J . Org. Chem. 1998, 63, 6425-6426
6425
Sch em e 1
A Mild a n d Efficien t Ep oxid a tion of Olefin s
Usin g in Situ Gen er a ted
Dim eth yld ioxir a n e a t High p H
Michael Frohn, Zhi-Xian Wang, and Yian Shi*
Department of Chemistry, Colorado State University,
Fort Collins, Colorado 80523
Received April 2, 1998
Epoxides are important synthetic intermediates,1 and
epoxidation of olefins provides a powerful strategy for
their construction.2 Dioxiranes, either isolated or gener-
ated in situ (Scheme 1), have been shown to be extremely
versatile epoxidation reagents.3-5 The reaction is rapid,
mild, and safe, and a variety of efficient protocols for this
type of epoxidation have been developed. Due to the
concern for the autodecomposition of Oxone at high pH,
the reaction pH for most of the epoxidations mediated
by in situ generated dioxiranes have generally been
controlled at 7 to 85 with few exceptions.5f
During our studies on chiral ketone mediated asym-
metric epoxidations,6 we found that the catalytic ef-
ficiency for certain chiral ketones were highly pH de-
pendent and that high pH was actually beneficial in these
cases.6b,c In a subsequent comparison study, we also
found that the epoxidation of â-methylstyrene mediated
by acetone displayed a similar behavior under the reac-
tion conditions (homogeneous organic solvent/water
system).6c In this case, the substrate conversion in-
creased from 3 to 90% within the same reaction time
when the apparent pH changed from 7.5 to 12. The
enhanced epoxidation efficiency of acetone at higher pH
could be due to the fact that the high pH favored the
formation of oxy-anion intermediate 3 and led to more
efficient generation of dimethyldioxirane (the step from
3 to 4 could be the rate-determining step). Considering
that the basic reaction conditions would also be very
attractive for the synthesis of acid-sensitive epoxides,7
we thought that this acetone-mediated epoxidation at
high pH could provide a valuable epoxidation procedure.
We therefore decided to undertake a survey of various
olefins to ascertain the generality of the reaction.
(1) For reviews, see: (a) Gorzynski Smith, J . Synthesis 1984, 629.
(b) Besse, P.; Veschambre, H. Tetrahedron 1994, 50, 8885.
(2) For some recent leading references on epoxidation, see: (a) Sato,
K.; Aoki, M.; Ogawa, M.; Hashimoto, T.; Noyori, R. J . Org. Chem. 1996,
61, 8310. (b) Sato, K.; Aoki, M.; Ogawa, M.; Hashimoto, T.; Panyella,
D.; Noyori, R. Bull. Chem. Soc. J pn. 1997, 70, 905. (c) Rudolph, J .;
Reddy, K. L.; Chiang, J . P.; Sharpless, K. B. J . Am. Chem. Soc. 1997,
119, 6189. (d) Coperet, C.; Adolfsson, H.; Sharpless, K. B. Chem.
Commun. 1997, 1565. (e) Yudin, A. K. Sharpless, K. B. J . Am. Chem.
Soc. 1997, 119, 11536. (f) Nakajima, M.; Sasaki, Y.; Iwamoto, H.;
Hashimoto, S.-i. Tetrahedron Lett. 1998, 39, 87. (g) Murray, R. W.;
Iyanar, K. J . Org. Chem. 1998, 63, 1730. (h) Ueno, S.; Yamaguchi, K.;
Yoshida, K.; Ebitani, K.; Kaneda, K. Chem. Commun. 1998, 295. (i)
J ames, A. P.; J ohnstone, R. A. W.; McCarron, M.; Sankey, J . P.;
Trenbirth, B. Chem. Commun. 1998, 429.
(3) For general leading references on dioxiranes, see: (a) Murray,
R. W. Chem. Rev. 1989, 89, 1187. (b) Adam, W.; Curci, R.; Edwards, J .
O. Acc. Chem. Res. 1989, 22, 205. (c) Curci, R.; Dinoi, A.; Rubino, M.
F. Pure Appl. Chem. 1995, 67, 811. (d) Clennan, E. L. Trends Org.
Chem. 1995, 5, 231-252. (e) Adam, W.; Smerz, A. K. Bull. Soc. Chim.
Belg. 1996, 105, 581.
The epoxidation was carried out at apparent pH 10.5-
11.5 (precise control of pH was unnecessary in most
cases). As shown in Table 1, the epoxidation method
appears to be relatively general and effective with
substrates containing terminal, trans, cis, and trisubsti-
tuted olefins. Furthermore, a wide variety of functional
groups are compatible with the basic reaction conditions;
acetylenes, allyl silanes, allyl chlorides, alcohols, esters,
ketals, and TBS ethers are all unaffected by the reaction.
The conversions of many substrates were greater than
95% as judged by the 1H NMR spectra of the crude
reaction mixtures. Side oxidations were also minimal,
as only a trace (<5%) of allylic oxidation was seen in the
reaction of allylic alcohols (Table 1, entries 5 and 6).
Substrates containing hydroxy groups were also epoxi-
dized in good yield even in the absence of acetone. For
olefins without hydroxy groups, acetone was required for
the epoxidation (for a detailed study on this topic, see
ref 6e). The epoxidations of electron-deficient olefins
were not efficient under the current reaction conditions.
For example, only 21% conversion was obtained for ethyl
trans-cinnamate. The low efficiency could be due to the
fact that the dimethyldioxirane generated was converted
back to acetone by Oxone via pathway e (Scheme 1), as
(4) Murray, R. W.; Singh, S. Org. Synth. 1996, 74, 91.
(5) For examples of in situ generation of dioxiranes, see: (a)
Edwards, J . O.; Pater, R. H.; Curci, R.; Di Furia, F. Photochem.
Photobiol. 1979, 30, 63. (b) Curci, R.; Fiorentino, M.; Troisi, L.;
Edwards, J . O.; Pater, R. H. J . Org. Chem. 1980, 45, 4758. (c) Gallopo,
A. R.; Edwards J . O. J . Org. Chem. 1981, 46, 1684. (d) Cicala, G.; Curci,
R.; Fiorentino, M.; Laricchiuta, O. J . Org. Chem. 1982, 47, 2670. (e)
Corey, P. F.; Ward, F. E. J . Org. Chem. 1986, 51, 1925. (f) Kurihara,
M.; Ito, S.; Tsutsumi, N.; Miyata, N. Tetrahedron Lett. 1994, 35, 1577.
(g) Yang, D.; Wong, M. K.; Yip, Y. C. J . Org. Chem. 1995, 60, 3887
and references therein. (h) Denmark, S. E.; Forbes, D. C.; Hays, D. S.;
DePue, J . S.; Wilde, R. G. J . Org. Chem. 1995, 60, 1391 and references
therein. (i) Denmark, S. E.; Wu, Z.; Crudden, C. M.; Matsuhashi, H.
J . Org. Chem. 1997, 62, 8288. (j) Boehlow, T. R.; Buxton, P. C.; Grocock,
E. L.; Marples, B. A.; Waddington, V. L. Tetrahedron Lett. 1998, 39,
1839. (k) Denmark, S. E.; Wu, Z. J . Org. Chem. 1998, 63, 2810.
(6) (a) Tu, Y.; Wang, Z.-X.; Shi, Y. J . Am. Chem. Soc. 1996, 118,
9806. (b) Wang, Z.-X.; Tu, Y.; Frohn, M.; Shi, Y. J . Org. Chem. 1997,
62, 2328. (c) Wang, Z.-X.; Tu, Y.; Frohn, M.; Zhang, J .-R.; Shi, Y. J .
Am. Chem. Soc. 1997, 119, 11224. (d) Frohn, M.; Dalkiewicz, M.; Tu,
Y.; Wang, Z.-X.; Shi, Y. J . Org. Chem. 1998, 63, 2948. (e) Wang, Z.-X.;
Shi, Y. J . Org. Chem. 1998, 63, 3099. (f) Cao, G.-A.; Wang, Z.-X.; Tu,
Y.; Shi. Y. Tetrahedron Lett. 1998, 39, 4425.
(7) For great success and discussion on this topic, see: refs 2c-e.
(8) Rossiter, B. E.; Sharpless, K. B. J . Org. Chem. 1984, 49, 3707.
(9) Vankar, Y. D.; Chaudhuri, N. C.; Rao, C. T. Tetrahedron Lett.
1987, 28, 551.
(10) Alexakis, A.; Marek, I.; Mangeney, P.; Normant, J . F. Tetra-
hedron 1991, 47, 1677.
S0022-3263(98)00604-5 CCC: $15.00 © 1998 American Chemical Society
Published on Web 08/20/1998