Design and synthesis of chiral ketones for catalytic asymmetric epoxidation of unfunctionalized olefins

Article abstract of DOI:10.1021/ja980428m

A series of C₂ symmetric chiral ketones were designed and synthesized for catalytic asymmetric epoxidation of unfunctionalized olefins. Among those ketones screened, (R)-7, (R)-9, and (R)-10 were found to be highly efficient catalysts for epoxidation of trans-stilbenes with enantioselectivities in the range of 84-95%. Convincing evidence was provided for a spiro transition state of dioxirane epoxidation. Through the ¹⁸O-labeling experiment, chiral dioxiranes were found to be the intermediates in chiral ketone catalyzed epoxidation reactions.

Full text of DOI:10.1021/ja980428m

J. Am. Chem. Soc. 1998, 120, 5943-5952
5943
Design and Synthesis of Chiral Ketones for Catalytic Asymmetric
Epoxidation of Unfunctionalized Olefins
Dan Yang,* Man-Kin Wong, Yiu-Chung Yip, Xue-Chao Wang, Man-Wai Tang,
Jian-Hua Zheng, and Kung-Kai Cheung
Contribution from the Department of Chemistry, The UniVersity of Hong Kong,
Pokfulam Road, Hong Kong
ReceiVed February 6, 1998
Abstract: A series of C2 symmetric chiral ketones were designed and synthesized for catalytic asymmetric
epoxidation of unfunctionalized olefins. Among those ketones screened, (R)-7, (R)-9, and (R)-10 were found
to be highly efficient catalysts for epoxidation of trans-stilbenes with enantioselectivities in the range of 84-
95%. Convincing evidence was provided for a spiro transition state of dioxirane epoxidation. Through the
18O-labeling experiment, chiral dioxiranes were found to be the intermediates in chiral ketone catalyzed
epoxidation reactions.
Introduction
Catalytic asymmetric epoxidation of unfunctionalized olefins
has attracted a lot of attention for two reasons. First, chiral
epoxides are important building blocks for natural product
synthesis. Second, asymmetric induction based on molecular
recognition of olefin substitution patterns has been a particularly
challenging problem for modern organic chemistry.1 In the past
several years substantial progress has been made in developing
catalysts for asymmetric epoxidation of a broad range of unfunc-
tionalized olefins. The most notable catalysts include chiral
Mn-salen complexes,2-5 metalloporphyrins,6 and biocatalysts.7
We have initiated a program using chiral dioxiranes for
asymmetric epoxidation of unfunctionalized olefins. Dioxiranes
Figure 1.
are powerful organic oxidants under mild and neutral condi-
tions.8 Epoxidation mediated by dioxiranes is stereospecific and
highly efficient toward both electron-rich9 and electron-defi-
cient olefins.10 Furthermore, dioxirane epoxidation can be a
catalytic process as dioxiranes can be generated in situ from
ketones and Oxone (2KHSO5‚KHSO4‚K2SO4).11 Therefore, chi-
ral ketones12-16 are expected to be catalysts for asymmetric
epoxidation (Figure 1). In 1984, Curci et al. reported the first
asymmetric epoxidation of olefins catalyzed by chiral ketones
(up to 20% ee for trans-â-methylstyrene epoxide).12
(1) For recent reviews on catalytic asymmetric epoxidation of unfunc-
tionalized olefins, see: (a) Jacobsen, E. N. In Catalytic Asymmetric
Synthesis; Ojima, I., Ed.; VCH: New York, 1993; Chapter 4.2. (b) Collman,
J. P.; Zhang, X.; Lee, V. J.; Uffelman, E. S.; Brauman, J. I. Science 1993,
261, 1404. For a excellent review on catalytic asymmetric dihydroxylation
of unfunctionalized olefins, see: Kolb, H. C.; VanNieuwenhze, M. S.;
Sharpless, K. B. Chem. ReV. 1994, 94, 2483.
Recently, we reported an efficient epoxidation protocol that
used in situ generated methyl(trifluoromethyl)dioxirane in a
(2) For highly enantioselective epoxidation of cis-disubstituted olefins
using chiral Mn-salen catalysts, see: (a) Jacobsen, E. N.; Zhang, W.; Muci,
A. R.; Ecker, J. R.; Deng, L. J. Am. Chem. Soc. 1991, 113, 7603. (b) Lee,
N. H.; Muci, A. R.; Jacobsen, E. N. Tetrahedron Lett. 1991, 32, 5055. (c)
Deng, L.; Jacobsen, E. N. J. Org. Chem. 1992, 57, 4320. (d) Palucki, M.;
McCormick, G. J.; Jacobsen, E. N. Tetrahedron Lett. 1995, 36, 5457. (e)
Irie, R.; Noda, K.; Ito, Y.; Katsuki, T. Tetrahedron Lett. 1991, 32, 1055.
(f) Hosoya, N.; Hatayama, A.; Irie, R.; Sasaki, H.; Katsuki, T. Tetrahedron
Lett. 1994, 50, 4311.
(3) For highly enantioselective epoxidation of trisubstituted olefins using
chiral Mn-salen catalysts, see: (a) Brandes, B. D.; Jacobsen, E. N. J. Org.
Chem. 1994, 59, 4378. (b) Fukada, T.; Irie, R.; Katsuki, T. Synlett 1995,
197.
(4) For highly enantioselective epoxidation of tetrasubstituted olefins
using chiral Mn-salen catalysts, see: Brandes, B. D.; Jacobsen, E. N.
Tetrahedron Lett. 1995, 36, 5123.
(5) For highly enantioselective, low-temperature epoxidation of styrene
using chiral Mn-salen catalysts, see: Palucki, M.; Pospisil, P. J.; Zhang,
W.; Jacobsen, E. N. J. Am. Chem. Soc. 1994, 116, 9333.
(6) For asymmetric epoxidation of unfunctionalized olefins using chiral
metalloporphyrins, see: (a) Groves, J. T.; Myers, R. S. J. Am. Chem. Soc.
1983, 105, 5791. (b) Groves, J. T.; Viski, P. J. Org. Chem. 1990, 55, 3628.
(c) Collman, J. P.; Lee, V. J.; Zhang, X.; Ibers, J. A.; Brauman, J. I. J. Am.
Chem. Soc. 1993, 115, 3834. (d) 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. (e) Naruta, Y.; Ishihara, N.; Tani, F.; Maruyama, K. Bull. Chem. Soc.
Jpn. 1993, 66, 158.
(7) For biological catalysts in asymmetric epoxidation of unfunctionalized
olefins, see: (a) Allain, E. J.; Hager, L. P.; Deng, L.; Jacobsen, E. N. J.
Am. Chem. Soc. 1993, 115, 4115. (b) Dexter, A. F.; Lakner, F. J.; Campbell,
R. A.; Hager, L. P. J. Am. Chem. Soc. 1995, 117, 6412. (c) Koch, A.;
Reymond, J.; Lerner, R. A. J. Am. Chem. Soc. 1994, 116, 803.
(8) For reviews on dioxiranes, see: (a) Adam, W.; Curci, R.; Edwards,
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.
(9) 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.
(10) (a) Adam, W.; Hadjiarapoglou, L. P.; Nestler, B. Tetrahedron Lett.
1990, 31, 331. (b) Adam, W.; Hadjiarapoglou, L. P.; Wang, X. Tetrahedron
Lett. 1991, 32, 1295.
(11) (a) Edwards, J. O.; Pater, R. H.; Curci, R.; DiFuria, 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) Corey, P. F.; Ward,
F. E. J. Org. Chem. 1986, 51, 1925. (d) Kurihara, M.; Ito, S.; Tsutsumi,
N.; Miyata, N. Tetrahedron Lett. 1994, 35, 1577. (e) Denmark, S. E.; Forbes,
D. C.; Hays, D. S.; DePue, J. S.; Wilde, R. G. J. Org. Chem. 1995, 60,
1391.
S0002-7863(98)00428-4 CCC: $15.00 © 1998 American Chemical Society
Published on Web 06/05/1998

5944 J. Am. Chem. Soc., Vol. 120, No. 24, 1998
Yang et al.
Table 1. Asymmetric Epoxidation of Unfunctionalized Olefins
Scheme 1a
Catalyzed by Ketone 2a
time yieldc
epoxide
confign
epoxide
eed (%)
entry catalystb substrate (min)
(%)
a (a) Preparation: see ref 21; (b) Et3N, CH3CN, reflux, 12 h, 25%.
1e
2
3
4
5
(R)-2
(R)-2
(R)-2
(R)-2
(R)-2
(R)-2g
(S)-2g
(R)-2
(R)-2
(R)-2
(R)-2
(R)-2
15
16
17
18
19
20
20
22
23
24
25
26
20
40
40
40
40
480
480
75
90
210
80
99
99
96
98
95
82h
80h
97
83
70
85
83
(-)-(S,S)f
(-)-(S,S)f
(-)-(S,S)f
(-)-(S,S)f
(-)-(S,S)f
(-)-(S,S)f
(+)-(R,R)f
(+)-(S)i
(-)-(S,S)i
ndl
47
50
60
71
76
87
87
48
33
18
<5
18
homogeneous acetonitrile-water solvent system under neutral
reaction conditions.17 This simple protocol allowed us to per-
form catalytic asymmetric epoxidation with various chiral ke-
tones. In particular, we focused on developing C2 symmetric
chiral ketones. Herein we report the preparation of a series of
novel C2 symmetric chiral ketones and their activities in catalytic
asymmetric epoxidations. A portion of this work was published
earlier.18,19
6
7
8
9j
10k
11k
12k
ndl
60
(-)-(S)m
Results and Discussion
a Unless otherwise indicated, reaction conditions were as follows:
room temperature, 0.1 mmol of substrate, 0.01 mmol of ketone 2, 0.5
mmol of Oxone, 1.55 mmol of NaHCO3, 2.0 mL of CH3CN, 1.7 mL
of aqueous Na2‚EDTA solution (4 × 10-4 M). b Optical purity: 98%
ee. Ketone 2 was recovered in over 80% yield by flash column
chromatography with Et3N buffered silica gel (Merck 230-400 mesh)
and reused without loss of catalytic activity and chiral induction.
c Isolated yield after flash column chromatography. d Enantiomeric
excess was determined by 1H NMR using chiral shift reagent Eu(hfc)3
(Aldrich catalog no. 16,474-7). e 0.1 mmol of substrate, 0.1 mmol of
ketone 2. f Determined by circular dichroism spectroscopy. g Ketone 2
was not recovered. h Isolated yield after washing with CH2Cl2 (see
I. Rational Design of Binap Ketone 2 for Catalytic
Asymmetric Epoxidation of Unfunctionalized Olefins. In our
screening for efficient ketone catalysts,20 cyclic ketone 1 was
found to have high activity in catalytic epoxidation of olefins
by Oxone, and therefore became an ideal template for introduc-
tion of chiral elements. Since ketones with chiral centers at R
positions are prone to racemization, we chose to put the C2
symmetric chiral element away from the catalytic center (i.e.,
the keto group). Therefore, a C2 symmetric, 11-membered-
ring chiral ketone 2 was designed when the diphenic unit of
ketone 1 was replaced by a chiral binaphthalene unit. This C2
symmetric chiral ketone was found to be a promising catalyst
for asymmetric epoxidation of unfunctionalized trans-olefins
and trisubstituted olefins.
Preparation of Binap Ketone (R)-2. Chiral ketone (R)-2
was synthesized in one step from chiral (R)-1,1′-binaphthyl-
2,2′-dicarboxylic acid 2a21 and 1,3-dihydroxyacetone using
2-chloro-1-methylpyridinium iodide (Mukaiyama reagent) in
20-30% yield22 (Scheme 1).
Asymmetric Epoxidation of Unfunctionalized Olefins
Catalyzed by Ketone (R)-2. Results of asymmetric epoxidation
of unfunctionalized olefins catalyzed by chiral ketone 2 are
summarized in Table 1.
i
j
experimental section). Reference 3a. 0.5 mmol of substrate, 0.1 mmol
of ketone 2. k 0.2 mmol of substrate, 0.1 mmol of ketone 2. l Not
determined. m Reference 6a.
trisubstituted olefins (entry 8-9) but not for cis-olefins or
terminal olefins (entries 10-12). (2) When the para substituents
of trans-stilbenes became larger (from methyl to ethyl to
isopropyl to tert-butyl to phenyl), the ee values of trans-epoxides
increased gradually from 47% to 87% (entries 1-6). (3) When
epoxidation of (E)-4,4′-diphenylstilbene 20 was catalyzed by
ketone (R)-2, the enantiomerically enriched (S,S)-epoxide with
87% ee was obtained (entry 6) whereas epoxidation catalyzed
by ketone (S)-2 gave enantiomerically enriched (R,R)-epoxide
(entry 7). This suggests that enantiomerically enriched epoxides
can be obtained by using ketone catalysts of proper configura-
tions. (4) Ketone 2 was stable under the reaction conditions
and can be recovered in over 80% yield by flash column
chromatography with Et3N buffered silica gel and reused without
loss of catalytic activity and chiral induction.
X-ray analysis revealed that ketone-218 has a rigid and C2
symmetric structure: the keto group lies on the C2 axis of the
molecule; the two ester groups, antiparallel to each other, retain
the favorable s-trans geometry and are nearly perpendicular to
the macrocyclic ring plane; and the dihedral angle of the two
naphthalene rings is ca. 70°. With the Chem 3D program, the
structure of C2 symmetric chiral dioxirane (R)-2b was created
by using the coordinates of the X-ray structure of ketone 2 (Fig-
ure 2). The distance between H-3 or H-3′ and the dioxirane
group is ca. 5 Å, which is approximately the length of a phenyl
ring. In addition, H-3 and H-3′ are closer to the dioxirane group
than other atoms on the chiral binaphthalene unit and may there-
fore be the steric sensors in the oxygen atom transfer process.
Several interesting features were observed. (1) It is important
to note that ketone (R)-2 gave moderate to good enantioselec-
tivities for epoxidation of trans-olefins (entries 1-6) and
(12) (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.
(13) (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) Wang, Z.-X.; Shi, Y. J. Org. Chem. 1997,
62, 8622.
(14) Brown, D. S.; Marples, B. A.; Smith, P.; Walton, L. Tetrahedron
1995, 51, 3587.
(15) Denmark, S. E.; Wu, Z.; Crudden, C. M.; Matsuhashi, H. J. Org.
Chem. 1997, 62, 8288.
(16) Adam, W.; Zhao, C.-G. Tetrahedron: Asymmetry 1997, 8, 3995.
(17) Yang, D.; Wong, M.-K.; Yip, Y.-C. J. Org. Chem. 1995, 60, 3887.
(18) Yang, D.; Yip, Y.-C.; Tang, M.-W.; Wong, M.-K.; Zheng, J.-H.;
Cheung, K.-K. J. Am. Chem. Soc. 1996, 118, 491.
(19) Yang, D.; Wang, X.-C.; Wong, M.-K.; Yip, Y.-C.; Tang, M.-W. J.
Am. Chem. Soc. 1996, 118, 11311.
(20) Manuscript in preparation.
(21) Synthesis and optical resolution of 1,1′-binaphthy1-2,2′-dicarboxylic
acid were carried out according to the literature procedures: (a) Hall, D.
M.; Turner, E. E. J. Chem. Soc. 1955, 1242. (b) Kanoh, S.; Hongoh, Y.;
Motoi, M.; Suda, H. Bull. Chem. Soc. Jpn. 1988, 61, 1032.
(22) Mukaiyama, T.; Usui, M.; Saigo, K. Chem. Lett. 1976, 49.
Importance of Ester Groups in Ketone 2. To examine
whether the ester groups in the ketone skeleton were essential
for chiral induction, a nine-membered-ring cyclic ketone 323
was prepared where the ester groups were replaced by the ether

Chiral Ketones for Epoxidation of Olefins
J. Am. Chem. Soc., Vol. 120, No. 24, 1998 5945
Figure 2.
Chart 1
Figure 3. X-ray structure of (R)-3 (ORTEP view).
Figure 4.
NMR) after 6 h, and the ee value of trans-stilbene epoxide was
12%. The poor reactivity of the ketone could be attributed to
the fact that an ether group is a weaker electron withdrawing
group than an ester group. The X-ray structure of ketone (R)-3
was shown in Figure 3, which suggests a non C2 symmetric
conformation in contrast to that of ketone 2. The ester groups
that gave rigid and C2 symmetric structures of cyclic ketones
seemed to be essential for effective asymmetric epoxidation.
Effect of Chiral Elements in Ketone 2. To test the effect
of chiral elements, a new ketone catalyst (R)-4 was obtained
when the C2 symmetric chiral element was changed from (R)-
1,1′-binaphthyl-2,2′-dicarboxylic acid to (R)-6,6′-dinitro-2,2′-
diphenic acid. If the H-3 and H-3′ in the chiral dioxiranes (R)-
2b and (R)-4c are the steric sensors in the oxygen atom transfer
process, (R)-2 and (R)-4 are expected to give similar ee values
for epoxidation (Figures 2 and 4).
Scheme 2a
Optical resolution of 6,6′-dinitro-2,2′-diphenic acid24 was
achieved by the use of (R)-(+)-1,1′-bi-2-naphthol (98% ee).
Since the (R)-form of the binaphthol could only react with the
(R)-form of dinitrodiphenic acid to form the cyclic diolide (R,R)-
4b, the kinetic resolution of racemic diacid took place. Both
1H and 13C NMR spectra showed that only one diastereomer,
i.e., diolide (R,R)-4b, was formed (31% yield). After a mild
basic hydrolysis, (R)-6,6′-dinitro-2,2′-diphenic acid (R)-4a was
obtained in quantitative yield with (R)-(+)-1,1′-bi-2-naphthol
recovered. Ketone (R)-4 was easily prepared in one step from
the corresponding diacid (R)-4a and 1,3-dihydroxyacetone using
the Mukaiyama reagent (22% yield).
a (a) DMF, 60 °C, 12 h; (b) RuCl3, NaIO4, CCl4, CH3CN, H2O, room
temperature, 10 h.
groups. The chiral element used was the commercially available
(R)-1,1′-bi-2-naphthol (Scheme 2).
The ketone (R)-3 (10 mol %) was examined in asymmetric
epoxidation of trans-stilbene 15 under the same reaction
conditions as that for (R)-2. It was found that the epoxidation
As shown in Table 2, similar enantioselectivities were
observed for epoxidation catalyzed by ketones (R)-2 and (R)-4.
This confirms that H-3 and H-3′ in both C2 symmetric dioxiranes
(24) Synthesis of 6,6′-dinitro-2,2′-diphenic acid was carried out according
to the literature procedures: (a) Whitmore, F. C.; Culhane, P. J.; Neher,
H. T. Organic Syntheses; Wiley: New York, Collect. Vol. 1; 1976; p 56.
(b) Culhane, P. J. Organic Syntheses; Wiley: New York, Collect. Vol. 1;
1976; p 125. (c) Ingersoll, A. W.; Little, J. R. J. Am. Chem. Soc. 1934, 56,
2123. (d) Newman, P.; Rutkin, P.; Mislow, K. J. Am. Chem. Soc. 1958, 80,
465.
1
reaction proceeded with 10% conversion (determined by H
(23) After our experimental work was completed, a report by Song
et al. appeared on the preparation of ketone (R)-3. Song, C. E.; Kim, Y.
H.; Lee, K. C.; Lee, S.-g.; Jin, B. W. Tetrahedron: Asymmetry 1997, 8,
2921.

5946 J. Am. Chem. Soc., Vol. 120, No. 24, 1998
Yang et al.
Table 4. Effect of Reaction Temperature on the Enantiomeric
Table 2. Asymmetric Epoxidation of Unfunctionalized Olefins
Catalyzed by Ketone (R)-2a and (R)-4b
Excess of (E)-4,4′-Di-tert-butylstilbene Epoxide 19aa
time
yieldd
(%)
epoxide
confign
eee
(%)
entry temp (°C)
time
yieldb (%) epoxide confignc eed (%)
entry catalystc substrate (min)
1
2
3
25
0e
-20e
45 min
20 h
20 h
97
91
(-)-(S,S)
(-)-(S,S)
(-)-(S,S)
77
83
84
1f
2
3
4
5
6
7
8
(R)-2
(R)-4
(R)-2
(R)-4
(R)-2
(R)-4
(R)-2
(R)-4
15
15
18
18
19
19
22
22
20
35
40
35
40
35
75
60
99
94
98
94
95
91
97
82
(-)-(S,S)g
(-)-(S,S)g
(-)-(S,S)g
(-)-(S,S)g
(-)-(S,S)g
(-)-(S,S)g
(+)-(S)h
47
50
71
66
76
77
48
49
2f
a Unless otherwise indicated, reaction conditions were as follows:
0.1 mmol of (E)-4,4′-di-tert-butylstilbene 19, 0.01 mmol of ketone (R)-
2, 0.5 mmol of Oxone, 1.55 mmol of NaHCO3, 1.5 mL of DME, 1.0
mL of aqueous Na2‚EDTA solution (4 × 10-4 M). b Isolated yield after
flash column chromatography. c Absolute configuration was determined
by circular dichroism spectroscopy. d Enantiomeric excess was deter-
(+)-(S)h
1
mined by H NMR using chiral shift reagent Eu(hfc)3. e 1.0 mmol of
a Unless otherwise indicated, reaction conditions were as follows:
room temperature, 0.1 mmol of substrate, 0.01 mmol of ketone (R)-2,
0.5 mmol of Oxone, 1.55 mmol of NaHCO3, 2.0 mL of CH3CN, 1.7
mL of aqueous Na2‚EDTA solution (4 × 10-4 M). b Unless otherwise
indicated, reaction conditions were as follows: room temperature, 0.1
mmol of substrate, 0.01 mmol of ketone (R)-4, 0.5 mmol of Oxone,
1.55 mmol of NaHCO3, 1.5 mL of CH3CN, 1.0 mL of aqueous
Na2‚EDTA solution (4 × 10-4 M). c Optical purity: 98% ee. Ketone
(R)-2 and (R)-4 were recovered in over 80% yield by flash column
chromatography with Et3N buffered silica gel (Merck 230-400 mesh).
d Isolated yield after flash column chromatography. e Enantiomeric
excess was determined by 1H NMR using chiral shift reagent Eu(hfc)3.
f 0.1 mmol of substrate, 0.1 mmol of ketone (R)-2. g Determined by
circular dichroism spectroscopy. h Reference 3a.
Oxone and 3.1 mmol of NaHCO3 were used. f Substrate 19 was
recovered in 95%.
Scheme 3. Synthetic Pathway of Ketone (R)-5a
Table 3. Effect of Solvent System on the Enantiomeric Excess of
(E)-4,4′-Di-tert-butylstilbene Epoxide 19aa
time yieldb
eed
entry solvent system
(h)
(%)
epoxide confignc (%)
1
2
3
4
DME-H2O
CH3CN-H2Oe
dioxane-H2O
THF-H2O
0.5
0.7
24
24
92
(-)-(S,S)
(-)-(S,S)
(-)-(S,S)
(-)-(S,S)
77
76
76
75
95
91f
93g
a Unless otherwise indicated, reaction conditions were as follows:
room temperature, 0.1 mmol of (E)-4,4′-di-tert-butylstilbene 19, 0.01
mmol of ketone (R)-2, 0.5 mmol of Oxone, 1.55 mmol of NaHCO3,
1.5 mL of organic solvent, 1.0 mL of aqueous Na2‚EDTA solution (4
× 10-4 M). b Isolated yield after flash column chromatography.
c Absolute configuration was determined by circular dichroism spec-
troscopy. d Enantiomeric excess was determined by 1H NMR using
chiral shift reagent Eu(hfc)3. e 2.0 mL of CH3CN, 1.7 mL of aqueous
Na2‚EDTA solution (4 × 10-4 M). f Yield based on 57% conversion.
g Yield based on 44% conversion.
a (a) Preparation: see ref 21; (b) oxalyl chloride, catalyst DMF,
CH2Cl2, room temperature, 1.5 h; 2-amino-2-methyl-1-propanol, CH2Cl2,
room temperature, SOCl2, CH2Cl2, room temperature, 6 h; (c) TMEDA,
THF, -78 °C, 1 h; (d) -78 °C; 3 h; (e) MeOH, room temperature, 20
h; (f) reflux; (g) MeOH, reflux; (h) DMF, room temperature, 1 h; (i)
10% NaOH, MeOH, reflux; (j) DMF, 90 °C, 8 h; (k) RuCl3, NaIO4,
CCl4, CH3CN, H2O, 0 °C, 1 h.
(R)-2b and (R)-4c are the steric sensors in the oxygen atom
transfer process (Figures 2 and 4).
84%. However, the isolated yield of trans-epoxide 19a at -20
°C was only 2% (entry 3) with 95% of recovery of the starting
material. It seemed that the most suitable reaction temperature
was 0 °C at which both excellent yield (91%) and high ee value
(83%) of trans-epoxide 19a were achieved (entry 2).
Effect of Solvent System on the Enantiomeric Excess of
(E)-4,4′-Di-tert-butylstilbene Epoxide 19a. To optimize the
reaction conditions, asymmetric epoxidation of (E)-4,4′-di-tert-
butylstilbene 19 catalyzed by 10 mol % of ketone (R)-2 was
investigated in four solvent systems (CH3CN-H2O, DME-H2O,
dioxane-H2O, THF-H2O) (Table 3).
Both (E)-4,4′-di-tert-butylstilbene 19 and ketone (R)-2 were
completely soluble in the four solvent systems. The time for
complete epoxidation was 30 min in the homogeneous DME-
H2O solvent system, even shorter than that required in the
CH3CN-H2O system (ca. 45 min). It seems that there is no
appreciable change in the ee values of trans-epoxide 19a in
the four solvent systems. This suggests that the ketone catalyst
recognizes various olefin substitution patterns entirely through
the nonbonded steric interactions.
II. Design and Synthesis of Ketone Catalysts with Larger
Sensor Groups. From structural analysis of (R)-2b (Figure 2),
we expected that, by replacing the H-3 and H-3′ of the binaph-
thyl unit with sterically bulky substituents, the resulting chiral
ketones would give better enantioselectivities than ketone 2.
Preparation of Bis-MOM Ketone (R)-5. As shown in
Scheme 3, binap bisoxazoline (R)-5a was prepared from (R)-
1,1′-binaphthyl-2,2′-dicarboxylic acid (R)-2a according to lit-
erature procedure.25 Hydroxymethyl groups were introduced
by the ortho-directed lithiation, followed by quenching with
DMF and reduction with NaBH4 to afford (R)-5b.26 The
bislactone (R)-5c obtained after acidic hydrolysis (95% yield)
was converted to the diester (R)-5d (76% yield) which gave
the ortho-substituted carboxylic acid (R)-5e (80% yield) after
basic hydrolysis. However, cyclization with Mukaiyama reagent
failed to give ketone (R)-5. An alternative approach was taken.
Effect of Reaction Temperature on the Enantiomeric Ex-
cess of (E)-4,4′-Di-tert-butylstilbene Epoxide 19a. Asym-
metric epoxidation of (E)-4,4′-di-tert-butylstilbene 19 catalyzed
by 10 mol % of ketone (R)-2 in DME-H2O solvent system
was carried out at different temperatures (Table 4).
When the reaction temperature was decreased from 25 to -20
°C, the ee values of trans-epoxide 19a increased from 77% to
(25) Gant, T. G.; Meyers, A. I. J. Am. Chem. Soc. 1992, 114, 1010.
(26) Meyers, A. I.; Avila, W. B. J. Org. Chem. 1981, 46, 3881.

Chiral Ketones for Epoxidation of Olefins
J. Am. Chem. Soc., Vol. 120, No. 24, 1998 5947
Scheme 5. Synthetic Pathways of Ketones 9-13a
Scheme 4. Synthetic Pathways of Ketones (R)-6-8a
a (a)Preparation: see ref 21; (b) TMEDA, THF, -90 °C; (c)
hexachloroethane for (R)-9a; 2,4,4,6-tetrabromo-2,5-cyclohexadienone
for (R)-10a; 1,2-diiodoethane for (R)-11a; MeI for (S)-12a; TMSCl
for (S)-13a; -78 °C to room temperature; (d) DMF, 90-100 °C; (e)
RuCl3, NaIO4, CCl4, CH3CN, H2O, room temperature.
a (a) TMEDA, THF, -78 °C, 1 h; (b) -78 °C to room temperature,
4 h; (c) reflux; (d) DMF, 45 °C, 8 h; (e) 1,2-ethanediol for (R)-6a;
1,3-propanediol for (R)-7b; pinacol for (R)-8a; catalyst p-TsOH,
benzene; (f) RuCl3, NaIO4, CCl4, CH3CN, H2O, room temperature.
Treatment of (R)-5e with 3-chloro-2-chloromethyl-1-propene
and cesium carbonate in DMF27 at 95 °C for 24 h gave (R)-5f
as a single product (25% yield). The oxidative cleavage of (R)-
5f was achieved using the conditions reported by Sharpless et
al. (30% yield).28
Figure 5.
Preparation of Diacetal Ketones (R)-6-8. Dilithiation of
(R)-5a using sec-BuLi/TMEDA in THF at -78 °C for 1 h
followed by addition of DMF and treatment with 6 N HCl
afforded the hydroxylactone (R)-7a in 51% yield (Scheme 4).
Cyclization of (R)-7a with 3-chloro-2-chloromethyl-1-propene
in the presence of Cs2CO3 in DMF at 45 °C for 8 h and
protection with the corresponding diols afforded (R)-6a, 7b, and
8a (23-35% yield). Using the Sharpless procedure, cleavage
of (R)-6a, 7b, and 8a with RuCl3/NaIO4 gave ketones (R)-6-8
after flash column chromatography (23-59% yield).
Preparation of Ketones 9-14. We found it difficult to
introduce other ortho-substituents using the synthetic schemes
outlined above, because the hindered oxazolines could not be
cleaved without the assistance of a neighboring hydroxyl group.
Recently, Jacques Mortier et al. reported the use of carboxylic
acid group as an effective director for ortho-lithiation.29 This
immediately drew our attention to the possibility of using
carboxylic acid group as an ortho-metalation directing group
in our ketone synthesis. We found the resulting synthetic
scheme for the ketone catalysts 9-13 more efficient and con-
vergent (Scheme 5).
1,1′-Binaphthyl-2,2′-dicarboxylic acid 2a ((R)-2a for ketones
(R)-9, (R)-10, and (R)-11; (S)-2a for ketones (S)-12 and (S)-
13) was treated with sec-BuLi/TMEDA in THF at -90 °C and
quenched with the corresponding electrophiles. The ortho-
substituted carboxylic acids 9a-13a were coupled with 3-chloro-
2-chloromethyl-1-propene in the presence of cesium carbo-
nate in DMF at 95-100 °C. Oxidative cleavage of 9b-13b to
ketones 9-13 was carried out successfully. On the other hand,
ketone (R)-14 was synthesized in 59% yield from (R)-11 by
cross-coupling with phenyl boric acid in the presence of Pd-
(PPh3)4 and K3PO4 in DMF.30
Chiral Ketones as Probes for Transition State of Dioxirane
Epoxidation: Evidence for a Spiro Transition State. While
dioxirane epoxidation follows a concerted and stereospecific
pathway, there are two extreme transition states, i.e., spiro and
planar (Figure 5). Baumstark et al. proposed a spiro TS rather
than a planar TS for dioxirane epoxidation based on the
observation that certain cis-dialkyl alkenes were ca. 7-10 times
more reactive than their trans-isomers.31 However, for phenyl-
substituted alkenes, certain trans-isomers were slightly more
reactive than cis-isomers. Besides, computational studies by
Bach et al.32 and Houk et al.33 showed that the optimized
transition state for oxygen atom transfer from dioxirane to
ethylene was spiro.
The 10 new chiral ketones 5-14 were therefore used as
probes to address the question of whether dioxirane epoxidation
follows a spiro or a planar transition state. Epoxidation results
obtained using ketones 5-14 are summarized in Table 5 in
comparison with that of ketone (R)-2.
Several interesting trends are observed. (1) As the size of
the steric sensor X became larger (from H to Cl to Br to I, see
entries 1-4; from H to Me to MOM to acetal to Ph to TMS,
see entries 5-9; and also see entries 10-12), enantioselectivity
first increased and then decreased. This means that ketones
with steric sensors of appropriate sizes are desirable. (2) While
Cl is smaller in size than Me, higher ee was obtained with chloro
ketone 9 than methyl ketone 12, which suggests that the presence
of electronegative atoms on the steric sensors is also important.
(3) With (R)-ketones as catalysts, (S,S)-epoxides of trans-
stilbenes were obtained as the major enantiomers.
Note that trans-stilbene 15 has a large phenyl group and a
small hydrogen atom on one side of the double bond. When
(27) (a) Pfeffer, P. E.; Silbert, L. S. J. Org. Chem. 1976, 41, 1373. (b)
Wang, S.-S.; Gisin, B. F.; Winter, D. P.; Makofske, R.; Kulesha, I. D. J.
Org. Chem. 1977, 42, 1286.
(28) Carlsen, Per H. J.; Katsuki, T.; Martin, V. S.; Sharpless, K. B. J.
Org. Chem. 1981, 46, 3936.
(31) (a) Baumstark, A. L.; McCloskey, C. J. Tetrahedron Lett. 1987,
28, 3311. (b) Baumstark, A. L.; Vasquez, P. C. J. Org. Chem. 1988, 53,
3437. (c) Baumstark, A. L.; Harden. D. B. J. Org. Chem. 1993, 58, 7615.
(32) Bach, R. D.; Andres, J. L.; Su, M.-D.; McDouall, J. J. W. J. Am.
Chem. Soc. 1993, 115, 5768.
(29) Mortier, J.; Moyroud, J. J. Org. Chem. 1994, 59, 4042.
(30) Watanabe, T.; Miyaura, N.; Suzuki, A. Synlett 1992, 207.
(33) Houk, K. N.; Liu, J.; DeMello, N. C.; Condroski, K. R. J. Am. Chem.
Soc. 1997, 119, 10147.

5948 J. Am. Chem. Soc., Vol. 120, No. 24, 1998
Yang et al.
Table 5. Asymmetric Epoxidation of trans-Stilbene 15a Catalyzed
by Ketones 2 and 5-14
entry catalystb time (h) yieldc (%) epoxide confignd eee (%)
high enantioselectivities (84-95% ee) were achieved for
epoxidation of trans-stilbenes 15-19.
Asymmetric Epoxidation of Trisubstituted Olefins. As
chiral ketones (R)-7, (R)-9, and (R)-10 are excellent catalysts
for asymmetic epoxidation of trans-olefins, they are expected
to be effective for trisubstituted olefins. Results for asymmetric
epoxidation of trisubstituted olefins 22 and 23 are summarized
in Table 7.
For triphenylethylene 22, approach of chiral dioxiranes from
the disubstituted side of the olefin double bond would be
sterically hindered by the two phenyl rings under a spiro TS.
On the monosubstituted side, there are a large phenyl ring and
a small hydrogen atom present, similar to the steric environment
of trans-stilbene 15. Therefore, for any given catalyst, similar
enantioselectivities were obtained for epoxidation of 15 and 22
(compared Table 6 with Table 7).
On the other hand, the two identical methylene groups of
1-phenylcyclohexene 23 are not bulky enough to block diox-
iranes approaching from the disubstituted side. Competing
approaches from the monosubstituted and disubstituted sides
of 23 would occur. Therefore, lower enantioselectvities as
compared with trans-stilbene 15 were observed for the epoxi-
dation of 23 catalyzed by ketones (R)-9 and (R)-10. Ketone
(R)-7 with more extended steric sensors seemed to be suitable
for recognizing olefin 23.
III. Evidence for the Involvement of the Dioxirane
Intermediates in Epoxidation of trans-Stilbene 15 Catalyzed
by Ketone (S)-2. Recently, based on an 18O-labeling experi-
ment, Armstrong et al. suggested that dioxirane intermediates
might not be involved in ketone-catalyzed epoxidation by Oxone
in a biphasic system (CH2Cl2/aqueous buffer).35 This intrigued
us to investigate whether dioxirane intermediates are involved
in our epoxidation reactions.36
An 18O-labeling experiment was designed to probe whether
dioxirane intermediate (S)-2b was involved in epoxidation of
trans-stilbene 15 catalyzed by ketone (S)-2.
A 1:1 mixture of unlabeled and 18O-labeled ketones (S)-2
was prepared by stirring a solution of ketone (S)-2 in a
CH3CN-H218O solvent system at room temperature for 1 h.
Evidence for 18O-label incorporation was provided by mass
spectrometry and 13C NMR analysis. The mass spectrum of
ketone (S)-2 showed two peaks at m/z 397 (M+ + 1) and 399
((M+ + 1) + 2) in a 1:1 ratio. Also, the 13C NMR spectrum
showed two carbonyl resonances at δ 202.15 and 202.10 in a
1:1 ratio. There was ca. 0.05 ppm upfield shift for the 18O-
labeled carbonyl group.
When epoxidation of trans-stilbene 15 was carried out using
the 1:1 mixture of unlabeled and 18O-labeled ketones (S)-2 with
Oxone/NaHCO3 in a CH3CN-H218O solvent system, 18O-label
incorporation into the epoxide was observed (Scheme 6). The
reaction was complete in 2.5 h. The mass spectrum of the
resulting trans-stilbene epoxide revealed two peaks at m/z 197
(M+ + 1) and 199 ((M+ + 1) + 2) in a ratio of 1:0.31. The
13C NMR spectrum also showed two epoxide carbon resonances
at δ 62.85 and 62.82; there was ca. 0.03 ppm upfield shift for
the 18O-labeled epoxide. Since addition of KHSO5 to ketone
(S)-2 is nonstereoselective, dioxirane intermediate (S)-2b would
result in 25% 18O-label incorporation into the epoxide, provided
that (i) both 16O and 18O oxygen atoms of the dioxirane group
1f
2
3
4
5
(R)-2
(R)-9
(R)-10
(R)-11
(R)-12
(R)-5
(R)-7
(R)-14
(R)-13
(R)-6
(R)-7
(R)-8
1
2
3
22
1
1.8
0.7
24
20
20
20
20
91
95
92
90g
93
92
95
50h
nci
90
93
91
(-)-(S,S)
(-)-(S,S)
(-)-(S,S)
(-)-(S,S)
(+)-(R,R)
(-)-(S,S)
(-)-(S,S)
(-)-(S,S)
(+)-(R,R)
(-)-(S,S)
(-)-(S,S)
(-)-(S,S)
47
76
75
32
56
66
71
55
44
77
84
75
6
7
8
9
10j
11j
12j
a Unless otherwise indicated, reaction conditions were as follows:
room temperature, 0.1 mmol of trans-stilbene 15, 0.01 mmol of ketone,
0.5 mmol of Oxone, 1.55 mmol of NaHCO3, 1.5 mL of CH3CN, 1.0
mL of aqueous Na2‚EDTA solution (4 × 10-4 M). b Optical purity:
98% ee. All ketones listed were recovered in over 80% yield by flash
column chromatography with Et3N buffered silica gel (Merck 230-
400 mesh). c Isolated yield after flash column chromatography. d De-
termined by circular dichroism spectroscopy. e Enantiomeric excess was
determined by 1H NMR using chiral shift reagent Eu(hfc)3. f 0.1 mmol
of trans-stilbene 15, 0.1 mmol of ketone (R)-2. g Yield based on
recovery of trans-stilbene (50% conversion). h Yield based on recovery
of trans-stilbene (44% conversion). i Not completed. j 0-1 °C, 0.1
mmol of trans-stilbene 15, 0.01 mmol of ketone, 1.0 mmol of Oxone,
3.1 mmol of NaHCO3, 1.5 mL of DME, 1.0 mL of aqueous Na2‚EDTA
solution (4 × 10-4 M).
encountering trans-stilbene, C2 symmetric chiral dioxirane (R)-
2b has two possible orientations (favored and disfavored
orientations based on steric considerations) under either a spiro
or a planar transition state (Figure 6). The favored orientation
has the phenyl group of trans-stilbene positioned away from
the naphthalene rings of the dioxirane. When the steric sensors
at the 3- and 3′-positions of dioxirane become larger up to a
certain size (e.g., from H to Cl to Br), there is little increase of
steric interactions in the favored orientation, whereas steric
interactions are significantly increased in the disfavored orienta-
tion, thereby giving higher enantioselectivity. However, when
the steric sensors become even larger (e.g., from Br to I), the
nonbonded steric interactions are increased significantly in both
favored and disfavored orientations, resulting in lower enan-
tioselectitivity and slower epoxidation.
As illustrated in Figure 6, with (R)-ketones as catalysts, (S,S)-
epoxides of trans-stilbenes are expected to be the major products
under a spiro TS, whereas (R,R)-epoxides are expected under a
planar TS. Results listed in Table 5 are consistent with a spiro
TS. In addition, docking experiments using the MacroModel
program34 suggested that the steric sensors recognize the para/
meta positions of trans-stilbene under a spiro TS but ortho/
meta positions under a planar TS. It is thus expected that, under
a spiro TS, higher ee values are obtained when the para
substituents of trans-stilbenes 15-19 become larger. As shown
in Table 6, this was indeed the case for effective chiral catalysts
(R)-7, (R)-9, and (R)-10. The meta substituents of substrate 21
seemed to have little effect on enantioselectivity. Our results
suggest that those chiral ketones recognize para substituents
much better than meta substituents of trans-stilbenes.
We also discovered that when epoxidation was carried out
in an aqueous DME solution at 0 °C, further increases in
enantioselectivities (up to 13%) were obtained (Table 6). Most
significantly, with the most active ketone (R)-7 as the catalyst,
(35) Armstrong, A.; Clarke, P. A.; Wood, A. J. Chem. Soc., Chem.
Commun. 1996, 849.
(36) Denmark et al. recently reported that dioxiranes are the active agents
in ketone-catalyzed epoxidation reactions with Oxone. This is consistent
with our conclusion. See: Denmark, S. E.; Wu, Z. J. Org. Chem. 1997,
62, 8964.
(34) MacroModel version 4.5: Mohamadi, F.; Richards, N. G. J.; Guida,
W. C.; Liskamp, R.; Caufield, C.; Chang, G.; Hendrickson, T.; Still, W. C.
J. Comput. Chem. 1990, 11, 440.

Chiral Ketones for Epoxidation of Olefins
J. Am. Chem. Soc., Vol. 120, No. 24, 1998 5949
Figure 6. Proposed TS for epoxidation of olefins.
Table 6. Enantioselective Epoxidation of trans-Stilbenes 15-19
and 21 Catalyzed by Ketones 7, 9, and 10a
Table 7. Enantioselective Epoxidation of Trisubstituted Olefins
Catalyzed by Ketones 5, 7, 9, and 10a
epoxide eeb (%)
(R)-9c,d (R)-10c,d (R)-10e (R)-7c,f (R)-7e,g
time yieldc
epoxide
confign
eed
(%)
entry substrate catalystb
(h)
24
24
2.3
3
1.5
4
(%)
entry
substrate
1
2
3
4
5
6
7
8
22
22
22
22
23
23
23
23
(R)-9
(R)-10
(R)-5
(R)-7
(R)-9
(R)-10
(R)-5
(R)-7
96
82
95
90
75
81
80
90
(+)-(S)e
76
81
67
73
65
64
67
71
1
2
3
4
5
6
15 (R ) H)
16 (R ) Me)
17 (R ) Et)
18 (R ) i-Pr)
19 (R ) t-Bu)
21
76
80
85
85
91
75
85
88
90
93
74
80h
88g
92i
92j
95k
71
84
82
88
90
73
84
88
91
91
95
(+)-(S)e
(+)-(S)e
(+)-(S)e
(-)-(S,S)e
(-)-(S,S)e
(-)-(S,S)e
(-)-(S,S)e
1.5
1.3
a Optical purity of ketone catalysts: 98% ee. b Enantiomeric excess
was determined by H NMR using chiral shift reagent Eu(hfc)3. The
1
a Unless otherwise indicated, reaction conditions were as follows:
room temperature, 0.1 mmol of substrate, 0.01 mmol of ketone, 0.5
mmol of Oxone, 1.55 mmol of NaHCO3, 1.5 mL of CH3CN, 1.0 mL
of aqueous Na2‚EDTA solution (4 × 10-4 M). b Optical purity: 98%
ee. c Isolated yield after flash column chromatography. d Enantiomeric
excess was determined by 1H NMR using chiral shift reagent Eu(hfc)3.
e Reference 3a.
reaction products isolated were predominantly the (-)-(S,S)-epoxides
as determined by circular dichroism spectroscopy. c Method A: room
temperature, 0.1 mmol of substrate, 0.01 mmol of catalyst, 0.5 mmol
of Oxone, 1.55 mmol of NaHCO3, 1.5 mL of CH3CN, and 1.0 mL of
aqueous Na2‚EDTA solution (4 × 10-4 M). The epoxides were isolated
in over 90% yield. d Reaction was complete in 2-3 h. e Method B:
0-1 °C, 0.1 mmol of substrate, 0.01 mmol of catalyst, 1.0 mmol of
Oxone, 3.1 mmol of NaHCO3, 1.5 mL of DME, and 1.0 mL of aqueous
Na2‚EDTA solution (4 × 10-4 M). f Reaction was complete in 40 min.
g The epoxides were isolated in over 90% yield. Reactions were
complete in 20 h. h 94% yield based on 88% conversion after 25 h.
i 85% yield based on 60% conversion after 24 h. j 83% yield based on
60% conversion after 21 h. k 55% yield based on 40% conversion after
18 h.
Scheme 6
can be transferred to trans-stilbene with little rate difference;37
and (ii) the equilibrium ratio of unlabeled and 18O-labeled ke-
tones (S)-2 remains unchanged during epoxidation reaction. The
experimental result showed ca. 23% 18O-label incorporation into
the epoxide. In addition, as suggested by 1H NMR no detectable
amount of epoxides was formed under identical conditions in
the absence of ketone (S)-2. The excellent agreement between
the prediction and experimental observation supports the
conclusion that the dioxirane intermediate (S)-2b is responsible
for epoxidation of trans-stilbene 15 catalyzed by ketone (S)-2.
can be performed with only 10 mol % of ketone catalysts, which
can be recovered and reused without loss of activity and chiral
induction. Convincing evidence for a spiro transition state of
dioxirane epoxidation was provided. Through the 18O-labeling
experiment, chiral dioxiranes were found to be the intermediates
in chiral ketone catalyzed epoxidation reactions.
Conclusion
In this paper, we have demonstrated the potential of C2
symmetric chiral ketones for catalytic asymmetric epoxidation
of trans-olefins and trisubstituted olefins. Epoxidation reactions
Experimental Section
16
18
(37) The primary kinetic isotope effect k O/k O for C-O bond cleavage
was estimated to be 1.073 at 25 °C. Melander, L.; Saunders, Jr., W. H. In
Reaction Rates of Isotopic Molecules; Wiley-Interscience: New York, 1980;
p 272-275.
General Methods. All reactions were performed in oven-dried
apparatus. Air and moisture-sensitive compounds were introduced via
syringes through a rubber septum. THF was distilled from sodium-

5950 J. Am. Chem. Soc., Vol. 120, No. 24, 1998
Yang et al.
benzophenone. Dichloromethane and acetonitrile were distilled from
calcium hydride. Flash column chromatography was performed using
the indicated solvent system on Merck silica gel 60 (230-400 mesh
ASTM). Enantioselectivity (% ee) of epoxides was determined by 1H
NMR using chiral shift reagent Eu(hfc)3 (Aldrich Cat. No. 16,474-7).
Absolute configuration was determined by circular dichroism spec-
troscopy (ethanol as solvent) with a JASCO J-720 spectropolarimeter.
The olefins and Oxone were purchased from Aldrich Chemical Co.
and used without further purification. The known epoxides were
identified by comparison of the spectral and physical data with those
reported. Synthesis of various substituted stilbenes 16-19 and 21 were
carried out according to the literature procedure.38
to give the acetal (R)-7b (47 mg, 23% yield) as a white solid. Analytical
TLC (silica gel 60), 50% EtOAc in hexane, Rf ) 0.33; mp 362-363
1
°C (hexane-CH2Cl2); H NMR (300 MHz, CDCl3) δ 8.24 (s, 2H),
7.91 (d, J ) 8 Hz, 2H), 7.46 (t, J ) 7 Hz, 2H), 7.20 (t, J ) 7 Hz, 2H),
6.97 (d, J ) 8 Hz, 2H), 5.90 (s, 2H), 5.53 (d, J ) 14.1 Hz, 2H), 5.15
(s, 2H), 4.43 (dd, J ) 12 Hz, 4.9 Hz, 2H), 4.25-4.04 (m, 6H), 3.91
(td, J ) 12 Hz, 2.4 Hz, 2H), 2.28-2.17 (m, 2H), 1.47 (br d, J ) 13.5
Hz, 2H); 13C NMR (75.47 MHz, CDCl3) δ 167.16, 141.34, 134.96,
133.08, 132.79, 132.37, 129.28, 128.54, 127.66, 127.38, 127.17, 126.02,
112.68, 99.44, 67.46, 67.23, 64.05, 25.77; CIMS m/z 567 (M+ + 1,
100), 154 (38).
A stock solution of NaIO4 (877 mg, 4.1 mmol) and ruthenium
trichloride hydrate (5 mg, 0.024 mmol) in water (5 mL) was prepared.
The acetal (R)-7b (47 mg, 0.083 mmol) was dissolved in CCl4 (2 mL),
CH3CN (2 mL) and water (2.6 mL). The stock solution (0.4 mL) was
transferred to the reaction mixture. The biphasic mixture was stirred
vigorously for 6 h at room temperature. Then CH2Cl2 (30 mL) and
water (20 mL) were added, and the phases were separated. The aqueous
phase was extracted with CH2Cl2 (2 × 10 mL). The combined organic
layers were dried (Na2SO4) and concentrated. The residue was purified
by flash column chromatography: 20 g of silica gel (Merck, 230-400
mesh) in hexane (100 mL) and NEt3 (2 mL) was poured into a column
of 20 mm diameter. The column was eluted with hexane (100 mL),
followed by 40% EtOAc in hexane (200 mL) to give ketone (R)-7 (28
mg, 59% yield) as a white solid. Analytical TLC (silica gel 60), 50%
Preparation of Ketones (R)-7, (R)-9 and (R)-10. (R)-2,10-Bis-
(1,3-dioxan-2-yl)-5H-dinaphtho[2,1-g:1′,2′-i][1,5]dioxacycloundecin-
3,6,9(7H)-trione ((R)-7). To a THF solution (50 mL) of bisoxazoline
(R)-5a (0.68 g, 1.51 mmol) at -78 °C under N2 atmosphere was added
TMEDA (1.2 mL, 7.58 mmol) and sec-butyllithium (5.8 mL, 1.3 M in
cyclohexane, 7.58 mmol). The reaction mixture was stirred at -78
°C for 1 h. DMF (0.6 mL, 6.06 mmol) was added. The mixture was
slowly warmed to room temperature for 4 h and quenched with aqueous
NH4Cl (5 mL). After dilution with EtOAc (100 mL), the reaction
mixture was washed with water (100 mL), dried (MgSO4), and
concentrated. The crude substituted bisoxazoline was treated with 6
N HCl (40 mL) and refluxed overnight. After dilution with water (200
mL), the mixture was extracted with EtOAc (200 mL). The EtOAc
layer was treated with saturated NaHCO3 solution (200 mL) and
separated. The organic layer was discarded. The aqueous layer was
acidified to pH 3 with 2 N HCl, saturated with NaCl salts, and extracted
with EtOAc (2 × 100 mL). The combined organic layers were washed
with brine (2 × 100 mL), dried over anhydrous MgSO4, filtered through
a pad of silica gel (Merck, 230-400 mesh), and concentrated to give
a pale yellow viscous liquid (R)-7a (0.31 g, 51% yield). Analytical
TLC (silica gel 60), EtOAc, Rf ) 0.29; 1H NMR (500 MHz, CD3CN)
δ 8.32 (s, 1H), 8.31 (s, 1H), 8.21-8.20 (m, 2H), 7.72-7.69 (m, 2H),
7.45-7.41 (m, 2H), 7.26-7.23 (m, 2H), 6.81 (d, J ) 6 Hz, 1H), 6.77
(d, J ) 6 Hz, 1H), 6.01 (d, J ) 6 Hz, 1H), 5.87 (d, J ) 6 Hz, 1H) (a
mixture of diastereomers); 13C NMR (125.77 MHz, CD3CN) δ 167.04,
166.98, 140.97, 140.94, 140.81, 140.79, 135.95, 135.90, 135.86, 133.72,
133.66, 133.55, 133.50, 133.25, 133.05, 128.86, 128.83, 128.82, 128.78,
128.75, 128.69, 127.71, 127.65, 127.63, 127.56, 126.54, 126.51, 126.40,
126.35, 123.40, 123.37, 123.25, 123.22, 122.90, 122.67, 122.63, 122.42,
96.90, 96.76 (a mixture of diastereomers); IR (Nujol mull) 3453 (br),
1745, 1629, 1463, 1093, 932 cm-1; FABMS m/z 398 (M+, 13), 380
(20), 252 (14), 250 (23), 153 (68), 136 (41), 108 (15), 107 (62), 106
(24), 77 (100).
1
EtOAc in hexane, Rf ) 0.30; H NMR (300 MHz, CDCl3) δ 8.26 (s,
2H), 7.94 (d, J ) 8 Hz, 2H), 7.49 (t, J ) 7 Hz, 2H), 7.23 (t, J ) 7 Hz,
2H), 6.98 (d, J ) 8 Hz, 2H), 5.86 (s, 2H), 5.63 (d, J ) 15.3 Hz, 2H),
4.41 (dd, J ) 11 Hz, 4.9 Hz, 2 H), 4.19 (dd, J ) 11 Hz, 4.9 Hz, 2H),
4.11-4.01 (m, 4H), 3.87 (td, J ) 12 Hz, 2.4 Hz, 2H), 2.30-2.14 (m,
2H), 1.48 (br d, J ) 13.6 Hz, 2H); 13C NMR (75.47 MHz, CDCl3) δ
203.24, 165.78, 135.00, 132.97, 132.90, 132.49, 128.63, 128.24, 127.63,
127.57, 126.48, 99.39, 67.51, 67.27, 66.17, 25.69; IR (CCl4) 2928, 2856,
1765, 1738, 1378, 1248, 1121 cm-1; HRMS for C33H28O9 (M+), calcd
568.1733, found 568.1727; EIMS (20 eV) m/z 568 (M+, 83), 509 (21),
495 (100), 437 (29), 395 (34); FABMS m/z 568 (M+, 64), 509 (19),
495 (100), 437 (28), 395 (36); CD (EtOH) λmax (θ) 296 (5.3 × 105),
263 (-5.2 × 105), 231 (-9.2 × 106), 219 (8.2 × 106).
(R)-2,10-Dichloro-5H-dinaphtho[2,1-g:1′,2′-i][1,5]dioxacyclo-
undecin-3,6,9(7H)-trione ((R)-9). A solution of (R)-1,1′-binaphthyl-
2,2′-dicarboxylic acid (R)-2a21 (0.20 g, 0.58 mmol; azeotroped three
times with toluene) and TMEDA (0.7 mL, 4.6 mmol) in THF (20 mL)
was treated dropwise with sec-butyllithium (3.2 mL, 1.3 M in
cyclohexane, 4.2 mmol) at -90 °C for 1.5 h. A solution of hexa-
chloroethane (1.40 g, 5.8 mmol) in THF (5 mL) was added dropwise
at -78 °C. Stirring was continued at this temperature for 1 h. The
mixture was warmed slowly to room temperature, quenched with
aqueous NH4Cl (5 mL), and diluted with CH2Cl2 (30 mL). The
resulting mixture was extracted with 0.5 N NaOH solution (40 mL).
The aqueous phase was acidified with concentrated HCl and extracted
with EtOAc (3 × 30 mL). The combined organic layers were washed
with brine (50 mL), dried over anhydrous MgSO4, and concentrated.
The residue was purified by preparative TLC (1% acetic acid in EtOAc,
three elutions) to provide diacid (R)-9a (0.121 g, 50% yield) as a solid.
1H NMR (300 MHz, CD3OD) δ 8.19 (s, 2H), 7.95 (d, J ) 8.4 Hz,
2H), 7.57 (t, J ) 7 Hz, 2H), 7.35 (t, J ) 7 Hz, 2H), 7.06 (d, J ) 8.4
Hz, 2H); 13C NMR (67.9 MHz, CD3OD) δ 155.78, 121.35, 121.28,
120.56, 118.45, 116.13, 115.35, 114.58, 114.51, 114.25; HRMS for
C22H12Cl2O4 (M+), calcd 410.0113, found 410.0117; EIMS (20 eV)
m/z 410 (100), 366 (10), 348 (13), 286 (15).
Hydroxylactone (R)-7a (80 mg, 0.2 mmol) and 3-chloro-2-chloro-
methyl-1-propene (25 mg, 0.2 mmol) were dissolved in anhydrous DMF
(20 mL), and then cesium carbonate (138 mg, 0.42 mmol) was added.
The resulting solution was stirred at 45 °C under N2 atmosphere for 8
h. The reaction mixture was diluted with EtOAc (100 mL), washed
with water (4 × 50 mL), and dried over anhydrous MgSO4. The solvent
was removed under reduced pressure to give the crude aldehyde (32
mg, 94% yield based on 38% conversion) which was used in the next
step without further purification. The aqueous layer was acidified to
pH 3 with 2 N HCl, and extracted with EtOAc (100 mL). The EtOAc
layer was washed with brine (2 × 50 mL), dried (MgSO4), and
concentrated to give back the hydroxylactone (R)-7a (50 mg, 62% yield
of recovery) which was reused in the cyclization step.
The crude aldehyde (160 mg, 0.36 mmol) and 1,3-propanediol (100
mg, 1.3 mmol) were dissolved in anhydrous benzene (15 mL).
Anhydrous p-toluenesulfonic acid (2-3 mg) was added. The resulting
solution was refluxed under N2 for 5 h. The reaction mixture was
diluted with CH2Cl2 (50 mL), washed with water (20 mL), and dried
(Na2SO4). After evaporation of solvents, the residue was purified by
flash column chromatography: 20 g of silica gel (Merck, 230-400
mesh) in hexane (100 mL) with NEt3 (2 mL) was poured into a column
of 20 mm diameter. The column was eluted with hexane (100 mL),
30% EtOAc in hexane (100 mL), and 40% EtOAc in hexane (200 mL)
Diacid (R)-9a (0.132 g; 0.32 mmol, azeotroped three times with
toluene) and 3-chloro-2-chloromethyl-1-propene (0.040 g, 0.32 mmol)
were dissolved in anhydrous DMF (32 mL). Cesium carbonate (0.229
g, 0.704 mmol) was added to this solution. The resulting reaction
mixture was stirred at 100 °C under N2 atmosphere for 17 h, poured
into water (50 mL), and extracted with EtOAc (100 mL). The organic
layer was washed three times with water and dried over anhydrous
MgSO4. After removal of the solvent under reduced pressure, the
residue was purified by flash column chromatography (30% EtOAc in
hexane) to give (R)-9b (88.5 mg, 60% yield) as a white solid.
(38) Ogawa, K.; Sano, T.; Yoshimura, S.; Takeuchi, Y.; Toriumi, K. J.
Am. Chem. Soc. 1992, 114, 1041.
1
Analytical TLC (silica gel 60), 30% EtOAc in hexane, Rf ) 0.48; H

Chiral Ketones for Epoxidation of Olefins
J. Am. Chem. Soc., Vol. 120, No. 24, 1998 5951
NMR (300 MHz, CDCl3) δ 8.04 (s, 2H), 7.48 (d, J ) 8.2 Hz, 2H),
7.52 (t, J ) 7 Hz, 2H), 7.26 (t, J ) 7 Hz, 2H), 6.90 (d, J ) 8.2 Hz,
2H), 5.46 (d, J ) 14 Hz, 2H), 5.18 (s, 2H), 4.43 (d, J ) 14 Hz, 2H);
13C NMR (67.9 MHz, CDCl3) δ 165.65, 139.72, 134.95, 133.70, 131.54,
131.07, 129.10, 128.21, 127.60, 127.36, 127.21, 113.62, 65.18; IR
(CCl4) 1752 cm-1; HRMS for C26H16Cl2O4 (M+), calcd 462.0426, found
462.0422; EIMS (20 eV) m/z 462 (100), 418 (8), 348 (14).
To a solution of (R)-10b (0.043 g, 0.081 mmol) in a mixture of CCl4
(2 mL), CH3CN (2 mL), and H2O (2.6 mL) was added the stock solu-
tion (0.4 mL). Stirring was continued at room temperature for 19 h.
CH2Cl2 (20 mL) and water (20 mL) were added to this mixture. The
aqueous layer was extracted with CH2Cl2 (2 × 20 mL). The combined
organic layers were dried over anhydrous Na2SO4 and concentrated.
The residue was purified by flash column chromatography (30% EtOAc
in hexane) to provide ketone (R)-10 (17 mg, 40% yield) as a white
solid. Mp 252-254 °C (hexane-CH2Cl2); analytical TLC (silica gel
A stock solution of NaIO4 (877 mg, 4.1 mmol) and ruthenium
trichloride hydrate (5 mg, 0.024 mmol) in water (5 mL) was prepared.
To a solution of (R)-9b (0.046 g, 0.103 mmol) in a mixture of CCl4 (2
mL), CH3CN (2 mL), and H2O (2.5 mL) was added the stock solu-
tion (0.5 mL). Stirring was continued at room temperature for 17 h.
CH2Cl2 (20 mL) and water (20 mL) were added to this mixture. The
aqueous layer was extracted with CH2Cl2 (2 × 20 mL). The combined
organic layers were dried over anhydrous Na2SO4 and concentrated.
The residue was purified by flash column chromatography (30% EtOAc
in hexane) to provide ketone (R)-9 (10 mg, 21% yield) as a white solid.
Mp 256-258 °C (hexane-CH2Cl2); analytical TLC (silica gel 60), 30%
1
60), 20% EtOAc in hexane, Rf ) 0.3; H NMR (300 MHz, CDCl3) δ
8.28 (s, 2H), 7.86 (d, J ) 8.2 Hz, 2H), 7.56 (t, J ) 7.1 Hz, 2H), 7.31
(t, J ) 7.1 Hz, 2H), 6.91 (d, J ) 8.2 Hz, 2H), 5.56 (d, J ) 15.4 Hz,
2H), 4.23 (d, J ) 15.4 Hz, 2H); 13C NMR (67.9 MHz, CDCl3) δ 201.42,
164.64, 134.89, 134.25, 133.01, 131.71, 131.67, 128.58, 128.03, 127.40,
127.27, 115.42, 67.00; IR (CCl4) 1763, 1743, 1278, 1246, 1159, 1140
cm-1; HRMS for C25H14Br2O5 (M+), calcd 553.9208, found 553.9216;
EIMS (20 eV) m/z 554 (100), 496 (17), 438 (49); CD (EtOH) λmax (θ)
301 (3.0 × 104), 267 (-3.9 × 104), 253 (8.8 × 104), 236 (-9.1 ×
105), 220 (6.1 × 105).
1
EtOAc in hexane, Rf ) 0.5; H NMR (300 MHz, CDCl3) δ 8.08 (s,
2H), 7.87 (d, J ) 8.4 Hz, 2H), 7.56 (t, J ) 7 Hz, 2H), 7.29 (t, J ) 7
Hz, 2H), 6.93 (d, J ) 8.4 Hz, 2H), 5.57 (d, J ) 15.4 Hz, 2H), 4.23 (d,
J ) 15.4 Hz, 2H); 13C NMR (67.9 MHz, CDCl3) δ 201.36, 164.32,
135.03, 133.90, 131.36, 130.17, 129.44, 128.63, 127.88, 127.50,
General Epoxidation Procedure. Method A. General in Situ
Epoxidation Procedure in CH3CN-H2O Solvent System at Room
Temperature (Table 6, Entry 1). To an CH3CN solution (1.5 mL)
of trans-stilbene 15 (18 mg, 0.1 mmol) and ketone (R)-9 (4.6 mg, 0.01
mmol) at room temperature was added an aqueous Na2‚EDTA solution
(1 mL, 4 × 10-4 M). To this mixture was added in portions a mixture
of Oxone (307 mg, 0.5 mmol) and sodium bicarbonate (130 mg, 1.55
mmol). The reaction was complete in 2 h at room temperature as shown
by TLC. The reaction mixture was poured into water (20 mL) and
extracted with CH2Cl2 (3 × 20 mL). The combined organic layers
were dried over anhydrous Na2SO4. After removal of the solvent under
reduced pressure, the residue was purified by flash column chrom-
atography: 20 g of silica gel (Merck, 230-400 mesh) in hexane (100
mL) and NEt3 (2 mL) was poured into a column of 20 mm diameter.
The column was eluted with hexane (50 mL), followed by 5% EtOAc
in hexane (100 mL) to give trans-stilbene epoxide 15a (18.6 mg, 95%
yield), and 35% EtOAc in hexane (100 mL) to recover ketone (R)-9
(3.7 mg, 81% recovery).
Method B. General in Situ Epoxidation Procedure in DME-
H2O Solvent System at 0-1 °C (Table 6, Entry 1). To a 1,2-
dimethoxyethane (DME) solution (1.5 mL) of trans-stilbene 15 (18
mg, 0.1 mmol) and ketone (R)-7 (5.7 mg, 0.01 mmol) at 0-1 °C was
added an Na2‚EDTA solution (1 mL, 4 × 10-4 M). To this mixture
was added in portions a mixture of Oxone (614.8 mg, 1.0 mmol) and
sodium bicarbonate (260.4 mg, 3.1 mmol). The reaction was complete
in 20 h at 0 °C as shown by TLC. The reaction mixture was poured
into water (20 mL) and extracted with CH2Cl2 (3 × 20 mL). The
combined organic layers were dried over anhydrous Na2SO4. After
removal of the solvent under reduced pressure, the residue was purified
by flash column chromatography: 20 g of silica gel (Merck, 230-400
mesh) in hexane (100 mL) and NEt3 (2 mL) was poured into a column
of 20 mm diameter. The column was eluted with hexane (50 mL),
followed by 5% EtOAc in hexane (100 mL) to give trans-stilbene
epoxide 15a (17.7 mg, 90% yield), and EtOAc (100 mL) to recover
ketone (R)-7 (4.6 mg, 80% recovery).
Preparation of (E)-4,4′-Diphenylstilbene Epoxide 20a (Table 1,
Entry 6). To an CH3CN solution (2.0 mL) of (E)-4,4′-diphenylstilbene
20 (33.2 mg, 0.1 mmol) and ketone (R)-2 (3.9 mg, 0.01 mmol) at room
temperature was added an aqueous Na2‚EDTA solution (1.7 mL, 4 ×
10-4 M). To this mixture was added in portions a mixture of Oxone
(307 mg, 0.5 mmol) and sodium bicarbonate (130 mg, 1.55 mmol).
The reaction was complete in 8 h at room temperature. The reaction
mixture was poured into water (20 mL) and extracted with CH2Cl2 (3
× 40 mL). The combined organic layers were dried over anhydrous
Na2SO4. After removal of the solvent under reduced pressure, the
residue solid was triturated carefully with CH2Cl2 (2 × 4 mL) to give
epoxide 20a (27.8 mg, 80% yield) as a white solid. 1H NMR (300
MHz, CDCl3) δ 7.64-7.59 (m, 8H), 7.48-7.43 (m, 8H), 7.39-7.34
(m, 2H), 3.96 (s, 2H); 13C NMR (125.77 MHz, CDCl3) δ 141.39,
140.67, 136.12, 128.84, 127.47, 127.36, 127.10, 125.98, 62.77; HRMS
for C26H20O (M+), calcd 348.1514, found 348.1512; EIMS (20 eV)
m/z 348 (11), 333 (27), 332 (100), 320 (15), 319 (56), 181 (9).
127.42, 127.25, 67.06; IR (CCl4) 1762, 1281, 1247, 1160, 1141 cm-1
;
HRMS for C25H14Cl2O5 (M+), calcd 464.0218, found 464.0223;
EIMS (20 eV) m/z 464 (100), 406 (26), 376 (20), 348 (61); CD (EtOH)
λmax (θ) 300 (1.1 × 104), 263 (-1.4 × 104), 234 (-2.9 × 105), 219
(1.9 × 105).
(R)-2,10-Dibromo-5H-dinaphtho[2,1-g:1′,2′-i][1,5]dioxacyclo-
undecin-3,6,9(7H)-trione ((R)-10). A solution of (R)-1,1′-binaphthyl-
2,2′-dicarboxylic acid (R)-2a (0.205 g, 0.58 mmol; azeotroped three
times with toluene) and TMEDA (0.7 mL, 4.6 mmol) in THF (20 mL)
was treated dropwise with sec-butyllithium (3.2 mL, 1.3 M in
cyclohexane, 4.2 mmol) at -90 °C for 1.5 h. A solution of 2,4,4,6-
tetrabromo-2,5-cyclohexadienone (3.8 g, 9.3 mmol) in THF (10 mL)
was added dropwise at -78 °C. Stirring was continued at this tem-
perature for 1 h. The mixture was warmed slowly to room temperature,
quenched with aqueous NH4Cl (5 mL), and diluted with CH2Cl2 (30
mL). The resulting mixture was extracted with saturated NaHCO3
solution (40 mL). The aqueous phase was acidified with concentrated
HCl and extracted with EtOAc (3 × 30 mL). The combined organic
layers were washed with brine (50 mL), dried over anhydrous MgSO4,
and concentrated. The residue was purified by preparative TLC (1%
acetic acid in EtOAc, three elutions) to provide diacid (R)-10a (0.061
g, 21% yield) as a solid. 1H NMR (300 MHz, CD3OD) δ 8.33 (s,
2H), 7.89 (d, J ) 8.3 Hz, 2H), 7.50 (t, J ) 7.5 Hz, 2H), 7.31 (t, J )
7.5 Hz, 2H), 7.06 (d, J ) 8.3 Hz, 2H); 13C NMR (67.9 MHz, CD3OD)
δ 173.35, 139.44, 135.24, 133.51, 132.35, 128.64, 128.56, 128.41,
128.29, 127.80, 116.42.
Diacid (R)-10a (0.171 g, 0.342 mmol; azeotroped three times with
toluene) and 3-chloro-2-chloromethyl-1-propene (0.047 g, 0.376 mmol)
were dissolved in anhydrous DMF (34 mL). Cesium carbonate (0.244
g, 0.748 mmol) was added to this solution. The resulting reaction
mixture was stirred at 100 °C under N2 atmosphere for 18 h, poured
into water, and extracted with EtOAc (100 mL). The organic layer
was washed three times with water and dried over anhydrous MgSO4.
After removal of the solvent under reduced pressure, the residue was
purified by flash column chromatography (30% EtOAc in hexane) to
give (R)-10b (71 mg, 39% yield) as a white solid. Analytical TLC
1
(silica gel 60), 30% EtOAc in hexane, Rf ) 0.5; H NMR (300 MHz,
CDCl3) δ 8.24 (s, 2H), 7.83 (d, J ) 8.3 Hz, 2H), 7.51 (t, J ) 7.5 Hz,
2H), 7.27 (t, J ) 7.5 Hz, 2H), 6.89 (d, J ) 8.3 Hz, 2H), 5.46 (d, J )
14 Hz, 2H), 5.18 (s, 2H), 4.43 (d, J ) 14 Hz, 2H); 13C NMR (67.9
MHz, CDCl3) δ 165.99, 139.72, 134.81, 134.05, 132.69, 132.61, 131.84,
128.18, 127.76, 127.28, 127.24, 115.42, 113.56, 65.09; IR (CCl4) 1751
cm-1; HRMS for C26H16Br2O4 (M+), calcd 551.9572, found 551.9586;
EIMS (20 eV) m/z 552 (100), 508 (10), 438 (12), 399 (15). Anal.
Calcd for C26H16Br2O4: C, 56.13; H, 2.93. Found: C, 55.95; H,
3.01.
A stock solution of NaIO4 (877 mg, 4.1 mmol) and ruthenium
trichloride hydrate (5 mg, 0.024 mmol) in water (5 mL) was prepared.

5952 J. Am. Chem. Soc., Vol. 120, No. 24, 1998
Yang et al.
Evidence for Involvement of Dioxirane Intermediate in Epoxi-
dation of trans-Stilbene 15 Catalyzed by Ketone (S)-2. To an
CH3CN solution (0.6 mL) of ketone (S)-2 (7.9 mg, 0.02 mmol) at room
temperature was added H218O (Aldrich, 95 at. % 18O, 0.4 mL). After
stirring at room temperature for 1 h, the solution mixture was divided
into two portions by using a micro-pipet. The first portion of the
solution mixture (0.2 mL) was diluted with CH2Cl2 (10 mL), dried
over anhydrous Na2SO4, filtered, and concentrated under reduced
pressure. The recovered ketone (S)-2 was subjected to mass spec-
trometry (CIMS) and 13C NMR analysis. The mass spectrum of ketone
(S)-2 showed two peaks at m/z 397 (M+ + 1) and 399 ((M+ + 1) + 2)
in a 1:1 ratio. Also, the 13C NMR spectrum (125.77 MHz, CDCl3)
showed that two carbonyl resonances at δ 202.15 and 202.10 in a 1:1
ratio were observed; there was ca. 0.05 ppm upfield 13C shift for the
18O-labeled ketone.
To the second portion of solution mixture (0.8 mL) was added trans-
stilbene 15 (3.6 mg, 0.02 mmol). To this reaction mixture was added
a mixture of Oxone (61.5 mg, 0.1 mmol) and sodium bicarbonate (26
mg, 0.31 mmol). The reaction was complete in 2.5 h at room
temperature as shown by TLC. After dilution with CH2Cl2 (10 mL),
the organic layer was dried over anhydrous Na2SO4, filtered, and
concentrated under reduced pressure. The residue was subjected to
mass spectrometry (CIMS) and 13C NMR analysis. The mass spectrum
of trans-stilbene epoxide 15a revealed two peaks at m/z 197 (M+ + 1)
and 199 ((M+ + 1) + 2) in a 1:0.31 ratio. There was ca. 23% 18O-
label incorporation into the epoxide. The 13C NMR spectrum showed
two epoxide resonances at δ 62.85 and 62.82; there was ca. 0.03 ppm
upfield 13C shift for the 18O-labeled epoxide.
Acknowledgment. This work was supported by The Uni-
versity of Hong Kong and Hong Kong Research Grants Council.
M.-K. Wong, Y.-C. Yip, and X.-C. Wang are recipients of the
University Postdoctoral Fellowships.
Supporting Information Available: Experimental details
for preparation of ketones 2-6, 8, and 11-14; characterization
data for ketones 2-6, 8, and 11-14, trans-stilbenes 16-19 and
21 and epoxides 15a-19a and 21a-26a; CI-MS and 13C NMR
spectra of 18O-labeled ketone (S)-2 and epoxide 15a; CD spectra
for assignment of absolute configurations of epoxides 15a-
21a; determination of enantiomeric excess of epoxide 19a; and
X-ray structural analysis of ketone (R)-3 containing tables of
atomic coordinates, thermal parameters, bond lengths, and angles
(33 pages, print/PDF). See any current masthead page for
ordering information and Web access instructions.
JA980428M