Catalytic stereoselective alkene aziridination with sulfonimidamides

Article abstract of DOI:10.1016/j.tetasy.2010.03.032

Diastereoselective copper-catalyzed alkene aziridination has been investigated using chiral nitrenes generated from sulfonimidamides in the presence of an iodine(III) oxidant. Starting from a stoichiometric amount of the substrates, the corresponding azir

Full text of DOI:10.1016/j.tetasy.2010.03.032

Tetrahedron: Asymmetry 21 (2010) 1447–1457
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Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Catalytic stereoselective alkene aziridination with sulfonimidamides
Fabien Robert-Peillard, Pablo H. Di Chenna, Chungen Liang, Camille Lescot, Florence Collet, Robert H. Dodd,
*
Philippe Dauban
Institut de Chimie des Substances Naturelles, UPR 2301 CNRS, Centre de Recherche de Gif-sur-Yvette, Avenue de la Terrasse, 91198 Gif-sur-Yvette Cedex, France
a r t i c l e i n f o
a b s t r a c t
Article history:
Diastereoselective copper-catalyzed alkene aziridination has been investigated using chiral nitrenes
generated from sulfonimidamides in the presence of an iodine(III) oxidant. Starting from a stoichiometric
amount of the substrates, the corresponding aziridines were isolated with excellent yields of up to 96%.
Good levels of asymmetric induction were obtained in the case of electron-poor olefins, with an optimal
de of 94% being reached starting from tert-butyl acrylate. Matching and mismatching effects were also
observed upon the use of chiral copper catalysts for the aziridination of styrene.
Received 2 March 2010
Accepted 29 March 2010
Available online 11 May 2010
Dedicated with respect and admiration to
Professor Henri Kagan on the occasion of his
80th birthday
Ó 2010 Elsevier Ltd. All rights reserved.
1. Introduction
efficient catalytic olefin aziridinations have been reported starting
from N-aminoheterocycles,9 azides,10 metal-nitrido complexes,11
Aziridines, the smallest of saturated nitrogen heterocycles, offer
unique opportunities for the preparation of nitrogen-containing
compounds.1 Most applications of aziridines in either natural prod-
uct synthesis or medicinal chemistry derive from their ability to
undergo ring-opening with a wide variety of nucleophiles as a con-
sequence of their strained structure.2 The latest developments in
this field have culminated in the discovery of highly efficient chiral
catalysts for the asymmetric ring-opening of meso aziridines.3
Their use is not limited to the production of 1,2-difunctionalized
scaffolds and new transformations based on these small-ring het-
erocycles have recently been uncovered. Thus, they can be engaged
in ring-expansion reactions under various conditions to afford five-
haloamines,12 or N-sulfonyloxycarbamates.13 In parallel, signifi-
cant improvements have been achieved with the development of
nitrene addition to alkenes mediated by hypervalent iodine
reagents.14 Under these conditions, inter- and intramolecular
olefin aziridinations can be catalyzed by several transition metals
such as copper15 and rhodium,16 but also ruthenium, manganese,
iron, silver, gold, and rhenium.17 Worthy of note has been the
discovery of practical procedures for the in situ generation of
iminoiodanes, which have allowed the formation of nitrenes from
various synthetically useful precursors.18 All these achievements
have found applications in the total syntheses of natural prod-
ucts19 and bioactive compounds20 thereby highlighting the effi-
ciency of catalytic olefin aziridination mediated by iodine(III)
oxidants.
or six-membered rings,1d,4 whereas their
a-lithiated counterparts
can be considered as carbenoid precursors useful, for example, in
cyclopropanation.5 Finally, not only are aziridines versatile syn-
thetic intermediates, they are also found in the structures of vari-
ous natural products the biological activity of which is generally
the consequence of their nucleophilic ring-opening.6
The synthetic importance of aziridines has caused a surge of
interest over the last two decades in developing efficient protocols
for their preparation as reported by several recent reviews devoted
to the field.1,2,7 Classical ‘cyclization methods’ involve functional
group transformations starting from epoxides, aminoalcohols, or
azidoalcohols, while ‘addition processes’ include the addition of
carbenes or ylides to imines, the aza-Darzens reaction and catalytic
nitrene transfer to olefins.8 The latter has recently received consid-
erable attention with the emergence of new precursors and cata-
lysts for the generation of highly reactive metallanitrenes. Thus,
Several chiral ligands for copper21 and rhodium22 catalysts have
been designed in order to induce enantioselective nitrene addition
to alkenes. Very good to excellent enantiomeric excesses of greater
than 99% have been reported for the catalytic intermolecular asym-
metric aziridination of substituted styrenes, cinnamates, and
chalcones. Yields were also generally very high provided that an
excess (5 equiv) of substrate was used. Of course, the need to use
an over-stoichiometric amount of substrate does not apply to anal-
ogous intramolecular processes that, in turn, allow extension of the
scope of the reaction to aliphatic olefins.21j,22a,b Despite these note-
worthy results, we felt that there was still room for improvement
providing that the scope of the aforementioned one-pot procedure
could be widened.18 Whereas the in situ generation of iminoiod-
anes from carbamates and sulfamates had proved successful, we
envisaged applying this protocol to the conception of a stereoselec-
tive alkene aziridination, which relies on the addition of a chiral
metallanitrene formed by the combination of a copper salt with a
* Corresponding author. Tel.: +33 (0)1 69 82 45 60; fax: +33 (0)1 69 07 72 47.
E-mail address: Philippe.dauban@icsn.cnrs-gif.fr (P. Dauban).
0957-4166/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2010.03.032

1448
F. Robert-Peillard et al. / Tetrahedron: Asymmetry 21 (2010) 1447–1457
1. SOCl2
toluene, rt
chiral nitrogen source (Scheme 1). Good levels of asymmetric
induction were expected from the use of chiral sulfur agents based
on theoretical calculations of Andersson and Norrby that have sug-
gested a bidentate coordination of an N-(sulfonyl)nitrene to cop-
per.15g Since in initial tests, sulfinamides did not survive the
oxidizing conditions of the aziridination reaction, we were partic-
ularly attracted by the opportunities offered by the uncommon sul-
fonimidoyl moiety.
O
S
O
S
O
S
Na
O
aq. NH3
p-Tol
p-Tol
Cl
NH2
2. TsNNaCl
toluene, 80ºC
N
N
CH3CN, rt
55%
over 3 steps
Ts
Ts
2a
3a
1a
NH2
32% over 3 steps
Ph (R)
R
X
O
O
X
S
O
S
(S)
TFA, 40ºC
S
S
p -Tol
p-Tol
N
(R) Ph
NH2
N
R
N
72%
N
NH2
H
?
O
CuLn
*
R1
+
I(III)
Ts
Ts
(R,S)-4a
(-)-(S)-1a
Scheme 2. Synthesis of sulfonimidamide 1a.
X
R
O
CuLn
PhI
S
R1
N
to prepare differently substituted sulfonimidamides (vide infra)
from various sulfinyl chlorides31 and by reaction with several
chloramines. Moreover, X-ray crystallography studies allowed us
to determine that the (ꢀ)-enantiomer corresponds to the (S)-con-
figuration of the sulfonimidamide,28b an observation which is in
agreement with previous literature data.24f
Sulfonimidamide 1a was then tested as the nitrene precursor in
the copper-catalyzed aziridination of olefins. Optimization of the
reaction conditions was first undertaken using, as the test sub-
strate, methyl acrylate which has previously been shown to be
poorly reactive with sulfonamide-derived nitrenes (Scheme 3).15b
Scheme 1. Principle of the copper-catalyzed alkene aziridination with sulfonimid-
amides.
Sulfonimidamides were first described by Levchenko nearly
50 years ago but have received little attention until recently.23–25
Initially used for the purpose of fundamental studies related to
the stereochemistry of sulfur compounds,24d they then found
applications in medicinal chemistry.24g–i Whereas recent studies
have revisited their synthesis,24f,25a,e sulfonimidamides have also
proven to be useful in coupling reactions,25b,c as organocata-
lysts,25d and in oxidative alkene addition for the formation of het-
erocycles.25f However, more significant contributions were made
in the field of catalytic nitrene transfers26 and the use of sulfonimi-
damides as nitrene precursors has resulted in the development of
highly efficient diastereoselective processes such as catalytic azir-
idination,27,28 sulfur imination,29 and, particularly, rhodium-cata-
lyzed C–H amination.30 Herein we report a full account of our
studies related to the stereoselective copper-catalyzed olefin azir-
idination with sulfonimidamides.28a
O
S
p-Tol
NH2
O
S
N
Ts 1.2 eq. 1a
p-Tol
N
1.2 eq. PhIO
N
CO2Me
CO2Me
Ts
10 mol% Cu catalyst
4Å molecular sieves
solvent, T
1.0 eq.
methyl acrylate
5a
Scheme 3.
2. Results and discussion
Moreover, the corresponding aziridine 5a displays significant syn-
thetic interest as a direct precursor of
- and b-amino acids.15h The
Sulfonimidamides are sulfur(VI) compounds analogous to sul-
fonamides in which one oxygen atom has been replaced by an imi-
do moiety thereby offering the possibility of introducing various
additional functions such as an alkyl group and an electron-with-
drawing substituent. Free amido derivatives can be easily obtained
by reaction between ammonia and sulfonimidoyl chlorides them-
selves prepared by either oxidation of sulfinamides with a chlori-
nating agent or imidation of sulfinyl chlorides with the sodium
salt of haloamines.23,24 Our initial experiments focused on the
use of N-(alkyl)arenesulfonimidamides,24b,24c which did not prove
satisfactory. Since the low yields of aziridination were obtained
as a consequence of starting material degradation, we decided to
turn our attention to sulfonimidamides substituted by a sulfonyl
group on the imido function. Thus, we prepared N-(p-toluenesulfo-
nyl)-p-toluenesulfonimidamide 1a as described in the literature
(Scheme 2).24f Starting from commercially available sodium p-tol-
uenesulfinate 2a, successive reactions with thionyl chloride and
anhydrous chloramine-T afforded the sulfonimidoyl chloride 3a.
Whereas the addition of ammonia led to racemic 1a, enantiomeri-
cally pure material was accessible via reaction of the racemic
chloride 3a with (R)-1-phenylethylamine and fractional recrystalli-
zation of the resulting sulfonimidamide 4a. Cleavage of the crystal-
line (R,S)-4a with trifluoroacetic acid finally afforded (S)-1a, the
(R)-enantiomer being also isolated with a good enantiomeric pur-
ity from (S)-1-phenylethylamine. The procedure was well adapted
a
results are summarized in Table 1. In agreement with the seminal
paper of Evans et al.,15b the copper-catalyzed alkene aziridination
proceeded best in polar solvents, acetonitrile being the solvent of
choice (entry 3). Both reactivity and selectivity increased by
decreasing the reaction temperature to ꢀ20 °C (entries 3–5). Opti-
mal conversions were finally observed by concentrating the reac-
tion medium (entry 6 vs 3) and using a copper(I) salt (entries 6
Table 1
Screening of the reaction parameters for the copper-catalyzed aziridination of methyl
acrylate
Entry
Catalyst
Solvent
T (°C)
Yielda (%)
deb (%)
1
2
3
4
5
6
7
8
9
Cu(MeCN)4PF6
Cu(MeCN)4PF6
Cu(MeCN)4PF6
Cu(MeCN)4PF6
Cu(MeCN)4PF6
Cu(MeCN)4PF6
CuOTf
Toluene
CH2Cl2
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
ꢀ20
ꢀ20
ꢀ20
0
—
—
30
50
46
40
50
45
43
48
17
67
62
57
81c
81c
50c
22c
20
ꢀ20
ꢀ20
ꢀ20
ꢀ20
Cu(OTf)2
Cu(acac)2
a
b
c
Isolated yield after flash chromatography.
Diastereoisomeric excess (de) was determined by NMR.
The quantity of solvent introduced was reduced by 50%.

F. Robert-Peillard et al. / Tetrahedron: Asymmetry 21 (2010) 1447–1457
1449
and 7 vs 8 and 9). Methyl acrylate proved to be an efficient nitrene
acceptor under these conditions and an optimal yield of 81% was
obtained starting from a stoichiometric amount of the olefin.32,33
The diastereoisomeric excess of 50%, though modest, was encour-
aging since no stereoselective aziridination of methyl acrylate
had been previously reported.
With the optimized experimental conditions in hand, we then
decided to screen various alkenes (Scheme 4). The conditions
appear particularly appropriate for the aziridination of a,b-unsatu-
rated esters (Table 2). Thus, their application to methyl methacry-
late and tiglate afforded nearly quantitative yields of aziridines 6a
and 8a (96% and 92%, respectively, entries 2 and 4) whereas methyl
crotonate proved to be less reactive affording the corresponding
aziridine 7a with a modest yield of 35% (entry 3). As with methyl
acrylate, the diastereoselectivities remained moderate ranging
from 38% to 50%. In the case of a terminal olefin with low reactivity
such as 1-heptene, the good yield observed (60%, entry 5) once
again demonstrated the higher efficiency of the nitrene species.
This was also clearly indicated by the reaction with internal and
cyclic alkenes (entries 6–9). Moreover, the exclusive isolation of
trans- and cis-aziridines 10a and 11a from, respectively, trans-
and cis-2-hexene supports a concerted stereospecific addition of
the nitrene. However, the asymmetric induction in the case of
these non-activated olefins was very low. Finally, the reaction with
styrene and 1,2-dihydronaphthalene led to good conversions (iso-
lated yields of 63%, entries 10 and 11) but low diastereoselectivi-
ties in the 20–25% range.34
These initial results convinced us of the superior performance of
the sulfonimidamides as nitrene precursors. Screening of their
substituted analogues was therefore envisaged in order to improve
the yields and selectivities. The optimal conditions defined in
Table 1 were thus applied to the catalytic aziridination of styrene
and methyl acrylate, that is, two different classes of olefins, in
the presence of various nitrene precursors. The results are summa-
rized in Table 3.
The introduction of a p-nitro substituent onto one of the aro-
matic rings generally led to better diastereoselectivities in the case
of methyl acrylate, however, this sometimes led to a decrease in
the yield (entries 2, 4 and 6 vs entry 1). The best compromise
was thus afforded by sulfonimidamide 1b which led to aziridine-
2-carboxylate 5b in 70% yield and 75% de. Nevertheless, the nitro
group appeared to be deleterious in the case of styrene since the
corresponding aziridines 14b, 14d, and 14f were isolated in 40–
60% yields and with a very low diastereoselectivity. The use of
the di-p-nitro sulfonimidamide 1e induced the stereoselective
aziridination of both methyl acrylate and styrene with des in the
60–70% range (entry 5). This good result, however, was counter-
balanced by the observed modest yields of, respectively, 43% 5e
and 32% 14e due to the low solubility of 1e. In contrast, the pres-
ence of a p-methoxy, a p-chloro or a hydrogen substituent proved
to be favorable to the reactivity in the case of styrene, the corre-
sponding aziridines 14c, 14g, and 14h being isolated in 86%, 83%,
and 82% yield, respectively (entries 3, 7, and 8). This positive influ-
ence was less pronounced with methyl acrylate since products 5c,
5g, and 5h were obtained in 50–66% yields and 35–65% des. Based
on the coordination-assisted approach previously reported by
Chang,15p,q we also prepared the pyridinylsulfonimidamide 1i that,
however, gave low yields of the expected derivatives 5i and 14i
(entry 9). Finally, sulfonimidamides 1j and 1k allowed us to deter-
mine the influence of each aromatic ring with respect to the reac-
tivity of these nitrene precursors. Replacement of the p-tolyl group
on the imido function by a methyl demonstrated that the aromatic
ring seems to play an important role because compounds 5k and
14k were isolated in moderate yields and selectivities (entry 11).
By contrast, the other phenyl ring does not prove to be as impor-
tant, with the ethylsulfonimidamide 1j affording the correspond-
ing products 5j with a very good diastereoselectivity of 85% and
14j in 75% yield (entry 10). Based on this screening, we ultimately
decided to continue our studies using sulfonimidamide 1b. Since
the latter gives the best overall results with methyl acrylate, it
paves the way for the development of a stereoselective synthesis
of amino acids.35 Moreover, it can be prepared on a multi-gram
scale in either its racemic form or enantiomerically pure form.
The reactivity of several olefins was thus tested under slightly
modified conditions, that is, using copper(I) triflate as the catalyst
in the presence of 1.5 equiv of sulfonimidamide 1b and iodosyl-
benzene (Scheme 5). As previously observed with sulfonimidamide
1a, electron-poor alkenes such as acrylates and methyl methacry-
late were highly reactive affording the corresponding aziridines 5b,
16b, and 6b with yields ranging from 80% to 95% (Table 4, entries
1–3).36 However, as an exception to this trend, acrylonitrile proved
to react moderately (entry 4). The high efficiency of 1b was also
clearly demonstrated by the nearly quantitative yields obtained
in the cases of 1-heptene and cyclic olefins (entries 5–7). Moreover,
the use of sulfonimidamide 1b resulted in very good levels of
asymmetric induction, with t-butyl acrylate-derived aziridine
16b being isolated with an excellent de of 94%.
O
S
p-Tol
NH2
N
O
R2
Ts 1.2 eq. 1a
S
R2
1.2 eq. PhIO
p-Tol
N
R1
N
R1
10 mol% Cu(CH3CN)4PF6
4Å molecular sieves
CH3CN, -20ºC
Ts
R3
R3
1.0 eq.
Scheme 4.
Table 2
Copper-catalyzed alkene aziridination with sulfonimidamide 1a
Entry
1
Substrate
CO2Me
CO2Me
Aziridine
Yielda (%)
81
deb (%)
50
5a
2
3
4
6a
7a
8a
96
35
92
41
50
38
CO2Me
CO2Me
5
6
9a
60
10
4
10a
40c
<10
2
2
7
11a
12a
13a
14a
57d
62
59
63
<10
—
8
9
—
10
20
11
15a
63
25
a
b
c
Isolated yield after flash chromatography.
Diastereoisomeric excess (de) was determined by NMR.
trans-Aziridine.
cis-Aziridine.
The combination of chiral copper complexes with sulfonimida-
mides was also investigated in order to induce matching and mis-
matching effects (Scheme 6). An initial screening of the ligands led
d

1450
F. Robert-Peillard et al. / Tetrahedron: Asymmetry 21 (2010) 1447–1457
Table 3 (continued)
Table 3
Screening of sulfonimidamides 1 in the aziridination of methyl acrylate and styrene
CO2Me
Ph
CO2Me Ph
Yielda (%)
Yielda (%)
Entry Sulfonimidamide
Yielda (%)
Yielda (%)
deb (%)
deb (%)
Entry Sulfonimidamide
deb (%)
deb (%)
O
O
O
O
S
5k
54
35
14k
60
5
O
N
S
5a
81
50
14a
63
20
O
N
11
S
1
2
NH2
1k
S
NH2
1a
a
b
c
Isolated yield after flash chromatography.
Diastereoisomeric excess (de) was determined by NMR.
Reactions were conducted in MeNO2 since the sulfonimidamide 1f is only very
O
O
S
N
O
5b
70
75
14b
40
10
slightly soluble in MeCN.
S
NH2
1b
O2N
O
S
O
O
S
O
N
p-NO2Ph
5c
66
35
14c
86
10
NH2
O
S
N
3
4
S
R2
Ts
1.5 eq. 1b
1.5 eq. PhIO
NH2
O
R2
p-NO2Ph
N
1c
N
R1
MeO
R1
10 mol% CuOTf
4Å molecular sieves
CH3CN, -20ºC
Ts
R3
R3
O
S
1.0 eq.
5d
80
55
14d
60
10
N
O
S
Scheme 5.
NH2
NO2
1d
O
O
S
Table 4
Copper-catalyzed alkene aziridination with sulfonimidamide 1b
O
N
5e
43
70
14e
32
60
5
6
7
S
NH2
NO2
Entry
Substrate
CO2Me
Aziridine
Yielda (%)
deb (%)
1e
O2N
1
2
5b
88
80
16b
80 (65)c
94 (94)c
O
O
CO2tBu
S
5fc
45
73
14fc
50
N
O
CO2Me
3
6b
95
36
30
S
NH2
OMe
15
CN
4
5
17b
9b
48
92
1f
O2N
<10
O
O
S
4
O
N
5g
50
65
14g
83
10
6
7
12b
13b
93
95
—
—
S
S
NH2
1g
Cl
O
O
a
b
c
Isolated yield after flash chromatography.
Diastereoisomeric excess (de) was determined by NMR.
Reaction performed on a 1 mmol scale.
5h
60
55
14h
82
7
N
O
8
9
S
NH2
1h
O
O
O
S
5i
<5
—
14i
21
—
O
N
S
S
p-R-Ph
NH2
1.2 eq. 1
1.2 eq. PhIO
O
S
N
NH2
Ts
H
p-R-Ph
N
N
1i
N
Ph
Ph
1.0 eq.
Ts
O
O
10 mol% CuOTf
12 mol% L*
4Å molecular sieves
C6H6, 5ºC
L*:
S
5j
55
85
14j
75
10
N
O
O
O
10
S
N
N
NH2
t-Bu
t-Bu
1j
Scheme 6.

F. Robert-Peillard et al. / Tetrahedron: Asymmetry 21 (2010) 1447–1457
1451
Table 5
de of 94%. This methodology can therefore be applied to the syn-
thesis of substituted amino acids, since the resulting aziridines also
undergo nucleophilic ring-opening under smooth conditions.
Matching and mismatching effects have also been induced by com-
bining the sulfonimidamide with a chiral copper catalyst thereby
allowing us to improve the stereoselectivity of the aziridination,
though only in the case of styrene. A particularly noteworthy fea-
ture of this transformation is that the addition of the electron-defi-
cient nitrene species best occurs in the case of electron-poor
olefins. Further studies are therefore currently underway in order
to elucidate the mechanism as well as to understand the origin
of the high reactivity of sulfonimidamide-derived nitrenes.
Aziridination of styrene with a chiral copper catalyst
Entry
Sulfonimidamide
Aziridine
Yielda (%)
deb (%)
1
2
3
4
(S)-1a; R = Me
(R)-1a; R = Me
(S)-1b; R = NO2
(S)-1g; R = Cl
14a
14a
14b
14g
91
68
39
70
61
10
54
65
a
Isolated yield after flash chromatography.
Diastereoisomeric excess (de) was determined by NMR.
b
us to find that the best selectivities could be obtained with C2-sym-
metric bis(oxazolines)37 and, particularly, tert-butyl-bis(oxazoline)
which has been found optimal for various catalytic processes.38
The application of classical conditions for the asymmetric cop-
per-catalyzed aziridination21 then allowed us to isolate the sty-
rene-derived aziridine 14a in 91% yield and 61% de by combining
the (S,S)-tert-butylbis(oxazoline)-copper complex with sulfonimi-
damide (S)-1a (Table 5, entry 1). A mismatched pair for double
induction was formed with (R)-1a thereby leading to a lower yield
and a very weak asymmetric induction (entry 2). The matched
pairing was confirmed with (S)-1b but the yield was lower due
to the poor solubility of the p-nitrosulfonimidamide (entry 3). Fi-
nally, a slightly better de was observed with p-chlorosulfonimida-
mide (S)-1g, with the corresponding product 14g being obtained
with a yield of 70% and a de of 65% (entry 4). All our attempts to
extend the double stereodifferentiation strategy to other alkenes
were unsuccessful, with no reaction taking place starting with
acrylates under these conditions.
Finally, N-(sulfinimidoyl)aziridines have been found to react
with nucleophiles under mild conditions (Scheme 7). Reaction of
aziridines 5b and 16b with methanol at room temperature quanti-
tatively afforded the C-3 ring-opened products 18 and 19,39
whereas the direct introduction of a hydroxy group at the same
position efficiently occurred using a mixture of trifluoroacetic acid,
THF, and water leading to compound 20 in 77% yield. Since the
sulfonimidoyl moiety can be cleaved under reductive conditions,30
4. Experimental
Melting points were measured in capillary tubes on a Büchi
B-540 apparatus and are uncorrected. Infrared spectra were re-
corded on a Perkin Elmer Spectrum BX FT-IR spectrometer. Proton
(1H) and carbon (13C) NMR spectra were recorded on Bruker spec-
trometers: Avance 300 MHz or 500 MHz. Carbon NMR (13C) spectra
were recorded at 125 or 75 MHz, using a broadband decoupled
mode with the multiplicities obtained using a JMOD or DEPT se-
quence. NMR experiments were carried out in deutero-chloroform
(CDCl3), -methanol (CD3OD), and -dimethylsulfoxide (DMSO).
Chemical shifts (d) are reported in parts per million (ppm) with ref-
erence to CDCl3 (1H: 7.26; 13C: 77.00), CD3OD (1H: 3.31; 13C:
49.00), and DMSO (1H: 2.50; 13C: 39.50). The following abbrevia-
tions are used for the proton spectra multiplicities: s: singlet, d:
doublet, t: triplet, q: quartet, m: multiplet, br: broad. Coupling con-
stants (J) are reported in hertz (Hz). Values in italics refer to the
minor diastereomer, where applicable. Mass spectra were obtained
either with a LCT (Micromass) instrument using electrospray ioni-
zation (ES), or from a Time of Flight analyzer (ESI-MS) for the high
resolution mass spectra (HRMS). Elemental analyses were per-
formed on a Perkin Elmer CHN 2400 analyzer with a detection by
catharometry. Thin-layer chromatography was performed on Silica
Gel 60 F254 on aluminum plates (Merck) and visualized under a
UVP Mineralight UVLS-28 lamp (254 nm) and with ninhydrin and
phosphomolybdic acid in ethanol. Flash chromatography was con-
access to optically active b-substituted a-amino acids can be envis-
aged by application of this catalytic alkene aziridination.
ducted on Merck Silica Gel 60 (40–63 lm) at medium pressure
O
(300 mbar) or on CombiFlash (Serlabo Technologies). All reagents
were obtained from commercial suppliers unless otherwise stated.
Where necessary, organic solvents were routinely dried and/or dis-
tilled prior to use and stored over molecular sieves under nitrogen.
All solvents were freshly distilled when required.
S
p -NO2Ph
MeOH
CH2Cl2, rt
NH
TsN
*
CO2R
O
S
MeO
18 : R = Me; 99%
19 : R = tBu; 97%
p-NO2Ph
N
O
S
N
CO2R
*
4.1. N-(p-Toluenesulfonyl)-p-toluenesulfonimidamide 1a
Ts
p-NO2Ph
TsN
TFA, H2O
THF, rt
NH
5b : R = Me
16b :R = tBu
To an ice cooled suspension of anhydrous sodium p-toluenesulf-
inate 2a (3.75 g, 21 mmol) in toluene (40 mL) under argon was
slowly added thionyl chloride (7.5 mL). The reaction mixture was
stirred at room temperature for 14 h before being evaporated un-
der vacuum. The resulting yellow oil was dissolved in toluene
(60 ml) and anhydrous chloramine-T (4.78 g, 21 mmol) (Caution!
The trihydrate was dried in a drying pistol at 80 °C for 8 h. Explo-
sion may occur at higher temperatures) was added at room tem-
perature. The reaction mixture was stirred at 80 °C for 1.5 h. The
sodium chloride precipitate was removed by filtration while the
reaction mixture was still hot and the filtrate was evaporated.
The crude N-(p-toluenesulfonyl)-p-toluenesulfonimidoyl chloride
3a was dissolved in acetonitrile (80 ml) and aqueous ammonia
(80 ml) was added at 0 °C. After 30 min, the ice bath was removed
and the reaction mixture was stirred overnight at room tempera-
ture. The organic layer was separated and washed successively
with 10% HCl and water, dried with MgSO4, and concentrated
*
CO2Me
HO
20; 77%
Scheme 7. Nucleophilic ring-opening of acrylate-derived aziridines.
3. Conclusion
The reaction between the iodine(III) oxidant iodosylbenzene
and a sulfonimidamide in the presence of a copper catalyst leads
to the formation of a highly reactive chiral metallanitrene. The lat-
ter adds to various types of olefins used in stoichiometric amounts
to afford the corresponding aziridines in very good yields of up to
96%. The catalytic aziridination can also take place with good
diastereoselectivities, particularly in the case of
esters. Thus, the addition of the nitrene derived from p-nitrosulfon-
imidamide 1b to tert-butyl acrylate takes place with an optimized
a,b-unsaturated

1452
F. Robert-Peillard et al. / Tetrahedron: Asymmetry 21 (2010) 1447–1457
under vacuum to afford a pasty yellow solid which was recrystal-
lized from ethyl acetate. A white crystalline solid (2.4 g) was ob-
tained while a second crop was obtained from the mother liquor
(1.33 g) yielding a total of 3.73 g (11.6 mmol, 55%) of pure com-
occur at higher temperatures) (14.8 g, 65 mmol) was added at
room temperature. The reaction mixture was stirred at 80 °C for
1.5 h. The sodium chloride precipitate was filtered while the reac-
tion mixture was still hot and the filtrate was evaporated. The
crude N-(p-toluenesulfonyl)-p-nitrobenzenesulfonimidoyl chloride
was dissolved in acetonitrile (80 ml) and aqueous ammonia
(80 ml) was added at 0 °C. After 30 min, the ice bath was removed
and the reaction mixture was stirred overnight at room tempera-
ture. The organic layer was separated and washed successively
with 10% HCl and water, dried with MgSO4, and concentrated un-
der vacuum to afford a yellow solid which was recrystallized from
ethyl acetate. Pure compound 1b was obtained as a white solid
(4.6 g, 13.5 mmol, 21%). Mp 210–211 °C; IR (neat, cmꢀ1) 3306,
3207, 1598, 1522, 1351, 1272, 1142, 1108, 1098; 1H NMR
(300 MHz, CDCl3) d 2.40 (s, 3H), 7.30 (d, J = 7.5 Hz, 2H), 7.50 (br
s, 2H), 7.68 (d, J = 7.9 Hz, 2H), 8.18 (d, J = 7.5 Hz, 2H), 8.41 (d,
J = 7.6 Hz, 2H); 13C NMR (75 MHz, CDCl3) d 21.3, 125.0, 127.4,
129.4, 130.0, 142.0, 143.4, 148.8, 151.2; mass spectrum (ES) m/z
378 (M+Na)+; HRMS m/z (M+Na)+ calcd for C13H13N3NaO5S2
378.0194, found 378.0173.
pound 1a. Mp 152.0–152.5 °C (lit. 162–163 °C);23a IR (KBr, cmꢀ1
)
3212, 1284, 1149, 1107, 1087, 810, 748, 660; 1H NMR (300 MHz,
CDCl3) d 2.40 (s, 3H), 2.42 (s, 3H), 5.60 (s, 2H), 7.25 (d, J = 7.5 Hz,
2H), 7.29 (d, J = 7.9 Hz, 2H), 7.79 (d, J = 7.5 Hz, 2H), 7.84 (d,
J = 7.6 Hz, 2H); 13C NMR (75 MHz, CDCl3) d 21.5, 21.6, 126.7,
127.2, 129.3, 129.8, 137.1, 140.0, 143.1, 145.0; mass spectrum
(ES) m/z 347 (M+Na)+; Anal. Calcd for C14H16N2O3S2: C, 51.83;
H, 4.97; N, 8.63; S, 19.77. Found: C, 51.58; H, 4.92; N, 8.55;
S, 20.04.
4.2. (S)- and (R)-N-(p-Toluenesulfonyl)-p-toluenesulfonimidamide
(S)- and (R)-1a
The previously obtained crude N-(p-toluenesulfonyl)-p-tolu-
enesulfonimidoyl chloride 3a was dissolved in dichloromethane
(80 ml) and a mixture of (R)-(ꢀ)-a-methylbenzylamine (3.24 mL,
25.2 mmol) and sodium hydrogenocarbonate (2.1 g, 25.2 mmol)
in water (50 ml) was added at 0 °C. After 30 min, the ice bath
was removed and the reaction mixture was stirred overnight at
room temperature. The organic layer was separated and washed
successively with 10% HCl and water, dried with MgSO4, and con-
centrated under vacuum to afford a pasty yellow solid. The latter
was dissolved in ethyl ether (40 ml) and after cooling, filtration
afforded 2.1 g of a white solid (de >95% as estimated by 1H
NMR). A second crop was obtained from the mother liquor
(0.8 g) yielding a total of 2.9 g (6.77 mmol, 32%) of pure com-
4.4. (S)-N-(p-Toluenesulfonyl)-p-nitrobenzenesulfonimidamide
(S)-1b
The crude N-(p-toluenesulfonyl)-p-nitrobenzenesulfonimidoyl
chloride was dissolved in dichloromethane (150 ml) and a mixture
of (R)-(ꢀ)-a-methylbenzylamine (9.86 mL, 76.2 mmol) and so-
dium hydrogenocarbonate (6.4 g, 76.2 mmol) in water (110 ml)
was added at 0 °C. After 30 min, the ice bath was removed and
the reaction mixture was stirred overnight at room temperature.
The organic layer was separated and washed successively with
10% HCl and water, dried with MgSO4, and concentrated under
vacuum to afford a pasty yellow solid. The latter was dissolved
in a mixture of ethyl acetate (100 mL) and ethyl ether (200 mL).
After refrigerating (in a few cases where no precipitate was
formed, the two diastereoisomers were separated by flash chro-
matography on silica gel), filtration afforded 3.2 g of a white solid
(de >90 % as estimated by 1H NMR). A second crop was obtained
from the mother liquor (2.1 g) yielding a total of 5.3 g (11.5 mmol,
18%) of pure compound. mp 148–149 °C; IR (neat, cmꢀ1) 3306,
1607, 1529, 1349, 1319, 1258, 1152, 1058, 1010, 950; 1H NMR
(300 MHz, CDCl3) d 1.62 (d, J = 6.9 Hz, 3H), 2.44 (s, 3H), 4.60 (q,
J = 6.9 Hz, 1H), 7.01 (m, 5H), 7.14 (d, J = 6.7 Hz, 1H), 7.30 (d,
J = 7.8 Hz, 2H), 7.74 (d, J = 7.8 Hz, 2H), 7.86 (d, J = 7.8 Hz, 2H),
7.94 (d, J = 7.8 Hz, 2H); 13C NMR (75 MHz, CDCl3) d 21.6, 23.5,
54.4, 123.5, 126.6, 126.8, 127.9, 128.4, 128.8, 129.4, 139.9, 140.1,
143.5, 144.9, 149.7; mass spectrum (ES) m/z 482 (M+Na)+; HRMS
pound (R,S)-4a. Mp 156–156.5 °C; ½a D20
¼ þ118:8 (c 0.44, CHCl3);
ꢁ
IR (cmꢀ1) 3232, 1594, 1301, 1152, 1106, 1070, 1017, 813, 755,
700, 657; 1H NMR (300 MHz, CDCl3) d 1.35 (d, J = 7.0 Hz, 3H),
2.41 (s, 3H), 2.43 (s, 3H), 4.52 (q, J = 7.0 Hz, 1H), 6.18 (d,
J = 7.0 Hz, 1H), 7.26 (m, 9H), 7.82 (m, 4H); 13C NMR (75 MHz,
CDCl3) d 21.5, 21.6, 23.0, 54.0, 126.4, 126.9, 127.8, 127.9, 128.7,
129.3, 129.7, 136.2, 140.5, 141.8, 142.9, 144.7; mass spectrum
(ES) m/z 451 (M+Na)+; Anal. Calcd for C22H24N2O3S2: C, 61.66;
H, 5.64; N, 6.54; S, 14.96. Found: C, 61.26; H, 5.53; N, 6.57; S,
14.93.
The pure diastereoisomer (2.9 g, 6.77 mmol) was dissolved in
trifluoroacetic acid (6 mL). After stirring for 40 h at 35 °C, the reac-
tion mixture was evaporated under vacuum, leaving a crude green
solid. The latter was purified by flash chromatography (heptane/
ethyl acetate 1:1) and then crystallized from ethyl acetate to afford
(ꢀ)-N-(p-toluenesulfonyl)-p-toluenesulfonimidamide (S)-2a (1.6 g,
72%). Mp 152.0–152.5 °C; ½a D20
ꢁ
¼ ꢀ110 (c 0.47, acetone); ee >99%
).
(HPLC, Chiracel AD, 4.6 ꢂ 250, 10
l
m/z ((M+Na)+) calcd for C21H21N3NaO5S2 482.0820, found
482.0787.
Following the same procedure using (S)-(ꢀ)-
a-methylbenzyl-
amine, (R)-1a was isolated in 21% yield as a white solid. ½a D20
ꢁ
¼
The pure diastereoisomer (5.3 g, 11.5 mmol) was dissolved in
trifluoroacetic acid (11 mL). After stirring for 40 h at 35 °C, the
reaction mixture was evaporated under vacuum, leaving a crude
green solid. The latter was purified by flash chromatography (hep-
tane/ethyl acetate 1:1) and then crystallized from ethyl acetate to
afford (ꢀ)-N-(p-toluenesulfonyl)-p-nitrobenzenesulfonimidamide
þ110 (c 0.47, acetone); ee >99% (HPLC, Chiracel AD, 4.6 ꢂ 250, 10
l).
4.3. N-(p-Toluenesulfonyl)-p-nitrobenzenesulfonimidamide 1b
A well-stirred mixture of p-nitrothiophenol (10 g, 64.4 mmol)
and acetic acid (3.7 mL, 64.4 mmol) was cooled to ꢀ40 °C. Sulfuryl
chloride (10.9 mL, 135.2 mmol) was added dropwise (gas evolution
was observed). Stirring was continued for 30 min at ꢀ40 °C, and
the mixture was then allowed to return to room temperature over
a period of 2 h. The mixture was then stirred at room temperature
for 2 h, and then overnight at 30 °C (gas evolution ceased). The
reaction mixture was then concentrated under vacuum to remove
acetyl chloride, affording a yellow solid. This solid was dissolved in
toluene (200 mL) and anhydrous chloramine-T (Caution! The trihy-
drate was dried in a drying pistol at 80 °C for 8 h. Explosion may
(S)-1b (3.0 g, 71%). ½a D20
¼ ꢀ140:7 (c 0.54, acetone); ee >99% (HPLC,
ꢁ
Chiracel OD, 4.6 ꢂ 250, 10
l, hexane + 0.1%HCOOH/EtOH + 0.1%H-
COOH: 90/10, 1 mL/min).
4.5. (S)-N-(p-Toluenesulfonyl)-p-chlorobenzenesulfonimidamide
(S)-1g
Prepared from p-chlorothiophenol according to the procedure
described for the synthesis of (S)-1b, the corresponding sulfonimi-
damide (S)-1g was obtained as a white solid in 98% ee (HPLC,

F. Robert-Peillard et al. / Tetrahedron: Asymmetry 21 (2010) 1447–1457
1453
Chiracel OD, 4.6 ꢂ 250, 10
l
, hexane + 0.1%HCOOH/EtOH + 0.1%H-
cmꢀ1) 2939, 2868, 1749, 1595, 1438, 1325, 1157, 1100, 1089,
900, 811, 758, 700; 1H NMR (300 MHz, CDCl3) d 1.60 (s, 3H), 1.72
(s, 3H), 2.37 (s, 3H), 2.43 (s, 3H), 2.68 (s, 1H), 2.75 (s, 1H), 2.93 (s,
1H), 3.03 (s, 1H), 3.66 (s, 3H), 3.72 (s, 3H), 7.27 (m, 4H), 7.81 (m,
4H); 13C NMR (75 MHz, CDCl3) d 14.5, 21.4, 21.6, 37.6, 39.2, 48.2,
48.9, 53.0, 53.1, 126.6, 127.7, 128.1, 128.9, 129.0, 129.7, 129.8,
135.5, 135.7, 140.3, 142.5, 142.6, 145.4, 145.5, 167.6, 167.7; Mass
spectrum (ES) 423 (M+H)+, 445 (M+Na)+; Anal. Calcd for
COOH: 90/10, 1 mL/min). Mp 196–197 °C; ½a D20
¼ ꢀ132:8 (c 1.00,
ꢁ
acetone); IR (KBr, cmꢀ1) 3173, 1573, 1394, 1248, 1051, 808, 752,
696, 655; 1H NMR (300 MHz, CD3COCD3) d 2.40 (s, 3H), 7.24–
7.31 (m, 4H), 7.61 (d, J = 8.8 Hz, 2H), 7.66 (d, J = 8.3 Hz, 2H), 7.90
(d, J = 8.3 Hz, 2H); 13C NMR (75 MHz, CDCl3) d 21.4, 127.3, 129.7,
129.9, 130.0, 140.0, 142.0, 142.3, 143.2; mass spectrum (ES) m/z
344 (M+); HRMS m/z (M+Na)+ calcd for C13H13ClN2NaO3S2
366.9954, found 366.9940.
C19H22N2O5S2: C, 54.01; H, 5.25; N, 6.63; S, 15.18. Found: C,
54.25; H, 5.34; N, 6.46; S, 14.99.
4.6. Typical aziridination procedure with Cu(CH3CN)4PF6
4.10. trans-N-[N-(p-Toluenesulfonyl)-p-toluenesulfonimidoyl]-
2-methoxycarbonyl-3-methylaziridine 7a
In an oven-dried tube were introduced activated 4 Å molecular
sieves (50 mg), Cu(CH3CN)4PF6 (8 mg, 0.02 mmol), the sulfonimi-
damide (0.24 mmol), and PhI@O (54 mg, 0.24 mmol). The tube
was cooled to ꢀ30 °C and, under argon, acetonitrile (0.7 mL) fol-
lowed by the olefin (0.2 mmol) were added. The mixture was
placed in a freezer (ꢀ25 °C) for 48 h. After dilution with dichloro-
methane (5 mL), the molecular sieves were removed by filtration
and the filtrate was evaporated to dryness under reduced pressure.
The oily residue was purified by flash chromatography on silica gel,
affording the aziridines as a mixture of diastereomers.
Prepared according to the general procedure with Cu(CH3CN)4-
PF6 from trans-methyl crotonate, the corresponding aziridine 7a
was obtained (heptane/ethyl acetate 75/25) as a pasty white solid
in 35% yield and 50% de. Rf (silica, EtOAc/heptane: 1/1): 0.55; IR
(neat, cmꢀ1) 3031, 2955, 2925, 1748, 1595, 1442, 1404, 1320,
1244, 1156, 1106, 1089, 1063, 1016, 971, 908, 877, 814, 736,
705, 678, 657; 1H NMR (300 MHz, CDCl3) d 1.49 (d, J = 6.4 Hz, 3H),
1.63 (d, J = 6.4 Hz, 3H), 2.38 (s, 3H), 2.39 (s, 3H), 2.43 (s, 3H), 2.45
(s, 3H), 3.14 (m, 1H), 3.26 (m, 1H), 3.30 (d, J = 4.6 Hz, 1H), 3.64 (s,
3H), 3.68 (d, J = 4.6 Hz, 1H), 3.76 (s, 3H), 7.23 (m, 4H), 7.80 (m,
4H); 13C NMR (75 MHz, CDCl3) d 12.2, 13.0, 21.4, 21.6, 42.8, 44.5,
46.1, 46.4, 52.5, 52.8, 126.6, 127.7, 128.0, 129.0, 129.1, 129.7,
129.8, 135.1, 140.3, 142.9, 145.4, 166.6; Mass spectrum (ES) m/z
445 (M+Na)+; Anal. Calcd for C19H22N2O5S2: C, 54.01; H, 5.25; N,
6.63; S, 15.18. Found: C, 54.18; H, 5.39; N, 6.49; S, 15.03.
4.7. Typical aziridination procedure with CuOTf
In an oven-dried tube were introduced activated 4 Å molecular
sieves (50 mg), the sulfonimidamide (0.24 mmol), and PhI@O
(54 mg, 0.24 mmol). The tube was purged with argon and placed
in a Sigma–Aldrich AtmosBag which was filled with argon. Under
argon, CuOTf (10 mg, 0.02 mmol) was added, the tube was tightly
closed and removed from the AtmosBag. The tube was cooled to
ꢀ30 °C and, under argon, acetonitrile (0.7 mL) followed by the ole-
fin (0.2 mmol) were added. The mixture was placed in a freezer
(ꢀ25 °C) for 48 h. After dilution with dichloromethane (5 mL),
the molecular sieves were removed by filtration and the filtrate
was evaporated to dryness under reduced pressure. The oily resi-
due was purified by flash chromatography on silica gel, affording
the aziridines as a mixture of diastereomers.
4.11. trans-N-[N-(p-Toluenesulfonyl)-p-toluenesulfonimidoyl]-
2,3-dimethyl-2-methoxycarbonylaziridine 8a
Prepared according to the general procedure with Cu(CH3CN)4-
PF6 from trans-methyl tiglate, the corresponding aziridine 8a was
obtained (heptane/ethyl acetate 80/20) as a pasty white solid in
92% yield and 38% de. Rf (silica, EtOAc/heptane: 1/1): 0.60; IR (neat,
cmꢀ1) 3023, 2955, 2910, 1748, 1595, 1442, 1404, 1320, 1244, 1156,
1106, 1089, 1063, 1016, 971 , 908, 877, 814, 736, 705, 678, 657; 1H
NMR (300 MHz, CDCl3) d 1.19 (d, J = 5.8 Hz, 3H), 1.39 (d, J = 5.8 Hz,
3H), 1.40 (s, 3H), 1.48 (s, 3H), 2.37 (s, 3H), 2.44 (s, 3H), 3.62 (s, 3H),
3.63 (s, 3H), 3.65 (q, J = 5.8 Hz, 1H), 3.90 (q, J = 5.8 Hz, 1H), 7.21 (m,
4H), 7.81 (m, 4H); 13C NMR (75 MHz, CDCl3) d 12.3, 15.4, 15.6,
21.5, 21.7, 44.5, 45.8, 52.9, 54.2, 54.5, 126.7, 126.9, 127.8, 128.0,
128.9, 129.0, 129.1, 129.4, 129.7, 136.4, 140.4, 142.5, 145.1, 167.3,
167.4; Mass spectrum (ES) m/z 459 (M+Na)+; Anal. Calcd for
4.8. N-[N-(p-Toluenesulfonyl)-p-toluenesulfonimidoyl]-2-meth-
oxycarbonylaziridine 5a
Prepared according to the general procedure with Cu(CH3CN)4-
PF6 from methyl acrylate, the corresponding aziridine 5a was ob-
tained (heptane/ethyl acetate 7/3) as a pasty white solid in 81% yield
and 50% de. Rf (silica, EtOAc/heptane: 1/1): 0.40; IR (neat, cmꢀ1
)
2938, 2878, 1747, 1595, 1439, 1322, 1157, 1106, 1089, 909, 814,
758, 704, 660; 1H NMR (300 MHz, CDCl3) d 2.38 (s, 3H), 2.43 (s, 3H),
2.52 (d, J = 4.3 Hz, 1H), 2.67 (d, J = 4.3 Hz, 1H), 2.85 (d, J = 7.3 Hz, 1H),
3.02 (d, J = 7.3 Hz, 1H), 3.46 (dd, J = 7.6 and 4.3 Hz, 1H), 3.57 (dd,
J = 7.6 and 4.3 Hz, 1H), 3.70 (s, 3H), 3.74 (s, 3H), 7.20 (d, J = 8.0 Hz,
2H), 7.33 (d, J = 8.1 Hz, 2H), 7.78 (d, J = 8.0 Hz, 2H), 7.84 (d,
J = 7.8 Hz, 2H); 13C NMR (75 MHz, CDCl3) d 21.5, 21.7, 32.4, 34.1,
36.5, 37.9, 52.9, 53.0, 126.6, 128.1, 128.2, 129.2, 130.0, 133.3, 133.4,
140.1, 140.2, 142.9, 143.0, 146.2, 166.4; Mass spectrum (ES) m/z 409
(M+H)+, 431 (M+Na)+; Anal. Calcd for C18H20N2O5S2: C, 52.92; H,
4.93; N, 6.86; S, 15.70. Found: C, 52.88; H, 5.06; N, 6.68; S, 15.55.
C20H24N2O5S2: C, 55.03; H, 5.54; N, 6.42; S, 14.69. Found: C, 55.36;
H, 5.61; N, 6.33; S, 14.73.
4.12. N-[N-(p-Toluenesulfonyl)-p-toluenesulfonimidoyl]-2-
pentylaziridine 9a
Prepared according to the general procedure with Cu(CH3CN)4-
PF6 from heptene, the corresponding aziridine 9a was obtained
(heptane/ethyl acetate 70/30) as a pasty white solid in 60% yield
and 10% de. Rf (silica, EtOAc/heptane: 1/1): 0.50; IR (neat, cmꢀ1
)
2980, 2927, 2859, 1596, 1322, 1250, 1157, 1106, 1090, 1072, 975,
813, 757, 708, 664; 1H NMR (300 MHz, CDCl3) d 0.8 (m, 3H), 1.00–
1.5 (m, 8H), 2.09 (d, J = 5.8 Hz, 1H), 2.25 (d, J = 5.8 Hz, 1H), 2.36 (s,
3H), 2.43 (s, 3H), 2.74 (d, J = 7.5 Hz, 1H), 2.79 (m, 1H), 2.89 (d,
J = 7.5 Hz, 1H), 2.94 (m, 1H), 7.19 (d, J = 7.2 Hz, 2H), 7.31 (d,
J = 7.2 Hz, 2H), 7.81 (m, 4H); 13C NMR (75 MHz, CDCl3) d 13.8, 21.5,
21.7, 22.4, 26.1, 30.9, 31.2, 34.3, 43.0, 126.7, 128.1, 129.1, 129.8,
140.8, 142.0, 142.1, 142.6, 143.1, 144.5, 145.4; Mass spectrum (ES)
4.9. N-[N-(p-Toluenesulfonyl)-p-toluenesulfonimidoyl]-2-meth-
oxycarbonyl-2-methylaziridine 6a
Prepared according to the general procedure with Cu(CH3CN)4-
PF6 from methyl methacrylate, the corresponding aziridine 6a was
obtained (heptane/ethyl acetate 7/3) as a pasty white solid in 96%
yield and 41% de. Rf (silica, EtOAc/heptane: 1/1): 0.50; IR (neat,

1454
F. Robert-Peillard et al. / Tetrahedron: Asymmetry 21 (2010) 1447–1457
m/z 443 (M+Na)+; Anal. Calcd for C21H28N2O3S2: C, 59.97; H, 6.71; N,
6.66; S, 15.25. Found: C, 60.01; H, 6.54; N, 6.54; S, 15.01.
2937, 2865, 1587, 1494, 1398, 1318, 1226, 1155, 1133, 1108,
1093, 1014, 917, 853, 792, 755, 716; 1H NMR (300 MHz, CDCl3) d
1.61 (m, 4H), 1.86 (m, 1H), 1.98 (m, 1H), 2.37 (s, 3H), 2.42 (s,
3H), 3.45 (m, 1H), 3.63 (m, 1H), 7.20 (d, J = 8 Hz, 2H), 7.29 (d,
J = 8 Hz, 2H), 7.77 (d, J = 8 Hz, 2H), 7.81 (d, J = 8 Hz, 2H); 13C NMR
(75 MHz, CDCl3) d 19.4, 21.5, 21.7, 27.0, 27.1, 48.2, 49.9, 126.7,
127.7, 129.1, 129.8, 135.4, 140.8, 142.5, 145.0; Mass spectrum
(ES) m/z 391 (M+H)+, 413 (M+Na)+; Anal. Calcd for C19H22N2O3S2:
C, 58.44; H, 5.68; N, 7.17; S, 16.42. Found: C, 58.67; H, 5.91; N,
6.94; S, 16.13.
4.13. trans-N-[N-(p-Toluenesulfonyl)-p-toluenesulfonimidoyl]-
1-methyl-2-propylaziridine 10a
Prepared according to the general procedure with Cu(CH3CN)4-
PF6 from trans-hex-2-ene, the corresponding aziridine 10a was ob-
tained (heptane/ethyl acetate 80/20) as a pasty white solid in 40%
yield. Rf (silica, EtOAc/heptane: 1/1): 0.50; IR (neat, cmꢀ1) 2953,
2902, 1591, 1354, 1317, 1253, 1123, 1088, 1070, 953, 830, 755,
712, 698; 1H NMR (300 MHz, CDCl3) d 0.75 (t, J = 7.4 Hz, 3H), 0.85
(t, J = 7.4 Hz, 3H), 1.39 (d, J = 5.6 Hz, 3H), 1.43 (d, J = 5.7 Hz, 3H),
1.10–1.65 (m, 4H), 2.36 (s, 3H), 2.43 (s, 3H), 2.70–2.95 (m, 2H),
7.17 (t, J = 7.8 Hz, 2H), 7.29 (d, J = 7.7 Hz, 2H), 7.80 (m, 4H); 13C
NMR (75 MHz, CDCl3) d 13.5, 13.6, 14.2, 14.3, 20.3, 20.4, 21.6, 21.7,
31.5, 31.9, 47.1, 47.5, 49.6, 51.4, 126.7, 126.8, 127.6, 128.1, 129.0,
129.7, 136.9, 137.1, 140.7, 140.9, 142.3, 144.8; Mass spectrum (ES)
m/z 429 (M+Na)+; Anal. Calcd for C20H26N2O3S2: C, 59.08; H, 6.45;
N, 6.89; S, 15.77. Found: C, 59.21; H, 6.67; N, 6.73; S, 15.59.
4.17. N-[N-(p-Toluenesulfonyl)-p-toluenesulfonimidoyl]-2-
phenylaziridine 14a
Prepared according to the general procedure with Cu(CH3CN)4-
PF6 from styrene, the corresponding aziridine 14a was obtained
(heptane/ethyl acetate 75/25) as a pasty white solid in 63% yield
and 20% de. Rf (silica, EtOAc/heptane: 1/1): 0.45; IR (neat, cmꢀ1
)
3035, 2965, 1596, 1319, 1155, 1106, 1089, 909, 813, 752, 700,
665; 1H NMR (300 MHz, CDCl3) d 2.38 (s, 3H), 2.39 (s, 3H), 2.42
(s, 3H), 2.44 (d, J = 4.8 Hz, 1H), 2.58 (d, J = 4.8 Hz, 1H), 3.12 (d,
J = 7.6 Hz, 1H), 3.24 (d, J = 7.6 Hz, 1H), 3.84 (dd, J = 7.6 and 4.8 Hz,
1H), 3.98 (dd, J = 7.6 and 4.8 Hz, 1H), 7.20 (m, 9H), 7.82 (m, 4H);
13C NMR (75 MHz, CDCl3) d 21.3, 21.5, 36.0, 37.6, 42.0, 43.4,
126.4, 126.5, 126.6, 127.7, 128.5, 129.0, 129.1, 129.8, 133.7,
134.1, 134.2, 140.4, 142.5, 142.6, 145.5; Mass spectrum (ES) m/z
426 (M)+; Anal. Calcd for C22H22N2O3S2: C, 61.95; H, 5.20; N,
6.57; S, 15.03. Found: C, 61.74; H, 5.21; N, 6.36; S, 15.01.
4.14. cis-N-[N-(p-Toluenesulfonyl)-p-toluenesulfonimidoyl]-1-
methyl-2-propylaziridine 11a
Prepared according to the general procedure with Cu(CH3CN)4-
PF6 from cis-hex-2-ene, the corresponding aziridine 11a was ob-
tained (heptane/ethyl acetate 80/20) as a pasty white solid in
57% yield. Rf (silica, EtOAc/heptane: 1/1): 0.55; IR (neat, cmꢀ1
)
2955, 2902, 1592, 1356, 1317, 1249, 1123, 1088, 1071, 954, 830,
757, 712, 698; 1H NMR (300 MHz, CDCl3) d 0.79 (t, J = 7.4 Hz, 3H),
0.87 (t, J = 7.4 Hz, 3H), 1.16 (d, J = 5.8 Hz, 3H), 1.26 (d, J = 5.9 Hz,
3H), 1.10–1.55 (m, 4H), 2.36 (s, 3H), 2.43 (s, 3H), 2.85 (dt,
J = 7.5 Hz and J = 5.8 Hz, 1H), 3.00 (dt, J = 7.5 Hz and J = 5.8 Hz,
1H), 3.01 (dq, J = 5.8 Hz and J = 7.5 Hz, 1H), 3.20 (dq, J = 5.8 Hz and
J = 7.5Hz, 1H), 7.19 (d, J = 7.2 Hz, 2H), 7.31 (d, J = 7.2 Hz, 2H), 7.80
(m, 4H); 13C NMR (75 MHz, CDCl3) d 11.6, 13.6, 13.8, 20.1, 20.2,
21.6, 21.7 28.1, 41.2, 43.2, 46.9, 47.4, 126.7, 128.1, 129.1, 129.7,
135.0, 140.7, 142.5, 145.1; Mass spectrum (ES) m/z 429 (M+Na)+;
Anal. Calcd for C20H26N2O3S2: C, 59.08; H, 6.45; N, 6.89; S, 15.77.
Found: C, 59.13; H, 6.54; N, 6.78; S, 15.91.
4.18. N-[N-(p-Toluenesulfonyl)-p-toluenesulfonimidoyl]-
1,2,3,4-tetrahydronaphthalen-1,2-imine 15a
Prepared according to the general procedure with Cu(CH3CN)4-
PF6 from 1,2-dihydronaphthalene, the corresponding aziridine 15a
was obtained (heptane/ethyl acetate 80/20) as a pasty white solid
in 63% yield and 25% de. Rf (silica, EtOAc/Heptane: 1/1): 0.55; IR
(neat, cmꢀ1) 2923, 1596, 1316, 1302, 1252, 1153, 1107, 1089,
944, 907, 875, 813, 751, 707, 667; 1H NMR (300 MHz, CDCl3) d
1.68 (m, 2H), 2.33 (m, 2H), 2.38 (s, 3H), 2.39 (s,3H), 2.40 (s, 3H),
2.41 (s, 3H), 2.65 (m, 2H), 3.66 (d, J = 7.2Hz, 1H), 3.83 (d,
J = 7.2 Hz, 1H), 3.89 (m, 1H), 4.10 (m, 1H), 7.20 (m, 8H), 7.80 (m,
4H); 13C NMR (75 MHz, CDCl3) d 19.8, 19.9, 21.6, 21.7, 24.7, 42.9,
43.4, 44.7, 44.9, 126.3, 126.7, 127.6, 128.6, 128.8, 129.2, 129.5,
129.8, 133.1, 134.5, 135.2, 136.6, 136.8, 140.3, 140.6, 142.6, 142.8,
144.7, 145.2; Mass spectrum (ES) m/z 507 (M+Na+CH3OH)+; Anal.
Calcd for C24H24N2O3S2: C, 63.69; H, 5.34; N, 6.19; S, 14.17. Found:
C, 63.95; H, 5.61; N, 5.98; S, 13.83.
4.15. N-[N-(p-Toluenesulfonyl)-p-toluenesulfonimidoyl]-7-
azabicyclo[4.1.0]heptane 12a
Prepared according to the general procedure with Cu(CH3CN)4-
PF6 from cyclohexene, the corresponding aziridine 12a was ob-
tained (heptane/ethyl acetate 80/20) as a pasty white solid in
62% yield. Rf (silica, EtOAc/heptane: 1/1): 0.60; IR (neat, cmꢀ1
)
2939, 2865, 1596, 1494, 1438, 1401, 1318, 1253, 1228, 1155,
1108, 1090, 1016, 962, 920, 847, 814, 794, 756, 718, 666; 1H
NMR (300 MHz, CDCl3) d 1.23 (m, 2H), 1.37 (m, 2H), 1.70 (m,
2H), 1.84 (m, 2H), 2.37 (s, 3H), 2.42 (s, 3H), 3.06 (m, 1H), 3.26
(m, 1H), 7.18 (d, J = 9.5 Hz, 2H), 7.28 (d, J = 9.5 Hz, 2H), 7.77 (d,
J = 9.5 Hz, 2H), 7.81 (d, J = 9.5 Hz, 2H); 13C NMR (75 MHz, CDCl3)
d 19.3, 19.4, 21.6, 21.7, 22.5, 22.7, 41.2, 43.0, 126.8, 127.7, 129.2,
129.8, 135.3, 140.9, 142.5, 145.0; Mass spectrum (ES) m/z 459
(M+Na+CH3OH)+; Anal. Calcd for C20H24N2O3S2: C, 59.38; H, 5.98;
N, 6.92; S, 15.85. Found: C, 59.52; H, 5.96; N, 6.78; S, 15.71.
4.19. N-[N-(p-Toluenesulfonyl)-p-nitrobenzenesulfonimidoyl]-
2-methoxycarbonylaziridine 5b
Prepared according to the general procedure with Cu(OTf) from
methyl acrylate, the corresponding aziridine 5b was obtained
(heptane/ethyl acetate 7/3) as a white solid in 88% yield and 80% de
(HPLC, Hypercarb column, 100 ꢂ 4.6 mm, 5
l, MeCN + 0.1%TFA/
H2O: 80/20, 1 mL/min). Rf (silica, EtOAc/heptane: 1/1): 0.50; mp
43–44 °C; IR (neat, cmꢀ1) 3106, 2929, 1745, 1606, 1530, 1494, 1440,
1401, 1349, 1318, 1231, 1154, 1104, 1061; 1H NMR (300 MHz, CDCl3)
d 2.41 (s, 3H), 2.69 (d, J = 4.3 Hz, 1H), 2.84 (d, J = 4.3 Hz, 1H), 2.98 (d,
J = 7.3 Hz, 1H), 3.15 (d, J = 7.3 Hz, 1H), 3.56 (dd, J = 7.6 and 4.3 Hz,
1H), 3.69 (dd, J = 7.6 and 4.3 Hz, 1H), 3.74 (s, 3H), 3.78 (s, 3H), 7.26 (d,
J = 8.0 Hz, 2H), 7.79 (d, J = 8.1 Hz, 2H), 8.19 (d, J = 8.0 Hz, 2H), 8.39
(d, J = 7.8 Hz, 2H); 13C NMR (75 MHz, CDCl3) d 21.6, 34.7, 36.9, 53.3,
124.6, 126.8, 129.5, 129.7, 139.5, 142.7, 143.7, 151.2, 165.8; Mass
spectrum (ES) m/z 462 (M+Na)+ HRMS m/z (M+Na)+ calcd for
4.16. N-[N-(p-Toluenesulfonyl)-p-toluenesulfonimidoyl]-6-
azabicyclo[3.1.0]hexane 13a
Prepared according to the general procedure with Cu(CH3CN)4-
PF6 from cyclopentene, the corresponding aziridine 13a was ob-
tained (heptane/ethyl acetate 70/30) as a pasty white solid in
59% yield. Rf (silica, EtOAc/heptane: 1/1): 0.50; IR (neat, cmꢀ1
)
C17H17N3NaO7S2 462.0406, found: 462.0449.

F. Robert-Peillard et al. / Tetrahedron: Asymmetry 21 (2010) 1447–1457
1455
4.20. N-[N-(p-Toluenesulfonyl)-p-nitrobenzenesulfonimidoyl]-
2-t-butyloxycarbonylaziridine 16b
34.9, 36.7, 42.6, 43.9, 124.4, 126.7, 129.1, 129.4, 139.9, 140.0, 143.2,
144.7, 150.8; Mass spectrum (ES) m/z 474 (M+Na)+ HRMS m/z
(M+Na)+ calcd for C20H25N3NaO5S2 474.1133, found 474.1130.
Prepared according to the general procedure with Cu(OTf) from
t-butyl acrylate, the corresponding aziridine 16b was obtained
(heptane/ethyl acetate 7/3) as a white solid in 80% yield and 94%
4.24. N-[N-(p-Toluenesulfonyl)-p-nitrobenzenesulfonimidoyl]-
7-azabicyclo[4.1.0]heptane 12b
de (HPLC, Hypercarb column, 100 ꢂ 4.6 mm, 5
l, MeCN + 0.1%T-
FA/H2O: 80/20, 1 mL/min). Rf (silica, EtOAc/heptane: 1/1): 0.45;
mp 133–134 °C; IR (neat, cmꢀ1) 3106, 2980, 1736, 1605, 1530,
1494, 1476, 1456, 1396, 1368, 1348, 1324, 1241, 1153, 1104,
1087, 1056, 1009; 1H NMR (300 MHz, CDCl3) d 1.41 (s, 9H), 2.41
(s, 3H), 2.66 (d, J = 4.6 Hz, 1H), 2.80 (d, J = 4.6 Hz, 1H), 2.96 (d,
J = 7.3 Hz, 1H), 3.10 (d, J = 7.3 Hz, 1H), 3.43 (dd, J = 7.6 and 4.3 Hz,
1H), 3.58 (dd, J = 7.6 and 4.3 Hz, 1H), 7.27 (d, J = 8.0 Hz, 2H), 7.79
(d, J = 8.1 Hz, 2H), 8.20 (d, J = 8.0 Hz, 2H), 8.40 (d, J = 7.8 Hz, 2H);
13C NMR (75 MHz, CDCl3) d 21.5, 27.8, 34.5, 38.0, 84.0, 124.4,
126.7, 129.4, 129.6, 139.5, 143.1, 143.6, 151.1, 164.2; Mass spec-
trum (ES) m/z 504 (M+Na)+; HRMS m/z (M+Na)+ calcd for
C20H23N3NaO7S2 504.0875, found 504.0859.
Prepared according to the general procedure with Cu(OTf) from
cyclohexene, the corresponding aziridine 12b was obtained (hep-
tane/ethyl acetate 7/3) as a white solid in 93% yield. Rf (silica,
EtOAc/heptane: 1/1): 0.50; mp 143–144 °C; IR (neat, cmꢀ1) 3104,
2932, 1604, 1528, 1440, 1400, 1349, 1308, 1255, 1153, 1091,
1058, 954; 1H NMR (300 MHz, CDCl3) d 1.32 (m, 4H), 1.82 (m,
4H), 2.39 (s, 3H), 3.19 (m, 1H), 3.41 (m, 1H), 7.23 (d, J = 8.0 Hz,
2H), 7.76 (d, J = 8.1 Hz, 2H), 8.16 (d, J = 8.0 Hz, 2H), 8.36 (d,
J = 7.8 Hz, 2H); 13C NMR (75 MHz, CDCl3) d 19.1, 19.2, 21.5, 22.4,
22.5, 42.1, 44.0, 124.4, 126.7, 129.1, 129.4, 140.0, 143.1, 144.5,
150.6; Mass spectrum (ES) m/z 458 (M+Na)+ HRMS m/z (M+Na)+
calcd for C19H21N3NaO5S2 458.0820, found 458.0805.
4.21. N-[N-(p-Toluenesulfonyl)-p-nitrobenzenesulfonimidoyl]-
2-methoxycarbonyl-2-methylaziridine 6b
4.25. N-[N-(p-Toluenesulfonyl)-p-nitrobenzenesulfonimidoyl]-
7-azabicyclo[4.1.0]heptane 13b
Prepared according to the general procedure with Cu(OTf) from
methyl methacrylate, the corresponding aziridine 6b was obtained
(heptane/ethyl acetate 7/3) as a white solid in 95% yield and 36%
de. Rf (silica, EtOAc/heptane: 1/1): 0.40; mp 44–45 °C; IR (neat,
cmꢀ1) 3106, 2957, 1745, 1530, 1494, 1440, 1401, 1349, 1318,
1257, 1231, 1154, 1104, 1086, 1055, 1009; 1H NMR (300 MHz,
CDCl3) d 1.68 (s, 3H), 1.77 (s, 3H), 2.40 (s, 3H), 2.78 (s, 1H), 2.87 (s,
1H), 3.00 (s, 1H), 3.17 (s, 1H), 3.69 (s, 3H), 3.77 (s, 3H), 7.24 (m,
2H), 7.75 (m, 2H), 8.18 (m, 2H), 8.37 (m, 2H); 13C NMR (75 MHz,
CDCl3) d 15.1, 15.6, 21.5, 38.3, 40.4, 48.9, 50.2, 53.3, 53.6, 124.3,
124.4, 126.7, 129.2, 129.3, 129.7, 139.8, 143.3, 143.4, 144.7, 145.2,
150.7, 167.2, 167.4; Mass spectrum (ES) m/z 476 (M+Na)+ HRMS m/
z (M+Na)+ calcd for C18H19N3NaO7S2 476.0562, found 476.0565.
Prepared according to the general procedure with Cu(OTf) from
cyclohexene, the corresponding aziridine 13b was obtained (hep-
tane/ethyl acetate 7/3) as a white solid in 95% yield. Rf (silica,
EtOAc/heptane: 1/1): 0.50; mp 148–149 °C; IR (neat, cmꢀ1) 3104,
2933, 1604, 1528, 1440, 1400, 1349, 1308, 1255, 1153, 1091,
1057, 955; 1H NMR (300 MHz, CDCl3) d 1.37 (m, 1H), 1.66 (m,
3H), 1.88 (m, 1H), 2.02 (m, 1H), 2.38 (s, 3H), 3.55 (m, 1H), 3.75
(m, 1H), 7.22 (d, J = 8.0 Hz, 2H), 7.76 (d, J = 8.1 Hz, 2H), 8.13 (d,
J = 8.0 Hz, 2H), 8.34 (d, J = 7.8 Hz, 2H); 13C NMR (75 MHz, CDCl3)
d 19.3, 21.5, 27.0, 27.1, 49.3, 51.0, 124.4, 126.7, 129.1, 129.4,
140.0, 143.1, 144.5, 150.6; Mass spectrum (ES) m/z 444 (M+Na)+
HRMS m/z (M+Na)+ calcd for C18H19N3NaO5S2 444.0664, found
444.0636.
4.22. N-[N-(p-Toluenesulfonyl)-p-nitrobenzenesulfonimidoyl]-
2-cyanoaziridine 17b
4.26. N-[N-(p-Toluenesulfonyl)-p-nitrobenzenesulfonimidoyl]-
2-phenylaziridine 14b
Prepared according to the general procedure with Cu(OTf) from
acrylonitrile, the corresponding aziridine was obtained (heptane/
ethyl acetate 7/3) as an oily solid in 48% yield and 33% de (HPLC,
Prepared according to the general procedure with Cu(CH3CN)4-
PF6 from styrene, the corresponding aziridine 14b was obtained
(heptane/ethyl acetate 6/4) as a pasty white solid in 40% yield
and 10% de. I.R. (neat, cmꢀ1) 2924, 2012, 1600, 1529, 1347, 1154,
1060, 853, 812, 743, 664; 1H NMR (300 MHz, CDCl3) d 2.32 (s,
3H), 2.33 (s, 3H), 2.49 (dd, J = 0.8 and 4.9 Hz, 1H), 2.64 (dd, J = 0.8
and 4.9 Hz, 1H), 3.14 (dd, J = 0.8 and 7.3 Hz, 1H), 3.28 (dd, J = 0.8
and 7.3 Hz, 1H), 3.87 (dd, J = 4.9 and 7.3 Hz, 1H), 4.04 (dd, J = 4.9
and 7.3 Hz, 1H), 7.05–7.10 (m, 4H), 7.21–7.27 (m, 3H), 7.72 (dd,
J = 8.3 and 10.0 Hz, 2H), 8.11 (d, J = 8.9 Hz, 2H), 8.21–8.28 (m,
2H); 13C NMR (75 MHz, CDCl3) d 21.4, 38.4, 40.2, 42.9, 44.5,
124.4, 126.5, 126.6, 126.7, 126.8, 128.8, 129.1, 129.3, 129.4, 133.0,
139.9, 143.3, 143.7, 148.4.
Hypercarb column, 100 ꢂ 4.6 mm, 5
l, MeCN + 0.1%TFA/H2O: 75/
25, 1 mL/min). Rf (silica, EtOAc/heptane: 1/1): 0.50; 1H NMR
(300 MHz, CDCl3) d 2.47 (s, 3H), 2.85 (d, J = 3.6 Hz, 1H), 3.01 (d,
J = 3.7 Hz, 1H), 3.18 (d, J = 7.1 Hz, 1H), 3.36 (d, J = 7.2 Hz, 1H), 3.68
(m, 1H), 3.78 (m, 1H), 7.34 (d, J = 8.0 Hz, 2H), 7.85 (d, J = 8.1 Hz,
2H), 8.27 (d, J = 8.0 Hz, 2H), 8.48 (d, J = 7.8 Hz, 2H); 13C NMR
(75 MHz, CDCl3) d 21.6, 24.8, 26.7, 33.4, 35.3, 114.0, 124.8, 126.8,
129.6, 129.7, 139.0, 141.8, 144.2, 151.5; Mass spectrum (ES) m/z
429 (M+Na)+ HRMS m/z (M+Na)+ calcd for C16H14N4NaO5S2
429.0303, found 429.0329.
4.23. N-[N-(p-Toluenesulfonyl)-p-nitrobenzenesulfonimidoyl]-
4.27. Methyl 3-methoxy-2-[N-(p-toluenesulfonyl)-p-nitrobenzene-
2-pentylaziridine 9b
sulfonimidoyl]amino-propionate 18
Prepared according to the general procedure with Cu(OTf) from
heptene, the corresponding aziridine 9b was obtained (heptane/
ethyl acetate 7/3) as an oily solid in 92% yield. Rf (silica, EtOAc/hep-
tane: 1/1): 0.50; 1H NMR (300 MHz, CDCl3) d 0.81 (m, 3H), 1.24 (m,
6H), 1.52 (m, 2H), 2.20 (d, J = 7.1 Hz, 1H), 2.37 (d, J = 7.1 Hz, 1H),
2.39 (s, 3H), 2.81 (d, J = 7.1 Hz, 1H), 2.96 (d, J = 7.1 Hz, 1H), 2.97 (m,
1H), 3.08 (m, 1H), 7.23 (d, J = 8.0 Hz, 2H), 7.77 (d, J = 8.1 Hz, 2H),
8.16 (d, J = 8.0 Hz, 2H), 8.36 (d, J = 7.8 Hz, 2H); 13C NMR (75 MHz,
CDCl3) d 13.8, 13.9, 21.5, 22.3, 22.4, 26.1, 26.2, 30.7, 30.8, 30.9, 31.1,
Aziridine 5b (439 mg, 1 mmol) was dissolved in CH2Cl2 (2 mL)
and MeOH (2 mL). The reaction mixture was stirred overnight at
room temperature and then concentrated under reduced pressure.
Trituration of the product with ethyl ether followed by evaporation
of the solvent afforded 18 as a white solid in 99% yield (468 mg,
0.99 mmol). Mp 46–48 °C; Rf (silica, heptane/ethyl acetate: 1/1):
0.35; IR (neat, cmꢀ1) 3220, 3107, 2926, 1744, 1606, 1528, 1495,
14,36, 1402, 1348, 1304, 1290, 1263, 1152, 1105, 1063; 1H NMR

1456
F. Robert-Peillard et al. / Tetrahedron: Asymmetry 21 (2010) 1447–1457
2. (a) Tanner, D. Angew. Chem., Int. Ed. Engl. 1994, 33, 599–619; (b) McCoull, W.
M.; Davis, F. A. Synthesis 2000, 1347–1365; (c) Dahanukar, V. H.; Zavialov, I. A.
Curr. Opin. Drug Disc. Dev. 2002, 5, 918–927; (d) Hu, X. E. Tetrahedron 2004, 60,
2701–2743.
3. Schneider, C. Angew. Chem., Int. Ed. 2009, 48, 2082–2084.
4. (a) Harrity, J. P. A.; Provoost, O. Org. Biomol. Chem. 2005, 3, 1349–1358; (b)
Dauban, P.; Malik, G. Angew. Chem., Int. Ed. 2009, 48, 9026–9029.
5. Hodgson, D. M.; Humphreys, P. G.; Hughes, S. P. Pure Appl. Chem. 2007, 79, 269–
279.
6. Lowden, P. A. S. In Aziridines and Epoxides in Organic Synthesis; Yudin, A., Ed.;
Wiley-VCH: Weinheim, 2006; pp 399–442. Chapter 11.
(300 MHz, CDCl3) d 2.43 (s, 3H), 3.38 (s, 3H), 3.61 (s, 3H), 3.70 (m,
1H), 3.87 (dd, J = 8.0 and 9.5 Hz, 1H), 4.27 (t, J = 3.3 Hz, 1H), 7.29 (d,
J = 8.6 Hz, 1H), 7.83 (d, J = 8.3 Hz, 2H), 8.14 (d, J = 8.6 Hz, 2H), 8.33
(d, J = 7.8 Hz, 2H); 13C NMR (75 MHz, CDCl3) d 21.5, 53.0, 55.8, 59.5,
72.5, 124.1, 126.7, 128.9, 129.5, 140.0, 143.3, 144.8, 150.3, 168.7;
MS (ES) m/z 494 (M+Na)+; HRMS m/z (M+Na)+ calcd for
C18H21N3NaO8S2 494.0668, found 494.0681.
4.28. tert-Butyl 3-methoxy-2-[N-(p-toluenesulfonyl)-p-nitroben-
zenesulfonimidoyl]amino-propionate 19
7. (a) Osborn, H. M. I.; Sweeney, J. Tetrahedron: Asymmetry 1999, 8, 1693–1715;
(b) Müller, P.; Fruit, C. Chem. Rev. 2003, 103, 2905–2919; (c) Halfen, J. A. Curr.
Org. Chem. 2005, 9, 657–669; (d) Wipf, P.; Lyon, M. A. Arkivoc 2007, xii, 91–98;
(e) Sweeney, J. Eur. J. Org. Chem. 2009, 4911–4919; (f) Pellissier, H. Tetrahedron
2010, 66, 1509–1555.
Aziridine 16b (120 mg, 0.25 mmol) was dissolved in CH2Cl2
(1 mL) and MeOH (1 mL). The reaction mixture was stirred over-
night at room temperature and then concentrated under reduced
pressure. Trituration of the product with ethyl ether followed by
evaporation of the solvent afforded 19 as a white solid in 97% yield
(124 mg). Mp 49–51 °C; Rf (silica, heptane/ethyl acetate: 1/1):
0.43; IR (neat, cmꢀ1) 3214, 3100, 2925, 1733, 1604, 1529, 1456,
1347, 1317, 1304, 1259, 1152, 1107, 1064, 1011; 1H NMR
(500 MHz, CDCl3) d 1.33 (s, 9H), 2.43 (s, 3H), 3.36 (s, 3H), 3.64–
3.66 (m, 1H), 3.77–3.79 (m, 1H), 4.09–4.11 (m, 1H), 6.27 (d,
J = 8.5 Hz, 1H), 7.29 (d, J = 8.5 Hz, 2H), 7.84 (d, J = 8.5 Hz, 2H),
8.14 (d, J = 8.5 Hz, 2H), 8.32 (d, J = 8.5 Hz, 2H); 13C NMR (75 MHz,
CDCl3) d 21.6, 27.7, 56.2, 59.4, 72.9, 83.5, 124.1, 126.8, 129.0,
129.4, 139.9, 143.4, 145.1, 150.4, 167.3; MS (ES) m/z 514 (M+H)+,
536 (M+Na)+; HRMS m/z (M+Na)+ calcd for C21H27N3NaO8S2
536.1137, found 536.1125.
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sulfonimidoyl]amino-propionate 20
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Aziridine 5b (439 mg, 1 mmol) was dissolved in THF (2 mL),
water (2 mL), and TFA (2 mL). The reaction mixture was stirred
overnight at room temperature and then diluted with water
(5 mL) and ethyl ether (5 mL). After addition of NaHCO3 until pH
ꢃ8, the organic layer was separated and the aqueous layer was ex-
tracted with ethyl acetate (2 ꢂ 10 mL). The combined organic ex-
tracts were dried on magnesium sulfate and concentrated under
reduced pressure. The resulting residue was then purified by flash
chromatography (heptane/ethyl acetate: 3/7) to afford compound
20 as an oily solid in 77% yield (353 mg, 0.77 mmol). Rf (silica, hep-
tane/ethyl acetate: 7/3): 0.15; 1H NMR (300 MHz, CDCl3) d 2.41 (s,
3H), 3.48 (s, 3H), 3.72–3.89 (m, 2H), 4.19 (t, J = 3.5 Hz, 1H), 6.97 (br
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J = 8.6 Hz, 2H), 8.30 (d, J = 7.8 Hz, 2H); 13C NMR (75 MHz, CDCl3)
d 21.5, 53.1, 58.5, 63.6, 125.2, 127.4, 129.9, 130.4, 141.2, 144.6,
145.9, 151.6, 170.1; MS (ES) m/z 480 (M+Na)+; HRMS m/z
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Acknowledgments
This work was supported by the Institut de Chimie des Sub-
stances Naturelles (fellowships to F.R.-P., P.H.D.C., C.L. and F.C.)
and ANR (grant 06-BLAN-0013-01 ‘NitCH’ and fellowship to C.L.).
Support and sponsorship concerted by COST Action D24 ‘Sustain-
able Chemical Processes: Stereoselective Transition Metal-Cata-
lysed Reactions’ and COST Action D40 ‘Innovative Catalysis: New
Processes and Selectivities’ are also kindly acknowledged.
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.
33. The one-pot protocol also proves to be very convenient since preparation of the
sulfonimidamide-derived iminoiodane is particularly troublesome.
34. Use of 5 equiv of styrene or 1,2-dihydronaphthalene allowed us to improve the
yields up to 96% but the diastereoselectivity remained low.
35. The results reported in the case of styrene were not taken into consideration to
make the final decision because, except with sulfonimidamide 1e, the catalytic
aziridination remains poorly stereoselective with des generally less than 20%.
Moreover, several studies have previously described the successful use of
chiral ligands for the enantioselective aziridination of styrene derivatives.
36. A slightly lower yield of 65% in the case of 5b was observed when the reaction
was performed at a larger scale because of the moderate solubility of 1b.
37. For reviews, see: (a) Hargaden, G. C.; Guiry, P. J. Chem. Rev. 2009, 109, 2505–
2550; (b) Desimoni, G.; Faita, G.; Jorgensen, K. A. Chem. Rev. 2006, 106, 3561–
3651; (c) Johnson, J. S.; Evans, D. A. Acc. Chem. Res. 2000, 33, 325–335; (d)
Ghosh, A. K.; Mathivanan, P.; Cappiello, J. Tetrahedron: Asymmetry 1998, 9, 1–
45; For an overview of asymmetric copper-catalyzed reactions, see: (e) Rovis,
T.; Evans, D. A. Prog. Inorg. Chem. 2001, 50, 1–150.
38. (a) Evans, D. A.; Woerpel, K. A.; Hinman, M. M.; Faul, M. M. J. Am. Chem. Soc.
1991, 113, 726–728; (b) Evans, D. A.; Peterson, G. S.; Johnson, J. S.; Barnes, D.
M.; Campos, K. R.; Woerpel, K. A. J. Org. Chem. 1998, 63, 4541–4544.
39. The same experiment realized starting from the analogous N-(tosyl)aziridine
proved successful only by heating the reaction mixture at 60 °C in the presence
of BF3ꢄOEt2. See: Robert-Peillard, F. Ph.D. Thesis, Paris-Sud 11 University, Orsay,
2006.