Highly diastereo- and enantioselective aziridination of α,β-unsaturated amides with diaziridine and mechanistic consideration on its stereochemistry

Article abstract of DOI:10.1002/hlca.200290012

During studies of aziridination of α,β-unsaturated amides with diaziridine, we found that we could prepare both the cis- and trans-aziridinecarboxamides by choosing an appropriately substituted diaziridine. While 3-monosubstituted diaziridine 2 was suitab

Full text of DOI:10.1002/hlca.200290012

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Helvetica Chimica Acta Vol. 85 (2002)
Highly Diastereo- and Enantioselective Aziridination of a,b-Unsaturated
Amides with Diaziridine and Mechanistic Consideration on Its
Stereochemistry
by Hiroyuki Ishihara, Kiyoto Hori, Hiroyasu Sugihara, Yoshio N. Ito*, and Tsutomu Katsuki
Department of Chemistry, Faculty of Science, Kyushu University Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan
(phone: ‡81-92-642-2587; fax: ‡81-92-642-2607, e-mail address: yito.scc@mbox.nc.kyushu-u.ac.jp)
Dedicated to Prof. Dieter Seebach on the occasion of his 65th birthday
During studies of aziridination of a,b-unsaturated amides with diaziridine, we found that we could prepare
both the cis- and trans-aziridinecarboxamides by choosing an appropriately substituted diaziridine. While 3-
monosubstituted diaziridine
2 was suitable for the trans-selective aziridination, employment of 3,3-
dialkyldiaziridine 1 resulted in the formation of cis-aziridine carboxamides, irrespective of the geometry of
the substrate (Scheme 1 and Tables 1 and 2). To elucidate the unique nonstereospecificity and to expand these
aziridinations to asymmetric ones, several optically active diaziridines were newly prepared. Aziridination with
an optically active 3-monosubstituted diaziridine, 3-cyclohexyl-1-[(1R)-1-phenylethyl]diaziridine 16, proceeded
smoothly with high trans-selectivity as well as excellent enantioselectivity (up to 98% ee; see Table 3). On the
other hand, highly enantioselective cis-aziridination was achieved (> 99% ee) with optically active 3,3-dimethyl-
1-[(1R)-1-phenylethyl]diaziridine 15, though the yield was low (4%). This aziridination was considered to
proceed stepwise by way of the enolate intermediate (Scheme 2). Careful inspection of the stereochemistry and
its solvent-dependence suggested that the diastereoselection of the reaction was kinetically controlled: the 1,4-
addition of N-lithiated diaziridine was a crucial step for determination of the stereochemical course of the
aziridination (Figs. 2 4).
Introduction. Aziridines are versatile synthetic intermediates for N-containing
compounds [1]. One of the most straightforward methods for their synthesis is addition
of a nitrene or nitrenoid to olefins. Enantioselective nitrene-transfer aziridination in
the presence of chiral copper, manganese, and ruthenium catalysts has recently been
reported [2]. In these reactions, [N-(p-toluenesulfonyl)imino]phenyliodinane
(PhIˆNTs) or a derivative is employed as the nitrene precursor, and the resulting
aziridines are N-(p-toluenesulfonyl)ated. However, it is difficult to remove the p-
toluenesulfonyl group without causing decomposition of the aziridine ring. Another
conventional method for aziridination is the 1,4-addition of an O-substituted hydroxyl-
amine derivative to a,b-unsaturated carbonyl compounds and the subsequent enolate
cyclization [3]. By these methods, optically active N-unsubstituted aziridines are
accessible, but the major products are thermodynamically stable trans-aziridines, even
in the reaction of cis-a,b-unsaturated carbonyl compounds. Still, cis-selective aziridi-
nation remains unsettled.
To explore the potential of the latter method, we examined the use of diaziridine as
an amine nucleophile in place of O-substituted hydroxylamine. Although there was no
previous example of the use of diaziridine as an N-donor, diaziridine was expected to be

Helvetica Chimica Acta Vol. 85 (2002)
4273
highly nucleophilic due to the presence of two vicinal N-atoms (a-effect). Furthermore,
it was expected that its NÀN bond would be cleaved readily due to the strain energy of
the three-membered ring. Thus, we examined the reaction of diaziridine and a,b-
unsaturated amide under various reaction conditions and disclose now a unique
reagent-controlled stereoselective aziridination as shown in Scheme 1. We describe in
detail here the stereoselective aziridination with racemic or optically active diaziridines
and discuss the mechanism of the stereoselection1).
Scheme 1. Reagent-Controlled Diastereoselectivity in Aziridination with Diaziridines
NH
BuLi
NH
CONR1R2
1
R
R
NH
CONR1R2
trans
cis-aziridine
R
NH
CONR1R2
CONR1R2
R
trans-aziridine
cis
N
Me
BuLi
NH
H
2
cis-Selective Aziridination of a,b-Unsaturated Amides (Table 1). Examination of
the aziridination of a,b-unsaturated amides commenced with 3,3-pentamethylenedi-
aziridine (ˆ1,2-diazaspiro[2.5]octane; 1), which was readily available from cyclo-
hexanone by treatment with hydroxylamine-O-sulfonic acid in aqueous ammonia [5a].
Diaziridine 1 itself did not undergo the desired 1,4-addition at room temperature.
However, N-lithiated 1, prepared by treatment of 1 with 1 equiv. of butyllithium (BuLi)
at À788, readily reacted with a,b-unsaturated amides 3 10, 12, and 14 to give 2,3-cis-
aziridinecarboxamides (Table 1). Although many hydroxylamine or hydrazine deriv-
atives have been reported to add to a,b-unsaturated carbonyl compounds, the resulting
1,4-adducts do not undergo the subsequent ring closure to give the desired aziridine
under the addition-reaction conditions. Lewis acid or base treatment is required for
further conversion of the 1,4-adducts to aziridines. On the other hand, the present
reaction directly gives the desired aziridine under the addition-reaction conditions. The
configuration of the aziridine obtained from 9 was confirmed to be 2,3-cis by chemical
correlation to the corresponding 2,3-cis-N-(p-toluenesulfonyl)aziridinecarboxamide,
which was prepared independently by a reported method [6]. The coupling constant
between methine protons at the aziridine ring was 7.5 Hz for the cis-aziridinecarbox-
amide, while 4.0 Hz was observed for the trans-aziridinecarboxamide. These observa-
tions are consistent with the coupling constants predicted by the Karplus equation.
Thus, the geometry of other aziridinecarboxamides described in Table 1 was assigned
1
)
Preliminary results have been communicated in [4].

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Helvetica Chimica Acta Vol. 85 (2002)
O
O
O
N
R
N
R
N
10 R=Me
11 R=H
12
3 R=Ph
4 R=4-MeOC6H4
5 R=4-ClC6H4
6 R=1-C10H7
7 R=2-Furyl
8 R=Me2C=CH
9 R=Me
O
N
C6H5
O
N
13
14
Table 1. cis-Selective Aziridination of a,b-Unsaturated Amides with 1a)
Entry
Substrate
Time [h]
Yield [%]b)
1
2
3
4
11
3
97 (72)c)
99
3
5
4
98
4
5
6
7
8
9
10
11d)
12
6
7
8
9
10
11
12
13
14
4
16
4
24
8
78
8
6
3
99 (82)c)
24
89 (63)c)
c
1840 (39)
24
6
)
30
70
c
852 (39)
)
a) All the reactions were conducted in THF at À308 with 2 equiv. of diaziridine 1 and BuLi unless otherwise
noted. b) Isolated yields of the corresponding cis-aziridinecarboxamides after silica-gel column chromatog-
raphy. Isomeric trans-aziridinecarboxamide could not be isolated. c) The previously reported result is cited in
parentheses. d) The reaction was conducted at 08. No aziridination occurred at À308.
by their 1H-NMR analyses2). All the reactions showed remarkably high cis-selectivity,
and no trans-isomer was isolated in these reactions.
Although we previously communicated that the aziridination was carried out at
À788 to room temperature, we found that better yields could be obtained by carrying
out the reaction with 2 equiv. of N-lithiated 1 in THF at À308. The yields of the
aziridination of cinnamamide derivatives were more than 97% (Entries 1 3). The
yield of the aziridine from acrylamide 11 was moderate and formation of unidentified
by-products was detected (Entry 9). The reactions of trisubstituted olefin 12 and cis-
cinnamamide derivative 14 were relatively slow, and yields of the corresponding cis-
aziridines were somewhat reduced (Entries 10 and 12). Again, formation of trans-
isomers was not detected. Accordingly, cis-selectivity in this reaction was independent
on the geometry of the substrate used. Unfortunately, the reactions of other a,b-
2
)
The relative configurations of the aziridines obtained from trisubstituted a,b-unsaturated amide 12 were
confirmed by NOESY measurements. The trans-isomer showed an NOE between the MeÀC(2) and
MeÀC(3) groups.

Helvetica Chimica Acta Vol. 85 (2002)
4275
unsaturated carbonyl compounds such as a,b-unsaturated aldehydes, ketones, or esters
did not give the desired products in acceptable yields under the present conditions.
It is reasonable to consider that a two-step reaction mechanism is applicable to the
present aziridination as shown in Scheme 2. Namely, N-lithiated 1 attacks the C(b)
atom of a,b-unsaturated amides diastereoselectively to produce an enolate intermedi-
ate. Note that the N-atom introduced at C(b) is chiral. Subsequent intramolecular
substitution gives cis-aziridine from the conformer that does not suffer severe steric
interaction between one of the two geminal substituents of the diaziridine and the
amide enolate moiety upon cyclization. This consideration further led us to the idea
that trans-selectivity would be realized if one of the geminal substituents was removed:
the enolate conformation was considered to be dictated by the steric repulsion between
R and the amide enolate moiety. Accordingly, aziridination with a 3-monosubstituted
diaziridine was next examined.
Scheme 2. Stepwise Mechanism for the Aziridination with N-Lithiated Diaziridine. For convenience,
substituents or H-atoms at the diaziridine are represented by straight lines.
N
R
N
NH
CONR1R2
R
1,4-addition
Li
cis
LiO
NR1R2
N
R
N
hydrolysis
CONR1R2
N
NH
CONR1R2
OLi
NR1R2
N
R
R
trans
intramolecular substitution
trans-Selective Aziridination of a,b-Unsaturated Amides (Table 2).
As a 3-
monosubstituted diaziridine, 1-methyl-3-cyclohexyldiaziridine (2) was prepared from
cyclohexanecarboxaldehyde, methylamine, and hydroxylamine-O-sulfonic acid [5] or
chloramine [7]. Aziridination was carried out under the conditions described in the
preceding section. As expected, trans-aziridine was preferentially obtained in 52%, e.g.
from N-(E)-cinnamoylpyrrolidine (3), together with a small amount of cis-aziridine
(21%) as shown in Table 2, Entry 1. Furthermore, it was found that the aziridination at
À788 increased trans-selectivity up to 5.6 :1 (Entry 2). Employment of a less-polar
solvent further increased the selectivity, and the trans-isomer was obtained exclusively
in toluene (Entry 4). It is, however, noteworthy that the ratio of trans- and cis-aziridines
varied from 3 :1 to 1:3 by switching the solvent from THF to toluene in the
aziridination of N-(Z)-cinnamoylpyrrolidine (14) (Entries 15 and 17). The geometry of
the (Z)-substrate was considered to be reflected in the configuration of the product of
this reaction in less polar toluene. Chelate formation of the enolate intermediate in
such a nonpolar solvent was attributable to this stereochemical outcome. The other
substrates (3 10 and 12) were also converted preferentially to the corresponding trans-
aziridines though the yields of the aziridines from 8 10 and 12 bearing a b-alkyl or b-
alkenyl substituent were moderate (Entries 8 14).

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Helvetica Chimica Acta Vol. 85 (2002)
Table 2. trans-Selective Aziridination of a,b-Unsaturated Amides with 2a)
Entry
Substrate
Solvent
Temperature [8]
Time [h]
Yield [%]b)
trans
cis
21
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
3
3
3
3
4
5
6
7
8
THF
THF
ether
À 30
24
52
À 784
À6 784
À 784
À 784
À 784
À 784
À 784
À 7812
À 782
À 784
À 784
À 30c)
À 30c)
À 784
À 7812
À 784
14 78
5
8
toluene
toluene
toluene
toluene
toluene
toluene
ether
toluene
toluene
ether
74
58
76
65
61
< 1
< 1
3
< 1
< 1
30
3
9
9
61
45
32
< 1
< 1
< 1
< 1
< 1
10
12
12
14
14
14
24
17
16
6
toluene
THF
ether
16 48
39
11
20
31
toluene
a) All the reactions were conducted with 2 equiv. diaziridine 2 and BuLi. b) Isolated yields of corresponding
trans- and cis-aziridinecarboxamides after silica-gel column chromatography. c) The reaction was conducted at
À308. No aziridination occurred at À788.
Asymmetric Aziridination of a,b-Unsaturated Amides (Table 3). In general, the
configuration at the N-atom of trialkylamine (NR1R2R3) is invertible at room
temperature, and it is impossible to isolate it in an optically active form. However,
inversion of the N-atom in a three-membered ring system becomes remarkably slow.
Actually, some aziridines and diaziridines have been isolated in optically active forms
[8]. As discussed above, the N-atom introduced at C(b) of the a,b-unsaturated amide is
chiral. This suggested that asymmetric aziridination would be realized if an optically
active diaziridine were used. Thus, optically active diaziridines 15 and 16/16' were
prepared with (1R)-1-phenylethylamine as the chiral amine source. The config-
uration of 15 was assigned by Kostyanovsky and co-workers [9]. The relative
configuration between N(1) and the benzylic C-atom in the major diastereoisomer 16
was tentatively assigned as depicted, according to [9]. The substituents at N(1) and
C(3) were considered to be trans to each other for steric reasons. The diastereoisomer
ratio of 16/16' was 7:3 after column chromatography. While 15 gradually isomerized to
its diastereoisomer at room temperature, 16 was found to be stable, and no
isomerization to the diastereoisomer (16') was detected even after 8h at 55 8 in
3
CDCl3 ). The presence of the cis-methyl group in 15 probably facilitates the
isomerization.
The results of aziridination with 15 or 16 are summarized in Table 3. Aziridination
of 3 with N-lithiated 15 afforded cis-aziridine of > 99% ee as a single product, though
the yield was poor (Entry 1). Unfortunately, all attempts to increase the yield were
3
)
The isomerization was traced by H-NMR measurements.

Helvetica Chimica Acta Vol. 85 (2002)
4277
H
H
H
N
N
N
H
Ph
N
N
N
H
Ph
Ph
15
16'
16
Table 3. Asymmetric Aziridination of a,b-Unsaturated Amides with Optically Active Diaziridinesa)
Entry
Substrate
Diaziridine
Solvent
Temp. [8]
Time [h]
Yield [%] (ee [%]b)
trans
cis
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
3
3
3
3
3
3
4
5
6
7
8
9
9
10
11
13
14
14
15
16
16
16
16
16'
16
16
16
16
16
16
16
16
16
16
16
16
THF
À 30
11
4
4
56 (96)
12
4
4
4
4
4
4
4
12
2
4 (> 99)d)
5 (98)
THF
À 78to À30
À 78to À30
À 784
77 (94)
3 (
THFc)
ether
)
toluene
toluene
toluene
toluene
toluene
toluene
toluene
ether
toluene
toluene
toluene
toluene
THF
À 78to À30
À 78to À30
À 78to À30
À 78to À30
À 78to À30
À 78to À30
À 78to À30
À 30
76 (98)e)
54 (96)g)
70 (96)
80 (96)
76 (96)
69 (97)
47 (96)
32 (84)
40 (92)
16 (90)
3 (> 99)f)
7 (> 99)d)
3 (99)
6 (> 99)
3 (99)
<1 (
)
)
)
)
)
3 (
< 1 (
1 (
À 78to À30
À 78to À30
À 78to À30
À 78to À30
À 78to À30
À 78to À30
< 1 (
3 (82)
4 (87)
4
4
4
e
48(92)
)
8
f) (96)
f
toluene
39 (95)e)
31 (8
)
8
)
a) All the reactions were conducted with 2 equiv. of diaziridine and BuLi. b) Isolated yields of corresponding
trans- and cis-aziridinecarboxamides after silica-gel column chromatography. Enantiomer excesses (ee) are
shown in parentheses. c) Dimethylformamide (3 equiv.) was added. d) The absolute configuration was (2R,3R).
e) The absolute configuration was (2S,3R). f) The absolute configuration was (2S,3S). g) The absolute
configuration was (2R,3S).
fruitless. On the other hand, the reaction with 16 was found to proceed smoothly with
high trans-selectivity in a highly enantioselective manner. Namely, trans-aziridine of
98% ee was obtained as the major isomer in 76% yield from 3 (Entry 5). The minor cis-
aziridine was isolated in only 3%, and its ee was also greater than 99%. The absolute
configurations of the products were determined to be (2S,3S) for the cis-isomer and
(2S,3R) for the trans-isomer by chemical correlation as described in Scheme 34). This
result suggested that these diastereoisomers did not come from the common enolate
intermediate. Namely, the diastereoselectivity of the first 1,4-addition was reflected in
the ratio of cis- and trans-isomers (vide infra).
4
)
The retention time tR of the sample prepared from each aziridinecarboxamide was identical to that of
prepared from l-phenylalanine by HPLC with a chiral stationary-phase column (Daicel Chiralcel OD-H,
hexane PrOH 9:1, flow rate 0.5 ml/min): tR 18.9 min for the (S)-form and 22.3 min for the (R)-form.
i

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Helvetica Chimica Acta Vol. 85 (2002)
Scheme 3. Chemical Correlation of Aziridine Derivatives
NH
O
O
Ph
O
N
Ph
NH
NH
H
BuLi
+
Ph
N
Ph
N
N
trans
95%
cis
1) TsCl, Et3N
2) H2/Pd-C
96%
O
O
1) TsCl, NaOH
(S)
Ph
OH
Ph
N
2) Pivaloyl chloride, Et3N
then pyrrolidine
NH2
TsNH
60%
L-Phe
Diaziridine 16' is the diastereoisomer of 16. However, it behaved as the enantiomer
of 16 in the aziridination of 3. Namely, the reaction with 16' afforded (2R,3S)-aziridine
(trans) in 96% ee (Entry 6). The absolute configuration of the aziridine suggested that
the configuration of the diaziridine moiety mainly dictated the sense of asymmetric
induction in the aziridination, and the chiral N1 substituent, the (1R)-1-phenylethyl
group, did not play an important role in the asymmetric induction.
Mechanistic Consideration for the Stereoselectivity. The stereochemistry of an
asymmetric reaction and the solvent effect on the stereochemistry are good probes for
the inspection of the reaction mechanism. Therefore, we carefully analyzed the
stereochemistry of the present aziridination reactions of 3 with N-lithiated 16 in
toluene and THF. N-Lithiated 16 can adopt the two equilibrating structures Li-16a and
Li-16b shown in Fig. 1, whose lithiated N-atom attacks C(b) of a,b-unsaturated amides.
Considering 1,2-chelation, Li-16a is more favorable than Li-16b. Accordingly, 1,4-
addition of the more stable Li-16a to a,b-unsaturated amides is considered to be a
major path. Fig. 2 explains the stereoselectivity observed for the aziridination of 3 by
N-lithiated 16 (for convenience, substituents at the diaziridine and the a,b-unsaturated
amide are represented by straight lines). The distributions of the stereoisomers in the
aziridination in toluene and THF are given at the right side of Fig. 2. For the 1,4-
addition reaction of N-lithiated 16, there are four possible transition-state conforma-
tions A D leading to diastereoisomeric enolate intermediates a1 d1, respectively. By
the lack of 1,2-chelation depicted for Li-16a in Fig. 1, C and D are considered to be less
favorable, as compared with A and B. The observed configurations of the products
suggested that the attack of Li-16a from the Re-face of the olefin (A in Fig. 2) provides
enolate a1 in which the NÀN bond and the enolate are suitably aligned for cyclization:
the antibonding orbital of the NÀN bond can interact with the p-orbital of the amide
enolate in this conformation. Thus, the reaction proceeds preferentially via the enolate
intermediate a1 to give trans-(3R)-aziridine. On the other hand, the addition of Li-16a
from the Si-face is disfavored by the steric interaction between the N-substituent and
the b-substituent of the amide (see B). Minor intermediate b1 cyclizes to cis-(3S)-

Helvetica Chimica Acta Vol. 85 (2002)
4279
Fig. 1. Structure of lithiated diaziridine
Fig. 2. Proposed reaction mechanism for asymmetric trans-selective aziridination of trans-a,b-unsaturated
amides with optically active 3-monoalkyldiaziridine. For convenience, substituents at the diaziridine and the a,b-
unsaturated amide are represented by straight lines.

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Helvetica Chimica Acta Vol. 85 (2002)
aziridine under rotation of the C(2)ÀC(3) bond. Use of the polar THF solvent
facilitates the dissociation of the coordinating carbonyl group and, therefore, the
rotation of the CÀC bond to form the minor cis-(3S)-aziridine, lowering diastereo-
selectivity. Addition of 3 equiv. dimethylformamide that should coordinate to lithium
ion retards the aziridination (Entry 3 in Table 3). This suggests that coordination of the
N(2) atom to the lithium ion is indispensable for the cleavage of the NÀN bond
necessary for aziridination.
Fig. 3. Proposed reaction mechanism for asymmetric trans-selective aziridination of cis-a,b-unsaturated amides
with optically active 3-monoalkyldiaziridine. For convenience, substituents at the diaziridine and the a,b-
unsaturated amide are represented by straight lines.

Helvetica Chimica Acta Vol. 85 (2002)
4281
We also inspected the aziridination of cis-cinnamamide 14 in toluene (Fig. 3). For
the same diastereoselection in the addition step as in the reaction of 3, transition-state
conformation A' is considered to be the most favorable, but B' leading to the chelated
intermediate b2 is favored by chelate formation. Thus, in toluene, cis-aziridine is
produced in considerable amounts. In THF, 1,2-chelation in Li-16a is interrupted by
coordination of THF and thus, via sterically favored A', the formation of trans-(3R)-
aziridine is preferred.
Aziridination of 3 with optically active N-lithio-3,3-dialkyldiaziridine Li-15a
suffers severe steric repulsion between the alkyl group at C(3) or the substituent at
the N-atom and the b-substituent of the amide as shown by A'', B'', and D'' in Fig. 4.
Accordingly, intrinsically low reactive and minor Li-15b participates as C'' and gives the
corresponding cis-aziridines in low yield, albeit with excellent enantioselectivity.
N
N
N
N
N
N
NH
Li
O
Li
O
O
OLi
N
N
N
N
cis, 3R
4%, >99% ee
C''
N
N
N
N
N
N
N
Li
Li
Li
O
O
O
N
N
A''
B''
D''
Fig. 4. Proposed reaction mechanism for asymmetric cis-selective aziridination with optically active 3,3-
dimethyldiaziridine. For convenience, substituents at the diaziridine and the a,b-unsaturated amide are
represented by straight lines.
Conclusions. All of the stereoisomers of N-unsubstituted aziridinecarboxamides
became available when suitably designed diaziridines were used. Namely, the reaction
with 3-monosubstituted diaziridines is trans-selective and that with a 3,3-disubstituted
diaziridine is cis-selective. With optically active diaziridines, highly asymmetric
induction as well as diastereoselectivity was achieved. Through the analysis of the
stereochemistry and solvent effect, we were able to clarify the factors controlling the
stereochemical course of the present aziridination. It is worth noting that the
diastereoisomer ratio of the aziridines was largely dependent on the diastereoselec-
tivity in the 1,4-addition of the N-lithiated diaziridine to the a,b-unsaturated amides.
These new findings open a new approach to stereoselective synthesis of N-unprotected
aziridine derivatives and show the potential of diaziridine as an N-donor.

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Experimental Part
1. General. THF and Et2O were dried and freshly distilled before use. Dehydrated toluene was from Kanto
Chemical Co., Inc. Reactions were carried out under N2 if necessary. Column chromatography (CC): silica gel
60N (spherical, neutral) from Kanto Chemical Co., Inc., or basic silica gel NH (100 200 mesh) from Fuji Silysia
Chemical Ltd. HPLC: Shimadzu Class-VP equipped with chiral stationary phase column, Daicel Chiralcel OD-
H; tR in min. M.p.: uncorrected. [a]D: Jasco P-1020-GT automatic digital polarimeter. IR Spectra: Shimadzu
FTIR-8400 instrument; in cmÀ1. NMR Spectra: Jeol AL400 instrument; at 400 MHz; d in ppm downfield from
SiMe4 as internal standard, J in Hz.
2. Diaziridines. 3-Cyclohexyl-1-[(1R)-1-phenylethyl]diaziridine (16/16'). (1R)-1-Phenylethylamine
(1.29 ml, 10 mmol) was mixed with cyclohexanecarboxaldehyde (1.21 ml, 10 mmol) at r.t. After stirring for
1 h, EtOH (11 ml) and Et3N (5.3 ml) were added, and the mixture was cooled to 08. Then, hydroxylamine-O-
sulfonic acid (1.70 g, 15 mmol) was added to the mixture slowly. After stirring for 30 min at 08, the mixture was
diluted with Et2O (150 ml). The Et2O soln. was washed with H2O, dried (MgSO4), and evaporated and the
residue purified by CC (SiO2, hexane/AcOEt 9 :1 ! 4 :1): 16 (1.55 g, 68%) as colorless crystals and 16' (0.589 g,
26%) as a colorless oil. By analogy to the diastereoselectivity reported for the preparation of 15 and its
diastereoisomer [9], 16 and 16' were expected to have (1R,2R,3S)- and (1S,2S,3R)-configuration respectively.
Data of 16: M.p. 53.5 55.08. [a]2D1 ˆ ‡14.5 (c ˆ 1.10, EtOH). IR (KBr): 532, 698, 737, 843, 926, 1111, 1225,
1277, 1362, 1447, 1495, 2853, 2920, 3036, 3188. 1H-NMR (CDCl3): 7.38 7.21 ( m, 5 H); 2.66 (q, J ˆ 6.6, 1 H); 2.33
(dd, J ˆ 7.3, 7.1, 1 H); 1.89 (d, J ˆ 7.3, 1 H); 1.72 1.41 (m, 4 H); 1.51 (d, J ˆ 6.6, 3 H); 1.38 1.22 ( m, 1 H); 1.20
0.85 (m, 5 H); 0.77 0.65 (m, 1 H). 13C-NMR (CDCl3): 142.27: 128.19; 127.29; 127.19; 70.23; 64.21; 42.71; 29.18;
28.93; 26.25; 25.54; 25.40; 21.89. Anal. calc. for C15H22N2: C 78.21, H 9.63, N 12.16; found: C 78.05, H 9.59,
N 12.14.
Data of 16': [a]2D1 ˆ À59.5 (c ˆ 1.05, EtOH). IR (KBr): 567, 698, 760, 849, 924, 1009, 1122, 1205, 1283, 1356,
1448, 1495, 2853, 2926, 3031, 3200. 1H-NMR (CDCl3): 7.41 (d, J ˆ 7.5, 2 H); 7.33 (t, J ˆ 7.5, 2 H); 7.24 (t, J ˆ 7.5,
1 H); 2.73 (q, J ˆ 6.6, 1 H); 2.41 (t, J ˆ 7.3, 1 H); 1.72 (m, 5 H); 1.38( d, J ˆ 6.6, 3 H); 1.31 1.14 (m, 5 H); 1.07
(br., 1 H). 13C-NMR (CDCl3): 143.50; 127.92; 126.72; 126.69; 68.85; 64.96; 42.61; 29.52; 29.01; 26.21; 25.47;
25.37; 20.55.
1,2-Diazaspiro[2.5]octane (1) [5a]. Colorless crystals. M.p. 104.0 105.08. IR (KBr): 430, 837, 891, 1045,
1109, 1140, 1219, 1315, 1367, 1406, 1445, 2245, 2598, 2853, 2930, 3163. 1H-NMR (CDCl3): 1.84 1.30 (m, 12 H).
13C-NMR (CDCl3): 57.81; 36.41; 25.24; 25.09. Anal. calc. for C6H12N2: C 64.24, H 10.78, N 24.97; found: C 64.16,
H 10.78, N 24.97.
(1R,2R)-3,3-Dimethyl-1-[(1R)-1-phenylethyl]diaziridines (15). Colorless oil. [a]2D4 ˆ ‡3.3 (c ˆ 1.73,
EtOH). IR (KBr): 557, 606, 702, 758, 1069, 1132, 1238, 1304, 1385, 1452, 1493, 1603, 2928, 2972, 3213.
1H-NMR (CDCl3): 7.38 7.27 ( m, 4 H); 7.26 7.18( m, 1 H); 3.31 (t, J ˆ 6.4, 1 H); 1.97 (br. 1 H); 1.47 (d, J ˆ 6.4,
3 H); 1.38( s, 3 H); 1.21 (s, 3 H). 13C-NMR (CDCl3): 144.15; 128.19; 126.60; 126.31; 62.19; 58.09; 28.45; 24.11;
17.74.
3. a,b-Unsaturated Amides. 1-[(2E)-3-Phenylprop-2-enoyl]pyrrolidine (3). Pyrrolidine (0.4 ml, 4.8mmol)
and Et3N (0.84 ml, 6.0 mmol) were added to a soln. of cinnamoyl chloride (0.67 g, 4.0 mmol) and N,N-
dimethylpyridin-4-amine (DMAP; 50 mg, 0.4 mmol) in CH2Cl2 (10 ml) at 08. After stirring for 12 h, the mixture
was diluted with H2O. Extraction with AcOEt, washing with brine, drying, evaporation, and CC (SiO2, hexane/
AcOEt 7:3 ! 2 :2) afforded 3 (0.77 g, 96%). Colorless crystals. M.p. 99.5 100.08. IR (KBr): 490, 548, 569, 685,
706, 764, 866, 988, 1196, 1256, 1429, 1451, 1597, 1651, 2876, 2968, 3032, 3059. 1H-NMR (CDCl3): 7.70 (d, J ˆ 15.6,
1 H); 7.58 7.49 ( m, 2 H); 7.42 7.31 (m, 3 H); 6.80 (d, J ˆ 15.6, 1 H); 3.62 (m, 4 H); 2.07 1.96 (m, 2 H); 1.96
1.85 (m, 2 H). 13C-NMR (CDCl3): 164.47; 141.51; 135.23; 129.35; 128.61; 127.68; 118.77; 46.67; 46.13; 26.29;
24.49.
1-[(2E)-But-2-enoyl]pyrrolidine (9). Colorless oil. IR (KBr): 532, 827, 862, 914, 968, 1192, 1308, 1340, 1448,
1604, 1665, 2876, 2970. 1H-NMR (CDCl3): 6.92 (dq, J ˆ 7.0, 15.1, 1 H); 6.13 (d, J ˆ 15.1, 1 H); 3.56 3.46
(m, 4 H); 2.01 1.91 (m, 2 H); 1.91 1.81 (m, 2 H); 1.88 (d, J ˆ 7.0, 3 H). 13C-NMR (CDCl3): 165.40; 141.17;
123.61; 46.71; 45.97; 26.33; 24.52; 18.23.
(2E)-N,N-Dimethylbut-2-enamide (10). Colorless oil. IR (KBr): 496, 631, 831, 968, 1101, 1159, 1258, 1402,
1
1448, 1499, 1609, 1661, 2939. H-NMR (CDCl3): 6.87 (dq, J ˆ 7.0, 15.1, 1 H); 6.27 (dq, J ˆ 1.5, 15.1, 1 H); 3.07
(s, 3 H); 3.00 (s, 3 H); 1.88 (dd, J ˆ 1.5, 7.0, 3 H). 13C-NMR (CDCl3): 166.59; 140.94; 121.62; 37.37; 35.69; 18.28.
1-[(2E)-3-(4-Methoxyphenyl)prop-2-enoyl]pyrrolidine (4). A soln. of 4-methoxycinnamic acid (0.89 g,
5 mmol) in THF (35 ml) was cooled to À158, and Et3N (0.70 ml, 5 mmol) and pivaloyl chloride (0.62 ml,
5 mmol) were added. After stirring for 5 min, pyrrolidine (0.42 ml, 5 mmol) was added at À158, and the mixture

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was stirred for 20 min, then allowed to warm to r.t., stirred for 15 min, concentrated, dissolved in AcOEt, and
washed with 5% NaHCO3 soln., H2O, 1n HCl, and H2O. Column chromatography (SiO2, hexane/AcOEt 1 :1 !
3 :7) afforded 4 (0.90 g, 62%). Colorless crystals. M.p. 115.0 115.58. IR (KBr): 820, 984, 1018, 1175, 1248, 1304,
1
1431, 1510, 1597, 1643, 2841, 2874, 2957, 3059. H-NMR (CDCl3): 7.66 (d, J ˆ 15.3, 1 H); 7.48( d, J ˆ 8.5, 2 H);
6.89 (d, J ˆ 8.5, 2 H); 6.61 (d, J ˆ 15.3, 1 H); 3.83 (s, 3 H); 3.66 3.55 (m, 4 H); 2.06 1.95 (m, 2 H); 1.95 1.84
(m, 2 H). 13C-NMR (CDCl3): 165.66; 161.38; 141.87; 129.89; 128.63; 116.97; 114.67; 55.68; 46.86; 46.32; 26.43;
24.64.
1-[(2E)-3-(4-Chlorophenyl)prop-2-enoyl]pyrrolidine (5). Colorless crystals. M.p. 154.0 154.58. IR (KBr):
496, 976, 1086, 1398, 1429, 1489, 1605, 1651, 2872, 2966. 1H-NMR (CDCl3): 7.65 (d, J ˆ 15.6, 1 H); 7.46 (d, J ˆ 8.5,
2 H); 6.71 (d, J ˆ 15.6, 1 H); 3.61 (m, 4 H); 2.08 1.97 ( m, 2 H); 1.96 1.85 (m, 2 H). 13C-NMR (CDCl3): 165.02;
140.88; 135.86; 134.39; 129.53; 119.89; 46.92; 46.41; 26.42; 24.60.
1-[(2E)-3-(1-Naphthyl)prop-2-enoyl]pyrrolidine (6). Pyrrolidine (13.1 ml, 159 mmol) and Et3N (22.0 ml,
159 mmol) were added to a soln. of bromoacetyl chloride (25.0 g, 159 mmol) in CH2Cl2 (500 ml) at 08. After
stirring for 2 h, the mixture was diluted with H2O. The org. layer was washed with 1n HCl and H2O and dried.
Evaporation afforded 1-(bromoacetyl)pyrrolidine (18.3 g, 60%) as colorless crystals. A part of this sample
(3.33 g, 17.3 mmol) was mixed with triethyl phosphite (3.56 ml, 20.8mmol) and refluxed for 3.5 h at 180 8. CC
(SiO2, CH2Cl2/MeOH 33 :1) afforded the corresponding phosphonate in quant. yield. Na OMe (366 mg,
6.8mmol) was added to the phosphonate (1.0 g, 4.0 mmol) at 0 8. The mixture was stirred for 40 min, and 1-
naphthaldehyde (2.58ml, 4.4 mmol) was added at 0 8. After stirring at r.t. for 3 h, the mixture was diluted with
AcOEt and H2O. Extraction and CC afforded 6 (0.91 g, 91%). Colorless crystals. M.p. 131.0 132.58. IR (KBr):
1
422, 553, 596, 706, 746, 783, 814, 1003, 1169, 1348, 1429, 1599, 1641, 2872, 2941, 2976, 3047. H-NMR (CDCl3):
8.52 (d, J ˆ 15.1, 1 H); 8.25 (d, J ˆ 8.5, 1 H); 7.87 (d, J ˆ 8.0, 2 H); 7.72 (d, J ˆ 7.5, 1 H); 7.60 7.43 (m, 3 H); 6.80
(d, J ˆ 15.1, 1 H); 3.70 3.61 (m, 4 H); 2.08 1.98 ( m, 2 H); 1.98 1.88 ( m, 2 H). 13C-NMR (CDCl3): 164.36;
138.84; 133.49; 133.02; 131.40; 129.55; 128.39; 126.49; 125.99; 125.22; 124.40; 123.74; 121.88; 46.72; 46.16; 26.30;
24.50.
1-[(2E)-3-(2-Furyl)prop-2-enoyl]pyrrolidine (7). Colorless crystals. M.p. 100.5 101.58. IR (KBr): 762, 988,
1030, 1479, 1552, 1597, 1655, 2880, 2972, 3088, 3134. 1H-NMR (CDCl3): 7.46 (d, J ˆ 15.6, 1 H); 7.44 (s, 1 H); 6.64
(d, J ˆ 15.6, 1 H); 6.54 (d, J ˆ 3.1, 1 H); 6.45 (dd, J ˆ 2.0, 3.5, 1 H); 3.60 (m, 4 H); 2.05 1.95 (m, 2 H); 1.95 1.85
(m, 2 H). 13C-NMR (CDCl3): 164.38; 151.59; 143.56; 128.19; 116.51; 113.54; 112.00; 46.63; 46.07; 26.23; 24.50.
1-[(2E)-5-Methylhexa-2,4-dienoyl]pyrrolidine (8). Colorless crystals. M.p. 101.0 102.08. IR (KBr): 571,
1
710, 883, 991, 1045, 1196, 1254, 1315, 1340, 1420, 1583, 1645, 2874, 2968. H-NMR (CDCl3): 7.57 (dd, J ˆ 11.5,
14.7, 1 H); 6.06 (d, J ˆ 14.7, 1 H); 6.00 (d, J ˆ 11.5, 1 H); 3.58 3.48 ( m, 4 H); 2.02 1.92 (m, 2 H); 1.92 1.82
(m, 2 H); 1.8 9 (s, 3 H); 1.8 6 (s, 3 H). 13C-NMR (CDCl3): 166.16; 144.94; 138.70; 124.56; 119.86; 46.73; 46.15;
26.75; 26.38; 24.60; 19.11.
N,N-Dimethylprop-2-enamide (11). Colorless oil. IR (KBr): 797, 981, 1055, 1155, 1259, 1423, 1499, 1603,
1
1647, 2940. H-NMR (CDCl3): 6.59 (dd, J ˆ 10.5, 17.1, 1 H); 6.30 (dd, J ˆ 2.0, 17.1, 1 H); 5.67 (dd, J ˆ 2.0, 10.5,
1 H); 3.09 (s, 3 H); 3.02 (s, 3 H). 13C-NMR (CDCl3): 166.32; 127.50; 127.36; 37.41; 35.70.
1-[(2E)-2-Methylbut-2-enoyl]pyrrolidine (12). Colorless oil. IR (KBr): 648, 1165, 1437, 1609, 2878, 2972.
1H-NMR (CDCl3): 5.79 5.70 (m, 1 H); 3.55 3.36 (m, 4 H); 1.8 7 (m, 4 H); 1.8 4 (s, 3 H); 1.70 (d, J ˆ 17.5, 3 H).
13C-NMR (CDCl3): 171.76; 133.39; 126.20; 48.74; 45.60; 26.28; 24.51; 13.65; 13.39.
1-(3-Methylbut-2-enoyl)pyrrolidine (13). Colorless oil. IR (KBr): 529, 841, 1192, 1340, 1373, 1452, 1609,
1655, 2876, 2972. 1H-NMR (CDCl3): 5.79 (m, 1 H); 3.53 3.46 (m, 2 H); 3.46 3.39 (m, 2 H); 2.08( d, J ˆ 1.5,
3 H); 1.98 1.81 ( m, 4 H); 1.8 6 (s, 3 H). 13C-NMR (CDCl3): 166.00; 148.36; 117.83; 46.82; 46.65; 45.25; 26.93;
26.18; 24.41; 20.07.
1-[(2Z)-3-Phenylprop-2-enoyl]pyrrolidine (14). Thionyl chloride (6.51 ml, 89 mmol) was mixed with
phenylprop-2-ynoic acid (0.26 g, 1.79 mmol), and the mixture was heated at 508 for 6 h. After evaporation, the
mixture was diluted with CH2Cl2 (10 ml), pyrrolidine (0.15 ml, 1.79 mmol), and Et3N (0.25 ml, 1.79 mmol).
Extraction and CC (SiO2, hexane/AcOEt 7:3 ! 2 :3) afforded N-[phenylprop-2-ynoyl]pyrrolidine (0.26 g,
74%). Two drops of tert-amyl alcohol (ˆ2-methylbutan-2-ol), quinoline (0.53 ml) and 10% Pd/C (5.6 mg) were
added to the amide, and the mixture was cooled to À408, then stirred for 3 days under 1 atm of H2. Filtration and
CC (SiO2, hexane/AcOEt 3 :2 ! 3 :7) afforded 14 (0.20 g, 74%). Colorless oil. IR (KBr): 698, 779, 1377, 1441,
1609, 2876, 2970, 3023, 3057. 1H-NMR (CDCl3): 7.46 7.39 (m, 2 H); 7.35 7.24 (m, 3 H); 6.64 (d, J ˆ 12.6, 1 H);
6.06 (d, J ˆ 12.6, 1 H); 3.57 3.46 (m, 2 H); 3.24 3.14 (m, 2 H); 1.86 1.69 (m, 4 H). 13C-NMR (CDCl3): 166.85;
135.44; 133.35; 128.27; 128.24; 128.12; 124.05; 46.96; 45.33; 25.86; 24.38.
4. Typical Procedure for cis-Selective Aziridination. A soln. of 1.6m BuLi in hexane (0.254 ml, 0.40 mmol)
was added to a soln. of 1 (45 mg, 0.40 mmol) in THF (4 ml) at À788. A THF soln. of 3 (40 mg, 0.20 mmol) was

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Helvetica Chimica Acta Vol. 85 (2002)
added to the mixture at À788, and the mixture allowed to warm to À308. After stirring for 11 h at À308, the
mixture was diluted with H2O. Extraction with CH2Cl2 and CC (basic silica gel, hexane/AcOEt 4 :1 ! 3 :2)
afforded 2,3-cis-aziridinecarboxamide as colorless crystals (42 mg, 97%). NMR: identical to those of the
optically active sample prepared by asymmetric aziridination (vide infra).
N,N-Dimethylaziridinecarboxamide (from 11). Colorless oil. IR (KBr): 486, 606, 847, 1007, 1153, 1242, 1352,
1427, 1508, 1632, 2943, 3271. 1H-NMR (CDCl3): 3.19 (s, 3 H); 3.01 (s, 3 H); 2.68( dd, J ˆ 3.0, 5.0, 1 H); 1.85 1.78
(m, 2 H). 13C-NMR (CDCl3): 170.51; 36.52; 36.13; 27.86; 26.69.
1-{[(2R*,3R*)-2,3-Dimethylaziridin-2-yl]carbonyl}pyrrolidine (from 12). Colorless oil. IR (KBr): 623, 824,
897, 1065, 1190, 1277, 1344, 1450, 1616, 2882, 2972, 3275. 1H-NMR (CDCl3): 3.68 3.39 ( m, 4 H); 2.10 1.74
(m, 6 H); 1.46 (s, 3 H); 1.14 (d, J ˆ 6.0, 3 H). 13C-NMR (CDCl3): 169.74; 47.15; 46.09; 42.62; 38.86; 26.58; 24.00;
20.67; 15.60.
1-[(3,3-Dimethylaziridin-2-yl)carbonyl]pyrrolidine (from 13). Colorless oil. IR (KBr): 530, 664, 816, 858,
907, 1105, 1188, 1310, 1381, 1460, 1628, 2880, 2963, 3269. 1H-NMR (CDCl3): 3.63 3.41 (m, 4 H); 2.41 (s, 1 H);
2.11 1.79 (m, 4 H); 1.30 (s, 3 H); 1.24 (s, 3 H). 13C-NMR (CDCl3): 167.17; 46.12; 45.89; 43.59; 38.38; 26.02;
24.30; 21.61; 19.02.
5. Typical Procedure for trans-Selective Aziridination. A soln. of 1.6m BuLi in hexane (0.254 ml, 0.40 mmol)
was added to a soln. of 2 (56 mg, 0.40 mmol) in toluene (4 ml) at À788. A toluene soln. of 3 (40 mg, 0.20 mmol)
was added to the mixture. After stirring for 4 h at À788, the mixture was diluted with H2O. Extraction with
CH2Cl2 and CC (basic silica gel, hexane/AcOEt 4 :1 ! 3 :2) afforded trans-aziridinecarboxamide as colorless
crystals (32mg, 74%). NMR: identical with those of the optically active sample prepared by asymmetric
aziridination (vide infra).
1-{[(2R*,3S*)-2,3-Dimethylaziridin-2-yl]carbonyl}pyrrolidine (from 12). Colorless oil. IR (KBr): 629, 824,
966, 1067, 1111, 1188, 1259, 1342, 1448, 1620, 2882, 2936, 3281. 1H-NMR (CDCl3): 3.59 3.37 (m, 4 H); 2.06
(q, J ˆ 5.5, 1 H); 2.05 1.67 (m, 5 H); 1.40 (s, 3 H); 1.22 (d, J ˆ 5.5, 3 H). 13C-NMR (CDCl3): 172.33; 47.56;
46.52; 40.37; 35.74; 26.42; 24.16; 15.26; 14.29.
6. Typical Procedure for Asymmetric Aziridination. A soln. of 1.6m BuLi in hexane (0.254 ml, 0.40 mmol)
was added to a soln. of 16 (92 mg, 0.40 mmol) in toluene (4 ml) at À788. A toluene soln. of 3 (40 mg, 0.20 mmol)
was added slowly to the mixture at À788 for 1 h. After stirring for 1 h at À788, the mixture was allowed to warm
to À308. After stirring for 12 h at À308, the mixture was diluted with H2O. Extraction with CH2Cl2 and CC (basic
silica gel, hexane/AcOEt 4 :1 ! 2 :3) afforded 1-{[(2S,3R)-3-phenylaziridin-2-yl]carbonyl}pyrrolidine (33 mg,
76%) as colorless crystals from the more polar fraction. HPLC (Daicel Chiralcel OD-H, hexane/iPrOH 9 :1, flow
rate 0.5 ml/min): 98% ee; tR 28.3 (major (2S,3R)-isomer), 42.7 (minor (2R,3S)-isomer)5). M.p. 84.5 85.58.
[a]2D3 ˆ ‡148.5 (c ˆ 0.50, EtOH). IR (KBr): 540, 588, 694, 754, 799, 856, 1038, 1196, 1331, 1406, 1460, 1624, 2874,
1
2970, 3034, 3246. H-NMR (CDCl3): 7.40 7.19 (m, 5 H); 3.64 3.46 (m, 4 H); 3.14 (s, 1 H); 2.59 (s, 1 H); 2.24
(br. 1 H); 2.06 1.81 (m, 4 H). 13C-NMR (CDCl3): 165.34; 135.01; 128.01; 127.28; 126.75; 45.84; 45.75; 39.50;
26.00; 24.18. Anal. calc. for C13H16N2O: C 72.19, H 7.46, N 12.95; found: C 72.17, H 7.49, N 12.74.
From the less polar fraction, 1-{[(2S,3S)-3-phenylaziridin-2-yl]carbonyl}pyrrolidine (1.5 mg, 3%) was
isolated as colorless crystals. HPLC (Daicel Chiralcel OD-H Â 2 (2 columns connected in series), hexane/iPrOH
2 :1, flow rate 0.5 ml/min): >99% ee; tR 31.7 (minor (2R,3R)-isomer), 38.5 (major (2S,3S)-isomer)6). M.p.
132.0 133.08. [a]2D4 ˆ À79.1 (c ˆ 1.18, EtOH). IR (KBr): 523, 698, 748, 901, 1198, 1360, 1454, 1630, 2876, 2976,
3219. 1H-NMR (CDCl3): 7.35 7.10 (m, 5 H); 3.59 3.30 (m, 4 H); 3.20 3.11 (m, 1 H); 2.96 (br., 1 H); 2.10 (br.,
1 H); 2.03 1.65 (m, 4 H). 13C-NMR (CDCl3): 168.44; 139.31; 128.88; 127.93; 126.58; 46.64; 46.37; 40.07; 39.93;
26.10; 24.40. Anal. calc. for C13H16N2O: C 72.19, H 7.46, N 12.95; found: C 72.05, H 7.59, N 12.86.
1-{[(2S,3R)-3-(4-Methoxyphenyl)aziridin-2-yl]carbonyl}pyrrolidine (from 4). Colorless crystals. M.p.
75.0 77.08. HPLC: 96% ee. [a]2D6 ˆ ‡160.0 (c ˆ 1.87, EtOH). IR (KBr): 546, 820, 1032, 1178, 1250, 1306,
1456, 1516, 1632, 2878, 2966, 3261. 1H-NMR (CDCl3): 7.23 (d, J ˆ 8.5, 2 H); 6.86 (d, J ˆ 8.5, 2 H); 3.80 (s, 3 H);
3.65 3.46 (m, 4 H); 3.10 (s, 1 H); 2.55 (s, 1 H); 2.19 (br., 1 H); 2.08 1.80 ( m, 4 H). 13C-NMR (CDCl3): 167.70;
158.83; 130.65; 127.00; 113.72; 55.31; 46.38; 46.13; 39.74; 39.39; 25.97; 24.29. Anal. calc. for C14H18N2O2: C 68.27,
H 7.37, N 11.37; found: C 68.33, H 7.35, N 11.24.
1-{[(2S,3S)-3-(4-Methoxyphenyl)aziridin-2-yl]carbonyl}pyrrolidine (from 4). Colorless crystals. M.p.
120.0 121.58. HPLC: 99% ee. IR (KBr): 515, 677, 814, 839, 905, 1030, 1182, 1248, 1360, 1458, 1514, 1636,
2878, 2976, 3221. 1H-NMR (CDCl3): 7.15 (d, J ˆ 8.5, 2 H); 6.81 (d, J ˆ 8.5, 2 H); 3.77 (s, 3 H); 3.60 3.29
5
)
)
The same elution order was observed for the other aziridinecarboxamides prepared form 4 10.
The same elution order was observed for the other aziridinecarboxamides prepared form 4 6.
6

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(m, 4 H); 3.23 3.11 (m, 1 H); 2.92 (d, J ˆ 5.5, 1 H); 2.12 1.66 (m, 5 H). 13C-NMR (CDCl3): 158.64; 127.87;
113.55; 55.24; 45.89; 45.78; 40.11; 39.32; 26.04; 24.26. Anal. calc. for C14H18N2O2: C 68.27, H 7.37, N 11.37; found:
C 68.09, H 7.32, N 11.10.
1-{[(2S,3R)-3-(4-Chlorophenyl)aziridin-2-yl]carbonyl}pyrrolidine (from 5). Colorless crystals. M.p.
119.0 120.58. HPLC: 96% ee. [a]2D5 ˆ ‡150.8( c ˆ 1.03, EtOH). IR (KBr): 498, 534, 733, 812, 858, 1011,
1
1034, 1088, 1169, 1192, 1333, 1414, 1458, 1626, 2874, 2972, 3047, 3258. H-NMR (CDCl3): 7.31 7.21 (m, 4 H);
3.65 3.44 (m, 4 H); 3.11 (s, 1 H); 2.53 (s, 1 H); 2.24 (br., 1 H); 2.07 1.82 (m, 4 H). 13C-NMR (CDCl3): 167.32;
137.24; 133.06; 128.43; 127.32; 46.48; 46.19; 40.02; 39.13; 26.02; 24.32. Anal. calc. for C13H15ClN2O: C 62.28,
H 6.03, N 11.17; found: C 62.28, H 6.05, N 11.07.
1-{[(2S,3S)-3-(4-Chlorophenyl)aziridin-2-yl]carbonyl}pyrrolidine (from 5). Colorless crystals. M.p. 124.0
125.08. HPLC: >99% ee. IR (KBr): 519, 808, 858, 903, 1015, 1090, 1186, 1358, 1458, 1638, 2876, 2978, 3221.
1H-NMR (CDCl3): 7.29 7.10 (m, 4 H); 3.64 3.26 (m, 4 H); 3.24 3.11 (m, 1 H); 2.94 (br., 1 H); 2.15 1.56
(m, 5 H). 13C-NMR (CDCl3): 165.91; 133.80; 128.89; 128.86; 46.17; 46.04; 39.59; 26.18; 24.32. Anal. calc. for
C13H15ClN2O: C 62.28, H 6.03, N 11.17; found: C 62.46, H 6.07, N 11.08.
1-{[(2R,3S)-3-(1-Naphthyl)aziridin-2-yl]carbonyl}pyrrolidine (from 6). Colorless crystals. M.p. 126.0
127.08. HPLC: 96% ee. [a]2D5 ˆ À131.0 (c ˆ 0.50, EtOH). IR (KBr): 422, 515, 615, 773, 802, 851, 1032, 1192,
1261, 1339, 1460, 1630, 2882, 2978, 3058, 3244. 1H-NMR (CDCl3): 7.63 (dd, J ˆ 2.0, 8.3, 1 H); 7.43 (dd, J ˆ 2.0, 8.0,
1 H); 7.32 (d, J ˆ 8.5, 1 H); 7.20 (d, J ˆ 7.0, 1 H); 7.11 7.02 (m, 2 H); 7.04 6.97 (m, 1 H); 3.25 (d, J ˆ 1.5, 1 H);
3.22 3.13 (m, 2 H); 3.11 3.02 (m, 1 H); 2.13 (d, J ˆ 2.5, 1 H); 1.84 (br. 1 H); 1.58 1.36 (m, 4 H). 13C-NMR
(CDCl3): 168.72; 134.93; 133.89; 132.46; 129.31; 128.25; 126.70; 126.23; 126.15; 124.28; 123.26; 46.75; 46.53;
38.96; 38.13; 26.19; 24.47. Anal. calc. for C17H18N2O: C 76.66, H 6.81, N 10.57; found: C 76.38, H 6.81, N 10.48.
1-{[(2S,3S)-3-(1-Naphthyl)aziridin-2-yl]carbonyl}pyrrolidine (from 6). Colorless oil. HPLC: 99% ee. IR
(KBr): 519, 779, 799, 862, 1190, 1348, 1456, 1634, 2876, 2970, 3246. 1H-NMR (CDCl3): 8.15 (d, J ˆ 8.5, 1 H); 7.85
(dd, J ˆ 1.5, 8.3, 1 H); 7.76 (d, J ˆ 8.0, 1 H); 7.56 7.46 (m, 2 H); 7.46 7.40 (m, 1 H); 7.33 (d, J ˆ 7.0, 1 H); 3.81
(d, J ˆ 5.5, 1 H); 3.72 3.59 (m, 2 H); 3.34 3.25 (m, 1 H); 3.19 (d, 5.5, 1 H); 2.96 2.86 (m, 1 H); 2.00 1.40
(m, 5 H). 13C-NMR (CDCl3): 165.20; 133.11; 131.89; 130.89; 128.70; 127.86; 125.68; 125.47; 125.09; 124.36;
122.74; 46.26; 45.95; 39.33; 37.81; 25.95; 24.02.
1-{[(2R,3S)-3-(2-Furyl)aziridin-2-yl]carbonyl}pyrrolidine (from 7). Colorless crystals. M.p. 69.0 70.58.
HPLC: 97% ee. [a]2D4 ˆ ‡150.9 (c ˆ 1.33, EtOH). IR (KBr): 525, 677, 752, 804, 858, 932, 1013, 1190, 1229, 1319,
1464, 1626, 2872, 2976, 3109, 3223. 1H-NMR (CDCl3): 7.33 (d, J ˆ 2.0, 1 H); 6.33 (dd, J ˆ 2.0, 3.0, 1 H); 6.29
(d, J ˆ 3.0, 1 H); 3.71 3.46 (m, 4 H); 3.16 (s, 1 H); 2.92 (s, 1 H); 2.14 (br. 1 H); 2.10 1.78( m, 4 H). 13C-NMR
(CDCl3): 167.18; 151.72; 141.75; 110.37; 106.92; 46.44; 46.16; 36.87; 33.76; 25.99; 24.30. Anal. calc. for
C11H14N2O2: C 64.06, H 6.84, N 13.58; found: C 64.26, H 6.90, N 13.51.
1-{[(2S,3S)-3-(2-Furyl)aziridin-2-yl]carbonyl}pyrrolidine (from 7). Colorless crystals. M.p. 75.0 77.08.
HPLC: >99% ee. IR (KBr): 408, 455, 509, 598, 679, 706, 756, 820, 854, 989, 1043, 1097, 1159, 1352, 1462, 1638,
2880, 2953, 3117, 3153, 3258. 1H-NMR (CDCl3): 7.31 (d, J ˆ 2.0, 1 H); 6.29 (dd, J ˆ 2.0, 3.0, 1 H); 6.15 (d, J ˆ 3.0,
1 H); 3.60 3.42 (m, 3 H); 3.39 3.30 (m, 1 H); 3.29 (s, 1 H); 2.93 (s, 1 H); 2.13 1.76 (m, 5 H). 13C-NMR
(CDCl3): 165.27; 149.64; 141.88; 110.41; 106.40; 46.01; 45.83; 38.75; 33.55; 25.95; 24.29. Anal. calc. for
C11H14N2O2: C 64.06, H 6.84, N 13.58; found: C 64.11, H 6.94, N 13.53.
1-{[(2R,3S)-3-(2-Methylprop-1-enyl)aziridin-2-yl]carbonyl}pyrrolidine (from 8). Colorless oil. HPLC:
96% ee. [a]2D6 ˆ À31.1 (c ˆ 0.42, EtOH). IR (KBr): 496, 802, 856, 1167, 1246, 1342, 1454, 1632, 2878, 2968, 3260.
1H-NMR (CDCl3): 4.81 (d, J ˆ 8.79, 1 H); 3.68 3.44 (m, 4 H); 2.74 (dd, J ˆ 8.79, 2.44, 1 H); 2.46 (d, J ˆ 2.44,
1 H); 2.10 1.75 (m, 5 H); 1.76 (s, 3 H); 1.72 (s, 3 H).13C-NMR (CDCl3): 168.36; 137.00; 123.48; 46.38; 46.14;
37.02; 36.34; 26.06; 25.81; 24.35; 18.57.
1-{[(2S,3S)-3-(2-Methylprop-1-enyl)aziridin-2-yl]carbonyl}pyrrolidine (from 8). Colorless oil. IR (KBr):
419, 521, 692, 737, 806, 870, 1053, 1078, 1123, 1159, 1229, 1346, 1458, 1634, 2880, 2966, 3240. 1H-NMR (CDCl3):
4.89 (d, J ˆ 9.28,1 H); 3.60 3.45 (m, 4 H); 2.87 (dd, J ˆ 9.28, 5.62, 1 H); 2.79 (d, J ˆ 5.62, 1 H); 2.10 1.80
(m, 5 H); 1.78( s, 3 H); 1.71 (s, 3 H). 13C-NMR (CDCl3): 167.64; 139.22; 119.58; 46.35; 46.17; 37.88; 35.89; 26.23;
26.19; 24.48; 18.57.
1-{[(2R,3S)-3-Methylaziridin-2-yl]carbonyl}pyrrolidine (from 9). Colorless oil. HPLC: 92% ee. [a]D22
ˆ
‡3.3 (c ˆ 0.92, EtOH). IR (KBr): 451, 525, 723, 831, 941, 1090, 1165, 1246, 1323, 1412, 1464, 1628, 2880, 2970,
3269. 1H-NMR (CDCl3): 3.70 3.40 (m, 4 H); 2.28( d, J ˆ 2.5, 1 H); 2.16 (dq, J ˆ 2.5, 5.0, 1 H); 2.10 1.78
(m, 5 H); 1.24 (d, J ˆ 5.0, 3 H). 13C-NMR (CDCl3): 168.72; 46.30; 46.15; 36.53; 33.94; 26.08; 24.35; 18.38.
1-{[(2S,3S)-3-Methylaziridin-2-yl]carbonyl}pyrrolidine (from 9). Colorless oil. IR (KBr): 527, 681, 826, 858,
1009, 1175, 1231, 1350, 1462, 1628, 2880, 2970, 3263. 1H-NMR (CDCl3): 3.63 3.45 (m, 4 H); 2.61 (d, J ˆ 6.0,

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Helvetica Chimica Acta Vol. 85 (2002)
1 H); 2.27 (dq, J ˆ 6.0, 6.0, 1 H); 2.11 1.80 (m, 5 H); 1.23 (d, J ˆ 6.0, 3 H). 13C-NMR (CDCl3): 166.92; 46.01;
45.96; 36.04; 32.96; 26.06; 24.28; 13.22.
(2R,3S)-N,N,3-Trimethylaziridine-2-carboxamide (from 10). Colorless oil. HPLC: 90% ee. [a]2D3 ˆ À20.7
(c ˆ 0.42, EtOH). IR (KBr): 496, 621, 833, 941, 1088, 1165, 1252, 1329, 1404, 1435, 1504, 1638, 2934, 3271.
1H-NMR (CDCl3): 3.16 (s, 3 H); 3.00 (s, 3 H); 2.38( s, 1 H); 2.08(br., 1 H); 1.69 (br. 1 H); 1.25 ( d, J ˆ 5.5, 3 H).
13C-NMR (CDCl3): 170.27; 36.63; 36.05; 35.45; 33.89; 18.32.
(2S,3S)-N,N,3-Trimethylaziridine-2-carboxamide (from 10). Colorless oil. IR (KBr): 604, 833, 1009, 1105,
1134, 1169, 1261, 1406, 1426, 1504, 1638, 2936, 3269. 1H-NMR (CDCl3): 3.13 (s, 3 H); 3.02 (s, 3 H); 2.70 (d, J ˆ
6.0, 1 H); 2.29 (dq, J ˆ 6.0, 5.5, 1 H); 1.19 (d, J ˆ 5.5, 3 H). 13C-NMR (CDCl3): 168.53; 36.42; 35.73; 35.62; 32.86;
13.42.
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Received August 16, 2002