Asymmetric Darzens-type epoxidation via chiral ammonium ylides

Article abstract of DOI:10.1055/s-0030-1258015

Asymmetric Darzens-type epoxide formation of aryl aldehydes with chiral para-substituted benzylammonium ylides, prepared from brucine and corresponding benzylic chlorides and treated in situ under basic condition, was carried out to afford chiral 2,3-diaryl epoxides with moderate to good ee (84% ee). Brucine was found to be an excellent tertiary amine for a chirality transfer agent. Georg Thieme Verlag Stuttgart - New York.

Full text of DOI:10.1055/s-0030-1258015

2330
LETTER
Asymmetric Darzens-Type Epoxidation via Chiral Ammonium Ylides
Asymmetric
D
arze
i
ns-Typ
r
e
Epoxi
o
School of Pharmaceutical Sciences, Mukogawa Women’s University, 11-68 Kyuban-cho Koshien, Nishinomiya 663-8179, Hyogo, Japan
Fax +81(798)459952; E-mail: tkimachi@mukogawa-u.ac.jp
Received 9 June 2010
Abstract: Asymmetric Darzens-type epoxide formation of aryl al-
dehydes with chiral para-substituted benzylammonium ylides, pre-
X
N
pared from brucine and corresponding benzylic chlorides and
treated in situ under basic condition, was carried out to afford chiral
2,3-diaryl epoxides with moderate to good ee (84% ee). Brucine
was found to be an excellent tertiary amine for a chirality transfer
agent.
X
N+
Cl–
(X = CH, N)
Cl
THF, reflux, 2 h
Z
Z
Z = electron-withdrawing groups
(Z = CF3, Et2NC(O), NC, etc.)
ammonium chloride
2 KOt-Bu
THF, 1 h
Key words: brucine, 2,3-diaryl epoxides, chiral tertiary amines,
Darzens reaction
Z
X
N+
–
ArCHO
Ar
Chiral epoxides are important functional organic mole-
cules due to their presence in natural products,1 their bio-
logical activity, and their serving as intermediates2 for
chiral ring-opened products to obtain amino alcohols, di-
ols, and alcohols. To date, aside from the epoxidation of
olefins,3 chiral epoxides have been prepared by catalytic
asymmetric sulfur ylide mediated epoxidation4 and by
asymmetric Darzens reaction catalyzed by phase-transfer
catalysts.5 Epoxides are easily converted to amino alco-
hols, diols, and alcohols (often important components of
biologically active natural products) by the corresponding
nucleophilic, acidic, and reductive ring-opening reac-
tions.6 In a previous paper, we reported the trans-selective
synthesis of 2,3-diaryl epoxides by Darzens-type reaction
via ammonium ylides derived from electron-poor benzyl-
ammonium chlorides. We have also reported the effec-
tiveness of sterically demanding tertiary amines such as
DABCO and quinuclidine on the formation of quaternary
ammonium salts7 (Scheme 1).
O
Z
+
55–99% yield
(>95% trans)
ammonium ylide
X
N
(X = CH, N)
reusable
Scheme 1 Diastereoselective Darzens-type epoxidation via para-
substituted benzylammonium ylides
1) 1–5
F3C
THF, reflux, 3 h
Cl
Ar
2) ArCHO, 2 KOt-Bu
temp, time
F3C
O
up to 98% yield
trans selective
up to 84% ee (S,S)
Scheme 2 Chiral ammonium ylide mediated asymmetric Darzens
reaction
MeO
With the aim of advancing and expanding this useful
methodology, we studied the first example of one-pot
trans-selective asymmetric epoxidation of chiral ammoni-
um chlorides and aryl aldehydes (Scheme 2).
N
MeO
OH
H
H
N
N
H
O
N
There have been many reports on cinchonium or cin-
chonidium salt catalyzed asymmetric Darzens glycidic es-
ter formation,5 but many of the reactions proceed slowly,
taking a few days for completion. Encouraged by our re-
sults, we undertook the study of the scope and limitations
of the chirality transferring ability of tertiary amines on
the asymmetric Darzens-type epoxidation via ammonium
ylides. The epoxidations were carried out using cincho-
nine (1), brucine (2), and chiral quinuclidine derivatives
3–5 (Figure 1).
O
(1)
(2)
brucine
cinchonine
C6H13
O
Ph
t-Bu Si
N
N
O
N
Ph
t-Bu Si
Ph
3
4
5
O
Ph
Figure 1 Chiral tertiary amines
We initially prepared quaternary ammonium salts of
chiral tertiary amines 1–5 with p-trifluoromethyl benzyl
chloride under reflux conditions in THF. Only chinchoni-
um salt was prepared and isolated according to the litera-
SYNLETT 2010, No. 15, pp 2330–2334
Advanced online publication: 06.08.2010
DOI: 10.1055/s-0030-1258015; Art ID: U05210ST
© Georg Thieme Verlag Stuttgart · New York
x
x
.x
x
.2
0
1
0

LETTER
Asymmetric Darzens-Type Epoxidation
2331
ture,8 then in situ treatment of prepared ammonium salt summarized in Table 2. Chiral ammonium chlorides with
and benzaldehyde under basic condition afforded the cor- electron-rich aryl aldehydes afforded chiral epoxides 6–8
responding epoxide 6.7 The results are shown in Table 1.
in moderate to high yield (Table 2, entries 1–3), though
nicotinaldehyde and 4-cyanobenzaldehyde, which could
be regarded as electron-poor aryl aldehydes, led to the
corresponding 2,3-diaryl epoxides 9 and 10 in low yield
with low enantioselectivity (entries 4 and 5).
The epoxide formation using cinchonium salt resulted in
recovery of the starting material (Table 1, entry 1). The
ammonium salt prepared from brucine and p-trifluorome-
thylbenzyl chloride was treated with KOt-Bu in the pres-
ence of benzaldehyde to afford 6 in high yield (98%) with In a previous study,7 we successfully obtained 2,3-diaryl
moderate diastereoselectivity and enantioselectivity epoxides in a highly trans-selective manner with basic
(Table 1, entry 2). As for brucine-mediated epoxidation, treatment of electron-poor benzylammonium chlorides
diastereoselectivity and enantioselectivity were tempera- and aryl aldehydes. Thus, we carried out brucine-mediat-
ture-dependent. The highest diastereo- and enantioselec- ed epoxide formation using a series of electron-deficient
tivities were observed at –40 °C (Table 1, entries 2–4). para-substituted benzylammonium chlorides. The results
Silyl ethers of two vinylquinuclidine methanol derivatives are also shown in Table 2. Electron-deficient para-substi-
3 and 4,9 prepared from the corresponding commercially tuted benzylammonium chloride led to the formation of
available vinylquinuclidine methanol derivatives, pro- trans-2, 3-diaryl epoxides 11–14 in moderate to good
moted epoxidation to afford 6 in moderate yield with low chemical yield with high enantioselectivities (entries 6–
diastereoselectivity and enantioselectivity (Table 1, en- 9).12 Electron-rich para-substituted benzylammonium
tries 5 and 6). A series of epoxidations, using (R)-3-O- chlorides, for example p-methyl- and p-methoxybenzyl-
hexylquinuclidinol (5),11 gave adducts in poor chemical ammonium chloride, were also treated with KOt-Bu in the
and optical yield, even though trans selectivity was ob- presence of benzaldehyde to afford the corresponding 2,3-
served (Table 1, entries 7–10). Based on these preliminary diaryl epoxides in diastereomeric mixtures in low yields.
experimental results, attention was focused on a series of The ee value of each trans isomer was low (<10% ee, data
brucine-mediated asymmetric Darzens-type epoxide for- not shown). These results suggest that the presence of
mations. p-Trifluoromethylbenzyl chlorides and brucine electron-poor substituents is crucial not only for trans-se-
were refluxed in THF, upon in situ treatment with KOt-Bu lective epoxide formation but also for enantioselective ep-
and various aryl aldehydes, and afforded the correspond- oxidation.
ing epoxides. Hence, no isolation or purification of the
prepared ammonium salt was necessary. The results are
In conclusion, we achieved a highly trans-selective asym-
metric Darzens-type epoxidation of electron-poor benzyl-
Table 1 Asymmetric Darzens-Type Epoxidation Mediated by Chiral Tertiary Amines
PhCHO
2 KOt-Bu
temp, time
chiral amines
1–5
THF, reflux, 3 h
Cl–
N+
F3C
chiral amines
Cl
F3C
F3C
O
6
Entry
Amines
Time (h)
Temp (°C)
Yield (%)
dr (cis/trans)
–
ee (%)a
–
1
2
1
2
2
2
3
4
5
5
5
5
48
3
3
3
3
3
3
3
3
3
r.t.
0
98
80
79
49
71
75
86
13
7
r.t.
17:83
65 (S,S)b
70 (S,S)b
79 (S,S)b
30 (S,S)b
14 (R,R)b
9 (S,S)b
15 (S,S)b
30 (S,S)b
65 (S,S)b
3
–20
–40
r.t.
6:94
4
7:93
5
29:71
6
r.t.
17:83
7
r.t.
<1:>99
<1:>99
<1:>99
<1:>99
8
–20
–40
–40
9
10c
a The ee values were obtained by HPLC analysis on a CHIRALPAK AD-H column (250 × 4.6 mm i.d.) using n-hexane–2-PrOH (90:10) as
eluent (flow rate 1.0 mL/min) at 254 nm.
b The absolute configuration of the major enantiomer of 6 having trans orientation was determined by comparison with the optical rotation re-
ported by Aggarwal et al.4
c The reaction was carried out using CH2Cl2.
Synlett 2010, No. 15, 2330–2334 © Thieme Stuttgart · New York

2332
H. Kinoshita et al.
LETTER
Table 2 Asymmetric Darzens Reaction between Brucine para-Substituted Benzyl Ammonium Chlorides and Aryl Aldehydes
1) brucine, THF
reflux, 3 h
R
Cl
2) ArCHO, 2 KOt-Bu
–40 °C, 3 h
3) –40 to 0 °C
Ar
R
O
6–14
Entry
R
Ar-
Ph
Product
Yield (%)
dr (cis/trans)
7:93
ee (%)a
1
2
3
4
5
6
7
8
9
CF3
6
7
79
46
64
11
5
79 (S,S)b
83 (S,S)b
80 (S,S)b
60 (S,S)b
29 (S,S)b
69 (S,S)b
82 (S,S)b
84 (S,S)b
83 (S,S)b
CF3
4-MeOC6H4
<1:>99
<1:>99
21:79
CF3
4-t-BuC6H4
3-pyridyl
4-NCC6H4
Ph
8
CF3
9
CF3
10
11
12
13
14
10:90
CN
33
75
54
58
<1:>99
11:89
t-BuOC(O)
Et2NC(O)
Et2NC(O)
Ph
Ph
19:81
4-MeOC6H4
10:90
a The ee values were obtained by HPLC analysis on a CHIRALPAK AD-H column (250 × 4.6 mm i.d.) using n-hexane–2-PrOH (90:10) as
eluent (flow rate 1.0 mL/min) at 254 nm.
b The absolute configuration of the major enantiomer of 6 having a trans orientation was determined by the comparison with the optical rotation
reported by Aggarwal et al.4
Catalytic Asymmetric Synthesis; Ojima, I., Ed.; VCH: New
York, 1993, 159. (c) Katsuki, T.; Martin, V. S. Org. React.
1996, 48, 1.
ammonium chlorides with aromatic aldehydes via the
corresponding benzylammonium ylides. Brucine was
found to function as an effective chirality-transfer agent.
Further work on synthetic applications of the derived
enantioenriched 2, 3-diaryl epoxides for biologically ac-
tive compounds is now in progress.
(4) (a) Li, A.-H.; Dai, L.-X.; Aggarwal, V. K. Chem. Rev. 1997,
97, 2341. (b) Aggarwal, V. K.; Calamai, S.; Ford, J. G.
J. Chem. Soc., Perkin Trans. 1 1997, 593. (c) Aggarwal, V.
K.; Ford, J. G.; Fonquerna, S.; Adams, H.; Jones, R. V. H.;
Fieldhouse, R. J. Am. Chem. Soc. 1998, 1120, 8328.
(d) Julienne, K.; Metsner, P.; Henryon, V. J. Chem. Soc.,
Perkin Trans. 1 1999, 731. (e) Aggarwal, V. K.; Winn, C. L.
Acc. Chem. Res. 2004, 37, 611.
Acknowledgment
We thank Professor Yoshiji Takemoto (Graduate School of Phar-
maceutical Sciences, Kyoto University, Japan) for the informative
discussions and advice.
(5) (a) Arai, S.; Shioiri, T. Tetrahedron Lett. 1998, 39, 2145.
(b) Arai, S.; Shioiri, T. Tetrahedron 2002, 58, 1407; and
references cited therein.
(6) Alcoholysis: (a) Tamami, B.; Iranpoor, N.; Razaei, R. Synth.
Commun. 2004, 34, 2789. (b) Iranpoor, N.; Salehi, P.
Synthesis 1994, 1152. (c) Surendra, K.; Krishnaveni, N. S.;
Nageswar, Y. V. D.; Rao, K. R. J. Org. Chem. 2003, 68,
4994. Aminolysis: (d) Murai, T.; Sano, H.; Kawai, H.; Aso,
H.; Shibahara, F. J. Org. Chem. 2005, 70, 8148.
(e) Mirkhani, V.; Tangestaninejad, S.; Yadollahi, B.;
Alipanah, L. Catal. Lett. 2005, 101, 93. (f) Lupi, V.;
Albanese, D.; Landini, D.; Scaletti, D.; Penso, M.
Tetrahedron 2004, 60, 11709. (g) Sundararajan, G.;
Vijayakrishna, K.; Varghese, B. Tetrahedron Lett. 2004, 45,
8253. Azidolysis: (h) Marie, J.-C.; Courillon, C.; Malarcia,
M. Synlett 2002, 553. Reductive ring opening: (i) Ley, S.
V.; Mitchell, C.; Pears, D.; Ramarao, C.; Yu, J.-Q.; Zhou, W.
Org. Lett. 2003, 5, 4665. Lewis acid catalyzed ring opening
of epoxides: (j) Blum, S. A.; Rivera, V. A.; Ruck, R. T.;
Michael, F. E.; Bergman, R. G. Organometallics 2005, 24,
1647. (k) Asandei, A. D.; Moran, I. W. J. Am. Chem. Soc.
2004, 126, 15932.
References and Notes
(1) (a) Oda, T.; Watanuki, M.; Sakakibara, Y.; Sato, Y. Biol.
Pharm. Bull. 1995, 18, 1435. (b) Zhang, Z.-B.; Wang,
Z.-M.; Wang, Y.-X.; Liu, H.-Q.; Lei, G.-X.; Shi, M.
Tetrahedron: Asymmetry 1999, 10, 837; and references cited
therein.
(2) (a) Shirota, T.; Pathak, V.; Sekita, S.; Satake, M.;
Nagashima, Y.; Hirayama, Y.; Hakamata, Y.; Hayashi, T.
J. Nat. Prod. 2003, 66, 1128. (b) Watanabe, M.; Kawanishi,
K.; Akiyoshi, R.; Furukawa, S. Chem. Pharm. Bull. 1991,
3123. (c) Adger, B. M.; Barkley, J. V.; Bergeron, S.; Cappi,
M. W.; Flowerdew, B. E.; Jackson, M. P.; McCague, R.;
Nugent, T. C.; Roberts, S. M. J. Chem. Soc., Perkin Trans. 1
1997, 3501. (d) Cappi, M. W.; Chen, W.-P.; Flood, R. W.;
Liao, Y.-W.; Roberts, S. M.; Skidmore, J.; Smith, J. A.;
Williamson, N. M. Chem. Commun. 1998, 1159. (e) Carde,
L.; Davies, D. H.; Roberts, S. M. J. Chem. Soc., Perkin
Trans. 1 2000, 2455. (f) Ray, P. C.; Roberts, S. M. J. Chem.
Soc., Perkin Trans. 1 2001, 149.
(7) Kimachi, T.; Kinoshita, H.; Kusaka, K.; Takeuchi, Y.; Aoe,
M.; Ju-ichi, M. Synlett 2005, 842.
(8) Corey, E. J.; Xu, F.; Noe, M. C. J. Am. Chem. Soc. 1997,
119, 12414.
(3) (a) Berrisford, D. J.; Bolm, C.; Sharpless, K. B. Angew.
Chem., Int. Ed. Engl. 1995, 34, 1059. (b) Jacobsen, E. N. In
Synlett 2010, No. 15, 2330–2334 © Thieme Stuttgart · New York

LETTER
Asymmetric Darzens-Type Epoxidation
2333
(9) Compound 3 is a known catalyst developed by Yamamoto et
al.10 and compound 4 is a new compound.
(10) (a) Saito, S.; Kano, T.; Muto, H.; Nakadai, M.; Yamamoto,
H. J. Am. Chem. Soc. 1999, 121, 8943. (b) Kano, T.;
Ohyabu, Y.; Saito, S.; Yamamoto, H. J. Am. Chem. Soc.
2002, 124, 5365.
(250 × 4.6 mm, i.d.) from Daicel Co., using n-hexane–2-
PrOH (90:10) as eluent (flow rate 1.0 mL/min) at 254 nm.
The major enantiomer (2S,3S) was eluted after 4.6 min, and
the minor enantiomer after 5 min.
(2S,3S)-2-(3-Pyridyl)-3-(4-trifluoromethylphenyl)-
oxirane (9)
(11) Stotter, P. L.; Friedman, M. D.; Dorsey, G. O.; Shiely, R. W.;
Williams, R. F.; Minter, D. E. Heterocycles 1987, 25, 251.
(12) Typical Procedure for the Synthesis of (2S,3S)-2-Phenyl-
3-(4-trifluoromethylphenyl)oxirane (6)
Colorless solid; mp 54–56 °C; [a]D23 –77.4 (c 0.57 acetone).
1H NMR (400 MHz, CDCl3): d = 3.88 (d, 1 H, J = 1.8 Hz),
3.96 (d, 1 H, J = 1.8 Hz), 7.33 (dd, 1 H, J = 4.4, 8.1 Hz), 7.47
(d, 2 H, J = 8.1 Hz), 7.63 (dt, 1 H, J = 8.1, 1.8 Hz), 8.61 (dd,
1 H, J = 1.8, 4.4 Hz), 8.64 (d, 1 H, J = 1.8 Hz). 13C NMR
(100 MHz, CDCl3): d = 60.9, 61.9, 123.6, 124.3 (q, J = 272
Hz), 125.7 (q, J = 4 Hz), 125.9, 131.0, 132.2, 132.7, 140.5,
147.9, 150.0. IR (CHCl3): 3000, 1600 cm–1. The ee, found to
be 60%, was obtained by HPLC on a CHIRALPAK AD-H
column (250 × 4.6 mm, i.d.) from Daicel Co., using n-
hexane–2-PrOH (90:10) as eluent (flow rate 1.0 mL/min) at
254 nm. The major enantiomer (2S,3S) was eluted after 7.0
min, and the minor enantiomer after 9.2 min.
A THF (3 mL) solution of trifluoromethyl benzyl chloride
(0.15 mL, 1.0 mmol) and brucine (591 mg, 1.5 mmol) in a
flame-dried round-bottom flask (30 mL volume) was heated
under reflux for 3 h. Subsequently, the reflux condenser was
removed, and a septa cap was placed on the top of the flask.
The resulting precipitate in THF was treated with further
addition of THF (6 mL) and benzaldehyde (0.1 mL, 1.0
mmol) at r.t., and then the mixture was cooled to –40 °C
under argon atmosphere. Two equiv of KOt-Bu (224 mg, 2.0
mmol) were slowly added, and the mixture was stirred at this
temperature for 3 h. The mixture was warmed up to 0 °C and
kept for 3 h and worked up. The general workup procedure
is as follows. First, 5 mL of EtOAc and sat. aq NH4Cl (5 mL)
were added and then separated. The aqueous layer was
extracted three times with EtOAc and combined. The
organic layer was washed with H2O, brine, and then dried
over MgSO4. Removal of the solvent and purification by
flash chromatography afforded (2S,3S)-2-phenyl-3-(4-
trifluoromethylphenyl)oxirane as a colorless solid; mp
57 °C; [a]D26 –173.4 (c 1.21 acetone). 1H NMR (400 MHz,
CDCl3): d = 3.84 (d, 1 H, J = 1.8 Hz), 3.92 (d, 1 H, J = 1.8
Hz), 7.33–7.42 (m, 5 H), 7.46 (d, 2 H, J = 8.0 Hz), 7.64 (d, 2
H, J = 8.0 Hz). 13C NMR (126 MHz, CDCl3): d = 62.0, 63.1,
124.1 (q, J = 271 Hz), 125.5, 125.6 (q, J = 3 Hz), 125.8,
128.6, 128.7, 130.5 (q, J = 33 Hz), 136.6, 141.2. IR (CHCl3):
1620, 1320, 1160, 1120 cm–1. HRMS (EI+): m/z calcd for
C15H11OF3: 264.0762; found: 264.0753. The ee, found to be
79%, was obtained by HPLC on a CHIRALPAK AD-H
column (250 × 4.6 mm, i.d.) from Daicel Co., using n-
hexane–2-PrOH (90:10) as eluent (flow rate 1.0mL/min) at
254 nm. The major enantiomer (2S,3S) was eluted after 9.6
min, and the minor enantiomer after 5.0 min.
(2S,3S)-2-(4-Cyanophenyl)-3-(4-trifluoromethylphenyl)-
oxirane (10)
Colorless solid; 87–91 °C; [a]D24 –43.5 (c 1.0 EtOH). 1H
NMR (400 MHz, CDCl3): d = 3.89 (s, 2 H), 7.45–7.47 (m, 4
H), 7.65–7.70 (m, 4 H). 13C NMR (100 MHz, CDCl3):
d = 62.0, 62.4, 112.5, 118.5, 124.0 (q, J = 272 Hz), 125.7 (q,
J = 4 Hz), 125.9, 126.3, 131.0 (q, J = 33 Hz), 132.5, 140.3,
141.9. IR (CHCl3): 3000, 2200, 1600, 1500 cm–1. The ee,
found to be 29%, was obtained by HPLC on a CHIRALPAK
AD-H column (250 × 4.6 mm, i.d.) from Daicel Co., using n-
hexane–2-PrOH (90:10) as eluent (flow rate 1.0 mL/min) at
254 nm. The major enantiomer (2S,3S) was eluted after 10
min, and the minor enantiomer after 19.0 min.
(2S,3S)-2-(4-Cyanophenyl)-3-phenyloxirane (11)
Colorless solid; mp 76–83 °C; [a]D24 –227.0 (c 1.04 EtOH).
1H NMR (400 MHz, CDCl3): d = 3.82 (d, 1 H, J = 1.8 Hz),
3.91 (d, 1 H, J = 1.8 Hz), 7.32–7.42 (m, 5 H), 7.45 (d, 2 H,
J = 8.4 Hz), 7.67 (d, 2 H, J = 8.4 Hz). IR (CHCl3): 3000,
2210, 1605, 1500 cm–1. The ee, found to be 69%, was
obtained by HPLC on a CHIRALPAK AD-H column
(250 × 4.6 mm, i.d.) from Daicel Co., using n-hexane–2-
PrOH (90:10) as eluent (flow rate 1.0 mL/min) at 254 nm.
The major enantiomer (2S,3S) was eluted after 11.2 min, and
the minor enantiomer after 20.0 min.
(2S,3S)-2-(4-Methoxyphenyl)-3-(4-trifluoromethyl-
phenyl)oxirane (7)
4-[(2S,3S)-3-Phenyloxiranyl]benzoic Acid 1,1-Dimethyl-
ethyl Ester (12)
Colorless solid; mp 63–67 °C; [a]D27 –164.4 (c 1.04 EtOH).
1H NMR (400 MHz, CDCl3): d = 3.78 (d, 1 H, J = 1.8 Hz),
3.83 (s, 3 H), 3.91 (d, 1 H, J = 1.8 Hz), 6.92 (d, 2 H, J = 8.8
Hz), 7.26 (d, 2 H, J = 8.8 Hz), 7.45 (d, 2 H, J = 8.4 Hz), 7.60
(d, 2 H, J = 8.4 Hz). 13C NMR (126 MHz, CDCl3): d = 55.4,
61.8, 63.0, 114.2, 125.5, 125.7, 126.8, 128.5, 141.3, 160.1.
IR (CHCl3): 3000, 1610, 1510, 1320 cm–1. The ee, found to
be 83%, was obtained by HPLC on a CHIRALPAK AD-H
column (250 × 4.6 mm, i.d.) from Daicel Co., using n-
hexane–2-PrOH (90:10) as eluent (flow rate 1.0 mL/min) at
254 nm. The major enantiomer (2S,3S) was eluted after 10
min, and the minor enantiomer after 6.6 min.
Colorless solid; mp 101–105 °C; [a]D26 –177.6 (c 1.13
acetone). 1H NMR (400 MHz, CDCl3): d = 1.60 (s, 9 H),
3.84 (d, 1 H, J = 1.8 Hz), 3.90 (d, 1 H, J = 1.8 Hz), 7.32–7.39
(m, 7 H), 7.99 (d, 2 H, J = 8.1 Hz). 13C NMR (100 MHz,
CDCl3): d = 28.2, 62.3, 63.0, 81.1, 125.2, 125.5, 128.5,
128.6, 129.7, 132.0, 136.7, 141.6, 165.4. IR (CHCl3): 3000,
1700, 1610, 1160, 1120 cm–1. HRMS (EI+): m/z calcd for
C19H20O3: 296.1412; found: 296.1402. The ee, found to be
82%, was obtained by HPLC on a CHIRALPAK AD-H
column (250 × 4.6 mm i.d.) from Daicel Co., using n-
hexane–2-PrOH (90:10) as eluent (flow rate 1.0 mL/min) at
254 nm. The major enantiomer (2S,3S) was eluted after 8.4
min, and the minor enantiomer after 6.8 min.
(2S,3S)-2-(4-tert-Butylphenyl)-3-(4-trifluoromethyl-
phenyl)oxirane (8)
Colorless solid; mp 104–108 °C; [a]D22 –156.8 (c 1.33
acetone). 1H NMR (400 MHz, CDCl3): d = 1.33 (s, 9 H),
3.81 (d, 1H, J = 1.8 Hz), 3.93 (d, 1 H, J = 1.8 Hz), 7.28 (d, 2
H, J = 8.2 Hz), 7.42 (d, 2 H, J = 8.2 Hz), 7.45 (d, 2 H, J = 8.2
Hz). 13C NMR (126 MHz, CDCl3): d = 31.3, 34.7, 61.9,
63.0, 124.2 (q, J = 272 Hz), 125.4, 125.5(q, J = 4 Hz), 125.6,
125.8, 130.5 (q, J = 33 Hz), 133.6, 141.4, 151.9. IR (CHCl3):
3000, 1620, 1170, 1130 cm–1. The ee, found to be 76%, was
obtained by HPLC on a CHIRALPAK AD-H column
N,N-Diethyl-4-[(2S,3S)-phenyloxyranyl]benzamide (13)
Colorless oil; [a]D24 –150.2 (c 1.16 acetone). 1H NMR (400
MHz, CDCl3): d = 1.20 (m, 6 H), 3.30 (m, 2 H), 3.54 (m, 2
H), 3.86 (d, 1 H, J = 1.83 Hz), 7.32–7.41 (m, 9 H). 13C NMR
(126 MHz, CDCl3): d = 13.0, 14.2, 39.3, 43.3, 62.4, 62.9,
125.6, 126.7, 128.5, 128.6, 136.9, 137.4, 138.2, 170.9. IR
(CHCl3): 3000, 1612, 1565, 1510 cm–1. The ee, found to be
86%, was obtained by HPLC on a CHIRALPAK IA column
(250 × 4.6 mm i.d.) from Daicel Co., using n-hexane–2-
Synlett 2010, No. 15, 2330–2334 © Thieme Stuttgart · New York

2334
H. Kinoshita et al.
LETTER
PrOH (90:10) as eluent (flow rate 1.0 mL/min) at 254 nm.
The major enantiomer (2S,3S) was eluted after 22.6 min, and
the minor enantiomer after 27.8 min.
J = 8.8 Hz), 7.39 (d, 2 H, J = 8.8 Hz). 13C NMR (100 MHz,
CDCl3): d = 13.0, 14.2, 39.4, 43.8, 55.4, 62.3, 62.8, 114.2,
125.5, 126.6, 126.9, 128.9, 137.3, 138.4, 160.0, 170.9. IR
(CHCl3): 3000, 1610, 1510 cm–1. The ee, found to be 80%,
was obtained by HPLC on a CHIRALPAK IB column
(250 × 4.6 mm i.d.) from Daicel Co., using n-hexane–2-PrOH
(90:10) as eluent (flow rate 1.0 mL/min) at 254 nm. The
major enantiomer (2S,3S) was eluted after 20.8 min, and the
minor enantiomer after 23.3 min.
N,N-Diethyl 4-[(2S,3S)-3-(p-Anisyl)oxiranyl]benzamide
(14)
Colorless oil; [a]D22 –88.16 (c 1.01 CHCl3). 1H NMR (400
MHz, CDCl3): d = 1.26 (m, 6 H), 3.40 (m, 4 H), 3.80 (d, 1 H,
J = 1.8 Hz), 3.82 (s, 3 H), 3.87 (d, 1 H, J = 1.8 Hz), 6.91 (d,
2 H, J = 8.8 Hz), 7.27 (d, 2 H, J = 8.8 Hz), 7.36 (d, 2 H,
Synlett 2010, No. 15, 2330–2334 © Thieme Stuttgart · New York

Copyright of Synlett is the property of Georg Thieme Verlag Stuttgart and its content may not
be copied or emailed to multiple sites or posted to a listserv without the copyright holder's
express written permission. However, users may print, download, or email articles for
individual use.