J. Am. Chem. Soc. 1996, 118, 491-492
491
Table 1. Activities of Various Ketones in Catalyzing in Situ
Epoxidation of trans-Stilbenea
A C2 Symmetric Chiral Ketone for Catalytic
Asymmetric Epoxidation of Unfunctionalized
Olefins
Dan Yang,* Yiu-Chung Yip, Man-Wai Tang,
Man-Kin Wong, Jian-Hua Zheng,† and Kung-Kai Cheung
Department of Chemistry, The UniVersity of Hong Kong
Pokfulam Road, Hong Kong
catalyst
R2
CH3
CF3
CH2F
CH2Cl
CH2OAc
CH2OAc
CF3
ReceiVed August 28, 1995
reaction
entry
R1
CH3
CH3
CH3
CH3
CH3
CH2OAc
Ph
R3
time (min)b
Dioxiranes1 are important oxidants for organic reactions such
as epoxidation,2 heteroatom oxidation,3 and oxygenation of C-H
bonds.4 In particular, epoxidation mediated by dioxiranes is
stereospecific and highly efficient toward both electron-rich and
electron-deficient olefins.5 Moreover, dioxirane epoxidation can
be a catalytic process as dioxiranes can be generated in situ
from ketones and Oxone.6 Chiral ketones are thus expected to
be ideal catalysts for asymmetric epoxidation. However, limited
progress has been made in this direction, as the reported chiral
ketones exhibit poor catalytic activities and low asymmetric
induction.7,8 Here we report the first C2 symmetric chiral ketone
as a promising catalyst for asymmetric epoxidation of unfunc-
tionalized trans-olefins and trisubstituted olefins.9-11
1
2
3
4
5
6
7
8
9
(1a)
(1b)
(1c)
(1d)
(1e)
(1f)
(1g)
(2a)
(2b)
(2c)
300
<4
20
18
30
30
70
210
15
>720
H
Cl
CH3
10
a Reaction conditions: room temperature, 0.1 mmol of trans-stilbene,
1.0 mmol of catalyst, 0.5 mmol of Oxone, 1.55 mmol of NaHCO3, 1.5
mL of CH3CN, 1.0 mL of aqueous Na2‚EDTA (4 × 10-4 M). b Time
when epoxidation was completed as shown by TLC.
We recently discovered that, in a homogeneous CH3CN-
H2O solvent system, epoxidation with Oxone can be catalyzed
efficiently by trifluoroacetone.6d This simple protocol allows
us to directly compare the catalytic activities of various ketones
in epoxidation of trans-stilbene. The results for acyclic ketones
1a-g and cyclic ketones 2a-c are summarized in Table 1.
Here two general trends are observed. (1) Ketones with
electron-withdrawing groups, such as F, Cl, and OAc, at R
positions show higher activities (entries 2-6 vs entry 1; entry
9 vs entry 8). (2) Steric hindrance at R positions decreases the
activity (entry 7 vs entry 2; entry 10 vs entry 8). Therefore,
both steric and electronic factors need to be considered in
designing efficient ketone catalysts.
We also note that dioxiranes have two faces for oxygen
transfer. It is expected that ketone catalysts with C2 symmetry
and rigid conformations have the potential for asymmetric
epoxidation. Therefore, cyclic analogs of 1,3-diacetoxyacetone
1f were designed and synthesized.12 Among them, ketone 3
showed unprecedented catalytic activity (Table 2).13 In a 1:1
ketone:substrate ratio at room temperature, in situ epoxidation
of trans-stilbene catalyzed by ketone 3 proceeded faster than
that by trifluoroacetone (1b) or acyclic ketone 1f. Ketone 3
was stable under the reaction conditions and can be recovered
in high yield without loss of catalytic activity.14 To further
demonstrate the catalytic efficiency of ketone 3, epoxidation
of trans-stilbene was carried out using 1 mol % of ketone 3 at
* Author to whom correspondence should be addressed.
† On leave from the Shanghai Institute of Organic Chemistry.
(1) (a) Adam, W.; Curci, R.; Edward, J. O. Acc. Chem. Res. 1989, 22,
205. (b) Murray, R. W. Chem. ReV. 1989, 89, 1187. (c) Curci, R. In
AdVances in Oxygenated Processes; Baumstark, A. L., Ed.; JAI Press:
Greenwich, CT, 1990; Vol. 2, p 1. (d) Adam, W.; Hadjiarapoglou, L. P.;
Curci, R.; Mello, R. In Organic Peroxides; Ando, W., Ed.; J. Wiley and
Sons: New York, 1992; Chapter 4. (e) Adam, W.; Hadjiarapoglou, L. P.
In Topics in Current Chemistry; Springer-Verlag: Berlin, 1993; Vol. 164,
p 45.
(2) For recent examples of dioxirane epoxidation, see: (a) Curci, R.;
Detomaso, A.; Prencipe, T.; Carpenter, G. B. J. Am. Chem. Soc. 1994, 116,
8112. (b) Mello, R.; Ciminale, F.; Fiorentino, M.; Fusco, C.; Prencipe, T.;
Curci, R. Tetrahedron Lett. 1990, 31, 6097. (c) Murray, R. W.; Singh, M.;
Williams, B. L.; Moncrieff, H. M. Tetrahedron Lett. 1995, 36, 2437. (d)
Lluch, A.-M.; Sanchez-Baeza, F.; Messeguer, A.; Fusco, C.; Curci, R.
Tetrahedron 1993, 49, 6299.
(3) (a) Murray, R. W.; Rajadhyaksha, S. N.; Mohan, L. J. Org. Chem.
1989, 54, 5783. (b) Wittman, M. D.; Halcomb, R. L.; Danishefsky, S. J. J.
Org. Chem. 1990, 55, 1981. (c) Colonna, S.; Gaggero, N. Tetrahedron Lett.
1989, 30, 6233. (d) Ferrer, M.; Sanchez-Baeza, F.; Messeguer, A.; Diez,
A.; Rubiralta, M. J. Chem. Soc., Chem. Commun. 1995, 293.
(4) (a) Kuck, D.; Schuster, A.; Fusco, C.; Fiorentino, M.; Curci, R. J.
Am. Chem. Soc. 1994, 116, 2375. (b) Murray, R. W.; Jeyarman, R.; Mohan,
L. J. Am. Chem. Soc. 1986, 108, 2470. (c) Adam, W.; Asensio, G.; Curci,
R.; Gonzalez-Nunez, M. E.; Mello, R. J. Org. Chem. 1992, 57, 953. (d)
Reference 2a. (e) Bach, R. D.; Andres, J. L.; Su, M.-D.; McDouall, J. J.
W. J. Am. Chem. Soc. 1993, 115, 5768.
(5) For examples, see: (a) Dushin, R. G.; Danishefsky, S. J. J. Am. Chem.
Soc. 1992, 114, 3471. (b) Adam, W.; Hadjiarapoglou, L. P.; Jagger, V.;
Klicic, J.; Seidel, B.; Wang, X. Chem. Ber. 1991, 124, 2361. (c) Adam,
W.; Hadjiarapoglou, L.; Nestler, B. Tetrahedron Lett. 1990, 31, 331. (d)
Adam, W.; Hadjiarapoglou, L.; Wang, X. Tetrahedron Lett. 1991, 32, 1295.
(6) (a) Curci, R.; Fiorentino, M.; Troisi, L.; Edwards, J. O.; Pater, R. H.
J. Org. Chem. 1980, 45, 4758. (b) Kurihara, M.; Ito, S.; Tsutsumi, N.;
Miyata, N. Tetrahedron Lett. 1994, 35, 1577. (c) Denmark, S. E.; Forbes,
D. C.; Hays, D. S.; DePue, J. S.; Wilde, R. G. J. Org. Chem. 1995, 60,
1391. (d) Yang, D.; Wong, M.-K.; Yip, Y.-C. J. Org. Chem. 1995, 60,
3887.
(10) For recent examples on asymmetric synthesis of trans epoxides from
trans olefins, see: (a) Zhang, W.; Loebach, J. L.; Wilson, S. R.; Jacobsen,
E. N. J. Am. Chem. Soc. 1990, 112, 2801. (b) Groves, J. T.; Viski, P. J.
Org. Chem. 1990, 55, 3628. (c) Sakaki, H.; Irie, R.; Katsuki, T. Synlett
1993, 300. (d) Hosoya, N.; Hatayama, A.; Yanai, K.; Fujii, H.; Irie, R.;
Katsuki, T. Synlett 1993, 641. (e) Collman, J. P.; Lee, V. J.; Zhang, X.;
Ibers, J. A.; Brauman, J. I. J. Am. Chem. Soc. 1993, 115, 3834. (f) Collman,
J. P.; Lee, V. J.; Kellen-Yuen, C. J.; Zhang, X.; Ibers, J. A.; Brauman, J.
I. J. Am. Chem. Soc. 1995, 117, 692. For examples on asymmetric synthesis
of trans epoxides from cis olefins using chiral Mn-salen catalysts, see:
(g) Lee, N. H.; Jacobsen, E. N. Tetrahedron Lett. 1991, 32, 6533. (h) Chang,
S.; Galvin, J. M.; Jacobsen, E. N. J. Am. Chem. Soc. 1994, 116, 6937.
(11) For highly enantioselective epoxidation of conjugated trisubstituted
olefins using chiral Mn-salen catalysts, see: (a) Brandes, B. D.; Jacobsen,
E. N. J. Org. Chem. 1994, 59, 4378. (b) Palucki, M.; McCormick, G. J.;
Jacobsen, E. N. Tetrahedron Lett. 1995, 36, 5457. For asymmetric
epoxidation of trisubstituted olefins catalyzed by enzymes, see: (c) Allain,
E. J.; Hager, L. P.; Deng, L.; Jacobsen, E. N. J. Am. Chem. Soc. 1993, 115,
4415. (d) Koch, A.; Reymond, J.; Lerner, R. A. J. Am. Chem. Soc. 1994,
116, 803.
(7) Pioneering work by Curci et al. demonstrated that, for unfunction-
alized olefins, epoxidation catalyzed by acyclic chiral ketones gave up to
20% ee. See: (a) Curci, R.; Fiorentino, M.; Serio, M. R. J. Chem. Soc.,
Chem. Commun. 1984, 155. (b) Curci, R.; D’Accolti, L.; Fiorentino, M.;
Rosa, A. Tetrahedron Lett. 1995, 36, 5831.
(8) Brown, D. S.; Marples, B. A.; Smith, P.; Walton, L. Tetrahedron
1995, 51, 3587.
(9) For a recent review on catalytic asymmetric epoxidation of unfunc-
tionalized olefins, see: Jacobsen, E. N. In Catalytic Asymmetric Synthesis;
Ojima, I., Ed.; VCH: New York, 1993; Chapter 4.2.
(12) Yang, D.; Yip, Y.-C.; Tang, M.-W.; Wong, M.-K.; Cheung, K.-K.
Manuscript in preparation.
(13) Ketone 3 was synthesized in one step from diphenic acid and 1,3-
dihydroxyacetone in 45% yield using 2-chloro-1-methylpyridinium iodide
as the coupling reagent (Mukaiyama, T.; Usui, M.; Saigo, K. Chem. Lett.
1976, 49).
0002-7863/96/1518-0491$12.00/0 © 1996 American Chemical Society