Enantioselective organocatalytic oxidation of ketimine

Article abstract of DOI:10.1039/c5ob02042e

C₃-Symmetric chiral trisimidazolines with m-chloroperbenzoic acid promoted the organocatalytic oxidation of N-sulfonyl ketimine. The present imidazoline catalysis produced oxaziridines bearing a tetrasubstituted carbon stereogenic center in hig

Full text of DOI:10.1039/c5ob02042e

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Enantioselective organocatalytic oxidation of
ketimine†
Cite this: DOI: 10.1039/c5ob02042e
a
a
a
b
Shinobu Takizawa,* Kenta Kishi, Mohamed Ahmed Abozeid, Kenichi Murai,*
b
a
Hiromichi Fujioka and Hiroaki Sasai
Received 1st October 2015,
Accepted 10th November 2015
3
C -Symmetric chiral trisimidazolines with m-chloroperbenzoic acid promoted the organocatalytic
DOI: 10.1039/c5ob02042e
oxidation of N-sulfonyl ketimine. The present imidazoline catalysis produced oxaziridines bearing a
www.rsc.org/obc
tetrasubstituted carbon stereogenic center in high yields with up to 87% ee.
Introduction
Oxaziridines are three-membered heterocycles that consist of
oxygen, nitrogen and carbon atoms. These strained small het-
erocycles function as purely organic, non-acidic agents for the
electrophilic transfer of oxygen and/or nitrogen to alkenes,
1
enolates, and heteroatoms. Among existing oxaziridines,
those with a sulfonyl group on the nitrogen atom are the most
2
widely used as Davis’ reagents because of their easy handling.
In 2011, Jørgensen reported the first catalytic and enantio-
selective synthesis of oxaziridines from N-tosyl aldimines
using the cinchona alkaloid-derived organocatalyst with
3
a
Scheme 1 Enantioselective organocatalytic oxidation of ketimines 2
using C -symmetric chiral trisimidazolines 1 with mCPBA.
m-chloroperbenzoic acid (mCPBA). Following this success, a
catalytic enantioselective oxidation of N-sulfonyl aldimines has
been recognized as one of the most straightforward methods
3
4
to construct chiral oxaziridines.
To date, the synthetic utility of chiral oxaziridine derivatives 3 bearing a chiral tetrasubstituted carbon stereogenic center in
1
,5
has been markedly enhanced, although few reports on the high yields with up to 87% ee (Scheme 1).
catalytic and enantioselective oxidation of ketimines have been
published. As a solitary example, in 2012, Yamamoto reported
that a chiral hafnium(IV) complex facilitated oxygen–atom
transfer from cumene hydroperoxide to N-tosyl ketimine to
Results and discussion
give the corresponding oxaziridine with a chiral tetrasubsti- Our group previously reported the enantioselective organocata-
6
tuted carbon stereogenic center in 38% yield with 98% ee.
lytic Michael reaction, bromolactonization, and Friedel–Crafts-
The development of an efficient method for constructing type reactions involving C -symmetric chiral trisimidazoline
3
7
chiral oxaziridines from ketimines has been a challenge in 1. In the imidazoline catalysis, a synergistic activation by the
recent asymmetric chemistry. Here, we report the enantio- imidazolines can lead to specific control of the transition-state
selective organocatalytic oxidation of ketimines 2 using C3- structure, leading to products with high enantioselectivity.
symmetric chiral trisimidazolines 1 with mCPBA. The present
We assumed that in the trisimidazoline-catalyzed oxidation
imidazoline catalysis afforded the corresponding oxaziridines of ketimine with mCPBA, one imidazoline could function as a
Brønsted base and another could act as a Brønsted acid, result-
ing in the in situ formation of a chiral peroxide that could
transfer oxygen to the ketimine, thereby furnishing the desired
oxaziridine with high enantiocontrol (Fig. 1).
a
The Institute of Scientific and Industrial Research (ISIR), Osaka University,
8
-1 Mihogaoka, Ibaraki-shi, Osaka 567-0047, Japan. E-mail: taki@sanken.osaka-u.ac.jp
b
Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka,
As the first step in the development of the oxaziridination,
the oxidation of ketimine 2a with mCPBA (1.1 eq.) was
Suita-shi, Osaka 565-0871, Japan. E-mail: murai@phs.osaka-u.ac.jp
Electronic supplementary information (ESI) available. See DOI: 10.1039/
†
7
a–d
c5ob02042e
attempted using 10 mol% of chiral trisimidazoline 1a
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bisimidazoline 4 (entry 15), the three chiral imidazoline units
on catalyst 1a were essential. Next, to establish high
asymmetric induction to substrate 2a, we tested chiral catalysts
1
with various substituents on their imidazoline rings (entries
t
7e
16–19). The catalysts bearing 4- Bu-C H (1b), 4-MeO-C H
6 4 6 4
7
f
7g
(
2 6 3
1c), and 2,3-Me -C H (1d) did not improve the stereo-
selectivity (entries 16–18). The use of the newly designed
trisimidazoline 1e, which was derived from (1S,2S)-1,2-bis(3,5-
di-tert-butylphenyl)ethane-1,2-diamine, improved ee of 3a
Fig. 1 A plausible mode of activation of mCPBA for the oxidation of
ketimines.
8
(
76% ee, entry 19) while maintaining the high chemical yield.
In the absence of catalyst, no background reaction was
observed under the optimized conditions (entry 20). Hydrogen
peroxide, sodium hypochlorite, or peracetic acid was tested as
a co-oxidant in the reaction and did not give successful results.
The organocatalyst 1e with mCPBA efficiently promoted the
oxidation of various substituted ketimines 2 to afford the
corresponding oxaziridines 3 bearing a tetrasubstituted carbon
stereogenic center (Scheme 2). The oxaziridination of
ketimines 2b–2h, and 2j–2l with electron-withdrawing or
electron-donating groups on their aromatic rings afforded
products 3b–3h, and 3j–3l in 78% to quantitative yields with
Table 1 Oxidation of ketimine 2a catalyzed by chiral imidazolines
a
b
Catalyst
(mol %)
Temp.
(°C)
Yield
(%)
ee
Entry
Solvent
(%)
1
2
3
4
5
6
7
8
9
1a (10)
1a (10)
1a (10)
1a (10)
1a (10)
1a (10)
1a (10)
1a (10)
1a (10)
1a (10)
1a (10)
1a (10)
1a (5)
1a (1)
4 (15)
1b (10)
1c (10)
1d (10)
1e (10)
None
−20
−30
−40
−50
−30
−30
−30
−30
−30
−30
−30
−30
−30
−30
−30
−30
−30
−30
−30
−30
Toluene
Toluene
Toluene
Toluene
Quant
Quant
Quant
53
Quant
Quant
Quant
73
12
58
51
Quant
90
48
52
51
45
42
48
45
32
11
42
35
52
47
25
12
20
50
46
76
—
60–87% ees. The oxidation of aldimines 2m and 2n readily
afforded their corresponding oxaziridines 3m and 3n in good
yields and enantioselectivities. Although the introduction of a
EtC
ClC
6
H
5
6
H
5
2
(
-naphthyl, methyl or 2-pyridyl group onto the ketimine
2o–2q) was tolerated, 4-methoxyphenyl and 2-thiophenyl
o-Xylene
m-Xylene
n-Hexane
ketimines (2i and 2r) were decomposed under the optimized
10
11
12
13
14
15
16
17
18
19
20
CH
Cl
2 2
CHCl
3
c
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
66
Quant
Quant
Quant
Quant
Quant
Trace
a
b
c
Isolated yield. Determined by HPLC (Daicel Chiralpak IA). m-Cl-
6 4 2
C H CO H (40 mol %) was added.
(
1
Table 1). A screening of the reaction conditions with catalyst
a (entries 1–11) revealed that the process in toluene at −30 °C
gave the desired oxaziridine 3a in quantitative yield and with
2% ee (entry 2). In the oxidation of 2a with 1a and mCPBA,
5
m-chlorobenzoic acid (mCBA) was also formed as a side
product. In the presence of mCBA (40 mol%), the reaction
produced 3a in 52% ee quantitatively (entry 12). Because
mCBA is insoluble in toluene at −30 °C, the acid did not affect
the reaction. When a catalyst loading of 1 mol% was applied to
the reaction, the product’s yield and ee decreased (entry 14).
Since a lower enantioselectivity was observed when using
Scheme 2 Substrate scope. Yield values were based on the isolated
products. The ee values were determined by HPLC (Daicel Chiralpak IA
for 3a, 3b, 3k and 3l; Chiralpak ID for 3c, 3d, 3e, 3f, 3g, 3h, 3p, 3q and
3
a
o; Daicel Chiralcel OD-H for 3j and 3n; Daicel Chiralcel OJ for 3m).
After a single recrystallization.
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conditions. Optically pure 3a and 3c were obtained after a
single recrystallization of the product from hexane/CH Cl .
2
2
The absolute configuration of 3a was assigned as the (R)-
form by comparison with optical rotation data reported in the
3
a,4d–e,6,9
literature.
To investigate how the substrates interacted with imidazo-
1
line catalyst 1, we conducted H-NMR experiments using cata-
lyst 1a, ketimine 2j and mCPBA (Fig. 2). When ketimine 2j and
catalyst 1a were mixed, no signal shift was observed (see ESI†).
In contrast, the mixing of catalyst 1a and mCPBA resulted in a
shift of the proton signal of catalyst 1a (aromatic protons on
the core benzene ring: from δ = 8.97 to 10.49 (ppm); benzylic
protons on the imidazoline rings: from δ = 4.88 to 5.12 (ppm),
Fig. 2a and c, also see ESI†) and of the signal of the peracid
proton of mCPBA from δ = 11.17 to 6.60–7.60 (ppm)
(
Fig. 2b and c). Additionally, a 2D-NOESY NMR spectrum also
showed the interaction between the catalyst 1a and mCPBA
Fig. 3 and also see ESI†). These observations suggest that an
(
ion pair formed between the catalyst and mCPBA. This associ-
1
ation was implied by H-NMR measurements of a 1 : 3 mixture
of catalyst 1a and mCPBA, inducing a characteristic downfield
shift of the signal for the protons of catalyst 1a and mCPBA.
8
7
,10
Fig. 3 2D-NOESY NMR spectrum of catalyst 1a and mCPBA in d -
toluene.
A competition experiment between phenyl-substituted keti-
mine 2a and 4-bromophenyl-substituted ketimine 2g showed
that the 3a/3g product ratio was 1.0/1.7. In a similar compe-
tition study, oxaziridine 3f having a 4-methylphenyl group was
obtained in a 1.0/2.0 ratio against 3g (Scheme 3). In the
present process, an electron deficient group tends to accelerate
the reaction rate.
These obtained results are in agreement with the oxidation
mechanism shown in Fig. 1 and 4. Initially, one imidazoline
nitrogen atom in catalyst 1e is protonated by mCPBA, whereas
the other imidazoline group coordinates to the oxygen atom of
Scheme 3 Comparison of reactivity.
Fig. 4 Possible mode of enantioselection.
the peroxy carbonyl group, leading to tight-ion-pair aggrega-
tion. Next, attack of the generated chiral oxidant to ketimine 2
3
forms oxaziridine 3 through an α-aminoperoxy intermediate.
After the oxaziridination, mCBA was released from imidazoline
1e because mCBA is insoluble under the optimized conditions.
The chiral peracid species was regenerated from imidazoline 1e
with mCPBA.
1
8
The oxidation of ketimine 2 mediated by the chiral peracid
occurred via an intermediate formation with the least steric
Fig. 2 H-NMR spectra in d -toluene: (a) catalyst 1a, (b) mCPBA, (c)
catalyst 1a + mCPBA.
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1
3
hindrance between the tert-butyl moieties of the catalyst and solid; m.p. >300 °C; H-NMR (CDCl ) δ 8.70 (s, 3H), 7.35 (dd,
the fused aromatic ring of the substrate. Therefore the reaction 6H, J = 1.8, 1.8 Hz), 7.18 (d, 6H, J = 1.8 Hz), 7. 13 (d, 6H, J = 1.8
using (S)-1e would favor the generation of the (R)-configuration Hz), 5.64 (brs., 3H), 5.15 (d, 3H, J = 7.8 Hz), 4.90 (d, 3H, J = 7.8
1
3
products 3a–3h and 3j–3p or the (S)-configuration product 3q Hz), 1.30 (s, 54H), 1.29 (s, 54H); C NMR (CDCl
Fig. 4). 151.2, 150.8, 142.8, 142.4, 131.1, 128.2, 121.8, 121.6, 121.2,
20.2, 80.7, 69.9, 34.88, 34.86, 31.52, 31.47; HRMS (MALDI-
3
) δ 161.2,
(
1
+
TOF): calcd for C99
H
139
N
6
, m/z = 1412.1056 [(M + H) ], found
2
5
m/z = 1412.1016; [α] = –85.1 (c 1.39, CHCl ); IR (KBr): ν 3374,
Conclusions
D
3
1
2
963, 2904, 2868, 1624, 1599, 1581, 1477, 1362 cm−
.
We have demonstrated the first imidazoline-mediated enantio-
selective organocatalytic oxidation of ketimine. Various keti-
mine substrates bearing either electron-withdrawing or
electron-donating groups were successfully oxidized in the
Preparation of ketimine 2j
To a mixture of Mg turnings (2 eq., 5.46 mmol, 130 mg) and
iodine (one crystal) in THF (dry, degassed), 5-bromo-m-xylene
3
presence of 10 mol% of C -symmetric chiral trisimidazolines 1
(
2 eq., 5.46 mmol, 1.00 g, 0.73 mL) was added dropwisely at
with mCPBA (1.1 eq.). An investigation into the detailed reac-
tion mechanism and an improvement of the asymmetric
induction ability of catalyst 1 as well as a synthetic utility of
the chiral oxaziridines 3 is currently underway.
room temperature under N . After stirring for 30 min, the
resulting Grignard reagent was transferred by using syringe
2
under N , and then added dropwisely to other flask containing
2
saccharin (2.73 mmol, 0.50 g) dissolved in 5.5 mL THF. The
reaction was stirred overnight at room temperature followed by
quenching using sat. NH Cl solution. The reaction mixture
4
aq.
Experimental section
General information
was extracted by using dichloromethane followed by washing
using brine, drying by Na SO and finally the solvent was
2
4
removed in vacuo. The remaining residue was dissolved in dry
toluene (14 mL) followed by adding of tosyl acid (2.2 mmol,
All reactions were performed with standard Schlenk technique
1
13
19
under N
2
atmosphere. H-, C- and F-NMR spectra were
0.38 g). Then the reaction was heated under reflux using Dean-
recorded with JEOL JMN LA-400 FT NMR or JNM ECA600 FT
1
13
Stark system overnight. After cooling to room temperature, the
solvent was removed using rotavap followed by the addition of
NMR ( H-NMR 600 or 400 MHz, C-NMR 150 or 100 MHz).
1
H-NMR spectra are reported in ppm (δ) relative to the chemi-
sat. NH Cl
solution (20 mL). The resulting mixture was
4
aq.
cal shift of tetramethylsilane. Multiplicity (s = singlet, d =
1
3
extracted by dichloromethane and subsequently dried using
sodium sulfate. After removing of the solvent under vaccum,
the remaining solid was chromatographed over silica gel
doublet, q = quartet, t = triplet, m = multiplet). C-NMR
spectra reported in ppm (δ) relative to the central line of triplet
for CDCl at 77.00 ppm. CF CO H used as external standards
3
3
2
1
9
(hexane : ethyl acetate = 2 : 1) to give the product 2j (394 mg,
for F-NMR. Mass spectra were obtained on JMS-T100LC-JEOL
ESI), JMS-700-JEOL (FAB) and Shimadzu AXIMA-TOF (MALDI)
1
5
8
2
3%). Pale yellow solid; m.p. 189–190 °C; H-NMR (CDCl
3
) δ
(
.02–8.00 (m, 1H, ArH), 7.90–7.90 (m, 1H, ArH), 7.79–7.74 (m,
H, ArH), 7.58–7.57 (m, 2H, ArH), 7.33–7.32 (m, 1H, ArH), 2.44
s, 6H, 2 × CH ); C-NMR (CDCl ) δ 171.4, 141.0, 139.1 (2 × C),
3 3
spectrometers. Optical rotations were measured with JASCO
P-1030 polarimeter. HPLC analyses were performed on a
JASCO HPLC system (JASCO PU 980 pump and UV-975 UV/Vis
detector) using a mixture of hexane and 2-propanol eluents.
FT-IR spectra were recorded on a JASCO FT-IR system (FT/
IR4100). Melting point was measured with SHIMADZU
1
3
(
1
2
2
3
35.2, 133.6, 133.3, 130.7, 130.3, 127.2 (2 × C), 126.7, 123.0,
1.3 (2 × C); HRMS (ESI) calcd for C H NNaO S, m/z =
1
5
13
2
+
94.0559 [(M + Na) ], found m/z = 294.0552; IR (KBr): ν 3062,
008, 2921, 1602, 1530, 1458, 1382, 1237 cm−
1
.
DSC-60. Column chromatography on SiO was performed with
2
Kanto Silica Gel 60 (40–100 μm). Commercially available
organic and inorganic compounds were used without further General procedure for enantioselective organocatalytic
purification. The solvents were purified and dried by the stan- oxidation of ketimine
dard procedures. Cyclic ketimines 2a–g and 2i–l, aldimine 2m
A mixture of ketimine 2 (0.0145 mmol) and trisimidazoline 1e
1
1
were prepared following the reported procedures.
(
10 mol%, 1.45 μmol, 2 mg) was dissolved in 0.15 mL toluene
and then cooled to −30 °C. After that m-chloroperbenzoic acid
1.1 eq., 0.0158 mmol, 3.9 mg) was added one time at the
Preparation of trisimidazoline 1e
(
7
e
Trimethyl benzene-1,3,5-tris(carboxylimidate) (0.124 mmol, same temperature and then the reaction was stirred for 24 h
3
1
1.0 mg) and (1S,2S)-1,2-bis (3,5-di-tert-butylphenyl)ethane- under N . The final oxaziridine product 3 was purified by
2
8
,2-diamine (0.435 mmol, 190 mg) were dissolved in PTLC (SiO
2
, hexane : ethyl acetate = 2 : 1).
mixture of EtOH and pyridine (4.4 mL, 10 : 1) under N
resulting solution was heated at 80 °C for 24 h. After cooling to literature. White solid (quant); H-NMR (CDCl ) δ 7.88 (dd,
2
. The 3a: Analytical data were well matched with the reported
1
2
1
3
room temperature, the solvent was removed in vacuo and the 1H, ArH, J = 2.0, 7.60 Hz), 7.80–7.70 (m, 2H, ArH),
2
remaining residues were purified by SiO column chromato- 7.65–7.49 (m, 6H, ArH); enantiomeric excess: 76%, determined
graphy (hexane : AcOEt = 5 : 1) to give 1e (160 mg, 91%). White by HPLC (Chiralpak IA, hexane/2-propanol = 9/1, flow rate =
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1
+
1
mL min− , 25 °C, 214 nm) minor peak: t
R
= 12.5 min, major
14 3
C H11NNaO S, m/z = 296.0352 [(M + Na) ], found m/z =
2
6
peak: t = 11.4 min; [α] = +81.3 (c 0.92, CHCl ).
b: White solid (quant); m.p. 110–111 °C; H-NMR (CDCl )
3
δ 7.89–7.87 (m, 1H, ArH), 7.79–7.71 (m, 2H, ArH), 7.65–7.62 min , 25 °C, 237 nm) minor peak: t
296.0352; enantiomeric excess: 65%, determined by HPLC
(Chiralpak ID, hexane/2-propanol = 9/1, flow rate = 1 mL
R
D
3
1
3
−
1
R
= 23.4 min, major peak:
2
3
(
m, 1H, ArH), 7.41–7.36 (m, 4H, ArH), 2.42 (s, 3H, CH ); tR = 18.9 min; [α] = +137.0 (c 0.87, CHCl ); IR (KBr): ν 3035,
3
D
3
1
3
−1
C-NMR (CDCl
3
) δ 139.1, 134.8, 134.5, 133.8, 132.7, 132.1, 1611, 1359, 1328, 1179, 1101, 944 cm
3g: White solid (quant); m.p. 133–134 °C; H-NMR (CDCl
calcd for C H NNaO S, m/z = 296.0352 [(M + Na) ], found m/z δ 7.90–7.88 (m, 1H, ArH), 7.81–7.73 (m, 2H, ArH), 7.69–7.65
.
1
1
28.9, 128.5, 128.1, 127.8, 125.2, 124.1, 85.4, 21.4; HRMS (ESI)
3
)
+
1
4
11
3
=
296.0346; enantiomeric excess: 81%, determined by HPLC (m, 2H, ArH), 7.62–7.60 (m, 1H, ArH), 7.89 (dd, 1H, ArH, J =
1
3
(Chiralpak IA, hexane/2-propanol = 9/1, flow rate = 1 mL 1.60, 6.80 Hz); C-NMR (CDCl
3
) δ 134.6, 134.1, 133.2, 132.5 (3
−
1
min , 25 °C, 214 nm) minor peak: t = 10.7 min, major peak: × C or 2 × C), 129.9 (2 × C or 3 × C), 128.0, 127.1, 126.3, 124.5,
R
2
3
t
R
= 8.8 min; [α]
852, 1454, 1363, 1334, 1236, 1185, 1132, 1094 cm
3
D
= +174.0 (c 0.92, CHCl
3
). IR (KBr): ν 2924, 84.9 (Oxaziridine C); HRMS (ESI) calcd for C13
H
8
BrNNaO
m/z = 359.9300 [(M + Na) ], found m/z = 359.9292; enantio-
c: White solid (78%); m.p. 130–131 °C; H-NMR (CDCl ) δ meric excess: 74%, determined by HPLC (Chiralpak ID,
3
S,
−
1
+
2
.
1
3
−
1
7
1
1
1
8
.90 (d, 1H, ArH, J = 7.20 Hz), 7.83–7.70 (m, 4H, ArH), 7.63 (d, hexane/2-propanol = 9/1, flow rate = 1 mL min , 25 °C,
H, ArH, J = 7.20 Hz), 7.55 (d, 1H, ArH, J = 7.80 Hz), 7.41 (t, 214 nm) minor peak: t = 23.3 min, major peak: t = 26.8 min;
H, ArH, J = 7.80 Hz); C-NMR (CDCl ) δ 134.5, 134.4, 134.0, [α]D = +70.6 (c 1.33, CHCl ); IR (KBr): ν 3068, 1595, 1399, 1359,
R
R
1
3
25
3
3
33.8, 133.1, 131.0, 130.6, 130.2, 127.8, 126.8, 124.3, 123.1, 1327, 1188, 1166, 1129 cm−
1
.
1
4.3 (Oxaziridine C); HRMS (ESI) calcd for C13 BrNNaO S, 3h: White solid (97%); m.p. 144–145 °C; H-NMR (CDCl ) δ
H
8
3
3
+
m/z = 359.9300 [(M + Na) ], found m/z = 359.9299; enantio- 7.89 (dd, 1H, ArH, J = 1.20, 6.80 Hz), 7.82–7.75 (m, 2H, ArH),
meric excess: 87%, determined by HPLC (Chiralpak ID, 7.62 (dd, 1H, ArH, J = 0.80, 6.80 Hz), 7.57–7.50 (m, 4H, ArH);
hexane/2-propanol = 9/1, flow rate = 0.5 mL min , 25 °C,
−
1
13
3
C-NMR (CDCl ) δ 137.8, 134.5, 134.02, 133.95, 133.0, 129.5 (2
2
14 nm) minor peak: t = 62.6 min, major peak: t = 54.6 min; × C), 129.4 (2 × C), 127.8, 126.4, 124.3, 84.7 (Oxaziridine C);
R
R
2
2
[α]
D
= +116.0 (c 0.20, CHCl
364, 1325, 1157, 1126, 1112 cm
3
8 3
); IR (KBr): ν 3094, 3076, 2230, HRMS (ESI) calcd for C13H ClNNaO S, m/z = 315.9806 [(M +
−
1
+
1
.
Na) ], found m/z = 315.9806; enantiomeric excess: 60%, deter-
1
3
d: White solid (88%); m.p. 125–126 °C; H-NMR (CDCl ) δ mined by HPLC (Chiralpak ID, hexane/2-propanol = 9/1, flow
3
.91–7.88 (m, 1H, ArH), 7.82–7.74 (m, 2H, ArH), 7.64–7.60 (m, rate = 1 mL min− , 25 °C, 254 nm) minor peak: t
H, ArH), 7.56 (dt, 1H, ArH, J = 2.00, 7.20 Hz), 7.52–7.45 (m, major peak: t
1
= 20.9 min,
= +161 (c 1.03, CHCl ); IR
H, ArH); C-NMR (CDCl ) δ 135.3, 134.5, 134.0, 133.9, 133.0, (KBr): ν 3096, 3080, 2926, 1598, 1494, 1454, 1405, 1358, 1188,
7
2
2
1
R
2
2
R
= 18.0 min; [α]
D
3
1
3
3
31.6, 130.4, 130.0, 128.2, 127.9, 126.3, 124.3, 84.4 (Oxaziridine 1131, 1091, 944, 813, 768, 572 cm−1
ClNNaO S, m/z = 315.9806 [(M 3j: White solid (87%); m.p. 103–104 °C; H-NMR (CDCl
Na) ], found m/z = 315.9800; enantiomeric excess: 73%, 7.88–7.86 (m, 1H, ArH), 7.78–7.70 (m, 2H, ArH), 7.64–7.62 (m,
.
1
C); HRMS (ESI) calcd for C13
+
determined by HPLC (Chiralpak ID, hexane/2-propanol = 9/1, 1H, ArH), 7.19 (brs, 3H, ArH), 2.37 (s, 6H, 2 × CH
flow rate = 1 mL min , 25 °C, 214 nm) minor peak: t
H
8
3
3
) δ
+
1
3
3
); C-NMR
) δ 138.9 (2 × C), 134.9, 134.4, 133.8, 132.9, 132.7, 128.1,
4.4 min, major peak: tR = 14.5 min; [α]D = +245.0 (c 0.44, 127.7, 125.6 (2 × C), 124.0, 85.5 (oxaziridine C), 21.3 (2 × C);
−
1
R
=
(CDCl
3
1
8
2
−
1
CHCl
3
); IR (KBr): ν 3063, 1463, 1363, 1320, 1182, 1166 cm
.
HRMS (ESI) calcd for C15
H
13NNaO
Na) ], found m/z = 310.0500; enantiomeric excess: 65%, deter-
δ 7.90–7.88 (m, 1H, ArH), 7.82–7.74 (m, 2H, ArH), 7.66–7.64 mined by HPLC (Chiralpak OD-H, hexane/2-propanol = 9/1,
3
S, m/z = 310.0508 [(M +
1
+
3
3
e: White solid (quant); m.p. 132–133 °C; H-NMR (CDCl )
m, 1H, ArH), 7.54–7.49 (m, 1H, ArH), 7.42–7.40 (m, 1H, ArH), flow rate = 1 mL min− , 25 °C, 214 nm) minor peak: t
1
=
(
R
1
3
1
21
7
2
1
2
.34–7.26 (m, 2H, ArH); C-NMR (CDCl
3
) δ 162.8 (d, JC–F
=
R D
8.7 min, major peak: t = 12.4 min; [α] = +148.0 (c 0.63,
3
47.9 Hz), 134.4, 134.0, 133.8, 133.0, 130.9 (d, J
= 7.7 Hz), CHCl ); IR (KBr): ν 3062, 3008, 2921, 1602, 1530, 1458, 1382,
3
C–F
3
2
−1
30.3 (d, JC–F = 7.6 Hz), 127.9, 124.3, 124.0, 118.6 (d, JC–F
=
1333, 1237 cm
3k: White solid (quant); m.p. 174–175 °C; H-NMR (CDCl
−110.2; HRMS (ESI) calcd for δ 7.87 (dd, 1H, ArH, J = 0.80, 6.40 Hz), 7.78–7.70 (m, 2H, ArH),
.
2
1
1.0 Hz), 115.3 (d,
F-NMR (CDCl3):
J
C–F = 23.8 Hz), 84.4 (Oxaziridine C);
3
)
1
9
δ
+
C
3
(
13
H
8
FNNaO
00.0096; enantiomeric excess: 68%, determined by HPLC 7.32 (d, 2H, ArH, J = 8.40 Hz), 2.44 (s, 3H, CH
Chiralpak ID, hexane/2-propanol = 9/1, flow rate = 1 mL (CDCl ) δ 141.7, 134.8, 134.6, 133.8, 132.7, 129.7 (3 × C), 128.0
3
S, m/z = 300.0101 [(M + Na) ], found m/z = 7.64 (dd, 1H, ArH, J = 0.80, 7.60 Hz), 7.50–7.47 (m, 2H, ArH),
1
3
3
); C-NMR
3
−
1
R
min , 25 °C, 214 nm) minor peak: t = 24.4 min, major peak: (2 × C), 124.9, 124.1, 85.4, 21.5; HRMS (ESI) calcd for
2
0
+
t
R
= 15.8 min; [α]
D
= +26.8 (c 1.40, CHCl
3
); IR (KBr): ν 3096,
14 3
C H11NNaO S, m/z = 296.0352 [(M + Na) ], found m/z =
−1
3
074, 1594, 1449, 1366, 1326, 1180, 1165 cm
.
296.0347; enantiomeric excess: 77%, determined by HPLC
) δ (Chiralpak IA, hexane/2-propanol = 9/1, flow rate = 1 mL
1
3
f: White solid (91%); m.p. 106–107 °C; H-NMR (CDCl
3
−
1
7
.99 (dd, 1H, ArH, J = 1.20, 6.60 Hz), 7.79–7.69 (m, 2H, ArH), min , 25 °C, 214 nm) minor peak: t
R
= 10.3 min, major peak:
2
0
7
.64 (dd, 1H, ArH J = 1.20, 6.60 Hz), 7.49 (d, 2H, ArH, J = 7.60 tR = 8.4 min; [α] = +160.0 (c 0.95, CHCl ); IR (KBr): ν 3446,
D
3
1
3
−1
3
Hz), 7.32 (d, 2H, ArH, J = 8.40 Hz), 2.44 (s, 3H, CH ); C-NMR 1598, 1451, 1361, 1330, 1184, 1147, 1123 cm .
1
(CDCl
3
) δ 141.7, 134.8, 134.6, 133.8, 132.7, 129.7, 128.0 (2 × C),
3
3l: White solid (90%); m.p. 127–128 °C; H-NMR (CDCl )
1
24.9, 124.1, 85.4 (Oxaziridine C), 21.5; HRMS (ESI) calcd for δ 7.81 (d, 1H, ArH, J = 8.00 Hz), 7.73 (dd, 1H, ArH, J = 1.60,
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1
3
8
1
1
3
.00 Hz), 7.63–7.52 (m, 6H, ArH); C-NMR (CDCl
36.8, 133.4, 132.9, 131.8, 129.4 (2 × C), 128.4, 128.1 (2 × C),
27.4, 125.5, 84.8; HRMS (ESI) calcd for C13 ClNNaO S, m/z = This study was supported by a Grant-in-Aid for Scientific
15.9806 [(M + Na) ], found m/z = 315.9806; enantiomeric Research on Innovative Areas – Advanced Molecular Trans-
3
) δ 140.7,
Acknowledgements
H
8
3
+
excess: 60%, determined by HPLC (Chiralpak IA, hexane/2-pro- formations by Organocatalysis – from The Ministry of Edu-
−
1
panol = 20/1, flow rate = 0.5 mL min , 25 °C, 212 nm) minor cation, Culture, Sports, Science and Technology (MEXT),
2
4
peak: t
R
= 23.5 min, major peak: t
R
= 20.1 min; [α]
D
= +11.4 (c Japan, the CREST project of the Japan Science and Technology
1
1
.27, CHCl ); IR (KBr): ν 3090, 1587, 1454, 1363, 1330, 1184, Corporation (JST), and JST Advance Catalytic Transformation
3
085, 960 cm−
1
.
Program for Carbon Utilization (ACT-C). We acknowledge the
3
m: Analytical data were well matched with the reported lit- technical staff of the Comprehensive Analysis Center of ISIR,
3
a
1
erature. White solid (85%); H-NMR (CDCl ) δ 7.92 (d, 2H, Osaka University (Japan).
3
ArH, J = 8.40 Hz), 7.43 (d, 2H, ArH, J = 8.40 Hz), 7.38 (s, 4H,
ArH), 5.43 (s, 1H, oxaziridine H), 2.49 (s, 3H, CH
3
). enantio-
meric excess: 51%, determined by HPLC (Chiralcel OJ, hexane/
-propanol = 9/1, flow rate = 1 mL min− , 25 °C, 254 nm)
1
2
Notes and references
R R
minor peak: t = 20.7 min, major peak: t = 25.9 min.
3
n: Analytical data were well matched with the reported lit-
1 For recent reviews, see: (a) K. S. Williamson, D. J. Michaelis
and T. P. Yoon, Chem. Rev., 2014, 114, 8016; (b) G. D. Sala
and A. Lattanzi, ACS Catal., 2014, 4, 1234.
3
a
1
erature. White solid (75%); H-NMR (CDCl
ArH), 7.96 (d, 2H, ArH, J = 8.0), 7.90–7.80 (m, 3H, ArH),
3
) δ 8.03 (br s, 1H,
7
1
3
.60–7.50 (m, 2H, ArH), 7.44 (d, 2H, ArH, J = 8.0 Hz), 7.40 (dd,
H, ArH, J = 1.60, 8.80 Hz), 5.62 (s, 1H, oxaziridine H), 2.51 (s,
H, CH ). enantiomeric excess: 72%, determined by HPLC
3
2 (a) F. A. Davis and A. C. Sheppard, Tetrahedron, 1989, 45,
5703; (b) F. A. Davis and B.-C. Chen, Chem. Rev., 1992, 92,
919; (c) V. A. Petrov and G. Resnati, Chem. Rev., 1996, 96,
1809.
(Chiralcel OD-H, hexane/2-propanol = 9/1, flow rate = 1 mL
−
1
min , 25 °C, 230 nm) minor peak: t
= 8.6 min.
R
= 9.7 min, major peak:
3 (a) L. Lykke, C. Rodríguez-Escrich and K. A. Jørgensen,
J. Am. Chem. Soc., 2011, 133, 14932; (b) L. Lykke,
K. S. Halskov, B. D. Carlsen, V. X. Chen and
K. A. Jørgensen, J. Am. Chem. Soc., 2013, 135, 4692.
4 (a) D. Uraguchi, R. Tsutsumi and T. Ooi, J. Am. Chem. Soc.,
2013, 135, 8161; (b) T. Zhang, W. He, X. Zhao and Y. Jin,
Tetrahedron, 2013, 69, 7416; (c) Y. Jin, T. Zhang, W. Zhang,
S. Chang and B. Feng, Chirality, 2014, 26, 150;
(d) R. Tsutsumi, S. Kim, D. Uraguchi and T. Ooi, Synthesis,
2014, 871; (e) D. Uraguchi, R. Tsutsumi and T. Ooi, Tetra-
hedron, 2014, 70, 1691.
5 For recent examples of transformations of N-sulfonyl
oxiaziridines, see: (a) S. Dong, X. Lui, Y. Zhu, P. He, L. Lin
and X. Feng, J. Am. Chem. Soc., 2013, 135, 10026;
(b) K. S. Williamson, J. W. Sawicki and T. P. Yoon, Chem.
Sci., 2014, 5, 3524, see also references therein.
t
R
1
3
o: White solid (quant); m.p. 110–111 °C; H-NMR (CDCl )
3
δ 8.15 (d, 1H, ArH, J = 1.60 Hz), 7.98 (d, 1H, ArH, J = 8.00 Hz),
7
.94–7.90 (m, 3H, ArH), 7.80 (td, 1H, ArH, J = 1.20, 7.60 Hz),
.45 (td, 1H, ArH, J = 1.60, 8.00 Hz), 7.69–7.57 (m, 4H, ArH);
7
1
3
3
C-NMR (CDCl ) δ 134.7, 134.5, 134.4, 133.9, 132.8, 132.6,
1
1
m/z
29.1, 128.9, 128.5, 128.1, 128.0, 127.9, 127.2, 125.2, 124.2,
23.8, 85.5; HRMS (ESI) calcd for C H NNaO S,
1
7
11
3
+
= 332.0352 [(M + Na) ], found m/z = 332.0344;
enantiomeric excess: 70%, determined by HPLC (Chiralpak ID,
−
1
hexane/2-propanol = 9/1, flow rate = 1 mL min , 25 °C,
14 nm) minor peak: t = 29.5 min, major peak: t = 23.0 min;
= +193.0 (c 0.73, CHCl ); IR (KBr): ν 3058, 1452, 1369,
2
R
R
2
0
[α]
D
3
185, 1165 cm−
1
.
1
3
p: Analytical data were well matched with the reported lit-
1
2
1
erature. White solid (83%); H-NMR (CDCl
4
3
) δ 7.82–7.68 (m,
6 J. L. Olivares-Romero, Z. Li and H. Yamamoto, J. Am. Chem.
Soc., 2012, 134, 5440.
H, ArH), 2.14 (s, 3H, CH ); enantiomeric excess: 62%, deter-
3
mined by HPLC (Chiralpak ID, hexane/2-propanol = 9/1, flow
7 (a) K. Murai, S. Fukushima, S. Hayashi, Y. Takahara and
H. Fujioka, Org. Lett., 2010, 12, 964; (b) K. Murai,
T. Matsushita, A. Nakamura, S. Fukushima, M. Shimura
and H. Fujioka, Angew. Chem., Int. Ed., 2010, 49, 9174;
(c) K. Murai, S. Fukushima, A. Nakamura, M. Shimura and
H. Fujioka, Tetrahedron, 2011, 67, 4862; (d) K. Murai,
A. Nakamura, T. Matsushita, M. Shimura and H. Fujioka,
Chem. – Eur. J., 2012, 18, 8448; (e) K. Murai, T. Matsushita,
A. Nakamura, N. Hyogo, J. Nakajima and H. Fujioka, Org.
Lett., 2013, 15, 2526; (f) S. Takizawa, S. Hirata, K. Murai,
H. Fujioka and H. Sasai, Org. Biomol. Chem., 2014, 12,
5827; (g) K. Murai, N. Shimizu and H. Fujioka, Chem.
Commun., 2014, 50, 12530; (h) K. Murai, J. Nakajima,
A. Nakamura, N. Hyogo and H. Fujioka, Chem. – Asian J.,
2014, 9, 3511.
rate = 1 mL min− , 25 °C, 214 nm) minor peak: t
1
= 27.4 min,
major peak: t = 25.1 min; [α] = +13.4 (c 0.38, CHCl ).
R
1
7
R
D
3
1
3
3
q: White solid (91%); m.p. 144–145 °C; H-NMR (CDCl ) δ
8
1
.73 (d, 1H, ArH, J = 4.00 Hz), 8.19–8.15 (m, 1H, ArH), 7.90 (td,
H, ArH, J = 1.60, 8.00 Hz), 7.86–7.82 (m, 1H, ArH), 7.79–7.73
(
4
1
m, 2H, ArH), 7.71 (d, 1H, ArH), 7.50 (ddd, 1H, ArH, J = 0.80,
1
3
.40, 7.20 Hz); C-NMR (CDCl
33.7, 133.4, 132.5, 130.0, 125.7, 123.7, 123.3, 83.1 (Oxaziridine
NaO S, m/z = 283.0148 [(M +
3
) δ 149.4, 149.1, 137.6, 134.3,
C); HRMS (ESI) calcd for C12
Na) ], found m/z = 283.0143; enantiomeric excess: 71%, deter-
H
8
N
2
3
+
mined by HPLC (Chiralpak ID, hexane/2-propanol = 9/1, flow
rate = 1 mL min− , 25 °C, 214 nm) minor peak: t
1
= 28.8 min,
= +134.0 (c 0.60, CHCl ); IR
R
2
0
major peak: t
R
= 24.7 min; [α]
KBr): ν 3096, 3068, 1454, 1373, 1336, 1186, 1165 cm
D
3
−
1
(
.
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Paper
8
J. H. Barnard, C. Wang, N. G. Berry and J. Xiao, Chem. Sci.,
013, 4, 1234.
T. Fukuzumi and J. W. Bode, J. Am. Chem. Soc., 2009, 131,
864.
0 (a) A. Kraft and R. Fröhlich, Chem. Commun., 1998, 1085;
b) A. Kraft, F. Osterod and R. Fröhlich, J. Org. Chem., 1999,
4, 6425.
(c) T. Nishimura, A. Noishiki, G. C. Tsui and T. Hayashi,
J. Am. Chem. Soc., 2012, 134, 5056; (d) A. G. Kravina,
J. Mahatthananchai and J. W. Bode, Angew. Chem., Int. Ed.,
2012, 51, 9433; (e) T. Nishimura, Y. Ebe and T. Hayashi,
J. Am. Chem. Soc., 2013, 135, 2092; (f) S. Takizawa,
F. A. Arteaga, Y. Yoshida, M. Suzuki and H. Sasai, Asian
J. Org. Chem., 2014, 3, 412.
2
9
3
1
1
(
6
1 (a) K. Y. Lee, C. G. Lee and J. N. Kim, Tetrahedron Lett., 12 F. A. Davis, J. C. Towson, D. B. Vashi, R. ThimmaReddy,
2
003, 44, 1231; (b) M. Rommel, T. Fukuzumi and
J. P. McCauley, Jr., M. E. Harakal and D. J. Gosciniak,
J. W. Bode, J. Am. Chem. Soc., 2008, 130, 17266;
J. Org. Chem., 1990, 55, 1254.
This journal is © The Royal Society of Chemistry 2015
Org. Biomol. Chem.