Ligand and substrate π-stacking interaction controlled enantioselectivity in the asymmetric aziridination

Article abstract of DOI:10.1016/j.tetasy.2007.03.032

Both the steric hindrance and the electronic effect are important factors for controlling the enantioselectivity in asymmetric catalysis. The substituent-dependent enantioselectivity in the asymmetric aziridination of chalcones catalyzed by 1,8-anthracene

Full text of DOI:10.1016/j.tetasy.2007.03.032

Tetrahedron: Asymmetry 18 (2007) 878–884
Ligand and substrate p-stacking interaction controlled
enantioselectivity in the asymmetric aziridination
Linge Ma, Peng Jiao, Qihan Zhang, Da-Ming Du and Jiaxi Xu*
Beijing National Laboratory for Molecular Sciences (BNLMS), Key Laboratory of Bioorganic Chemistry and Molecular Engineering of
Ministry of Education, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, People’s Republic of China
Received 2 March 2007; accepted 30 March 2007
Abstract—Both the steric hindrance and the electronic effect are important factors for controlling the enantioselectivity in asymmetric
catalysis. The substituent-dependent enantioselectivity in the asymmetric aziridination of chalcones catalyzed by 1,8-anthracene-linked
bis-oxazoline (AnBOX) was rationalized to the p-stacking interaction between the ligand backbone and substrates and primarily con-
firmed by the use of bulky substrates and catalysts without aromatic backbones. The results provide important information for designing
novel ligands and for understanding the influence of the electronic effect in asymmetric catalysis.
ꢀ
2007 Elsevier Ltd. All rights reserved.
1
. Introduction
tallic reactions involving aromatic substrates and ligands
with aryl substituents after their theoretical investigation
on the platinum-catalyzed asymmetric hydroformylation
Interactions between aromatic rings or other unsaturated
systems, including p-stacking and face-to-edge complexes,
are at the origin of many phenomena in both organic
and biological chemistry. It is well known that the interac-
tions play an important role in the stabilization of the ste-
9
of olefins. Sharpless et al. reported the first example on
the influence of the ligand–substrate p-stacking interaction
1
0
in the asymmetric dihydroxylation of olefins. Jacobsen
et al. elucidated the enantiofacial selective binding of
prochiral styrenes to a chiral catalyst via simultaneous
face-to-face and edge-to-face aromatic interactions in the
1
reo-structure of DNA and the tertiary structure of many
2
proteins. The stability and macroscopic properties of
many liquid crystal phases have been proven to originate
from an aromatic p-stacking interaction. Over the last
C -symmetric 1,2-diimine-copper complex catalyzed aziri-
2
3
dination and cyclopropanation. However, no influence of
the electronic effect of substrates on the enantioselectivity
two decades, it has been found that the p-stacking interac-
tions are key factors in the chiral recognition. The arene–
arene p-stacking interactions are very important in inclu-
sion complexes, such as cyclophanes and molecular clefts.4
Some of chromatographic chiral stationary phases were de-
signed and prepared on the basis of the aromatic p-stacking
1
1
existed in their system. Recently Brandt and Andersson
et al. observed that the achiral coligand–substrate aromatic
p-stacking interaction plays an important role in the enan-
tioselective Ru(arene)(amino alcohol)-catalyzed transfer
hydrogenation of ketones with an obvious influence of
the electronic effect of substrates on the enantioselectiv-
5
interaction. It is also well documented that p-stacking
1
2
interactions play a crucial role in some asymmetric
ity. They concluded that the electrostatic effects are of
importance for aromatic p-stacking interaction. These re-
sults clearly indicate that the ligand–substrate attractive
aromatic p-stacking interaction can generally reduce con-
formational degrees of freedom and enhance chiral dis-
crimination in the selectivity-determining transition state.
To the best of our knowledge, although many examples
on the aromatic p-stacking interaction on the diastereo-
selectivity in the asymmetric synthesis with aromatic chiral
6
inductions. Some chiral auxiliaries, such as Corey’s
7
8
-phenylmenthol and Evans’ oxazolidinone-based chiral
8
auxiliaries, show excellent asymmetric induction due to
intramolecular aromatic p-stacking interactions between
the auxiliaries and the substrates. Rappe et al. first pro-
posed the p-stacking interaction as a factor in organome-
6
*
Corresponding author. Tel.: +86 10 52751497; fax: +86 10 62751708;
e-mail: jxxu@pku.edu.cn
auxiliaries were reported, only a few examples have
been observed on the obvious effect of the ligand–substrate
0957-4166/$ - see front matter ꢀ 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2007.03.032

L. Ma et al. / Tetrahedron: Asymmetry 18 (2007) 878–884
879
aromatic p-stacking interaction on the enantioselectivity in
asymmetric catalysis.
that the coordination step is an enantioselectivity-deter-
1
0–12
13b,14
mining step in the catalytic cycle.
However, after con-
ducting cyclohexane-linked bis-oxazoline (cHBOXes)
1
5
catalyzed asymmetric aziridination of chalcones, we
found that cHBOXes did not show obvious substrate-
dependent enantioselectivity. This suggests that the elec-
tronic effect-dependent enantioselectivity of AnBOX could
not be simply attributed to the Lewis basicity of the car-
bonyl group in chalcones (Scheme 1).
2
. Results and discussion
We recently observed that the 1,8-anthracene-linked bis-
oxazoline (AnBOX) ligand shows obvious substituent-
dependent enantioselectivity in the asymmetric aziridin-
ation of chalcones (Table 1, entries 1–6).13 Electron-rich
chalcones show higher enantioselectivities than electron-
deficient ones. It seemed that the electronic effect-depen-
dent enantioselectivity was related to the Lewis basicity
of the oxygen atom of the carbonyl group in chalcones.
The oxygen atom of electron-rich chalcones showed a
stronger Lewis basicity to facilitate a stronger coordination
with the catalyst, resulting in higher enantioselectivity be-
cause the stronger coordination would preferentially allow
the reaction to proceed via the asymmetric catalytic path,
as observed in the asymmetric borane reduction of ketones
To further study this phenomenon, we conducted the
asymmetric aziridination of chalcones with Evans’ ligand
1
6
(BOX). These results indicate that no obvious influence
of the electronic effect of substrates on the enantioselectiv-
ity was observed when under the catalysis of cHBOX
1
5
(Table 1, entries 8–13). This caused us to assume that
the AnBOX ligand shows obvious substrate electronic
effect-dependent enantioselectivity possibly due to the
ligand–substrate aromatic p-stacking interaction because
the AnBOX ligand possesses an aromatic anthracene back-
bone, which locates in an appropriate position to form
the p-stacking interaction with chalcones in our proposed
1
4
catalyzed by chiral boroxazolidines. The substrate elec-
tronic effect-dependent enantioselectivity also indicated
Table 1. Catalytic asymmetric aziridination of a,b-unsaturated ketones
Ts
O
O
5
mol% CuOTf
N
R2
6 mol% Ligand
*
R2
+
PhI=NTs
*
R1
CH2Cl2
R1
1
2
1
2
a
b
c
Entry
Ligand
Product
R
R
Yield (%)
ee (%)
Configuration
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
AnBOX
AnBOX
AnBOX
AnBOX
AnBOX
AnBOX
S-cBOX
BOX
BOX
BOX
BOX
BOX
BOX
AnBOX
BOX
S-cHBOX
AnBOX
BOX
S-cHBOX
AnBOX
BOX
S-cHBOX
AnBOX
BOX
S-cHBOX
AnBOX
BOX
2a
2b
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
Me
Me
Me
H
H
H
H
H
H
4-MeC
Ph
4-FC H
6 4
6
H
4
92
80
72
74
64
70
56
24
38
10
10
12
4
>99
96
54
58
50
44
85
85
86
86
81
84
65
66
76
85
70
87
98
71
81
89
20
30
48
(2S,3R)
(2S,3R)
(2S,3R)
(2S,3R)
(2S,3R)
2c
2d
6 4
4-ClC H
2e
2f
4-BrC
6
H
4
d
4-CF
4-CF
3
C
C
6
H
H
4
4
(2S,3R)
(2R,3S)
d
ent-2f
ent-2a
ent-2b
ent-2c
ent-2d
ent-2e
ent-2f
2g
3
6
4-MeC
Ph
6
H
4
(2R,3S)
(2R,3S)
(2R,3S)
(2R,3S)
(2R,3S)
(2R,3S)
(2S,3R)
(2R,3S)
(2R,3S)
(2S,3R)
(2R,3S)
(2R,3S)
(2S,3R)
(2R,3S)
(2R,3S)
(2S,3R)
(2R,3S)
(2S,3R)
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
4-FC
4-ClC
4-BrC
4-CF
6 4
H
6 4
H
6
H
4
3
C
6
H
4
i
d
4- PrC
6
6
6
H
4
H
4
H
4
72
6
i
d
ent-2g
ent-2g
2h
4- PrC
i
d
4- PrC
24
79
10
43
86
7
53
54
9
t
d
4- BuC
6
H
4
t
d
ent-2h
ent-2h
2i
4- BuC
6
H
6
H
6
H
6
H
6
H
4
4
4
4
4
t
d
4- BuC
t
d
4- BuC
t
d
ent-2i
ent-2i
2j
4- BuC
t
d
4- BuC
d
trans-4-Pr-cC
trans-4-Pr-cC
trans-4-Pr-cC
Me
Me
Me
6
6
6
H
10
H
10
H
10
d
ent-2j
2j
2k
d
9
c
65
15
37
50
85
0
(2S,3R)
(2R,3S)
ent-2k
rac-2k
S-cHBOX
a
b
c
Isolated yields after the silica gel column chromatography.
Determined by HPLC analysis with chiral column (4.6 · 250 mm, Chiralpak).
Determined by comparing the measured specific rotation with the reported one.
Determined tentatively on the basis of the same mechanism and transition state.
13,15
d

880
L. Ma et al. / Tetrahedron: Asymmetry 18 (2007) 878–884
cate that the p-stacking interaction is
a complex
interaction, including charge transfer (also called p-acid/
base), van der Vaals (dispersive), and polar electrostatic
(Coulombic) components. The AnBOX ligand shows
O
O
O
O
18
O
N
N
O
N
N
N
N
higher enantioselectivity with electron-rich chalcones than
Pri Pri
AnBOX
Ph
Ph
Ph Ph
(S)-cHBOX
13
with electron-deficient chalcones. It seems reasonable to
BOX
consider the anthracene ring in AnBOX as a relatively elec-
tron-deficient aromatic system as it possesses two electron-
withdrawing oxazolin-2-yl groups. The substituent-depen-
dent enantioselectivity could be rationalized to the stabil-
ization generated from the charge-transfer complexation
between the ligand–substrate aromatic p-stacking interac-
tion in the transition state. Electron-rich chalcones show
more obvious charge-transfer complexation with the ligand
than electron-deficient ones. Thus, their ligand–substrate
aromatic p-stacking interaction in the transition state is
more stable than that between the anthracene ring and elec-
tron-deficient chalcones. These can reduce the conforma-
tional degrees of freedom and enhance the chiral
discrimination in the selectivity-determining transition
state via the ligand–substrate attractive aromatic p-stack-
ing interaction.
Scheme 1. The structures of AnBOX, BOX, and S-cHBOX ligands.
transition state in the catalytic asymmetric aziridination
1
3
(
Fig. 1).
R
O
N
O
R
N
Cu
S
N
O
O
R
O
Figure 1. p-Stacking interaction between AnBOX and chalcones in the
transition state in the asymmetric aziridination.
On the basis of our proposed transition state (Fig. 1),13 if
chalcones form a stable p-stacking complex, they will
undergo stereospecific aziridination from the upper face
of the chalcones to afford (2S,3R)-aziridine products due
to p-shielding (the same products should be obtained from
To verify this assumption, we prepared three chalcones
0
1
g–1i with 4 -branched isopropyl and tert-butyl groups,
which could disrupt the formation of the ligand–substrate
attractive aromatic p-stacking interaction due to bulky
steric hindrance. These were aziridinated asymmetrically
under the catalysis of AnBOX, BOX, and (S)-cHBOX,
respectively. The results are summarized in Table 1 (entries
the bottom due to C -symmetric ligand). The racemic
2
products should be obtained from a non-catalytic pathway.
Thus, the enantiomeric excesses should present the percents
of chalcones that formed stable p-stacking complex with
AnBOX. The stability should be related to the Hammett
constants because both the stability and the Hammett con-
stants are related to the electronic density of the aromatic
rings of chalcones. The ee values and Hammett constants
show a satisfactory correlation (Fig. 2). This further indi-
cates that the p-stacking interaction is predominant in the
charge-transfer interaction between the ligand and sub-
strates. The enantioselective catalytic reaction provides a
sensitive probe to investigate weak intermolecular interac-
tions, such as p-stacking interaction.
1
4–22). The results clearly indicate that the AnBOX ligand
gives relatively lower enantioselectivity for these three chal-
0
cones in comparison with 4 -methylchalcone due to little
p-stacking interaction effectively (entries 1, 14, 17, and
2
0). However, BOX and (S)-cHBOX ligands still show high
0
enantioselectivities for these three chalcones as for 4 -meth-
ylchalcone (entries 1, 15, 16, 18, 19, 21, and 22).
To further confirm our rationale, 1-(trans-4-propyl-
cyclohexyl)-3-phenyl-2-propen-1-one 1j and 4-phenyl-but-
3
-en-2-one 1k were asymmetrically aziridinated under the
1
00
action of these three catalysts. The results indicate that
lower enantioselectivities were obtained under the catalysis
of AnBOX because of no p-stacking interaction between
the ligand and substrates, due to the absence of a phenyl
group attached to the carbonyl group in substrates. These
results also support our rationale.
y = -92.9x + 83.3
R = 0.89
80
6
0
40
2
0
0
Although these three ligands are somewhat different in
terms of bite angle, the inter-N-heteroatom distance, and
disposition of chirality, ligands AnBOX and (S)-cHBOX
possess similar chiral environments. It is impossible to de-
sign and synthesize two ligands with identical chiral envi-
ronments; one with an aromatic backbone and the other
with aliphatic backbone. However, ligands have similar
structural features.
-0.2
0
0.2
0.4
0.6
Hammett constant (Sigma)
Figure 2. Hammett plot of the enantiomeric excesses versus Hammett
constants in the AnBOX catalyzed aziridination of chalcones.
To further confirm our rationale, we attempted to prepare
modified AnBOX with electron-rich substituents (such as
The origin of the p-stacking interaction has been investi-
Me, MeO, Me N) on its anthracene backbone and hoped
to observe a positive slope in the corresponding Hammett
2
gated experimentally and theoretically.17 The results indi-

L. Ma et al. / Tetrahedron: Asymmetry 18 (2007) 878–884
881
plot. Unfortunately, we failed in the synthesis of the
designed AnBOX ligands.
data of all the known unsaturated ketones are identical to
the reported ones.
2
3
4.2.1. (E)-1-(4-tert-Butylphenyl)-3-(4-methylphenyl)-2-pro-
pen-1-one 1i.
3. Conclusion
24
Yellow needle crystals, yield 70%; mp
1
9
10–112 ꢁC; R 0.53 [ethyl acetate–petroleum ether (60–
f
ꢀ
1
In conclusion, factors governing enantioselectivity in the
catalytic asymmetric reaction are usually interpreted in ste-
ric terms of catalysts, affected by the temperature and sol-
0 ꢁC) 1:8 (v/v), silica gel plate]. IR (KBr) m (cm ): 1667
1
(s); H NMR (200 MHz, CDCl ) d: 1.36 (s, 9H), 2.39 (s,
3
3
H), 7.22 (d, J = 8.0 Hz, 2H), 7.46–7.56 (m, 5H), 7.79 (d,
1
9
1
3
vent, etc. Recently, much attention has been paid to the
influence of electronic effects on the enantioselectivity in
the asymmetric catalysis.20–22 However, the underlying rea-
sons are poorly understood in the most cases. Our results
indicate that the origin of the substituent-dependent
enantioselectivity in the asymmetric aziridination of chal-
cones catalyzed by AnBOX is the p-stacking interaction be-
tween the ligand backbone and substrates. The results also
indicate that the p-stacking interaction between the ligand
backbone and substrates is one of more important factors
for controlling the enantioselectivity in asymmetric cataly-
sis. The results provide very useful information for under-
standing the influence of the electronic effect of catalysts
possessing aromatic backbones or substituents on aromatic
substrates and for designing novel ligands. The results also
reveal that the enantioselective catalytic reaction provides a
sensitive probe to investigate weak intermolecular interac-
tions, such as p-stacking interaction.
J = 15.6 Hz, 1H), 7.97 (d, J = 8.0 Hz, 2H); C NMR
(50 MHz, CDCl ) d: 21.5, 31.1, 35.1, 121.1, 125.5, 128.4,
3
1
29.6, 132.2, 135.6, 140.9, 144.4, 156.4, 190.1. MS (EI)
+
m/z: 278 (M ); Anal. Calcd for C H O: C, 86.29; H,
7
2
0
22
.97. Found: C, 85.98; H, 8.09.
4
1
0
.2.2. (E)-3-Phenyl-1-(trans-4-propylcyclohexyl)-2-propen-
-one 1j. Yellow crystals, yield 77%; mp 43–45 ꢁC; Rf
.72 [ethyl acetate–petroleum ether (60–90 ꢁC) 1:8 (v/v), sil-
ꢀ1
1
ica gel plate]. IR (KBr) m (cm ): 1680 (s); H NMR
(300 MHz, CDCl ) d: 0.89 (d, J = 7.2 Hz, 3H), 0.98 (q,
3
J = 7.2 Hz, 2H), 1.15–1.50 (m, 7H), 2.60 (m, 1H), 6.81
d, J = 16.0 Hz, 1H), 7.32–7.58 (m, 5H), 7.59 (d, J =
(
13
1
2
1
6.0 Hz, 1H); C NMR (75 MHz, CDCl ) d: 14.3, 19.8,
3
8.6, 32.3, 36.7, 39.5, 49.5, 124.7, 128.2, 128.8, 130.2,
+
34.6, 142.1, 203.2. MS (EI) m/z: 256 (M ); Anal.
Calcd for C H O: C, 84.32; H, 9.44. Found: C, 84.18;
H, 9.26.
1
8
24
4.3. General procedure for the asymmetric aziridination of
chalcones
4. Experimental
4
.1. General method
A three-necked flask (25 mL) was charged with a,b-unsat-
urated ketone 1 (1.50 mmol), ligand (0.06 mmol), and
Melting points were measured on a Yanaco MP-500 melt-
ing point apparatus and are uncorrected. IR spectra were
recorded on a Bruker Vector 22 FT IR spectrophotometer,
CuOTfÆ1/2C H (13 mg, 0.05 mmol) under a nitrogen
6
6
atmosphere. Dichloromethane (8 mL) was added by syr-
inge and the resulting mixture was stirred for 1 h at
1
13
H NMR and C NMR spectra were on a Varian Mercury
00 (200 MHz) or Varian Mercury Plus 300 (300 MHz)
24 ꢁC. PhI@NTs (373 mg, 1.00 mmol) was added portion-
2
wise to the mixture over 2 h. After the addition, the reac-
tion mixture was kept stirring for another 3 h. The
aziridine product was obtained after flash silica gel chro-
matography with a mixture of petroleum ether (60–90 ꢁC)
and ethyl acetate (6:1, v/v) as an eluent.
spectrometer in CDCl solution with TMS as an internal
3
standard while chemical shifts are reported in parts per mil-
lion. Low and high resolution mass spectra were obtained
on a VG-ZAB-HS spectrometer. CH analyses were per-
formed on an Elementar Vario EL analyzer. Optical rota-
tions were measured on a Perkin Elmer Model 341LC
polarimeter with a thermally jacketed 10 cm cell (concen-
tration c expressed as g/100 mL). The ee values were deter-
mined by HPLC analysis on an HP1100 HPLC equipment
with chiral columns (4.6 · 250 mm) applying a mixture of
hexane–isopropanol as an eluent. Dichloromethane was
heated at reflux over calcium hydride and distilled prior
to use.
4.3.1. (2S,3R)-3-Phenyl-2-(4-trifluoromethylbenzoyl)-1-(p-
tolylsulfonyl)aziridine 2f. Colorless crystals, yield 70%;
mp 135–137 ꢁC; R 0.48 [ethyl acetate–petroleum ether
f
(60–90 ꢁC) 1:5 (v/v), silica gel plate]; The ee value was
determined by HPLC with Chiralcel OD-H column with
hexane–2-propanol (97:3, v/v) as an eluent at flow
rate 1.0 mL/min (s
= 41.6 min; sminor = 46.2 min):
major
1
6
½
aꢁ ¼ þ8:85 (c 0.87, CHCl , 44% ee); IR (KBr) m
D
3
ꢀ
1
1
4.2. General procedure for the synthesis of unsaturated
ketones 1f–j
(cm ): 1702 (s), 1326 (s), 1161 (s); H NMR (200 MHz,
CDCl ) d: 2.40 (s, 3H), 4.20 (d, J = 4.0 Hz, 1H), 4.57 (d,
3
J = 4.0 Hz, 1H), 7.22–7.34 (m, 7H), 7.68–7.76 (m, 4H),
1
3
To a stirred solution of the aldehyde (10 mmol) and ketone
8.16 (d, J = 7.8 Hz, 2H); C NMR (50 MHz, CDCl ) d:
3
(
10 mmol) in 5 mL of ethanol was added 2.5 mL of 10%
21.7, 47.0, 50.5, 125.8, 125.9, 127.5, 127.7, 128.6, 129.0,
NaOH at 0 ꢁC. After this addition, the ice-bath was re-
moved and the mixture allowed to warm to room temper-
ature and stirred for 1 h. After filtration, a yellow solid was
obtained as crude unsaturated ketone. The solid was
recrystallized from EtOH to give yellow crystals. Analytical
129.3, 129.5, 132.8, 136.4, 138.5, 144.5, 189.7; MS (EI)
m/z (relative intensity, %): 445 (M , 4.1), 290 (100), 173
+
(97), 145 (26), 91 (17); Anal. Calcd for C H F NO S:
2
3
18
3
3
C, 62.01; H, 4.07; N, 3.14. Found: C, 61.95; H, 4.09; N,
3.01.

882
L. Ma et al. / Tetrahedron: Asymmetry 18 (2007) 878–884
4
.3.2. (2R,3S)-3-Phenyl-2-(4-trifluoromethylbenzoyl)-1-(p-
90 ꢁC) 1:6 (v/v), silica gel plate]; The ee value was deter-
mined by HPLC with Chiralcel OD-H column with hex-
ane–2-propanol (90:10, v/v) as an eluent at flow rate
tolylsulfonyl)aziridine ent-2f. Colorless crystals, yield 4%;
mp 141–143 ꢁC; R 0.48 [ethyl acetate–petroleum ether
f
20
(
60–90 ꢁC) 1:5 (v/v), silica gel plate]; The ee value was
0.8 mL/min (smajor = 16.8 min; sminor = 20.0 min): ½aꢁ
¼
D
ꢀ
1
determined by HPLC with Chiralcel OD-H column with
hexane–2-propanol (97:3, v/v) as an eluent at flow rate
þ5:1 (c 0.81, CHCl , 70% ee); IR (KBr) m (cm ): 1689
3
1
(s), 1333 (s), 1162 (s); H NMR (300 MHz, CDCl ) d:
3
1
D
6
1
.0 mL/min (sminor = 41.6 min; smajor = 45.7 min): ½aꢁ
¼
1.34 (s, 9H), 2.40 (s, 3H), 4.25 (d, J = 4.2 Hz, 1H), 4.51
(d, J = 4.2 Hz, 1H), 7.22 (d, J = 8.1 Hz, 2H), 7.33 (m,
5H), 7.45 (d, J = 8.7 Hz, 2H), 7.72 (d, J = 8.1 Hz, 2H),
ꢀ
1
ꢀ
13:9 (c 1.0, CHCl , 65% ee); IR (KBr) m (cm ): 1701
3
1
(
s), 1326 (s), 1163 (s); H NMR (200 MHz, CDCl ) d:
3
1
3
2
1
.41 (s, 3H), 4.20 (d, J = 4.0 Hz, 1H), 4.57 (d, J = 4.0 Hz,
7.96 (d, J = 8.7 Hz, 2H); C NMR (75.5 MHz, CDCl3)
d: 21.7, 31.0, 35.3, 47.4, 50.1, 125.8, 127.8, 128.6, 128.8,
128.9, 129.4, 132.7, 133.4, 136.6, 144.1, 158.0, 189.6; MS
H), 7.24–7.34 (m, 7H), 7.69–7.76 (m, 4H), 8.16 (d,
1
3
J = 7.8 Hz, 2H); C NMR (50 MHz, CDCl ) d: 21.6,
4
3
+
7.0, 50.4, 125.76, 125.84, 127.3, 127.7, 128.7, 129.0,
(EI) m/z (relative intensity, %): 433 (M , 2.9), 278 (19),
1
29.3, 129.6, 132.8, 136.2, 138.5, 144.7, 189.7; MS (EI)
277 (30), 262 (46), 161 (100), 91 (35); Anal. Calcd for
C H NO S: C, 72.03; H, 6.28; N, 3.23. Found: C,
+
m/z (relative intensity, %): 445 (M , 4), 290 (100), 173
2
6
27
3
(
97), 145 (26), 91 (17); Anal. Calcd for C H F NO S:
70.91; H, 6.23; N, 3.01.
2
3
18
3
3
C, 62.01; H, 4.07; N, 3.14. Found: C, 61.99; H, 4.00; N,
3
.05.
4.3.6. (2R,3S)-2-(4-tert-Butylbenzoyl)-3-phenyl-1-(p-tolyl-
sulfonyl)aziridine ent-2h. Colorless crystals, yield 43%;
4
.3.3. (2S,3R)-2-(4-Isopropylbenzoyl)-3-phenyl-1-(p-tolyl-
mp 121–123 ꢁC; R 0.37 [ethyl acetate–petroleum ether
f
sulfonyl)aziridine 2g. Colorless crystals, yield 72%; mp
(60–90 ꢁC) 1:6 (v/v), silica gel plate]; The ee value was
determined by HPLC with Chiralcel OD-H column with
hexane–2-propanol (90:10, v/v) as an eluent at flow rate
1
9
06–108 ꢁC; R 0.32 [ethyl acetate–petroleum ether (60–
f
0 ꢁC) 1:8 (v/v), silica gel plate]; The ee value was deter-
2
D
0
mined by HPLC with Chiralcel OD-H column with hex-
ane–2-propanol (90:10, v/v) as an eluent at flow rate
0.8 mL/min (sminor = 16.6 min; smajor = 19.2 min): ½aꢁ
¼
ꢀ
1
ꢀ6:1 (c 0.66, CHCl , 98% ee); IR (KBr) m (cm ): 1688
3
2
D
0
1
0
.8 mL/min (smajor = 16.9 min; sminor = 21.5 min): ½aꢁ
¼
(s), 1333 (s), 1163 (s); H NMR (300 MHz, CDCl ) d:
3
ꢀ
1
þ5:7 (c 0.80, CHCl , 66% ee); IR (KBr) m (cm ): 1685
1.35 (s, 9H), 2.40 (s, 3H), 4.25 (d, J = 4.2 Hz, 1H), 4.51
(d, J = 4.2 Hz, 1H), 7.23 (d, J = 8.1 Hz, 2H), 7.36 (m,
5H), 7.45 (d, J = 8.7 Hz, 2H), 7.72 (d, J = 8.1 Hz, 2H),
3
1
(
s), 1332 (s), 1162 (s); H NMR (300 MHz, CDCl ) d:
3
1
.27 (d, J = 6.9 Hz, 6H), 2.39 (s, 3H), 2.98 (heptet,
1
3
J = 6.9 Hz, 1H), 4.29 (d, J = 4.2 Hz, 1H), 4.52 (d, J =
4
7
7.95 (d, J = 8.7 Hz, 2H); C NMR (75.5 MHz, CDCl3)
d: 21.6, 31.0, 35.3, 47.4, 50.1, 125.8, 127.6, 128.6, 128.8,
128.9, 129.4, 132.9, 133.4, 136.6, 144.3, 158.0, 189.8; MS
.2 Hz, 1H), 7.20–7.24 (m, 2H), 7.33–7.36 (m, 7H), 7.71–
1
3
.75 (m, 2H), 7.98–8.00 (m, 2H); C NMR (75.5 MHz,
+
CDCl ) d: 21.6, 23.7, 23.6, 34.3, 47.6, 50.1, 126.9, 127.4,
(EI) m/z (relative intensity, %): 433 (M , 3), 278 (19), 277
3
1
1
4
27.7, 128.6, 128.8, 129.1, 129.4, 132.9, 133.8, 136.6,
(30), 262 (44), 161 (100), 91 (34); Anal. Calcd for
C H NO S: C, 72.03; H, 6.28; N, 3.23. Found: C,
70.95; H, 6.20; N, 3.12.
44.4, 155.8, 189.9; MS (EI) m/z (relative intensity, %):
2
6
27
3
+
19 (M , 1.5), 264 (100), 248 (61), 209 (53), 147 (93), 91
(
49); HRMS Calcd for C H NO S: 419.1555. Found:
25 25 3
4
19.1556.
.3.4. (2R,3S)-2-(4-Isopropylbenzoyl)-3-phenyl-1-(p-tolyl-
4.3.7.
(2S,3R)-2-(4-tert-Butylbenzoyl)-3-tolyl-1-(p-tolyl-
sulfonyl)aziridine 2i. Colorless crystals, yield 86%; mp
4
129–130 ꢁC; R 0.28 [ethyl acetate–petroleum ether (60–
90 ꢁC) 1:6 (v/v), silica gel plate]; The ee value was deter-
mined by HPLC with Chiralcel OD-H column with hex-
ane–2-propanol (90:10, v/v) as an eluent at flow rate
f
sulfonyl)aziridine ent-2g. Colorless crystals, yield 24%;
mp 106–108 ꢁC; R 0.32 [ethyl acetate–petroleum ether
f
(
60–90 ꢁC) 1:8 (v/v), silica gel plate]; The ee value was
2
D
0
determined by HPLC with Chiralcel OD-H column with
hexane–2-propanol (90:10, v/v) as an eluent at flow rate
0.8 mL/min (smajor = 15.5 min; sminor = 17.2 min): ½aꢁ
¼
ꢀ1
ꢀ3:42 (c 0.76, CHCl , 71% ee); IR (KBr) m (cm ): 1685
3
2
D
0
1
0
.8 mL/min (sminor = 17.2 min; smajor = 21.7 min): ½aꢁ
¼
(s), 1332 (s), 1162 (s); H NMR (300 MHz, CDCl ) d:
3
ꢀ
1
ꢀ
7:29 (c 1.00, CHCl , 85% ee); IR (KBr) m (cm ): 1685
1.35 (s, 9H), 2.35 (s, 3H), 2.39 (s, 3H), 4.35 (d,
J = 4.2 Hz, 1H), 4.45 (d, J = 4.2 Hz, 1H), 7.15 (d,
J = 7.8 Hz, 2H), 7.20–7.25 (m, 4H), 7.49 (d, J = 9.0 Hz,
2H), 7.73 (d, J = 8.4 Hz, 2H), 7.98 (d, J = 8.7 Hz, 2H);
3
1
(
s), 1332 (s), 1162 (s); H NMR (300 MHz, CDCl ) d:
3
1
6
1
2
2
1
1
.28 (d, J = 6.9 Hz, 6H), 2.39 (s, 3H), 2.98 (heptet, J =
.9 Hz, 1H), 4.29 (d, J = 4.2 Hz, 1H), 4.51 (d, J = 4.2 Hz,
H), 7.21–7.24 (m, 2H), 7.32–7.37 (m, 7H), 7.71–7.74 (m,
1
3
C NMR (75.5 MHz, CDCl ) d: 21.2, 21.7, 31.2, 35.2,
3
1
3
H), 7.99–8.01 (m, 2H); C NMR (75.5 MHz, CDCl ) d:
47.8, 49.7, 125.7, 127.6, 127.7, 128.8, 129.3, 129.4, 129.6,
133.4, 136.9, 138.8, 144.3, 158.0, 190.2; MS (EI) m/z (rela-
tive intensity, %): 447 (M , 0.21), 292 (17), 291 (67), 276
(100), 248 (10), 91 (33); Anal. Calcd for C H NO S: C,
3
1.6, 23.5, 23.6, 34.3, 47.4, 50.1, 126.9, 127.5, 127.7,
28.6, 128.8, 129.2, 129.4, 132.9, 133.8, 136.6, 144.2,
+
55.8, 189.7; MS (EI) m/z (relative intensity, %): 419
2
7
29
3
+
(
M , 2), 264 (100), 248 (60), 209 (53), 147 (91), 91 (49);
72.45; H, 6.53; N, 3.13. Found: C, 72.41; H, 6.56; N, 2.99.
HRMS Calcd for C H NO S: 419.1555. Found:
2
5
25
3
4
19.1554.
4.3.8. (2R,3S)-2-(4-tert-Butylbenzoyl)-3-tolyl-1-(p-tolyl-
sulfonyl)aziridine ent-2i. Colorless crystals, yield 53%;
4
.3.5. (2S,3R)-2-(4-tert-Butylbenzoyl)-3-phenyl-1-(p-tolyl-
mp 131–133 ꢁC; R 0.28 [ethyl acetate–petroleum ether
f
sulfonyl)aziridine 2h. Colorless crystals, yield 79%; mp
22–124 ꢁC; R 0.37 [ethyl acetate–petroleum ether (60–
(60–90 ꢁC) 1:6 (v/v), silica gel plate]; The ee value was
1
determined by HPLC with Chiralcel OD-H column with
f

L. Ma et al. / Tetrahedron: Asymmetry 18 (2007) 878–884
883
hexane–2-propanol (90:10, v/v) as an eluent at flow rate
References
2
0
0
.8 mL/min (sminor = 15.1 min; smajor = 16.2 min): ½aꢁ
¼
D
ꢀ
1
þ4:6 (c 0.65, CHCl , 89% ee); IR (KBr) m (cm ): 1685
1. Saenger, W. Principles of Nucleic Acid Structure; Springer:
3
1
New York, 1984.
(
s), 1331 (s), 1163 (s); H NMR (300 MHz, CDCl ) d:
3
2
3
. Burley, S. K.; Petsko, G. A. Science 1985, 229, 23.
. (a) Miyamura, K.; Mihara, A.; Fujii, T.; Gohshi, Y.; Ishii, Y.
J. Am. Chem. Soc. 1995, 117, 2377; (b) Zhang, J.; Moore, J. S.
J. Am. Chem. Soc. 1994, 116, 2655.
. (a) Diederich, F. Angew. Chem., Int. Ed. Engl. 1988, 27, 362;
(b) Rebek, J. Angew. Chem., Int. Ed. Engl. 1990, 29, 245; (c)
Zimmerman, S. In Topics in Current Chemistry; Springer:
Berlin, 1993; Vol. 165, p 72.
1
.35 (s, 9H), 2.35 (s, 3H), 2.39 (s, 3H), 4.34 (d,
J = 4.2 Hz, 1H), 4.45 (d, J = 4.2 Hz, 1H), 7.15 (d,
J = 7.8 Hz, 2H), 7.21–7.27 (m, 4H), 7.49 (d, J = 9.0 Hz,
2
H), 7.73 (d, J = 8.4 Hz, 2H), 7.99 (d, J = 8.7 Hz, 2H);
4
1
3
C NMR (75.5 MHz, CDCl ) d: 21.2, 21.6, 31.0, 35.2,
3
4
1
7.8, 49.7, 125.7, 127.6, 127.7, 128.8, 129.3, 129.4, 129.6,
33.4, 136.8, 138.8, 144.2, 158.0, 190.0; MS (EI) m/z (rela-
+
tive intensity, %): 447 (M , 0.5), 292 (17), 291 (69), 276
5. For a review, see: Pirkle, W. H.; Pockapsky, T. C. Chem. Rev.
1989, 82, 362.
. For recent reviews, see: (a) Jones, G. B.; Chapman, B. J.
(
100), 248 (11), 91 (35); Anal. Calcd for C H NO S: C,
27 29 3
6
7
8
7
2.45; H, 6.53; N, 3.13. Found: C, 72.39; H, 6.50; N, 3.03.
Synthesis 1995, 475; (b) Jones, G. B. Tetrahedron 2001, 57,
7
999.
. (a) Corey, E. J.; Ensley, H. E. J. Am. Chem. Soc. 1975, 97,
908; (b) Ensley, H. E.; Parnell, C. A.; Corey, E. J. J. Org.
4
1
.3.9. (2S,3R)-3-Phenyl-2-(trans-4-propylcyclohexylformyl)-
-(p-tolylsulfonyl)aziridine 2j. Colorless crystals, yield 9%;
6
mp 135–137 ꢁC; R 0.33 [ethyl acetate–petroleum ether (60–
f
Chem. 1978, 43, 1610.
9
0 ꢁC) 1:10 (v/v), silica gel plate]; The ee value was deter-
. (a) Evans, D. A.; Chapman, K. T.; Bisaha, J. Tetrahedron
Lett. 1984, 25, 4071; (b) Evans, D. A.; Chapman, K. T.;
Bisaha, J. J. Am. Chem. Soc. 1988, 110, 1238.
9. Castonguay, L. A.; Rappe, A. K.; Casewit, C. J. J. Am.
Chem. Soc. 1991, 113, 7177.
mined by HPLC with Chiralcel OJ-H column with hex-
ane–2-propanol (90:10, v/v) as an eluent at flow rate
2
D
0
0
.8 mL/min (smajor = 23.9 min; sminor = 37.2 min): ½aꢁ
¼
ꢀ
1
þ5:05 (c 1.00, CHCl , 48% ee); IR (KBr) m (cm ): 1716
3
1
1
1
1
1
0. Kolb, H. C.; Andersson, P. G.; Sharpless, K. B. J. Am. Chem.
(
s), 1334 (s), 1163 (s); H NMR (300 MHz, CDCl ) d:
3
Soc. 1994, 116, 1278.
0
2
4
.86–0.96 (m, 5H), 1.13–1.45 (m, 7H), 1.76–2.00 (m, 4H),
.41 (s, 3H), 2.56–2.60 (m, 1H), 3.77 (d, J = 4.2 Hz, 1H),
.27 (d, J = 4.2 Hz, 1H), 7.24–7.33 (m, 7H), 7.74 (d,
1. Quan, R. W.; Li, Z.; Jacobsen, E. N. J. Am. Chem. Soc. 1996,
1
18, 8156.
2. Brandt, P.; Roth, P.; Andersson, P. J. Org. Chem. 2004, 69,
885.
3. (a) Xu, J. X.; Ma, L. G.; Jiao, P. Chem. Commun. 2004, 1616;
b) Ma, L. G.; Jiao, P.; Zhang, Q. H.; Xu, J. X. Tetrahedron:
Asymmetry 2005, 16, 3718.
1
3
J = 8.4 Hz, 2H); C NMR (75.5 MHz, CDCl ) d: 14.3,
3
4
1
5
2
2
9.9, 21.6, 27.6, 28.2, 32.1, 32.2, 36.6, 39.4, 48.9, 49.9,
0.2, 127.5, 127.9, 128.5, 128.9, 129.5, 132.2, 137.1, 144.2,
(
+
04.9; MS (EI) m/z (relative intensity, %): 425 (M , 3.0),
70 (100), 118 (65), 91 (75); Anal. Calcd for C H NO S:
14. Xu, J. X.; Wei, T. Z.; Zhang, Q. H. J. Org. Chem. 2004, 69,
2
5
31
3
C, 70.55; H, 7.34; N, 3.29. Found: C, 70.55; H, 7.20; N,
6860.
1
1
5. Ma, L. G.; Du, D. M.; Xu, J. X. J. Org. Chem. 2005, 70,
0155.
3
.03.
1
6. (a) Evans, D. A.; Woerpel, K. A.; Hinman, M. M.; Faul, M.
M. J. Am. Chem. Soc. 1991, 113, 726; (b) Evans, D. A.; Faul,
M. M.; Bilodeau, M. T.; Anderson, B. A.; Barnes, D. M. J.
Am. Chem. Soc. 1993, 115, 5328; Asymmetric aziridination
under catalysis of diimine ligands, see: (c) Shi, M.; Wang, C.
J.; Chan, A. S. C. Tetrahedron: Asymmetry 2001, 12, 3105; (d)
Shi, M.; Wang, C. J. Chirality 2002, 14, 412.
4
.3.10.
(2R,3S)-3-Phenyl-2-(trans-4-propylcyclohexyl-
formyl)-1-(p-tolylsulfonyl)aziridine ent-2j. Colorless crys-
tals, yield 9%; mp 130–132 ꢁC; R 0.33 [ethyl acetate–petro-
leum ether (60–90 ꢁC) 1:10 (v/v), silica gel plate]; The ee
value was determined by HPLC with Chiralcel OJ-H col-
umn with hexane–2-propanol (90:10, v/v) as an eluent at
f
flow rate 0.8 mL/min (s
= 24.0 min; smajor = 39.0
17. (a) Jorgensen, W. L.; Severance, D. L. J. Am. Chem. Soc.
1990, 112, 4768; (b) Hunter, C. A.; Sanders, J. K. M. J. Am.
Chem. Soc. 1990, 112, 5525.
minor
20
min): ½aꢁ ¼ ꢀ3:0 (c 1.00, CHCl , 30% ee); IR (KBr) m
D
3
ꢀ1
1
(
cm ): 1717 (s), 1332 (s), 1161 (s); H NMR (300 MHz,
1
8. (a) Cozzi, F.; Cinquini, M.; Annuziata, R.; Siegel, J. S. J. Am.
Chem. Soc. 1993, 115, 5330; (b) Paliwal, S.; Geib, S.; Wilcox,
C. S. J. Am. Chem. Soc. 1994, 116, 4497; (c) Williams, V. E.;
Lemieux, R. P.; Thatcher, G. R. J. J. Org. Chem. 1996, 61,
CDCl ) d: 0.85–0.96 (m, 5H), 1.13–1.46 (m, 7H), 1.78–
3
2
.00 (m, 4H), 2.41 (s, 3H), 2.55–2.60 (m, 1H), 3.78 (d,
J = 4.2 Hz, 1H), 4.27 (d, J = 4.2 Hz, 1H), 7.25–7.34 (m,
1
3
7
H), 7.73 (d, J = 8.4 Hz, 2H); C NMR (75.5 MHz,
1
927.
19. Xu, J. X.; Wei, T. Z.; Zhang, Q. H. J. Org. Chem. 2003, 68,
0146.
CDCl ) d: 14.3, 19.8, 21.6, 27.6, 28.1, 32.1, 32.2, 36.6,
3
3
1
%
9.4, 48.9, 49.9, 50.2, 127.5, 127.8, 128.5, 128.9, 129.5,
1
32.2, 137.0, 144.3, 204.9; MS (EI) m/z (relative intensity,
20. For examples on the influence of the electronic effect of
substrates on the enantioselectivity, see: (a) Wong, H. L.;
Tian, Y.; Chan, K. S. Tetrahedron Lett. 2000, 41, 7723; (b)
Corey, E. J.; Bo, Y. X.; Busch-Petersen, J. J. Am. Chem. Soc.
+
): 425 (M , 3.0), 270 (100), 118 (67), 91 (76); Anal. Calcd
for C H NO S: C, 70.55; H, 7.34; N, 3.29. Found: C,
2
5
31
3
7
0.58; H, 7.21; N, 3.12.
1
998, 120, 13000; (c) Wieger, A.; Scharf, H.-D. Tetrahedron:
Asymmetry 1996, 7, 2303; (d) Yokomatsu, T.; Yamagishi, T.;
Shibuya, S. Tetrahedron: Asymmetry 1993, 4, 1783; (e) Refs.
Acknowledgments
1
3 and 14.
2
1. For the influence of the electronic effect of ligands on the
enantioselectivity, for a review, see: (a) Flanagan, S. P.;
Guiry, P. J. J. Organometal. Chem. 2006, 691, 2125; For
examples, see: (b) Tu, T.; Hou, X.-L.; Dai, L.-X. J.
Organomet. Chem. 2004, 689, 3847; (c) Fu, Y.; Hou, G.-H.;
This work was supported by the National Natural Science
Foundation of China (Project Nos. 20272002 and
2
0472005) and the Ministry of Education of China
(
EYTP).

884
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2
nana-Vidal, V.; Genet, J.-P.; Champion, N.; Dellis, P. Proc.
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Xu, J. X.; Zhang, Q. H.; Choi, M. C. K.; Chan, A. S. C.
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Fu, G. C. Chirality 2000, 12, 318–324; (j) RajanBabu, T. V.;
Radetich, B.; You, K. K.; Ayers, T. A.; Casalnuovo, A. L.;
Calabrese, J. C. J. Org. Chem. 1999, 64, 429; (k) Tanner, D.;
Johansson, F.; Harden, A.; Andersson, P. G. Tetrahedron
22. For examples on the influence of the electronic effects of both
substrates and ligands on the enantioselectivity, see: (a) Liu,
H.; Xu, J. X. J. Mol. Catal. A: Chem. 2006, 244, 68;
(b) Nakagawa, H.; Sei, Y.; Yamaguchi, K.; Nagano, T.;
Higuchi, T. Tetrahedron: Asymmetry 2004, 15, 3861; (c)
Nelson, D. W.; Gypser, A.; Ho, P. T.; Kolb, H. C.; Kondo,
T.; Kwong, H.-L.; McGrath, D. V.; Rubin, A. E.; Norrby, P.-
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119, 1840.
23. Weygand, C.; Mensdorf, L.; Strobelt, F. Chem. Ber. 1935,
68B, 1825.
1
998, 54, 15731; (l) Palucki, M.; Finney, N. S.; Pospisil, P. J.;
24. Matthias, C.; Weniger, K.; Kuck, D. Eur. Mass Spectrom.
1995, 1, 445.
Gueler, M. L.; Ishida, T.; Jacobsen, E. N. J. Am. Chem. Soc.