One-pot stereoselective synthesis of anti 3-alkyl and 3-aryl-N-p-tosyl- aziridine-2-ketones and 3-aryl-N-p-tosyl-aziridine-2-carboxylates

Article abstract of DOI:10.1055/s-2004-831203

An efficient and practical synthesis of N-p-tosyl-aziridine-2-ketones and carboxylates through the use of α,β-unsaturated esters and ketones has been reported. The synthesis was conducted via a one-pot procedure consisting of aminohalogenation and in situ intramolecular S_N2 substitution. Triethylamine was found to be an effective base for the in situ cyclization for most substrates. Interestingly, for several enone cases, a slightly modified procedure in which 1.0 equivalent of p-TsNCl₂ was slowly added into 2.0 equivalents of enone for aminohalogenation followed by quenching with aqueous Na₂SO₃ resulted in crude aziridines which were proven to be nearly pure by the crude ¹H NMR analysis. Moderate to good yields and excellent anti stereoselectivity were achieved for 21 examples.

Full text of DOI:10.1055/s-2004-831203

PAPER
2479
One-Pot Stereoselective Synthesis of anti 3-Alkyl and 3-Aryl-N-p-tosyl-aziri-
dine-2-ketones and 3-Aryl-N-p-tosyl-aziridine-2-carboxylates
O
ne-Pot Stereosele
i
ctive
S
a
ynthesis of
n
Aziridine
C
j
arboxyl
u
ate
s
n Chen, Cody Timmons, Li Guo, Xin Xu, Guigen Li*
Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, TX 79409-1061, USA
E-mail: guigen.li@ttu.edu
Received 22 April 2004; revised 14 June 2004
Dedicated to Professor Iwao Ojima on the occasion of his 60th birthday
Ts
N
O
Abstract: An efficient and practical synthesis of N-p-tosyl-aziri-
dine-2-ketones and carboxylates through the use of a,b-unsaturated
esters and ketones has been reported. The synthesis was conducted
via a one-pot procedure consisting of aminohalogenation and in situ
intramolecular SN2 substitution. Triethylamine was found to be an
effective base for the in situ cyclization for most substrates. Inter-
estingly, for several enone cases, a slightly modified procedure in
which 1.0 equivalent of p-TsNCl2 was slowly added into 2.0 equiv-
alents of enone for aminohalogenation followed by quenching with
aqueous Na2SO3 resulted in crude aziridines which were proven to
1) CuOTf, 4 Å MS CH3CN
2) Na2SO3, Et3N
COR2
+ 4-TsNCl2
R1
R2
R1
R1 = Aryl or Alkyl, R2 = Aryl, Alkyl or Alkoxyl
Scheme 1
The synthesis was performed by the formation of amino-
halogenation products at first and then followed by in situ
cyclization via intramolecular SN2 reaction. Entry 1 of
Table 1 was used as the model synthesis. Methyl cin-
namate was subjected to aminochlorination reaction as
previously described, in which the combination of MeCN
(as solvent) and copper(I) triflate (as catalyst) was found
to give the highest efficiency. The next work is to find ef-
fective in situ intramolecular SN2 cyclization. Simply us-
ing common inorganic bases, such as NaOH, K2CO3,
ammonia hydroxide, etc., together with reductive quench-
ing reagent (aqueous sodium sulfite) resulted in partial cy-
clization with major haloamino products remained. We
then turned our attention to the use of organic bases at-
tempting to complete in situ intramolecular SN2 cycliza-
tion.
1
be nearly pure by the crude H NMR analysis. Moderate to good
yields and excellent anti stereoselectivity were achieved for 21 ex-
amples.
Key words: aziridination, aminohalogenation, haloamines, cin-
namates, enones
Aziridines are versatile building blocks in organic
synthesis1,2 because they can be readily converted into nu-
merous biologically important compounds. For example,
upon treatment with various nucleophiles, aziridines can
undergo regio- and stereoselective ring-opening reactions
to give unnatural amino acids, alkaloids, and amino sug-
ars.1,2
Among several organic amines we employed, Et3N was
found to give complete cyclization within a period of 10
minutes. The results of a variety of cinnamate substrates
are listed in Table 1. It was also found that at least 5 equiv-
alents of Et3N were necessary for the complete cycliza-
tion. Other organic amines, such as pyridine, DBU and
DABCO, either failed to give any aziridine product or
gave unknown products under the current conditions. Di-
isopropylamine did give aziridine products with dimin-
ished chemical yields.
Olefin-based aziridination reactions have served as major
approaches to a variety of aziridine-2-ketones and carbox-
ylates.1,3–7 In these known processes, PhI=N-Ts, chloram-
ine-T and TsNKI were commonly used as both nitrogen
sources and oxidants in the presence of metal catalysts.
Although much work on aziridination has been done so
far, the large-scale and practical aziridination methods
have not been very well documented in literature.8
Recently, we have reported the synthesis of N-protected
aziridine carboxylates from cinnamate-based haloamines
which were obtained from the aminohalogenation of cin-
namate esters.9,10 In this synthesis, haloamine products
were obtained at first, and then were subjected to the reac-
tion with K2CO3 in MeCN to give aziridine carboxylates.
This work spurred our next efforts to further improve the
experimental procedure. In this paper, we report the ste-
reoselective synthesis of anti 3-alkyl and 3-aryl-N-p-to-
syl-aziridine-2-ketones and carboxylates via a simple
one-pot procedure (Scheme 1).
As shown in Table 1, N-tosyl-aziridine-2-carboxylates
were formed with excellent stereoselectivities. In fact,
only trans isomers were observed in all cases as revealed
by crude 1H NMR analysis. As anticipated, the group on
the ester side has no obvious effect on the cyclization
(Table 1, entries 9 and 10). However, it was found that the
aromatic substrates with electron-donating groups on
their aromatic rings proceeded at faster rates than those
with electron-withdrawing groups.
Under the similar conditions, a,b-unsaturated ketones
(enones) resulted in of N-tosyl-aziridine-2-ketones, but
the yields were diminished because more side products
were produced. a,b-Unsaturated ketones showed higher
SYNTHESIS 2004, No. 15, pp 2479–2484
Advanced online publication: 02.09.2004
DOI: 10.1055/s-2004-831203; Art ID: M02704SS
© Georg Thieme Verlag Stuttgart · New York
x
x.
x
x
.
2
0
0
4

2480
D. Chen et al.
PAPER
Table 1 Indirect Aziridination of Cinnamate Esters
As revealed in Table 2, for most cases only one isomer
(trans isomer) was obtained. Interestingly, for entries 2, 5
and 8, 10% aqueous NH4OH was proven to be better than
Et3N in controlling stereoselectivity. Essentially, only
trans isomers were observed for entries 2 and 8 when
aqueous ammonia hydroxide was used. Unfortunately, the
aziridine product of methyl vinyl ketone cannot be puri-
fied by column chromatography, which resulted in the
complete decomposition. Therefore, a modified proce-
dure was developed in which the reaction was conducted
at 0 °C with slow addition of 1.0 equivalent of 4-TsNCl2
into 2 equivalents of methyl vinyl ketone. As revealed by
1H NMR analysis, nearly pure products were obtained
without further purification. Under the new condition, al-
most quantitative yields were achieved for cases de-
scribed in entries 9, 10 and 11. The excess amount of
unreacted enone starting materials can be recovered sim-
ply by distillation, which makes large scale reaction much
easier to be performed. A noteworthy aspect of this mod-
ified procedure is shown by the fact that there was no base
needed together with the quenching reagent. The quench-
ing reagent, aqueous Na2SO3, is basic enough for exclu-
sive aziridine formation.
Ts
N
O
1) CuOTf, 4 Å MS CH3CN
+ 4-TsNCl2
COOR'
Ar
OR'
Ar
2) Na2SO3, Et3N
Ar
R¢
Products
Yielda (%)
66
1
2
Me
1-1
Me
1-2
67
3
4
Me
Me
1-3
1-4
64
65
5
6
Me
Me
1-5
1-6
64
57
The major limitation of the present aziridine synthesis was
found on the use of terminal disubstituted a,b-unsaturated
ketones as the substrates. These substrates only gave di-
amination products predominantly under the current con-
ditions.11
7
8
Me
Me
1-7
1-8
81b
78b,c
In summary, an efficient and practical one-pot protocol
for the synthesis of N-tosyl-aziridine-2-ketones and car-
boxylates has been developed. The synthesis can be easily
conducted via a one-pot procedure consisting of aminoha-
logenation and intramolecular SN2 reactions. The modi-
fied procedure resulted in crude N-tosyl-aziridine-2-
ketones, which were proven to be nearly pure by the crude
1H NMR analysis.
9
i-Pr
1-9
67
65
10
CH2Ph
1-10
a Yields after purification via flash chromatography. Only trans iso-
mers were observed.
b This reaction required 2.5 equiv of 4-TsNCl2 for 2 d; otherwise, stan-
dard conditions.
All starting materials were commercially available and were used
without further purification. Solvents were technical grade and
carefully distilled before use. All IR spectra were obtained on sam-
ples deposited on NaCl plates. NMR spectra were recorded at 500
MHz for 1H NMR and 125 MHz for 13C NMR. CDCl3 was used as
solvent with TMS as the internal standard. Chemical shifts are re-
ported downfield from TMS (0.00 ppm) for 1H NMR and relative to
CDCl3 (77.0 ppm) for 13C NMR. The HRMS analysis was conduct-
ed by the mass spectroscopy laboratory of the Scripps Research In-
stitute. Column chromatography was performed with silica gel
Merck 60 (230–400 mesh).
c Even after 4 d there remained about 44% cinnamate ester unreacted.
reactivity toward N,N-dichloro-p-toluenesulfonamide (4-
TsNCl2) during aminohalogenation reaction than their es-
ter counterparts. The aminohalogenation of enone sub-
strates needed only 10 hours; but most alkylcinnamates
took more than 20 hours for complete consumption of the
starting materials. Furthermore, for aliphatic enones such
as methyl vinyl ketone, the total reaction time for amino-
halogenation and cyclization was only 2 hours.
Aziridination of Cinnamate Esters; General Procedure
Into a dry capped vial were added the cinnamate ester (1.0 mmol),
copper(I) trifluoromethanesulfonate (CuOTf) benzene complex
(50.3 mg, 0.10 mmol, 10 mol%), 4 Å molecular seives (500 mg) and
newly distilled CH3CN (2 mL). 4-TsNCl2 (360 mg, 1.5 mmol) was
dissolved in freshly distilled CH3CN (4 mL), then the resulting so-
lution was introduced into the reaction vial via syringe pump in a
period of 30 min. The resulting solution was stirred at r.t. for 22 h
under N2 protection. The reaction was monitored by TLC. Upon
completion the reaction was quenched with sat. aq Na2SO3 solution
(5 mL) followed by Et3N (5 mL), and stirred for 10 min to finish the
cyclization. The phases were separated, and the aqueous phase was
Efforts to optimize the reaction conditions for aromatic
enones were performed. The improvement was made by
slowly adding the MeCN solution of TsNCl2 into the re-
action mixture at 0 ºC in the presence of CuOTf catalyst
for aminohalogenation, and then followed by the reduc-
tive quenching and cyclization. The results are listed in
Table 2.
Synthesis 2004, No. 15, 2479–2484 © Thieme Stuttgart · New York

PAPER
One-Pot Stereoselective Synthesis of Aziridine Carboxylates
2481
Table 2 Aziridination Synthesis from a,b-Unsaturated Ketones
Entry
R1
R2
Product
Stereoselectivitya
(trans/cis)
Yield (%)b
55
1
Me
2-1
> 20:1
2
3
Ph
2-2
2-3
0.6:1 (> 20:1)
> 20:1
66
65
4
5
6
2-4
2-5
2-6
> 20:1
53
71
54
1.4:1 (3:1)
> 20:1
7
8
2-7
2-8
> 20:1
63c
86c
0.3:1 (> 20:1)
9
10
11
Me
H
Et
2-9
1.6:1
N/A
N/A
54 (quant.)e
66 (quant.)e
-d (quant.)e
Et
2-10
2-11
H
Me
a Estimated by crude 1H NMR determination. >20:1 means only anti isomers were observed. The ratios in parentheses are reactions quenched
with 10% aq NH3.
b Yields after purification via column chromatography.
c Required 2 equiv of 4-TsNCl2 and 48 h to finish the reaction.
d Decomposed during purification by column chromatography.
e Yields in parentheses are obtained from modified method without further purification; 4-TsNCl2 was used as the limiting reagent.
extracted with EtOAc (3 × 15 mL). The combined organic phase
was washed with brine, and dried with anhyd Na2SO4. Purification
by flash chromatography (EtOAc–hexane, 1:3) provided the pure
product.
Aziridination of Aliphatic Enones; Modified Procedure
Into a dry vial were added the enone (2.0 mmol), 4 Å molecular
sieves (500 mg), CuOTf benzene complex (50 mg, 0.1 mmol, 10
mol%) and freshly distilled MeCN (3.0 mL). A solution of 4-
TsNCl2 (240 mg, 1.0 mmol) in freshly distilled MeCN (6.0 mL) was
then added slowly into the above mixture by syringe pump in 1 h
under 0 ºC. The resulting solution was stirred at 0 ºC under Ar pro-
tection for 10 h, then quenched with sat. aq Na2SO3 solution (5 mL).
The two phases were separated, and the aqueous phase was extract-
ed with EtOAc (3 × 20 mL). The combined organic phase was
washed with brine, and dried with anhyd Na2SO4. Evaporation of
the solvent afforded nearly pure products as revealed by crude puri-
fication.
Aziridination of Enones; General Procedure
Into a dry capped vial were added the enone (1.0 mmol), copper(I)
trifluoromethanesulfonate (CuOTf) benzene complex (50.3 mg,
0.10 mmol, 10 mol%), 4 Å molecular seives (500 mg) and newly
distilled CH3CN (2 mL). The reaction vial was put into 0 °C bath.
4-TsNCl2 (360 mg, 1.5 mmol) was dissolved in newly distilled
CH3CN (4 mL), then the resulting solution was introduced into the
reaction vial via slow addition over 30 min. The resulting solution
was stirred at 0 °C for about 10 h under N2 protection. The reaction
was monitored by TLC. Later the reaction was quenched with sat aq
Na2SO3 solution (5 mL) followed by Et3N (5 mL) or 10% aq
NH4OH (5 mL). The phase was separated, and the aqueous phases
were extracted with EtOAc (3 × 5 mL). The combined organic
phase was washed with brine, and dried with anhyd Na2SO4. Purifi-
cation by flash chromatography (EtOAc–hexane, 1:3) provided the
pure product.
Methyl 1-[(4-Methylphenyl)sulfonyl]-3-phenylaziridine-2-car-
boxylate (1-1)
White solid; mp 44–45 °C.
IR: 1748, 1439, 1337, 1162 cm–1.
1H NMR (500 MHz, CDCl3): d = 7.76–7.80 (m, 2 H), 7.23–7.33 (m,
7 H), 4.44 (d, J = 4.0 Hz, 1 H), 3.86 (s, 3 H), 3.53 (d, J = 4.0 Hz, 1
H), 2.42 (s, 3 H).
Synthesis 2004, No. 15, 2479–2484 © Thieme Stuttgart · New York

2482
D. Chen et al.
PAPER
Methyl 3-(4-Nitrophenyl)-1-[(4-methylphenyl)sulfonyl]aziri-
13C NMR (125 MHz, CDCl3): d = 166.3, 144.4, 137.0, 132.5, 129.6,
128.9, 128.6, 127.5, 127.4, 127.3, 53.2, 47.7, 46.7, 21.6.
dine-2-carboxylate (1-7)
White solid; mp 114–116 °C.
Methyl 3-(2-Methylphenyl)-1-[(4-methylphenyl)sulfonyl]aziri-
dine-2-carboxylate (1-2)
White solid; mp 87–88 °C.
IR: 1753, 1599, 1450, 1341, 1167 cm–1.
1H NMR (500 MHz, CDCl3): d = 7.76–7.80 (m, 2 H), 7.02–7.32 (m,
6 H), 4.44 (d, J = 4.0 Hz, 1 H), 3.87 (s, 3 H), 3.55 (d, J = 4.0 Hz, 1
H), 2.44 (s, 3 H), 2.38 (s, 3 H).
13C NMR (125 MHz, CDCl3): d = 166.6, 144.5, 138.0, 136.6, 130.5,
130.1, 129.6, 128.8, 127.8, 126.5, 125.9, 53.2, 46.8, 45.3, 21.6,
19.1.
IR: 1746, 1523, 1444, 1346, 1162 cm–1.
1H NMR (500 MHz, CDCl3): d = 8.16–8.20 (m, 2 H), 7.80–7.84 (m,
2 H), 7.42–7.46 (m, 2 H), 7.31–7.35 (m, 2 H), 4.53 (d, J = 4.0 Hz, 1
H), 3.89 (s, 3 H), 3.49 (d, J = 4.0 Hz, 1 H), 2.45 (s, 3 H).
13C NMR (125 MHz, CDCl3): d = 165.5, 148.2, 144.9, 140.1, 136.6,
129.7, 128.2, 127.5, 123.9, 53.4, 47.6, 45.9, 21.7.
HRMS (MALDI–FTMS): m/z [M + H+] calcd for C17H17N2O6S:
377.0802; found: 377.0812.
Methyl 3-(2-Nitrophenyl)-1-[(4-methylphenyl)sulfonyl]aziri-
dine-2-carboxylate (1-8)
HRMS (MALDI–FTMS): m/z [M + H+] calcd for C18H20NO4S:
346.1107; found: 346.1104.
White solid; mp 128–129 °C.
IR: 1752, 1529, 1441, 1345, 1163 cm–1.
Methyl 3-(4-Bromophenyl)-1-[(4-methylphenyl)sulfonyl]aziri-
dine-2-carboxylate (1-3)
White solid; mp 133–134 °C.
IR: 1745, 1602, 1446, 1337, 1167 cm–1.
1H NMR (500 MHz, CDCl3): d = 7.76–7.80 (m, 2 H), 7.42–7.46 (m,
2 H), 7.28–7.32 (m, 2 H), 7.10–7.15 (m, 2 H), 4.38 (d, J = 4.0 Hz, 1
H), 3.87 (s, 3 H), 3.49 (d, J = 4.0 Hz, 1 H), 2.43 (s, 3 H).
13C NMR (125 MHz, CDCl3): d = 166.0, 144.6, 136.8, 131.8, 131.6,
129.7, 129.0, 127.5, 123.1, 53.2, 46.9, 46.8, 21.6.
1H NMR (500 MHz, CDCl3): d = 8.15–8.18 (m, 2 H), 7.86–7.90 (m,
2 H), 7.48–7.57 (m, 2 H), 7.30–7.38 (m, 2 H), 5.03 (d, J = 4.0 Hz, 1
H), 3.91 (s, 3 H), 3.36 (d, J = 4.0 Hz, 1 H), 2.47 (s, 3 H).
13C NMR (125 MHz, CDCl3): d = 165.5, 148.1, 144.8, 136.8, 134.1,
129.8, 129.7, 129.6, 129.4, 127.7, 125.1, 53.4, 47.1, 46.2, 21.7.
Isopropyl 1-[(4-Methylphenyl)sulfonyl]-3-phenylaziridine-2-
carboxylate (1-9)
Colorless oil.
HRMS (MALDI–FTMS): m/z [M + H+] calcd for C17H17NO4BrS:
IR: 1739, 1598, 1458, 1421, 1338, 1162 cm–1.
410.0056; found: 410.0054.
1H NMR (500 MHz, CDCl3): d = 7.77–7.81 (m, 2 H), 7.24–7.32 (m,
7 H), 5.17(m, 1 H), 4.43 (d, J = 4.0 Hz, 1 H), 3.48 (d, J = 4.0 Hz, 1
H), 2.42 (s, 3 H), 1.33 (m, 6 H).
13C NMR (125 MHz, CDCl3): d = 165.2, 144.2, 137.3, 132.8, 129.5,
128.8, 128.6, 127.4, 127.3, 70.4, 47.7, 47.5, 21.63, 21.60, 21.57.
Methyl 3-(2-Chlorophenyl)-1-[(4-methylphenyl)sulfonyl]aziri-
dine-2-carboxylate (1-4)
White solid; mp 105–106 °C.
IR: 1750, 1442, 1338, 1183 cm–1.
1H NMR (500 MHz, CDCl3): d = 7.81–7.85 (m, 2 H), 7.30–7.38 (m,
3 H), 7.23–7.28 (m, 1 H), 7.14–7.19 (m, 1 H), 7.07–7.10 (m, 1 H),
4.67 (d, J = 4.0 Hz, 1 H), 3.89 (s, 3 H), 3.44 (d, J = 4.0 Hz, 1 H),
2.45 (s, 3 H).
13C NMR (125 MHz, CDCl3): d = 166.0, 144.5, 136.7, 134.7, 131.0,
130.0, 129.7, 129.4, 128.0, 127.7, 126.9, 53.3, 46.3, 45.8, 21.7.
Benzyl 1-[(4-Methylphenyl)sulfonyl]-3-phenylaziridine-2-car-
boxylate (1-10)
White solid; mp 98–99 °C.
IR: 1746, 1597, 1456, 1336, 1163 cm–1.
1H NMR (500 MHz, CDCl3): d = 7.75–7.79 (m, 2 H), 7.34–7.42 (m,
5 H), 7.28–7.32 (m, 3 H), 7.22–7.28 (m, 4 H), 5.28 (d, J = 5.5, 2 H),
4.46 (d, J = 4.0 Hz, 1 H), 3.57 (d, J = 4.0 Hz, 1 H), 2.41 (s, 3 H).
13C NMR (125 MHz, CDCl3): d = 165.7, 144.3, 137.0, 134.8, 132.5,
129.6, 128.9, 128.64, 128.60, 128.59, 128.57, 127.5, 127.4, 68.2,
47.8, 46.9, 21.6.
Methyl 3-(3-Chlorophenyl)-1-[(4-methylphenyl)sulfonyl]aziri-
dine-2-carboxylate (1-5)
Colorless oil.
IR: 1748, 1600, 1453, 1344, 1180 cm–1.
1H NMR (500 MHz, CDCl3): d = 7.76–7.80 (m, 2 H), 7.14–7.32 (m,
6 H), 4.40 (d, J = 4.0 Hz, 1 H), 3.87 (s, 3 H), 3.48 (d, J = 4.0 Hz, 1
H), 2.43 (s, 3 H).
1-{1-[(4-Methylphenyl)sulfonyl]-3-phenylaziridin-2-yl}etha-
none (2-1)
Colorless oil.
13C NMR (125 MHz, CDCl3): d = 165.8, 144.6, 136.6, 134.7, 134.6,
IR: 1724, 1597, 1332, 1162 cm–1.
129.9, 129.6, 129.0, 127.5, 127.3, 125.5, 53.2, 46.9, 46.5, 21.6.
1H NMR (500 MHz, CDCl3): d = 7.68–7.73 (m, 2 H), 7.24–7.34 (m,
7 H), 4.27 (d, J = 4.5 Hz, 1 H), 3.73 (d, J = 4.5 Hz, 1 H), 2.42 (s, 3
H), 2.33 (s, 3 H).
13C NMR (125 MHz, CDCl3): d = 200.4, 144.5, 136.5, 131.6, 129.6,
129.0, 128.5, 128.0, 127.5, 51.0, 48.7, 28.5, 21.6.
Methyl 3-(4-Fluorophenyl)-1-[(4-methylphenyl)sulfonyl]aziri-
dine-2-carboxylate (1-6)
White solid; mp 118–120 °C.
IR: 1749, 1602, 1514, 1444, 1337 cm–1.
1H NMR (500 MHz, CDCl3): d = 7.75–7.79 (m, 2 H), 7.27–7.32 (m,
2 H), 7.22–7.27 (m, 2 H), 6.97–7.02 (m, 2 H), 4.40 (d, J = 4.0 Hz, 1
H), 3.86 (s, 3 H), 3.53 (d, J = 4.0 Hz, 1 H), 2.43 (s, 3 H).
{1-[(4-Methylphenyl)sulfonyl]-3-phenylaziridin-2-yl}(phe-
nyl)methanone (2-2)
White solid; mp 138–140 °C.
13C NMR (125 MHz, CDCl3): d = 166.1, 164.0, 162.0, 144.5, 136.8,
129.6, 129.3, 129.2, 128.20, 128.18, 127.5, 115.7, 115.5, 53.2, 47.0,
46.6, 21.6.
IR: 1692, 1597, 1449, 1331, 1225, 1162 cm–1.
1H NMR (500 MHz, CDCl3): d = 8.04–8.08 (m, 2 H), 7.70–7.74 (m,
2 H), 7.60–7.64 (m, 1 H), 7.46–7.51 (m, 2 H), 7.34 (s, 5 H), 7.20–
Synthesis 2004, No. 15, 2479–2484 © Thieme Stuttgart · New York

PAPER
One-Pot Stereoselective Synthesis of Aziridine Carboxylates
2483
7.26 (m, 2 H), 4.52 (d, J = 4.0 Hz, 1 H), 4.29 (d, J = 4.0 Hz, 1 H),
{3-(3-Nitrophenyl)-1-[(4-methylphenyl)sulfonyl]aziridin-2-
2.40 (s, 3 H).
yl}(phenyl)methanone (2-8)
White solid; mp 183–185 °C.
IR: 1684, 1596,1530, 1350, 1228, 1161 cm–1.
13C NMR (125 MHz, CDCl3): d = 190.3, 144.4, 136.6, 135.9, 134.1,
132.9, 129.5, 128.9, 128.8, 128.7, 128.6, 127.7, 127.5, 50.2, 47.5,
21.6.
1H NMR (500 MHz, CDCl3): d = 8.17–8.21 (m, 1 H), 8.11–8.14 (m,
1 H), 8.03–8.08 (m, 2 H), 7.69–7.76 (m, 3 H), 7.63–7.67 (m, 1 H),
7.47–7.57 (m, 3 H), 7.24–7.28 (m, 2 H), 4.64 (d, J = 4.5 Hz, 1 H),
4.25 (d, J = 4.0 Hz, 1 H), 2.41 (s, 3 H).
13C NMR (125 MHz, CDCl3): d = 189.4, 148.4, 145.0, 135.9, 135.7,
135.6, 134.4, 133.8, 129.8, 129.7, 129.1, 128.9, 127.8, 123.8, 122.2,
50.6, 45.2, 21.6.
(4-Methoxyphenyl){1-[(4-methylphenyl)sulfonyl]-3-phenyl-
aziridin-2-yl}methanone (2-3)
White solid; mp 108–110 °C.
IR: 1677, 1599, 1330, 1264, 1241, 1162 cm–1.
1H NMR (500 MHz, CDCl3): d = 8.03–8.07 (m, 2 H), 7.70–7.74 (m,
2 H), 7.33 (s, 5 H), 7.21–7.24 (m, 2 H), 6.93–6.97 (m, 2 H), 4.50 (d,
J = 4.0 Hz, 1 H), 4.26 (d, J = 4.0 Hz, 1 H), 3.89 (s, 3 H), 2.40 (s, 3 H).
1-{3-Methyl-1-[(4-methylphenyl)sulfonyl]aziridin-2-yl}propan-
1-one (2-9)
Colorless oil.
IR: 1711, 1597, 1326, 1161, 1090 cm–1.
13C NMR (125 MHz, CDCl3): d = 188.5, 164.3, 144.3, 136.7, 133.0,
131.4, 129.5, 129.1, 128.8, 128.6, 127.7, 127.5, 114.0, 55.6, 50.1,
47.4, 21.6.
Trans-isomer: 1H NMR (500 MHz, CDCl3): d = 7.82–7.86 (m, 2 H),
7.31–7.36 (m, 2 H), 3.36 (d, J = 4.5 Hz, 1 H), 3.00–3.05 (m, 1 H),
2.44 (s, 3 H), 2.37–2.47 (m, 1 H), 2.17–2.26 (m, 1 H), 1.76 (d, J =
6.0 Hz, 3 H), 0.90 (t, J = 7.0 Hz, 3 H).
Cis-isomer: 1H NMR (500 MHz, CDCl3): d = 7.82–7.86 (m, 2 H),
7.33–7.38 (m, 2 H), 3.40 (d, J = 7.5 Hz, 1 H), 3.06–3.12 (m, 1 H),
2.46 (s, 3 H), 2.48–2.55 (m, 1 H), 2.23–2.31 (m, 1 H), 1.20 (d, J =
5.5 Hz, 3 H), 1.00 (t, J = 7.0 Hz, 3 H).
(4-Chlorophenyl){1-[(4-methylphenyl)sulfonyl]-3-phenylaziri-
din-2-yl}methanone (2-4)
White solid: mp 158–160 °C.
IR: 1693, 1596, 1448, 1333, 1224, 1163 cm–1.
1H NMR (500 MHz, CDCl3): d = 7.94–7.98 (m, 2 H), 7.78–7.82 (m,
2 H), 7.34–7.39 (m, 4 H), 7.17 (s, 5 H), 4.33 (d, J = 2.0 Hz, 2 H),
2.45 (s, 3 H).
13C NMR (125 MHz, CDCl3): d = 188.2, 145.3, 140.4, 134.2, 134.0,
131.0, 129.9, 129.7, 129.0, 128.6, 128.4, 128.1, 127.2, 47.9, 46.4,
21.7.
1-{1-[(4-Methylphenyl)sulfonyl]aziridin-2-yl}propan-1-one (2-
10)
White solid; mp 62–64 °C.
(4-Fluorophenyl){1-[(4-methylphenyl)sulfonyl]-3-phenylaziri-
din-2-yl}methanone (2-5)
Colorless oil.
IR: 1685, 1597, 1507, 1330, 1232, 1160 cm–1.
1H NMR (500 MHz, CDCl3): d = 8.08–8.13 (m, 2 H), 7.69–7.74 (m,
2 H), 7.30–7.36 (m, 5 H), 7.23–7.27 (m, 2 H), 7.14–7.19 (m, 2 H),
4.52 (d, J = 4.0 Hz, 1 H), 4.21 (d, J = 4.0 Hz, 1 H), 1.55 (s, 3 H).
IR: 1715, 1596, 1328, 1163, 1093 cm–1.
1H NMR (500 MHz, CDCl3): d = 7.81–7.86 (m, 2 H), 7.35–7.39 (m,
2 H), 3.33 (dd, J = 4.0, 7.5 Hz, 1 H), 2.77 (d, J = 7.5 Hz, 1 H), 2.49
(d, J = 4.0 Hz, 1 H), 2.46 (s, 3 H), 2.34–2.52 (m, 2 H), 1.00 (t, J =
7.5 Hz, 3 H).
13C NMR (125 MHz, CDCl3): d = 203.8, 145.3, 133.9, 129.9, 128.1,
41.1, 32.6, 32.1, 21.7, 7.0.
13C NMR (125 MHz, CDCl3): d = 188.8, 144.5, 136.5, 132.9, 131.8,
131.7, 129.5, 128.7, 127.7, 127.4, 116.1, 115.9, 50.2, 47.3, 21.6.
1-{1-[(4-Methylphenyl)sulfonyl]aziridin-2-yl}ethanone (2-11)
Colorless oil.
{3-(2-Chlorophenyl)-1-[(4-methylphenyl)sulfonyl]aziridin-2-
yl}(phenyl)methanone (2-6)
White solid; mp 159–161 °C.
IR: 1692, 1596, 1448, 1331, 1223, 1162 cm–1.
IR: 1713, 1597, 1329, 1163, 1093 cm–1.
1H NMR (500 MHz, CDCl3): d = 7.81–7.87 (m, 2 H), 7.35–7.40 (m,
2 H), 3.29 (dd, J = 4.0, 7.5 Hz, 1 H), 2.81 (d, J = 7.5 Hz, 1 H), 2.50
(d, J = 4.0 Hz, 1 H), 2.47 (s, 3 H), 2.08 (S, 3 H).
1H NMR (500 MHz, CDCl3): d = 7.96–8.00 (m, 2 H), 7.90–7.94 (m,
2 H), 7.52–7.57 (m, 1 H), 7.49–7.54 (m, 2 H), 7.35–7.39 (m, 2 H),
7.32–7.36 (m, 1 H), 7.17–7.21 (m, 1 H), 7.10–7.15 (m, 2 H), 4.61
(d, J = 8.0 Hz, 1 H), 4.57 (d, J = 7.5 Hz, 1 H), 2.45 (s, 3 H).
13C NMR (125 MHz, CDCl3): d = 188.3, 145.3, 135.5, 134.2, 133.9,
133.4, 129.9, 129.7, 129.4, 129.0, 128.9, 128.6, 128.5, 128.1, 126.7,
47.1, 45.0, 21.7.
13C NMR (125 MHz, CDCl3): d = 201.7, 145.6, 134.1, 130.2, 128.9,
42.2, 32.1, 26.1, 21.9.
Acknowledgment
We gratefully acknowledge the National Institutes of Health, Gene-
ral Medical Sciences (R15-GM-60261) and the Robert A. Welch
foundation (D-1361) for the generous support of this work, and the
National Science Foundation (CHE-9808436) for partial funding of
the 500 MHz NMR spectrometer.
{3-(4-Nitrophenyl)-1-[(4-methylphenyl)sulfonyl]aziridin-2-
yl}(phenyl)methanone (2-7)
White solid; mp 103–105 °C.
IR: 1692, 1598, 1522, 1449, 1346, 1223, 1162 cm–1.
References
1H NMR (500 MHz, CDCl3): d = 8.02–8.06 (m, 2 H), 7.95–7.99 (m,
2 H), 7.83–7.87 (m, 2 H), 7.54–7.59 (m, 1 H), 7.36–7.45 (m, 6 H),
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13C NMR (125 MHz, CDCl3): d = 188.2, 147.9, 145.7, 138.4, 135.2,
134.3, 133.9, 130.1, 128.9, 128.4, 128.3, 128.1, 123.5, 47.9, 45.2,
21.7.
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