Using conditions developed for the enantioselective cata-
lyzed epoxidation of chalcone, we turned our attention to
establishing the generality of the phase-transfer catalyzed
asymmetric epoxidation with A2 as catalyst. As shown in Table
3, most chalcone derivatives 1a–j afforded the corresponding
epoxides 2a–j with good yields and modest to high enantio-
meric excesses. It was found that 4-nitro chalcone can be
transferred to the epoxide with 96% ee. In a number of cases the
crude reaction products were most conveniently purified by
recrystallisation, giving the epoxides in excellent enantiomeric
purity. However, in the case of 4-methoxy chalcone, 4-methoxy
4A-chloro chalcone and benzalacetone (1k, 1l and 1m, Table 3),
the desired product was not obtained even within 96 h, and some
of the recovery materials were the starting chalcones. We were
able to detect the presence of monochlorinated products of 1k
and 1l in GC-MS because of electrophilic chlorination. As for
1m, the reaction mixture turned brown rapidly, probably due to
a haloform type reaction.9
In conclusion, the present study provides the first evidence
that TCCA might possess general utility for the catalytic
epoxidation of enones. We have developed a mild, efficient
phase-transfer catalyzed asymmetric epoxidation of chalcone
derivatives with modest to excellent enantioselectivity with
TCCA as the oxidant. The procedure reported here is simple and
allows for epoxidation under very mild conditions. Further
studies aimed at improving the enantioselectivity of epoxidation
and reaction scope are currently under investigation.
Notes and references
‡ All chemicals were purchased from Acros and used as received. Chiral
catalysts A1, A2 and A3 were prepared according to the references, and the
NMR results were consistant with the references.3,4,5,10
§ General procedure for catalytic epoxidation of enones under phase-
transfer conditions: A solution of enone (1.00 mmol) and chiral PTC (0.100
mmol) in toluene (3 ml) was cooled to 0 °C. TCCA (156 mg, 0.67 mmol)
was added slowly by portions and then 50% KOH aq. (0.336 g, 3.00 mmol)
was added dropwise via syringe. The reaction mixture was stirred at 0 °C
until chalcone disappeared (detected by TLC), followed by addition of ether
and filtration. The filtrate was washed with water and dried over MgSO4.
Evaporation of the solvents and purification of the residue on a silica gel
column with 50 : 1 petroleum ether/ethyl acetate as eluent gave the
epoxidation product. The enatiomeric excess was determined by chiral
HPLC analysis with a Chiralpak® AD-H column.
Table 2 Optimized effect of solvent, base and temperature on the
asymmetric epoxidation of chalcone
PTC/
equiv.
TCCA/
equiv.
KOH/
equiv.
Conv.a
(%)
Eeb
(%)
Entry
Time/h
1
2
3
4
5
6
7
8
0.1
0.1
0.1
0.1
0.1
0.1
0.05
0.01
1.67
1.0
0.67
0.5
0.67
0.67
0.67
0.67
10.0
6.0
4.0
3.0
3.0
2.4
3.0
3.0
8
8
100
100
100
100
100
88
81
83
83
81
82
82
82
77
1 R. A. Johnson and K. B. Sharpless, in Comprehensive Organic
Synthesis, ed. B. M. Trost and I. Fleming, Pergamon Press, Oxford, New
York, Seoul, Tokyo, 1991, vol. 7, p. 389.
2 For a recent review on the asymmetric epoxidation of electron-deficient
alkenes, see: M. J. Porter and J. Skidmore, Chem. Commun., 2000,
1215.
3 (a) B. Lygo and P. G. Wainwright, Tetrahedron Lett., 1998, 39, 1599;
(b) B. Lygo and P. G. Wainwright, Tetrahedron, 1999, 55, 6289; (c) B.
Lygo and D. C. M. To, Tetrahedron Lett., 2001, 42, 1343; (d) B. Lygo
and D. C. M. To, Chem. Commun., 2003, 2360.
4 (a) S. Arai, H. Tsuge and T. Shioiri, Tetrahedron Lett., 1998, 39, 7563;
(b) S. Arai, H. Tsuge, M. Oku, M. Miura and T. Shioiri, Tetrahedron,
2002, 58, 1623.
24
48
24
48
96
96
94
50
a The values of conversion (%) were obtained by HPLC analyses.
b Determined by HPLC using a Chiralpak® AD-H column with racemic
epoxides as standards.
5 E. J. Corey and F.-Y. Zhang, Org. Lett., 1999, 1, 1287.
6 W. Adam, P. B. Rao, H-G. Degen, A. Levai, T. Patonay and C. R. Saha-
Möller, J. Org. Chem., 2002, 67, 259.
Table 3 Asymmetric epoxidation of enones 1a–m to give the epoxides
2a–m employing A2 as PTC
7 For a recent review on use of trichloroisocyanuric acid, see: U. Tilstam
and H. Weinmann, Org. Process Res. Dev., 2002, 4, 384. For selected
examples on the use of trichloroisocyanuric acid see: (a) E. C. Juenge
and D. A. Beal, Tetrahedron Lett., 1968, 55, 5819; (b) T. Cohen, Z.
Kosarych, K. Suzuki and L.-C. Yu, J. Org. Chem., 1985, 50, 2965; (c)
T. R. Walters, W. W. Jr. Zajac and J. M. Woods, J. Org. Chem., 1991,
56, 316; (d) G. A. Hiegel and M. Nalbandy, Synth. Commun., 1992, 22,
1589; (e) L. De Luca, G. Giacomelli and A. Porcheddu, Org. Lett., 2001,
3, 3041; (f) L. De Luca, G. Giacomelli, M. Simonetta and A. Porcheddu,
J. Org. Chem., 2003, 68, 4999.
8 The preparation of racemic epoxides from alkenes by reaction with
TCCA in aqueous acetone followed by treatment of the resulting
chlorohydrin with aqueous KOH in ether/pentane, see: M. Wengert, A.
M. Sanseverino and M. C. S. de Mattos, J. Braz. Chem. Soc., 2002, 13,
700.
Yielda
(%)
Enone
R
RA
Eeb (%)
1a
1b
1c
1d
1e
1f
1g
1h
1i
Ph
Ph
Ph
90
82
92
79
83
85
97
89
93
74
0
89 (96)c
90
92 (96)c
88 (99)c
96 (99)c
93
84 (99)c
64
79
93 (98)c
—
p-MeOC6H4
p-FC6H4
p-FC6H4
Ph
p-ClC6H4
Ph
p-ClC6H4
Ph
p-NO2C6H4
Ph
p-ClC6H4
o-ClC6H4
p-ClC6H4
p-ClC6H4
p-MeOC6H4
p-MeOC6H4
Ph
Ph
p-ClC6H4
p-MeOC6H4
Ph
p-ClC6H4
Me
1j
1k
1l
0
0
—
—
9 (a) T. Schlama, L. Alcaraz and C. Mioskowski, Synlett, 1996, 571; (b)
W. S. Johnson, C. D. Gutsche and R. D. Offenhauer, J. Am. Chem. Soc.,
1946, 68, 1648; (c) R. Levine and J. R. Stephens, J. Am. Chem. Soc.,
1950, 72, 1642.
10 H.-g. Park, B.-s. Jeong, M.-S. Yoo, J.-H. Lee, M.-k. Park, Y.-J. Lee, M.-
J. Kim and S.-s. Jew, Angew. Chem., Int. Ed., 2002, 41, 3036.
1m
a Isolated yield by chromatography. b Determined by HPLC using a
Chiralpak® AD-H column with racemic epoxides as standards. c The ees in
parentheses were determined after recrystallisation.
CHEM. COMMUN., 2003, 2714–2715
2715