Novel chiral thiourea organocatalysts for the catalytic asymmetric oxaziridination

Article abstract of DOI:10.1016/j.tet.2015.12.010

Catalytic enantioselective oxaziridination is one of the challenging reactions in the oxidation of organic molecules. In this article, a series of novel chiral thiourea moleculars were synthesized from natural cinchona alkaloids and primary amines. By usi

Full text of DOI:10.1016/j.tet.2015.12.010

Tetrahedron 72 (2016) 512e517
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Novel chiral thiourea organocatalysts for the catalytic asymmetric
oxaziridination
Nan Ji, Jiani Yuan, Shanshan Xue, Junna Zhang, Wei He *
Department of Chemistry, School of Pharmacy, Fourth Military Medical University, Xi’an 710032, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 4 October 2015
Received in revised form 30 November 2015
Accepted 2 December 2015
Available online 10 December 2015
Catalytic enantioselective oxaziridination is one of the challenging reactions in the oxidation of organic
molecules. In this article, a series of novel chiral thiourea moleculars were synthesized from natural
cinchona alkaloids and primary amines. By using these molecules as organocatalysts and m-chloroper-
oxybenzoicacid (m-CPBA) as the oxidant, a methodology on highly enantioselective epoxidation of al-
dimines has been developed. Several optically active oxaziridines have been constructed in good yields
(
up to 95%) and moderate to excellent enantioselectivities (up to 99% ee). A plausible transition state was
Keywords:
also proposed.
Asymmetric catalysis
Oxaziridination
Cinchona alkaloids
Organic catalysis
Ó 2015 Elsevier Ltd. All rights reserved.
1. Introduction
catalyzed enantioselective epoxidation of N-tosyl imines.12c In
2013, Ooi employed the P-spiro chiral triaminoiminophosphorane
Oxaziridines are pivotal building blocks in many molecules, and
and trichloroacetonitrile in a Payne-type oxidation of N-sulfonyl
12d
are often useful synthetic intermediates for the preparation of
imines.
Besides, in 2014, Yoon reported an elegant kinetic reso-
1
12e
some important biologically relevant natural products. In the past
lution of N-sulfonyl oxaziridines catalyzed by Iron.
Although
two decades, oxaziridine chemistry has been widely expanded into
these successful examples have been developed by the research
specialist staff noted above, efforts to apply new catalyst systems
are worth further investigation.
2
3
oxygen, nitrogen atom transfer reaction types, transition-metal-
4
5
promoted rearrangements, and cycloadditions. Because of these
potent capabilities, oxaziridines have also been applied in the total
synthesis field, including in the synthesis of natural products like
rabeprazole,6 asperlicin,7 and trigonoliimine. A common way to
obtain enantiopure oxaziridines includes the oxidation of chiral
In the organocatalysts development process, small chiral mol-
ecules bearing hydrogen bonding donors, such as chiral thiourea
organocatalysts have emerged as an important and popular ap-
8
13
proach in enantioselective catalysis. By applying the hydrogen
bonding, thiourea group is often used to activate the electrophiles
and usually plays important roles in the process of designing and
9
10
11
imines, chiral camphor derivatives or ketimines with Oxone or
m-CPBA. However, the approach via asymmetric synthetic oxida-
tion to access optically active oxaziridines is more appealing.
Fortunately, several scientists have recently successfully re-
ported their works on the catalytic enantioselective synthesis of
chiral oxaziridines.12 In 2011, the first catalytic asymmetric oxa-
ziridination was reported by Jørgensen group using cinchona
14
building new catalysts. In the past several decades, chiral thiourea
organocatalysts have been applied successfully in catalytic asym-
metric reactions, such as Strecker, Michael addition, aza-Henry,
BayliseHillma, Mannich, Acyl-PicteteSpengler and tandem
15
reaction.
12a
alkaloid-derived ether catalyst. Since then, several other groups
have reported enantioselective oxaziridination involving metallic
as well as purely organic catalysts. Jin found that the cinchona al-
kaloid sulfurether derivatives could catalyze the reaction to gen-
Herein, we report a series of novel cinchona alkaloids derived
thiourea catalysts and their application in the enantioselective
oxaziridination.
erate high yields and good enantioselectivities for some
2. Results and discussion
substrates.1
2b
In 2012, Yamamoto reported the first Hf (IV)-
A series of modular bifunctional chiral thioureas were de-
veloped by our group recently, and the experimental results show
that they could be successfully applied in the aza-Henry reaction
*
Corresponding author. Tel.: þ86 29 84774470; e-mail address: weihechem@
14a
fmmu.edu.cn (W. He).
and Michael addition.
These studies prompted us to test these
http://dx.doi.org/10.1016/j.tet.2015.12.010
0
040-4020/Ó 2015 Elsevier Ltd. All rights reserved.

N. Ji et al. / Tetrahedron 72 (2016) 512e517
513
modular catalysts in some other catalytic asymmetric reactions.
Moreover, in 2011, the work published by the Jørgensen group
Table 1
12a
Screening of the thiourea catalysts in the asymmetric oxaziridination
investigated a bifunctional hydroquinine-derived thiourea cata-
lyst in the catalytic enantioselective oxaziridination. The results
demonstrated that 95% conversion and 40% ee value of the oxa-
ziridine was detected. The data from our repeated experiments also
produced moderate results. Both of these encouraged us to test
a new series of chiral thiourea organocatalysts in the catalytic
enantioselective oxaziridination.
Entrya
Yieldb (%)
Eec (%)
R
Cat
Cat loading (mol %)
1
2
3
4
5
6
7
8
9
Ts-
Ts-
Ts-
Ts-
Ts-
Ts-
Ts-
Ts-
Ts-
Ts-
Ts-
Ts-
Ts-
Ns-
Ms-
2a
2b
2c
2d
2e
2f
2g
2h
2i
2j
2f
2f
2k
2f
15
15
15
15
15
15
15
15
15
15
12
5
75
80
83
80
88
85
82
87
83
81
83
79
80
76
55
11
5
Chiral organocatalysts 2a and 2b were synthesized according to
14a
our previous publication, and the synthetic routes of 2cej were
42
57
38
69
60
58
63
61
69
55
ꢀ62
51
35
shown in Scheme 1. 9-amino-(9-deoxy)-epiquinine was synthe-
sized according to the known procedure.16 In this process, the
configuration of quinine’s 9-position was changed from R to S. Then
the 9-amino-(9-deoxy)-epiquinine was reacted with CS and DCC
2
in THF to obtain the isothiocyanate intermediate, followed by
treatment of the isothiocyanate with the corresponding primary
amines. Chiral organocatalysts 2ce2j were obtained in good yields
10
11
12
13
14
15
(
71e82%).
12
12
12
2f
a
All reaction were performed with 1a (0.20 mmol), m-CPBA (0.24 mmol) and
ꢁ
catalyst 2 (5e15 mol %) in toluene (2 mL) at ꢀ24 C. Ts-¼p-toluenesulfonyl. Ns-¼p-
nitrobenzenesulfonyl. Ms-¼methanesulfonyl.
b
Isolated yield; reaction for 24 h.
Enantiomeric excess of 3a, determined by chiral HPLC analysis using Chiralcel
c
OD-H column. Absolute configuration was established by comparing with the lit-
erature data.1
2a
configuration of the product. The experimental results demon-
strated that the primary amine exert little effect on the absolute
configuration of the product (the configuration was not changed).
Also the ee value and yield were not influenced significantly by
either catalyst derived from primary amine bearing R, or S config-
uration (Table 1, entries 9, 10). Catalyst 2k, which was derived from
quinidine gave the opposite enantiomer as the major product, but
with a lower ee value (Table 1, entry 13). These results indicate that
the absolute configuration of the oxaziridines was determined by
cinchona skeleton. In the end, catalyst 2f was chosen to catalyze this
reaction, on which further condition optimization was based.
Temperatures were also tested for the reaction, and the results
are shown in Table 2. When the temperature was decreased from
Scheme 1. General synthetic route for organocatalysts 2cej.
Compounds 2ae2b were initially tested in the oxaziridination of
ꢁ
ꢁ
ꢀ
24 C to ꢀ40 C, the ee value increased (Table 2, entries 1, 2).
N-tosyl benzaldimine with m-CPBA (Table 1), and the results were
not satisfactory, with only around 10% ee value detected (Table 1,
entries 1, 2). After the catalysts were structurally modified to gen-
erate a better catalytic effect through the replacement of the chiral
alkamine parts with some common primary amines, the new cat-
alysts 2ce2e were developed. The ee value was increased sub-
stantially during model reaction (Table 1, entries 3e5) (see Fig. 1).
Based on the observation from the structures of catalysts 2c, 2d,
and 2e, we discovered that the ee value was influenced by the steric
hindrance of the primary amine and the length of the carbon chain.
Therefore, the new catalysts 2fe2h were synthesized for testing.
When catalyst 2f was applied into the reaction, 69% ee value was
observed with good yield (Table 1, entry 6). When 2f loading was
decreased to 12 mol %, the ee value was maintained with minimal
decrease in yield (Table 1, entry 11). The N-p-nitrobenzenesulfonyl
benzaldimine and N-methanesulfonyl benzaldimine were also
tested, and the results indicated that the N-tosyl benzaldimine was
more suitable for this catalytic system (Table 1, entries 14,15). There
was no significant outcome, whether implementing a longer car-
bon chain amine-derived catalyst like 2h (Table 1, entry 8), or
a shorter carbon chain amine-derived catalyst like 2g in this re-
action (Table 1, entry 7).
ꢁ
When the reaction temperature reached ꢀ55 C, the de-escalation
of the yield was obvious; at the same time the ee value did not
increase (Table 2, entry 3). When the temperature reached ꢀ78 C,
ꢁ
Table 2
Effects of concentration and temperature on the 2f catalyzed asymmetric oxazir-
idination of N-tosyl benzaldimine
Entrya
Temp ( C)
ꢁ
Conc (M)
Yieldb (%)
Eec (%)
1
2
3
4
5
6
ꢀ24
ꢀ40
ꢀ55
ꢀ78
ꢀ40
ꢀ40
0.10
0.10
0.10
0.10
0.05
0.15
83
81
73
55
85
80
69
75
71
7
85
70
a
Reactions were carried out on varied content of 1a in toluene with catalyst 2f
12 mol %) and m-CPBA (1.2 equiv) in different reaction temperatures.
(
b
Catalysts 2ie2j were synthesized to further test whether the
optical activity primary amine part could influence the
Isolated yield; reaction for 24 h.
Enantiomeric excess of 3a, determined by HPLC on a Chiralcel OD-H column.
c

514
N. Ji et al. / Tetrahedron 72 (2016) 512e517
the ee value decreased to 7% (Table 2, entry 4). It might be because
the catalyst had minor activity at this low temperature. After this
which can be easily observed (Table 4, entries 8, 11). When 2-
naphthaldehyde substrate was tested in this experiment, the re-
sult was impressive (Table 4, entry 12). Then, aliphatic substrate
was also tested in this oxaziridination, and 3m was obtained in
good yield with moderate enantioselectivity (Table 4, entry 13).
Compared with data in previous literature, some corresponding
products had been obtained by moderate ee values (Table 4, entries
7, 10, 14, 15), several oxaziridines’ enantiomeric excess had reached
99% by using this catalyst system (Table 4, entries 1, 8, 11, 12).
ꢁ
series of experiments, ꢀ40 C was chosen to be the best reaction
temperature.
The effect of reaction concentration was also tested as shown in
Table 2. There were some fluctuations of the ee value when the
reaction concentration reached 0.05 M, 0.10 M and 0.15 M. All in all,
0
.05 M was chosen to be the best reaction concentration (Table 2,
entry 5).
The solvent plays an important role in the catalytic reaction.
Some common solvents were tested in this reaction. From Table 3, it
is clearly shown that, when alcohols were selected as solvent, the
results were not satisfactory. Even though higher reaction yields
were produced, the products were almost racemic (Table 3, entries
Table 4
Scope of the asymmetric oxaziridination of aromatic and aliphatic aldimines
2
, 3). For other solvents, especially when xylol was used as solvent
regardless meta-, ortho-, or para-substituted, Table 3, entries 5e7),
the product’s yield was satisfactory, and the ee value increased to
(
12a
9
3% (Table 3, entry 4). Based on the article of Jørgensen, when
nondried toluene was used in the catalytic reaction, the ee value
increased (the specific reason is unclear). We observed similar
phenomena in our reaction. By using nondried xylol as solvent, the
ee jumped to 99% (Table 3, entry 8). Experiments using dried xylol
and adding different amounts of water were also done. More details
on these experiments were included in the supplemental in-
formation. THF, DCM, acetone and other solvents were tested for
this reaction also, but the results were insignificant (Table 3, entries
Entrya
R
Yieldb (%)
Eec (%)
3
1
2
3
4
5
6
7
8
9
Ph (1a)
89
91
88
87
86
90
94
92
94
85
93
95
89
82
85
99
91
93
95
81
85
69
99
69
77
99
99
61
61
51
3a
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
3m
3n
3o
2-MeC
3-MeC
4-MeC
2-MeOC
3-MeOC
4-EtC
4- PrC
4-PhC
3,4-Me
4- Butyl C
2-Naphthyl (1l)
Cyclopropyl (1m)
6
H
H
H
4
(1b)
(1c)
(1d)
6
6
4
4
6
H
4
(1e)
(1f)
6
H
4
6
H
4
(1g)
(1h)
(1i)
i
6
H
H
4
4
9
e11). Therefore commercial available nondried xylol was selected
6
to be the reaction solvent.
10
11
12
13
14
15
2
C
6
H
3
(1j)
t
6
H
4
(1k)
Table 3
Screening the solvents in the asymmetric oxaziridination of N-tosyl benzaldimine
2-FC
2-ClC
6
H
4
(1n)
(1n)
6 4
H
a
All reaction were performed with 1 (0.20 mmol), m-CPBA (0.24 mmol) and 2f
ꢁ
(
12 mol %) in nondried xylol (4 mL) at ꢀ40 C.
b
Isolated yield; reaction for 24 h.
Enantiomeric excess of 3, determined by chiral HPLC analysis using Chiralcel
c
OD-H, OJ-H, AD-H columns. Absolute configuration of 3 were established according
to the literature data.1
2a,b
Entrya
Solvent
Yieldb (%)
Eec (%)
1
2
3
4
5
6
7
Toluene
Ethanol
Isopropanol
Xylol
o-Xylene
m-Xylene
p-Xylene
Xylol
85
96
95
86
85
83
87
89
85
92
76
85
rac.
rac.
93
90
91
86
99
65
72
73
Based on the experimental results as shown above and the
previous mechanism studies of the catalytic asymmetric oxazir-
12a,17
idination,
a plausible transition state model for this trans-
formation is proposed (Fig. 2). As shown in this transition state,
both the tosyl group and the nitrogen of the imine were activated
by the multiple hydrogen bonding interactions. In the meantime,
d
8
9
DCM
THF
Acetone
1
1
0
1
a
All reaction were performed for 24 h with 1a (0.20 mmol), m-CPBA (0.24 mmol)
ꢁ
and 2f (12 mol %) in different solvents (4 mL) at ꢀ40 C.
b
Isolated yield.
c
Enantiomeric excess of 3a, determined by chiral HPLC analysis using Chiralcel
OD-H column.
d
Nondried xylol.
When the optimal conditions were established for this trans-
formation, the enantioselective oxaziridination by using 2f as cat-
alyst underwent substrates expansion. A broad range of aldimines
were used for this reaction. Overall, almost all tested substrates
generated good yields and moderate to excellent enantioselectiv-
ities. From Table 4, we found out that the substrates bearing
electron-donating group generated higher ee values, compared to
the ones with electron-withdrawing group (Table 4, entries 2, 3 vs
entries 14, 15). Comparing the similar p-substituted substrates,
higher yields and ee values were generated by the substrates that
had greater steric like isopropyl or tertiary butyl in the experiment,
Fig. 1. Structures of the chiral thiourea organocatalysts.

N. Ji et al. / Tetrahedron 72 (2016) 512e517
515
mixture was filtrated, and the solvent was subsequently removed by
reduced pressure. The residuewas purified byflash chromatography
on silica gel (DCM/methanol¼15:1) to afford product 9-
deoxyepiquinidine isothiocyanate (577.4 mg, 79% yield). A solution
of phenethylamine (272.7 mg, 2.25 mmol) was added to stirred
solution the 9-deoxyepiquinidine isothiocyanate (550.2 mg,
1.50 mmol) in THF (5 mL) at room temperature. After 24 h, the sol-
vent was removed under reduced pressure. The residue was purified
by recrystallization to afford the product 2c (517.8 mg, 71% yield).
4.3. 1H NMR and 13C NMR and HR-Mass spectra data for the
Fig. 2. Proposed transition state for the reaction.
organocatalysts 2cej
the nitrogen atom of the quinine catalyst 2f is protonated by the m-
CPBA to generate a negative oxygen ion. Then, the oxidant part was
much more conceivable to attack the Si-face of the activated N-Ts-
protected imine and form the S,S enantiomer product. (Absolute
configuration of three were established according to the literature
ꢁ
20
Catalyst 2c: White solid; 71% yield; mp 102.7e104.5 C; ½
a
ꢂ
D
ꢀ
117.3 (c 0.25, CHCl
3
); IR (KBr):
n
¼3232, 3062, 3028, 2931, 2882,
2
7
8
835, 1620, 1558, 1346, 1299, 1265, 1226, 1134, 1083, 1029, 918, 852,
ꢀ1 1
36, 702 cm ; H NMR (400 MHz, CDCl
.03 (d, J¼9.2 Hz, 1H), 7.65 (br s, 1H), 7.40 (dd, J¼2.8, 9.2 Hz, 1H),
.34 (br s, 1H), 7.25e7.21 (m, 3H), 7.05 (d, J¼5.2 Hz, 2H), 6.79 (br s,
H) 5.70e5.61 (m, 1H), 4.98e4.94 (m, 2H), 3.97 (s, 3H), 3.97e3.63
(m, 2H), 3.13 (s, 3H), 2.80e2.64 (m, 5H), 2.47 (br s, 1H), 2.27 (br s,
H), 1.67 (br s, 1H), 1.59 (s, 2H), 1.37e1.31 (m, 1H), 0.89 (br s, 1H)
3
):
d
¼8.69 (d, J¼4.4 Hz, 1H),
12a,b
data.
) In this transition model, both the hydrogen bonding and
counter ion pair strategy worked in synergy to give good results.
7
1
3
. Conclusion
1
13
In summary, a series of novel chiral thiourea organocatalysts
ppm; C NMR (400 MHz, CDCl ):
d
¼182.4, 158.0, 147.5, 144.8, 140.7,
3
have been developed for the catalytic asymmetric oxaziridination.
To the best of our knowledge, this is the first time cinchona alkaloids
derived thiourea catalysts were used in this reaction to achieve
high enantioselectivities (up to 99% ee). It performed well over
several aldimines to give the desired products with good yields (up
to 95%). The catalysts are easily synthetized and low cost, and the
reaction condition is mild. Further investigations into the mecha-
nism of this methodology and its application to the natural prod-
ucts total synthesis are ongoing in our laboratory.
138.4, 131.8, 128.6 (ꢃ3), 128.5 (ꢃ2), 126.5, 122.0, 114.9 (ꢃ2), 102.1,
55.8 (ꢃ2), 55.2, 45.8, 40.9, 39.1, 34.9, 29.7, 27.5, 27.2 (ꢃ2), 25.7 ppm;
þ
HRMS-ESI (m/z): [MþH] calcd for C
2
9
35 4
H N OS 487.2532, found
487.2540.
ꢁ
20
D
Catalyst 2d: White solid; 76% yield; mp 102.4e104.6 C; ½ ꢂ
a
ꢀ138.2 (c 0.25, CHCl ); IR (KBr): ¼3271, 3070, 2854, 2831, 1620,
3
n
ꢀ
1 1
1550, 1357, 1285, 1226, 1029, 918, 852, 736 cm
(400 MHz, CDCl ):
¼8.75 (d, J¼4.4 Hz, 1H), 8.05 (d, J¼9.2 Hz, 1H),
7.66 (br s, 1H), 7.43e7.40 (m, 2H), 7.36 (s, 1H), 6.60 (br s, 1H),
.73e5.64 (m, 1H), 4.99e4.94 (m, 2H), 3.98 (s, 3H), 3.26e3.20 (m,
2H), 3.15e3.12 (m, 3H), 2.80e2.73 (m, 2H), 2.31 (br s, 1H), 1.68 (s,
H), 1.62 (t, J¼6 Hz, 3H), 1.40e1.34 (m, 1H), 0.97e0.91 (m, 2H), 0.70
;
H NMR
3
d
5
4
4
. Experimental section
1
13
.1. General
(s, 6H) ppm; C NMR (400 MHz, CDCl ):
d
¼182.6, 158.2, 147.8,
3
1
45.1, 141.2 (ꢃ2), 132.2, 122.2, 115.0 (ꢃ2), 101.8, 69.9, 55.9 (ꢃ2), 55.7,
All the starting materials and reagents were purchased from
41.0, 39.6, 28.1, 28.0, 27.5, 25.9, 20.2, 20.1, 19.0 ppm; HRMS-ESI (m/
z): [MþH] calcd for C25H35N OS 439.2532, found 439.2500.
þ
commercial suppliers and used without further purification. Sol-
vents were purified by standard procedures. DCM, toluene and
xylene were freshly distilled prior to use, nondried toluene and
xylol were also used in the experimental section. The reactions
were monitored by thin layer chromatography (TLC) and analysis of
TLCs was done either via UV light (254 nm) or phosphomolybdic
acid. Melting points were determined using a standard melting
4
ꢁ
20
D
Catalyst 2e: White solid; 82% yield; mp 228.3e231.7 C; ½
a
ꢂ
ꢀ214.3 (c 0.25, CHCl ); IR (KBr): ¼3290, 2947, 2869, 1620, 1508,
3
n
ꢀ
1 1
1473, 1419, 1226, 1029, 918, 852, 736 cm
CDCl ):
; H NMR (400 MHz,
3
d
¼8.73 (d, J¼4.4 Hz, 1H), 7.99 (d, J¼9.2 Hz, 1H), 7.85 (br s,
1H), 7.43e7.35 (m, 2H), 6.93 (br s, 1H), 5.72e5.63 (m, 2H),
4.98e4.92 (m, 2H), 3.99 (s, 3H), 3.63e3.59 (m, 4H), 3.29e3.23 (m,
1H), 3.18e3.17 (m, 1H), 3.18e3.09 (m, 1H), 2.72e2.69 (m, 2H), 2.31
(br s, 1H), 1.98 (s, 4H), 3.06 (s, 3H), 1.38e1.32 (m, 1H), 1.11e1.06 (m,
point apparatus and were uncorrected. NMR spectra were recorded
1
as CDCl
shifts are reported as
tetramethylsilane (TMS,
dard. The 13C NMR chemical shifts are reported as
per million (ppm) downfield from TMS and referenced with respect
to the CDCl signal (triplet, centerline
3
solution on 400 MHz instrument. The H NMR chemical
13
d
value in parts per million (ppm) relative to
¼0.00)/CHCl ¼7.26) as internal stan-
values in parts
1H) ppm; C NMR (400 MHz, CDCl ):
d
¼179.2, 157.4, 147.6, 146.5
3
d
3
(
d
(ꢃ2), 144.6, 140.9, 131.4, 128.5, 121.5, 119.8, 114.7 (ꢃ2), 102.7, 61.3,
d
55.8 (ꢃ2), 55.7 (ꢃ2), 41.1, 39.4, 27.7, 27.3 (ꢃ2), 25.7 ppm; HRMS-ESI
þ
(m/z): [MþH] calcd for C
2
5
H
33
N OS 437.2375, found 437.2374.
4
ꢁ
20
D
3
d
¼77.0 ppm). High-resolution
Catalyst 2f: White solid; 81% yield; mp 118.9e122.3 C; ½
a
ꢂ
mass spectra (HRMS) were measured with ESI. IR spectra were
recorded as KBr disks. The yields are of materials isolated by col-
umn chromatographygel plates. Enantiomeric excess (ee) de-
termination was carried out on an Agilent 1260 interfaced to a HP
ꢀ127.7 (c 0.25, CHCl ); IR (KBr): ¼3232, 3066, 2954, 2866, 1508,
n
3
ꢀ
1 1
1299, 1261, 1226, 1029, 914, 852, 736 cm
CDCl ):
; H NMR (400 MHz,
3
d
¼8.77 (d, J¼3.6 Hz, 1H), 8.06 (d, J¼9.2 Hz, 1H), 7.64 (br s,
1H), 7.42 (d, J¼9.2 Hz 2H), 5.72e5.64 (m, 1H), 4.99e4.93 (m, 2H),
3.98 (s, 3H), 3.28e3.03 (m, 4H), 2.80e2.71 (m, 2H), 2.31 (br s, 1H),
1.91 (br s, 1H), 1.70 (s, 1H), 1.62 (s, 2H), 1.40e1.33 (m, 1H), 1.31e1.26
71
series computer workstation with Chiralcel AD/OD/OJ-H
column.
13
(m, 1H), 0.99 (br s, 1H), 0.87e0.84 (m, 2H), 0.55 (s, 7H) ppm;
C
4
.2. Preparation of the organocatalysts with 2c as example
8S,9S)-9-amino-(9-deoxy)-epiquinine was prepared according
NMR (400 MHz, CDCl ):
3
d
¼182.5, 158.1, 147.6, 144.9, 140.8 (ꢃ2),
1
32.0, 122.1, 114.8 (ꢃ2), 101.6, 55.7 (ꢃ2), 55.5, 40.9, 39.3 (ꢃ2), 31.4,
þ
(
27.7 (ꢃ2), 27.3 (ꢃ2), 27.0 (ꢃ3), 25.6 ppm; HRMS-ESI (m/z): [MþH]
16
to the literature. Dissolved (8S,9S)-9-amino-(9-deoxy)-epiquinine
calcd for C26
37 4
H N OS 453.2688, found 453.2672.
ꢁ
ꢁ
20
D
(
(
646.4 mg, 2.0 mmol) in fresh dry THF (10 mL) at ꢀ10 C, CS
2
Catalyst 2g: White solid; 79% yield; mp 114.9e117.1 C; ½ ꢂ
a
0.73 mL,12 mmol) and DCC (412.6 mg, 2.0 mmol) were added then.
ꢀ135.9 (c 0.25, CHCl
3
); IR (KBr):
n
¼3267, 3074, 2869, 1620, 1535,
The reactionwas stirred in this temperature overnight. The resulting
1512, 1296, 1265, 1203, 1137, 1029, 918, 852, 829, 736, 667, 617,

516
N. Ji et al. / Tetrahedron 72 (2016) 512e517
ꢀ
ꢁ
4
(
2
3
1
1
51 cm 1; 1H NMR (400 MHz, CDCl
3
):
d
¼8.75 (d, J¼4.4 Hz, 1H), 8.03
(purity 85%, 0.24 mmol) was added at ꢀ40 C, stirring continued for
the time indicated in Table 4, and the crude mixture was purified by
flash chromatography on silica gel (petroleum ether/ethyl
acetate¼7:1) to provide the corresponding oxaziridines 3aeo.
d, J¼9.2 Hz, 1H) 7.67 (d, J¼2 Hz, 1H), 7.47 (br s, 1H), 7.40e7.36 (m,
H), 6.23 (br s, 1H), 5.71e5.62 (m, 1H), 4.98e4.91 (m, 2H), 3.98 (s,
H), 3.29e3.23 (m, 1H), 3.08 (s, 2H), 2.76e2.69 (m, 2H), 2.31 (s, 1H),
.70 (s, 1H), 1.67e1.62 (m, 2H), 1.39 (s, 9H), 1.28e1.24 (m, 1H),
13
.11e1.04 (m, 1H), 0.92 (d, J¼6.8 Hz, 1H) ppm; C NMR (400 MHz,
Acknowledgements
CDCl ):
3
d
¼181.3, 157.6, 147.7, 144.7, 141.0, 131.8, 128.1, 121.5, 114.8,
1
2
02.2, 69.7, 55.7 (ꢃ2), 55.6, 52.9, 40.7, 39.5, 30.8, 29.2 (ꢃ3), 27.8,
We thank the National Natural Science Foundation of China
(21272272) and the Young Scholar Foundation of the Fourth Mili-
tary Medical University for financial support. We also would like to
express our great thanks to Mr. Huanfei Meng and Mr. Hanpeng Qin
for language revision.
7.2, 25.8, 18.8 ppm; HRMS-ESI (m/z): [MþH]þ calcd for
25 35 4
C H N OS 439.2532, found 439.2499.
ꢁ
20
D
Catalyst 2h: White solid; 72% yield; mp 110.4e113.9 C; ½ ꢂ
a
ꢀ
86.8 (c 0.25, CHCl
3
); IR (KBr):
n
¼3240, 3070, 3047, 2886, 2831,
1
8
1
5
5
620, 1512, 1473, 1361, 1319, 1261, 1226, 1134, 1083, 1029, 918, 852,
29, 736, 567 cm ; H NMR (400 MHz, CDCl ):
H), 8.05 (d, J¼9.6 Hz, 1H), 7.73 (br s, 1H), 7.43e7.40 (m, 2H),
.74e5.65 (m, 1H), 5.05e5.00 (m, 2H), 4.01 (s, 3H), 3.39e3.26 (m,
H), 2.87e2.81 (m, 2H), 2.44e2.40 (m, 2H), 1.77 (s, 3H), 1.44e1.42
ꢀ1 1
3
d¼8.77 (d, J¼4.4 Hz,
Supplementary data
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2015.12.010.
13
(
m, 1H), 1.36e1.30 (m, 2H), 1.05e0.99 (m, 1H), 0.88 (s, 9H) ppm;
C
NMR (400 MHz, CDCl
3
):
d
¼182.2, 158.0, 147.6, 144.8, 140.0, 131.8,
References and notes
1
2
27.9, 122.0, 115.4, 114.7, 102.1, 60.8, 55.8 (ꢃ2), 55.1, 42.5, 41.2, 38.8,
9.8, 29.3 (ꢃ3), 29.0, 27.2, 25.3, 22.6, 11.4 ppm; HRMS-ESI (m/z):
1. (a) Williamson, K. S.; Michaelis, D. J.; Yoon, T. P. Chem. Rev. 2014, 114,
þ
8016e8036; (b) Sala, G. D.; Lattanzi, A. ACS Catal. 2014, 4, 1234e1245.
[MþH] calcd for C27
39 4
H N OS 467.2845, found 467.2840.
20
D
2
. (a) Davis, F. A.; Abdul-malik, N. F.; Awad, S. B.; Harakal, M. E. Tetrahedron Lett.
1981, 22, 917e920; (b) Beak, P. Acc. Chem. Res. 1992, 25, 215e222; (c) Davis, F.
A.; Jenkins, L. A.; Billmers, R. L. J. Org. Chem. 1986, 51, 1033e1040; (d) Davis, F. A.;
Billmers, J. M.; Stringer, O. D. Tetrahedron Lett. 1983, 24, 3191e3194; (e) Davis, F.
A.; Sheppard, A. C. Tetrahedron Lett. 1988, 29, 4365e4368; (f) Li, F.; Tartakoff, S.
S.; Castle, S. L. J. Org. Chem. 2009, 74, 9082e9093; (g) Amone, A.; Cavicchioli, M.;
Montanan, V.; Resnati, G. J. Org. Chem. 1994, 59, 5511e5513.
ꢁ
Catalyst 2i: Yellow solid; 66% yield; mp 114.0e117.2 C; ½ ꢂ
a
ꢀ
92.6 (c 0.25, CHCl
3
); IR (KBr):
n¼3240, 3062, 2954, 2869, 1620,
1
558, 1508, 1338, 1265, 1226, 1029, 918, 852, 829, 740, 678, 528,
ꢀ
1 1
415 cm ; H NMR (400 MHz, CDCl
3
):
d¼8.77 (d, J¼4.4 Hz, 1H), 8.07
(
d, J¼9.2 Hz, 1H), 7.64 (br s, 1H), 7.45e7.41 (m, 2H), 6.03 (br s, 1H),
3. (a) Boger, D. L.; Sch
u€ le, G. J. Org. Chem. 1998, 63, 6421e6424; (b) Vidal, J.; Guy,
5
3
1
1
.72e5.64 (m, 1H), 5.01e4.95 (m, 2H), 4.16 (br s, 1H), 3.99 (s, 3H),
.30e3.24 (m, 1H), 3.19e3,16 (m, 2H), 2.86e2.75 (m, 3H), 2.34 (br s,
H), 1.73 (s, 1H), 1.66 (d, J¼6.4 Hz, 2H), 1.44e1.39 (m, 1H), 1.26 (s,
L.; St eꢀ rin, S.; Collet, A. J. Org. Chem. 1993, 58, 4791e4793; (c) Choong, I. C.;
Ellman, J. A. J. Org. Chem. 1999, 64, 6528e6529; (d) Allen, C. P.; Benkovics, T.;
Turek, A. K.; Yoon, T. P. J. Am. Chem. Soc. 2009, 131, 12560e12561.
4. (a) Suda, K.; Hino, F.; Yijima, C. J. Org. Chem. 1986, 51, 4232e4239; (b) Splitter, J.
S.; Calvin, M. J. Org. Chem. 1965, 30, 3427e3436; (c) Aub eꢀ , J.; Burgett, P. M.;
Wang, Y. G. Tetrahedron Lett. 1988, 29, 151e154; (d) Aub eꢀ , J.; Ghosh, S.; Tanol, M.
13
H), 1.01 (d, J¼6.4 Hz, 4H), 0.46 (s, 9H) ppm; C NMR (400 MHz,
CDCl
3
):
d¼182.4, 158.0, 147.4, 144.7, 140.7 (ꢃ2), 131.8, 121.9, 114.6
(
2
ꢃ2), 101.4, 55.6,55.4, 40.7, 39.2, 33.7, 31.3, 27.6, 27.1, 26.8 (ꢃ3), 25.5,
J. Am. Chem. Soc. 1994, 116, 9009e9018; (e) Minisci, F.; Galli, R.; Malatesta, V.;
Caronna, T. Tetrahedron 1970, 26, 4083e4091.
þ
4.7, 22.4, 13.9, 11.2 ppm; HRMS-ESI (m/z): [MþH] calcd for
5. (a) Murai, N.; Komatsu, M.; Ohshiro, Y.; Agawa, T. J. Org. Chem. 1977, 42,
C
27
39
H N
4
OS 467.2845, found 467.2843.
20
4
48e451; (b) Lam, W. Y.; DesMarteau, D. D. J. Am. Chem. Soc. 1982, 104,
ꢁ
Catalyst 2j: White solid; 75% yield; mp 125.9e127.8 C; ½
a
ꢂ
D
4034e4035; (c) Michaelis, D. J.; Shaffer, C. J.; Yoon, T. P. J. Am. Chem. Soc. 2007,
129, 1866e1867; (d) Benkovics, T.; Guzei, I. A.; Yoon, T. P. Angew. Chem., Int. Ed.
-
2
91.3 (c 0.25, CHCl
835,1620,1527,1361,1261,1226,1029, 918, 852, 829, 736 cm ; H
NMR (400 MHz, CDCl ):
¼8.76 (d, J¼4.4 Hz, 1H), 8.05 (d, J¼9.2 Hz,
H), 7.66 (br s, 1H), 7.49 (s, 1H), 7.45e7.40 (m, 2H), 5.96 (br s, 1H),
3
); IR (KBr):
n
¼3274, 3255, 3066, 2962, 2869,
ꢀ
1 1
2010, 49, 9153e9157; (e) Dong, S.-X.; Liu, X.-H.; Zhu, Y.; He, P.; Lin, L.-L.; Feng,
X.-M. J. Am. Chem. Soc. 2013, 135, 10026e10029.
. Mahale, R. D.; Rajput, M. R.; Maikap, G. C.; Gurjar, M. K. Org. Process Res. Dev.
2010, 14, 1264e1268.
3
d
6
1
5
1
3
1
.71e5.63 (m, 1H), 4.99e4.93 (m, 2H), 3.99 (s, 3H), 3.28e3.22 (m,
H), 3.12 (s, 2H), 2.80e2.71 (m, 2H), 2.31 (br s, 1H), 1.71e1.64 (m,
H), 1.43e1.35 (m, 2H), 1.26 (s, 2H), 1.03e0.98 (m, 2H), 0.88 (br s,
7. He, F.; Foxman, B. M.; Snider, B. B. J. Am. Chem. Soc. 1998, 120, 6417e6418.
8. (a) Han, S.; Movassaghi, M. J. Am. Chem. Soc. 2011, 133, 10768e10771; (b) Qi, X.-
B.; Bao, H.-L.; Tambar, U. K. J. Am. Chem. Soc. 2011, 133, 10050e10053.
9
. (a) Troisi, L. S.; Lorenzis, D.; Fabio, M.; Rosato, F.; Granito, C. Tetrahedron:
Asymmetry 2008, 19, 2246e2251; (b) Armstrong, A.; Edmonds, I. D.; Swarbrick,
M. E. Tetrahedron Lett. 2003, 44, 5335e5338; (c) Davis, F. A.; Jenkins, R. H.;
Awad, S. B.; Stringer, O. D.; Watson, W. H.; Galloy, J. J. Am. Chem. Soc. 1982, 104,
H), 0.76 (s, 9H) ppm; 13C NMR (400 MHz, CDCl
):
d
¼182.4, 158.1,
3
1
47.6, 144.8, 140.8 (ꢃ2), 132.0, 122.1, 114.9 (ꢃ2), 101.5, 55.8, 55.4,
4
0.9, 39.4, 39.2, 31.5, 29.0, 27.6, 27.2, 27.0 (ꢃ3), 25.6, 22.6, 14.1,
412e5418; (d) Boh eꢀ , L.; Lusinchi, M.; Lusinchi, X. Tetrahedron 1999, 55,
141e154.
0. (a) Davis, F. A.; Weismiller, M. C. J. Org. Chem. 1990, 55, 3715e3717; (b) Davis, F.
5
1
1.4 ppm; HRMS-ESI (m/z): [MþH]þ calcd for C27
39 4
H N OS 467.2845,
1
found 467.2839.
A.; Reddy, R. T.; Han, W.; Carroll, P. J. J. Am. Chem. Soc. 1992, 114, 1428e1437; (c)
Davis, F. A.; Towson, J. C.; Weismiller, M. C.; Lal, S.; Carroll, P. J. J. Am. Chem. Soc.
1988, 110, 8477e8482; (d) Davis, F. A.; Haque, M. S.; Ulatowski, T. G.; Towson, J.
C. J. Org. Chem. 1986, 51, 2402e2404.
ꢁ
20
D
Catalyst 2k: White solid; 79% yield; mp 115.3e117.2 C; ½ ꢂ
a
þ139.3 (c 0.25, CHCl
237, 1203, 1011, 915, 851, 736 cm
¼8.74 (d, J¼4.4 Hz, 1H), 8.05 (d, J¼9.2 Hz, 1H), 7.71 (br s, 1H),
.61e7.60 (m, 1H), 7.45e7.39 (m, 2H), 6.26e6.25 (m, 1H), 5.66e5.63
m, 1H), 4.94e4.87 (m, 2H), 3.99 (s, 3H), 3.31e3.05 (m, 5H),
3
); IR (KBr):
n
¼3280, 3054, 2932, 1523, 1189,
ꢀ
1 1
1
d
3
; H NMR (400 MHz, CDCl ):
1
1. (a) Davis, F. A.; Lamendola, J., Jr.; Nadir, U.; Kluger, E. W.; Sedergran, T. C.;
Panunto, T. W.; Billmers, R.; Jenkins, R., Jr.; Turchi, I. J.; Watson, W. H.; Chen, J. S.;
Kimuralb, M. J. Am. Chem. Soc. 1980, 102, 2000e2005; (b) Sandrinelli, F.; Fon-
taine, G.; Perrio, S.; Beslin, P. J. Org. Chem. 2004, 69, 6916e6919.
7
(
1
2. (a) Lykke, L.; Rodríguez-Escrich, C.; Jørgensen, K. A. J. Am. Chem. Soc. 2011, 133,
4932e14935; (b) Zhang, T.-Y.; He, W.; Zhao, X.-Y.; Jin, Y. Tetrahedron 2013, 69,
7416e7422; (c) Olivares-Romero, J.; Li, Z.; Yamamoto, H. J. Am. Chem. Soc. 2012,
34, 5440e5443; (d) Uraguchi, D.; Tsutsumi, R.; Ooi, T. J. Am. Chem. Soc. 2013,
35, 8161e8164; (e) Williamson, K. S.; Sawicki, J. W.; Yoon, T. P. Chem. Sci. 2014,
, 3524e3527; (f) Jin, Y.; Zhang, T.-Y.; Wang, W.; Chang, S.; Feng, B. Chirality
2
.86e2.71 (m, 3H), 2.32 (br s, 1H), 1.69e1.62 (m, 3H), 1.39e1.34 (m,
1
13
1
CDCl
H), 1.00e0.95 (m, 1H), 0.62 (s, 9H) ppm; C NMR (400 MHz,
):
¼182.3, 158.0, 147.5, 144.7, 140.7 (ꢃ2), 131.8, 127.6, 127.5,
1
1
5
3
d
1
22.0, 114.7 (ꢃ2), 101.5, 55.6 (ꢃ2), 55.3, 40.8, 39.1 (ꢃ2), 31.4, 27.5,
þ
27.1, 26.9 (ꢃ3), 25.5 ppm; HRMS-ESI (m/z): [MþH] calcd for
2014, 26, 150e154.
C
26 37
H N
4
OS 453.2688, found 453.2692.
13. (a) Shi, X.; He, W.; Li, H.; Zhang, X.; Zhang, S.-Y. Tetrahedron Lett. 2011, 52,
3
1
(
204e3207; (b) Taylor, M. S.; Jacobsen, E. N. Angew. Chem., Int. Ed. 2006, 45,
520e1543; (c) Doyle, A. G.; Jacobsen, E. N. Chem. Rev. 2007, 107, 5713e5743;
d) Yu, L.; Li, P.-F. P. Tetrahedron Lett. 2014, 55, 3697e3700; (e) Chen, J.-C.; Zou,
4
.4. Catalytic asymmetric oxaziridination
Y.-Q.; Fu, L.; Ren, F.; Tan, F.; Xiao, W.-J. Tetrahedron 2010, 66, 5367e5372; (f) Li,
J.; Yang, G.-X.; Qin, Y.-Y.; Yang, X.-R.; Cui, Y.-C. Tetrahedron: Asymmetry 2011, 22,
The corresponding imine (0.20 mmol), catalyst 2f (0.024 mmol)
were dissolved in xylene (4.0 mL) at room temperature, and the
mixture was stirred at room temperature for 5 min. Then, m-CPBA
6
13e618; (g) Asymmetric Domino Reactions, 2013; pp 251e467.
4. (a) Li, H.; Zhang, X.; Shi, X.; Ji, N.; He, W.; Zhang, S.-Y.; Zhang, B.-L. Adv. Synth.
Catal. 2012, 354, 2264e2274; (b) Zhang, Z.-G.; Schreiner, P. R. Chem. Soc. Rev.
1

N. Ji et al. / Tetrahedron 72 (2016) 512e517
009, 38, 1187e1198; (c) He, C.-Y.; Ren, X.-C.; Feng, Y.-H.; Zhang, S.-Y.; Chen, W.-
517
2
Peng, Y.-G. Org. Biomol. Chem. 2012, 10, 3730e3738; (h) Demir, A. S.; Basceken,
S. Tetrahedron: Asymmetry 2013, 24, 515e525; (i) Bai, S.; Liang, X.-P.; Song, B.-A.;
Bhadury, P. S.; Hu, D.-Y.; Yang, S. Tetrahedron: Asymmetry 2011, 22, 515e523; (j)
You, S.-L.; Cai, Q.; Zeng, M. Chem. Soc. Rev. 2009, 38, 2190e2201.
P. Tetrahedron Lett. 2015, 56, 4036e4038; (d) Wang, H.-Y.; Chai, Z.; Zhao, G.
Tetrahedron 2013, 69, 5104e5111; (e) Serdyuk, O. V.; Heckel, C. M.; Tsogoeva, S.
B. Org. Biomol. Chem. 2013, 11, 7051e7071.
5. (a) Liu, Y.-L.; Wang, X.; Wang, X.-Y.; He, W. Org. Biomol. Chem. 2014, 12,
163e3166; (b) Konda, S.; Zhao, J. C.-G. Tetrahedron Lett. 2014, 55, 5216e5218;
c) Takemoto, Y. Org. Biomol. Chem. 2005, 3, 4299e4306; (d) Fang, X.; Wang, C.-
1
16. (a) Henri, B.; J u€ rgen, B.; Bernhard, N. Tetrahedron: Asymmetry 1995, 6,
3
(
1699e1702; (b) Larrow, J. F.; Jacobsen, E. N. J. Org. Chem. 1994, 59, 1939e1942;
(c) He, W.; Liu, P.; Zhang, B.-L.; Sun, X.-L.; Zhang, S.-Y. Appl. Organomet. Chem.
2006, 20, 328e334.
J. Chem. Commun. 2015, 1185e1197; (e) Reddy, B. V. S.; Swain, M.; Reddy, S. M.;
Yadav, J. S.; Sridhar, B. RSC Adv. 2014, 4, 42299e42307; (f) Vesely, J.; Rios, R.
Chem. Soc. Rev. 2014, 43, 611e630; (g) Gao, J.-Z.; Chuan, Y.-M.; Li, J.-L.; Xie, F.;
17. Chen, X.-H.; Dong, S.-X.; Qiao, Z.; Zhu, Y.; Xie, M.-S.; Lin, L.-L.; Liu, X.-H.; Feng,
X.-M. Chem.dEur. J. 2011, 17, 2583e2586.