Asymmetric epoxidation of α,β-unsaturated aldehydes catalyzed by a spiro-pyrrolidine-derived organocatalyst

Article abstract of DOI:10.1016/j.tetasy.2016.02.009

The asymmetric epoxidation of α,β-unsaturated aldehydes, catalyzed by a spiro-pyrrolidine (SPD)-derived organocatalyst, has been accomplished with good diastereoselectivities (up to dr >20:1) and with high to excellent enantioselectivities (up to 99% ee).

Full text of DOI:10.1016/j.tetasy.2016.02.009

Tetrahedron: Asymmetry xxx (2016) xxx–xxx
Contents lists available at ScienceDirect
Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Asymmetric epoxidation of a,b-unsaturated aldehydes catalyzed
by a spiro-pyrrolidine-derived organocatalyst
a
a
a
a
Ming-Hui Xu a, Yong-Qiang Tu a,b, , Jin-Miao Tian , Fu-Min Zhang , Shao-Hua Wang , Shi-Heng Zhang ,
⇑
Xiao-Ming Zhang a
a State Key Laboratory of Applied Organic Chemistry & College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000, PR China
b School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, Shanghai 200240, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
The asymmetric epoxidation of
derived organocatalyst, has been accomplished with good diastereoselectivities (up to dr >20:1) and with
high to excellent enantioselectivities (up to 99% ee).
a,b-unsaturated aldehydes, catalyzed by a spiro-pyrrolidine (SPD)-
Received 12 December 2015
Accepted 14 February 2016
Available online xxxx
Ó 2016 Elsevier Ltd. All rights reserved.
1. Introduction
tion.1 To prove that this catalyst might be a beneficial complement
for current secondary amine catalysts, we employed 10 to catalyze
The
a,b-epoxy aldehydes have been employed as important
the asymmetric epoxidation of
a,b-unsaturated aldehydes to pre-
building blocks for the synthesis of natural products and bioactive
molecules,1 such as (R)-methyl palmoxirate,2 epoxyisoprostanes,3
(+)-amphidinolide K4 and (+)-stagonolide C.5 Although a number
of related studies for preparing enantiomerically pure epoxides
have been documented,6 no method using organocatalysis had
emerged until Jørgensen et al.’s pioneering work on the asymmet-
pare various enantiomerically pure
with good to excellent diastereoselectivities and enantioselectivi-
ties (Scheme 1).
a
,b-epoxy aldehydes/alcohols
2. Results and discussion
ric epoxidation of
Hayashi catalyst
a
3
,b-unsaturated aldehydes using Jørgensen–
in combination with hydrogen peroxide
Initially, cinnamic aldehyde 1a was selected as a model sub-
strate with hydrogen peroxide as the oxidant to test the catalytic
efficiency of organocatalyst 10 in anhydrous MeOH. The desired
epoxide 2a was obtained with excellent enantioselectivity (99%
ee) and diastereoselectivity (dr >20:1), albeit with moderate yield
(68%) after the in situ reduction of the aldehyde intermediate by
NaBH4 (Table 1, entry 1). Encouraged by this result, we further
optimized the reaction conditions to increase the reaction yield.
Solvent screening (Table 1) showed that other aprotic solvents,
such as anhydrous DCM, THF and MeCN, decreased the yield while
maintaining the selectivity (entries 2–4). In contrast, non-polar
solvents such as toluene prohibited the reaction (entry 5). Impor-
tantly, the direct use of commercially available MeOH without
any treatment gave a much higher yield of 87% (entry 6 vs entry
1), which indicated the pivotal role of a small amount of water in
enhancing the efficiency of the reaction. Next, other commonly
used oxidants were examined (entries 8–10), but all of them gave
poor results. Increasing the concentration (50%) of H2O2 also
afforded a comparable result (entry 11 vs entry 6), while lowering
the catalyst loading from 20 mol % to 10 mol % significantly
decreased the yield (61%) (entry 12). Therefore, entry 6 was chosen
(Scheme 1).7 Afterwards, a variety of pyrrolidine-derived catalysts,
such as 4,8 52,9 and 6,10 have been developed and successfully
applied to this type of epoxidation for the purpose of enhanced
enantioselectivities and better substrate scope. Additionally, other
organocatalysts, such as chiral imidazolidinone 7,11 amine salts 812
and quinine-derived amine 9,13 have also found their exceptional
utility in such epoxidation reactions. Despite these achievements
in organocatalytic asymmetric epoxidations of
a,b-unsaturated
aldehydes, developing novel catalysts to further enhance the enan-
tioselectivity and diastereoselectivity is still highly desirable.
Considering the excellent a stereocontrol and extensive applica-
tions of catalysts with chiral spiro-backbone14 as well as the struc-
tural features of pyrrolidine-based catalysts 3–6, we have designed
and prepared the spiro-pyrrolidine derived (SPD) organocatalyst
10 on a gram scale (Scheme 1). The catalytic efficiency of this type
of catalyst has been supported by an asymmetric Michael reac-
⇑
Corresponding author. Fax: +86 931 8912973.
E-mail addresses: tuyq@lzu.edu.cn, tuyq@sjtu.edu.cn (Y.-Q. Tu).
http://dx.doi.org/10.1016/j.tetasy.2016.02.009
0957-4166/Ó 2016 Elsevier Ltd. All rights reserved.
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2
M.-H. Xu et al. / Tetrahedron: Asymmetry xxx (2016) xxx–xxx
R1
O
O
O
R1
organocatalst
solvent
oxidant
R2
R2
1
2'
R1
O
O
R3
R2
3 R = OTMS
Me
Ar
R
O
H
4
5
Ar = Ph, R = OTMS
N
N
P
Ar
R = OSiMePh2
6 Ar = Ph, R = F
Bn
N
O
O
N
H
H
t-Bu
H
7
HX
R1
8
NH2
N
H
N
OTBDPS
MeO
10
SPD organocatalyst
N
9
Scheme 1. Organocatalytic asymmetric epoxidation of a,b-unsaturated aldehydes.
reported under the current reaction conditions (entries 4–7);10a,12a
these results further demonstrate the potential utility of catalyst
10 as a complement for known secondary amine catalysts. In
Table 1
Optimization for the asymmetric epoxidation of cinnamic aldehydea
O
1. H2O2 (3 equiv),10 (20 mol%)
O
addition, the aliphatic substituted a,b-unsaturated aldehydes are
H
MeOH, rt, 48 h
OH
also amenable to this catalytic peroxidation system, which
provided epoxides 2i–2n with good to excellent dr, ee and
moderate to high yields after subsequent reduction and
esterification of the aldehyde intermediates (entries 9–14).
However, both the yields and enantioselectivities decreased
considerably compared with the results of the aromatic
substituted aldehydes. Generally, higher enantioselectivities were
observed in the epoxidation of b-monosubstituted substrates
(entries 1–11) than those of b-disubstituted ones (entries 12–14),
which may be caused by the steric hindrance of the
corresponding substrates 1l–1n.
2. NaBH4 (4 equiv)
0°C
1a
2a
Entry
Solvent
Oxidant
drc
eed (%)
Yielde (%)
1
2
3
4
5
6
8
9
MeOHb
30% H2O2
30% H2O2
30% H2O2
30% H2O2
30% H2O2
30% H2O2
UHP
m-CPBA
TBHP
50% H2O2
30% H2O2
>20:1
>20:1
>20:1
>20:1
—
>20:1
—
—
99
99
99
99
—
99
—
—
68
40
62
59
<5
87
<5
<5
nd
86
61
DCMb
THFb
MeCNb
Tolueneb
MeOH (AR)
MeOH (AR)
MeOH (AR)
MeOH (AR)
MeOH (AR)
MeOH (AR)
According to the experimental results, a possible mechanism is
proposed for the SPD catalyzed asymmetric reaction (Scheme 2).
10
11
12f
—
>20:1
>20:1
—
98
99
Firstly, an iminium ion is formed from dehydration of an
a,b-
unsaturated aldehyde with catalyst 10. Next, the iminium ion is
attacked by H2O2, leading to an enamine intermediate. Finally,
the formation of epoxide 20 takes place by the attack of the nucle-
ophilic enamine carbon atom on the electrophilic oxygen atom.
Due to the steric hindrance caused by the bulky silyl ether from
the Si-face, the nucleophilic H2O2 could only approach the iminium
ion from the Re-face, thus affording the (S,R)-epoxide.
AR = analytical reagent, UHP = urea hydrogen peroxide, m-CPBA = 3-chloroperben-
zoic acid, TBHP = tert-butyl hydroperoxide.
a
Unless otherwise noted, the reaction was conducted in solvent (1.0 mL) with
cinnamic aldehyde (0.3 mmol), oxidant (3 equiv), catalyst 10 (0.2 equiv) at room
temperature for 48 h. The reaction was cooled to 0 °C followed by the addition of
NaBH4 (4 equiv). Since the epoxy aldehyde is not stable during work-up, the dr and
ee data of its corresponding primary alcohol compound 2a were determined.
b
Solvents were distilled by standard procedure.
Determined by NMR.
Determined by HPLC.
Isolated yield for two steps.
c
d
3. Conclusion
e
f
10 mmol % catalyst were used.
In conclusion, we have demonstrated that the SPD-derived
organocatalyst 10 is able to catalyze the asymmetric epoxidation
as the general experimental conditions for subsequent substrate
scope investigations.
of a variety of
a,b-unsaturated aldehydes with good to excellent
dr and ee. Some examples give better results than previously
reported ones. Overall, this is a complement to the field of enan-
tioselective, organocatalytic epoxidation. Further studies on the
catalytic efficiency of this type of catalysts towards other reactions
are ongoing in our laboratory.
With the optimal conditions in hand, a series of a,b-unsaturated
aldehydes bearing different b-aromatic substituents were applied
to this reaction; most of them could be oxidized into the corre-
sponding epoxides with good to excellent diastereoselectivities
as well as enantioselectivities (up to dr >20:1 and 99% ee; Table 2,
entries 1–8). Generally, substrates with electron deficient aromatic
substituents gave better results in terms of both yields and enan-
tioselectivities than those with electron rich aromatic substituents
(entries 3, 6 vs entry 7). Meanwhile, the position of substituents
slightly affected the diastereoselectivities; the ortho-substituted
substrate gave the worst result (entries 3, 5, 6). In addition, a bulky
aromatic group such as naphthyl could seriously decrease the
diastereoselectivity and enantioselectivity (entry 8). It should be
noted that substrates 1d–1g all gave better results than previously
4. Experimental
4.1. General
All reactions were carried out under an argon atmosphere. All
solvents were purified and dried by standard techniques and dis-
tilled prior to use. All reactions under standard conditions were
monitored by thin-layer chromatography (TLC) on gel GF254
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M.-H. Xu et al. / Tetrahedron: Asymmetry xxx (2016) xxx–xxx
3
plates. Silica gel (200ꢀ300 mesh), petroleum ether (bp 60ꢀ90 °C)
and ethyl acetate are used for product purification by flash column
chromatography. The phosphate buffer used (1 M, PH = 7.0) was
prepared from KH2PO4 (136 g), solid NaOH (23.3 g) and both were
dissolved in H2O (1 L). 1H, 13C and 19F NMR spectra, which were
recorded in CDCl3 solution, were acquired on a Bruker AM-
400 MHz spectrometer. Chemical shifts (d) are reported in ppm rel-
ative to residual solvent signals (CDCl3: 7.26 ppm for 1H NMR,
77.0 ppm for 13C NMR). The following abbreviations are used to
indicate the multiplicity in NMR spectra: s, singlet; d, doublet; t,
triplet; q, quartet; m, multiplet. High-resolution mass spectral
analysis (HRMS) data were determined on an APEXII 47e FT-ICR
spectrometer by means of the ESI technique. IR spectra were
recorded on a fourier transform infrared spectrometer. The enan-
Table 2
Scope of the epoxidation of
a
a
,b-unsaturated aldehydes with H2O2
R1
10
1. H2O2 (3 equiv),
(20 mol%)
R1
R2
O
O
MeOH, rt, 48 h
R2
OH
H
2. NaBH4 (4 equiv)
0°C
1a-n
2a-n
Entry
1
Product
Yieldb (%)
87
drd
eee (%)
99
O
OH
2a
2b
>20:1
O
OH
2
3
4
62
78
61
85
99
98
>20:1
Br
Cl
O
OH
2c
>20:1
18:1
O
O
OH
2d
F
OH
5
6
2e
2f
60
74
98
99
>20:1
>20:1
F
O
OH
F
O
OH
7
8
2g
2h
36
75
96
92
>20:1
10:1
O
OH
O
O
O
9f
2i0
2j0
2k0
2l0
29c
37c
62c
15c
94
98
94
83
O
>20:1
>20:1
NO2
O
O
O
10f
11f
12f
NO2
O
O
O
>20:1
—
NO2
O
O
NO2
O
O
O
13
2m0
54c
—
75
NO2
(continued on next page)
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M.-H. Xu et al. / Tetrahedron: Asymmetry xxx (2016) xxx–xxx
Table 2 (continued)
Entry
Product
Yieldb (%)
drd
eee (%)
85
O
O
O
14f
2n0
73c
>20:1
NO2
Unless otherwise noted, the reaction was conducted in MeOH (AR) (1.0 mL) with
a
a
,b-unsaturated aldehyde (0.3 mmol), H2O2 (30% in water, 3 equiv), catalyst 10
(0.2 equiv), at rt for 48 h. Then, NaBH4 (4 equiv) was added at 0 °C. The dr and ee of aldehydes 20a–20h were determined after they were reduced to the corresponding primary
alcohols 2a–2h. The dr and ee of compounds 20i–20n were determined after they were reduced and then transformed into the corresponding p-nitrobenzoate ester 2i0–2n0 due
to the volatility of the resulting alcohol. For details, please see Supporting information.
b
Isolated yield for two steps.
Isolated yield for three steps.
The major dr was determined by NMR.
The major ee was determined by HPLC.
c
d
e
f
The solvent was TBME.
H2O
N
OTBDPS
H
R1
HO OH
R1
O
1
path b
H2O2
N
favored
N
O
H
N
H
R1
OTBDPS
10
OTBDPS
OH
Ph Si
Ph
tBu
R1
path a
H2O2
disfavored
O
R1
O
2'
N
H2O
H2O
OTBDPS
O
R1
Scheme 2. The proposed mechanism of asymmetric epoxidation of
a,b-unsaturated aldehydes.
tiomeric excess (ee) of the products was determined by high per-
formance liquid chromatography (HPLC) analysis employing Daicel
Chiralpak AD, IA-3, OJ and OD-H column. Optical rotations were
detected on RUDOLPH A21202-J APTV/GW.
Aldehydes 1a–l were commercially available and used as
received. Organocatalyst 10 was prepared according to the pub-
lished procedure.15 Substrates 1m–n were synthesized according
to literature procedures.16 The analytical reagents (AR) were pur-
chased from commercial suppliers and used without further purifi-
cation unless stated otherwise. The oxidation H2O2 was degassed
for 30 min by bubbling argon. Racemic epoxides were prepared
of H2O2 (30% in H2O, 92 lL, 0.9 mmol). The reaction was stirred
for 48 h under argon. After completion, the reaction was cooled
to 0 °C (ice bath) followed by the addition of NaBH4 (45.6 mg,
1.2 mmol). The reaction mixture was then stirred for a further
30 min at 0 °C, and quenched with a pH = 7.0 phosphate buffer
solution. The aqueous phase was extracted with CH2Cl2
(3 ꢁ 5 mL) and the combined organic extracts were dried over
anhydrous MgSO4 and concentrated in vacuo after filtration. The
crude product was purified by column chromatography (silica
gel; petroleum ether/AcOEt = 8:1) to give target compounds 2a–h.
The crude products 2i–n were dissolved in anhydrous CH2Cl2
and cooled to 0 °C followed by the continuous addition of Et3N
by epoxidation of the corresponding
a,b-unsaturated aldehydes
with H2O2 through direct catalysis by the racemic catalyst 10.
(166 lL, 1.2 mmol), DMAP (7.2 mg, 0.06 mmol) and p-nitrobenzoyl
chloride (167 mg, 0.9 mmol). The mixture was stirred for 15 min at
0 °C and then stirred for a further 1 h at rt. After completion, the
mixture was quenched with NaHCO3 saturated solution. The aque-
ous phase was extracted with CH2Cl2 (3 ꢁ 5 mL), and the combined
organic extracts were dried over anhydrous MgSO4 and
concentrated in vacuo after filtration. Purification by column
4.1.1. General procedure for the enantioselective asymmetric
epoxidation
Catalyst 10 (22.8 mg, 0.06 mmol) was added at rt to a solution
of the
a,b-unsaturated aldehyde (0.3 mmol) in MeOH (1.0 mL).
The mixture was stirred for 10 min at rt followed by the addition
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M.-H. Xu et al. / Tetrahedron: Asymmetry xxx (2016) xxx–xxx
5
chromatography (silica gel; petroleum ether/AcOEt = 15:1) gave
4.1.1.5.
2e.
((2S,3S)-3-(3-Fluorophenyl)oxiran-2-yl)methanol
Compound 2e was prepared according to the general pro-
target compounds 2i0–2n0.
cedure in 60% yield as a colourless oil. 1H NMR (400 MHZ, CDCl3) d
7.29–7.34 (m, 1H), 7.09 (d, J = 7.6 Hz, 1H), 6.97–7.03 (m, 2H), 4.05
(d, J = 12.8 Hz, 1H), 3.94 (d, J = 1.6 Hz, 1H), 3.82 (d, J = 12.8 Hz, 1H),
3.17–3.19 (m, 1H), 1.97 (s, 1H); 13C NMR (100 MHZ, CDCl3) d 163.0
(d, JF = 245 Hz), 139.5 (d, JF = 8 Hz), 130.1 (d, JF = 8 Hz), 121.4 (d,
JF = 3 Hz), 115.2 (d, JF = 21 Hz), 112.4 (d, JF = 23 Hz), 62.5, 60.9,
54.8 (d, JF = 3 Hz); 19F NMR (376 MHZ, CDCl3) d ꢂ112.8 (m, 1F)
ppm; HRMS (ESI) Calcd for C9H8F1O1 [MꢂH2O+H]+: 151.0554,
Found: 151.0553, Error: 0.7 ppm; IR (neat) cmꢂ1 3380, 2924,
4.1.1.1. ((2S,3S)-3-Phenyloxiran-2-yl)methanol 2a6e
confirm the configuration of the product, we compared the specific
rotation of 2a0 with the literature values, [ 20 = +53 (c 1.0, CHCl3),
99% ee, Lit.
]D23 = +14.3 (c 0.48, CHCl3), 94% ee.6e The
.
To
a]
D
[a
configuration of 20a is (2R,3S), so the configuration of 2a is
(2S,3S). All other absolute configurations were assigned by
analogy. Compound 2a was prepared according to the general
procedure in 87% yield as a white solid. 1H NMR (400 MHZ,
CDCl3) d 7.25–7.37 (m, 5H), 4.05 (ddd, J = 2.4 Hz, 5.2 Hz, 12.8 Hz,
1H), 3.93 (d, J = 2 Hz, 1H), 3.77–3.84 (m, 1H), 3.21–3.24 (m, 1H),
1.86 (dd, J = 5.2 Hz, 7.6 Hz, 1H); 13C NMR (100 MHZ, CDCl3) d
136.6, 128.5, 128.3, 125.7, 62.3, 61.2, 55.5; HRMS (ESI) Calcd for
C9H9O [MꢂH2O+H]+: 133.0648, Found: 133.0646, Error: 1.5 ppm;
IR (neat) cmꢂ1 3373, 2924, 2371, 1596, 1384, 1260, 1118, 869,
2374, 1721, 1592, 1457, 1258, 1079, 788, 690. [
a]
20 = ꢂ44 (c 1.0,
D
CHCl3). Enantiomeric excess is 98% determined by HPLC (Chiralpak
IA-3, Hexane/Isopropanol = 95:5, flow rate = 1.0 mL/min, 220 nm):
major
enantiomer:
tR = 16.23 min;
minor
enantiomer:
tR = 19.18 min.
768, 698; [
determined
a]
20 = ꢂ47 (c 1.0, CHCl3). Enantiomeric excess is 99%
4.1.1.6.
2f.
((2S,3S)-3-(4-Fluorophenyl)oxiran-2-yl)methanol
Compound 2f was prepared according to the general pro-
D
by
HPLC
(Chiralpak
OD-H,
Hexane/
Isopropanol = 96:4, flow rate = 1.0 mL/min, 215 nm); major
enantiomer: tR = 32.05 min; minor enantiomer: tR = 28.64 min.
cedure in 74% yield as a colourless oil. 1H NMR (400 MHZ, CDCl3) d
7.23–7.25 (m, 2H), 7.01–7.06 (m, 2H), 4.05 (d, J = 12.8 Hz, 1H), 3.92
(d, J = 2 Hz, 1H), 3.80 (d, J = 12.8 Hz, 1H), 3.18–3.20 (m, 1 H), 2.10 (s,
1H); 13C NMR (100 MHZ, CDCl3) d 162.5 (d, JF = 245 Hz), 132.3 (d,
JF = 3 Hz), 127.4 (d, JF = 8 Hz), 115.5 (d, JF = 21 Hz), 62.4, 61.0,
54.9; 19F NMR (376 MHZ, CDCl3) d ꢂ113.5 (m, 1F) ppm; HRMS
(ESI) Calcd for C9H8F1O1 [MꢂH2O+H]+: 151.0554, Found:
151.0552, Error: 1.3 ppm; IR (neat) cmꢂ1 3396, 2959, 2374, 1722,
4.1.1.2.
2b.
((2S,3S)-3-(4-Bromophenyl)oxiran-2-yl)methanol
Compound 2b was prepared according to the general pro-
cedure in 62% yield as a white solid. 1H NMR (400 MHZ, CDCl3) d
7.47 (d, J = 8.4 Hz, 2H), 7.15 (d, J = 8.4 Hz, 2H), 4.04 (dd, J = 2.4 Hz,
13.2 Hz, 1H), 3.90 (d, J = 2 Hz, 1H), 3.80 (dd, J = 3.2 Hz, 12.8 Hz,
1H), 3.16–3.18 (m, 1H), 2.18 (s, 1H); 13C NMR (100 MHZ, CDCl3) d
135.8, 131.6, 127.3, 122.2, 62.4, 60.9, 54.9; HRMS (ESI) Calcd for C9-
1607, 1513, 1224, 1076, 830, 557. [
a
]
D
20 = ꢂ35 (c 1.0, CHCl3). Enan-
tiomeric excess is 99% determined by HPLC (Chiralpak OD-H, Hex-
ane/Isopropanol = 99:1, flow rate = 1.0 mL/min, 220 nm): major
enantiomer: tR = 65.78 min.
H
10Br1O2 [M+H]+: 228.9859, Found: 228.9858, Error: 0.4 ppm, IR
(neat) cmꢂ1 3298, 2925, 2398, 1720, 1595, 1490, 1381, 1261,
1073, 766; [
a]
20 = ꢂ32 (c 1.0, CHCl3). Enantiomeric excess is 85%
D
determined by HPLC (Chiralpak OD-H, Hexane/Isopropanol = 98:2,
flow rate = 1.0 mL/min, 220 nm); major enantiomer: tR = 55.75 -
min; minor enantiomer: tR = 51.36 min.
4.1.1.7. ((2S,3S)-3-(p-Tolyl)oxiran-2-yl)methanol 2g.
Com-
pound 2g was prepared according to the general procedure in
36% yield as a colourless oil. 1H NMR (400 MHZ, CDCl3) d 7.15–
7.20 (m, 4H), 4.05 (d, J = 12.8 Hz, 1H), 3.9 (d, J = 2 Hz, 1H), 3.77–
3.83 (m, 1H), 3.22–3.25 (m, 1H), 2.36 (s, 3H) 1.95 (t, J = 6 Hz,
1H); 13C NMR (100 MHZ, CDCl3) d 138.1, 133.5, 129.2, 125.6,
62.2, 61.2, 55.5, 21.1; HRMS (ESI) Calcd for C10H11O1 [MꢂH2O
+H]+: 147.0804, Found: 147.0803, Error: 0.7 ppm; IR (neat) cmꢂ1
3402, 2924, 2369, 1721, 1455, 1261, 1079, 1022, 815, 758.
4.1.1.3.
2c.
((2S,3S)-3-(4-Chlorophenyl)oxiran-2-yl)methanol
Compound 2c was prepared according to the general pro-
cedure in 78% yield as a colourless oil. 1H NMR (400 MHZ, CDCl3) d
7.31–7.33 (m, 2H), 7.20–7.23 (m, 2H), 4.05 (ddd, J = 2.4 Hz, 5.2 Hz,
12.8 Hz, 1H), 3.92 (d, J = 2 Hz, 1H), 3.78–3.84 (m, 1H), 3.17–3.19
(m, 1H), 2.03 (dd, J = 5.2 Hz, 7.6 Hz, 1H); 13C NMR (100 MHZ,
CDCl3) d 135.2, 134.0, 128.7, 127.0, 62.4, 61.0, 54.9; HRMS (ESI)
Calcd for C9H10Cl1O2 [M+H]+: 185.0364, Found: 185.0362, Error:
1.1 ppm; IR (neat) cmꢂ1 3391, 2924, 2373, 1720, 1600, 1493,
[
a
]
20 = ꢂ36 (c 1.0, CHCl3). Enantiomeric excess is 96% determined
D
by HPLC (Chiralpak OD-H, Hexane/Isopropanol = 98:2, flow
rate = 1.0 mL/min, 230 nm): major enantiomer: tR = 52.23 min;
minor enantiomer: tR = 46.64 min.
1383, 1260, 1086, 820. [
a
]
20 = ꢂ38 (c 1.0, CHCl3). Enantiomeric
D
excess is 99% determined by HPLC (Chiralpak OJ, Hexane/Iso-
propanol = 99:1, flow rate = 1.0 mL/min, 230 nm): major enan-
tiomer: tR = 74.4 min.
4.1.1.8.
2h.
((2S,3S)-3-(Naphthalen-1-yl)oxiran-2-yl)methanol
Compound 2i was prepared according to the general pro-
cedure in 75% yield as a light yellow oil. 1H NMR (400 MHZ, CDCl3)
d 8.10–8.13 (m, 1H), 7.89–7.92 (m, 1H), 7.82 (d, J = 8 Hz, 1H), 7.45–
7.58 (m, 4H), 4.63 (dd, J = 4.4 Hz, 14.4 Hz 1H), 4.18 (dd, J = 1.6 Hz,
12.8 Hz, 1H), 3.98 (dd, J = 2 Hz, 12.6 Hz, 1H) 3.23–3.25 (m, 1H),
2.57 (s, 1H); 13C NMR (100 MHZ, CDCl3) d 133.1, 132.7, 131.1,
128.6, 128.1, 126.3, 125.8, 125.4, 122.7, 122.2, 61.6, 61.2, 53.8;
HRMS (ESI) Calcd for C13H12O2Na1 [M+Na]+: 233.0730, Found:
233.0729, Error: 0.4 ppm; IR (neat) cmꢂ1 3400, 2925, 2372, 1721,
4.1.1.4.
2d.
((2S,3S)-3-(2-Fluorophenyl)oxiran-2-yl)methanol
Compound 2d was prepared according to the general pro-
cedure in 61% yield as a colourless oil. 1H NMR (400 MHZ, CDCl3) d
7.03–7.26 (m, 4H), 4.21 (d, J = 2 Hz, 1H), 4.07 (ddd, J = 2.4 Hz,
5.6 Hz, 12.8 Hz, 1H), 3.82 (ddd, J = 4 Hz, 7.2 Hz, 8.4 Hz, 1H), 3.23–
3.25 (m, 1H), 2.23 (dd, J = 5.6 Hz, 7.2 Hz, 1H); 13C NMR (100 MHZ,
CDCl3) d 161.3 (d, JF = 245 Hz), 129.5 (d, JF = 8 Hz), 126.2 (d, JF = 3
Hz), 124.3 (d, JF = 3 Hz), 124.0 (d, JF = 12 Hz), 115.2 (d, JF = 20 Hz),
61.7, 61.2, 50.2 (d, JF = 6 Hz); 19F NMR (376 MHZ, CDCl3) d ꢂ120.7
(m, 1F) ppm; HRMS (ESI) Calcd for C9H10F1O2 [M+H]+: 169.0659,
Found: 169.0657, Error: 1.2 ppm; IR (neat) cmꢂ1 3368, 2924,
1395, 1261, 1085, 1022, 800, 778, 759. [a]
20 = 66 (c 1.0, CHCl3).
D
Enantiomeric excess is 92% determined by HPLC (Chiralpak OD-
H, Hexane/Isopropanol = 96:4, flow rate = 1.0 mL/min, 215 nm):
major
enantiomer:
tR = 57.57 min;
minor
enantiomer:
tR = 42.29 min.
2371, 1720, 1588, 1458, 1260, 1075, 760. [
a
]
20 = ꢂ23 (c 1.0, CHCl3).
D
Enantiomeric excess is 98% determined by HPLC (Chiralpak IA-3,
Hexane/Isopropanol = 99:1, flow rate = 1.0 mL/min, 225 nm):
major enantiomer: tR = 51.55 min; minor enantiomer r:
tR = 59.73 min.
4.1.1.9. ((2S,3S)-3-Methyloxiran-2-yl) methyl 4-nitrobenzoate
2i0.
Compound 2i0 was prepared according to the general pro-
cedure in 29% yield as a light yellow oil. 1H NMR (400 MHZ, CDCl3)
d 8.29–8.31 (m, 2H), 8.23–8.25 (m, 2H), 4.70 (dd, J = 2.8 Hz, 12 Hz,
Please cite this article in press as: Xu, M.-H.; et al. Tetrahedron: Asymmetry (2016), http://dx.doi.org/10.1016/j.tetasy.2016.02.009

6
M.-H. Xu et al. / Tetrahedron: Asymmetry xxx (2016) xxx–xxx
1H), 4.20 (dd, J = 6.4 Hz, 12 Hz, 1H), 3.08–3.11 (m, 1H), 3.01–3.06
(m, 1H), 1.40 (d, J = 5.2 Hz, 3H); 13C NMR (100 MHZ, CDCl3) d
164.4, 150.6, 135.0, 130.8, 123.5, 66.0, 56.0, 52.5, 17.1; HRMS
(ESI) Calcd for C11H12N1O5 [M+H]+: 238.0710, Found: 238.0708,
Isopropanol = 95:5, flow rate = 1.0 mL/min, 230 nm): major enan-
tiomer: tR = 23.21 min; minor enantiomer: tR = 25.53 min.
4.1.1.14.
((2S,3R)-3-Heptyl-3-methyloxiran-2-yl)methyl
4-
Error: 0.8 ppm. [
a
]
D
20 = ꢂ14 (c 1.0, CHCl3); IR (neat) cmꢂ1 3432,
nitrobenzoate 2n0.
Compound 2n0 was prepared according
2926, 2373, 1726, 1608, 1527, 1449, 1273, 1102, 718. Enantiomeric
excess is 94% determined by HPLC (Chiralpak AD, Hexane/Iso-
propanol = 90:10, flow rate = 1.0 mL/min, 230 nm): major enan-
tiomer: tR = 13.01 min; minor enantiomer: tR = 17.41 min.
to the general procedure in 73% yield as a white solid. 1H NMR
(400 MHZ, CDCl3) d 8.29–8.31 (m, 2H), 8.23–8.26 (m, 2H), 4.62-
4.69 (m, 1H), 4.31-4.36 (m, 1H), 1.62–1.71 (m, 4H), 1.37–1.50 (m,
3H), 1.25–1.29 (m, 8H), 0.85-0.89 (m, 3H); 13C NMR (100 MHZ,
CDCl3) d 164.5, 150.7, 135.1, 130.8, 123.5, 64.9, 60.9, 59.4, 38.2,
4.1.1.10. ((2S,3S)-3-Ethyloxiran-2-yl) methyl-4-nitrobenzoate
31.7, 29.4, 29.2, 25.0, 22.6, 16.9, 14.0; HRMS (ESI) Calcd for C18H25-
2j0.
Compound 2j0 was prepared according to the general pro-
N1O5Na [M+Na]+: 358.1625, Found: 358.1622, Error: 0.8 ppm; IR
(neat) cmꢂ1 3439, 2929, 2372, 1729, 1530, 1273, 1102, 720.
cedure in 37% yield as a white solid. 1H NMR (400 MHZ, CDCl3) d
8.30 (dd, J = 2 Hz, 6.8 Hz, 2H), 8.24 (dd, J = 2 Hz, 6.8 Hz, 2H), 4.70
(dd, J = 2.8 Hz, 12 Hz, 1H), 4.20 (dd, J = 6.8 Hz, 12.4 Hz, 1H), 3.12–
3.15 (m, 1H), 2.92–2.95 (m, 1H), 1.61–1.70 (m, 2H), 1.02 (t,
J = 7.6 Hz, 3H); 13C NMR (100 MHZ, CDCl3) d 164.3, 150.6, 135.0,
130.8, 123.5, 66.1, 57.5, 54.7, 24.5, 9.6; HRMS (ESI) Calcd for
[
a
]
20 = ꢂ11 (c 1.0, CHCl3). Enantiomeric excess is 85% determined
D
by HPLC (Chiralpak OD-H, Hexane/Isopropanol = 98:2, flow
rate = 1.0 mL/min, 230 nm): major enantiomer r: tR = 15.00 min;
minor enantiomer: tR = 13.78 min.
C
12H14N1O5 [M+H]+: 252.0866, Found: 252.0865, Error: 0.4 ppm;
4.1.1.15. Catalyst 10.
Catalyst 10 was prepared according to
IR (neat) cmꢂ1 3367, 2962, 2368, 1727, 1528, 1270, 1103, 757,
the published procedure.15 1H NMR (400 MHZ, CDCl3) d 7.64–
7.68 (m, 4H),7.34–7.45 (m, 6H), 3.85 (t, J = 5.8 Hz, 1H), 2.76–2.84
(m, 2H), 2.24 (s, 1H), 1.53–1.86 (m, 6H), 1.32–1.49 (m, 4H), 1.08
(s, 9H); 13C NMR (100 MHZ, CDCl3) d 135.8, 134.4, 133.8, 129.6,
129.5, 127.6, 127.4, 78.2, 71.8, 45.8, 36.1, 34.8, 32.3, 27.0, 25.9,
19.4, 19.3; HRMS Calcd for C24H34N1O1Si1 [M+H]+: 380.2404,
Found: 380.2400, Error: 1.1 ppm; IR (neat) cmꢂ1 3353, 2955,
505. [
a]
D
20 = ꢂ23 (c 1.0, CHCl3). Enantiomeric excess is 98% deter-
mined by HPLC (Chiralpak AD, Hexane/Isopropanol = 95:5, flow
rate = 1.0 mL/min, 220 nm): major enantiomer: tR = 16.01 min;
minor enantiomer: tR = 22.12 min.
4.1.1.11. ((2S,3S)-3-Propyloxiran-2-yl) methyl-4-nitrobenzoate
2k0.
Compound 2k0 was prepared according to the general
2860, 1657, 1589, 1471, 1427, 1112, 739, 702, 508. [
1.0, CHCl3).
a]
20 = +6 (c
D
procedure in 62% yield as a light red oil. 1H NMR (400 MHZ, CDCl3)
d 8.22–8.31 (m, 4H), 4.68 (dd, J = 2.8 Hz, 12 Hz, 1H), 4.21 (dd,
J = 6.4 Hz, 12 Hz, 1H), 3.10–3.13 (m, 1H), 2.92–2.96 (m, 1H),
1.57–1.63 (m, 2H), 1.46–1.54 (m, 2H), 0.98 (t, J = 7.4 Hz, 3H); 13C
NMR (100 MHZ, CDCl3) d 164.4, 150.6, 135.0, 130.8, 123.5, 66.1,
56.4, 54.9, 33.4, 19.1, 13.8; HRMS (ESI) Calcd for C13H16N1O5 [M
+H]+: 266.1023, Found: 266.1018, Error: 1.9 ppm; IR (neat) cmꢂ1
Acknowledgements
This work was supported by the NSFC (No.: 21202073,
21290180, 21272097, 21372104 and 21472077), the ‘111’ Program
of MOE, the Project of MOST (2012ZX 09201101–003) and the fun-
damental research funds for the central universities (lzujbky-2014-
K20 and lzujbky-2015-k12).
3435, 2960, 1944, 1728, 1529, 1271, 1102, 720, 505. [
a
]
20 = ꢂ32
D
(c 1.0, CHCl3). Enantiomeric excess is 94% determined by HPLC
(Chiralpak AD, Hexane/Isopropanol = 90:10, flow rate = 1.0 mL/
min, 220 nm): major enantiomer: tR = 11.24 min; minor enan-
tiomer: tR = 13.65 min.
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetasy.2016.02.
009.
4.1.1.12. (S)-(3,3-Dimethyloxiran-2-yl)methyl-4-nitrobenzoate
2l0.
Compound 2l0 was prepared according to the general pro-
cedure in 15% yield as a white solid. 1H NMR (400 MHZ, CDCl3) d
8.23–8.31 (m, 4 H), 4.67 (dd, J = 4 Hz, 12 Hz, 1H), 4.31 (dd,
J = 7.2 Hz, 12 Hz, 1H), 3.15 (dd, J = 4 Hz, 7.2 Hz, 1H), 1.40 (s, 6H);
13C NMR (100 MHZ, CDCl3) d 164.5, 150.6, 135.1, 130.8, 123.5,
64.9, 60.2, 58.3, 24.5, 18.9; HRMS (ESI) Calcd for C12H14N1O5 [M
+H]+: 252.0866, Found: 252.0863, Error: 1.2 ppm; IR (neat) cmꢂ1
3344, 2961, 2370, 1728, 1640, 1525, 1347, 1262, 1108, 758, 507.
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Compound 2m0 was prepared according to the general
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a
]
D
20 = ꢂ17 (c 1.0, CHCl3). Enan-
Please cite this article in press as: Xu, M.-H.; et al. Tetrahedron: Asymmetry (2016), http://dx.doi.org/10.1016/j.tetasy.2016.02.009

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