 5c in 38% yield and poor di-
astereomeric ratio (cis/trans ratio of 55 to 45). One should note that
despite the addition of an extra amount of 2b during the reaction,
complete conversion was not reached. In order to improve the yield
of the reaction, an extensive survey of the reaction conditions was
undertaken thus allowing to set up new optimized conditions for
the Mg-Barbier formation of imines. With these new conditions in
hands (excess of benzal bromide and 50 mmol of Mg powder in-
stead of 30 mmol), we moved to the examination of the scope of the
Barbier reaction with various imines (Table 2).
Scheme 1. Formation of epoxide 3a under Mg-Barbier conditions.
Several epoxides were thus prepared from benzal bromide 2b
and a variety of carbonyl compounds 1aef (aldehydes or ketones)
(
Table 1). All products gave satisfactory IR, NMR and mass spectra
19,20
according to the spectral references data.
Results previously
obtained using an electrochemical approach are given compara-
tively in Table 1.
Table 1
Epoxide formation by Mg-Barbier reaction in DMF from aldehydes or ketones and
benzal bromide
From a general viewpoint, imines bearing aromatic substituents
on the nitrogen of imines were found to give the best results in
terms of isolated yield (Table 2, entries 4e8 vs 1e2 and 10). Among
them, those having a halogen at the meta or para position of the
phenyl ring allowed to increase the yield by 10e13% in comparison
with the unsubstituted phenyl ring (Table 2, entries 4e6 vs 3).
Moreover, the steric hindrance of the ortho-halogen, seems to
somehow impede the formation of the aziridine (Table 2, entries 4
vs 5e6). The donating mesomeric effect of the para-methoxy in the
benzylidene group prevents the approach of the nucleophilic spe-
cies (Table 2, entry 9). Consequently, in this case, the (E)-stilbene
was the major product. It appears that this Mg-Barbier process for
the preparation of aziridines is efficient in the presence of suffi-
ciently electrophilic imines. In addition, the N-phenylsulfonyl imine
Entry
1
R1
R2
3
Mg-Barbiera yield % Electroreductionb
(cis/trans)
yield % (cis/trans)
1
2
3
4
5
6
1a
6
C H
5
H
H
H
3a 53 (49/51)
3b 50 (47/53)
3c
40 (25/75)
36 (22/78)
Traces
c
1b 2-Me-C
1c 4-CNC
1d
1e
1f
6
H
4
6
H
4
0
C
C
6
H
H
5
Me 3d 46 (50/50)
Et 3e 51 (48/52)
3f 22
54 (56/44)
70 (50/50)
32
6
5
2 5
(CH )
4j that is somewhat more electrophilic than the N-aryl imine 4c,
a
According to the structure of the carbonyl compound, the reaction time is range
failed to provide the corresponding aziridine in our reaction con-
ditions despite its complete consumption (Table 2, entry 10). This
result could be explained by the fact that 4j bearing a strong
electron-withdrawing group allowing its easy reduction by Mg
from 5 to 40 h.
b
c
See Ref. 19
mmol of benzal bromide is added to ensure the complete consumption of the
5
carbonyl compound.

S. Oudeyer et al. / Tetrahedron 70 (2014) 919e923
921
Table 2
chlorotoluene and N-propylimines in Et
O and under ultrasonic
2
Formation of aziridines by Mg-Barbier reaction from imines 4aej and benzal bro-
mide 2b
23
irradiations. The mechanism postulated by the authors relies on
the first generation of an electrophilic phenylcarbene, which is then
attacked by nucleophilic imines leading to cis-aziridines as major
products. As key difference, our process is conducted in DMF
known to have a Lewis base behaviour. Thus, we postulated that the
first step would be the generation of the same electrophilic car-
2
3
benoid species A as reported by Fry et al. The generation of such
an intermediate could explain the formation of the observed stil-
bene by-products through a dimerization pathway. As main dif-
ference from Fry’s mechanism, in our case, the intermediate A
18
would then be trapped by DMF to form a nucleophilic species B
,
which would be able to react with the carbonyl compounds 1 or
imines 4 to furnish the corresponding epoxides 3 or aziridines 5,
respectively, according to an 1,2-addition/intramolecular nucleo-
philic substitution sequence (Fig. 1). Nevertheless, the influence
of DMF only as an appropriate polar solvent (without the formation
of covalent bond) allowing the reaction to proceed cannot be
ruled out.
R3
R4
Entry
4
5
Yield % (cis/trans)
1
2
3
4
5
6
7
8
9
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
6
C H
6
C H
6
C H
6
C H
6
C H
6
C H
6
C H
6
C H
5
5
5
5
5
5
5
5
Me
Bn
5a
5b
5c
5d
5e
5f
5g
5h
5i
d
d
b
C
6
H
5
42 (53/47)
40 (53/47)
57 (53/47)
57 (56/44)
54 (54/46)
46 (70/30)
Traces (GC)
d
a
2-BrC
3-BrC
4-BrC
4-ClC
2,4-F
6
6
6
H
H
H
4
4
4
a
c
a
a
d
c
6
H
4
a
2
C
6
H
3
a
4-MeOC
Ph
H
6 4
C
6
H
5
10
SO
2
Ph
5j
a
b
c
20
Imines prepared according to literature procedure.
ꢁ
ꢁ
Trans CAS n : [34310-77-5]/cis CAS n : [7042-42-4].
New products.
d
ꢁ
Cis CAS n : [58265-18-1].
during the reaction according to
a desulfonylation process
(
2
PhCHBr being totally recovered).
We also tried to prepare aziridine 5c electrochemically accord-
19
ing to the method used for the preparation of epoxides. The re-
sults were disappointing (no more than 20% isolated yield) partly
due to the difficult separation of the aziridine 5c from a raw mix-
ture containing large amounts of iron salts (Scheme 3).
Fig. 1. Postulated mechanism for the formation of nucleophilic species B and its
subsequent reaction with carbonyl compounds 1 or imines 4.
Such a mechanism is supported in one hand by Burton’s work24
showing the intermediate involving DMF, and in the other hand by
different experimental observations. First, less nucleophilic imines
such as N-benzylidenemethylamine (Table 2, entry 1) closely re-
2
3
lated to those used by Fry et al. or p-methoxybenzylideneaniline
Table 2, entry 9) were unreactive in our conditions. Moreover, the
(
2
3
conditions of Fry et al. applied to our substrates did not provide
any addition-cyclisation products (i.e., epoxides or aziridines) thus
demonstrating the involvement of different pathways in DMF and
in THF.
Scheme 3. Synthesis of aziridine 5c by electrochemical process.
Nevertheless, our simple Mg-Barbier conditions led to 1,2,3-
triarylaziridines 5 from N-benzylideneanilines 4 and benzal bro-
mide 2b with global isolated yields about 40% (two steps from
benzaldehyde including the formation of the imine and the azir-
idination reaction). This method can be considered as an in-
teresting alternative of the use of diazo compounds that are well
3. Conclusion
In conclusion, we have reported in this study that the in-
termediate, which is generated from benzal bromide 2b and mag-
nesium in DMF is a rather nucleophilic species that reacts with
electrophiles, such as carbonyl compounds 1 or electrophilic imines
4. Such an intermediate is not a mere carbene that would be
electrophilic, as shown by Fry et al., but more likely an adduct
between a carbene and DMF. This remains to be clearly demon-
strated. We have also found that the access to epoxides is more
21
known for their unpredictable explosive behaviour and the acidic
2
2
hydrolysis of organic azides forms highly toxic hydrogen azide
toxicity similar to that of hydrogen cyanide).
From a mechanistic point of view, Fry et al. have already de-
scribed a Mg-Barbier reaction from benzal bromide or -bromo-a-
2
3
(
a

922
S. Oudeyer et al. / Tetrahedron 70 (2014) 919e923
conveniently carried out electrochemically, whereas the chemical
approach is more efficient for preparing aziridines. Furthermore,
one should note that these two ‘one pot’ processes involve less
pollutant and more user-friendly reagents than those previously
described in the literature for the synthesis of epoxides or
aziridines.
solution (2 M), dried (Na
this work-up, the products are isolated by flash-chromatography on
silica gel (eluent: pentane/CH Cl ) and characterized as above.
2 4
SO ) and evaporated after filtration. After
2
2
4.2.2.1. 1,2,3-Triphenylaziridine (5c). cis [7042-42-4], trans
[34310-77-5].
Mp: cis: 98e99 C; trans:16e 87e88 C; isolated yield: 42%, cis/
trans: 53/47. Purification by flash-chromatography: elution with
ꢁ
ꢁ
4
4
. Experimental section
ꢀ
1
2 2 3
pentane/CH Cl (80/20) followed by (50/50). IRFT (CDCl , cm ): n
.1. General information
3087, 3065, 3033, 2978, 1951e1666 (multiple bands with low in-
tensity), 1598, 1488, 1454, 1411, 1316, 1269, 1234, 1140, 1075, 1027,
1
10a,b
Solvents and chemicals were used as received. Melting points
891, 882. H NMR (CDCl
3
, 300 MHz): cis
: d 7.55e7.15 (m, 15H),
16e
13
were determined with an Electrothermal IA 9100 digital mp ap-
4.0 (s, 2H). trans:
100 MHz): cis:
49.3. trans:
(EI, 70 eV): m/z (%): cis: 271 (47) [M] , 270 (100), 178 (27), 168 (12),
167 (41), 166 (16), 165 (24), 152 (13), 77 (9). trans: 271 (40) [M] ,
d
7.6e7.2 (m, 15H), 3.9 (s, 2H). C NMR (CDCl ,
d 154.9, 136.1, 129.5, 128.1, 127.3, 123.0, 120.2,
148.3, 134.4, 128.2, 127.5, 127.3, 122.0, 120.9, 50.0. MS
3
1
13 19
10a,b,25
paratus. H, C, F, NMR spectra were recorded on a Bruker AM-
00 (300, 75, 282 MHz) spectrometer. Mass spectra (electron im-
3
d
þ
pact) were obtained on a GCQ Thermoquest spectrometer coupled
to a Finigan-GCQ, fitted with a DB5-ms capillary column. High-
resolution mass spectral analyses and elemental analyses were
carried out at Service Central d’Analyse du CNRS, Vernaison, France.
Gas chromatography was performed on a Varian 3300 chromato-
graph fitted with a SIL-5 CP capillary column. Compounds labelled
by (*) are, to the best of our knowledge, new compounds. The CAS
numbers were given in square brackets for known compounds.
þ
270 (100), 178 (27), 167 (42), 166 (9), 165 (25), 152 (16), 77 (8).
4.2.2.2. 1-(2-Bromophenyl)-2,3-diphenylaziridine
[1048636-57-2], trans [1048636-62-9].
Mp: cis: 110e111 C; trans: 51e55 C (purity: 80%); isolated
yield: 40%, cis/trans: 53/47. Purification by flash-chromatography:
(5d).26 cis
ꢁ
ꢁ
elution with pentane/CH
purification for the trans isomer eluted with pentane/CH
2
Cl
2
(80/20) followed by (50/50), second
Cl (60/
3087, 3065,
3032, 2979, 1951e1766 (multiple bands with low intensity), 1590,
4
.2. General procedures
2
2
ꢀ
1
2 2 3
40), pentane/CH Cl (70/30). IRFT (CDCl , cm ): n
4.2.1. Typical Mg-Barbier procedure for the preparation of epoxides
1
3
. Magnesium grits (50e100 mesh) (30 mmol) are suspended in
3
1568, 1495, 1473, 1455, 1426, 1411, 934, 913, 881. H NMR (CDCl ,
DMF (40 mL) in a three-neck flask fitted with a thermometer and
300 MHz): cis:
14H), 3.75 (s, 2H). C NMR (CDCl
127.7, 127.0, 123.9, 121.6, 116.5, 50.1. trans:
d
7.8e7.1 (m, 14H), 3.95 (s, 2H). trans:
d
7.25e7.0 (m,
151.6, 135.3,
ꢁ
13
a dropping funnel and cooled at ꢀ10 C under an argon atmo-
3
, 100 MHz): cis:
d
sphere. Half of the solution containing aldehyde or ketone 1
d 145.5, 136.4, 133.0,
(
10 mmol), benzal bromide 2b (12 mmol), and DMF (5 mL) is rap-
128.1, 127.5, 127.0, 123.2, 121.9, 116.6, 51.0, 50.9. MS (EI, 70 eV): m/z
(%): cis: 350 (88) [M] , 349 (48), 348 (100), 270 (12), 269 (18), 268
þ
idly introduced in the flask. The start of the reaction is clearly in-
dicated by the rise of the temperature up to 0 C and the mixture
turning yellow. The remaining of the reactants is then added within
ꢁ
(23), 247 (22), 245 (25), 179 (10), 178 (38), 167 (18), 166 (45), 165
þ
(42). trans: 350 (100) [M] , 349 (47), 348 (96), 270 (12), 269 (18),
5
min and the reaction is allowed to proceed until the complete
268 (23), 267 (10), 247 (29), 245 (23), 179 (12), 178 (48), 167 (16),
166 (49), 165 (40), 152 (10).
consumption of the carbonyl compound. Then the reaction mixture
is filtered on a Buchner funnel. DMF is evaporated under reduced
pressure. The reaction mixture is poured into a cold mixture of aq
4.2.2.3. 1-(3-Bromophenyl)-2,3-diphenylaziridine (5e). New pro-
ꢁ
ꢁ
HCl (1 M, 50 mL) and Et
extracted with Et O (three portions of 25 mL). The combined Et
extracts are washed with saturated aq NH Cl and NaHCO solutions
and brine. They are dried (MgSO ) and evaporated after filtration.
Products are isolated by column chromatography on silica gel
230e400 mesh) using pentane/Et O (95%/5%) as eluent and
2
O (50 mL). The layers are separated and
duct. Mp: cis: 116e117 C; trans: 100e101 C, isolated yield: 57%,
cis/trans: 53/47. Purification by flash-chromatography: elution with
2
2
O
4
3
pentane/CH
2
Cl
2
(80/20) followed by (50/50); purification of the
Cl (60/40). IRFT (CDCl
n 3085, 3061, 3034, 2980, 1590, 1560, 1493, 1472, 1450, 1422,
4
trans isomer: elution with pentane/CH
2
2
3
,
ꢀ1
cm ):
924e864 (multiple bands). H NMR (CDCl
(m, 14H), 3.6 (s, 2H). trans: 7.25e6.85 (m, 12H), 6.55e6.5 (m, 2H),
, 100 MHz): cis: 155.9, 135.1, 130.5,
127.2,127.1,125.7,123.1,122.9,122.6,118.5, 49.1. trans: 149.8,135.7,
1
(
2
3
, 300 MHz): cis: d 7.3e7.0
1
13
characterized by H and C NMR, GCeMS, and IR analysis. All
isolated products described in the literature show satisfactory
physical characteristics and spectroscopic data.
d
5
13
3.6 (s, 2H). C NMR (CDCl
3
d
d
1
29.8, 128.3, 127.7, 127.2, 124.9, 123.6, 123.5, 122.3, 119.7, 50.1. MS
þ
4.2.2. Typical Mg-Barbier procedure for the preparation of aziridines
(EI, 70 eV): m/z (%): cis: 350 (100) [M] , 349 (48), 348 (92), 269 (14),
5
. Magnesium grits (50e100 mesh) (50 mmol) are suspended in
268 (14), 247 (14), 245 (14), 179 (10), 178 (39), 167 (14), 166 (41), 165
(30). trans: 350 (97) [M] , 349 (44), 348 (100), 269 (17), 268 (12),
247 (16), 245 (15), 179 (10), 178 (44), 167 (15), 166 (42), 165 (27).
HRMS (in electron ionization mode): cis isomer: m/z calculated for
þ
DMF (40 mL) in a three-neck flask fitted with a thermometer and
ꢁ
a dropping funnel and cooled at ꢀ10 C under an argon atmo-
sphere. Half of the solution containing imine 4 (5 mmol), benzal
bromide 2b (10 mmol), and DMF (5 mL) is rapidly introduced in the
flask. The start of the reaction is clearly indicated by the tempera-
C
20
H16BrN 348.0388; found: 348.0396.
ꢁ
ture rising up to 0 C and the mixture turning yellow. The
4.2.2.4. 1-(4-Bromophenyl)-2,3-diphenylaziridine
(5f). cis
remaining of the reactants is then added within 5 min and the
reaction allowed to proceed until the complete consumption of the
imine obtained after addition of a large excess of benzal bromide 2b
[1048636-56-1], trans [1048636-61-8].
Mp: cis: 99e100 C; trans: oil (purity: 93%); isolated yield: 57%,
cis/trans: 56/44. Purification by flash-chromatography: elution with
ꢁ
(
þ15 mmol: 3ꢂ5 mmol). Then the reaction mixture is filtered on
a Buchner funnel. The DMF is evaporated under reduced pressure
and the residual mixture is solubilized in CH Cl (50 mL) and
hydrolysed with saturated aq NH Cl solution. The layers are sepa-
rated and the aqueous layer is extracted with CH Cl (three por-
tions of 25 mL). The combined CH Cl extracts are washed aq NH
pentane/CH
2
Cl
2
(80/20) followed by (50/50), second purification
Cl (60/40). IRFT
3
, cm ): n 3090, 3061, 3025, 2982, 1595, 1570, 1496, 1465,
for the trans isomer: elution with pentane/CH
2
2
ꢀ
1
2
2
(CDCl
1450, 1409, 930e860 (multiple bands). H NMR (CDCl
cis: 7.55e7.1 (m, 14H), 3.8 (s, 2H). trans: 7.4e7.1 (m, 12H),
6.5e6.45 (m, 2H), 3.5 (s, 2H). C NMR (CDCl , 100 MHz): cis:
1
4
3
, 300 MHz):
2
2
d
d
13
2
2
3
3

S. Oudeyer et al. / Tetrahedron 70 (2014) 919e923
923
d
153.5, 135.1, 131.8, 127.7, 127.5, 126.9, 121.5, 115.0, 49.0. trans:
solubilized in CH
NH
extracted with CH
CH Cl extracts are washed aq NH
and evaporated after filtration. After this work-up, the aziridines 5c
was obtained in 20% yield (cis/trans mixture: 53:47) after purifi-
cation by flash-chromatography on silica gel (eluent: pentane/
2
Cl
2
(50 mL) and hydrolysed with saturated aq
d
147.4, 145.6, 135.8, 131.7, 128.3, 127.4, 122.5, 114.5, 50.0. MS (EI,
4
Cl solution. The layers are separated and the aqueous layer is
Cl (three portions of 25 mL). The combined
4
solution (2 M), dried (Na SO )
þ
7
2
0 eV): m/z (%): cis: 350 (89) [M] , 349 (48), 348 (100), 269 (21),
2
2
68 (19), 247 (35), 245 (34),179 (11),178 (36),167 (18),166 (59),165
2
2
3
2
þ
(
34). trans: 350 (100) [M] , 349 (53), 348 (99), 269 (18), 268 (18),
2
47 (31), 245 (31), 179 (12), 178 (36), 167 (15), 166 (53), 165 (32).
HRMS (in electron ionization mode): cis isomer: m/z calculated for
16BrN 348.0388; found: 348.0393.
C
20
H
2 2
CH Cl ).
4
.2.2.5. 1-(4-Chlorophenyl)-2,3-diphenylaziridine
(5g). cis
Acknowledgements
[
58268-18-1], trans compound was characterized by reference to
ꢁ
16g
the data of the cis known compound. Mp: cis: 95e96 C;
oil (purity¼94%), isolated yield: 54%, cis/trans: 54/46. Purification
by flash-chromatography: elution with pentane/CH Cl (80/20)
3089, 3065, 3033, 2977,
951e1645 (multiple bands with low intensity), 1605, 1594, 1488,
456, 1410, 1317, 1264, 1140, 1093, 1026, 932e886 (multiple band),
trans:
S.O. thanks the MENRT for a grant. The authors thank Dr.
St eꢀ phane Sengmany for his helpful contribution to this work.
2
2
ꢀ1
3
followed by (50/50). IRFT (CDCl , cm ): n
1
References and notes
1
8
2
1
16g
34. H NMR (CDCl
H). trans: 7.45e7.0 (m, 12H), 6.8e6.7 (m, 2H), 3.75 (s, 2H).
, 100 MHz): cis: 153.0, 135.2, 128.9, 128.1, 127.6, 127.4,
26.9, 121.0, 49.1. trans:
3
, 300 MHz): cis
: d 7.3e7.0 (m, 14H), 3.6 (s,
1. For reviews or book related to epoxides and/or aziridines, see: (a) Sweeney, J. B.
13
d
C
Chem. Soc. Rev. 2002, 31, 247; (b) Padwa, A.; Murphree, S. S. Arkivoc 2006, 6; (c)
Singh, G. S.; D’hooghe, M.; De Kimpe, N. Chem. Rev. 2007, 107, 2080; (d) Stan-
kovic, S.; D’hooghe, M.; Catak, S.; Eum, H.; Waroquier, M.; Van Speybroeck, V.;
De Kimpe, N.; Ha, H.-J. Chem. Soc. Rev. 2012, 41, 643; (e) Yudin, A. K. Aziridines
and Epoxides in Organic Synthesis; Wiley-VCH: New York, 2006; (f) Pelissier, H.
Tetrahedron 2010, 66, 1509.
2. (a) Larock, R. C. Comprehensive Organic Transformation, A Guide to Functional
Group Preparation, 2nd ed.; Wiley-VCH: New York, NY, 1999; pp 915e927; (b)
Jana, N. K.; Verkade, J. G. Org. Lett. 2003, 5, 3787.
NMR (CDCl
3
d
1
1
3
d
146.8, 135.8, 128.7, 128.5, 128.3, 127.1,
þ
26.8, 122.0, 50.1, 50.0. MS (EI, 70 eV): m/z (%): cis: 305 (47) [M] ,
04 (100), 203 (10), 201 (25), 178 (25), 166 (21), 165 (22), 138 (10).
trans: 305 (46) [M] , 304 (100), 203 (9), 201 (28), 178 (23), 166 (19),
65 (20), 138 (10).
þ
1
3
4
5
. Hunt, R. H.; Chinn, L. J.; Johnson, W. S. Org. Synth. 1963, 4, 459.
. Corey, E. J.; Chaykovsky, M. Tetrahedron Lett. 1963, 4, 169.
. (a) Rasmussen, K. G.; Jorgensen, K. A. J. Chem. Soc., Chem. Commun. 1995, 1401;
4
.2.2.6. 1-(2,4-Difluorophenyl)-2,3-diphenylaziridine (5h). New
ꢁ
product. Mp: cis: 134e135 C; trans: oil (purity¼90%); isolated
(b) Zhu, Z.; Espenson, J. H. J. Org. Chem. 1995, 60, 7090; (c) Zhang, X.; Yan, M.;
yield¼46%, cis/trans: 70/30. Purification by flash-chromatography:
Huang, D. Org. Biomol. Chem. 2009, 7, 187.
6. (a) Corey, E. J.; Chaykovsky, M. J. Am. Chem. Soc. 1965, 87, 1353; (b) Aggarwal, V.
2 2
elution with pentane/CH Cl (80/20) followed by (50/50), second
K.; Stenson, R. A.; Jones, R. V. H.; Fieldhouse, R.; Blacker, J. Tetrahedron Lett.
purification for the trans isomer: elution with pentane/CH
2
Cl
3089, 3065, 3032, 2981, 1951e1764
multiple bands with low intensity), 1599, 1505, 1455, 1433, 1412,
2
(75/
2001, 42, 1587.
ꢀ
1
2
(
1
(
3
5). IRTF (CDCl , cm ): n
7. Trippett, S.; Walker, M. A. J. Chem. Soc. C 1971, 1114.
8
. (a) Deyrup, J. A. J. Org. Chem. 1969, 34, 2724; (b) Wartski, L. J. Chem. Soc., Chem.
Commun. 1977, 602; (c) Florio, S.; Troisi, L. J. Org. Chem. 1996, 61, 4148; (d)
Sweeney, J. Eur. J. Org. Chem. 2009, 29, 4911.
1
366, 1317, 1264, 1217, 1141, 1100, 1027, 967, 908, 852. H NMR
CDCl , 300 MHz): cis: 7.4e7.05 (m, 11H), 7.0e6.9 (m, 2H), 3.8 (s,
H). trans: 7.4e6.5 (m, 13H), 3.7 (s, 2H). C NMR (CDCl
00 MHz): cis:
3
d
9. Kadaba, P. K.; Stanovnik, B.; Tisler, M. Adv. Heterocycl. Chem. 1984, 37, 219.
13
1
0. (a) Bartnik, R.; Mloston, G. Synthesis 1983, 924; (b) Mayer, M. F.; Hossain, M. M.
J. Org. Chem. 1998, 63, 6839; (c) Rasmussen, K. G.; Juhl, K.; Hazell, R. G.; Jor-
gensen, K. A. J. Chem. Soc., Perkin Trans. 2 1998, 1347; (d) Xie, W.; Fang, J.; Li, J.;
Wang, P. G. Tetrahedron 1999, 55, 12929.
2
d
3
,
1
3
1
d
158.2 (dd, J¼243.7 Hz, J¼10.6 Hz), 155.6 (dd,
1
3
J¼250.1 Hz, J¼11.9 Hz), 138.4e138.2, 135.8, 127.9, 127.8, 127.2,
2
4
2
1
21.7, 111.0 (dd, J¼23.5 Hz, J¼3.8 Hz), 104.5 (dd, J¼26.7 Hz,
11. (a) Scheiner, P. J. Org. Chem. 1967, 32, 2022; (b) Broeckx, W.; Overbergh, N.;
2
1
3
Samyn, C.; Smets, G.; L’Abb eꢀ , G. Tetrahedron 1971, 27, 3527.
J¼23.6 Hz), 49.5. trans: 157.7 (dd, J¼242.8 Hz, J¼10.6 Hz), 155.0
d
12. Abramovitch, R. A.; Challand, S. R.; Yamada, Y. J. Org. Chem. 1975, 40, 1541.
1
3
2
(
dd, J¼248.9 Hz, J¼11.9 Hz), 135.8, 132.4 (dd, J¼11.1 Hz,
13. Takeuchi, H.; Ihara, R. J. Chem. Soc., Chem. Commun. 1983, 175.
4
3
J¼3.5 Hz),128.3,128.2,127.8, 127.1, 122.4 (broad d, J¼9.1 Hz), 110.6
14. (a) Pereira, M. M.; Santos, P. P. O.; Reis, L. V.; Lobo, A. M.; Prabhakar, S. J. Chem.
Soc., Chem. Commun. 1993, 38; (b) Aires-de-Sousa, J.; Lobo, A. M.; Prabhakar, S.
Tetrahedron Lett. 1996, 37, 3183; (c) Murugan, E.; Siva, A. Synthesis 2005, 2022.
2
4
2
2
(
dd, J¼21.7 Hz, J¼3.5 Hz), 104.2 (dd, J¼23.8 Hz, J¼23.6 Hz), 49.8.
9
1
F NMR (CDCl
3
, 282 MHz): cis:
d
ꢀ117.6, ꢀ122.0. trans:
d
ꢀ118.0,
15. Shahak, I.; Ittah, Y.; Blum, J. Tetrahedron Lett. 1976, 17, 4003.
þ
ꢀ
120.7. MS (EI, 70 eV): m/z (%): cis: 307 (46) [M] , 306 (100), 203
17), 183 (14), 178 (31), 140 (9). trans: 307 (47) [M] , 306 (100), 203
18), 183 (16), 178 (29), 140 (11). HRMS (in electron ionization
15 2
mode): cis isomer: m/z calculated for C20H F N 307.1172; found:
16. (a) Rudesill, J. T.; Severson, R. F.; Pomonis, J. G. J. Org. Chem. 1971, 36, 3071; (b)
Taylor, T. W. J.; Owen, J. S.; Whittaker, D. J. Chem. Soc. 1938, 206; (c) Heine, H.
W.; Peavy, R. Tetrahedron Lett. 1965, 35, 3123; (d) Heine, H. W.; Peavy, R.;
Durbetaki, A. J. J. Org. Chem. 1966, 31, 3924; (e) Hall, J. H.; Huisgen, R.; Ross, C.
H.; Scheer, W. J. Chem. Soc., Chem. Commun. 1971, 1187e1188; (f) Loeppky, R. N.;
Smith, D. H. J. Org. Chem. 1976, 41, 1578; (g) Oehlschlager, A. C.; Yim, A. S.;
Akhtar, M. H. Can. J. Chem. 1978, 56, 273; (h) Lassalle, G.; Gr eꢀ e, R.; Toupet, L. Bull.
þ
(
(
3
07.1168.
Soc. Chim. Fr. 1990, 127, 453; (i) Matsumoto, K.; Iida, H.; Uchida, T.; Yabe, Y.;
Kakehi, A.; Lown, J. W. Can. J. Chem. 1994, 72, 2108.
17. Oudeyer, S.; Aaziz, A.; L
4
.2.3. Typical electrochemical procedure for the preparation of azir-
eꢀ onel, E.; Paugam, J. P.; N eꢀ d eꢀ lec, J.-Y. Synlett 2003, 485.
idines 5c. The reactions are conducted in an undivided cell fitted
with a Fe rod as the anode and a nickel foam as the cathode (area:
ca. 40 cm ). A solution of CuBr (144 mg, 1 mmol) and Bu
1
8. Oudeyer, S.; L eꢀ onel, E.; Paugam, J. P.; Sulpice-Gaillet, C.; N eꢀ d eꢀ lec, J.-Y. Tetrahe-
dron 2006, 62, 1583.
19. Oudeyer, S.; L eꢀ onel, E.; Paugam, J. P.; N eꢀ d eꢀ lec, J.-Y. Synthesis 2004, 389.
2
4
NBr
(
300 mg) in DMF (45 mL) and pyridine (5 mL) is electrolysed at
20. Echevarria, A.; Miller, J.; Nascimento, M. G. Magn. Reson. Chem. 1985, 23, 809.
21. Fulton, J. R.; Aggarwal, V. K.; De Vicente, J. Eur. J. Org. Chem. 2005, 1479.
constant current intensity (0.3 A) during 15 min at
22. Wiss, J.; Fleury, C.; Onken, U. Org. Process Res. Dev. 2006, 10, 349.
ꢁ
ꢁ
ꢀ
10 C<T<ꢀ5 C. Then, the activated imine 4a (10 mmol) and
23. Biscoe, M. R.; Fry, A. J. Tetrahedron Lett. 2001, 42, 2759.
benzal bromide 2b (20 mmol) are added and electrolysed (0.1 A)
until the complete consumption of the imine 4a (20 mmol of 2b
were added in order to reach complete conversion). The DMF is
evaporated under reduced pressure and the residual mixture is
24. Burton, D. J.; Wiemers, D. M. J. Am. Chem. Soc. 1985, 107, 5014.
2
5. Matsumoto, K.; Nakamura, S.; Uchida, T.; Takemoto, Y. Heterocycles 1980, 14,
37.
8
26. Xue, Z.; Mazumdar, A.; Hope-Weeks, L. J.; Mayer, M. F. Tetrahedron Lett. 2008,
49, 4601.