Asymmetric oxaziridination catalyzed by cinchona alkaloid derivatives containing sulfide

Article abstract of DOI:10.1016/j.tet.2013.06.061

A new method has been developed for the asymmetric oxaziridination of aryl aldimines with m-chloroperbenzoic acid, involving the use of cinchona alkaloid derivatives containing a sulfide moiety as a catalyst. The new method provided access to optically active oxaziridines in good yields with high enantiomeric excess (ee) values of up to 95%.

Full text of DOI:10.1016/j.tet.2013.06.061

Tetrahedron 69 (2013) 7416e7422
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Asymmetric oxaziridination catalyzed by cinchona alkaloid
derivatives containing sulfide
,b,
Tianyi Zhang a, Wei He b, Xingyu Zhao a, Ying Jin a
*
a Department of Pharmacy, Jilin Medical College, Jilin, Jilin 132013, China
b Department of Chemistry, School of Pharmacy, Fourth Military Medical University, Xi’an 710032, Shaanxi, China
a r t i c l e i n f o
a b s t r a c t
Article history:
A new method has been developed for the asymmetric oxaziridination of aryl aldimines with m-
chloroperbenzoic acid, involving the use of cinchona alkaloid derivatives containing a sulfide moiety as
a catalyst. The new method provided access to optically active oxaziridines in good yields with high
enantiomeric excess (ee) values of up to 95%.
Received 18 January 2013
Received in revised form 6 June 2013
Accepted 17 June 2013
Available online 26 June 2013
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
Asymmetric reaction
Oxaziridination
Cinchona alkaloid derivative
1. Introduction
Oxaziridine derivatives, which consist of a three-membered ring
containing an oxygen and a nitrogen atom, were first synthesized in
the 1950s by Emmons1 Following on from this work, oxaziridines
have become the subject of increasing levels of attention and in-
terest in the synthesis and application of these compounds has
grown considerably. The unusual electronics of the oxaziridine ring
may be exploited to enable the electrophilic transfer of oxygen or
nitrogen to other functionalities.2 The application of optically active
oxaziridines as organic oxidants has recently been reported as
a reliable strategy in asymmetric synthesis.3e8 Chirality in oxazir-
idine compounds can be derived from the substituents on the
oxaziridine ring, or from the conformational nitrogen atom. Several
protocols have been developed for the oxidation of chiral imines to
give optically active oxaziridines.9 In 2011, Jørgensen et al.10 re-
ported the first catalytic enantioselective synthesis of oxaziridines,
where the oxidation of aldimines with m-chloroperbenzoic acid
(m-CPBA) using cinchona alkaloid-derived catalysts gave optically
active oxaziridines in good yields with ee values of up to 94%
(Scheme 1). Jørgensen’s work focused predominantly on 9-
substituent ether derivatives and achieved the trans (S,S)-oxazir-
idines. Yamamoto11 recently reported the Hf (IV)-catalyzed enan-
tioselective oxaziridination of N-tosyl imines using a C2-symmetric
chiral bis-hydroxamic acid (BHA) ligand. In this case, the trans
Scheme 1. Enantioselective oxidation of imines to oxaziridines.
(R,R)-oxaziridines were formed with ee values of up to 98%, al-
though only four N-tosyl imines were subjected to the oxaziridi-
nation. Until recently, advances in research toward the
development of this asymmetric reaction have been slow because
of limitations associated with the catalysts, substrate scope, prod-
uct configuration, and ee values under organocatalytic conditions,
and the relationship between the enantioselectivity and catalyst
structure therefore requires further investigation.
Herein, we report the development of a series of cinchona al-
kaloid derivatives (1aek, Fig. 1), which were prepared by making
modifications to the 9-OH, 60-OH, and terminal vinyl groups of
quinine and quinidine. Pleasingly, the catalysts containing a sulfide
ether (1eeg) induced the oxaziridination reaction of N-tosyl imines
to give the trans (R,R)-oxaziridine products with high levels of
enantioselectivity (up to 95%ee). It is well known that it can be very
challenging in asymmetric catalysis to obtain both enantiomers
using the same chiral source. The current methodology effectively
compliments the existing literature on asymmetric oxaziridination.
Moreover, Jørgensen’s proposed mechanism indicates that the
catalytic process involves Brønsted base/hydrogen-bonding bi-
functional activation.10 In our newly synthesized catalysts (1eeg),
the sulfide group may be regarded as a third point of catalytic
* Corresponding author. Tel.: þ86 432 64560532; fax: þ86 432 64560316; e-mail
address: jinying2288@163.com (Y. Jin).
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.06.061

T. Zhang et al. / Tetrahedron 69 (2013) 7416e7422
7417
Scheme 3. Synthesis of catalysts 1dek.
Fig. 1. The organocatalysts screened in the current study (1aek).
catalyst 1f starting from quinine. Catalyst 1k was prepared by the
esterificationof the9-OHmoietyin1jwithbenzoylchloride, followed
by deprotection of 500-TBS group.
induction for this reaction, except for the Brønsted base/hydrogen-
bonding effect, and this could perhaps provide new ideas for the
design of multi-functional chiral catalyst.
The catalysts 1aek were applied to the enantioselective oxa-
ziridination of N-tosyl benzaldimine using m-CPBA as the oxidizing
agent (Table 1). All of the catalysts effectively catalyzed the reaction
to provide the desired product in good yields (80e93%). Catalyst 1a
and catalyst 1b exhibited similar levels of stereoinduction with low
enantioselectivities (23 and 40%ee, Table 1, entries 2 and 3). These
results were different to those reported by Jørgensen, where a cin-
chona derived catalyst bearing a free hydroxyl group at the 9- or 60-
position exhibited a contrasting level of stereoinduction.10 Catalyst
1c, which was derived from quinine, gave the opposite enantiomer
as the major product, but with a low ee value (ꢁ20%ee, Table 1,
entry 4). The introduction of sulfur to the vinyl group of quinidine
gave catalyst 1d, which provided a moderate level of enantiose-
lectivity (51%ee). We considered that the two free hydroxyl groups
in 1d were unfavorable on the basis of the opposite stereo-
induction. Pleasingly, when the 500-OH group in 1d was trans-
formed into corresponding benzoate ester (1e) or TBS ether (1f),
the ee value increased significantly (86 and 88%ee, Table 1, entries 6
2. Results and discussion
The synthetic route to catalysts 1aec is outlined in Scheme 2.
Quinidine was heated with NaSEt in N,N-dimethylformamide
(DMF) to give diol 2 (80% yield),12 which was selectively protected
at the 60-OH position with tert-butyldimethylsilyl chloride (TBSCl)
to give the TBS-ether 1a in 92% yield. Subsequent protection of the
9-OH position of 1a with tert-butyldiphenylsilyl chloride (TBDPSCl)
in DMF at 60 ꢀC, followed by deprotection of the 60-TBS group under
acidic conditions gave catalyst 1b (76% yield for two steps). Catalyst
1c was prepared in a similar manner starting from quinine, in 52%
overall yield.
The route used for the synthesis of catalysts 1dek is outlined in
Table 1
The enantioselective oxaziridination of N-tosyl benzaldiminea
Entry
Catalyst
Yieldb (%)
eec (%)
Config.d
[a]
D
e
Scheme 2. Synthesis of catalysts 1aec.
1
2
3
4
5
6
7
8
Quinidine
88
91
90
92
88
91
93
91
80
88
85
87
45
23
40
ꢁ20
51
86
88
72
3
R,R
R,R
R,R
S,S
R,R
R,R
R,R
R,R
R,R
R,R
d
1a
1b
1c
1d
1e
1f
1g
1h
1i
Scheme 3. Quinidine was heated in 2-mercaptoethanol (4 equiv) at
110 ꢀC for 8 h to give the terminal alcohol 1d (78% yield). This thio-
leene reaction usually proceeds through a radical pathway in the
presence of a radical initiator, such as AIBN, or under UV irradiation
conditions.13 Unexpectedly, we accidently found this reaction
worked well under mere heating condition.14 Then the alcohol 1d
was reacted with benzoic acid in the presence of 1-(3-dimethyl-
aminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI) and 4-
dimethylamiopryidine (DMAP) to give catalyst 1e (86% yield). The
reaction of the terminal hydroxyl of 1d with the different chlor-
osilanes gave catalysts 1feh. Catalyst 1i was prepared by the esteri-
fication of the 200-OH moiety in compound 4 with benzoylchloride,
followed by the TBAF-mediated deprotection of the 9-TBS group.
Compound 4 was synthesized according to a procedure described in
the literature.15 Catalyst 1j was prepared in a similar manner to
þ47.0 (þ27.2)f
9
10
11
12
67
0
ꢁ15
1j
1k
S,S
a
All of the reactions were performed with the N-tosyl benzaldimine (0.20 mmol),
catalyst (0.02 mmol), and m-CPBA (0.28 mmol) in 2 mL of toluene for 5e6 h.
b
Isolated yield.
Determined by HPLC analysis (Chiralcel OD-H).
The configuration was established by comparison with the optical rotation from
c
d
the literature.11
e
Measured on a polarimeter.
f
Optical rotation from the literature.11

7418
T. Zhang et al. / Tetrahedron 69 (2013) 7416e7422
and 7). These results indicated that the sulfur atom could be par-
ticipating in the asymmetric induction in a favorable manner,
whereas the free 500-OH group could be having an adverse impact
on the level of chiral discrimination. When the TBS group in 1f was
changed to a TBDPS group, as in catalyst 1g, the enantioselectivity
was reduced from 88 to 72%ee (Table 1, entry 8 vs 7). These results
demonstrated the unfavorable effect of the bulky moiety on the
stereoselectivity. To confirm that the sulfide performed some cat-
alytic function, we synthesized catalyst 1i, which did not contain
a sulfur, and this catalyst gave the desired product with an enan-
tioselectivity of 67% ee value (Table 1, entry 10). This result in-
Fig. 2. Proposed structure of the oxidation product 5.
lowered to ꢁ60 ꢀC, no improvement was observed in the enan-
tioselectivity (Table 2, entry 9). Based on these results, the opti-
mized conditions were confirmed to include toluene as the solvent
with a 10 mol % loading of catalyst 1f at ꢁ40 ꢀC.
dicated that sulfur performed
a critical role in catalyst for
stereoinduction. Furthermore, catalyst 1h was prepared through
the protection of the 9-OH group of catalyst 1f with TBS and applied
to the oxaziridination reaction. This catalyst gave the racemic
product (3% ee, Table 1, entry 9), and indicated that the free 9-OH in
catalyst 1f was significant. Based on a comparison of the optical
rotation of the product material with a value from the literatur-
e,11 the configuration of the major product was determined to be
trans (R,R). We have proposed that the trans (S,S) isomer could be
obtained as the major product by applying the pseudoenantiomer.
Unexpectedly, however, when catalyst 1j, which was derived from
quinine, was used in the reaction, the racemic product was formed
(Table 1, entry 11). To optimize the catalyst toward the formation of
the trans (S,S) product, we synthesized catalyst 1k, bearing a free
hydroxyl group at the 500 position and a benzoyl group on the 9-OH
group, and this catalyst still provided a low enantioselectivity
(ꢁ15% ee, Table 1, entry 12). Further investigations focused on the
optimization of the catalyst are currently underway.
To optimize the enantioselectivity, we investigated the effects of
different solvents, catalyst loading amounts, and temperatures on
the reaction profile. The results of these experiments are shown in
Table 2. It is clear from the results that the solvent had a significant
impact on the reaction, with toluene being optimal with respect to
the yield and enantioselectivity (Table 2, entry 5). The screening of
different catalyst amounts revealed that a 10 mol % loading pro-
vided the best results. The application of a catalyst loading of 5 or
20 mol % led to a reduction in the enantioselectivity (Table 2, en-
tries 6 and 7 vs entry 5). Based on the mode of oxidation proposed
for catalyst 1f in the presence of m-CPBA (Fig. 2), an additional
charge of m-CPBA (0.08 mmol) was added to the reaction mixture
when a 20 mol % catalyst loading was used, to compensate for
potential losses of m-CPBA. This led to a 9% increase in the ee value
(Table 2, entry 8 vs 7). When the temperature of the reaction was
With the optimized conditions in hand, we proceeded to eval-
uate the enantioselective oxaziridination reaction with a variety of
different aromatic aldimines to investigate the general applicability
and scope of the different catalyst systems (Scheme 4). All of the
aldimines tested reacted smoothly to give the corresponding oxa-
ziridines in good yields with moderate to high enantioselectivities.
Interestingly, the enantioselectivity values were significantly af-
fected by the type and position of the substituents of the phenyl
ring. For example, the meta-substituted substrates reacted
smoothly under the optimized conditions to give the correspond-
ing oxaziridines with high enantioselectivities, whereas the cor-
responding ortho-substituted substrates gave much lower levels of
enantioselectivity. Interestingly, electron-donating groups at the
para-position appeared to favor higher enantioselectivities. Fur-
thermore, when the para-methyl group was changed to an iso-
propyl or tert-butyl group, the ee value increased significantly (3f
and 3d vs 3k). According to a report from the literature, ortho-
substituted substrates should provide the highest enantioselectiv-
ities when a quinidine derivative is used as the catalyst.10 In con-
trast, however, the use of a quinidine derivative with the same
stereoconfiguration in the current study gave the opposite enan-
tiomer, and a different substrate scope was observed. Modification
to the catalyst structure therefore represents an effective method to
expand the scope of the reaction, even when the same chiral source
is used. Of the different substrates listed above, the oxaziridination
of the meta-methyl aromatic aldimine afforded the highest enan-
tioselectivity (3b, 95%ee), whereas the oxaziridination of the 1-
naphthyl-based imine gave the lowest enantioselectivity (3p,
53% ee).
Considering the nitrogen and sulfide groups in catalyst 1f, it was
envisaged that 1f would be oxidized in presence of m-CPBA to give
Table 2
Screening of reaction conditions for the enantioselective oxaziridination of N-tosyl
benzaldiminea
Entry
Solvent
Cat loading
(mmol%)
Yieldb (%)
eec (%)
1
2
3
4
5
6
DCM
THF
10
10
10
10
10
5
20
20
10
85
75
80
72
90
83
93
95
89
76
7
CH3CN
Acetone
Toluene
Toluene
Toluene
Toluene
Toluene
63
38
88
50
76
85
86
7
8d
9e
a
All of the reactions were performed with N-tosyl benzaldimine (0.20 mmol), and
m-CPBA (0.28 mmol) in different solvent for 5e6 h.
b
Isolated yield.
Determined by HPLC analysis (Chiralcel OD-H).
m-CPBA (0.36 mmol).
ꢁ60 ꢀC.
c
d
e
Scheme 4. Scope of the enantioselective oxaziridination of aromatic aldimines.

T. Zhang et al. / Tetrahedron 69 (2013) 7416e7422
7419
the corresponding N-oxide and sulfone moieties. Within the first
10 min of the reaction, which was monitored by thin layer chro-
matography, the catalyst was found to have been completely oxi-
dized, whereas only a small amount of the oxaziridine had been
formed. Analysis of the reaction mixture by high-resolution mass
spectrometry revealed the presence of a material that was consis-
tent with the proposed oxidation product 5 (Fig. 2).16 Under the
general oxaziridination conditions, the imine and catalyst were
initially stirred at ambient temperature for a short period of time
before being cooled to ꢁ40 ꢀC and treated with m-CPBA, which was
added as a single portion. In a separate experiment, catalyst 1f and
m-CPBA were combined and stirred for 10 min to furnish com-
pound 5. Benzaldimine was then added to the reaction and the
resulting mixture was stirred continuously for 5 h. Unexpectedly,
this reaction provided the desired oxaziridine product in a 45%
yield with a 53% ee, which indicated that the order of m-CPBA
addition was critical to the enantioselectivity and yield of the
reaction.
Mp 109e110 ꢀC. 1H NMR (500 MHz, CDCl3):
d
8.53 (d, J¼4.5 Hz, 1H,
ArH), 7.89 (d, J¼9.5 Hz, 1H, ArH), 7.48 (d, J¼4.5 Hz, 1H, ArH), 7.34 (d,
J¼2.5 Hz, 1H, ArH), 7.21 (dd, J¼2.5, 9.0 Hz, 1H, ArH), 6.08e5.96 (m,
1H, CH2]CH), 5.52 (d, J¼4.5 Hz,1H, CH2]CH), 5.04 (d, J¼6.0 Hz,1H,
CH2]CH), 5.01 (br s, 1H, CHOH), 3.38e3.27 (m, 1H, CH), 3.05e3.02
(m, 1H, 1/2CH2), 2.87e2.81 (m, 2H, CH2), 2.73e2.70 (m, 1H, 1/2CH2),
2.48e2.42 (m, 1H, 1/2CH2), 2.21e2.13 (m, 1H, 1/2CH2), 2.05e1.95
(m, 1H, CH), 1.73 (br s, 1H, OH),1.49e1.45 (m, 2H, CH2), 1.13e1.11 (m,
1H, CH), 1.02 (s, 9H, C(CH3)3), 0.23 (d, J¼2.5 Hz, 6H, Si(CH3)2); 13C
NMR (125 MHz, CDCl3):
d 153.6, 148.0, 147.7, 144.1, 140.6, 131.3,
126.7, 124.9, 118.6, 114.4, 110.4, 71.9, 59.8, 50.1, 49.6, 40.1, 28.2, 26.4,
25.7 (ꢂ3), 21.5, 18.2, ꢁ4.4 (ꢂ2). HRMS (ESIþ): m/z calcd for
C25H37N2O2Si [MþH]: 425.2624, found: 425.2626.
4.2.2. Synthesis of catalyst 1b. To
a solution of 1a (0.20 g,
0.62 mmol) in DMF (3 mL) were added Et3N (0.45 mL, 0.31 mmol),
DMAP (7.50 mg, 0.06 mol), and TBDPSCl (0.14 g, 0.93 mmol). The
mixture was allowed to stir for 6 h and worked up by adding tol-
uene and washing with water. The toluene was removed under
vacuum and the remaining oil was used in next step reaction
without further purification.
3. Conclusion
In conclusion, a series of cinchona alkaloid sulfide derivatives
were synthesized and evaluated for their catalytic performances in
the enantioselective oxaziridination reaction. The oxaziridine
products were obtained in high yields and with enantioselectivities
of up to 95%ee. Furthermore, the organocatalysts screened in the
current study performed especially well for substrates bearing
meta- and para-substituted electron-donating groups, and there-
fore effectively compliment the methods already available in the
literature. Further investigations aimed at clarifying the exact cat-
alytic mechanism of this process, as well as expanding upon the
substrate scope, are currently underway in our laboratory.
The crude product was dissolved in methanol (2 mL). p-Tolue-
nesulfonic acid (0.21 g, 1.24 mmol) was then added. The mixture
was stirred for 3 h at rt (monitored by TLC). Then the methanol was
evaporated under vacuum and the residue was purified by flash
column chromatography (dichloromethane/methanol 20:1) to
yield the product 1b (0.26 g, 76%) as white solid. Mp 112e113 ꢀC. 1H
NMR (500 MHz, CDCl3):
d
8.48 (d, J¼4.5 Hz, 1H, ArH), 7.89 (d,
J¼9.0 Hz, 1H, ArH), 7.81 (d, J¼8.0 Hz, 1H, ArH), 7.61 (d, J¼7.0 Hz, 2H,
ArH), 7.39 (d, J¼4.5 Hz, 1H, ArH), 7.34e7.30 (m, 2H, ArH), 7.23e7.14
(m, 7H, ArH), 6.61 (s, 1H, CHOSi), 5.90e5.79 (m, 1H, CH2]CH), 5.16
(d, J¼10.5 Hz, 1H, CH2]CH), 5.08 (d, J¼17.0 Hz, 1H, CH2]CH),
3.80e3.63 (m, 2H, CH2), 3.39e3.30 (m, 1H, CH), 3.08e2.98 (m, 2H,
CH2), 2.90e2.81 (m, 1H, 1/2CH2), 2.66e2.58 (m, 1H, 1/2CH2),
2.49e2.41 (m, 1H, CH), 2.08 (br s, 1H, OH), 1.88e1.60 (m, 2H, CH2),
1.37e1.30 (m, 1H, CH), 1.06 (s, 9H, C(CH3)3); 13C NMR (125 MHz,
4. Experimental section
4.1. General
CDCl3):
d
157.3, 145.9, 143.6, 141.9, 135.7 (ꢂ2), 135.6 (ꢂ2), 132.7,
The 1H NMR spectra were recorded on 500 and 400 MHz
spectrometers using CDCl3 as a solvent. The chemical shifts were
reported in parts per million with the solvent signal used as a ref-
erence (7.26 ppm). The splitting patterns of the signals were re-
ported as s singlet; d, doublet; t, triplet; q, quartet; dd, doublet of
doublets; m, multiplet; br s, broad signal. The 13C NMR spectra were
recorded on 125 and 100 MHz instruments using CDCl3 as a solvent.
The chemical shifts were reported in ppm with the solvent signal
used as a reference (77.0 ppm). High-resolution mass spectra
(HRMS) were measured on a mass spectrometer equipped with an
electrospray ionization (ESI) source in the positive-ion mode. The
enantiomeric excess (ee) values of the products were determined
by Chiral HPLC using Daicel chiralcel OD-H/OJ-H and Chiralpak AD-
H columns. The melting points were uncorrected. The reactions
were monitored by thin layer chromatography (TLC). Purifications
by column chromatography were conducted over silica gel
(200e300 mesh). The aromatic imines were prepared according to
literature procedures.17
131.9, 131.6, 130.2, 130.0, 127.9 (ꢂ2), 127.8 (ꢂ2), 125.3, 122.6, 118.4,
118.0, 103.6, 70.6, 61.3, 49.6, 48.1, 46.0, 37.3, 27.4, 27.0, 23.3 (ꢂ3),
19.7, 18.1. HRMS (ESIþ): m/z calcd for C35H41N2O2Si [MþH]:
549.2937, found: 549.2932.
4.2.3. Synthesis of catalyst 1c. Compound 1c was prepared in
a similar manner starting from quinine in 52% overall yield as white
solid. Mp 115e116 ꢀC. 1H NMR (500 MHz, CDCl3):
d
8.33 (d, J¼4.5 Hz,
1H, ArH), 7.75 (d, J¼9.0 Hz,1H, ArH), 7.54 (d, J¼6.5 Hz, 2H, ArH), 7.37
(d, J¼6.5 Hz, 2H, ArH), 7.26 (d, J¼4.5 Hz, 1H, ArH), 7.20e7.14 (m, 4H,
ArH), 7.08 (dd, J¼2.5, 9.0 Hz, 1H, ArH), 7.04 (t, J¼7.5 Hz, 2H, ArH),
6.99e6.93 (m, 1H, ArH), 6.00 (s, 1H, CHOSi), 5.56e5.43 (m, 1H,
CH2]CH), 4.96e4.77 (m, 2H, CH2]CH), 3.55e3.47 (m, 1H, CH),
3.00e2.83 (m, 2H, CH2), 2.68e2.60 (m, 2H, CH2), 2.33e2.20 (m, 1H,
CH), 2.05e1.98 (m,1H,1/2CH2),1.82 (br s,1H, OH),1.77e1.63 (m,1H,
1/2CH2), 1.61e1.42 (m, 2H, CH2), 1.29e1.20 (m, 1H, CH2), 0.99 (s, 9H,
C(CH3)3); 13C NMR (125 MHz, CDCl3):
d 155.9, 146.1, 140.4, 136.3,
135.8 (ꢂ2), 135.7 (ꢂ2), 133.2, 132.7, 131.0, 129.8, 129.7, 127.6 (ꢂ2),
127.5 (ꢂ2), 127.1, 122.1, 119.2, 115.4, 105.5, 71.9, 61.3, 55.9, 42.3, 39.2,
27.5, 27.3 (ꢂ3), 26.9, 26.8, 21.0, 19.6; HRMS (ESIþ): m/z calcd for
4.2. Preparation of catalysts
C35H41N2O2Si [MþH]: 549.2937, found: 549.2933.
4.2.1. Synthesis of catalyst 1a. To a solution of compound 2 (0.50 g,
1.60 mmol) in DCM (3 mL) were added imidazole (0.22 g,
3.20 mmol) and TBSCl (0.30 g, 1.95 mmol) at 0 ꢀC. Then the solution
was allowed to stir for 3 h at rt. DCM (10 mL) was then added to
dilute the mixture. The organic layer was separated and washed
with water (10 mL), dried over Na2SO4, concentrated in vacuo, and
purified by flash column chromatography (dichloromethane/
methanol 20:1) to yield the product 1a (0.62 g, 92%) as white solid.
4.2.4. Synthesis of catalyst 1d. Quinidine (0.65 g, 2 mmol) was
dissolved in mercaptoethanol (3 mL) and stirred for 8 h at 110 ꢀC.
After the reaction was completed (monitored by TLC), the excess
mercaptoethanol was removed under vacuum and the residue was
purified by flash column chromatography (ethyl acetate/methanol
9:1), to yield product 1d (0.63 g, 78%) as white solid. Mp
201e202 ꢀC. 1H NMR (400 MHz, CDCl3):
d
8.68 (d, J¼4.4 Hz, 1H,

7420
T. Zhang et al. / Tetrahedron 69 (2013) 7416e7422
ArH), 7.82 (d, J¼7.2 Hz,1H, ArH), 7.62 (d, J¼4.8 Hz,1H, ArH), 7.12 (dd,
J¼2.4, 7.2 Hz, 1H, ArH), 6.95 (d, J¼2.4 Hz, 1H, ArH), 6.17 (br s, 1H,
CHOH), 3.79 (t, J¼6.4 Hz, 2H, OCH2), 3.73 (s, 3H, OCH3), 3.24e3.13
(m, 3H), 3.12e2.90 (m, 2H, CH2), 2.82e2.71 (m, 2H, SCH2),
2.58e2.51 (m, 2H, SCH2), 2.26e2.18 (m, 2H, CH2), 2.02e1.91 (m, 1H,
CH), 1.89e1.55 (m, 6H), 1.10e1.01 (m, 1H, CH); 13C NMR (100 MHz,
131.8 (ꢂ2), 129.8, 127.7, 126.2, 126.1 (ꢂ4), 121.6, 118.5, 100.9, 70.1,
64.0, 59.8, 55.9, 50.3, 49.6, 34.4, 33.6, 31.9, 30.3, 26.9 (ꢂ3), 26.1, 24.0,
19.7, 19.2. HRMS (ESIþ): m/z calcd for C38H49N2O3SSi [MþH]:
641.3233, found: 641.3218.
Catalyst 1h: To a solution of compound 1d (0.70 g, 1.8 mmol) in
DMF (5 mL) were added Et3N (1.2 mL, 9.0 mmol) and TBSCl (0.60 g,
4 mmol). The mixture was stirred for 3 h (monitored by TLC). Then
DCM (15 mL) was added to dilute the mixture. The organic layer
was separated and washed with water (10 mLꢂ2), dried over
Na2SO4, concentrated, and purified by flash column chromatogra-
phy (dichloromethane/methanol 30:1) to yield the product (0.96 g,
CDCl3):
d 169.8, 158.0, 147.4, 144.1, 131.6, 125.9, 121.8, 118.5, 100.6,
60.9, 59.8, 56.0, 50.7, 50.1, 35.0, 34.4, 32.2, 29.6, 26.4, 23.2, 14.8.
HRMS (ESIþ): m/z calcd for C22H31N2O3S [MþH]:403.2055, found:
403.2052.
4.2.5. Synthesis of catalyst 1e. To a solution of compound 1d
(100 mg, 0.24 mmol) and benzoic acid (30.5 mg, 0.25 mmol) in
DCM (3 mL) were added EDCI (140 mg, 0.72 mmol) and DMAP
(0.12 g, 0.98 mmol). The mixture was stirred for 5 h. After the re-
action was completed (monitored by TLC), DCM (10 mL) and water
(5 mL) were added to quench the reaction. The organic phase was
separated and washed with water (10 mLꢂ2), dried over Na2SO4,
concentrated, and purified by flash column chromatography (hex-
ane/dichloromethane/methanol/triethylamine 100:20:2:5) to yield
the product 1e (104 mg, 86%) as white solid. Mp 118e119 ꢀC. 1H
85% yield) as yellow oil. 1H NMR (500 MHz, CDCl3):
d 8.67 (d,
J¼4.5 Hz, 1H, ArH), 7.95 (d, J¼4.0 Hz, 1H, ArH), 7.51 (d, J¼2.0 Hz, 1H,
ArH), 7.45 (d, J¼4.5 Hz, 1H, ArH), 7.32 (dd, J¼2.5, 9.0 Hz, 1H, ArH),
6.59 (br s, 1H, CHOH), 4.04 (s, 3H, OCH3), 3.70 (t, J¼7.0 Hz, 2H,
OCH2), 3.69e3.62 (m, 1H, CH), 3.31e3.42 (m, 2H, CH2), 3.18e3.02
(m, 2H, CH2), 2.57 (t, J¼7.0 Hz, 2H, SCH2), 2.55e2.48 (m, 2H, SCH2),
2.40e2.31 (m, 1H, CH), 2.07e2.01 (m, 1H, CH), 1.92 (s, 1H, OH),
1.83e1.75 (m, 3H), 1.69e1.59 (m, 1H), 1.15e1.10 (m, 1H, CH), 0.91 (s,
9H, C(CH3)3), 0.81 (s, 9H, C(CH3)3), 0.79 (s, 3H, SiCH3), 0.25 (s, 3H,
SiCH3), 0.01 (s, 3H, SiCH3), ꢁ0.35 (s, 3H, SiCH3); 13C NMR (125 MHz,
NMR (500 MHz, CDCl3):
d
8.62 (d, J¼4.5 Hz, 1H, ArH), 7.97 (d,
CDCl3): d 159.4, 146.5, 144.4, 144.0, 131.6, 125.6, 123.4, 118.8, 100.0,
J¼7.0 Hz, 2H, ArH), 7.93 (d, J¼8.5 Hz, 1H, ArH), 7.49e7.46 (m, 2H,
ArH), 7.36 (t, J¼8.0 Hz, 2H, ArH), 7.26 (dd, J¼2.5, 9.5 Hz, 1H, ArH),
7.19 (s, 1H, ArH), 7.13 (d, J¼2.5 Hz, 1H, ArH), 5.55 (br s, 1H, CHOH),
4.41 (t, J¼7.0 Hz, 2H, OCH2), 3.81 (s, 3H, OCH3), 3.11e2.97 (m, 2H,
CH2), 2.87e2.78 (m, 4H), 2.73e2.62 (m, 1H, CH), 2.55e2.46 (m, 2H,
SCH2), 1.96e1.88 (m, 1H, CH), 1.81e1.64 (m, 2H, CH2), 1.63e1.53 (m,
2H, CH2), 1.46e1.37 (m, 2H, CH2), 1.11e1.02 (m, 1H, CH); 13C NMR
68.2, 63.4, 60.4, 57.4, 49.1, 49.0, 34.6, 32.2, 31.2, 29.9, 29.7, 26.4 (ꢂ3),
25.9 (ꢂ3), 25.6, 23.6, 18.3, 17.9, ꢁ3.6, ꢁ4.5, ꢁ4.8, ꢁ5.3. HRMS (ESIþ):
m/z calcd for C34H59N2O3SSi2 [MþH]: 631.3785, found: 631.3664.
4.2.7. Synthesis of catalyst 1i. Catalyst 1i: To a solution of com-
pound 4 (150 mg, 0.41 mmol) and TEA (0.1 mL) in DCM (3 mL) were
added benzoylchloride (96 ml, 0.80 mmol). The mixture was stirred
(125 MHz, CDCl3):
d
166.5, 157.7, 147.6, 147.4, 144.3, 133.1, 131.7,
for 30 min. After the reaction was completed, the solvent was re-
moved under vacuum and the remaining oil was used in next step
reaction without further purification.
The crude product was dissolved in THF (3 mL), TBAF (1 M in
THF, 2 mL, 2 mmol) was added and the mixture was stirred for 2 h.
After the reaction was completed (monitored by TLC), ethyl acetate
(15 mL) and water (5 mL) were added. The organic phase was
separated and washed with water (5 mLꢂ2), dried over Na2SO4,
concentrated and the resulting oil was purified by flash column
129.9, 129.6 (ꢂ2), 128.4 (ꢂ2), 126.5, 121.5, 118.3, 101.2, 72.2, 64.0,
59.6, 55.6, 50.8, 50.2, 34.7, 32.6, 30.4, 30.3, 27.0, 26.5, 20.7. HRMS
(ESIþ): m/z calcd for C29H35N2O4S [MþH]: 507.2318, found:
507.2313.
4.2.6. Synthesis of catalysts 1feh. To a solution of compound 1d
(0.70 g, 1.80 mmol) in DCM (3 mL) were added imidazole (4.3 mL,
3.10 mmol) and chlorosilane (1.8 mmol). The solution was stirred
for 3 h. After the reaction was completed (monitored by TLC), DCM
(20 mL) was then added to dilute the mixture. The organic phase
was separated and washed with water (10mLꢂ2), dried over
Na2SO4, concentrated, and purified by flash column chromatogra-
phy (ethyl acetate/methanol 20:1) to yield the products.
chromatography
(hexane/dichloromethane/methanol/TEA
100:30:8:8), to yield product 1i (155 mg, 85% yield over two steps)
as white solid in 85% yield over two steps. Mp 123e124 ꢀC. 1H NMR
(500 MHz, CDCl3):
d
8.69 (d, J¼4.5 Hz, 1H, ArH), 8.04 (dd, J¼1.0,
8.5 Hz, 2H, ArH), 7.99 (d, J¼9.0 Hz, 1H, ArH), 7.59e7.53 (m, 2H, ArH),
7.47e7.42 (m, 2H, ArH), 7.33 (dd, J¼2.5, 9.0 Hz, 1H, ArH), 7.18 (d,
J¼3.0 Hz, 1H, ArH), 5.66 (d, J¼8.5 Hz, 1H, CHOH), 4.34 (t, J¼6.5 Hz,
2H, OCH2), 3.86 (s, 3H, OCH3), 3.28e3.23 (m,1H, CH), 3.08 (td, J¼3.5,
9.0, 19.0 Hz, 1H, CH), 3.00 (d, J¼10.0, 13.0 Hz, 1H, CH), 2.94e2.88 (m,
1H, CH), 2.82e2.75 (m, 1H, CH), 2.07e2.00 (m, 1H, CH), 1.99e1.88
(m, 2H, CH2), 1.76e1.69 (m, 2H, CH2), 1.55e1.48 (m, 2H, CH2),
Catalyst 1f: 93% yield. White solid. Mp 146e147 ꢀC. 1H NMR
(500 MHz, CDCl3):
d
8.73 (d, J¼5.0 Hz, 1H, ArH), 7.99 (d, J¼9.0 Hz,
1H, ArH), 7.55 (d, J¼4.5 Hz,1H, ArH), 7.34 (d, J¼3.0 Hz,1H, ArH), 7.32
(dd, J¼3.0, 9.5 Hz,1H, ArH), 7.19 (d, J¼3.0 Hz,1H, ArH), 5.71 (br s,1H,
CHOH), 3.89 (s, 3H, OCH3), 3.71 (t, J¼7.0 Hz, 2H, OCH2), 3.22e3.12
(m, 1H, CH), 3.11e2.78 (m, 4H, 2CH2), 2.65 (t, J¼7.0 Hz, 2H, SCH2),
2.54 (t, J¼7.5 Hz, 2H, SCH2), 2.02e1.96 (m, 1H, CH), 1.77e1.68 (m,
4H, 2CH2), 1.57e1.51 (m, 2H, CH2), 1.18e1.10 (m, 1H, CH), 0.91 (s, 9H,
1.27e1.26 (m, 1/2H), 1.18e1.12 (m, 1H, CH), 0.91e0.86 (m, 1/2H); 13
NMR (125 MHz, CDCl3): 166.6, 157.7, 147.6, 147.3, 144.2, 132.9,
C
d
C(CH3)3), 0.08 (s, 6H, Si(CH3)2); 13C NMR (125 MHz, CDCl3):
d
157.9,
131.7, 130.3, 129.5 (ꢂ2), 128.4 (ꢂ2), 126.4, 121.6, 118.3, 101.1, 72.2,
63.6, 59.6, 55.6, 51.0, 50.2, 32.6, 31.6, 26.9, 26.7, 20.5. HRMS (ESIþ):
m/z calcd for C27H31N2O4 [MþH]:447.2284, found: 447.2279.
147.7, 146.8, 144.4, 131.8, 126.5, 121.6, 118.4, 101.2, 71.8, 63.4, 59.8,
55.7, 50.8, 50.1, 34.6, 34.5, 32.4, 30.6, 26.8, 26.4, 25.9 (ꢂ3), 20.7, 18.3,
ꢁ5.3 (ꢂ2). HRMS (ESIþ): m/z calcd for C28H45N2O3SSi [MþH]:
517.2920, found: 517.2913.
4.2.8. Synthesis of catalysts 1j,k. Catalyst 1j was prepared in a sim-
ilar manner of catalyst 1f starting from quinine in 72% overall yield
Catalyst 1g: 89% yield. White solid. Mp 54e55 ꢀC. 1H NMR
(500 MHz, CDCl3):
d
8.73 (d, J¼4.5 Hz, 1H, ArH), 7.96 (d, J¼9.0 Hz,
as white solid. Mp 130e131 ꢀC. 1H NMR (500 MHz, CDCl3):
d 8.62 (s,
1H, ArH), 7.69e7.66 (m, 4H, ArH), 7.58 (d, J¼4.5 Hz, 1H, ArH),
7.43e7.35 (m, 6H, ArH), 7.22 (dd, J¼3.0, 9.5 Hz, 1H, ArH), 7.14 (d,
J¼2.0 Hz, 1H, ArH), 5.97 (br s, 1H, CHOH), 3.85 (s, 3H, OCH3), 3.81 (t,
J¼7.0 Hz, 2H, OCH2), 3.47 (br s, 1H, CH), 3.19e2.85 (m, 4H, 2CH2),
2.67 (t, J¼7.0 Hz, 2H, SCH2), 2.44 (t, J¼7.5 Hz, 2H, SCH2), 2.09e2.01
(m, 1H, CH), 2.00 (s, 1H, OH), 1.80e1.68 (m, 4H, 2CH2), 1.63e1.51 (m,
2H, CH2), 1.27e1.23 (m, 1H, CH), 0.99 (s, 9H, C(CH3)3); 13C NMR
1H, ArH), 7.91 (d, J¼9.0 Hz, 1H, ArH), 7.43 (s, 1H, ArH), 7.25 (d,
J¼9.5 Hz, 1H, ArH), 7.14 (s, 1H, ArH), 5.49 (br s, 1H, CHOH), 3.82 (s,
3H, OCH3), 3.63 (t, J¼7.0 Hz, 2H, OCH2), 3.37 (br s, 1H, CH),
3.08e2.98 (m, 2H, CH2), 2.60e2.51 (m, 1H, CH), 2.58 (t, J¼7.0 Hz, 2H,
SCH2), 2.48 (t, J¼7.5 Hz, 2H, SCH2), 2.33e2.26 (m, 1H, CH), 1.72e1.53
(m, 4H, 2CH2), 1.52e1.32 (m, 4H, 2CH2), 0.79 (s, 9H, C(CH3)3), -0.05
(s, 6H, Si(CH3)2); 13C NMR (125 MHz, CDCl3):
144.4, 131.8, 126.6, 121.6, 118.4, 101.2, 72.0, 63.4, 59.8, 58.3, 55.8,
d157.8, 147.6, 147.2,
(125 MHz, CDCl3):
d
158.0, 147.6, 145.8, 144.3, 135.6 (ꢂ4), 133.6,

T. Zhang et al. / Tetrahedron 69 (2013) 7416e7422
7421
43.3, 34.8, 34.7, 34.5, 30.6, 28.0, 25.9 (ꢂ3), 25.7, 21.6, 18.3, ꢁ5.3 (ꢂ2).
HRMS (ESIþ): m/z calcd for C28H45N2O3SSi [MþH]: 517.2920, found:
517.2911.
Vi-PrOH¼95:5, 0.5 mL/min, 225 nm), tR¼28.0 min (major), 36.7 min
(minor).
Compound 3d. (R,R)-3-(4-tert-Butylphenyl)-2-tosyloxaziridine
Catalyst 1k: To a solution of compound 1j (260 mg, 0.50 mmol)
(91% ee). White solid. Mp 81.5e83 ꢀC. 1H NMR (500 MHz, CDCl3):
and TEA (0.2 mL) in DCM (3 mL) was added benzoylchloride (180
m
l,
d
7.92 (d, J¼7.5 Hz, 2H), 7.42 (d, J¼8.0 Hz, 4H), 7.37 (d, J¼8.0 Hz, 2H),
1.50 mmol). The solution was stirred for 30 min. After the reaction
was completed, the solvent was removed under vacuum and the
remaining oil was used in next step reaction without further
purification.
The crude product was dissolved in THF (3 mL), TBAF (1 M in
THF, 2 mL, 2 mmol) was added and the mixture was stirred for 2 h.
After the reaction was completed (monitored by TLC), ethyl acetate
(20 mL) and water (5 mL) were added. The organic phase was
separated and washed with water (5 mLꢂ2), dried over Na2SO4,
concentrated and the resulting oil was purified by flash column
5.43 (s, 1H), 2.49 (s, 3H), 1.31 (s, 9H). 13C NMR (125 MHz, CDCl3):
154.9, 146.3, 131.7, 130.0 (ꢂ2), 129.4 (ꢂ2), 128.0 (ꢂ2), 127.6, 125.7
(ꢂ2), 76.3, 34.9, 31.1 (ꢂ3), 21.8. HRMS (ESIþ): m/z calcd for
C
18H21NNaO3S [MþNa]: 354.1140, found: 354.1142. HPLC (Daicel
Chiralpak OD-H, Vhex/Vi-PrOH¼97:3, 0.4 mL/min, 225 nm),
tR¼21.5 min (major), 23.1 min (minor).
Compound 3e. (R,R)-3-(3-Bromophenyl)-2-tosyloxaziridine (90%
ee). White solid. Mp100e101 ꢀC. 1H NMR (500 MHz, CDCl3):
d 7.91
(d, J¼8.0 Hz, 2H), 7.58 (d, J¼8.0 Hz, 1H), 7.55 (s, 1H), 7.43 (d,
J¼8.0 Hz, 2H), 7.28 (d, J¼7.5 Hz, 1H), 7.25 (s, 1H), 5.40 (s, 1H), 3.78 (s,
3H), 2.49 (s, 3H). HPLC (Daicel Chiralcel OD-H, Vhex/Vi-PrOH¼95:5,
0.4 mL/min, 230 nm), tR¼27.3 min (major), 28.8 min (minor).
Compound 3f. (R,R)-3-(4-Isopropylphenyl)-2-tosyloxaziridine
(88%ee). White solid. Mp 69e70.5 ꢀC. 1H NMR (500 MHz, CDCl3):
chromatography
100:30:8:8) to yield product 1k (204 mg, 79% yield) as colorless oil.
1H NMR (500 MHz, CDCl3):
8.70 (d, J¼4.5 Hz, 1H, ArH), 8.13 (d,
(hexane/dichloromethane/methanol/TEA
d
J¼8.0 Hz, 2H, ArH), 8.06 (d, J¼9.0 Hz, 1H, ArH), 7.85e7.75 (m, 1H,
ArH), 7.72e7.66 (m, 1H, ArH), 7.58e7.53 (m, 2H, ArH), 7.46 (dd,
J¼2.5, 9.5 Hz, 1H, ArH), 7.36 (d, J¼4.5 Hz, 1H, ArH), 4.18 (s, 3H,
OCH3), 3.72 (t, J¼6.0 Hz, 2H, OCH2), 3.60e3.42 (m, 3H), 3.20e3.06
(m, 2H, CH2), 2.84e2.73 (m, 1H, CH), 2.68 (t, J¼6.0 Hz, 2H, SCH2),
2.48 (m, 2H, SCH2), 2.40e2.28 (m, 1H, CH), 2.24e2.12 (m, 3H),
1.96e1.77 (m, 2H, CH2), 1.66e1.58 (m, 2H, CH2), 0.90e0.87 (m, 1H,
d
7.92 (d, J¼7.5 Hz, 2H), 7.42 (d, J¼8.0 Hz, 2H), 7.36 (d, J¼8.0 Hz, 2H),
7.25 (d, J¼7.5 Hz, 2H), 5.42 (s, 1H), 2.96e2.87 (m, 1H), 2.48 (s, 1H),
1.23 (d, J¼7.0 Hz, 6H). 13C NMR (125 MHz, CDCl3): 152.6, 146.3,
131.6,130.0 (ꢂ2),129.4 (ꢂ2),128.3 (ꢂ2),127.9,126.8 (ꢂ2), 76.4, 34.1,
29.7, 23.8, 21.8. HRMS (ESIþ): m/z calcd for C17H19NNaO3S [MþNa]:
340.0983, found: 340.0980. HPLC (Daicel Chiralcel OD-H, Vhex
/
CH); 13C NMR (125 MHz, CDCl3):
d
174.9, 150.9, 146.6, 144.5, 134.0,
Vi-PrOH¼95:5, 0.4 mL/min, 230 nm), tR¼19.5 min (major), 20.8 min
131.5, 129.5 (ꢂ2), 129.1, 128.9 (ꢂ2), 126.1, 123.5, 117.3, 116.6, 100.9,
68.4, 60.6, 58.4, 56.7, 42.8, 35.3, 33.8, 29.7, 29.2, 25.6 (ꢂ2), 25.4,
20.6. HRMS (ESIþ): m/z calcd for C29H35N2O4S [MþH]: 507.2318,
found: 507.2311.
(minor).
Compound 3g. (R,R)-3-(3-Fluorophenyl)-2-tosyloxaziridine (86%
ee). White solid. Mp 71e72 ꢀC. 1H NMR (500 MHz, CDCl3):
d 7.82 (d,
J¼8.0 Hz, 2H), 7.33 (d, J¼8.0 Hz, 2H), 7.30e7.26 (m, 1H), 7.18 (d,
J¼7.5 Hz, 2H), 7.08e7.00 (m, 2H), 5.36 (s, 1H), 2.39 (s, 3H). 13C NMR
(125 MHz, CDCl3): 165.7,161.8, 146.6,133.1 (d, J¼7.5 Hz),131.3,130.4
(d, J¼7.5 Hz), 130.1 (ꢂ2), 129.4 (ꢂ2), 124.2 (d, J¼2.5 Hz), 118.5 (d,
J¼21.25 Hz), 114.8 (d, J¼23.75 Hz), 75.4, 21.8. HRMS (ESIþ): m/z
calcd for C14H12FNNaO3S [MþNa]: 316.0420, found: 316.0416. HPLC
(Daicel Chiralcel OD-H, Vhex/Vi-PrOH¼95:5, 0.6 mL/min, 225 nm),
tR¼17.2 min (major), 18.4 min (minor).
4.3. General procedure for asymmetric oxaziridination
To a solution of corresponding imine (0.20 mmol) in toluene
(2 mL) was added catalyst (0.02 mmol). After stirring shortly at rt,
the mixture was cooled to ꢁ40 ꢀC. Then m-CPBA (purity 70%,
0.28 mmol) was added in one portion and the mixture was stirred
for 5e6 h at ꢁ40 ꢀC. The crude mixture was directly loaded onto
a column packed with silica gel using hexane/EtOAc (15:1) to fur-
nish pure oxaziridines 3aep.
Compound 3h. (R,R)-3-(3-Chlorophenyl)-2-tosyloxaziridine
(86% ee). White solid. Mp83e84 ꢀC. 1H NMR (500 MHz, CDCl3):
d
7.92 (d, J¼8.0 Hz, 2H), 7.47e7.38 (m, 4H), 7.37e7.30 (m, 2H), 5.42
(s, 1H), 2.50 (s, 3H). 13C NMR (125 MHz, CDCl3): 146.6, 134.9, 132.6,
131.5, 131.3, 130.1 (ꢂ2), 129.9, 129.4 (ꢂ2), 128.1, 126.6, 75.4, 21.8.
HRMS (ESIþ): m/z calcd for C14H12ClNNaO3S [MþNa]: 332.0124,
found: 332.0127. HPLC (Daicel Chiralcel OD-H, Vhex/Vi-PrOH¼95:5,
0.3 mL/min, 230 nm), tR¼36.0 min (major), 37.9 min (minor).
Compound 3i. (R,R)-3-(4-Fluorophenyl)-2-tosyloxaziridine (80%
4.4. Characterization data for oxaziridines 3aep
Compound 3a. (R,R)-3-Phenyl-2-tosyloxaziridine (88%ee). White
solid. Mp 89e90.5 ꢀC. 1H NMR (400 MHz, CDCl3):
2H), 7.49e7.39 (m, 7H), 5.46 (s, 1H), 2.51 (s, 3H). HPLC (Chiralcel
OD-H column, Vhex/Vi-PrOH¼90:10, 1.0 mL/min, 225 nm), tR¼8.9 min
(major), 11.8 min (minor).
d
7.94 (d, J¼8.0 Hz,
ee). White solid. Mp 65e66 ꢀC. 1H NMR (500 MHz, CDCl3):
d 7.92
(d, J¼8.0 Hz, 2H), 7.45e7.40 (m, 4H), 7.09 (t, J¼8.5 Hz, 2H), 5.44 (s,
1H), 2.49 (s, 3H). 13C NMR (125 MHz, CDCl3): 165.6, 163.6, 146.5,
131.4, 130.3 (d, J¼2.5 Hz), 130.0 (ꢂ2), 129.4 (ꢂ2), 126.5, 116.0, 115.9,
75.6, 21.8. HRMS (ESIþ): m/z calcd for C14H12FNNaO3S [MþNa]:
Compound 3b. (R,R)-3-(3-Tolyl)-2-tosyloxaziridine (95%ee).
White solid. Mp 57e58 ꢀC. 1H NMR (500 MHz, CDCl3):
d 7.85 (d,
J¼8.0 Hz, 2H), 7.34 (d, J¼8.0 Hz, 2H), 7.21e7.15 (m, 4H), 5.34 (s, 1H),
2.42 (s, 3H), 2.27 (s, 3H). 13C NMR (125 MHz, CDCl3): 146.3, 138.6,
132.1, 131.6, 130.4, 130.0 (ꢂ2), 129.4 (ꢂ2), 128.6, 128.5, 125.5, 76.4,
21.8, 21.2. HRMS (ESIþ): m/z calcd for C15H15NNaO3S [MþNa]:
316.0420, found: 316.0417. HPLC (Daicel Chiralcel OJ-H, Vhex/
Vi-PrOH¼80:20, 1.0 mL/min, 225 nm), tR¼17.5 min (major), 26.3 min
(minor).
Compound 3j. (R,R)-3-(2-Fluorophenyl)-2-tosyloxaziridine (75%
312.0670, found: 312.0668. HPLC (Daicel Chiralcel OD-H, Vhex
/
ee). White solid. Mp 88e90 ꢀC. 1H NMR (400 MHz, CDCl3):
d 7.94 (d,
Vi-PrOH¼95:5, 0.5 mL/min, 225 nm), tR¼19.2 min (major), 27.6 min
J¼8.4 Hz, 2H), 7.46e7.40 (m, 3H), 7.29e7.25 (m, 1H), 7.18e7.10 (m,
2H, ArH), 5.79 (s, 1H), 2.50 (s, 3H). HPLC (Daicel Chiralcel OD-H,
Vhex/Vi-PrOH¼95:5, 1.0 mL/min, 225 nm), tR¼8.5 min (major),
10.0 min (minor).
(minor).
Compound 3c. (R,R)-3-(3-Methoxyphenyl)-2-tosyloxaziridine
(92% ee). White solid. Mp78e79.5 ꢀC. 1H NMR (500 MHz, CDCl3):
d
7.92 (d, J¼8.5 Hz, 2H), 7.42 (d, J¼8.5 Hz, 2H), 7.30 (t, J¼8.0 Hz, 1H),
Compound 3k. (R,R)-3-(4-Tolyl)-2-tosyloxaziridine (74% ee).
7.06 (d, J¼7.5 Hz, 1H), 6.99 (dd, J¼2.5, 8.5 Hz, 1H), 6.90 (s, 1H), 5.42
(s, 1H), 3.78 (s, 3H), 2.49 (s, 3H). 13C NMR (125 MHz, CDCl3): 160.0,
146.4, 132.0, 131.5, 130.0 (ꢂ2), 129.8, 129.4 (ꢂ2), 120.8, 117.8, 112.4,
76.3, 55.4, 21.8. HRMS (ESIþ): m/z calcd for C15H15NNaO4S [MþNa]:
White solid. Mp78e79.5 ꢀC. 1H NMR (500 MHz, CDCl3):
d 7.92 (d,
J¼8.0 Hz, 2H), 7.41 (d, J¼8.5 Hz, 2H), 7.31 (d, J¼8.0 Hz, 2H), 7.19 (d,
J¼8.0 Hz, 2H), 5.41 (s, 1H), 2.48 (s, 3H), 2.36 (s, 3H). HPLC (Daicel
Chiralcel OD-H, Vhex/Vi-PrOH¼95:5, 0.6 mL/min, 225 nm),
tR¼15.5 min (major), 17.0 min (minor).
328.0619, found: 328.0613. HPLC (Daicel Chiralcel OJ-H, Vhex
/

7422
T. Zhang et al. / Tetrahedron 69 (2013) 7416e7422
2. (a) Davis, F. A.; Chen, B.-C. Chem. Rev. 1992, 92, 919e934; (b) Davis, F. A. J.
Compound 3l. (R,R)-3-(2-Bromophenyl)-2-tosyloxaziridine (67%
ee). White solid. Mp103e105 ꢀC. 1H NMR (400 MHz, CDCl3):
7.95
(d, J¼8.4 Hz, 2H), 7.61e7.58 (m, 1H), 7.43 (d, J¼8.4 Hz, 2H),
7.33e7.28 (m, 3H), 5.80 (s, 1H), 2.50 (s, 3H). HPLC (Daicel Chiralcel
OD-H, Vhex/Vi-PrOH¼95:5, 1.0 mL/min, 225 nm), tR¼11.3 min (major),
14.9 min (minor).
Org. Chem. 2006, 71, 8993e9003; (c) Dounay, A. B.; Forsyth, C. J. Org. Lett.
1999, 1, 451e453; (d) Petrov, V. A.; Resnati, G. Chem. Rev. 1996, 96,
d
ꢀ
1809e1824; (e) Aube, J. Chem. Soc. Rev. 1997, 26, 269e277; (f) Malgesini, B.;
Forte, B.; Borghi, D.; Quartieri, F.; Gennari, C.; Papeo, G. Chem.dEur. J. 2009,
15, 7922e7929.
3. Davis, F. A.; Sheppard, A. C.; Chen, B.-C.; Haque, M. S. J. Am. Chem. Soc. 1990, 112,
6679e6690.
4. (a) Page, P. C. B.; Rassias, G. A.; Bethell, D.; Schilling, M. B. J. Org. Chem. 1998, 63,
2774e2777; (b) Aggarwal, V. K.; Wang, M. F. Chem. Commun. 1996, 191e192.
5. Davis, F. A.; Thimma Reddy, R.; Weismiller, M. C. J. Am. Chem. Soc. 1989, 111,
5964e5965.
6. Davis, F. A.; Jenkins, R. H., Jr.; Awad, S. B.; Stringer, O. D.; Watson, W. H.; Galloy, J.
J. Am. Chem. Soc. 1982, 104, 5412e5418.
7. Davis, F. A.; Thimma Reddy, R. J. Org. Chem. 1992, 57, 2599e2603.
8. Davis, F. A.; Thimma Reddy, R.; Reddy, R. E. J. Org. Chem. 1992, 57, 6387e6389.
9. (a) Davis, F. A.; Haque, M. S.; Ulatowski, T. G.; Towson, J. C. J. Org. Chem.
1986, 51, 2402e2404; (b) Davis, F. A.; McCauley, J. P., Jr.; Chattopadhyay, S.;
Harakal, M. E.; Towson, J. C.; Watson, W. H.; Tavanaiepour, I. J. Am. Chem.
Soc. 1987, 109, 3370e3377; (c) Bucciarelli, M.; Forni, A.; Moretti, I.; Torre, G. J.
Compound 3m. (R,R)-3-(2-Chlorophenyl)-2-tosyloxaziridine
(61% ee). White solid. Mp 97e98.5 ꢀC. 1H NMR (400 MHz, CDCl3):
d
7.94 (d, J¼8.4 Hz, 2H), 7.45e7.38 (m, 4H), 7.30e7.27 (m, 3H), 5.86
(s, 1H), 2.50 (s, 3H). 13C NMR (100 MHz, CDCl3): 146.4, 134.8, 131.8,
131.0, 129.9 (ꢂ2), 129.5 (ꢂ2), 128.6, 128.3, 127.1, 118.1, 73.7, 21.7.
HRMS (ESIþ): m/z calcd for C14H12ClNNaO3S [MþNa]: 332.0124,
found: 332.0121. HPLC (Daicel Chiralcel OD-H, Vhex/Vi-PrOH¼95:5,
1.0 mL/min, 225 nm), tR¼10.0 min (major), 14.6 min (minor).
Compound 3n. (R,R)-3-(2-Tolyl)-2-tosyloxaziridine (60% ee).
White solid. Mp56e58 ꢀC. 1H NMR (500 MHz, CDCl3):
d 7.92 (d,
Chem. Soc., Perkin Trans.
2 1983, 923e928; (d) Bucciarelli, M.; Forni, A.;
Marcaccioli, S.; Moretti, I.; Torre, G. Tetrahedron 1983, 39, 187e192; (e)
Zheng, W.; Wojtas, L.; Antilla, J. C. Angew. Chem., Int. Ed. 2010, 49,
6589e6591.
J¼8.0 Hz, 2H), 7.42 (d, J¼8.0 Hz, 2H), 7.31 (t, J¼7.5 Hz, 1H), 7.24 (d,
J¼8.5 Hz, 1H), 7.18 (d, J¼7.5 Hz, 2H), 5.67 (s, 1H), 2.50 (s, 3H), 2.49 (s,
3H). HPLC (Daicel Chiralcel OD-H, Vhex/Vi-PrOH¼95:5, 1.0 mL/min,
230 nm), tR¼6.8 min (major), 8.9 min (minor).
10. Lykke, L.; Rodríaguez-Escrich, C.; Jørgensen, K. A. J. Am. Chem. Soc. 2011, 133,
14932e14935.
11. Olivares-Romero, J. L.; Li, Z.; Yamamoto, H. J. Am. Chem. Soc. 2012, 134,
5440e5443.
12. Liu, Y.; Sun, B.; Wang, B.; Wakem, M.; Deng, L. J. Am. Chem. Soc. 2009, 131,
418e419.
13. (a) Tucker-Schwartz, A. K.; Farrell, R. A.; Garrell, R. L. J. Am. Chem. Soc. 2011, 133,
11026e11029; (b) Kuang, Y. Q.; Zhang, S. Y.; Jiang, R.; Wei, L. L. Tetrahedron Lett.
2002, 43, 3669e3671; (c) Jin, Y.; Sun, X. L.; Zhang, S. Y.; Yao, Z. J.; Wang, Q. F.
Chem. J. Chin. Univ. 2004, 25, 2028e2030.
14. We accidently found this thioleene reaction worked well under mere heating
condition and repeated this procedure for several times, and the desired
compound 1d was obtained in high yields (75e83%). Moreover, the above
transformation was proved to be preceded smoothly in large scale (6.5 g,
2 mmol of material). The exact mechanism of this process need to be further
studied.
Compound 3o. (R,R)-3-(4-Chlorophenyl)-2-tosyloxaziridine (57%
ee). White solid. Mp93e94.5 ꢀC. 1H NMR (400 MHz, CDCl3):
d 7.93
(d, J¼8.4 Hz, 2H), 7.72 (d, J¼6.4 Hz, 1H), 7.71e7.50 (m, 3H), 7.43 (d,
J¼8.0 Hz, 2H), 5.72 (s, 1H), 2.50 (s, 3H). 13C NMR (75.4 MHz, CDCl3):
146.5, 132.2, 130.5 (d, J¼3.8 Hz), 130.0 (ꢂ2), 129.5 (ꢂ2), 128.1, 125.8,
125.7, 124.9, 122.2, 72.8 (d, J¼2.4 Hz), 21.7. HPLC (Daicel Chiralcel
OJ-H, Vhex/Vi-PrOH¼80:20, 1.0 mL/min, 225 nm), tR¼17.2 min (ma-
jor), 21.4 min (minor).
Compound 3p. (R,R)-3-(1-Naphthyl)-2-tosyloxaziridine (53% ee).
White solid. Mp 75e77 ꢀC. 1H NMR (500 MHz, CDCl3):
d 8.17 (d, 2H,
J¼8.5 Hz), 7.98 (d, J¼8.0 Hz, 2H), 7.92 (dd, J¼8.0, 11.5 Hz, 2H), 7.62 (t,
J¼7.5 Hz, 1H), 7.58e7.54 (m, 2H), 7.48e7.43 (m, 3H), 6.15 (s, 1H),
2.50 (s, 3H). 13C NMR (125 MHz, CDCl3): 146.4, 133.3, 131.6, 131.3,
131.2, 130.1 (ꢂ2), 129.4 (ꢂ2), 128.9, 127.4, 126.4, 126.3, 125.9, 125.0,
122.3, 75.3, 21.8. HRMS (ESIþ): m/z calcd for C18H15NNaO3S
[MþNa]:348.0670, found: 348.0673. HPLC (Daicel Chiralpak AD-H,
Vhex/Vi-PrOH¼95:5, 1.0 mL/min, 225 nm), tR¼16.9 min (major),
18.4 min (minor).
15. Rowan, S. J.; Sanders, J. K. M. J. Org. Chem. 1998, 63, 1536e1546.
16. In order to prove the proposed structure of compound 5, we performed the
oxidation of hydroquinidine and diethyl sulfide with m-CPBA at ꢁ40 ꢀC and
obtained the desired N-oxide product 6 and diethyl sulfone 7, respectively (see
Supplementary data for HRMS). For other similar oxidation of sulfide or ni-
trogen with m-CPBA, see: (a) Seo, J. S.; Kim, H. W.; Yoon, C. M.; Ha, D. C.; Gong,
Y. D. Tetrahedron 2005, 61, 9305e9311; (b) Korshin, E. E.; Hoos, R.; Szpilman, A.
M.; Konstantinovski, L.; Posner, G. H.; Bachi, M. D. Tetrahedron 2002, 58,
2449e2469; (c) Ghosh, S.; Tiwari, P.; Pandey, S.; Misra, A. K.; Chaturvedi, V.;
Gaikwad, A.; Bhatnagar, S.; Sinha, S. Bioorg. Med. Chem. Lett. 2008, 18,
4002e4005
Acknowledgements
We thank the National Natural Science Foundation of China
(21102055, 21072228) and the Natural Science Foundation of Jilin
province (201015237).
Supplementary data
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2013.06.061.
.
References and notes
17. (a) Cheng, L.; Liu, L.; Jia, H.; Wang, D.; Chen, Y. J. J. Org. Chem. 2009, 74,
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