Palladium(II) mediated aziridination of olefins with bromamine-T as the nitrogen source: scope and mechanism

Article abstract of DOI:10.1016/j.tet.2007.05.020

The palladium(II)-promoted reaction of a variety of olefins and bromamine-T provided N-tosyl-2-substituted aziridines under mild conditions. Olefins bearing chiral appendages gave only a poor to modest diastereoselectivity. Appropriate deuterated olefins

Full text of DOI:10.1016/j.tet.2007.05.020

Tetrahedron 63 (2007) 7009–7017
Palladium(II) mediated aziridination of olefins with bromamine-T
as the nitrogen source: scope and mechanism
ꢀ
Alexandra M. M. Antunes, Vasco D. B. Bonifacio, Susana C. C. Nascimento,
*
Ana M. Lobo, Paula S. Branco and Sundaresan Prabhakar
REQUIMTE/CQFB, Departamento de Quꢀımica, FCT, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal
Received 3 January 2007; revised 3 May 2007; accepted 4 May 2007
Available online 22 May 2007
Abstract—The palladium(II)-promoted reaction of a variety of olefins and bromamine-T provided N-tosyl-2-substituted aziridines under
mild conditions. Olefins bearing chiral appendages gave only a poor to modest diastereoselectivity. Appropriate deuterated olefins were
selected to study the stereochemistry of the reaction. A Pd(IV) intermediate is proposed as the aziridinating species.
Ó 2007 Elsevier Ltd. All rights reserved.
1. Introduction
enantio- and diastereoselection by employing appropriate
substrates.
Aziridines are versatile substances for the synthesis of
biologically important substances such as amino acids, b-
lactam antibiotics, and alkaloids.1,2 Of late there has been
an increased interest in the catalytic use of copper,3–8 rho-
dium,9,10 manganese,11 and rhenium,12 for the conversion
of olefins to aziridines. Among these metals, copper in con-
junction with tosylimino-phenyliodane3–8,11,12 has been
widely used as the nitrogen transfer reagent. Chloramine-
T13 or bromamine-T14 extensively used to prepare epox-
ides,15 a-hydroxyamines16,17 and a- chloroamines18 have
2. Results and discussion
A variety of acrylic acid derivatives and other simple allyl
alcohols were subjected to the palladium(II) promoted
aziridination with bromamine T as the nitrogen transfer re-
agent under two different experimental conditions. Method
A consisted of addition of bromamine T (0.18 mmol) to
a previously stirred solution of olefin (0.45 mmol) and bis-
(acetonitrile)dichloropalladium (0.075 mmol) in acetonitrile
(1/2 h). Method B involved addition in portions, of brom-
amine-T (0.06 mmol) to a previously stirred solution of
olefin (0.15 mmol) and dichloropalladium (0.024 mmol) in
acetonitrile (1/2 h), each addition being done only after
a negative starch-iodide test for the oxidant was observed.
Appropriate choice of the method led occasionally to
a marked improvement in the yield. For example whilst
method A gave 57% of aziridine for N,N-dimethylacryl-
amide, method B furnished the same product in 81% (Table
1, entry c). The catalytic efficiency of other palladium(II)
compounds, such as Pd(OAc)2, Pd(CF3COO)2, and PdBr2,
bearing different leaving groups on the metal was also exam-
ined. Palladium(II) chloride or bis(acetonitrile)dichloropal-
ladium(II) was found to give best result. An examination
of the Table 1 shows that a wide variety of olefins are aziri-
dinated with varying degrees of efficiency. It can also be
noted that the greater the deactivation of the double bond
in acrylic acid derivatives the lower was the yield of aziri-
dines (CN<COR<CO2R<CONMe2). A b substituent
caused a dramatic fall in the yield (81% for entry c; 16%
for entry d). Irrespective of the electronic nature of the
also been amply used in aziridination reactions.13,14,17,19
A
combination of bromamine-T with porphyrin complexes of
transition metals such as Mn, Fe, Ru, and Co was also shown
to yield aziridines.20,21 Polymers incorporating Mn and Fe
were found to be efficient in aziridination reactions with
bromamine-T.22 In spite of the extensive use of palladium
in organic synthesis,23 intermolecular amination of simple
olefins involving Pd+2 and primary or secondary amine
was found to be inefficient.24 The poor yield was attributed
to strong coordination of the amines with palladium(II)
catalyst.25,26
We had previously reported27 a novel PdCl2-assisted aziri-
dination of olefins with bromamine-T as the nitrogen
transfer reagent. Full details of this method, its probable re-
action mechanism, its scope, and limitations are described
herein. Also briefly summarized are our efforts to achieve
Keywords: Aziridination; Palladium(II); Catalysis; Bromamine-T.
* Corresponding author. Tel.: +351 294 8300; fax: +351 294 8550; e-mail:
psb@dq.fct.unl.pt
0040–4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.05.020

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A. M. M. Antunes et al. / Tetrahedron 63 (2007) 7009–7017
Table 1. Palladium(II) mediated aziridination of olefins with bromamine-T
as the nitrogen source
the necessity of the presence of a suitable functional group
not too far removed from the double bond.
2.1. Stereochemistry and mechanism
Geometrically defined diols, (Z)-but-2-en-1,4-diol (entry s)
and (E)-but-2-en-1,4-diol30,31 (entry t) gave exclusively the
corresponding aziridines cis-[30-(hydroxymethyl)-10-tosyl-
aziridin-20-yl]methanol (1s) and trans-[30-(hydroxymethyl)-
10-tosylaziridin-20-yl]methanol (1t). The 1H NMR spectrum
of the crude product did not reveal the presence of both iso-
mers in the same reaction. However, the yields (12% and 5%,
respectively) were poor, which prompted us to examine the
reaction with cis-deutero propen-1-ol (4a)30 (Table 3). Thus,
4a gave aziridine 5-cis exclusively. Such specificity, how-
ever, was not observed for cis-N,N-b-deutero-dimethylacryl-
amide (4b).32 It gave rise to a 4:1 mixture of the cis- and the
trans-aziridines. Interestingly, cis-b-deutero ethylacrylate
(4c)33–35 provided the trans isomer as the major product
(cis/trans¼1:2).
Entry R1
R2
X
1a (%)/Time of 1b %/Time of
reaction (h)
reaction (h)
a
b
c
d
e
f
g
h
i
j
k
l
H
H
H
Me
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
COOMe
COOC(Me)3
CONMe2
CONMe2
COMe
SOPh
CN
CH2CN
CH2COOMe
60/48
60/24
57/24
16/192
25/24
10/24
22/48
23/2
39/24
46/120
81/24
—/192
23/24
19/72
13/24
18/72
13/24
—/168
—
25/2
33/96
—
CO(CH2)3
CO(CH2)2
(CH2)4
11/24
53/2
30/24
54/3
21/17
2/72
mc
n
o
p
qc
rc
sc
tc
u
H
H
H
H
H
H
CH2OH
CH2OEt
CH2OCOMe
(CH3)2COH
48/24
12/72
8/24
—
Table 3. Aziridination of b-deutero olefins
(ꢀ) CH(OH)Me 30/2
20/24
32/24
6/72
CHOHCH2OH 27/0.5
CH2OH CH2OH
CH2OH
COPh
12/4
5/4
CH2OH H
Ph
6/72
H
5/120
—
4
R
5-cis
5-trans
a
Method A—olefin (2.5 equiv), TsNBrNa (1.0 equiv), and Pd(MeCN)2Cl2
(0.42 equiv).
Relative proportion
b
c
Method B—olefin (0.8 equiv), TsNBrNa (3ꢁ0.33 equiv), PdCl2
a
b
c
CH2OH
CONMe2
COOEt
1
4
1
0
1
2
(0.13 equiv).
At the end of the reaction the solvent was removed and the compound
purified by thin layer chromatography.
double bond, varying amounts of ring-opened products 2 and
3 were consistently obtained (Table 2).28
The cis- and trans-aziridines are clearly distinguished from
each other from their respective 1H NMR spectra. Thus, for
the cis isomer hydrogen at C-2 and C-3 appears as doublets
with coupling constants of 7.0 Hz. For the trans arrangement
it is 4 Hz.
Allyl alcohol (entry m) provided only a moderate yield of
aziridine (53%) possibly due to side reaction involving
oxidation of the hydroxyl group.29 tert-Alcohol (entry p)
furnished a lower yield (21%) vis a vis the secondary alcohol
(entry q) (30%) illustrating the deleterious effect of steric
congestion around the OH group. Whilst protection of the
OH group as its acetyl derivative (entry o) gave 1o (54%),
the ethyl ether (entry n) furnished the corresponding aziri-
dine in 30% yield. It should be mentioned that only traces,
if any, of aziridine was formed in the absence of Pd+2. Sim-
ple olefins such as styrene and cyclohexene failed to produce
any aziridine or products derived therefrom showing thereby
These results led us to conclude that the differing degree of
selectivity observed for allylic alcohol on one hand and
derivatives of acrylic acid on the other is likely to be due
to different coordinating capacities of these functionalities
for Pd. Thus, the OH group either by virtue of its strong
coordination to or by bond formation with palladium gives
exclusively the cis aziridines (5) (Table 3). The lack of ste-
reospecificity observed in the aziridination of acrylic acid
derivatives clearly indicates generation of an intermediate
with certain ionic character in which a measure of rotation
about the C1–C2 bond becomes possible. The degree of
such rotation and hence the proportion of isomers formed
would be dependent on the metal chelating property of the
electron-withdrawing group. The greater coordinating prop-
erty of a tertiary-amide compared with that of an ester group
would explain our results.
Table 2. Yields and reaction conditions for 2 and 3
Entry
R1
R2
X
2a h%
3a h%
a
b
c
d
e
f
g
m
n
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
COOMe
COOMe
CONMe2
COMe
COMe
SOPh
CN
CH2OH
CH2OEt
6 (A)
3 (B)
12 (B)
14 (A)
5 (B)
8 (B)
7 (B)
16 (B)
To gain a better understanding of the nature of the aziridinat-
ing species involved, the reaction (Pd+2, bromamine-T, acrylo-
nitrile) was followed by H NMR. As can be observed,
19 (B)
19 (A)
1
6 (B)
9 (B)
5.6 (B)
d values of olefinic hydrogens (Fig. 1a) remained unchanged
on addition of the palladium catalyst (Fig. 1b). The 1H NMR
spectra, acquired immediately after the addition of brom-
amine-T (Fig. 1c), showed new sets of peaks adjacent to
a
RC (Reaction conditions): (A) Method A—olefin (2.5 equiv), TsNBrNa
(1.0 equiv), Pd(MeCN)2Cl2 (0.42 equiv) and (B) Method B—olefin
(0.8 equiv), TsNBrNa (3ꢁ0.33 equiv), PdCl2 (0.13 equiv).

A. M. M. Antunes et al. / Tetrahedron 63 (2007) 7009–7017
7011
Figure 1. 1H NMR (CD3CN) recorded spectra for the aziridination reaction
of acrylonitrile: (a) acrylonitrile, (b) acrylonitrile (0.8 equiv)+PdCl2
(0.13 equiv), (c) acrylonitrile (0.8 equiv)+PdCl2 (0.13 equiv)+bromamine-
T (0.33 equiv) (after the addition), (d) acrilonitrile (0.8 equiv)+PdCl2
(0.13 equiv)+bromamine-T (0.33 equiv) (1/2 h after the addition), (e) brom-
amine-T (1.0 equiv)+PdCl2 (1.0 equiv), (f) bromamine-T.
Scheme 1. Proposed mechanism for the aziridination reaction.
optically active acrylic acid derivatives, containing chiral
appendages that were prepared and examined (Table 4), Op-
polzer sultam gave the best result. Although the chemical
the signals of bromamine-T (Fig. 1f), which indicated the
formation of at least two Pd containing species. The same
signals were present on the 1H NMR spectra when equimolar
amounts of bromamine-Tand PdCl2 are mixed (Fig. 1f vs e).
Signals due to aziridine became discernable only after a lapse
of 1/2 h (Fig. 1d).
Table 4. Yields and de for the aziridination reaction of chiral olefins 7
Based on these results, the following mechanism (Scheme 1)
can be proposed. It is suggested that an oxidative addition of
bromamine-T to PdCl2 results in the formation of two or-
gano Pd+4 complexes 6a and 6b in equilibrium36 (several geo-
metries for the intermediate Pd+4 can be written, 6a and 6b
represent two of them). An exclusive syn addition to the ole-
finic bond of allyl alcohol (4a) occurs due to strong coordi-
nation of OH to Pd. The palladocycle thus formed
subsequently collapses to aziridine, regenerating Pd+2 spe-
cies. A similar situation largely obtains for acrylic amide
4b. For acrylic ester (4c), however, the lack of such strong
coordination would result in a stepwise addition generating
a species with carbanionic character. A rotation about the
C–C bond places the ester away from the bulky Pd reagent
thus resulting in loss of stereospecificity.
Entry
Chiral auxiliary R*
Aziridines
h% (RC)a
de (%)
8a and 8b
9a and 9b
a
61 (B)
31 (B)
27
22
b
10a and 10b
c
42 (A)
3
The high selectivity observed in some substances led us to
examine the possibility of inducing enantio-selection. Ac-
cordingly, the reactions with allyl alcohol were performed
in the presence of (i) (L)-diethyl tartrate and (ii) (R)-1,10-
bi-2-naphtol as chiral complexing agents for PdCl2. How-
ever in no instance could any ee be observed. Use of chiral
phosphines such as DIOP and BINAP with PdCl2 and (+)-
di-m-chloro-bis{2-[1-(dimethylamine)-ethyl]phenyl-C,N}di-
palladium(II) also gave similar results.
11a and 11b
d
50 (A)
12
12a and 12b
41 (A)
e
0
a
Reaction conditions: (A) Method A—olefin (2.5 equiv), TsNBrNa
(1.0 equiv), Pd(MeCN)2Cl2 (0.42 equiv) and (B) Method B—olefin
(0.8 equiv), TsNBrNa (3ꢁ0.33 equiv), PdCl2 (0.13 equiv).
Optical induction employing chiral auxiliaries is a useful
method of achieving diastereoselection. Among many

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A. M. M. Antunes et al. / Tetrahedron 63 (2007) 7009–7017
conversion of acryloyl-10, 2-sultamabornane (7a) (Table 4)
into the corresponding aziridines 8a and 8b was reasonable
(60%), the de as determined from 1H NMR was disappoint-
ingly low (27%).37
INETI, Lisbon, Portugal, wereobtainedbyGC–MSonaFinni-
ganGCQpluswithaTRACE2000serieschromatographusing
a DB-5 column, 0.32 mm DI, 0.25 mm df (initial temperature
50 ꢂC held for 1 min, then 10 ꢂC minꢃ1 until 300 ꢂC).
Amide, N-[(10S)-10phenylethyl]-N-neopenthylpropenamide
(7b) afforded a similar de (22%) but in diminished yield
(31%). All optically active acrylic esters 7c–e were found
to be very unsatisfactory from the stand point of diastereose-
lection although modest yields of aziridines were obtained
(Table 4). The relative proportion of diastereoisomers in
each reaction was calculated from integration of H NMR
signals due to Ha and Hb hydrogens present in the aziridine
mixture.
4.1.1. Preparation of N-halo-N-sodium sulfonamides.
Bromamine-T.39
4.1.1.1.
Bromine
(0.8 ml,
15.57 mmol) was added to tosylamine (2.0 g, 11.69 mmol)
in water (8 ml) protected from light and after 1/2 h the solu-
tion was set to 0 ꢂC. A solution of NaOH 50% (3.0 ml,
37.5 mmol) was added dropwise. The precipitate was
filtered and dried at reduced pressure over phosphorous
pentoxide at 40 ꢂC until constant weight. A light yellow
solid (2.63 g) was obtained in 83% yield; mp 150–152 ꢂC
(lit.40 145–150 ꢂC). IR (KBr) nmax: 1244 (S]O), 1131
(S]O) cmꢃ1. 1H NMR (DMSO) d: 7.60 (2H, d, J¼7.8 Hz,
ArH2+6), 7.25 (2H, d, J¼7.7 Hz, ArH3+5), 2.41 (3H, s,
ArCH3). 13C NMR (DMSO) d: 143.6 (ArC1), 139.2
(ArC4), 128.7 (ArC3+5), 127.4 (ArC2+6), 21.1 (ArCH3).
1
3. Conclusion
An experimentally simple and mild method involving Pd(II)
induced aziridination of olefins and bromamine-T is de-
tailed. Synthetically useful N-tosyl-2-substituted aziridines
can be accessed by this procedure with moderate to good
yields for olefins containing a variety of functional groups.
4.1.2. Preparation of deutered olefins.
4.1.2.1. (Z)-[3-2H]Prop-2-en-1-ol (4c), (Z)-[4-2H]but-
3-en-2-ol (4a), and (S)-(Z)-[4-2H]but-3-en-2-ol (4b). These
were prepared following the procedure of Bellamy.31
1
The mechanism, probed by H NMR spectroscopy using
cis-b-deutero allyl alcohol, showed complete syn stereo-
specificity. Tertiary-amide and acrylic ester did not show
similar selectivity. The degree of selectivity achieved is at-
tributed to the ability of the functional group to coordinate
with an electrophilic Pd(IV) proposed as an intermediate.
Only Oppolzer sultam employed as the chiral auxiliary
amongst many tested gave a modest diastereoselection.
4.1.2.2. (Z)-[3-2H]Ethyl propenoate (4e). Prepared as
previously described33 by heating ethyl 11,12-cis-12-
deuterio-9,10-ethane-9,10-dihydroanthracene-11-carboxylate
(6.32 g, 22.65 mmol) at 290–300 ꢂC at atmospheric pressure.
The volatile ester was slowly released and was collected in
a cooled receiver affording pure (Z)-[3-2H] ethyl propenoate
(1.32 g) in 58% yield.
4. Experimental section
4.1.2.3. (Z)-[3-2H] N,N-Dimethylacrylamide (4d). To
a
solution of cis-b-iodo-N,N-dimethylacrylamide32
4.1. General experimental method
(1.0 equiv, 40 mg, 0.178 mmol) and Pd(OAc)2 (0.1 equiv,
4 mg, 1.78ꢁ10ꢃ2 mmol) in deutero methanol at room
temperature was added NaBD4 (1.0 equiv, 6.7 mg,
0.178 mmol). The mixture after remaining at room temper-
ature for 5 days was worked up in the usual manner. The title
compound isolated by PTLC in 14% yield was found to con-
sist of trans/cis isomers (a 1:19 mixture) as calculated by
integration of appropriate signals in the 1H NMR spectrum.
Solvents were purified by standard methods.38 All commer-
cial reagents were used as received unless otherwise men-
tioned. The chiral olefins, methylacrylate, bornyl acrylate,
and fenchyl acrylate were kindly offer by Professor Manuela
Pereira from our laboratory. For analytical and preparative
thin-layer chromatography, Merck, 0.2 mm and 0.5 mm
Kieselgel GF 254 percoated were used, respectively. The
spots were visualized using UV light and a KMnO4 solution
(1:0.02 mixture of 1% KMnO4 and 7% K2CO3 solution/5%
NaOH aqueous solution) followed by heating. Medium-
performance liquid chromatography and flash column chro-
matography were performed using Merck, Kieselgel 60 with
(0.063–0.200 mm) and (0.040–0.063 mm), respectively.
4.1.3. General methods for the preparation of aziridines.
MethodA: Bis(acetonitrile)dichloropalladium(II) (0.42 equiv,
19.5 mg, 0.075 mmol) was added to the olefin (2.5 equiv,
0.45 mmol) in dry acetonitrile (2.5 ml) under nitrogen atmo-
sphere. After 1/2 h of stirring at room temperature the brom-
amine-T (1.0 equiv, 50 mg, 0.18 mmol) was added and the
reaction protected from light, allowed to proceed until a
negative test (starch-iodide paper) for bromamine-T was ob-
served. Upon following solvent evaporation the obtained res-
iduewas dissolved in dichloromethane, washed with aqueous
sodium metabisulfite solution (15%) and water. The products
were isolated by preparative TLC.
€
Melting points were recorded on a Kofler apparatus, Reich-
ert Thermovar model and are uncorrected. Infrared spectra
were recorded on a Perkin Elmer 683 FT-IR spectrometer.
1H and 13C NMR spectra were recorded on a Bruker ARX
400 spectrometer at 400 and 100.62, respectively. 1H shifts
are reported relative to internal TMS. Carbon shifts are given
relative to the 13C signal of CDCl3 (d 77.0 ppm) or DMSO-d6
(d 39.5 ppm) as reference. High resolution mass spectra were
recorded on a Finnigan FT/MS 2001-DT, FT-ICR spectro-
meter furnished with a 3.0 T superconductor magnet, at the
Method B: Palladium(II) chloride (0.13 equiv, 4.2 mg,
0.024 mmol) was added to the olefin (0.8 equiv,
0.15 mmol) in dry acetonitrile (2.0 ml) under nitrogen atmo-
sphere. After 1/2 h of stirring at room temperature the brom-
amine-T was added (0.33 equiv, 16.3 mg, 0.06 mmol) and
the reaction protected from light was allowed to proceed.
ꢀ
Instituto Tecnologico Nuclear (ITN), Lisbon, Portugal. The
spectra were obtained by laser desorption (LD) or electron
impact (EI). The low resolution mass spectra recorded at

A. M. M. Antunes et al. / Tetrahedron 63 (2007) 7009–7017
7013
0
Two more bromamine-T additions (0.33 equiv each) were
made and each addition was performed only after a negative
test (starch-iodide paper) for bromamine-T was observed.
Upon solvent evaporation the obtained residue was dissolved
in dichloromethane, washed with aqueous sodium metabi-
sulfite solution (15%) and water. The products were isolated
by preparative TLC.
H2), 2.46 (3H, s, ArCH3), 2.30 (1H, d, J¼3.2 Hz, H3 trans).
13C NMR (CDCl3) d: 145.2 (ArC4), 134.6 (ArC1), 130.0
0
(ArC3+5), 128.0 (ArC2+6), 115.0 (CN), 33.7 (C2 ), 32.ꢃ5
0
(C3 ), 21.7 (ArCH3), 20.1 (C2). MSLD(ꢃ) m/z: 236 [M]
(30.2), 196 [MꢃCH2CN] (21.4), 155 [Ts]ꢃ (100.0).
HRMSLD(ꢃ) calcd for C11H12N2O2S [M]ꢃ 236.06250,
found 236.06254.
4.1.3.1. Methyl (10-tosylaziridin-20-yl)carboxylate
(1a). Colorless oil obtained in 60% (method A) and 39%
(method B) yields. Spectroscopic data were in agreement
with those previously reported.41
4.1.3.9. Methyl-2-(10-tosylaziridin-20-yl)acetate (1i).
Colorless oil obtained in 25% (method A) and 13% (method
B) yields. IR (film) nmax: 1734 (C]O), 1320 (S]O), 1160
1
(S]O) cmꢃ1. H NMR (CDCl3) d: 7.84 (2H, d, J¼8.0 Hz,
ArH2+6), 7.35 (2H, d, J¼8.0 Hz, ArH3+5), 3.56 (3H, s,
4.1.3.2. tert-Butyl-(10-tosylaziridin-20-yl)carboxylate
(1b). Colorless oil obtained in 60% (method A) and 46%
(method B) yields. Spectroscopic data were in agreement
with those previously reported.41
OCH3), 3.12–3.06 (1H, m, H2 ), 2.72 (1H, d, J¼6.8 Hz,
0
0
H3 cis), 2.50 (2H, dd, J¼6.4 and 4.0 Hz, H2), 2.16 (1H, d,
J¼4.4 Hz, H3 trans), 2.45 (3H, s, ArCH3). 13C NMR
0
(CDCl3) d: 165.1 (CO), 140.1 (ArC4), 133.8 (ArC1), 129.5
(ArC3+5), 128.1 (ArC2+6), 51.9 (OCH3), 38.5 (C2), 35.8
+
4.1.3.3. N,N-Dimethyl-(10-tosylaziridin-20-yl)carbox-
amide (1c). Colorless solid obtained in 57% (method A)
and 81% (method B) yields; mp 61–63 ꢂC (ethyl acetate/
hexane). Spectroscopic data were in agreement with those
previously reported.42
(C2 ), 32.7 (C3 ), 21.6 (ArCH3). MSEI(+) m/z: 269 [M]
(7.4), 155 [Ts]+ (1.8), 114 [MꢃTs]+ (100.0). HRMSEI(+)
calcd for C12H15NO4S [M]+ 269.07163, found 269.07134.
0
0
4.1.3.10. cis-7-Tosyl-7-azabicyclo[4.1.0]heptan-2-one
(1j). Colorless oil obtained in 33% yield (method A). Spec-
troscopic data were in agreement with those previously
reported.27
4.1.3.4. trans-N,N,30-Trimethyl-1-(10-tosylaziridin-20-
yl)carboxamide and cis-N,N,30-trimethyl-1-(10-tosylaziri-
din-20-yl)carboxamide (1d). Colorless oil (16%), consisting
of the trans (10%) and cis (6%) isomers (method A). IR (film)
4.1.3.11. cis-7-Tosyl-7-azabicyclo[4.1.0]heptane (1l).
Colorless oil obtained in 11% (method A) and 2% (method
B) yields. Spectroscopic data were in agreement with those
previously reported.5
1
nmax: 1658 (C]O), 1324 (S]O), 1159 (S]O) cmꢃ1. H
NMR (CDCl3) d: 7.86 (4H, d, J¼8.4 Hz, ArH2+6), 7.32
0
(4H, d, J¼8.0 Hz, ArH3+5), 3.50 (1H, d, J¼7.2 Hz, H2 cis),
0
0
3.45 (1H, d, J¼4.0 Hz, H2 trans), 3.24–3.21 (1H, m, H3 trans),
4.1.3.12. (10-Tosylaziridin-20-yl)methanol (1m). Color-
less oil obtained in 53% (method A) and 48% (method B)
yields. Spectroscopic data were in agreement with those
previously reported.44
0
3.13 (3H, s, NCH3 cis), 3.09 (3H, s, NCH3 trans), 3.07–3.03
0
(1H, m, H3 cis), 2.94 (3H, s, NCH3 trans), 2.92 (3H, s,
NCH3 cis), 2.44 (3H, s, ArCH3 cis), 2.43 (3H, s, ArCH3 trans),
1.63 (3H, d, J¼6.0 Hz, CH3 trans), 1.22 (3H, d, J¼5.6 Hz,
CH3 cis). 13C NMR (CDCl3) d: 165.0 (CO), 144.4 (ArC4),
0
136.9 (ArC1), 129.6 (ArC3+5), 127.6 (ArC2+6), 44.4 (C2 ),
4.1.3.13. 2-(Ethoxymethyl)-1-tosylaziridine (1n). Col-
orless oil obtained in 30% (method A) and 12% (method
B) yields. IR (film) nmax: 1323 (S]O), 1161 (S]O), 1091
0
43.9 (C3 ), 37.1 (NCH3), 35.7 (NCH3), 21.6 (ArCH3), 13.6
(CH3). HRMSEI(+) calcd for trans-C13H19N2O3S [MH]+
283.11109, found 283.11095.
(C–O–C) cmꢃ1
.
1H NMR (CDCl3) d: 7.84 (2H, d, J¼
8.0 Hz, ArH2+6), 7.34 (2H, d, J¼8.0 Hz, ArH3+5), 3.53
4.1.3.5. 1-(10-Tosylaziridin-20-yl)ethanone (1e). Color-
less solid obtained in 25% (method A) and 23% (method
B) yields; mp 69–70 ꢂC (ethyl ether/hexane). Spectroscopic
data were in agreement with those previously reported.42
(1H, dd, J¼11.2 and 4.4 Hz, H1 ), 3.44–3.88 (3H, m,
0
0
00
H1 +H1 ), 3.00–2.95 (1H, m, H2), 2.66 (1H, d, J¼7.2 Hz,
H3 cis), 2.45 (3H, s, ArCH3), 2.20 (1H, d, J¼4.4 Hz, H3 trans),
1.09 (3H, t, J¼6.8 Hz, H2 ). 13C NMR (CDCl3) d: 144.3
00
(ArC4), 134.3 (ArC1), 129.6 (ArC3+5), 128.1 (ArC2+6),
0
69.5 (C1 ), 66.6 (C1 ), 38.8 (C2), 31.0 (C3), 21.6 (ArCH3),
00
4.1.3.6. 2-(Phenylsulfinyl)-tosylaziridine (1f). Oil
obtained in 10% (method A) and 19% (method B) yields.
Spectroscopic data were in agreement with those previously
reported.27
+
00
15.0 (C2 ). GCMSEI(+) m/z: 210 [MꢃOEt] (0.9), 155
[Ts]+ (27.9), 91 [C7H7]+ (85.8), 56 [C3H6N]+ (100).
HRMSEI(ꢃ) calcd for C12H17NO3 [M]+ 255.093463, found
255.09345.
4.1.3.7. 1-Tosylaziridin-2-carbonitrile (1g). Oil ob-
tained in 22% (method A) and 13% (method B) yields.
Spectroscopic data were in agreement with those previously
reported.43
4.1.3.14. (10-Tosylaziridin-20-yl)methyl acetate (1o).
Colorless oil obtained in 54% (method A) and 8% (method
B) yields. IR (film) nmax: 1744 (C]O), 1324 (S]O), 1160
1
(S]O) cmꢃ1. H NMR (CDCl3) d: 7.84 (2H, d, J¼8.0 Hz,
4.1.3.8. 2-(10-Tosylaziridin-20-yl)acetonitrile (1h). Oil
obtained in 23% (method A) and 18% (method B) yields.
ArH2+6), 7.36 (2H, d, J¼8.4 Hz, ArH3+5), 4.21 (1H, dd,
J¼12.0 and 4.0 Hz, H1), 3.85 (1H, dd, J¼12.0 and 7.2 Hz,
0
0
IR (film) nmax
:
1592 (CN), 1320 (S]O), 1159
H1), 3.03–2.98 (1H, m, H2 ), 2.74 (1H, d, J¼7.2 Hz, H3 cis),
1
(S]O) cmꢃ1. H NMR (CDCl3) d: 7.83 (2H, d, J¼8.0 Hz,
2.45 (3H, s, ArCH3), 2.24 (1H, d, J¼4.0 Hz, H3 trans), 1.91
0
ArH2+6), 7.37 (2H, d, J¼7.6 Hz, ArH3+5), 3.01–3.00 (1H,
(3H, s, CH3). 13C NMR (CDCl3) d: 170.3 (CO), 144.7
(ArC4), 134.6 (ArC1), 129.6 (ArC3+5), 128.1 (ArC2+6),
0
0
m, H2 ), 2.74 (1H, d, J¼6.8 Hz, H3 cis), 2.68–2.66 (2H, m,

7014
A. M. M. Antunes et al. / Tetrahedron 63 (2007) 7009–7017
0
0
65.2 (C1), 37.3 (C2 ), 31.0 (C3 ), 21.6 (ArCH3), 20.4 (CH3).
MSEI(+) m/z: 269 [M]+ (1.6), 114 [MꢃTs]+ (100.0).
HRMSEI(+) calcd for C12H15NO4S [M]+ 269.07163, found
269.07134.
4.1.3.21. (20R) and (20S)-{(700R,100S,500R)-1000,1000-Di-
methyl-300-thia-tricyclo[5.2.1.01,5]decane-400-yl}-(10-tosyl-
aziridin-20-yl)carbonyls (8a and 8b). Oil obtained in 61%
yield (method B) and 27% de. IR (film) nmax: 1702 (C]O),
1333 (S]O), 1164 (S]O) cmꢃ1. 1H NMR (CDCl3) d: 7.88
[4H, d, J¼8.0 Hz, ArH2+6(a+b)], 7.34 [2H, d, J¼8.0 Hz,
ArH3+5a], 7.32 [2H, d, J¼8.0 Hz, ArH3+5b], 3.93–3.82 [4H,
4.1.3.15. 2-(10-Tosylaziridin-20-yl)propan-2-ol (1p).
Colorless oil obtained in 21% (method A) yield. Spectro-
scopic data were in agreement with those previously
reported.41
00
0
00
m, H5 (a+b)+H2 (a+b)], 3.55–3.43 [4H, m, H2 (a+b)], 2.88 [1H,
0
0
d, J¼7.2 Hz, H3 a cis], 2.82 [1H, d, J¼6.8 Hz, H3 b cis], 2.66
0
[2H, d, J¼4.0 Hz, H3 (a+b) trans], 2.43 [6H, s, ArCH3(a+b)],
4.1.3.16. (1S,20S), (1R,20R), (1S,20R), and (1R,20S)-1-
(10-Tosylaziridin-20-yl)ethanol (1q). Colorless oil obtained
in 30% (method A) and 20% (method B) yields. Spectro-
scopic data were in agreement with those previously
reported.45
+
00
00
2.09–1.96 [4H, m, H9 (a+b)], 1.96–1.76 [6H, m, H6 (a+b)
00
00
00
00
H8 (a+b)+H7 (a+b)], 1.43–1.27 (4H, m, H6 (a+b)+H8 (a+b)],
0.97 (6H, s, CH3a), 0.96 (6H, s, CH3b). 13C NMR (CDCl3)
d: 164.3 (COa+b), 145.0 [ArC4(a+b)], 135.3 [ArC1(a+b)],
129.7 [ArC3+5(a+b)], 128.7 [ArC2+6a], 128.5 [ArC2+6b], 65.2
00
(C5 a), 65.1 (C5 b), 54.9 [C2 (a+b)], 49.1 [C1 /10 (a+b)], 47.8
00
00
00
00
4.1.3.17. (1S,20S), (1R,20R), (1S,20R), and (1R,20S)-1-
(10-Tosylaziridin-20-yl)ethane-1,2-diol (1r). Colorless oil
obtained in 27% (method A) and 32% (method B) yields
and 0% de. IR (film) nmax: 3400 (O–H), 1321 (S]O), 1160
00
00
00
00
0
[C1 /10 (a+b)], 44.4 [C7 (a+b)], 38.0 [C9 (a+b)], 36.3 [C2 (a+b)],
00 00
0
0
00 00
32.7 [C8 /9 (a+b)], 32.4 (C3 a), 31.8 (C3 b), 26.3 [C8 /6 (a+b)],
21.5 [ArCH3(a+b)], 20.8 (CH3a), 20.6 (CH3b). MSEI(+) m/z:
439 [MH]+ (31.6), 283 [MꢃTs]+ (87.1), 224 [Mꢃ
NCH2SO2C9H14]+ (30.7), 214 [NCH2SO2C9H14]+ (100.0),
155 [Ts]+ (28.1). HRMSEI(+) calcd for C20H27N2O5S2
[MH]+ 439.13559, found 439.13544.
1
(S]O) cmꢃ1. H NMR (CDCl3) d: 7.83 (2H, d, J¼8.4 Hz,
ArH2+6a), 7.82 (2H, d, J¼8.0 Hz, ArH2+6b), 7.29 (4H, d, J¼
7.6 Hz, ArH3+5(a+b)), 3.76–3.54 (6H, m, H1+2(a+b)), 3.00–2.91
0
0
(2H, m, H2 (a+b)), 2.63 (1H, d, J¼6.8 Hz, H3 a cis), 2.56 (1H, d,
0
J¼7.2 Hz, H3 b cis), 2.46 (6H, s, ArCH3(a+b)), 2.38–2.36 (2H,
4.1.3.22. (20R) and (20S)-N-[(100S)-100-Phenylethyl]-N-
neopenthyl-(10-tosylaziridin-20-yl)carboxamides (9a and
9b). Oil obtained in 20% yield (method B) and 16% de,
a is the major diastereomer). IR (film) nmax: 1660 (C]O),
m, H3 (a+b) trans). 13C NMR (CDCl3) d: 144.9 (ArC4(a+b)),
134.5 (ArC1(a+b)), 129.8 (ArC3+5(a+b)), 128.1 (ArC2+6a),
128.0 (ArC2+6b), 69.3 (C2a), 68.5 (C2b), 64.8 (C1a), 64.0
0
0
0
0
0
(C1b), 40.2 (C2 a), 39.8 (C2 b), 31.5 (C3 a), 29.5 (C3 b), 21.6
(ArCH3(a+b)). MSLD(ꢃ) m/z: 257 [M]ꢃ (9.3), 155 [Ts]ꢃ
(100). HRMSLD(ꢃ) calcd for C11H15NO4S [M]ꢃ
257.072728, found 257.07272.
1328 (S]O), 1162 (S]O) cmꢃ1 1H NMR (CDCl3) d:
.
7.86 [2H, d, J¼8.0 Hz, ArH2+6b], 7.71 [2H, d, J¼8.0 Hz,
ArH2+6a], 7.40–7.27 [14H, m, ArH(a+b)], 5.27–5.22 (1H,
00
m, H1 a), 4.66–4.61 (1H, m, H1 b), 3.66–3.60 (2H, m,
00
0
0
H2 b+1H1b), 3.45 (1H, dd, J¼6.8 and 3.3 Hz, H2 a), 3.26–
4.1.3.18. cis-[30-(Hydroxymethyl)-10-tosylaziridin-20-
yl]methanol (1s). Colorless oil obtained in 6% (method
A) and 12% (method B) yields. IR (film) nmax: 3399 (O–
H), 1303 (S]O), 1156 (S]O) cmꢃ1. 1H NMR (CDCl3) d:
7.86 (2H, d, J¼8.0 Hz, ArH2+6), 7.35 (2H, d, J¼8.0 Hz,
ArH3+5), 4.02–3.99 (2H, m, H1), 3.81–3.20 (2H, m, H1),
0
3.18 (3H, m, 2H1a+H1b), 2.64–2.56 [4H, m, H3 (a+b)], 2.45
(3H, s, ArCH3b), 2.43 (3H, s, ArCH3a), 1.76 (3H, d,
00
00
J¼7.2 Hz, C1 CH3b), 1.68 (3H, d, J¼7.2 Hz, C1 CH3a),
1.09 [6H, s, (CH3)3(a+b)], 0.81 [12H, s, C(CH3)3(a+b)].
13C NMR (CDCl3) d: 167.0 (COa+b), 141.0 [ArC4(a+b)],
135.3 [ArC1(a+b)], 129.7 [ArC(a+b)], 129.0 [ArC], 128.2
[ArC2+6(a+b)], 127.7 [ArC(a+b)], 128.5 [ArC(a+b)], 60.5
0
0
3.22–3.20 (2H, m, H2 +3 ), 2.45 (3H, s, ArCH3), 2.31 (2H,
br s, exchange with D2O, OH). 13C NMR (CDCl3) d: 145.4
(ArC4), 137.5 (ArC1), 130.1 (ArC3+5), 128.7 (ArC2+6),
00
(C1 b), 79.3 (C1b), 57.3 (C1 a), 56.6 (C1a), 37.3 (C2 a), 36.2
00
0
0
0
(C2 b), 33.2 [C2(a+b)], 32.4 [C3 (a+b)], 28.8 [C(CH3)3a], 29.2
00
61.15 (C1), 48.4 (C2 +3 ), 22.3 (ArCH3). MSEI(+) m/z: 258
[MH]+ (100.0), 155 [Ts]+ (19.9). HRMSEI(+) calcd for
C11H16NSO4 [MH]+ 258.07955, found 258.07940.
[C(CH3)3b], 22.3 [ArCH3(a+b)], 20.4 [C1 CH3a],
0
0
00
18.1[C1 CH3b]. HRMSEI(+) calcd for C23H31N2O3S
[MH]+ 415.20499, found 415.20504.
4.1.3.19. trans-[30-(Hydroxymethyl)-10-tosylaziridin-
20-yl]methanol (1t). Colorless oil obtained in 5% (method
A) and 6% (method B) yields. IR (film) nmax: 3324 (O–H),
4.1.3.23. (20S) and (20R)-(100R,200S,500R)-200-Isopropyl-
500-methylcyclohexyl-(10-tosylaziridin-20-yl)carboxylates
(10a and 10b). Oil obtained in 42% yield and 3% de
(method A). IR (film) nmax: 1742 (C]O), 1334 (S]O),
1
3224 (O–H), 1325 (S]O), 1161 (S]O) cmꢃ1. H NMR
1
(CDCl3) d: 7.81 (2H, d, J¼7.6 Hz, ArH2+6), 7.37 (2H, d,
1164 (S]O) cmꢃ1. H NMR (CDCl3) d: 7.85 [2H, d, J¼
J¼7.6 Hz, ArH3+5), 3.77–3.75 (2H, m, H1), 3.61–3.59 (2H,
8.4 Hz, ArH2+6a], 7.84 [2H, d, J¼8.0 Hz, ArH2+6b], 7.34
0
0
00
m, H1), 3.09–3.04 (2H, m, H2 +3 ), 2.78 (2H, br s, exchange
with D2O, OH), 2.46 (3H, s, ArCH3). 13C NMR (CDCl3) d:
145.4 (ArC4), 134.7 (ArC1), 130.1 (ArC3+5), 128.2 (ArC2+6),
[2H, d, J¼8.0 Hz, ArH3+5(a+b)], 4.69–4.62 [2H, m, H1 (a+b)],
0
0
3.26–3.20 [2H, m, H2 (a+b)], 2.81 (1H, d, J¼7.2 Hz, H3 a cis),
0
2.80 (1H, d, J¼7.2 Hz, H3 b cis), 2.60 (1H, d, J¼4.4 Hz,
0
0
0
0
59.2 (C1), 44.1 (C2 +3 ), 21.8 (ArCH3). MSEI(+) m/z: 258
[MH]+ (100.0), 155 [Ts]+ (39.2). HRMSEI(+) calcd for
C11H16NSO4 [MH]+ 258.07955, found 258.07931.
H3 a trans), 2.57 (1H, d, J¼4.0 Hz, H3 b trans), 2.45 [6H, s,
00 00
ArCH3(a+b)], 1.92–1.86 [2H, m, H6 /4 (a+b)], 1.72–1.29
00 000
00
00
00 00
[12H, m, H2 /1 (a+b)+H3 (a+b)+H5 (a+b)+2H6 /4 (a+b)], 1.05–
00 00
00
0.92 [4H, m, H6 /4 (a+b)+H3 (a+b)], 0.88 (3H, d, J¼6.4 Hz,
00
00
4.1.3.20.
trans-2-Benzoyl-3-phenyl-1-tosylaziridine
C5 CH3a), 0.88 (3H, d, J¼6.4 Hz, C5 H3b), 0.82 (3H, d,
000
000
(1u). Colorless oil obtained in 5% yield as a mixture of cis
(1%) and trans (4%) isomers (method A). Spectroscopic
data were in agreement with those previously reported.46
J¼7.2 Hz, C1 CH3a), 0.80 (3H, d, J¼6.8 Hz, C1 CH3b),
000
0.64 (3H, d, J¼6.8 Hz, C1 CH3a), 0.60 (3H, d, J¼6.8 Hz,
000
C1 H3b). 13C NMR (CDCl3) d: 168.3 (CO), 145.0 (ArC4),

A. M. M. Antunes et al. / Tetrahedron 63 (2007) 7009–7017
7015
134.3 (ArC1), 129.7 (ArC3+5), 128.2 [ArC2+6a], 128.1
J¼6.7 and 4.4 Hz, H2), 3.78 (3H, s, OCH3), 3.53–3.35
(2H, m, H3), 2.44 (3H, s, ArCH3). 13C NMR (CDCl3) d:
168.6 (CO), 144.1 (ArC4), 136.8 (ArC1), 130.0 (ArC3+5),
127.1 (ArC2+6), 54.2 (C2), 53.2 (OCH3), 45.7 (C3), 21.4
(ArCH3). MS (EI) m/z: 338 [M (81Br)H]+ (5.9), 336 [M
(79Br)H]+ (5.8), 256 [MꢃBr]+ (100.0), [M (81Br)–Ts]+ 182
(39.1). HRMSEI(+) calcd for C11H15N81BrO4S [MH
(81Br)]+ 337.98792, found 337.98783, calcd for
C11H15N79BrO4S [MH (79Br)]+ 337.99052, found
335.98972.
00
[ArC2+6b], 76.9 [C1 (a+b)], 46.8 [C1 /2 (a+b)], 40.5
000 00
00 00
[C6 /4 (a+b)], 38.6 (C2 ), 34.0 [C6 /4 (a+b)], 31.6 (C5 a), 31.5
0
00 00
00
00
0
000 00
000 00
00
(C5 b), 33.3 (C3 ), 26.1 (C1 /2 a), 26.0 (C1 /2 b), 23.4 (C3 a),
00
00
23.2 (C5 CH3b), 21.9 (C5 CH3a), 20.7 [ArCH3(a+b)], 20.6
000
000
000
(C1 CH3b), 20.5 (C1 CH3a), 16.2 (C1 CH3a), 16.1
000
(C1 CH3b). HRMSEI(+) calcd for C20H30NO4S [MH]+
380.18900, found 380.18914.
4.1.3.24. (20R) and (20S)-(100S,200R)-100,300,300-Trimethyl-
bicyclo[2.2.1]hepta-200-yl-(10-tosylaziridin-20-yl)carboxyl-
ates (11a and 11b). Oil obtained in 50% yield (method A);
de 12% and 21% yield (method B); de 10% (11b is the pre-
dominant diastereomer). IR (film) nmax: 1744 (C]O), 1333
4.1.3.26.2. 2-Bromo-N,N-dimethyl-3-(tosylamino)propan-
amide (2c). Oil obtained in 10% (method A) and 12%
(method B) yields. IR (film) nmax: 3231 (N–H), 1643
1
(S]O), 1162 (S]O) cmꢃ1. H NMR (CDCl3) d: 7.86–
(C]O), 1330 (S]O), 1159 (S]O) cmꢃ1 1H NMR
.
7.85 [2H, m, ArH2+6(a+b)], 7.35 [4H, d, J¼8.0 Hz, Ar-
(CDCl3) d: 7.73 (2H, d, J¼8.4 Hz, ArH2+6), 7.31 (2H, d,
J¼8.0 Hz, ArH3+5), 5.11–5.08 (1H, m, exchange with
D2O, NH), 4.53 (1H, dd, J¼9.2 and 4.8 Hz, H2), 3.57–2.83
(2H, m, H3), 3.04 (3H, s, NCH3), 2.97 (3H, s, NCH3), 2.42
(3H, s, ArCH3). 13C NMR (CDCl3) d: 167.3 (CO), 143.6
(ArC4), 137.0 (ArC1), 129.6 (ArC3+5), 127.0 (ArC2+6),
46.0 (C3), 39.6 (C2), 37.4 (NCH3), 36.2 (NCH3), 21.5
(ArCH3). MS (EI) m/z: 351 [M (81Br)H]+ (10.0), 349 [M
(79Br)H]+ (11.2), 269 [MꢃBr]+ (100.0), 155 [Ts]+ (40.6).
HRMSEI(+) calcd for C12H18N279BrO3S [M (81Br)H]+
349.02160, found 349.02154.
00
H3+5(a+b)], 4.32 [2H, dd, J¼7.6 and 1.6 Hz, H2 (a+b)], 3.29–
0
3.25 [2H, m, H2 (a+b)], 2.86–2.83 [1H, m, H3 (a+b) cis], 2.63
0
0
[1H, d, J¼4.4 Hz, H3 a trans], 2.60 [1H, d, J¼4.0 Hz,
0
H3 b trans], 2.45 [6H, s, ArCH3(a+b)], 1.69–1.41 [12H, m,
00
00 00
00
00 00
H4 (a+b)+H6 /7 (a+b)+H5 (a+b)], 1.24–1.06 00[4H, m, H6 /7 (a+b)],
00
1.03 [3H, s, C3 CH3b], 1.02 [3H, s, C3 CH3a], 0.9100(3H, s,
00
00
C1 CH3a), 0.71 (3H, s, C1 CH3b), 0.64 (3H, s, C3 CH3b),
00
0.47 (3H, s, C3 CH3a). 13C NMR (CDCl3) d: 167.0 (COa+b),
145.1 [ArC4(a+b)], 134.3 [ArC1(a+b)], 128.9 [ArC3+5(a+b)],
00
127.5 [ArC2+6a], 128.0 [ArC2+6b], 87.3 (C2 a), 86.8 (C2 b),
00
00
00 00
00
48.2 [C4 (a+b)], 41.2 [C7 /6 (a+b)], 39.4 [C3 (a+b)], 36.6
0
00
[C2 (a+b)], 31.5 (C3 b), 31.3 (C3 a), 29.6 (C3 CH3b), 29.5
4.1.3.26.3. N-(2-Bromo-3-oxobutyl)tosylamine (2e). Col-
orless solid obtained in 14% (method A) and 5% (method B)
yields; mp 63–65 ꢂC (ethyl acetate/n-hexane). IR (KBr)
nmax: 3232 (N–H), 1734 (C]O), 1332 (S]O), 1161
0
0
00
(C3 CH3a), 26.4 [C6 /7 (a+b)], 25.5 [C5 (a+b)], 21.6
00 00
00
00
00
[Ar0C0 H3(a+b)], 19.8 (C1 CH3b), 19.4 (C1 CH3a), 19.2
00
(C3 CH3a), 19.1 (C3 CH3b). HRMSEI(+) calcd for
C20H28NO4S [MH]+ 378.173355, found 378.17317.
1
(S]O) cmꢃ1. H NMR (CDCl3) d: 7.74 (2H, d, J¼7.6 Hz,
ArH2+6), 7.33 (2H, d, J¼7.6 Hz, ArH3+5), 5.11–5.10 (1H,
m, exchange with D2O, NH), 4.45 (1H, dd, J¼8.4 and
5.2 Hz, H2), 3.49–3.31 (2H, m, H1), 2.44 (3H, s, ArCH3),
2.37 (3H, s, COCH3). 13C NMR (CDCl3) d: 201.6 (CO),
144.0 (ArC4), 139.8 (ArC1), 130.0 (ArC3+5), 127.1 (ArC2+4),
48.4 (C2), 44.5 (C1), 27.4 (COCH3), 21.5 (ArCH3). MSEI(+)
m/z: 321 [M (81Br)H]+ (2.4), 240 [MꢃBr]+ (100.0).
HRMSEI(+) calcd for C11H1581BrNO3S [M (81Br)H]+
321.99300, found 321.99342.
4.1.3.25. (20R) and (20S)-(100R,200R)-100,700,700-Trimethyl-
bicyclo[2.2.1]hepta-200-yl-(10-tosylaziridin-20-yl)carboxyl-
ates (12a and 12b). Oil obtained in 41% yield and 0% de
(method A). IR (film) nmax: 1743 (C]O), 1334 (S]O),
1164 (S]O) cmꢃ1 1H NMR (CDCl3) d: 7.86 [4H, d,
.
J¼8.0 Hz, ArH2+6(a+b)], 7.36 [4H, d, J¼8.0 Hz, ArH3+5(a+b)],
00
4.91–4.86 [2H, m, H2 (a+b)], 3.31–3.28 [2H, m, H2 (a+b)], 2.81
0
0
0
(1H, d, J¼7.2 Hz, H3 a cis), 2.80 (1H, d, J¼7.2 Hz, H3 b cis),
0
2.60 [2H, d, J¼4.0 Hz, H3 (a+b) trans], 2.45 [6H, s,
00 00
ArCH3(a+b)], 2.33–2.27 [2H, m, H5 /3 (a+b)], 1.84–1.65 [6H,
4.1.3.26.4. N-[2-Bromo-2-(phenylsulfinyl)ethyl]tosyl-
amine (2f). Oil obtained in 7% (method A) and 19% (method
B) yields. IR (film) nmax: 3261 (N–H), 1330 (S]O), 1158
00 00
m, H5 /3 (a+b)+H4 (a+b)+H6 (a+b)], 1.22–1.09 [4H, m,
00
00
00
00 00
00 00
H6 (a+b)+H5 /3 (a+b)], 0.95–0.93 [2H, m, H5 /3 (a+b)], 0.93
00
00
[12H, s, C7 CH3(a+b)], 0.77 [3H, s, C1 CH3a], 0.71 (3H, s,
(S]O), 1045 (S]O) cmꢃ1 1H NMR (CDCl3) d: 7.78
.
00
C1 CH3b). 13C NMR (CDCl3) d: 166.9 (COa+b), 144.1
[ArC4(a+b)], 135.2 [ArC1(a+b)], 129.8 [ArC3+5(a+b)], 128.1
(2H, d, J¼8.2 Hz, ArH2+6), 7.57–7.51 (5H, m, ArH), 7.36
(2H, d, J¼8.0 Hz, ArH3+5), 5.55 (1H, t, J¼6.2 Hz, exchange
with D2O, NH), 4.80 (1H, dd, J¼8.1 and 6.1 Hz, H2), 3.74–
3.49 (2H, m, H1), 2.46 (3H, s, ArCH3). 13C NMR (CDCl3) d:
144.1 (ArC4), 135.1 (ArC1), 132.1 (ArC), 130.0 (ArC3+5),
125.5 (ArC), 123.4 (ArC), 65.7 (C2), 45.6 (C1), 29.72
(ArCH3). MSEI(+) m/z: 404 [M (81Br)H]+ (1.8), 402 [M
(79Br)H]+ (1.9), 322 [MꢃBr]+ (3.8), 278 [M (81Br)ꢃPhSO]+
(5.4), 276 [M (79Br)ꢃPhSO]+ (5.3), 155 [Ts]+ (100.0).
HRMSEI(+) calcd for C15H1781BrNS2O3 [M (81Br)H]+
403.98072, found 403.98062; calcd for C15H1779BrNS2O3
[M (79Br)H]+ 401.98332, found 401.98293.
00
[ArC2+6(a+b)], 84.3 (C2 a), 81.7 (C2 b), 48.8 (C7 a), 47.8
00
00
00
00
00 00
0
(C7 b), 44.7 [C4 (a+b)], 36.5 [C5 /3 (a+b)], 36.3 [C2 (a+b)],
0
00 00
00 00
00
31.6 (C3 a+b), 27.9 (C5 /3 a), 27.8 [C5 /3 b], 26.9 [C6 (a+b)],
00
00
21.6 [ArCH3(a+b)], 19.6 00 (C7 CH3a), 18.7 (C7 CH3b),
00
13.3 (C1 CH3a), 13.2 (C1 CH3b). HRMSEI(ꢃ) calcd for
C20H26NO4S [MꢃH]ꢃ 376.15880, found 376.15868.
4.1.3.26. N-b-Substituted ethyl-p-toluenesulfonamides
(2 and 3).
4.1.3.26.1. Methyl 2-bromo-3-(tosylamino)propanoate
(2a). Oil obtained in 6% (method A) and 3% (method B)
yields. IR (film) nmax: 3289 (N–H), 1744 (C]O), 1331
(S]O), 1160 (S]O) cmꢃ1. 1H NMR (CDCl3) d: 7.75 (2H,
d, J¼8.1 Hz, ArH2+6), 7.33 (2H, d, J¼8.1 Hz, ArH3+5),
5.11–5.08 (1H, m, exchange with D2O, NH), 4.38 (1H, dd,
4.1.3.26.5. N-(2-Bromo-2-cyanoethyl)tosylamine (2g).
Colorless solid obtained in 19% (method A) and 5% (method
B) yields; mp 110–113 ꢂC (dichloromethane/n-hexane). IR
(KBr) nmax: 3306 (N–H), 2254 (CN), 1335 (S]O), 1154

7016
A. M. M. Antunes et al. / Tetrahedron 63 (2007) 7009–7017
1
(S]O) cmꢃ1. H NMR (CDCl3) d: 7.77 (2H, d, J¼8.2 Hz,
ArH2+6), 7.35 (2H, d, J¼8.1 Hz, ArH3+5), 5.43 (1H, t,
J¼6.6 Hz, exchange with D2O, NH), 4.43 (1H, t,
J¼7.2 Hz, H2), 3.59–3.44 (2H, m, H1), 2.45 (3H, s,
ArCH3). 13C NMR (CDCl3) d: 144.5 (ArC4), 137.0 (ArC1),
132.8 (ArC3+5), 127.2 (ArC2+6), 115.4 (CN), 47.3 (C1), 26.5
(C2), 21.5 (ArCH3). MSEI(+) m/z: 304 [M (81Br)H]+(12.2),
302 [M (79Br)]+ (14.7), 184 [TsNHNH2]+ (100.0), 155
[Ts]+ (12.2). HRMSEI(+) calcd for C10H10N2 81BrS [M
(81Br)H]+ 303.96986, found 303.97043, calcd for
C10H11N279BrS [M (79Br)]+ 301.97246, found 301.97134.
142 ꢂC (ethyl acetate/n-hexane). IR (KBr) nmax: 3269 (N–
1
H), 1720 (C]O), 1329 (S]O), 1161 (S]O) cmꢃ1. H
0
NMR (CDCl3) d: 7.81–7.66 [4H, m, ArH(2+6)+(2 +6 )], 7.33–
0
0
0
7.27 [4H, m, ArH(3+5)+(3 +5 )], 5.85 (1H, d, J¼6.7 Hz, ex-
change with D2O, NH), 5.01–5.84 (1H, m, exchange with
D2O, NH), 3.83–3.80 (1H, m, H2), 3.38–3.32 (1H, m, H1),
3.20–3.14 (1H, m, H1), 2.44 (3H, s, ArCH3), 2.43 (3H, s,
ArCH3), 2.22 (3H, s, CH3). 13C NMR (CDCl3) d: 203.6
0
0
(CO), 144.3 (ArC4/4 ), 144.1 (ArC4/4 ), 136.1 (ArC1/1 ),
0
0
135.9 (ArC1/1 ), 130.0 (ArC3+5/3 +5 ), 130.0 (ArC3+5/3 +5 ),
0
0
0
0
0
0
0
0
127.3 (ArC2+6/2 +6 ), 127.1 (ArC2+6/2 +6 ), 61.2 (C2), 44.1
(C1), 26.7 (CH3), 21.37 (ArCH3), 21.36 (ArCH3). MSEI(+)
m/z: 411 [MH]+ (37.9), 367 [MꢃCH3CO]+ (89.3), 227
[TsNHCH2CH]+ (100.0), 155 [Ts]+ (28.1). HRMSEI(+)
calcd for C18H23N2O5S2 [MH]+ 411.10429, found
411.10432.
4.1.3.26.6. N-[2-Bromo-1-(ethoxymethyl)ethyl]tosyl-
amine (2n). Oil obtained in 5.6% yield (method B). IR
(film) nmax: 3262 (N–H), 1331 (S]O), 1160 (S]O) cmꢃ1
.
1H NMR (CDCl3) d: 7.8 (2H, d, J¼8.0 Hz, ArH2+6), 7.32
(2H, d, J¼8.4 Hz, ArH3+5), 5.03 (1H, d, J¼7.6 Hz, exchange
0
00
with D2O, NH), 3.56–3.30 (7H, m, H1 +H1+H2+H1 ), 2.44
00
4.1.3.26.10. N-[(3-Hydroxy-2-tosylamino)propyl]tosyl-
amine (3m). Oil obtained in 6% yield (method B). IR
(film) nmax: 3520 (O–H), 3291 (N–H), 1319 (S]O), 1153
(3H, s, ArCH3), 1.20 (3H, t, J¼7.2 Hz, H2 ). 13C NMR
(CDCl3) d: 143.8 (ArC4), 137.4 (ArC1), 129.8 (ArC3+5),
1
(S]O) cmꢃ1. H NMR (CDCl3) d: 7.74 (2H, d, J¼8.0 Hz,
0
127.1 (ArC2+6), 70.5 (C1 ), 66.8 (C1 ), 53.2 (C1), 33.1 (C2),
21.5 (ArCH3), 14.9 (C2 ). MSEI(+) m/z: 338 [M ( Br)H]
00
81
+
00
0
0
0
0
ArH2+6/2 +6 ), 7.67 (2H, d, J¼8.4 Hz, ArH2+6/2 +6 ), 7.31–
(92.8), 336 [M (79Br)H]+ (87.6), 256 [MꢃBr]+ (15.8), 155
[Ts]+ (100.0). HRMSEI(+) calcd for C12H1881BrNSO3 [M
(81Br)H]+ 338.02485, found 338.02185, calcd for
C12H1879BrNSO3 [M (79Br)H]+ 336.02635, found
336.02661.
7.29 [4H, m, ArH(3+5)+(3 +5 )], 5.43 (1H, d, J¼7.6 Hz, ex-
change with D2O, NH), 5.23 (1H, t, J¼6.4 Hz, exchange
with D2O, NH), 3.64 (1H, m, H1), 3.52 (1H, m, H1), 3.28
(1H, m, H2), 3.06–3.04 (2H, m, H3), 2.42 (6H, s, ArCH3),
1.67 (1H, br s, exchange with D2O, OH). 13C NMR
0 0
0
(CDCl3) d: 143.8 (ArC4/4 ), 136.9 (ArC1/1 ), 138.3 (ArC1/1 ),
0
0
0
0
0
0
0
0
4.1.3.26.7. Methyl 2,3-bis(tosylamino)propanoate (3a).
Colorless solid obtained in 8% yield (method B); mp 135–
136 ꢂC (ethyl acetate/n-hexane). IR (KBr) nmax: 3307 (N–
H), 3279 (N–H), 1742 (C]O), 1345 (S]O), 1153
129.9 (ArC3+5/3 +5 ), 127.1 (ArC2+6/2 +6 ), 127.0 (ArC2+6/2 +6 ),
61.8 (C1), 53.9 (C2), 43.9 (C3), 21.5 (ArCH3). MSEI(+) m/z:
399 [MH]+ (100.0), 381 [MꢃH2O]+ (20.7). HRMSEI(+)
calcd for C17H23N2O5S2 [MH]+ 399.10429, found
399.10439.
(S]O) cmꢃ1 1H NMR (CDCl3) d: 7.72–7.68 (4H, m,
.
ArH2+6), 7.33–7.29 (4H, m, ArH3+5), 5.55 (1H, d, J¼
7.0 Hz, exchange with D2O, NH), 5.07 (1H, t, J¼6.7 Hz,
exchange with, NH), 3.93–3.89 (1H, m, H2), 3.62 (3H, s,
OCH3), 3.36–3.30 (2H, m, H3), 2.44 (3H, s, ArCH3), 2.43
(3H, s, ArCH3). 13C NMR (CDCl3) d: 169.4 (CO), 144.1
4.1.3.26.11. N-[(3-Ethoxy-2-tosylamino)propyl]tosyl-
amine (3n). Oil obtained in 9% yield (method B). IR (film)
1
nmax: 3292 (N–H), 1330 (S]O), 1159 (S]O) cmꢃ1. H
0
0
NMR (CDCl3) d: 7.73 (2H, d, J¼8.0 Hz, ArH2+6/2 +6 ),
0
0
0
0
0
0
(ArC4/4 ), 143.7 (ArC4/4 ), 136.5 (ArC1/1 ), 135.8 (ArC1/1 ),
129.8 (ArC3+5), 127.2 (ArC2+6), 127.1 (ArC2+6), 55.4 (C2),
53.3 (OCH3), 45.3 (C3), 21.5 (ArCH3). MSESI(+) m/z: 427
[MH]+, 449 [MNa]+, 425 [MꢃH]ꢃ.
7.69 (2H, d, J¼8.0 Hz, ArH2+6/2 +6 ), 7.30 [4H, d,
0 0
J¼8.4 Hz, ArH(3+5)+(3 +5 )], 5.14 (1H, d, J¼6.8 Hz, exchange
with D2O, N2H), 5.02 (1H, t, J¼6.2 Hz, exchange with D2O,
1
00
N H), 3.41–3.21 (6H, m, 1H1+2H3+1H2+2H1 ), 3.03–2.96
(1H, m, H1), 2.44 (6H, s, ArCH3), 1.07 (3H, t, J¼7.2 Hz,
4.1.3.26.8. N,N-Dimethyl-2,3-bis(tosylamino)propan-
amide (3c). Colorless solid obtained in 9% (method A) and
7% (method B) yields; mp 148–150 ꢂC (dichloromethane/
n-hexane). IR (KBr) nmax: 3259 (N–H), 3140 (N–H), 1640
H2 ). 13C NMR (CDCl3) d: 143.7 (ArC4/4 ), 143.6 (ArC4/4 ),
00 0 0
0
136.9 (ArC1/1 ), 136.5 (ArC1/1 ), 129.8 [ArC(3+5)+(3 +5 )],
0
0
0
0
127.2 (ArC2+6/2 +6 ), 127.1 (ArC2+6/2 +6 ), 60.8 (C3), 66.8
0
0
0
00
00
(C1 ), 53.3 (C2), 42.7 (C1), 21.5 (ArCH3), 14.9 (C2 ).
MSEI(ꢃ): 426 [M]ꢃ (22.4), 424 [MꢃH]ꢃ (100.0), 155
[Ts]ꢃ (28.7). HRMSEI(ꢃ) calcd for C19H26N2O5S2 [M]ꢃ
426.12831, found 426.12773.
.
(C]O), 1323 (S]O), 1158 (S]O) cmꢃ1 1H NMR
(CDCl3) d: 7.71–7.65 (4H, m, ArH2+6), 7.30–7.27 (4H, m,
ArH3+5), 6.18 (1H, d, J¼9.6 Hz, exchange with D2O, NH),
5.86 (1H, t, J¼7.6 Hz, exchange with D2O, NH), 4.37–4.21
(1H, m, H2), 3.13–3.06 (1H, m, H3), 2.92 (3H, s, NCH3),
2.95–2.84 (1H, m, H3), 2.72 (3H, s, NCH3), 2.42 (6H, s,
4.2. NMR studies
ArCH3). 13C NMR (CDCl3) d: 168.9 (CO), 143.9 (ArC4/4 ),
4.2.1. Aziridination reaction of acrylonitrile. A mixture of
acrylonitrile (0.8 equiv, 0.06 mmol, 4 ml) and palladium(II)
chloride (0.13 equiv, 0.01 mmol, 1.6 mg) in CD3CN
(750 mL) was stirred (1/2 h) at room temperature. First por-
tion of bromamine-T (0.33 equiv, 0.02 mmol, 6.3 mg) was
added followed by two further additions (0.02 mmol each).
Each addition was performed only after a negative test
0
0
0
0
143.7 (ArC4/4 ), 136.9 (ArC1/1 ), 136.6 (ArC1/1 ), 129.8
(ArC3+5), 129.7 (ArC3+5), 127.3 (ArC2+6), 127.2 (ArC2+6),
52.4 (C2), 44.7 (C3), 37.1 (NCH3), 35.8 (NCH3), 21.34
(ArCH3). MSEI(+) m/z: 440 [MH]+ (44.9), 155 [Ts]+ (8.2).
HRMSEI(+) calcd for C19H25N3O5S2 [MH]+ 440.13084,
found 440.13096.
1
(starch-iodide paper) for bromamine-T was observed. H
NMR spectra were acquired for every 7 min over a period
of 10 h.
4.1.3.26.9. 3,4-Bis(tosylamino)butan-2-one (3e). Color-
less solid obtained in 16% yield (method B); mp 140–

A. M. M. Antunes et al. / Tetrahedron 63 (2007) 7009–7017
7017
22. Chanda, B. M.; Vyas, R.; Landge, S. S. J. Mol. Catal. A: Chem.
2004, 223, 57–60.
Acknowledgements
23. Tsuji, J. Palladium Reagents and Catalysts. Innovations
in Organic Synthesis; John Wiley & Sons: Chichester, UK,
1995.
24. For use of Pd0 in conjunction with TsNCl2 as an efficient azir-
idinating agent for unactivated olefins, see: Han, J.; Li, Y.; Zhi,
S.; Pan, Y.; Timmons, C.; Li, G. Tetrahedron Lett. 2006, 47,
7225–7228.
~
^
We thank Fundac¸ao para a Ciencia e Tecnologia (Lisbon,
Portugal), PRAXIS program, for partial financial support.
Three of us (A.M.M.A., V.D.B.B., and S.C.C.N.) also thank
PRAXIS program for the award of research fellowships. Pro-
fessor Manuela Pereira of our laboratory is thanked for a gift
of methylacrylate, bornyl acrylate, and fenchyl acrylate.
25. Hosokawa, T.; Takano, M.; Kuroki, Y.; Murahashi, S.-I.
Tetrahedron Lett. 1992, 33, 6643–6646.
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