D. B. Cordes et al. / Tetrahedron Letters 47 (2006) 349–351
351
Table 2. Enantioselectivities obtained for preparation of chiral styrene
oxides from substituted a-bromoacetophenone substrates at 25 ꢁC
Supplementary data
Supplementary data associated with this article can be
O
OH
*
O
NaBH4 or
LiBH4
Br
Br
NaOH
*
(L)-TarB-NO2
R
R
R
References and notes
Substrate
LiBH4
NaBH4
Configuration/
sign of rotation
Sb/(ꢀ)
Sc/(ꢀ)
Sb/(+)
Sb/(+)
Sb/(ꢀ)
Sb/(+)
1. Barbieri, C.; Bossi, L.; DÕArrigo, P.; Fantoni, G. P.; Servi,
S. J. Mol. Catal. B: Enzym. 2001, 11, 415–421.
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J. Chem. Soc., Perkin Trans. 1 2002, 2237–2242.
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10515–10530.
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3, 2513–2515.
5. Palucki, M.; McCormick, G. J.; Jacobsen, E. N. Tetra-
hedron Lett. 1995, 36, 5457–5460.
R = o-NO2
m-NO2
13
73
71
35
83
p-NO2
73
o-OMe
m-OMe
p-OMe
86a
90
80a
94
85a
95a
All ees determined from chiral GC analysis using a Chiral BetaDex 120
column. According to the GC results, the conversion was greater than
99% for all substrates.
a Determined using HPLC with Chiracel OB/OB-H column (99
hex:1IPA).
6. Palucki, M.; Pospisil, P. J.; Zhang, W.; Jacobsen, E. N.
J. Am. Chem. Soc. 1994, 116, 9333–9334.
7. Brandes, B. D.; Jacobsen, E. N. Tetrahedron: Asymmetry
1997, 8, 3927–3933.
b Configuration based on mechanistic model.
c Configuration determined by comparison with the literature values.
8. Tokunaga, M.; Larrow, J. F.; Kakiuchi, F.; Jacobsen, E. N.
Science 1997, 277, 936–938.
9. Pastor, I. M.; Yus, M. Curr. Org. Chem. 2005, 9, 1–29.
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Soc. Rev. 2002, 31, 223–229.
11. Corey, E. J.; Shibata, S.; Bakshi, R. K. J. Org. Chem.
1988, 53, 2861–2863.
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Org. Lett. 2002, 4, 4373–4376.
does appear to cause a significant decrease in the
observed enantioselectivity giving only 13% and 35%
ee, respectively, for the LiBH4 and NaBH4 reductions
of the 2-nitro-substituted substrate. Similarly, among
the methoxy-substituted compounds, the lowest ee was
recorded with the methoxy substituents in the 2-posi-
tion. More generally, the presence of the electron-with-
drawing nitro groups gave lower ee as compared to
those obtained with substrates substituted with elec-
tron-donating methoxy groups. These results suggest
that enantioselectivity in the TarB-NO2/borohydride
reduction system is sensitive to both electron-withdraw-
ing effects and substitution at the 2-position.
13. Cordes, D. B.; Nguyen, T. M.; Kwong, T. J.; Suri, J. T.;
Luibrand, R. T.; Singaram, B. Eur. J. Org. Chem., in press.
14. Representative isolation scale procedure:
A 200-mL
round-bottomed flask was flame dried, cooled under N2,
then charged with a-bromoacetophenone (1.99 g,
10 mmol) and TarB-NO2 (40 mL of a 0.5 M solution in
THF, 20 mmol) and allowed to stir for 10 min. NaBH4
(0.755 g, 20 mmol), was then added in a single portion to
the ketone-TarB-NO2 solution causing rapid gas evolu-
tion. The reaction was left to stir for 1 h and then slowly
quenched with 3 M HCl until gas evolution was no longer
observed. The mixture was brought to pH 12 with 3 M
NaOH and stirred for 1 h and extracted with ether
(3 · 50 mL). The combined ether extracts were combined
and washed with DI H2O (2 · 50 mL) and dried over
MgSO4. GC analysis on a Supelco Beta-Dex 120 column
revealed >99% conversion and 94% ee of (S)-(ꢀ)-styrene
oxide. After solvent removal, the crude alcohol product
was distilled under reduced pressure to afford the pure
product in 80% yield. Alternatively, the pure epoxide
could be obtained by column chromatography (SiO2,
hexane/EtOAc 7:1) followed by removal of solvent under
reduced pressure.
In summary, we have demonstrated that chiral styrene
oxides can be obtained under mild conditions in high
enantiomeric excess and good yield using the chiral
Lewis acid TarB-NO2 with metal borohydrides. Gener-
ally, we observed that superior results are obtained
when using mild and inexpensive NaBH4 as the boro-
hydride reagent. Substitution with electron-withdraw-
ing groups tends to produce lower enantioselectivity,
while substitution with any group in the 2-position of
the substrate also tends to give lower ees. Enantiomeric
excesses as high as 95% were observed with substitu-
ents in the 4-position. We are currently investigating
the applicability of this reaction for the preparation
of other epoxides.