An improved and mild wenker synthesis of aziridines

Article abstract of DOI:10.1055/s-0030-1257913

The conventional Wenker synthesis of aziridines from vicinal amino alcohols has been modified by employing mild reaction conditions. Amino alcohols were converted into their hydrogen sulfates with chlorosulfonic acid. The sulfates were cyclized with sodium hydroxide, and even with non-nucleophilic sodium carbonate. The current, improved method extends the scope of the typical Wenker synthesis and is applicable to unstable amino alcohols in hot sulfuric acid and to unstable sulfates which favor elimination and hydroxide displacement in the presence of strong base. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-0030-1257913

PAPER
3423
An Improved and Mild Wenker Synthesis of Aziridines
I
mprove
d
W
enke
r
i
Synthe
n
sis of
A
zirid
y
ines ao Li, Ning Chen, Jiaxi Xu*
State Key Laboratory of Chemical Resource Engineering, Department of Organic Chemistry, Faculty of Science, Beijing University of
Chemical Technology, Beijing 100029, P. R. of China
Fax +86(10)64435565; E-mail: jxxu@mail.buct.edu.cn
Received 25 May 2010; revised 18 June 2010
the occurrence of the elimination of water from unstable
Abstract: The conventional Wenker synthesis of aziridines from
amino alcohols in hot sulfuric acid in the esterification
vicinal amino alcohols has been modified by employing mild reac-
step, and of the competing elimination and hydroxide nu-
cleophilic substitution with strong bases such as alkali
tion conditions. Amino alcohols were converted into their hydrogen
sulfates with chlorosulfonic acid. The sulfates were cyclized with
sodium hydroxide, and even with non-nucleophilic sodium carbon- metal hydroxides in the cyclization step. Herein, we
ate. The current, improved method extends the scope of the typical
present our improved Wenker synthesis of aziridines with
Wenker synthesis and is applicable to unstable amino alcohols in
a wide application scope. The current, improved method
hot sulfuric acid and to unstable sulfates which favor elimination
is an efficient version compared to the conventional meth-
and hydroxide displacement in the presence of strong base.
od.
Key words: amino alcohols, aziridines, hydrogen sulfates, Wenker
In the conventional Wenker synthesis of aziridines, amino
alcohol hydrogen sulfates are prepared from amino alco-
hols and sulfuric acid through vacuum dehydration at be-
low 130–140 °C; however, some amino alcohols, such as
tertiary alcohols and alcohols with a b-aryl or an alkenyl
group, favorably undergo elimination of water under the
Wenker conditions.7,8 To inhibit the elimination, mild es-
terification conditions are demanded. Even though mesy-
lation and tosylation can be used to activate the hydroxy
group, and the reactions can occur under mild conditions,
an amino group shows better nucleophilicity than the hy-
droxy group in the amino alcohols. The amino group
should be protected prior to the activation of the hydroxy
group. Protection and deprotection of the amino group,
however, shadow the advantage of the activation method.9
synthesis
Aziridines (both N-H aziridines and N-substituted aziri-
dines) are very important intermediates in synthetic or-
ganic chemistry.1 Although several synthetic methods for
aziridines have been developed,2,3 with most of them suit-
able for the preparation of N-substituted aziridines, few
methods can be applied in the direct synthesis of N-H azir-
idines. To date, the Wenker synthesis is still considered
one of the most efficient and practical routes for the syn-
thesis of aziridines, especially N-H aziridines, from vici-
nal amino alcohols.4 It has been used to prepare
structurally diverse N-H aziridines, including optically
pure aziridines.4e Recently, our working group has fo-
cused on the synthesis of structurally diverse substituted
taurines.5 We developed novel methods to synthesize sub-
stituted taurines using N-H aziridines4e,5b,d,g,i and
thiiranes5b,c,h as critical starting materials. Thus, we have
paid much attention to the synthesis of aziridines,6 espe-
cially N-H aziridines.3b,4e,5d,g,i,7 After comparing different
synthetic methods, we consider the Wenker synthesis to
be the more efficient and convenient method, with a short
synthetic route utilizing commercially available or easily
prepared amino alcohol starting materials. However,
some unexpected products were obtained after treatment
of certain amino alcohols under the conventional Wenker
conditions.7,8 Our further investigations indicated that vic-
inal amino alcohols which could readily undergo elimina-
tion of water are unsuitable starting materials for the
preparation of N-H aziridines via the Wenker synthesis.7
This limits the utility of the Wenker synthesis. To extend
the applied scope of the Wenker synthesis for the prepara-
tion of various aziridines, our hope was to conduct the
Wenker synthesis under mild reaction conditions to avoid
Chlorosulfonic acid is also a gentle reagent for forming
sulfate esters. The reaction of amino alcohols and chloro-
sulfonic acid produces hydrogen sulfates 2 under mild
conditions (Scheme 1).9,10 This provides a perfect esterifi-
cation method, considering that amphoteric amino alcohol
hydrogen sulfates do not dissolve in diethyl ether, but
most amino alcohols do. First, amino alcohols 1a,b were
dissolved in diethyl ether and chlorosulfonic acid was
added slowly. The amino alcohol hydrogen sulfates ap-
peared immediately as colorless crystals. After collection
by filtration and washing with diethyl ether, the sulfates
were obtained in excellent yields (Table 1, entries 1–4).
No obvious difference was observed for reactions con-
ducted at different temperatures. Amino alcohols 1c–f
with aryl substituents, however, show poor solubility in
diethyl ether. 2-Amino-2-phenylethanol (1c) was selected
as a model for optimization of the esterification conditions
in different solvents. The results are summarized in Table
1 (entries 5–11). 2-Amino-2-phenylethanol (1c) is soluble
in tetrahydrofuran, acetonitrile, dichloromethane, and
chloroform, and gave rise to the corresponding hydrogen
sulfate 2c in good to excellent yields (82–95% yield) in
these solvents. The amphoteric sulfate 2c precipitated eas-
ily from tetrahydrofuran and acetonitrile, but shows some
SYNTHESIS 2010, No. 20, pp 3423–3428
Advanced online publication: 30.07.2010
DOI: 10.1055/s-0030-1257913; Art ID: F08810SS
© Georg Thieme Verlag Stuttgart · New York
x
x.
x
x
.
2
0
1
0

3424
X. Li et al.
PAPER
solubility in dichloromethane and chloroform. When the After the successes in mild esterification, we hoped to
latter were used as solvents and after the reaction had fin- realize cyclization in good to excellent yields for various
ished completely, either diethyl ether was added to precip- amino alcohol hydrogen sulfates 2 (Scheme 2). Sulfates
itate the amphoteric sulfate or the solvent was removed 2a–c were converted into the corresponding aziridines
and the residue was solidified by stirring with diethyl 3a–c in satisfactory to good yields under traditional
ether. After washing with diethyl ether, colorless crystals Wenker conditions (6.2 M NaOH) (Table 2, entries 1–3).
of the product sulfate were obtained in good yields. For Aziridines 3a,b were obtained in relatively low yields due
convenient workup, 2-amino-2-phenylethanol (1c) was to loss on purification (better volatility and solubility in
firstly dissolved in chloroform and then the resulting solu- water). Sulfates 2d–f, however, show poor solubility in
tion was further diluted with diethyl ether or acetonitrile. 6.2 M NaOH and the cyclization did not occur at room
Addition of chlorosulfonic acid and stirring gave the sul- temperature. At 70 °C, the desired aziridines 3d–f were
fate precipitate. After collection by filtration and washing obtained in yields of 34%, 4%, and 20%, respectively (Ta-
with diethyl ether, the sulfate was obtained in excellent ble 2, entries 5, 7, and 9). Some byproducts were generat-
yields (Table 1, entries 10 and 11). When the same proce- ed from elimination and by hydroxide displacement of
dure was used for the esterification of 2-amino-1,1-diphe- sulfates 2d–f due to the strong basic conditions and good
nylethanol (1d), 2-amino-2,2-diphenylethanol (1e), and nucleophilicity of hydroxide. To avoid these competing
(1S,2R)-2-amino-1,2-diphenylethanol (1f), better yields reactions, we selected non-nucleophilic sodium carbonate
were achieved compared with those using the procedure as the base instead of sodium hydroxide. Sulfates 2d–f
with pure chloroform as solvent (Table 1, entries 12–19). were dissolved in saturated aqueous sodium carbonate so-
lution and the resulting mixtures were stirred at 70 °C for
R4 R3
R4 R3
3 hours. The yields of aziridines 3d–f were improved to
–
ClSO3H
OSO3
OH
43%, 13%, and 32%, respectively (Table 2, entries 6, 8,
and 10). Extension of the reaction time did not lead to fur-
ther increase in the yields. The sulfate 2e produced 2,2-
diphenylaziridine in the lowest yield due to the most
bulky steric hindrance of its amino group (Table 2, entries
7 and 8). Although 2-amino-1,1-diphenylethanol (1d), 2-
amino-2,2-diphenylethanol (1e), and (1S,2R)-2-amino-
1,2-diphenylethanol (1f) gave rise to the corresponding
aziridines in only low to satisfactory yields in our current,
improved Wenker synthesis, it should be noted that in the
traditional Wenker synthesis 2-amino-1,1-diphenyleth-
anol (1d) and 2-amino-2,2-diphenylethanol (1e) do not
produce the aziridine 3d, and (1S,2R)-2-amino-1,2-diphe-
nylethanol (1f) gave only a trace of aziridine 3f.7 This is
the first convenient synthesis of 2,2-diphenylaziridine
(3d) and (2R,3R)-2,3-diphenylaziridine (3f) from the cor-
responding amino alcohols via the Wenker synthesis. 2,2-
Diphenylaziridine (3d) has been previously prepared
from acetophenone oxime and phenylmagnesium bro-
mide,11 from 1,1,1-trimethyl-2-(1-phenylethylidene)hy-
drazinium iodide and phenylmagnesium bromide,11,12 and
from methyl N-(2-iodo-1,1-diphenylethyl)carbamate and
potassium hydroxide.13 (2R,3R)-2,3-Diphenylaziridine
(3f) has been synthesized from N-[(1R,2S)-2-(methyl-
thio)-1,2-diphenylethyl]-4-methylbenzenesulfinamide14
and from (1S,2R)-1,2-diphenylethanol,15 via multiple
steps. Compared with the reported methods, our current
synthetic method is a convenient and practical route from
commercially available starting materials in high efficien-
cy.
+H3N
H2N
R2 R1
R2 R1
1
2
Scheme 1 Synthesis of amino alcohol hydrogen sulfates 2
Table 1 Optimization of the Esterification of Amino Alcohols 1
Entry Amino alcohol 1
Solvent
Temp Yield
(°C)
(%)
OH
1
2
Et2O
Et2O
0
–20
93
93
NH2
1a
NH2
3
4
Et2O
Et2O
0
–20
96
95
OH
1b
5
6
7
8
9
10
11
THF
CH2Cl2
CHCl3
MeCN
0
0
0
0
–20
0
0
85
84
82
94
95
95
94
NH2
OH
Ph
MeCN
1c
CHCl3–MeCN
CHCl3–Et2O
OH
NH2
OH
12
13
14
CHCl3
0
0
0
83
95
93
Ph
NH2
OH
Ph
CHCl3–MeCN
CHCl3–Et2O
Ph
1d
15
16
17
CHCl3
0
0
0
80
94
94
Ph
CHCl3–MeCN
CHCl3–Et2O
Ph
1e
R4 R3
H
N
R3
R4
–
18
19
CHCl3–MeCN
CHCl3–Et2O
0
0
96
95
NaOH or Na2CO3
OSO3
Ph
R1
R2
+H3N
R2 R1
NH2
2
3
1f
Scheme 2 Synthesis of aziridines 3
Synthesis 2010, No. 20, 3423–3428 © Thieme Stuttgart · New York

PAPER
Improved Wenker Synthesis of Aziridines
3425
Table 2 Optimization of the Cyclization of Amino Alcohol Hydro-
gen Sulfates 2
Table 3 Synthesis of Aziridines from Amino Alcohols (continued)
Entry
2
Amino alcohol 1
Aziridine 3
Yielda (%)
53
Entry Amino alcohol hydro-Base
Temp Yield
H
N
gen sulfate 2
(°C)
(%)
NH2
OH
–
OSO3
+
1
2
6.2 M NaOH
6.2 M NaOH
r.t.
46
NH3
1b
3b
2a
2b
H
N
NH2
+
NH3
3
4
78
OH
Ph
–
r.t.
r.t.
56
82
Ph
OSO3
1c
(S)-3c
H
N
OH
+
NH3
Ph
41b
Ph
Ph
NH2
–
3
6.2 M NaOH
OSO3
Ph
Ph
1d
2c
3d
–
OSO3
4
5
6
6.2 M NaOH
6.2 M NaOH
sat. aq Na2CO3
r.t.
70
70
0
34
43
H
N
NH2
+
Ph
NH3
Ph
5
12b
Ph
OH
Ph
Ph
Ph
2d
1e
3d
+
NH3
OH
7
8
6.2 M NaOH
sat. aq Na2CO3
70
70
4
13
–
H
N
Ph
OSO3
Ph
Ph
Ph
6
7
31b
81
Ph
Ph
2e
NH2
–
3f
OSO3
1f
Ph
H
9
10
6.2 M NaOH
sat. aq Na2CO3
70
70
20
32
OH
Ph
N
+
NH2
Ph
NH3
Ph
2f
1g
( )-3c
H
NH2
OH
N
After successful improvement of the esterification and the
cyclization, the improved and mild Wenker synthesis was
applied to a series of vicinal amino alcohols (Scheme 3),
including 1- and 2-substituted, and 1,1-, 2,2-, 1,2-, and
2,N-disubstituted aminoethanols (covering aliphatic and
aromatic amino primary, secondary, and tertiary alco-
hols). The results are summarized in Table 3. Compared
with the traditional Wenker synthesis, the current method
can be used to prepare not only aliphatic, but also aromat-
ic, substituted aziridines in satisfactory to good overall
yields. The method is very general, practical, and versa-
tile.
8
9
68
85
67
1h
3h
H
NH2
N
Ph
OH
Ph
1i
3i
OH
NH
NH2
( )
10
3j
1j
H
N
N
OH
R5
R1 R2
H
11
12
75
ClSO3H
NaOH or Na2CO3
N
N
R3 R4
1
R3
R4
R5
R1
R2
HO
3k
1k
4-ClC6H4
4-ClC6H4
3
NH
56c
N
OH
OH
Scheme 3 Synthesis of aziridines from amino alcohols
Table 3 Synthesis of Aziridines from Amino Alcohols
1l
3l
4-ClC6H4
4-ClC6H4
NH
Yielda (%)
13
54c
Entry
Amino alcohol 1
Aziridine 3
N
Ph
Ph
H
N
OH
1m
3m
1
43
NH2
a Cyclization conducted in 6.2 M NaOH at r.t. unless otherwise indi-
cated. Yields are overall yields from amino alcohols 1.
b Cyclization conducted in sat. aq Na2CO3 at 70 °C.
c Cyclization conducted in 6.2 M NaOH at 70 °C.
1a
3a
Synthesis 2010, No. 20, 3423–3428 © Thieme Stuttgart · New York

3426
X. Li et al.
PAPER
with Et2O (3 × 50 mL). After drying (Na2SO4) and concentration
In summary, the Wenker synthesis is one of the most effi-
cient and practical routes for the preparation of aziridines,
especially N-H aziridines, from vicinal amino alcohols;
however, the conventional Wenker synthesis is unsuitable
for amino alcohols which favorably undergo the elimina-
tion of water in hot sulfuric acid and for sulfates which
predominantly undergo elimination and displacement in
the presence of strong base. The conventional Wenker
synthesis was modified and improved by employing mild
reaction conditions in which amino alcohols were con-
verted into their hydrogen sulfates with chlorosulfonic
acid. The sulfates can be cyclized with non-nucleophilic
sodium carbonate. The current, improved method extends
the scope of the typical Wenker synthesis and is applica-
ble to various amino alcohols, including amino alcohols
which favor the elimination of water in the presence of hot
sulfuric acid.
under reduced pressure, the product was obtained as a colorless oil.
Aromatic Aziridines 3; General Procedure
To an amino alcohol hydrogen sulfate (5 mmol) was added sat. aq
Na2CO3 (10 mL), and the mixture was stirred at 70 °C for 3 h, then
extracted with Et2O (3 × 50 mL). After removal of solvent, the res-
idue was purified on a silica gel column (basification with 1% Et3N
in petroleum ether) with petroleum ether–EtOAc (5:1, v/v) as eluent
to afford the product as a colorless oil.
2-Methylaziridine (3a)17
Yield: 1.23 g (43%) on 50 mmol scale; colorless oil; bp 63–65 °C/
760 Torr (Lit.18 63–64 °C/760 Torr).
1H NMR (200 MHz, CDCl3): d = 0.25 (br s, 1 H), 1.20 (d, J = 6.6
Hz, 3 H), 1.30 (d, J = 3.0 Hz, 1 H), 1.74 (d, J = 4.6 Hz, 1 H), 1.97
(ddq, J = 3.0, 4.6, 6.6 Hz, 1 H).
13C NMR (50.3 MHz, CDCl3): d = 20.0, 25.1, 25.8.
2,2-Dimethylaziridine (3b)17
Yield: 1.89 g (53%) on 50 mmol scale; colorless oil; bp 70–72 °C/
Melting points were measured on a Yanaco MP-500 melting point
760 Torr (Lit.18 69–70 °C/760 Torr).
1
apparatus and are uncorrected. H and 13C NMR spectra were re-
1H NMR (300 MHz, CDCl3): d = 1.05 (s, 6 H), 1.57 (br s, 1 H), 2.29
(s, 2 H).
13C NMR (75.5 MHz, CDCl3): d = 24.1, 30.2, 32.5.
corded in CDCl3 with TMS as an internal standard on a Varian Mer-
cury 200 (200 MHz) or a Varian Mercury Plus 300 (300 MHz)
spectrometer. HRMS data were obtained on a Bruker APEX IV
Fourier transform ion cyclotron resonance mass spectrometer. IR
spectra were determined on a Nicolet 5700 FT-IR spectrometer.
Some of the starting amino alcohols are commercially available and
were used as received without additional purification. 2-Amino-2,2-
diphenylethanol was prepared from 2-hydroxy-2,2-diphenylacetic
acid via the Ritter reaction.16 Other commercially unavailable ami-
no alcohols were synthesized according to our previous paper.7 The
analytical data of all known aziridines are identical to those data
previously reported in the literature.17–25
2-Phenylaziridine (3c)17
Yield: 0.49 g (81%); colorless oil; bp 77–79 °C/18 Torr (Lit.19
75 °C/15 Torr).
1H NMR (200 MHz, CDCl3): d = 1.51 (br s, 1 H), 1.81 (d, J = 3.0
Hz, 1 H), 2.20 (m, 1 H), 3.01 (m, 1 H), 7.18–7.40 (m, 5 H).
13C NMR (50.3 MHz, CDCl3): d = 29.2, 32.1, 125.6, 127.0, 128.4,
140.3.
Aliphatic Amino Alcohol Hydrogen Sulfates 2; General Proce-
dure
(S)-2-Phenylaziridine [(S)-3c]
Yield: 0.47 g (78%); colorless oil; bp 77–79 °C/18 Torr.
A 150-mL, two-necked, round-bottom flask was fitted with a mag-
netic stirrer bar and an addition funnel. The flask was charged with
a vicinal amino alcohol (10 mmol) and Et2O (100 mL). After the
vicinal amino alcohol was dissolved completely, the flask was
cooled to 0 °C in an ice bath. Then, ClSO3H (1.16 g, 10 mmol) was
slowly added under vigorous stirring; white solid was formed. The
solution was stirred for 2 h. The solid was collected and washed
with Et2O (3 × 10 mL). After drying under reduced pressure, the
amino alcohol hydrogen sulfate was obtained as colorless crystals.
[a]D20 –41.8 (c 8.6, EtOH) [Lit.20 [a]D22 –42.5 (c 10.30, EtOH)].
1H NMR (200 MHz, CDCl3): d = 0.72 (br s, 1 H), 1.80 (d, J = 3.2
Hz, 1 H), 2.21 (d, J = 6.0 Hz, 1 H), 3.02 (dd, J = 3.2, 6.0 Hz, 1 H),
7.22–7.32 (m, 5 H).
13C NMR (50.3 MHz, CDCl3): d = 29.2, 32.0, 125.6, 127.0, 128.4,
140.3.
2,2-Diphenylaziridine (3d)17
Yield: 0.40 g (41%); colorless oil.
1H NMR (300 MHz, CDCl3): d = 1.06 (br s, 1 H), 2.36 (s, 2 H),
7.22–7.36 (m, 10 H).
13C NMR (75.5 MHz, CDCl3): d = 35.4, 43.8, 127.1, 127.7, 128.3,
142.5.
Aromatic Amino Alcohol Hydrogen Sulfates 2; General Proce-
dure
A 150-mL, two-necked, round-bottom flask was fitted with a mag-
netic stirrer bar and an addition funnel. The flask was charged with
a vicinal amino alcohol (10 mmol) and a mixture of CaCl2-dried
CHCl3 and Na-dried MeCN or Et2O (1:10, v/v, 100 mL). After the
vicinal amino alcohol was dissolved completely, the flask was
cooled to 0 °C in an ice bath. Then, ClSO3H (1.16 g, 10 mmol) was
slowly added under vigorous stirring; white solid appeared. The so-
lution was stirred for 2 h, then concentrated under reduced pressure.
The residue was washed with Et2O (3 × 10 mL). After drying under
reduced pressure, the amino alcohol hydrogen sulfate was obtained
as colorless crystals.
(2R,3R)-2,3-Diphenylaziridine (3f)13
Yield: 0.31 g (31%); colorless crystals; mp 42–44 °C (Lit.13 43–
44 °C).
[a]D20 +330 (c 1.6, CH2Cl2) [Lit.13 [a]D20 +331 (c 1.27, CH2Cl2)].
1H NMR (300 MHz, CDCl3): d = 1.56 (br s, 1 H), 3.10 (s, 2 H),
7.27–7.39 (m, 10 H).
13C NMR (75.5 MHz, CDCl3): d = 43.7, 125.4, 127.3, 128.6, 139.5.
Aliphatic Aziridines 3; General Procedure
To an amino alcohol hydrogen sulfate (5 mmol) was added 6.2 M
NaOH (4 mL), and the mixture was stirred at r.t. or 70 °C for 2 h,
then steam-distilled. The distillate was saturated with KOH pellets
and the upper organic layer, which was separated, was extracted
(S)-2-Isopropylaziridine (3h)17
Yield: 1.45 g (68%) on 25 mmol scale; colorless oil; bp 106–
108 °C/760 Torr (Lit.21 100–101 °C/690 Torr).
[a]D20 –22.1 (c 1.6, EtOH) [Lit.21 [a]D20 –21.8 (c 1.5, EtOH)].
Synthesis 2010, No. 20, 3423–3428 © Thieme Stuttgart · New York

PAPER
Improved Wenker Synthesis of Aziridines
3427
1H NMR (300 MHz, CDCl3): d = 0.61 (br s, 1 H), 0.94 (d, J = 6.2
Hz, 3 H), 1.01 (d, J = 6.0 Hz, 3 H), 1.14 (m, 1 H), 1.33 (m, 1 H),
1.67 (m, 2 H).
13C NMR (75.5 MHz, CDCl3): d = 20.0, 20.6, 24.0, 32.9, 37.2.
Acknowledgment
The project was supported in part by the National Natural Science
Foundation of China (No. 20972013) and the Beijing Natural
Science Foundation (No. 2092022).
(S)-2-Benzylaziridine (3i)
Yield: 0.57 g (85%); colorless oil; bp 86–88 °C/3 Torr (Lit.21 73–
74 °C/1 Torr).
[a]D20 –26.5 (c 1.8, EtOH) [Lit.21 [a]D20 –26.9 (c 1.5, EtOH)].
1H NMR (300 MHz, CDCl3): d = 0.30 (br s, 1 H), 1.46 (d, J = 3.4
Hz, 1 H), 1.83 (s, 1 H), 2.20–2.26 (m, 1 H), 2.66 (dd, J = 5.6, 14.0
Hz, 1 H), 2.81 (dd, J = 4.6, 14.0 Hz, 1 H), 7.21–7.34 (m, 5 H).
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Chem. 1962, 27, 3532. (e) Xu, J. X. Tetrahedron:
Asymmetry 2002, 13, 1129.
(5) (a) Xu, J. X.; Xu, S. Synthesis 2004, 276. (b) Huang, J. X.;
Wang, F.; Du, D. M.; Xu, J. X. Synthesis 2005, 2122.
(c) Huang, J. X.; Du, D. M.; Xu, J. X. Synthesis 2006, 315.
(d) Hu, L. B.; Zhu, H.; Du, D. M.; Xu, J. X. J. Org. Chem.
2007, 72, 4543. (e) Wang, B. Y.; Zhang, W.; Zhang, L. L.;
Du, D.-M.; Liu, G.; Xu, J. X. Eur. J. Org. Chem. 2008, 350.
(f) Zhang, W.; Wang, B. Y.; Chen, N.; Du, D.-M.; Xu, J. X.
Synthesis 2008, 197. (g) Chen, N.; Zhu, M.; Zhang, W.; Du,
D. M.; Xu, J. X. Amino Acids 2009, 37, 309. (h) Yu, H.;
Cao, S.-L.; Zhang, L. L.; Liu, G.; Xu, J. X. Synthesis 2009,
2205. (i) Chen, N.; Jia, W. Y.; Xu, J. X. Eur. J. Org. Chem.
2009, 5841.
13C NMR (75.5 MHz, CDCl3): d = 25.1, 31.2, 40.4, 126.6, 128.7,
129.1, 139.6.
7-Azabicyclo[4.1.0]heptane (3j)22
Yield: 0.33 g (67%); colorless oil; bp 56–58 °C/3 Torr (Lit.23 50 °C/
1 Torr).
1H NMR (200 MHz, CDCl3): d = 1.11–1.43 (m, 4 H), 1.63–2.00 (m,
4 H), 2.18 (s, 2 H), 4.87 (br s, 1 H).
13C NMR (50.3 MHz, CDCl3): d = 19.8, 24.2, 29.2.
(S)-1-Azabicyclo[3.1.0]hexane (3k)24
Yield: 1.56 g (75%) on 25 mmol scale; colorless oil; bp 110–
112 °C/760 Torr (Lit.24 110–112 °C/760 Torr).
[a]D20 –18.7 (neat) [Lit.25 [a]D28 –19 (neat)].
1H NMR (300 MHz, CDCl3): d = 1.17 (d, J = 3.4 Hz, 1 H), 1.36–
1.50 (m, 1 H), 1.52 (d, J = 5.2 Hz, 1 H), 1.60 (dt, J = 13.4, 7.6 Hz,
1 H), 1.80–1.93 (m, 1 H), 2.08 (dd, J = 8.6, 13.2 Hz, 1 H), 2.28–2.38
(m, 1 H), 2.88 (dt, J = 11.6, 7.6 Hz, 1 H), 2.96 (dd, J = 8.6, 11.6 Hz,
1 H).
13C NMR (75.5 MHz, CDCl3): d = 19.4, 25.7, 26.4, 39.2, 52.5.
(S)-1-(4-Chlorobenzyl)-2-isobutylaziridine (3l)
Yield: 0.63 g (56%); colorless oil.
[a]D20 –1.1 (c 3.6, acetone).
IR (KBr): 3026.6, 2979.4, 2829.9, 1597.8, 913.3, 805.4, 742.6 cm–1.
1H NMR (300 MHz, CDCl3): d = 0.85 (d, J = 7.2 Hz, 3 H), 0.87 (d,
J = 7.2 Hz, 3 H), 1.12–1.24 (m, 1 H), 1.32–1.41 (m, 2 H), 1.41–1.50
(m, 1 H), 1.57–1.68 (m, 2 H), 2.38 (s, 2 H), 7.27–7.39 (m, 4 H).
13C NMR (75.5 MHz, CDCl3): d = 22.2, 22.9, 27.1, 34.3, 38.4, 42.0,
64.1, 128.4, 129.4, 132.6, 137.9.
(6) (a) Xu, J. X.; Ma, L. G.; Jiao, P. Chem. Commun. 2004,
1616. (b) Ma, L. G.; Du, D.-M.; Xu, J. X. J. Org. Chem.
2005, 70, 10155. (c) Ma, L. G.; Jiao, P.; Zhang, Q. H.; Xu, J.
X. Tetrahedron: Asymmetry 2005, 16, 3718.
(7) Zhu, M.; Hu, L. B.; Chen, N.; Du, D.-M.; Xu, J. X. Lett. Org.
Chem. 2008, 5, 212.
HRMS: m/z [M + H]+ calcd for C13H19NCl: 224.1200; found:
224.1198.
(8) (a) Adams, R.; Cairns, T. L. J. Am. Chem. Soc. 1939, 61,
2464. (b) Campbell, K. N.; Campbell, B. K.; McKenna, J. F.;
Chaput, E. P. J. Org. Chem. 1943, 8, 103.
(9) Olofsson, B.; Wijtmans, R.; Somfai, P. Tetrahedron 2002,
58, 5979.
(10) Fujita, M.; Miyashita, Y.; Amir, N.; Kawamoto, Y.;
Kanamori, K.; Fujisawa, K.; Okamoto, K. I. Polyhedron
2005, 24, 1991.
(11) Arseniyadis, S.; Laurent, A.; Mison, P. Bull. Soc. Chim. Fr.
1980, 246.
(12) Alvernhe, G.; Arsenyiadis, S.; Chaabouni, R.; Laurent, A.
Tetrahedron Lett. 1975, 355.
(13) Perlman, M. E.; Bardos, T. J. J. Org. Chem. 1988, 53, 1761.
(14) Arroyo, Y.; Meana, ; Rodríguez, J. F.; Santos, M.; Sanz-
Tejedor, M. A.; García-Ruano, J. L. Tetrahedron 2006, 62,
8525.
(S)-2-Benzyl-1-(4-chlorobenzyl)aziridine (3m)
Yield: 0.70 g (54%); colorless oil.
[a]D20 –4.6 (c 1.5, acetone).
IR (KBr): 3042.4, 2955.5, 2925.0, 2899.6, 1491.1, 1406.0, 1383.4,
1087.2, 1015.5, 805.8 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.44 (d, J = 6.1 Hz, 1 H), 1.68–
1.77 (m, 1 H), 1.76 (d, J = 3.5 Hz, 1 H), 2.65 (dd, J = 5.7, 14.4 Hz,
1 H), 2.75 (dd, J = 6.4, 14.4 Hz, 1 H), 3.28 (d, J = 13.4 Hz, 1 H),
3.44 (d, J = 13.4 Hz, 1 H), 7.14–7.24 (m, 9 H).
13C NMR (75.5 MHz, CDCl3): d = 33.8, 39.3, 40.8, 63.9, 126.1,
128.3, 128.6, 129.3, 132.6, 137.6, 139.4.
HRMS: m/z [M + H]+ calcd for C16H17NCl: 258.1044; found:
258.1041.
Synthesis 2010, No. 20, 3423–3428 © Thieme Stuttgart · New York

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Synthesis 2010, No. 20, 3423–3428 © Thieme Stuttgart · New York