A novel and highly efficient asymmetric synthesis of epoxides via chiral telluronium ylides

Article abstract of DOI:10.1055/s-2005-872169

The one-pot reaction of telluronium salt 8, aldehyde, and potassium tert-butoxide proceeded smoothly via chiral benzyl telluronium ylide, producing trans-(2S,3S)-diaryl epoxides with good yields as well as excellent diastereoselectivities and enantioselectivities (up to 99% ee). Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2005-872169

PAPER
2857
A Novel and Highly Efficient Asymmetric Synthesis of Epoxides via Chiral
Telluronium Ylides
A
W
symmetric Synthesis
o
e
f
E
poxides
n
via Chiral
T
-
elluroniu
H
m
Y
lides ua Ou, Zhi-Zhen Huang*
School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, P. R. China
Fax +86(25)83686240; E-mail: huangzhizhen0226@163.com
Received 26 April 2005; revised 27 May 2005
Abstract: The one-pot reaction of telluronium salt 8, aldehyde, and
potassium tert-butoxide proceeded smoothly via chiral benzyl tellu-
ronium ylide, producing trans-(2S,3S)-diaryl epoxides with good
yields as well as excellent diastereoselectivities and enantioselectiv-
ities (up to 99% ee).
S
Se
Te
CHPh
CHPh
CHR
1
2
3
Key words: telluronium ylide, asymmetric synthesis, chiral ep-
oxide, enantioselectivity, one-pot reaction
R = vinyl, phenyl
Figure 1 Sulfonium 1, selenonium 2, and telluronium ylides 3.
1
reaction conditions. It was found that the reaction via allyl
telluronium ylide 6 could proceed in one-pot to give the
desired 2-phenyl-3-vinyl epoxides 7 predominantly as the
trans-product. However, under the range of reaction con-
ditions tested (Table 1), yields, stereoselectivities, and
enantioselectivities were poor at room temperature. When
the reaction was carried out at a lower temperature even
poorer yields resulted (10–30%).
Owing to their significant biological activities and versa-
2
tile chemical transformations, chiral epoxides have be-
come one of the most important synthetic intermediates.3
The development of new and efficient syntheses of chiral
epoxides is still a challenging subject. Among various
syntheses of chiral epoxides, the chiral ylide route is one
of the most important methods due to the formation of a4
carbon–carbon bond and epoxidation in the one reaction.
Recently, novel and efficient methods for asymmetric
5
synthesis of epoxides via C symmetric sulfonium ylide 1
Et O
2
2
6
+
Br
and selenonium ylide 2 have been developed (Figure 1).
Te
r.t., 10 h
Te
However, the formation of chiral epoxides via sulfonium
ylide 1 takes two to six days while that via selenonium
ylide 2 results in a mixture of distereomers (1:1 to 1:2).
The enantioselectivities of the sulfonium ylide 1 and sele-
nonium ylide 2 reactions are high and the ee ranges from
Br
4
5
Te
6
6
4–94%, however, further improvements to the stereose-
lectivity are still required. Although there are many re-
ports concerned with the application of telluronium ylides
in the synthesis of epoxides, to our knowledge, there is no
report on their application to the asymmetric synthesis of
epoxides. Furthermore, considering that telluronium
ylides are more reactive than their corresponding sulfo-
nium ylides, better diastereoselectivity is achieved with
the telluronium ylide, which is more sterically hindered
than the corresponding sulfonium and selenonium ylide.
Therefore, we prepared new telluronium ylides 3 and tried
O
THF
r.t.
7
5
+
ArCHO
+
t-BuOK
Ar
7
7
7
a: Ar = 4-CH3C6H4
b: Ar = C6H5
Scheme 1 Formation of telluronium salt 5 and the formation of chir-
al epoxides via allyl telluronium ylide 6.
to develop a more efficient method for the asymmetric Compared with allyl telluronium ylide 6, benzyl telluroni-
synthesis of chiral epoxides.
um ylide 9 is more sterically hindered, this may lead to in-
creased stereoselectivity. It was found that the reaction of
telluride 4 with benzyl bromide proceeded smoothly giv-
ing telluronium salt 8 in good yield (Scheme 2). Next, salt
We found that allyl telluronium salt 5 could be prepared
in good yield by the reaction of allyl bromide with tellu-
ride 4 which was prepared from (2S,5S)-hexanediol5
,8
8
was reacted with 2-chlorobenzaldehyde in the presence
(
Scheme 1). Subsequently, telluronium salt 5 was reacted
of potassium hydroxide in acetonitrile at room tempera-
ture. We were pleased to find that the one-pot reaction via
benzyl telluronium ylide 9 took place smoothly to give ep-
oxide 10b in 75% yield, almost exclusively as the trans
isomer, and with high enantioselectivitiy (84% ee). En-
couraged by this result, the synthesis of a chiral epoxides
with aldehydes in the presence of a base under a range of
SYNTHESIS 2005, No. 17, pp 2857–2860
x
x.
x
x
.
2
0
0
5
Advanced online publication: 12.08.2005
DOI: 10.1055/s-2005-872169; Art ID: F07705SS
Georg Thieme Verlag Stuttgart · New York
©

2
858
W.-H. Ou, Z.-Z. Huang
PAPER
Table 1 Formation of Chiral Epoxides via Allyl Telluronium Ylide 6
b
trans/cisc
72:28
d
Entry
Aldehyde
Methoda
Reaction time (h) Yield (%)
trans ee (S,S) (%)
1
2
3
4
4-MeC H CHO
A
B
C
D
A
24
36
36
36
36
61
51
36
55
45
50
46
53
44
32
6
4
–
–
–
80:20
75:25
65:35
5
C H CHO
75:25
6
4
a
Method A: KOH, CH CN; Method B: t-BuOK, THF; Method C: NaH, THF; Method D: KOH, THF, and trace water. All reactions were car-
3
ried out at r.t.
b
c
d
9
1
All products are known compounds and were confirmed by H NMR, IR, and mass spectroscopy.
Determined by H NMR spectroscopy or GC.
Determined by chiral HPLC on a Chiralcel OB-H column.
1
via ylide 9 was carried out in a range of solvents – Et O, fore the diastereoselectivity of our protocol via
2
CH CN, CH Cl , and THF. These results are different telluronium ylide 9 for the synthesis of chiral epoxides is
3
2
2
from telluronium ylide 6; the modified conditions resulted much better than that via selenonium ylide 2. Moreover,
in excellent diastereoselectivities (trans/cis, 98:2 to quite different from allyl telluronium ylide 6, the enantio-
1
(
00:0) in all solvents, however THF gave optimal yield selectivities of the chiral epoxides via benzyl telluronium
81%) and enantioselectivity (90% ee). In an attempt to ylide 9 are excellent and up to 99% ee could be achieved.
optimize the reaction conditions further, a range of bases Noticeably the enantioselectivities achieved via telluroni-
NaOH, KOH, NaH, and t-BuOK) were applied to the um ylide 9 are also better than that via the sulfonium ylide
(
one-pot reaction of salt 8 with 2-chlorobezaldehyde in 1 and selenonium ylide 2. As expected, the reaction via
THF at room temperature. The experiment showed all the telluronium ylide 9 proceeded faster than that via sulfo-
bases furnished chiral epoxides via ylide 9 as the desired nium ylide 1 and took only 12–24 hours. The absolute
trans-diaryl epoxides 10b in good yields (53–88%) with configurations of 10a–h were assigned by comparison of
excellent diastereoselectivity (trans/cis, 98:2–100:0). Po- the sign of optical rotation with that of the known com-
tassium tert-butoxide and salt 8, in a ratio of 1:3, gave the pound and all 2S,3S isomers of 10a–h are levorotatory in
best results producing trans-diaryl epoxides in good yield ethanol.5
,9
(
88%) with excellent enantioselectivity (91% ee).
In conclusion, optically pure telluronium salts 5 and 8
were synthesized in good yields; these are the precursors
of two new chiral telluronium ylides. We found that the
one-pot reaction via telluronium ylide 6 proceeded readily
to give the desired vinyl epoxides 7. However, yields, ste-
reoselectivities, and enantioselectivities for the synthesis
of chiral epoxides were not satisfactory. Furthermore we
found that the one-pot reaction via more hindered telluro-
nium ylide 9 proceeded smoothly to give the trans-
(2S,3S)-diaryl epoxides 10a–h in good yields, with excel-
lent diastereoselectivities and enantioselectivities (ee up
to 99%). This protocol via telluronium ylide 9 is better
than that via sulfonium ylide 1 or selenonium ylide 2 in
terms of both enantioselectivity and diastereoselectivity.
The facile preparation of chiral telluronium ylide 9, good
yields, excellent diastereoselectivities, and enantioselec-
tivities of the reaction make this protocol a novel and
highly efficient synthetic method for the synthesis of
chiral epoxides which may have practical application in
organic synthesis and industry.
Et2O
+
PhCH2Br
Te
0
°C, 12 h
Te
Br CH2Ph
4
8
Te
CHPh
9
O
H
THF
Ph
8
+
ArCHO + t-BuOK
–5 or –40 °C
s
s
H
Ar
10
1
1
1
0a: Ar = C6H5,
0d: Ar = 2,4-Cl2C6H3,
0g: Ar = 4-CH3C6H4,
10b: Ar = 2-ClC6H4,
10e: Ar = 3-FC6H4,
10h: Ar = 4-CH3OC6H4,
10c: Ar = 4-ClC6H4,
10f: Ar = 4-FC6H4,
Scheme 2 Formation of telluronium salt 8 and the synthesis of chir-
al epoxide via benzyl telluronium ylide 9.
Following this optimization, a variety of aromatic alde-
hydes were reacted with telluronium salt 8 at –5 °C or
1
All reactions were carried out under a nitrogen atmosphere. H
–
40 °C in the presence of potassium tert-butoxide in THF.
NMR spectra were determined in CDCl on a Brucker ARX-300
Our experimental results showed that the yields of trans-
diaryl epoxides 10 are good and the diastereoselectivities
are excellent (Table 2). In many cases, only the trans-iso-
mer was obtained and no cis-isomer was observed. There-
3
(
300 MHz) with TMS as the internal standard. MS were obtained on
a VG-ZAB-HS mass spectrometer. IR spectra were taken with a
DX-FT-2 spectrometer. Melting points were uncorrected. Elemen-
5
Synthesis 2005, No. 17, 2857–2860 © Thieme Stuttgart · New York

PAPER
Asymmetric Synthesis of Epoxides via Chiral Telluronium Ylides
2859
Table 2 Asymmetric Synthesis of trans-Diaryl Epoxides via Telluronium Ylide 9
f
Entry
Aldehyde
C H CHO
Producta
10a
10b
10b
10c
Time (h)
12b
Yield (%)d
trans/cise
98:2
ee (S,S) (%)
1
2
3
4
5
6
7
8
9
72
90
78
92
85
82
80
75
77
81
87
64g
99
94
95
96
86
93
93
95
94
97
91
91
6
5
2-ClC H CHO
12b
100:0
99:1
6
4
–
24c
4-ClC H CHO
12b
92:8
6
4
2,4-Cl C H CHO
10d
10d
10e
12b
99:1
2
6
3
–
24c
100:0
98:2
3-FC H CHO
12b
6
4
–
10e
24c
100:0
99:1
4-FC H CHO
10f
12
6
4
10
11
12
–
10f
24c
100:0
95:5
4-MeC H CHO
10g
10h
12b
6
4
4-MeOC H CHO
12b
99:1
6
4
a
b
c
d
e
f
All products are known compounds10 and were confirmed by H NMR, IR, and mass spectroscopy .
1
–
5 °C.
40 °C.
Isolated yields.
–
1
Determined by H NMR spectroscopy or GC.
Determined by chiral HPLC on a Chiralcel OD-H column.
g
5d
Product unstable on silica gel.
tal analyses were determined on Perkin-Elmer 240C. Enantiomeric
excesses were determined by HPLC analysis under the following
conditions: Daicel Chiralcel OB-H column, hexane–i-PrOH, 95:5,
MS (EIS, positive): m/z = 305 (M – Br).
Anal. Calcd for C H TeBr: C, 40.79; H, 5.00. Found: C, 40.98; H,
1
3
19
4
.89.
0
.5 mL/min, l = 254 nm or Daicel Chiralcel OD-H column, hexane–
i-PrOH, 95:5 to 99:1, 0.5 mL/min, l = 254 or 234 nm.
trans-(2S,3S)-2-Aryl-3-vinyl Epoxides (7); General Procedure
To a solution of telluronium salt 5 (1.0 mmol) and aldehyde (1.0
mmol) in THF (10 mL) was added t-BuOK (0.33 g, 3.0 mmol) at r.t.
The reaction mixture was stirred for the time indicated in Table 2 at
r.t. Then the mixture was filtered and solvent was removed by evap-
oration. The residue was separated by preparative TLC to give the
Telluronium Salts 5 and 8; General Procedure
A mixture of telluride 4 (1.23 g, 5.78 mmol) and allyl bromide (0.64
g, 5.96 mmol) or benzyl bromide (1.02 g, 5.96 mmol) was stirred in
Et O at r.t. for 12 h. The mixture was filtered and the residue was
2
washed with Et O to give telluronium salt 5 or 8. Salt 5 or 8 could
2
2
-aryl-3-vinyl epoxide 7.
be recrystallized from CH Cl –Et O.
2
2
2
trans-(2S,3S)-2-(4-Methylphenyl)-3-vinyloxirane (7a)
Pale yellow oil.
Allyl Telluronium Salt 5
Yield: 81% (1.49g); colorless prisms; mp 114–115.5 °C;
9
–
1
20
IR (KBr): 1488, 1372, 1251, 1075, 923, 876, 823, 726 cm .
[
a]D +109.7 (c 0.62, CHCl3).
1
–
1
H NMR: d = 7.27–7.17 (m, 4 H), 5.75–5.28 (m, 3 H), 3.76 (d, J =
IR (KBr): 3085, 2795, 1635, 891 cm .
2
.0 Hz, 1 H), 3.40–3.37 (dd, J = 2.0 Hz, 1 H, trans), 2.37 (s, 3 H).
1
H NMR: d = 6.06–6.03 (m, 1 H), 5.39 (m, 1 H), 5.28 (m, 1 H), 4.30
m, 1 H), 3.80 (m, 1 H), 3.51–3.41 (m, 2 H), 2.80 (m, 1 H), 2.41–
(
trans-(2S,3S)-2-Phenyl-3-vinyloxirane (7b)
2
.37 (m, 2 H), 1.89–1.74 (m, 7H).
9
Pale yellow oil.
MS (EIS, positive): m/z = 255 (M – Br).
IR (KBr): 1495, 1446, 1251, 1183, 1061, 985, 921, 871, 790 cm–1.
Anal. Calcd for C H TeBr: C, 32.49; H, 5.15. Found: C, 32.78; H,
1
9
17
H NMR: d = 7.38–7.28 (m, 5 H), 5.60–5.28 (m, 3 H), 3.79 (d, J =
5
.09.
1
.9 Hz, 1 H), 3.40–3.37 (dd, J = 1.9 Hz, 1 H), 2.37 (s, 3 H).
Benzyl Telluronium Salt 8
Yield: 84%; colorless prisms; mp 135–137 °C; [a] +218.6
trans-(2S,3S)-Diaryl Epoxides 10; General Procedure
2
0
D
To the solution of telluronium salt 8 (1.0 mmol) and aldehyde (1.0
mmol) in THF (10 mL) was added t-BuOK (0.33 g, 3.0 mmol) at
–5 °C or –40 °C (Table 2). The reaction mixture was stirred for the
time indicated in Table 2 at this temperature. Then the mixture was
filtered and solvent was removed by evaporation. The residue was
(
c 0.61, CHCl ).
3
–
1
IR (KBr): 2915, 2862, 2846, 1595, 1489, 1448, 1230, 761 cm .
1
H NMR: d = 7.50–7.25 (m, 5 H), 4.52 (d, J = 12 Hz, 1 H), 3.85 (d,
J = 12 Hz, 1 H), 4.38 (m, 1 H), 3.35–3.29 (m, 1 H), 2.94–2.88 (m,
1
H), 2.44–2.37 (m, 2 H), 1.85–1.64 (m, 7 H).
Synthesis 2005, No. 17, 2857–2860 © Thieme Stuttgart · New York

2
860
W.-H. Ou, Z.-Z. Huang
PAPER
trans-(2S,3S)-2-(4-Methoxyphenyl)-3-phenyloxirane (10h)
separated by preparative TLC to give the trans-(2S,3S)-diaryl ep-
oxides 10.
5
d
White solid; mp 76–78 °C (Lit. 76–78 °C).
–
1
IR (KBr): 3043, 2967, 1614, 1517, 1254, 1032, 826 cm .
trans-(2S,3S)-2,3-Diphenyloxirane (10a)
Colorless prisms; mp 68–69 °C (Lit. 69 °C)
1
1
0a
H NMR: d = 7.40–6.91 (m, 9 H), 3.87 (d, J = 1.9 Hz, 1 H), 3.84 (s,
3
H), 3.83 (d, J = 1.9 Hz, 1 H).
–
1
IR: 3060, 2987, 1452, 1071, 851, 748, 695, 611 cm .
1
H NMR: d = 7.43–7.28 (m, 10 H), 3.90 (s, 2 H).
Acknowledgment
trans-(2S,3S)-2-(2-Chlorophenyl)-3-phenyloxirane (10b)
We gratefully acknowledge the National Natural Science Founda-
tion of China for its financial support of the project 20332050.
Colorless oil.1
0b
–
1
IR (KBr): 3065, 2986, 1478, 1275, 1128, 750, 700, 612 cm .
1
H NMR: d = 7.42–7.28 (m, 9 H), 4.25 (d, J = 1.9 Hz, 1 H), 3.79 (d,
References
J = 1.9 Hz, 1 H).
(
1) (a) Hatakeyama, S.; Ochi, N.; Takano, S. Chem. Pharm.
Bull. 1993, 41, 1358. (b) Jerina, D. M.; Daloy, J. W. Science
(Washington, D.C.) 1974, 185, 573. (c) Becker, A. R.;
Janusz, J. M.; Bruice, T. C. J. Am. Chem. Soc. 1979, 101,
trans-(2S,3S)-2-(4-Chlorophenyl)-3-phenyloxirane (10c)
Colorless prisms; mp 99–100 °C (Lit. 100 °C)
1
0a
–
1
IR (KBr): 3052, 1492, 1460, 1091, 819, 751, 700 cm .
5679.
1
H NMR: d = 7.39–7.15 (m, 9 H), 3.86 (d, J = 1.9 Hz, 1 H), 3.84 (d,
(2) (a) Hudlicky, T.; Tian, X.; Königsberger, K.; Rouden, J. J.
Org. Chem. 1994, 59, 4037. (b) Shao, H.; Zhu, Q.;
J = 1.9 Hz, 1 H).
Goodman, M. J. Org. Chem. 1995, 60, 790. (c) Shoulié, J.;
Boyer, T.; Lallemand, J. Y. Tetrahedron: Asymmetry 1995,
trans-(2S,3S)-2-(2,4-Dichlorophenyl)-3-phenyloxirane (10d)
Colorless prisms; mp 89–92 °C.
6, 625.
IR (KBr): 3084, 3065, 3023, 1588, 1462, 1459, 1096, 821, 733, 692
cm .
(3) (a) Bartók, M.; Lang, K. L. The Chemistry of Functional
Groups; Patai, S., Ed.; Wiley: New York, 1980, Supplement
E, 609–681. (b) Gorzynski, S. Synthesis 1984, 629. (c)Rao,
A. K.; Paknikar, S. K.; Kirtance, J. G. Tetrahedron 1983, 39,
–
1
1
H NMR: d = 7.29–7.45 (m, 8 H), 4.19 (d, J = 1.9 Hz, 1 H), 3.75 (d,
J = 1.9 Hz, 1 H).
2323.
+
MS (EI): m/z (%) = 248 (68.36) [M ], 264 (49), 248 (52), 235 (74),
(4) Li, A. H.; Dai, L. X.; Aggarwal, V. K. Chem. Rev. 1997, 97,
2341.
2
12 (24), 194 (48), 178 (100), 165 (68), 123 (86), 105 (28), 89 (90).
(
5) (a) Zanardi, J.; Leriverend, C.; Aubert, D.; Julienne, K.;
Metzner, P. J. Org. Chem. 2001, 66, 5620. (b) Breau, L.;
Ogilive, W.-W.; Durst, T. Tetrahedron Lett. 1990, 31, 35.
Anal. Calcd for C H Cl O: C, 63.42; H, 3.80. Found: C, 64.03; H,
1
4
10
2
3
.86.
(
c) Zanardi, J.; Lamazure, D.; Miniere, S.; Reboul, V.;
trans-(2S,3S)-2-(3-Fluorophenyl)-3-phenyloxirane (10e)
Colorless oil.1
0b
Metzner, P. J. Org. Chem. 2002, 67, 9083. (d) Julienne, K.;
Metzner, P.; Henryon, V. J. Chem. Soc., Perkin Trans. 1
IR (KBr): 3065, 3036, 2988, 1613, 1591, 1490, 1452, 1271, 1256,
1
999, 731. (e) Julienne, K.; Metzner, P.; Julienne, K.;
–
1
8
61, 782, 768, 692 cm .
Metzner, P.; Henryon, V.; Greiner, A. J. Org. Chem. 1998,
1
H NMR: d = 7.42–7.05 (m, 9 H), 3.88 (d, J = 1.7 Hz, 1 H), 3.85 (d,
J = 1.7 Hz, 1 H).
63, 4532.
(6) Takada, H.; Metzner, P.; Philouze, C. Chem. Commun. 2001,
350.
2
trans-(2S,3S)-2-(4-Fluorophenyl)-3-phenyloxirane (10f)
White solid; mp 76–78 °C (Lit. 76–77 °C).
(7) Huang, Y.-Z.; Tang, Y.; Zhou, Z.-L. Tetrahedron 1998, 54,
1667.
1
0c
–
1
(8) (a) Lieser, J.-K. Synth. Commun. 1983, 13, 765. (b) Liao,
W.-W.; Li, K.; Tang, Y. J. Am. Chem. Soc. 2003, 43, 13031.
IR (KBr): 3044, 2990, 1512, 1230, 1087, 831, 778, 697 cm .
1
H NMR: d = 7.41–7.09 (m, 9 H), 3.87 (d, J = 1.8 Hz, 1 H), 3.85 (d,
(9) (a) Endo, T.; Kanda, N. J. Polym. Sci., Polym. Chem. Ed.
J = 1.8 Hz, 1 H).
1
1
985, 23, 1931. (b) Auge, J.; David, S. Tetrahedron Lett.
983, 24, 4009.
trans-(2S,3S)-2-Phenyl-3-p-tolyloxirane (10g)
(
10) (a) Li, A.-H.; Dai, L.-X.; Hou, X.-L.; Huang, Y.-Z.; Li, F.-
W. J. Org. Chem. 1996, 61, 489. (b) Oudeyer, S.; Léonel,
E.; Paugam, J. P.; Nédélec, J.-Y. Synthesis 2004, 389.
1
0a
White solid; mp 60–61 °C (Lit. 62 °C).
–
1
IR (KBr): 3052, 2916, 1406, 1111, 816, 738, 509 cm .
(c) Aggarwal, V. K.; Alonso, E.; Bae, I.; Hynd, G.; Lydon,
1
H NMR: d = 7.40–7.19 (m, 9 H), 3.87 (d, J = 1.8 Hz, 1 H), 3.85 (d,
K. M.; Palmer, M. J.; Patel, M.; Porcelloni, M.; Richardson,
J.; Stenson, R. A.; Studley, J. R.; Vasse, J.-L.; Winn, C. L. J.
Am. Chem. Soc. 2003, 125, 10926. (d) Futamura, S.;
Kusunose, S. J. Chem. Soc., Perkin Trans. 1 1984, 15.
J = 1.8 Hz, 1 H), 2.38 (s, 3 H).
Synthesis 2005, No. 17, 2857–2860 © Thieme Stuttgart · New York