On the scope of diastereoselective aziridination of various chiral auxiliaries derived N- and O-enones with N-aminophthalimide in the presence of lead tetraacetate

Article abstract of DOI:10.1016/j.tetasy.2008.02.028

The treatment of a range of N- and O-enones derived from various camphor-based chiral auxiliaries A-D with N-aminophthalimide in the presence of lead tetraacetate is described. In general, N-phthalimidoaziridines were obtained with high diastereoselectivities (up to 98% de) and chemical yields (up to 95%) when 10,10-diphenyl-2,10-camphanediol A derived O-enones with a range of substituents were used under the same reaction conditions. Excellent stereoselectivity was obtained when the N-tosyl camphorpyrazolidinone E derived acrylate was used. The absolute configuration of the new stereogenic center(s) of the major diastereomer was established by X-ray crystallographic analysis. Chiral auxiliary cleavage was achieved under mild reaction conditions. A model to explain the stereochemical induction is also proposed.

Full text of DOI:10.1016/j.tetasy.2008.02.028

Available online at www.sciencedirect.com
Tetrahedron: Asymmetry 19 (2008) 682–690
On the scope of diastereoselective aziridination of various chiral
auxiliaries derived N- and O-enones with N-aminophthalimide
in the presence of lead tetraacetate
Pei-Wen Duan, Ching-Chen Chiu, Wei-Der Lee, Li Shiue Pan, Uppala Venkatesham,
Zheng-Hao Tzeng and Kwunmin Chen*
Department of Chemistry, National Taiwan Normal University, Taipei 116, Taiwan, ROC
Received 25 December 2007; accepted 22 February 2008
Abstract—The treatment of a range of N- and O-enones derived from various camphor-based chiral auxiliaries A–D with N-amino-
phthalimide in the presence of lead tetraacetate is described. In general, N-phthalimidoaziridines were obtained with high diastereo-
selectivities (up to 98% de) and chemical yields (up to 95%) when 10,10-diphenyl-2,10-camphanediol A derived O-enones with a
range of substituents were used under the same reaction conditions. Excellent stereoselectivity was obtained when the N-tosyl camp-
horpyrazolidinone E derived acrylate was used. The absolute configuration of the new stereogenic center(s) of the major diastereomer
was established by X-ray crystallographic analysis. Chiral auxiliary cleavage was achieved under mild reaction conditions. A model to
explain the stereochemical induction is also proposed.
Ó 2008 Elsevier Ltd. All rights reserved.
1. Introduction
asymmetric synthesis, four novel camphor-derived auxilia-
ries: 10,10-diphenyl-2,10-camphanediol A, 10,10-diphenyl-
10-methoxy-2-camphanol B, N-phenyl camphorpyrazoli-
dinone C, and N-tosyl camphorpyrazolidinone D have been
developed and utilized in various asymmetric reactions.8
Recently, we have reported the diastereoselective aziridin-
ation of N-enones derived from N-phenyl camphorpyrazo-
lidinone with N-aminophthalimide in the presence of lead
tetraacetate.9 High to excellent stereoselectivities of the
desired aziridines were obtained. In addition, the N-inversion
phenomena was observed for N-phenyl camphorpyrazolidi-
none derived N-phthalimidoaziridines.9 Based on these stud-
ies, we herein report on the scope of the diastereoselective
aziridination of N- and O-enones 1a–o derived from various
camphor-based chiral auxiliaries A–D. Generally, the desired
aziridines were obtained with high stereoselectivities and
chemical yields under mild reaction conditions. The stereo-
chemical inductions of the reaction were proposed based
on the conformational preference of the chiral N- and
O-enones in their solid state structures.
The synthesis of aziridine derivatives has received much
attention as they are important molecules as key components
of many biologically active natural products such as mito-
mycins, which display potent antitumor and antibiotic activ-
ity, and are also useful synthetic intermediates for nitrogen-
containing compounds.1 In addition, aziridines are highly
versatile synthetic precursors and have been used as synthons
for chiral amines, amino acids, b-aminosulfonic acids, amino
alcohols, alkaloids, and b-lactam antibiotics.2 Aziridines are
the nitrogen analogues of epoxides and exhibit similar reac-
tivity patterns as electrophilic reagents.3 It is not surprising
that much effort has been devoted to developing efficient
methods for the construction of the constrained three-mem-
bered ring system.4 Among the many routes that have been
developed, the reaction of nitrenes to olefins or carbenes to
imines has potential.5 The enantioselective and diastereo-
selective syntheses of non-racemic aziridines have constantly
reported in the literature.6 The Oppolzer camphorsultam is
among the most widely used chiral auxiliary in diastereoselec-
tive synthesis.7 In continuation of our research interest in
2. Results and discussion
*
The starting chiral O- 1a–k and N-enones 1l–1o can be
Corresponding author. Tel.: +886 2 89315831; fax: +886 2 29324249;
e-mail: kchen@ntnu.edu.tw
easily prepared from the corresponding chiral auxiliaries
0957-4166/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2008.02.028

P.-W. Duan et al. / Tetrahedron: Asymmetry 19 (2008) 682–690
683
A–D by using standard coupling reaction conditions
(Fig. 1). With the various N- and O-enones 1a–o in hand,
we then investigated the diastereoselective aziridination
reaction using N-aminophthalimide in the presence of lead
tetraacetate. Vederas et al. have explored the aziridination
by using N-enoylbornane[10,2]sultams in the presence of
N-aminophthalimide and lead tetraacetate. The corre-
sponding N-phthalimidoaziridines were obtained with 33–
95% de.10 In an initial experiment, 10,10-diphenyl-2,10-
camphanediol derived acrylate 1a was chosen as a probe
substrate under the optimal oxidation reaction conditions
that were developed previously.9 Unsatisfactory results
(47% yield and 56% de) were obtained when 1a was treated
with N-aminophthalimide and lead tetraacetate in CH2Cl2
at ambient temperature (Table 1, entry 1). A slight improve-
ment in both chemical yield and stereoselectivity was ob-
served when the reaction was carried out at 0 °C (Table 1,
entry 2). The solvent effects were then studied. High stere-
oselectivity was obtained when the reaction was carried
out in CHCl3 (Table 1, entry 3). Comparable results were
achieved when CH3CN was used (Table 1, entry 4). Satis-
factory results were obtained when non-polar solvents (ben-
zene and toluene) were used (Table 1, entries 5 and 6).
Further improvements in material yield were observed
when the reaction was carried out in THF at 0 °C (entry
7). It was obvious that THF is a solvent of choice for this
reaction. The structure of the major N-phthalimidoaziridine
1
2a was initially assigned by H, 13C NMR, and HRMS
analyses, and the absolute stereochemistry was assigned as
(1R) by analogy. The diastereomeric excess was deduced
1
from the relevant peak in the H NMR spectrum of the
crude mixture. The characteristic feature of the C2 methine
proton (camphor numbering) of the corresponding N-
phthalimidoaziridines 2 provides a convenient way to assign
the stereoselectivity. For example, the C2 methine in 2a ap-
peared at 5.28 ppm (dd, J = 8.4, 3.8 Hz), while it showed up
at 5.12 ppm in the minor product 3a. On the other hand, the
aziridine ring protons in 2a showed up at 2.91 (dd, 1H,
J = 7.8, 5.4 Hz), 2.62 (dd, 1H, J = 7.8, 1.8 Hz), and 2.48
(dd, 1H, J = 5.4, 1.8 Hz) ppm, respectively.
Me
Me
Me
Me
Xc:
R1
O
Xc
R2
N
Ph
Ph
N
O
OR
O
R3
R
1
A: R = H
C: R = Ph
D: R = Ts
B: R = Me
1a
1b
1c
1d
1e
: Xc = A, R1 = R2 = R3 = H
1h : Xc = A, R1 = R2 = Me, R3 = H
: Xc = A, R1 = H, R2 = Me, R3 = H
: Xc = A, R1 = H, R2 = Et, R3 = H
: Xc = A, R1 = H, R2 = n-pr, R3 = H
: Xc = A, R1 = H, R2 = i-pr, R3 = H
1i
1j
: Xc = A, R1 = Me, R2 = Et, R3 = H
: Xc = A, R1 = H, R2 = R3 = Me
1k : Xc = B, R1 = H, R2 = Me, R3 = H
: Xc = C, R1 = R2 = R3 = H
1l
1f : Xc = A, R1 = H, R2 = Ph, R3 = H
1g : Xc = A, R1 = Me, R2 = R3 = H
1m: Xc = C, R1 = H, R2 = Me, R3 = H
1n
1o
: Xc = D, R1 = R2 = R3 = H
: Xc = D, R1 = H, R2 = Me, R3 = H
Figure 1.
Table 1. Asymmetric aziridination of 10,10-diphenyl-2,10-camphandiol derived acrylate 1a with N-aminopthalimide in the presence of lead tetraacetatea
Me
Me
Me
Me
Me
Me
O
NPth
NPth
H
H
N
N
O
O
O
+
Ph
Ph
Ph
Ph
Ph
Ph
OH
OH
OH
O
O
3a (Xc = A)
1a (Xc = A)
Solvent
2a (Xc = A)
Entry
T
Yield (%)
Ratio (2a:3a)
1
2
3
4
5
6
7
CH2Cl2
CH2Cl2
CHCl3
CH3CN
Benzene
Toluene
THF
rt
47
53
68
75
71
73
90
78:22
86:14
94:06
94:06
94:06
88:12
94:06
0 °C
0 °C
0 °C
>5 °C
0 °C
0 °C
a All reactions were performed using chiral enone 1a (0.2 g, 0.53 mmol), N-aminophthalimide (1.5 equiv), Pb(OAc)4 (1.6 equiv) in THF (5.0 mL) at 0 °C.

684
P.-W. Duan et al. / Tetrahedron: Asymmetry 19 (2008) 682–690
Various 10,10-diphenyl-2,10-camphanediol derived O-
enones with a-, b-, a,b-di, and b,b-disubstituent(s) were
then subjected to the optimal reaction conditions. Moderate
stereoselectivities were obtained when acryoyl O-enones 1b
was used (Table 2, entry 1). High stereoselectivities and
material yields were obtained when other b-substituents
(ethyl-, n-propyl-, and isopropyl-) were used (Table 2,
entries 2–4). The electron-rich O-cinnamoyl enone 1f was
investigated and the desired products were isolated with
75% yield and 80% de (Table 2, entry 5). The stereoselectiv-
ity dropped significantly when an a-substituent is present.
The a-substituent effect on the yield has been observed
before.10 The a-substituent effect may come from the devia-
tion of dihedral angle from the planar geometry of the
enone. The a-substituent effect does not influence the
reactivity in the case of 10,10-diphenyl-2,10-camphanediol
derived O-enones. However, it does affect the stereoselectiv-
ity. Thus, the use of O-methacryloyl enone 1g gave only
moderate stereoselectivity (2g:3g = 61:39) (entry 6). Inter-
estingly, the selectivity rebounds with the presence of an
additional b-substituent. Toward this end, high stereoselec-
tivities were obtained when a,b-dimethyl 1h and a-methyl b-
ethyl 1i substrates were used under the same reaction condi-
tions (Table 2, entries 7 and 8). Similar result was observed
when b, b-dimethyl substituent 1j was used (Table 2, entry
9). A similar observation was noted when N-phenyl camp-
horpyrazolidinone derived N-enone was used.9 The abso-
lute stereochemistries of the major isomeric products of
2b–f were confirmed by single crystal X-ray analyses. Next,
the use of 10,10-diphenyl-10-methoxy-2-camphanol B
derived O-enone was also studied. The desired product 2k
was obtained with 74% de in favoring the (1R,2S)-configu-
ration of the newly generated aziridine ring (Table 2, entry
10). The use of N-phenyl camphorpyrazolidinone C
derived N-enones 1l and 1m gives the desired aziridine with
high selectivities (Table 2, entries 11 and 12).9 Further, the
treatment of N-tosyl camphorpyrazolidinone E derived
acrylate 1n with N-aminophthalimide in the presence of lead
tetraacetate afforded 2n with >95% de (Table 2, entry 13).
As mentioned, Vederas et al. have reported the aziridin-
ation of N-enoylbornane[10,2]sultams with N-amino-
phthalimide in the presence of lead tetraacetate. The
corresponding N-phthalimidoaziridines were obtained with
33–95% de in good to high material yields.10 Comparison
of the aziridination of the camphorsultam derived N-enon-
es and the current results indicate auxiliaries A–D provid-
ing better stereofacial discrimination. For example, the
aziridination of camphorsultam derived acrylate (R1 =
R2 = R3 = H) gave the corresponding N-phthalimidoaziri-
dines with 78% de, while with 88%, >90%, and >90% de,
respectively when auxiliaries A, C, and D derived acrylates
were used (Table 1, entry 7 and Table 2, entries 11 and 13).
Moreover, for auxiliaries A–D derived from N-crotonyl
substrates (R1 = H, R2 = Me, R3 = H), the diastereoselec-
tivities (64–90% de; Table 2, entries 1, 10, 12, and 14) are
also better than those of N-crotonyl camphorsultam
(33% de).
Table 2. Asymmetric aziridination of various enones 1b–o with N-aminopthalimide in the presence of lead tetraacetatea
NPth
R3
NPth
R3
R1
O
R1
O
N
N
Xc
Xc
R2
R2
2b-o
3b-o
Entry
Substrate
Time (min)
Yieldb (%)
Ratio (2:3)c
Configurationd
1
2
3
4
5
6
7
8
9
10
11f
12f
13
14
1b Xc = A, R1 = H, R2 = Me, R3 = H
1c Xc = A, R1 = H, R2 = Et, R3 = H
1d Xc = A, R1 = H, R2 = n-Pr, R3 = H
1e Xc = A, R1 = H, R2 = i-Pr, R3 = H
1f Xc = A, R1 = H, R2 = Ph, R3 = H
1g Xc = A, R1 = Me, R2 = R3 = H
1h Xc = A, R1 = R2 = Me, R3 = H
1i Xc = A, R1 = Me, R2 = Et, R3 = H
1j Xc = A, R1 = H, R2 = R3 = Me
1k Xc = B, R1 = H, R2 = Me, R3 = H
1l Xc = C, R1 = R2 = R3 = H
40
5
5
90
95
90
95
75
95
95
95
70
90
94
90
50
53
82:18
93:07
93:07
95:05
90:10
61:39
95:05
95:05
05:95
(1R,2S)
(1R,2S)e
(1R,2S)
(1R,2S)
(1R,2S)
(1R)e
(1R,2S)
(1R,2S)e
(1S)e
(1R,2S)e
(1R)
5
15
10
5
5
10
5
5
5
10
10
87:13
>95:05
>95:05
>95:05
>95:05
1m Xc = C, R1 = H R2 = Me, R3 = H
1n Xc = D, R1 = R2 = R3 = H
1o Xc = D, R1 = H, R2 = Me, R3 = H
(1R,2S)
(1R)
(1R,2S)e
a Unless otherwise noted, all reactions were performed using chiral enones (0.2 g), N-aminophthalimide (1.5 equiv), Pb(OAc)4 (1.6 equiv) in THF (5.0 mL)
at 0 °C.
b Total isolated yield (2 and 3).
c Diastereoselectivity was determined by 1H NMR analysis of relevant peaks of crude products.
d Absolute stereochemistry of the newly generated stereogenic centers deduced by single X-ray crystal analyses.
e Absolute stereochemistry was assigned by analogy.
f See Ref. 9.

P.-W. Duan et al. / Tetrahedron: Asymmetry 19 (2008) 682–690
685
An interesting N-interconversion phenomena of N-
phthalimidoaziridine was observed by both us and Atkin-
son et al.9,11 The kinetically formed trans-aziridine 2l
inverts at the aziridine nitrogen atom to the thermodynam-
ically preferred cis-aziridine. Similar phenomena were
observed for N-methacryloyl 10,10-diphenyl-2,10-cam-
phanediol derived aziridine 2g. Thus, the isolated pure dia-
stereomer of 2g (flash column chromatography, E. Merck
Silica Gel 60, Rf = 0.4, hexanes/ethyl acetate = 4:1) slowly
converts into its less polar N-invertomer (Rf = 0.6, hex-
anes/ethyl acetate = 4:1) and reached an equilibrium to
give a 3:2 ratio at ambient temperature over 30 min. The
1H NMR spectra of both diastereomers are identical in
CDCl3. It is pertinent to note that N-tosyl camphorpyrazo-
lidinone derived acrylate 1n produced exclusively one dia-
stereomer with moderate yield (Table 2, entry 13). The
absolute configuration of the newly generated stereogenic
center was established as (1R) by single X-ray crystal anal-
ysis. The rapid equilibrium of N-interconversion was also
observed for 1n (Rf = 0.1 and 0.3, hexanes/ethyl ace-
tate = 4:1). To complete one cycle of the chiral auxiliary,
the initial adduct was subjected to deacylation conditions.
Exposure of 2a with NaOMe in methanol at ambient tem-
perature provided the desired 2-carboxyl aziridine deriva-
tive 4a (67%) {[a]D = +109.5 (c 1, CHCl3)} and 10,10-
diphenyl-2,10-camphanediol A was recovered in 85% yield
(Scheme 1).
been examined by both Oppolzer12 and Curran.13 For
amide derived N-enone functionality, the s-cis conforma-
tion dominates with no substituent and b-substituents
while favoring the s-trans disposition if an a-substituent
is present. For example, a,b-substituted N-enones 1l ener-
getically favor s-trans geometry, while for b-substituted
N-enone 1m, planar s-cis conformation dominate.9,13,14 In
contrast to the amide N-enone C and D system, the ester
linkage O-enones exhibit different conformational behav-
iors. The s-trans conformation is energetically favored for
the unsubstituted, b-substituent, and an a,b-disubstituted
of exo-10,10-diphenyl-2, 10-camphane diol A derived O-
enones.15 This can be confirmed by the single X-ray crystal
analyses of compounds 1b–c and 1g–h. Interestingly, for
b,b-disubstituted O-enone 1j, the s-cis conformation is
energetically favored as indicated by the single X-ray
crystal analysis. Similar to the N-phenyl camphorpyrazo-
lidinone C derived N-enones, the bulky N-acetoxyamino-
phthalimide comes from the less hindered bottom face.
For 1a–i, the attack is from the Ca re-face, while from
the opposite si-face for 1j to give the observed
stereoisomers.
It is important to note that the amide carbonyl group ori-
ents away from the sulfonyl group in N-tosyl camphor-
pyrazolidinone D derived acrylate 1n. This is to minimize
the dipole–dipole repulsions between the sulfonyl and car-
bonyl groups. The planar s-cis conformation is favored in
the solid state (the dihedral angle of C@O–C@C is
À4.37). The attack of an N-acetoxyaminophthalimide
intermediate from the Ca re-face gives the desired major
diastereomer. The low levels of asymmetric induction were
obtained (Table 2, entry 6) when 1g was used, may be due
to the dihedral angle deviating from planarity (the dihedral
angle of C@O–C@C is 152.5).
The aziridination reaction using N-aminophthalimide in
the presence of lead tetraacetate proceeded with a non-che-
lation fashion. The stereochemical induction can be ratio-
nalized based on the conformational structures of the
auxiliaries derived N- and O-enones (Fig. 2). The relation-
ship of reaction rate/stereoselectivity and geometry
arrangement of camphorsultam conjugated N-enones have
Me
Me
Me
Me
NPth
H
NPth
H
N
N
NaOMe, MeOH
O
MeO
+
OH
Ph
Ph
Ph
OH
O
O
OH
Ph
2a (Xc = A)
4a (67%)
Xc = A (85%)
Scheme 1.
Me
PthNNHOAc
Me
Me
Me
Me
Me
O
R2
O
O
H
R1
R2
N
O
R3
O
H
Ph
Ph
Ph
Ph
H
H
OH
H
N
O
H
OH
H
Ts
PthNNHOAc
1j (s-cis)
1n (s-cis)
1a-i (s-trans)
AcONHNPth
Figure 2. Proposed mechanism for the diastereoselective aziridination of various chiral O- and N-enones derived from camphor-based auxiliaries.

686
P.-W. Duan et al. / Tetrahedron: Asymmetry 19 (2008) 682–690
3. Conclusion
bined organic extracts were dried over brine, dried over
MgSO4, and concentrated in vacuo. The obtained crude
products were subjected to flash column chromatography
eluted with hexanes/ethyl acetate 4:1 to afford product 1a
as a white solid (1.03 g, 88%).
In conclusion, the diastereoselective aziridinations of vari-
ous N- and O-enones derived from various chiral auxilia-
ries have been demonstrated. The treatment of the O-
and N-enones with N-aminophthalimide in the presence
of lead tetraacetate afforded the corresponding N-
phthalimidoaziridines with high diastereoselectivities (up
to 98% de) and chemical yields (up to 95%). The diastereo-
meric excess can be determined by the relevant peak in the
1H NMR spectrum (C2 methine proton of the camphor
scaffold) of the crude mixtures. The stereochemical bias
can be explained by the conformational preference of the
starting enones in the solid states. For exo-10,10-diphen-
yl-2,10-camphanediol A derived O-enones 1a-i, the addi-
tion of the N-acetoxyaminophthalimide intermediate
attacks from the Ca re-face, while from the opposite si-face
for 1j to give the observed stereoisomers. On the other
hand, for N-tosyl camphorpyrazolidinone D derived N-
enones, the oxidation reagent attack from the Ca re-face
afforded the desired major aziridine.
4.2.1. Acrylic acid 1-(hydroxy-diphenyl-methyl)-7,7-
dimethyl-bicyclo[2.2.1]hept-2-yl ester 1a. 1H NMR
(200 MHz, CDCl3) d 7.76–7.61 (m, 4H), 7.34–7.07 (m,
6H), 6.19–5.70 (m, 3H), 5.24 (dd, 1H, J = 8.1, 3.5 Hz),
3.80 (s, 1H), 2.41–2.26 (m, 1H), 2.07–1.50 (m, 8H), 1.24–
1.11 (m, 1H), 0.64 (s, 3H); 13C NMR (50 MHz, CDCl3) d
163.7, 148.9, 143.4, 130.5, 128.5, 128.0, 127.9, 126.9,
126.5, 126.2, 126.0, 81.8, 81.3, 59.2, 51.3, 47.7, 38.4, 31.0,
26.9, 24.4, 22.5; HRMS (EI): calcd for C25H28O3,
376.2038; found, 376.2049.
4.2.2. But-2-enoic acid 1-(hydroxy-diphenyl-methyl)-7,7-
dimethyl-bicyclo[2.2.1]hept-2-yl ester 1b. Yield 78%; 1H
NMR (200 MHz, CDCl3) d 7.78–7.61 (m, 4H), 7.30–7.05
(m, 6H), 6.68 (dq, 1H, J = 11.2, 1.8 Hz), 5.56 (dq, 1H,
J = 15.4, 1.8 Hz), 5.20 (dd, 1H, J = 8.1, 3.7 Hz), 3.93
(1H, s), 2.40–2.25 (m, 1H), 2.05–1.45 (m, 10H), 1.26–1.07
(m, 2H), 0.61 (s, 3H); 13C NMR (50 MHz, CDCl3) d
163.9, 148.9, 144.6, 143.4, 128.4, 127.9, 127.8, 126.8,
126.4, 126.1, 126.0, 125.9, 122.1, 81.3, 81.3, 59.0, 51.2,
47.6, 38.5, 30.8, 26.9, 24.4, 22.5, 17.7; HRMS (EI): calcd
for C26H30O3, 390.2195; found, 390.2202.
4. Experimental
4.1. General methods
All reagents were used as purchased from commercial sup-
pliers without further purification. NMR spectra were
recorded on a Varian Gemini-2000 200 NMR and Bruker
Avance 400 NMR spectrometer (200 and 400 MHz for
1H, and 50 and 100 MHz for 13C). Chemical shifts are re-
ported in d ppm referenced to an internal TMS standard
4.2.3. Pent-2-enoic acid 1-(hydroxy-diphenyl-methyl)-7,7-
dimethyl-bicyclo[2.2.1]hept-2-yl ester 1c. Yield 73%; 1H
NMR (200 MHz, CDCl3) d 7.76–7.63 (m, 4H), 7.26–7.07
(m, 6H), 6.81–6.67 (dt, 1H, J = 14.7, 6.5 Hz), 5.56 (d,
1H, J = 14.7 Hz), 5.19 (dd, 1H, J = 8.0, 4.0 Hz), 3.94 (s,
1H), 2.38–2.25 (m, 1H), 2.23–1.47 (m, 10H), 1.23–1.10
(m, 1H), 1.03 (t, 3H, J = 7.3 Hz), 0.62 (s, 3H); 13C NMR
(50 MHz, CDCl3) d 165.9, 148.9, 143.6, 137.0, 128.5,
128.3, 127.9, 126.9, 126.5, 126.2, 126.1, 81.6, 81.4, 59.1,
51.3, 47.8, 38.6, 31.0, 27.0, 24.5, 22.6, 14.2, 12.1; HRMS
(EI): calcd for C27H32O3, 404.2351; found, 404.2357; Crys-
tal data for 1c at 25 °C: C27H32O3, M = 404.54, ortho-
1
for H NMR and chloroform-d (d 77.0) for 13C NMR.
Optical rotations were measured on a JASCO P-1010
polarimeter. EI mass spectra were recorded on Finnigan
TSQ-700 at an ionizing energy of 70 eV and HRMS spectra
were recorded on MAT-95XL HRMS. Routine monitoring
of reactions was performed using silica gel, glass-backed
TLC plates (Merck Kieselgel 60 F254) and visualized by
UV light (254 nm). Solutions were evaporated to dryness
under reduced pressure with a rotary evaporator and the
residue was purified by flash column chromatography on
silica gel (230–400 mesh) with the indicated eluents. Air
and/or moisture sensitive reactions were performed under
the usual inert atmosphere conditions.
˚
˚
rhombic, P212121, a = 6.931(4) A, b = 13.806(5) A, c =
3
˚
˚
23.533(5) A, V = 2252.0(15) A , Z = 4, Dc = 1.193 Mg/
m3, l = 0.08 mmÀ1, 2293 reflections, 272 parameters,
R = 0.050, Rw = 0.146.
4.2.4. Hex-2-enoic acid 1-(hydroxy-diphenyl-methyl)-7,7-
dimethyl-bicyclo[2.2.1]hept-2-yl ester 1d. Yield 88%; 1H
NMR (200 MHz, CDCl3) d 7.76–7.63 (m, 4H), 7.26–7.05
(m, 6H), 6.67 (dt, 1H, J = 15.6, 7.0 Hz), 5.54 (dt, 1H,
J = 15.6, 1.6 Hz), 5.20 (dd, 1H, J = 7.8, 3.8 Hz), 3.92 (s,
1H), 2.40–2.25 (m, 1H), 2.14–1.27 (m, 9H), 1.53 (s, 3H),
1.24–1.08 (m, 1H), 0.89 (t, 3H, J = 7.4 Hz), 0.62 (s, 3H);
13C NMR (50 MHz, CDCl3) d 171.0, 164.0, 149.3, 148.8,
143.4, 128.4, 127.8, 126.7, 126.4, 126.1, 126.0, 120.8, 81.2,
60.2, 59.0, 51.2, 47.6, 38.4, 33.9, 30.9, 26.9, 24.4, 22.5,
21.0, 20.8, 14.0, 13.3; HRMS (EI): calcd for C28H34O3,
418.2508; found, 418.2505.
Crystallographic data for the structures in this paper have
been deposited at the Cambridge Crystallographic Data
Center and allocated the deposit numbers CCDC
655358–655366.16
4.2. General procedure for the synthesis of compounds 1a–k
and 1n–o
Under an N2 atmosphere exo-10,10-diphenyl-2,10-cam-
phanediol (1.0 g, 3.1 mmol) and NaH (110 mg, 4.6 mmol)
in dry THF (30 mL) were stirred at 0 °C for 20 min. This
was added to acryloyl chloride (0.39 mL, 4.6 mmol) drop-
wise and continued stir for 30 min at 0 °C. The reaction
mixture was then quenched with water (75 mL) and
extracted with dichloromethane (3 Â 50 mL). The com-
4.2.5. 4-Methyl-pent-2-enoic acid 1-(hydroxy-diphenyl-
methyl)-7,7-dimethyl-bicyclo[2.2.1]hept-2-yl ester 1e. Yield
1
76%; H NMR (200 MHz, CDCl3) d 7.76–7.63 (m, 4H),

P.-W. Duan et al. / Tetrahedron: Asymmetry 19 (2008) 682–690
687
7.26–7.06 (m, 6H), 6.65 (dd, 1H, J = 15.7, 6.8 Hz), 5.47 (dd,
1H, J = 15.7, 1.3 Hz), 5.19 (dd, 1H, J = 7.9, 3.9 Hz), 3.92
(s, 1H), 2.06–1.46 (m, 6H), 1.54 (s, 3H), 1.31–0.85 (m,
2H), 1.01 (d, 6H, J = 6.8 Hz,), 0.63 (s, 3H); 13C NMR
(50 MHz, CDCl3) d 164.6, 155.8, 149.0, 143.5, 128.5,
127.9, 126.9, 126.5, 126.3, 126.1, 118.0, 81.5, 81.4, 59.2,
51.3, 47.8, 38.5, 31.0, 30.9, 27.0, 24.5, 22.6, 21.1, 21.0;
HRMS (EI): calcd for C28H34O3, 418.2508; found,
418.2517.
3.9 Hz), 4.04 (s, 1H), 2.40–2.26 (m, 1H), 1.92(3H, d,
J = 1.2 Hz), 1.82(d, 3H, J = 1.4 Hz), 2.06–1.46 (m, 4H),
1.52 (s, 3H), 1.27–0.85 (m, 2H), 0.60 (s, 3H); 13C NMR
(50 MHz, CDCl3) d 164.0, 157.5, 149.0, 143.6, 128.5,
127.8, 126.9, 126.3, 126.2, 115.2, 81.3, 80.5, 59.1, 51.2,
47.8, 38.6, 30.9, 27.1, 27.0, 24.5, 22.6, 20.0; HRMS (EI):
calcd for C27H32O3, 404.2351; found, 404.2356; Crystal
data for 1j at 25 °C: C27H32O3, M = 404.54, orthorhombic,
˚
˚
˚
P212121, a = 12.621(3) A, b = 17.873(6) A, c = 20.580(4) A,
3
˚
V = 4642.3(20) A ,
Z = 8,
Dc = 1.158 Mg/m3,
l =
4.2.6. 3-Phenyl-acrylic acid 1-(hydroxy-diphenyl-methyl)-
7,7-dimethyl-bicyclo[2.2.1]hept-2-yl ester 1f. Yield 80%;
1H NMR (200 MHz, CDCl3) d 7.80–7.64 (m, 4H), 7.50–
7.36 (m, 6H), 7.29–7.05 (m, 6H), 5.28 (dd, 1H, J = 7.7,
4.1 Hz), 3.96 (s, 1H), 2.43–2.29 (m, 1H), 2.10–1.50 (m,
5H), 1.58 (s, 3H), 1.26–0.85 (m, 2H), 0.65 (s, 3H); 13C
NMR (50 MHz, CDCl3) d 163.9, 149.2, 148.9, 144.6,
143.5, 143.3, 128.4, 127.9, 127.8, 126.8, 126.4, 126.1,
126.0, 125.9, 122.1, 81.6, 81.3, 59.0, 51.2, 47.6, 38.5, 38.3,
31.0, 30.9, 26.9, 24.4, 22.5, 22.4, 20.7, 17.7; HRMS (EI):
calcd for C31H32O3, 452.2351; found, 452.2362.
0.07 mmÀ1, 4521 reflections, 542 parameters, R = 0.042,
Rw = 0.093.
4.2.11. But-2-enoic acid 1-(methoxy-diphenyl-methyl)-7,7-
dimethyl-bicyclo[2.2.1]hept-2-yl ester 1k. Yield 58%; 1H
NMR (200 MHz, CDCl3) d 7.82–7.78 (m, 2H), 7.52–7.48
(m, 2H), 7.34–7.19 (m, 6H), 6.21–6.20 (m, 1H), 5.50 (d,
J = 1.6 Hz, 1H), 4.75 (dd, 1H, J = 7.7, 3.1 Hz), 2.80–2.67
(m, 4H), 1.85–1.39 (m, 6H), 1.27–1.23 (m, 4H), 0.95–0.77
(m, 4H); 13C NMR (50 MHz, CDCl3) d 165.0, 145.0,
140.0, 139.4, 131.6, 129.5, 127.3, 126.8, 126.7, 126.6,
122.8, 88.0, 80.1, 60.9, 60.2, 52.4, 50.4, 48.7, 39.2, 31.4,
25.2, 23.6, 23.0, 22.5, 17.7, 14.0, 13.9.
4.2.7. 2-Methyl-acrylic acid 1-(hydroxy-diphenyl-methyl)-
7,7-dimethyl-bicyclo[2.2.1]hept-2-yl ester 1g. Yield 83%;
1H NMR (200 MHz, CDCl3) d 7.76–7.60 (m, 4H), 7.27–
7.01 (m, 6H), 5.83 (d, 1H, J = 1.1 Hz), 5.46 (d, 1H,
J = 1.1Hz), 5.27 (dd, 1H, J = 8.0, 3.8 Hz), 3.83 (s, 1H),
2.41–2.27 (m, 1H), 2.08–1.49 (m, 5H), 1.77 (s, 3H), 1.54
(s, 3H), 1.26–1.11 (m, 1H), 0.64 (s, 3H); 13C NMR
(50 MHz, CDCl3) d 165.0, 148.9, 143.4, 136.1, 128.5,
127.9, 126.9, 126.5, 126.2, 126.1, 125.1, 81.8, 81.4, 59.2,
51.3, 47.7, 38.5, 31.0, 27.0, 24.4, 22.6, 18.3; HRMS (EI):
calcd for C26H30O3, 390.2195; found, 390.2197.
4.2.12.
4-Acryloyl-10,10-dimethyl-3-(toluene-4-sulfonyl)-
3,4-diaza-tricyclo[5.2.1.01,5]decan-2-one 1n. Yield 90%;
1H NMR (400 MHz, CDCl3) d 7.86 (br s, 2H), 7.37 (d,
2H, J = 8.2 Hz), 6.72 (br s, 1H), 6.47 (dd, 1H, J = 16.8,
1.4 Hz), 5.80 (dd, 1H, J = 11.7, 1.4 Hz), 3.60 (br s, 1H),
2.79 (d, 1H, J = 12.0 Hz), 2.47 (s, 3H), 1.93–1.60 (m, 5H),
1.17–1.12 (m, 1H), 1.03 (s, 6H), 0.63 (br s, 1H); 13C NMR
(100 MHz, CDCl3) d 177.0, 165.0, 146.3, 134.6, 130.0,
129.0, 127.7, 70.2, 60.1, 52.7, 47.4, 34.8, 28.9, 26.9, 21.8,
20.3, 19.9; HRMS (EI): calcd for C20H24N2O4S, 388.1458;
found, 388.1456. Crystal data for 1n at 25 °C: C20H24N2O4S,
4.2.8. 2-Methyl-but-2-enoic acid 1-(hydroxy-diphenyl-
methyl)-7,7-dimethyl-bicyclo[2.2.1]hept-2-yl ester 1h. Yield
˚
M = 388.47, monoclinic, P212121, a = 12.4010(7) A, b =
1
3
˚
˚
˚
57%; H NMR (200 MHz, CDCl3) d 7.75–7.60 (m, 4H),
6.6250(4) A, c = 23.8760(17) A, V = 1961.6(2) A , Z = 4,
Dc = 1.315 Mg/m3, l = 0.193 mmÀ1, 12,175 reflections,
245 parameters, R = 0.1886, Rw = 0.2369.
7.27–7.06 (m, 6H), 6.55 (m, 1H), 5.25 (dd, 1H, J = 8.0,
3.6 Hz), 3.96 (s, 1H), 2.40–2.26 (m, 1H), 2.07–1.42 (m,
11H),1.55 (s, 3H) 1.29–1.10 (m, 1H), 0.62 (s, 3H); 13C
NMR (50 MHz, CDCl3) d 165.8, 148.9, 143.5, 136.9,
128.5, 128.3, 127.8, 126.8, 126.4, 126.2, 126.1, 81.5, 81.4,
59.1, 51.2, 47.7, 38.6, 31.0, 27.0, 24.5, 22.6, 14.2, 12.1;
HRMS (EI): calcd for C27H32O3, 404.2351; found,
404.2375.
4.2.13. 4-Methylacryloyl-10,10-dimethyl-3-(toluene-4-sulf-
1o. Yield
onyl)-3,4-diaza-tricyclo[5.2.1.01,5]decan-2-one
1
80%; H NMR (400 MHz, CDCl3) d 7.86 (m, 2H), 7.37
(d, 2H J = 8.0 Hz), 7.02 (m, 1H), 6.42 (s, 1H), 3.58 (s,
1H), 2.78 (d, 1H, J = 9.0 Hz), 2.47 (s, 3H), 2.04–1.86 (m,
7H), 1.17 (s, 1H), 1.03 (s, 6H), 0.54 (s, 1H); 13C NMR
(100 MHz, CDCl3) d 177.0, 165.6, 146.1, 143.1, 134.6,
129.0, 128.9, 70.1, 122.1, 52.6, 47.3, 33.8, 28.8, 26.8, 21.7,
20.2, 19.9, 18.2; HRMS (EI): calcd for C21H26N2O4S,
402.1613; found, 402.1622.
4.2.9. 2-Methyl-pent-2-enoic acid 1-(hydroxy-diphenyl-
methyl)-7,7-dimethyl-bicyclo[2.2.1]hept-2-yl ester 1i. Yield
1
95%; H NMR (200 MHz, CDCl3) d 7.75–7.61 (m, 4H),
7.25–7.06 (m, 6H), 6.43 (m, 1H), 5.24 (dd, 1H, J = 7.9,
3.7 Hz), 3.92 (s, 1H), 2.40–2.25 (m, 1H), 2.18–1.78 (m,
5H), 1.75–1.20 (m, 8H), 1.17–1.09 (m, 1H), 1.00 (t, 3H,
J = 7.5 Hz,), 0.63 (s, 3H); 13C NMR (50 MHz, CDCl3) d
166.0, 148.9, 143.8, 143.5, 128.4, 127.8, 126.8, 126.6,
126.4, 126.2, 126.0, 81.5, 81.3, 59.1, 51.2, 47.7, 38.5, 31.0,
26.9, 24.5, 22.5, 21.7, 12.8, 12.2; HRMS (EI): calcd for
C28H34O3 418.2508; found, 418.2489.
4.3. Typical procedure for the synthesis of N-
phthalimidoaziridines 2 and 3
To a solution of exo-10,10-diphenyl-2,10-camphanediol
derived acrylate 1a (0.20 g, 0.53 mmol) and N-amino-
phthalimide (0.12 g, 0.80 mmol) in dry THF (5.0 mL) was
added lead tetraacetate (0.38 g, 0.85 mmol) in one portion
under an N2 atmosphere at 0 °C. The mixture was allowed
to stir for 15 min and then quenched with water (25 mL)
and extracted with dichloromethane (3 Â 25 mL). The
organic layers were separated and washed with brine, dried
4.2.10. 3-Methyl-but-2-enoic acid 1-(hydroxy-diphenyl-
methyl)-7,7-dimethyl-bicyclo[2.2.1]hept-2-yl ester 1j. Yield
1
82%; H NMR (200 MHz, CDCl3) d 7.77–7.63 (m, 4H),
7.27–7.06 (m, 6H), 5.38 (m, 1H), 5.14 (1H, dd, J = 7.9,

688
P.-W. Duan et al. / Tetrahedron: Asymmetry 19 (2008) 682–690
over MgSO4, and concentrated in vacuo to give the crude
products. Purification by flash column chromatography
eluted with hexanes/ethyl acetate = 4:1 yielded the desired
aziridines 2a and 3a (0.26 g; 90%, ratio of diastereomers
94:06) as a white solid.
1H), 2.71 (d, 1H, J = 4.6 Hz), 2.34–2.20 (m, 1H), 1.97–
1.41 (m, 11H), 1.17–0.64 (m, 5H), 0.68 (s, 3H); 13C NMR
(50 MHz, CDCl3) d 164.8, 164.4, 149.3, 143.2, 134.3,
134.0, 130.2, 128.6, 128.5, 128.0, 126.9, 126.8, 126.5,
126.3, 125.9, 123.3, 122.9, 82.9, 81.4, 59.2, 51.5, 48.6,
47.7, 44.0, 37.2, 33.0, 31.2, 26.9, 24.5, 22.5, 19.4, 13.9;
HRMS (EI): calcd for C36H38N2O5 578.2781. Found
578.2795. Anal. Calcd for C36H38N2O5: C, 74.72; H, 6.62;
N, 4.84. Found: C, 74.74; H, 6.40; N, 4.63; Crystal data
for 2d at 25 °C: C36H38N2O5, M = 578.70, orthorhombic,
4.3.1. 1-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-aziridine-(2R)-
carboxylic acid 1-(hydroxy-diphenyl-methyl)-7,7-dimethyl-
bicyclo[2.2.1]hept-2-yl ester 2a. 1H NMR (200 MHz,
CDCl3) d 8.00–7.51 (m, 8H), 7.32–7.08 (m, 6H), 5.28 (dd,
1H, J = 8.4, 3.8 Hz), 4.01 (s, 1H), 2.91 (dd, 1H, J = 7.8,
5.4 Hz), 2.62 (dd, 1H, J = 7.8, 1.8 Hz), 2.48 (dd, 1H,
J = 5.4, 1.8 Hz), 2.39–2.21 (m, 1H), 2.02–1.51 (m, 8H),
1.29–0.85 (m, 1H), 0.66 (s, 3H); 13C NMR (50 MHz,
CDCl3) d 165.6, 164.3, 148.9, 143.5, 134.4, 134.3, 134.0,
130.0, 128.6, 128.4, 128.1, 128.0, 126.9, 126.8, 126.5,
126.2, 125.9, 123.6, 123.4, 123.0, 82.7, 60.3, 59.1, 51.5,
51.3, 47.7, 39.5, 38.3, 36.5, 31.0, 26.9, 24.4, 22.5, 22.4,
20.9, 14.1; HRMS (EI): calcd for C33H32N2O5, 536.2311;
found, 536.2308.
˚
˚
P212121,
a = 10.8763(20) A,
b = 14.442(4) A,
c =
3
˚
˚
19.914(6) A, V = 3127.9(14) A , Z = 4, Dc = 1.229 Mg/
m3, l = 0.08 mmÀ1, 3085 reflections, 389 parameters,
R = 0.044, Rw = 0.064.
4.3.5.
1-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-(3S)-iso-
propyl-aziridine-(2R)-carboxylic acid 1-(hydroxy-diphenyl-
methyl)-7,7-dimethyl-bicyclo[2.2.1]hept-2-yl ester 2e. 1H
NMR (200 MHz, CDCl3) d 7.78–7.55 (m, 8H), 7.26–7.07
(m, 6H), 5.09 (dd, 1H, J = 8.1, 3.5 Hz), 3.77 (s, 1H), 2.97
(dd, 1H, J = 7.8, 5 Hz), 2.78 (d, 1H, J = 5.0 Hz), 2.35–
2.21 (m, 1H), 2.01–1.50 (m, 7H), 1.28–0.84 (m, 9H), 0.66
(s, 3H); 13C NMR (50 MHz, CDCl3) d 164.8, 164.4,
149.2, 143.2, 133.9, 130.2, 128.5, 128.1, 126.9, 126.4,
126.3, 125.8, 122.8, 83.1, 81.3, 59.0, 54.0, 51.5, 47.7, 43.4,
37.2, 31.1, 30.0, 26.9, 24.5, 22.5, 19.6, 18.7; HRMS (EI):
calcd for C36H38N2O5, 578.2781; found, 578.2791. Anal.
Calcd for C36H38N2O5: C, 74.72; H, 6.62; N, 4.84. Found:
C, 74.50; H, 6.61; N, 4.70; Crystal data for 2e at 25 °C:
C36H38N2O5, M = 578.70, orthorhombic, P212121, a =
4.3.2. 1-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-(3S)-methyl-
aziridine-(2R)-carboxylic acid 1-(hydroxy-diphenyl-methyl)-
7,7-dimethyl-bicyclo[2.2.1]hept-2-yl ester 2b. 1H NMR
(200 MHz, CDCl3) d 7.84–7.59 (m, 8H), 7.28–7.10 (m,
6H), 5.34–5.08 (dd, 1H, J = 8.0, 3.6 Hz), 3.62 (s, 1H),
3.12 (d, 1H, J = 5.2 Hz), 2.88 (m, 1H), 2.67 (d, 1H,
J = 4.8 Hz), 2.60 (m, 1H), 2.39–2.18 (m, 1H), 2.01–1.53
(m, 7H), 1.42–0.86 (m, 7H), 0.70–0.59 (m, 3H); 13C
NMR (50 MHz, CDCl3) d 165.7, 165.4, 164.7, 164.4,
149.3, 143.7, 143.1, 134.3, 133.9, 130.4, 130.3, 128.6,
128.5, 128.0, 126.9, 126.8, 126.5, 126.3, 126.1, 125.9,
123.3, 122.9, 82.7, 82.3, 81.3, 81.2, 59.3, 59.1, 51.5, 51.4,
47.7, 44.8, 44.1, 43.1, 38.3, 37.2, 31.3, 31.1, 26.9, 24.6,
22.5, 22.4, 16.0, 12.2; HRMS (EI): calcd for C34H34N2O5,
550.2468; found, 550.2477; Crystal data for 2b at 25 °C:
C34H34N2O5, M = 550.65, monoclinic, P212121, a =
˚
˚
˚
8.745(4) A,
b = 24.056(7) A,
c = 14.938(4) A,
V =
3
3
À1
˚
3093.6(18) A , Z = 4, Dc = 1.243 Mg/m , l = 0.08 mm
5802 reflections, 775 parameters, R = 0.044, Rw = 0.076.
,
4.3.6. 1-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-(3S)-phenyl-
aziridine-(2R)-carboxylic acid 1-(hydroxy-diphenyl-methyl)-
7,7-dimethyl-bicyclo[2.2.1]hept-2-yl ester 2f. 1H NMR
(200 MHz, CDCl3) d 7.85–7.59 (m, 8H), 7.55–7.32 (m,
4H), 7.24–7.03 (m, 7H), 5.15 (dd, 1H, J = 8.2, 3.4 Hz),
3.91 (d, 1H, J = 5.2 Hz), 3.61 (s, 1H), (3.17, 1H, d,
J = 5.2 Hz), 2.32–2.19 (m, 1H), 2.03–1.55 (m, 8H), 1.28–
0.87 (m, 1H), 0.70 (s, 3H); 13C NMR (50 MHz, CDCl3) d
164.6, 163.8, 149.1, 143.0, 134.2, 134.1, 130.3, 129.6,
128.8, 128.6, 128.4, 128.1, 127.4, 127.0, 126.8, 126.5,
126.3, 126.0, 125.8, 123.1, 83.1, 81.3, 59.4, 51.5, 49.7,
47.8, 45.8, 37.3, 31.5, 31.3, 29.0, 26.9, 24.6, 22.6, 22.4,
14.0, 11.3; HRMS (EI): calcd for C39H36N2O5, 612.2624;
found, 612.2622; Crystal data for 2f at 25 °C:
C29H36N2O5, M = 612.72, orthorhombic, P212121,
˚
˚
˚
13.1296(18) A, b = 14.529(9) A, c = 15.1369(12) A, V =
3
3
À1
˚
2881.3(18) A , Z = 4, Dc = 1.269 Mg/m , l = 0.09 mm
5472 reflections, 738 parameters, R=0.061, Rw = 0.118.
,
4.3.3.
1-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-(3S)-ethyl-
aziridine-(2R)-carboxylic acid 1-(hydroxy-diphenyl-methyl)-
7,7-dimethyl-bicyclo[2.2.1]hept-2-yl ester 2c. 1H NMR
(200 MHz, CDCl3) d 7.84–7.59 (m, 8H), 7.27–7.10 (m,
6H), 5.13–5.07 (dd, 1H, J = 8.1, 3.5 Hz), 3.68 (s, 1H),
2.96 (m, 1H), 2.73 (d, 1H, J = 4.8 Hz), 2.34–2.16 (m,
1H), 1.98–1.42 (m, 9H), 1.29–0.83 (m, 5H), 0.79–0.65 (m,
3H); 13C NMR (50 MHz, CDCl3) d 164.8, 164.4, 149.3,
143.1, 134.3, 133.9, 130.3, 130.2, 128.6, 128.4, 128.0,
126.9, 126.8, 126.4, 126.3, 126.1, 125.8, 123.3, 122.9, 82.8,
81.3, 59.1, 51.5, 49.9, 47.7, 43.7, 37.2, 31.2, 26.9, 24.5,
24.0, 22.5, 22.4, 11.3, 10.2; HRMS (EI): calcd for
C35H36N2O5, 564.2624; found, 564.2636; Anal. Calcd for
C35H36N2O5: C, 74.45; H, 6.43; N, 4.96. Found: C, 74.78;
H, 6.33; N, 4.67.
˚
˚
˚
a = 13.206(3) A, b = 17.93(1) A, c = 30.597(7) A, V =
3
7246(5) A , Z = 8, Dc = 1.123 Mg/m3, l = 0.07 mmÀ1
,
˚
6994 reflections, 830 parameters, R = 0.138, Rw = 0.194.
4.3.7. 1-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-2-methyl-azi-
ridine-(2R)-carboxylic acid 1-(hydroxy-diphenyl-methyl)-
7,7-dimethyl-bicyclo[2.2.1]hept-2-yl ester 2g. 1H NMR
(200 MHz, CDCl3) d 7.85–7.60 (m, 8H), 7.38–7.12 (m,
6H), 5.30–5.14 (dd, 1H, J = 8.2, 3.5 Hz), 4.23 (s, 1H),
3.66 (s, 1H), 2.97 (d, 1H, J = 1.8 Hz), 2.82 (s, 1H), 2.47
(d, 1H, J = 1.8 Hz), 2.39–2.20 (m, 1H), 2.00–1.53 (m,
10H), 1.34–0.62 (m, 3H); 13C NMR (50 MHz, CDCl3) d
167.8, 165.7, 165.4, 164.7, 149.1, 148.6, 143.8, 143.2,
4.3.4. 1-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-(3S)-propyl-
aziridine-(2R)-carboxylic acid 1-(hydroxy-diphenyl-methyl)-
7,7-dimethyl-bicyclo[2.2.1]hept-2-yl ester 2d. 1H NMR
(200 MHz, CDCl3) d 7.84–7.60 (m, 8H), 7.27–7.09 (m,
6H), 5.11 (dd, 1H, J = 8.0, 3.6 Hz), 3.68 (s, 1H), 2.99 (m,

P.-W. Duan et al. / Tetrahedron: Asymmetry 19 (2008) 682–690
689
134.3, 133.9, 130.4, 130.3, 128.7, 128.5, 128.1, 128.0, 126.9,
126.8, 126.6, 126.6, 126.3, 126.0, 123.3, 122.9, 83.2, 82.6,
81.5, 81.3, 59.2, 59.0, 51.6, 51.2, 47.7, 44.4, 43.8, 43.6,
41.7, 38.5, 37.0, 31.3, 30.9, 27.0, 24.4, 24.3, 22.7, 22.5,
18.5, 13.4; HRMS (EI): calcd for C34H34N2O5, 550.2468;
found, 550.2451; Anal. Calcd for C34H34N2O5: C, 74.16;
H, 6.22; N, 5.09. Found: C, 73.95; H, 6.08; N, 4.93.
6H), 4.77 (dd, 1H, J = 7.9, 3.5 Hz), 3.21–2.61 (m, 2H),
2.82 (s, 3H), 2.48 (d, J = 5.0 Hz, 1H), 1.88–1.22 (m, 4H),
1.49 (d, 3H, J = 5.4 Hz), 1.14–0.66 (m, 2H), 1.14 (s, 3H),
0.82 (s, 3H); 13C NMR (50 MHz, CDCl3) d 165.2, 164.8,
140.5, 138.9, 133.9, 131.5, 130.3, 129.7, 129.5, 128.4,
127.4, 127.0, 126.8, 123.3, 122.9, 117.9, 87.6, 81.6, 61.2,
52.3, 49.9, 49.2, 45.1, 44.4, 37.8, 31.5, 25.5, 23.6, 22.6,
16.3, 14.0.
4.3.8.
1-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-(2R,3S)-di-
methyl-aziridine-2-carboxylic acid 1-(hydroxy-diphenyl-
methyl)-7,7-dimethyl-bicyclo[2.2.1]hept-2-yl ester 2h. 1H
NMR (200 MHz, CDCl3) d 7.76–7.58 (m, 8H), 7.27–7.09
(m, 6H), 5.17 (dd, 1H, J = 8.1, 3.5 Hz), 3.62 (s, 1H), 3.04
(qd, 1H, J = 5.8, 0.8 Hz), 2.32–2.17 (m, 1H), 1.93–1.84
(m, 4H), 1.70–1.51 (m, 7H), 1.37–1.29 (d, 3H,
J = 5.8 Hz), 1.16–0.85 (m, 1H), 0.71 (s, 3H); 13C NMR
(50 MHz, CDCl3) d 166.2, 164.7, 149.1, 143.1, 134.2,
133.8, 130.5, 128.5, 127.9, 126.9, 126.5, 126.3, 126.0,
123.2, 122.8, 82.7, 81.4, 60.3, 59.2, 51.5, 51.1, 49.5, 47.9,
47.7, 37.0, 31.4, 27.0, 24.5, 22.4, 21.0, 14.0, 12.24; HRMS
(EI): calcd for C35H36N2O5, 564.2624; found, 564.2622.
Anal. Calcd for C35H36N2O5: C, 74.45; H, 6.43; N, 4.96.
Found: C, 74.18; H, 6.21; N, 4.84; Crystal data for 2h at
25 °C: C35H36N2O5, M = 564.67, orthorhombic, P212121,
4.3.12. 2-{2-[10,10-Dimethyl-2-oxo-3-(toluene-4-sulfonyl)-3,
4-diaza-tricyclo[5.2.1.01,5]decane-4-carbonyl]-(2R)-aziridin-
1-yl}-isoindole-1,3-dione 2n. 1H NMR (400 MHz, CDCl3)
d 7.82 (br s, 2H), 7.78 (dd, 2H, J = 8.0, 3.0 Hz), 7.70 (dd,
2H, J = 8.0, 3.0 Hz), 7.37 (d, 2H, J = 8.1 Hz), 3.71 (br s,
1H), 3.56 (br s, 1H), 3.02 (br s, 1H), 2.96 (d, 2H, J =
6.6 Hz), 2.48 (s, 3H), 1.97–1.88 (m, 4H), 1.42 (s, 3H),
1.15 (br s, 1H), 1.09 (s, 3H), 0.42 (br s, 1H); 13C NMR
(125 MHz, CDCl3) d 177.4, 166.7, 164.3, 146.9, 134.2,
130.3, 130.1, 129.1, 123.2, 71.0, 60.2, 53.0, 47.5, 40.3,
38.5, 34.0, 29.2, 27.0, 21.8, 20.7, 20.4; HRMS (EI): calcd
for C28H28N4O6S, 548.1724; found, 548.1721. Crystal data
for 2n at 25 °C: C28H28N4O6S, M = 548.60, ortho-
˚
˚
rhombic, P212121, a = 6.7301(2) A, b = 14.1264(4) A, c =
3
˚
˚
27.8317(9) A, V = 2640.02(14) A , Z = 4, Dc = 1.377
Mg/m3, l = 0.173 mmÀ1, 10,184 reflections, 353 para-
meters, R = 0.0934, Rw = 0.1526.
˚
˚
˚
a = 6.842(6) A, b = 16.215(3) A, c = 25.986(5) A, V =
3
2883(3) A , Z = 4, Dc = 1.301 Mg/m3, l = 0.09 mmÀ1
,
˚
2897 reflections, 380 parameters, R = 0.055, Rw=0.097.
4.3.13. 2-{2-[10,10-Dimethyl-2-oxo-3-(toluene-4-sulfonyl)-
3,4-diaza-tricyclo[5.2.1.01,5]decane-4-carbonyl]-(3S)-methyl-
2R-aziridin-1-yl}-isoindole-1,3-dione 2o. Inseperable N-
invertomer mixture of diastereomers were obtained. Se-
lected peaks were shown.1 H NMR (400 MHz, CDCl3) d
7.66–7.63 (m, 2H), 7.38 (br s, 1H), 7.27(s, 1H), 3.64 (s,
1H), 3.61 (qd, 1H, J = 5.6, 5.6 Hz), 3.55 (br s, 1H), 3.29
(br s, 1H), 3.06 (qd, 1H, J = 5.6 5.6 Hz), 2.98 (d, 1H,
J = 13.5 Hz), 1.08 (s, 6H); 13C NMR(100 MHz, CDCl3) d
167.0, 166.4, 165.3, 146.7, 134.5, 134.2, 134.1, 134.0,
133.7, 130.4, 130.2, 129.1, 129.0, 123.4, 123.1, 122.8, 71.0,
67.1, 60.1, 53.0, 47.5, 47.3, 45.6, 45.2, 44.2, 34.0, 29.7,
29.2, 28.8, 27.0; MS (EI) (%): calcd for C29H30N4O6S,
562.1886; found, 562.4 (5), 406.9 (20), 379.0 (30), 260.2
(50), 247.0 (60), 229.0 (100), 201.2 (75), 155.1 (65).
4.3.9.
1-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-(3S)-ethyl-
(2R)-methyl-aziridine-2-carboxylic acid 1-(hydroxy-diphen-
yl-methyl)-7,7-dimethyl-bicyclo[2.2.1]hept-2-yl ester 2i. 1H
NMR (200 MHz, CDCl3) d 7.76–7.58 (m, 8H), 7.26–7.07
(m, 6H), 5.16 (dd, 1H, J = 8.1, 3.5 Hz), 3.68 (s, 1H), 3.06
(t, 1H, J = 7.1 Hz), 2.32–2.18 (m, 1H), 1.99–1.81 (m, 2H),
1.77–1.33 (m, 12H), 1.08–1.01(m, 3H), 0.69 (s, 3H); 13C
NMR (50 MHz, CDCl3) d 166.2, 164.7, 149.2, 143.2,
133.8, 130.4, 128.5, 128.0, 126.9, 126.4, 126.3, 125.9,
122.7, 82.9, 81.4, 60.3, 59.1, 54.9, 51.5, 48.0, 47.7, 36.9,
31.3, 27.0, 24.4, 22.5, 20.9, 14.1, 13.9, 10.9; HRMS (EI):
calcd for C36H38N2O5, 578.2781; found, 578.2764. Anal.
Calcd for C36H38N2O5: C, 74.72; H, 6.62; N, 4.84. Found:
C, 74.66; H, 6.62; N, 4.65.
4.3.10.
1-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-3,3-di-
methyl-aziridine-2S-carboxylic acid 1-(hydroxy-diphenyl-
methyl)-7,7-dimethyl-bicyclo[2.2.1]hept-2-yl ester 2j. 1H
NMR (200 MHz, CDCl3) d 7.90–7.58 (m, 8H), 7.30–7.08
(m, 6H), 5.34–5.28 (dd, 1H, J = 7.6, 3.9 Hz), 3.98 (s, 1H),
3.17 (s, 1H), 2.39–2.25 (m, 1H), 2.12–1.93 (m, 1H), 1.72–
1.40 (m, 3H), 1.60 (s, 3H), 1.26–0.88 (m, 2H), 1.29 (s,
3H), 1.10 (s, 3H), 0.64 (s, 3H); 13C NMR (50 MHz, CDCl3)
d 165.3, 165.3, 149.6, 143.7, 134.2, 130.5, 128.5, 128.0,
126.8, 126.5, 126.2, 123.2, 83.0, 81.3, 58.9, 51.5, 49.7,
49.4, 47.7, 38.8, 31.1, 26.9, 24.6, 22.6, 19.8, 18.5; HRMS
(EI): calcd for C35H36N2O5, 564.2624; found, 564.2634.
Anal. Calcd for C35H36N2O5: C, 74.45; H, 6.43; N, 4.96.
Found: C, 74.18; H, 6.29; N, 4.92.
4.3.14.
1-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-aziridine-
(2R)-carboxylic acid methyl ester 4a. To a solution of 2a
(0.10 g, 0.19 mmol) in MeOH (2.0 mL), was added sodium
methoxide (40 mg, 0.74 mmol) in one portion at ambient
temperature. The reaction was quenched with water
(25 mL) after 3 h and extracted with EtOAc (3 Â 25 mL).
The combined organic layers were washed with brine, dried
over MgSO4, and concentrated. The crude product was
purified further by flash column chromatography using
hexanes/ethyl acetate = 6:1 as a eluent to afford pure prod-
uct 4a (30 mg, 67%) and the auxiliary A was recovered with
1
85% yield. Compound 4a: [a]D = +109.5 (c 1, CHCl3); H
NMR (200 MHz, CDCl3) d 7.78–7.66 (m, 4H), 3.81 (s,
3H), 3.17 (dd, 1H, J = 7.6, 5.8 Hz), 2.82 (dd, 1H, J = 7.6,
1.6 Hz), 2.84 (dd, 1H, J = 5.8, 1.6 Hz); 13C NMR
(50 MHz, CDCl3) d 168.5, 164.5, 134.3, 129.9, 123.3,
52.7, 39.7, 36.4; HRMS (EI): calcd for C12H10N2O4,
246.0624; found, 246.0641.
4.3.11. 1-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-(3S)-methyl-
aziridine-(2R)-carboxylic acid 1-(methoxy-diphenyl-methyl)-
7,7-dimethyl-bicyclo[2.2.1]hept-2-yl ester 2k. 1H NMR
(200 MHz, CDCl3) d 8.02–7.42 (m, 8H), 7.38–7.14 (m,

690
P.-W. Duan et al. / Tetrahedron: Asymmetry 19 (2008) 682–690
M. Tetrahedron Lett. 2004, 45, 8987; (g) Calhorda, M. J.;
Acknowledgments
Vaz, P. D. Chemtracts-Inorg. Chem. 2004, 17, 396; (h) Muller,
P.; Fruit, C. Chem. Rev. 2003, 103, 2905; (i) Fioravanti, S.;
Morreale, A.; Pellacani, L.; Tardella, P. A. J. Org. Chem.
2002, 67, 4972; (j) Gillespie, K. M.; Sanders, C. J.; Shaugh-
nessy, P. O.; Westmoreland, I.; Thickitt, C. P.; Scott, P. J.
Org. Chem. 2002, 67, 3450; (k) Nishimura, M.; Minakata, S.;
Takahashi, T.; Oderaotoshi, Y.; Komatsu, M. J. Org. Chem.
2002, 67, 2101; (l) Aggarwal, V. K.; Alonso, E.; Ferrara, M.;
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This work was supported by the National Science Council
of the Republic of China (NSC 96-2113-M-003-005-MY3)
and the National Taiwan Normal University (96TOP001).
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