Cyclohexanones derived from dihydrocarvone as precursor of chiral dioxiranes for epoxidation of olefins

Article abstract of DOI:10.1016/j.tet.2004.09.089

New ketones having an axial α-fluorine atom and substituents other than fluorine at C8, derived from commercially available (+)-dihydrocarvone, have been prepared and used for epoxidations of trans stilbene, trans methyl p-methoxy cinnamate, trans cinnamyl alcohol and derivatives. It was found that replacement of the H at C8 by a substituent containing an oxygen atom increases the enantioselectivities in all cases. It was also shown that protic substituents (hydroxyl groups) provide a decrease in enantioselectivity in the case of cinnamates probably because of H-bonding dioxirane-substrate. It is noted that the absolute configurations of the various epoxides obtained hold with the usual model involving a spiro-approach on the dioxirane conformation C1 having the α-fluorine axial. Moreover, sub-stoichiometric amounts (0.3 equiv) of ketone can be used in all cases as these ketones do not undergo Baeyer-Villiger oxidation and are recovered. Graphical abstract.

Full text of DOI:10.1016/j.tet.2004.09.089

Tetrahedron 60 (2004) 11375–11381
Cyclohexanones derived from dihydrocarvone as precursor
of chiral dioxiranes for epoxidation of olefins
a,*
a
Arlette Solladi e´ -Cavallo, Lo ¨ı c Jierry, Paolo Lupattelli, Paolo Bovicelli
b
c
c
and Roberto Antonioletti
a
Laboratoire de St e´ r e´ ochimie Organom e´ tallique associ e´ au CNRS, ECPM/Universit e´ L. Pasteur, 25 rue Becquerel,
7087-Strasbourg, France
Dipartimento di Chimica, Universit a` degli studi della Basilicata, via N. Sauro 85, 85100 Potenza, Italy
6
b
c
CNR, Istituto di Chimica Biomolecolare, Sez. Roma c/o Dip. Chimica, Universit a` ‘La Sapienza’, P.le A. Moro 5, Roma, Italy
Received 1 July 2004; revised 17 September 2004; accepted 23 September 2004
Available online 8 October 2004
Abstract—New ketones having an axial a-fluorine atom and substituents other than fluorine at C8, derived from commercially available
C)-dihydrocarvone, have been prepared and used for epoxidations of trans stilbene, trans methyl p-methoxy cinnamate, trans cinnamyl
(
alcohol and derivatives. It was found that replacement of the H at C8 by a substituent containing an oxygen atom increases the
enantioselectivities in all cases. It was also shown that protic substituents (hydroxyl groups) provide a decrease in enantioselectivity in the
case of cinnamates probably because of H-bonding dioxirane-substrate. It is noted that the absolute configurations of the various epoxides
obtained hold with the usual model involving a spiro-approach on the dioxirane conformation C1 having the a-fluorine axial. Moreover,
sub-stoichiometric amounts (0.3 equiv) of ketone can be used in all cases as these ketones do not undergo Baeyer-Villiger oxidation and are
recovered.
q 2004 Elsevier Ltd. All rights reserved.
1. Introduction
Enantioselective oxygen transfer through dioxiranes
generated in situ from chiral ketones and oxone has
received, in recent years, greater attention for the asym-
1
,2
metric epoxidation of trans olefins and a significant
activating effect by a-fluorine substitution has been
observed.
3
–8
Among the enantiopure a-fluoro ketones involving a
six-membered ring 1–6
3
–8
designed for epoxidation of
trans olefins, the monocyclic ketone 6 is the most
efficient with stilbene. Moreover, compared to ketone 5,
ketone 6, due to the fluorine at the C8 position, led to
7
higher enantioselectivities with stilbene and methyl
p-methoxycinnamate.
Ketones 7–10, having an axial a-fluorine atom, but with
substituents other than fluorine at C8 have thus been
envisaged. We present here the synthesis of these ketones
from commercially available (C)-dihydrocarvone and their
Keywords: Chiral cyclohexanones; Fluoro ketones; Asymmetric epoxida-
tion; Chiral dioxiranes.
*
Corresponding author. Tel.: C33 3 90 24 27 72; fax: C33 3 90 24 27 06;
e-mail: cavallo@chimie.u-strasbg.fr
0040–4020/$ - see front matter q 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2004.09.089

11376
A. Solladi e´ -Cavallo et al. / Tetrahedron 60 (2004) 11375–11381
use for epoxidations of trans stilbene, methyl p-methoxy
cinnamate, trans cinnamyl alcohol and derivatives.
Scheme 2.
2
. Results and discussion
known, the absolute configurations were determined using
1
5
the sign of the optical rotations ([a]D measured under
identical conditions: same solvent, same concentration).
None of the ketones studied here underwent Baeyer-Villiger
oxidation. Used in sub-stoichiometric amounts (0.3 equiv)
they were recovered almost quantitatively after reaction
2
.1. Synthesis of ketones 7–10
All four ketones 7–10 were prepared from the common
intermediate 2-fluoro-5-isopropenyl-2-methylcyclohexanone
1
1 (Scheme 1), which was obtained from (C)-dihydro-
9
(through chromatography) and no lactones were detected by
NMR (400 MHz) of crude products in none of the reactions.
carvone, as previously described. The diastereomer
K)-(2S,5R)-11, having the a-fluorine atom axial according
to H NMR, was isolated pure after chromatography.
(
1
10
1
1
Conducted in dioxane/H O mixture at 25 8C, epoxidation of
2
From ketone 11, acid (H SO ) hydration afforded 7, while
2
4
1
epoxidation using dimethyldioxirane and dihydroxylation
2
trans stilbene 12 (Entries 1–4) and methyl p-methoxycin-
namate 13 (entries 5–9) went smoothly to completion and
the ee of the corresponding epoxides ranged between
82–88% (epoxide 17) and 26–66% (epoxide 18). In the case
of cinnamate 13 the enantioselectivities were slightly higher
but conversions significantly lower (entries 10 and 11) when
1
3
using OsO4
diastereomers mixtures, respectively (Scheme 1). Ketone
0 was then obtained from 9 via acidic protection in acetone
as a 1:1 diastereomers mixture). Separation of diastereo-
gave 8 and 9, as 57:43 and 65:35
1
(
mers of ketones 8 and 9 could not be performed by
chromatography, but it has been possible to isolate both
diastereomers of ketone 10 through repeated
chromatography.
the reaction was performed in DME/H O at 0 8C.
2
The epoxidation of cinnamyl alcohol and derivatives
performed in DME/CH CN/H O mixture at room tem-
perature) gave conversions from 80 to 99% with all ketones
(
3
2
2
.2. Epoxidation of olefins
and ee ranging between 60 and 75%.
The results of asymmetric epoxidation of stilbene 12,
methyl p-methoxy cinnamate 13, cinnamyl alcohol 14 and
derivatives 15, 16 (Scheme 2) with these ketones (7–10)
For substrates 12, 13 and 15, ketone 8 was more efficient
than the others with higher yields and enantioselectivities
(entries 2, 6 and 16). For substrates 14 and 16, the highest
enantioselectivities were achieved by ketone 10 (even used
as 1:1 diastereoisomeric mixture), with slightly higher
yields (entries 14 and 20). It must be noted that ketone 10 is
as efficient as ketone 8 in the case of substrate 15 (compare
entries 16 and 17).
1
4
are gathered in Table 1. The percentages of conversion have
been determined by combining weights and H NMR (300
1
and/or 400 MHz) of solvent-free crude products; then
epoxides were isolated by flash chromatography on silica
1
gel. The ees% were determined by H NMR using Eu(hfc)
3
in CDCl and optical rotations. All trans-epoxides being
3
Scheme 1.

Table 1. Epoxidation of trans stilbene 12, methyl p-methoxy cinnamate 13, cinnamyl alcohol 14 and derivatives 15, 16
a
b
c
d
Entry
Olefin
Ketone
Prod.
Solvent
React. time (h)
Conv. (%)
e.r. (%)
Absol. Config.
ee (%)
1
2
3
4
5
6
7
8
9
12
12
12
12
13
13
13
13
13
13
13
14
7
8
17
17
17
17
18
18
18
18
18
18
18
19
Diox/H
Diox/H
Diox/H
Diox/H
Diox/H
Diox/H
Diox/H
Diox/H
Diox/H
DME/H
DME/H
DME/CH
2
H O
DME/CH
H O
2
DME/CH
2
H O
DME/CH
2
H O
DME/CH
H O
2
DME/CH
2
O
O
O
O
O
O
O
O
O
4
4
2
3
6
6
6
6
6
8
8
1
100
100
100
100
100
100
100
100
100
50
92:8
94:6
93:7
91:9
63:37
83:17
77:33
80:20
80:20
84:16
83:17
80:20
(K)-(S,S)
(K)-(S,S)
(K)-(S,S)
(K)-(S,S)
(K)-(2R,3S)
(K)-(2R,3S)
(K)-(2R,3S)
(K)-(2R,3S)
(K)-(2R,3S)
(K)-(2R,3S)
(K)-(2R,3S)
(K)-(2S,3S)
84
88
86
82
26
66
44
60
60
68
66
60
2
2
2
2
2
2
2
2
9
10(ICII)
7
8
9
10I
10II
8
10(ICII)
e
1
1
1
0
1
2
2
O
O
e
2
53
85
5
3
3
3
3
3
3
3
3
3
CN/
CN/
CN/
CN/
CN/
CN/
CN/
CN/
CN/
1
1
1
1
1
1
1
2
3
4
5
6
7
8
9
0
14
14
15
15
15
16
16
16
8
19
19
20
20
20
21
21
21
1
1
1
1
1
1
1
1
90
99
80
80
99
95
95
99
80:20
88:12
80:20
82:18
82:18
80:20
82:18
88:12
(K)-(2S,3S)
(K)-(2S,3S)
(K)-(2S,3S)
(K)-(2S,3S)
(K)-(2S,3S)
(K)-(2S,3S)
(K)-(2S,3S)
(K)-(2S,3S)
60
75
60
65
65
60
65
75
e
10(ICII)
5
8
e
10(ICII)
2
H O
DME/CH
H O
2
DME/CH
H O
2
DME/CH
5
8
e
10(ICII)
2
H O
a
b
c
d
e
Diox/H
2
O 2:1 (3 equiv of Oxone), rt; DME/H
1
2
O 2:1 (1.4 equiv of Oxone), 0 8C; DME/CH
Determined by H NMR (300 and/or 400 MHz) on the crude products of the reactions.
3
2
CN/H O 1:1:1 (3 equiv of Oxone), rt.
1
Enantiomeric ratios have been determined by H NMR (400 MHz) using Eu(hfc)
Absolute configurations have been determined from the sign of specific rotation as compared with literature results (cf. Ref. 15).
:1 Diastereoisomeric mixture.
3 3
in CDCl : the precision is G2%.
1

11378
A. Solladi e´ -Cavallo et al. / Tetrahedron 60 (2004) 11375–11381
Figure 1.
It is worth noting that, under identical conditions,
diastereomers 10I and 10II provided identical results for
epoxidation of methyl p-methoxycinnamate (entries 8
and 9). Therefore, it seems that the chiral center C8, being
remote from the reacting dioxirane site, has no effect on the
asymmetric induction of epoxidation and one can extrapo-
late that it will be such also in the cases of ketones 8 and 9.
decrease in enantioselectivity (26 and 44% ee compared to
60–66% ee) with methyl cinnamate 13. And, according to
previous results, which had led to the conclusion that axial
8
approaches contributed to the reactions, one can envisaged
that, because of possible formation of H-bond, Figure 1,
0
between the olefin and the dioxirane, approach AII ,
Figure 2, is less disfavored than with aprotic substituents
and will provide larger amount of the epoxide of opposite
configuration.
Replacement of the H at C8 by a substituent containing an
oxygen atom (ketones 7–10) increases the enantioselectiv-
ities in the case of epoxidation of stilbene: compare the
Replacement of the H at C8 by a substituent containing an
oxygen atom (ketones 8 and 10) also increases the
enantioselectivities in the case of epoxidation of cinnamyl
alcohol (14) and derivatives (15 and 16): compare the 60%
ee obtained with 5 to the 65–75% obtained with 8 and 10.
8
2–88% ee (Table 1, lines 1–4) with the 60% ee obtained
with ketone 5. However, a fluorine atom at this C8 position
ketone 6) remains the most efficient one, with 90% ee.
(
The same trend holds for epoxidation of methyl
p-methoxycinnamate with ketones 8 and 10 (entries 6, 8
and 9), compare the 66 and 60% ee with the 40% ee
observed with unsubstituted ketone 5. Moreover, in this
case, ketone 8 provides higher enantioselectivities (66% ee)
than ketone 6 (60% ee).
3. Conclusion
It is thus clear that substitution at C8 (on the isopropyl group
located at C5), even with substituent different from
halogens, has a significant influence on the enantioselec-
tivity of epoxidation of trans olefins which has also been
However, protic substituents (ketones 7 and 9) provide a
1
1
Figure 2. Epoxidation of trans-cinnamate (R ZCO
chiral cyclohexanones 7–10.
2
Me) and trans cinnamyl derivatives (R ZCH
2
OH, CH OAc, CH
2
2
OSiTBDM) by dioxiranes derived from

A. Solladi e´ -Cavallo et al. / Tetrahedron 60 (2004) 11375–11381
11379
1
6
13
1H), 0.80 (s, 3H, Me), 0.79 (s, 3H, Me). C NMR
observed by Yang et al. with a-chloro cyclohexanones. It
appears also that the absolute configuration of the new chiral
center formed (C8) has no effect on the enantioselectivity.
However, protic substituents at C8 are not suitable for
epoxidation of cinnamate esters (probably because of
unfavorable H-bond during the reagents approaches, Fig. 1).
2
(100 MHz C D ) d 206.6 (d, JCFZ25 Hz), 95.2
6
6
1
3
(d, JCFZ172 Hz), 71.2, 50.7, 39.9 (d, JCFZ3 Hz),
38.3 (d, J Z23 Hz), 27.2, 26.8, 21.8 (d, JCFZ2 Hz),
20.2 (d, JCFZ24 Hz).
2
3
CF
2
4.1.2. (2S,5R)-2-Fluoro-2-methyl-5-(2-methyl-oxiranyl)-
It is worth noting that the absolute configurations of the
various epoxides obtained hold with the model (Fig. 2)
and
cyclohexanone 8. To a solution of 11 (144 mg,
0.847 mmol) in acetone (2 mL), under stirring, at 0 8C,
0.08 M dimethyldioxirane solution in acetone (20 mL,
16 mmol) was added. Upon stirring to completion, as
judged by TLC (about 1 h 30 min), the reaction mixture was
concentrated. Water was added and the crude extracted with
CH Cl . The organic phase was dried over Na SO , filtered
1
7
involving the spiro Model and both equatorial
18–20
8
axial approaches.
Considering the configuration of ketones 7–10 and using
both equatorial and axial approaches on the more reactive
2
1
2
2
2
4
22
and more populated conformation C1 of the dioxiranes
having the a-fluorine atom axial one could expect the
enantiomers (K)-(S,S)-17, (K)-(2R,3S)-18, (K)-(2S,3S)-
and concentrated, to give 8 as colorless oil (149 mg, 95%);
57:43 mixture of diastereomer 8I and 8II. Anal. calcd for
C H FO : C, 64.49; H, 8.11. Found: C, 64.10; H, 8.02. IR:
1
0
15
2
1
1
which is indeed observed (Table 1). Equatorial E-II (and/or
9, (K)-(2S,3S)-20 and (K)-(2S,3S)-21 to be obtained
3050, 1727, 1458; H NMR (400 MHz C D ) d 2.57 (td, JZ
6 6
JZ12.5 Hz, JZ6.0 Hz, 1H, 8I, 57%), 2.51 (td, JZJZ
13 Hz, JZ6.0 Hz, 1H, 8II, 43%), 2.34 (bd, JZ12.5 Hz, 1H,
8I, 57%), 2.20 (bd, JZ13.0 Hz, 1H, 8II, 43%), 2.11 (d, JZ
5.0 Hz, 1H, 8I, 57%), 2.07 (d, JZ4.5 Hz, 1H, 8II, 43%),
2.02 (d, JZ5.0 Hz, 1H, 8I, 57%), 2.01 (d, JZ4.5 Hz, 1H,
8II, 43%), 1.79 (m, 2H, 8I and 8II overlapped), 1.63 (qd,
JZJZJZ12.5 Hz, JZ3.5 Hz, 1H, 8II, 43%), 1.54 (qd, JZ
JZJZ13.0 Hz, JZ4.0 Hz, 1H, 8I, 57%), 1.29 (d, JZ
0
phenyl is expected to be favored over the E-I (and/or E-I )
E-II ) approach with no n$p repulsion between F and the
0
approach, which involves such a n$p repulsion. Similarly,
in the case of axial approaches A-I (and/or A-I ) which
0
involves no R$Ph repulsive interaction is favored over
A-II (and/or A-II ). And E-II, E-II , A-I and A-I provides
1
6
0
the same epoxide enantiomer.
0
0
2
2.5 Hz, 3H, 8I, 57%), 1.54 (d, JZ22.0 Hz, 3H, 8II, 43%),
.26 (m, 2H, 8II, 43%), 1.17 (m, 2H, 8I, 57%), 1.00 (m, 1H,
1
8II, 43%), 0.90 (m, 1H, 8I, 57%), 0.86 (s, 6H, 8I and 8II
4
. Experimental
1
3
overlapped); C NMR (100 MHz C D ) signals of both
6
6
4
.1. General
diastereomers not assigned d 205.3 (d, JZ25.5 Hz), 205.1
d, JZ25.5 Hz), 95.6 (d, JZ172.3 Hz), 95.5 (d, JZ
173.1 Hz), 57.6, 57.5, 52.2, 52.5, 45.9, 45.5, 40.8 (d, JZ
36 Hz), 40.7 (d, JZ36 Hz), 37.9 (d, JZ6.5 Hz), 37.8 (d,
JZ6.5 Hz), 22.8 (d, JZ1.5 Hz), 22.7 (d, JZ1.5 Hz), 20.3
(d, JZ24 Hz), 20.1 (d, JZ24 Hz), 18.1, 17.6. MS (m/z %)
178 (2), 153 (4), 130 (4), 109 (19), 99 (2), 75 (19), 48 (100).
(
1
13
H and C NMR spectra were recorded on a Bruker AC 300
and Avance 400 spectrometers with CDCl or C D as
3
6 6
solvents. Chemical shifts (d) are given in ppm downfield
from TMS as an internal standard. Optical rotation were
determined on a Perkin–Elmer 241 MC polarimeter. TLC
was performed on Merck’s glass plates with silica gel 60
F254. Silica gel Si 60 (40–60 mm) from Merck was used for
the chromatographic purifications and a Chiralcel OD
column was used for ee determination of epoxides.
4.1.3. (2S,5R)-5-(1,2-Dihydroxy-1-methyl-ethyl)-2-
fluoro-2-methyl-cyclohexanone 9. To a solution of 11
(100 mg, 0.59 mmol), in 9 mL of a mixture H O/acetone
2
(C)-Dihydrocarvone (99% R-configured) was purchased
from Fluka.
1:8, were added N-methylmorpholine N-oxide (138 mg,
1.18 mmol) and a solution of OsO in t-butanol (0.05 equiv
4
in 1.5 mL).Upon stirring at room temperature to completion
as judged by TLC (about 2 h) the reaction mixture was
quenched with a saturated solution of NaHSO . After
4
.1.1. (2S,5R)-2-Fluoro-5-(1-hydroxy-1-methyl-ethyl)-2-
methyl-cyclohexanone 7. To ketone 11 (200 mg,
.17 mmol) was added dropwise, at K5 to 0 8C, a solution
of H SO (0.75 mL) in distilled H O (2.25 mL). Stirring
3
1
10 min the mixture was extracted with EtOAc, filtered,
concentrated and purified by flash chromatography to give
the diol 9 as a colorless oil (105 mg, 95%). The ratio of
diastereomer was determined by NMR as 9I/9IIZ65:35.
Anal. calcd for C H FO : C, 58.80; H, 8.38. Found: C,
2
4
2
was maintained for one night at 0 8C (the temperature must
not rise above 0 8C). The reaction mixture was then
extracted four times with Et O (10 mL) and four times
with CH Cl (10 mL). The joined organic phases were
2
washed with a saturated NaHCO3 solution, dried over
Na SO , filtered and concentrated. A chromatographic
2
10 17
3
1
58.12; H, 8.03. IR: 3445, 2985, 1726, 1408; H NMR
(400 MHz C D ) d 3.35 (d, JZ11 Hz, 1H, 9II, 35%), 3.32
2
6
6
(d, JZ11 Hz, 1H, 9I, 65%), 3.25 (d, JZ11 Hz, 1H, 9I,
65%), 3.19 (d, JZ11 Hz, 1H, 9I, 65%), 3.13 (bs, 1H, 9II,
35%), 3.05 (bs, 1H, 9I, 65%), 2.98 (bs, 1H, 9II, 35%), 2.86
(bs, 1H, 9I, 65%), 2.77 (td, JZJZ12.5 Hz, JZ6.5 Hz, 1H,
9II, 35%), 2.64 (bd, JZ12.5 Hz, 1H, 9II, 35%), 2.61 (td,
JZJZ13.0 Hz, JZ6.5 Hz, 1H, 9I, 65%), 2.37 (bd, JZ
13.0 Hz, 1H, 9I, 65%), 1.87 (m, 6H, 9I and 9II overlapped),
1.60 (m, 2H, 9I and 9II overlapped), 1.34 (d, JZ22 Hz, 9II,
35%), 1.33 (d, JZ22 Hz, 9I, 65%), 1.20 (m, 2H, 9I and 9II
2
4
purification over silica gel (hexane/Et OZ4:6 to 1:9)
2
provide 116 mg of ketone 7 as a white solid (54% yield).
F. 36 8C. Anal. calcd for C H FO : C, 63.80; H, 9.10.
1
0
17
2
1
Found: C, 63.42; H, 9.22. H NMR (400 MHz C D ) d 2.58
6
6
(
td, JZJZ12 Hz, JHFZ6 Hz, 1H), 2.42 (broad d, JZ12 Hz,
2
1
2
1
0
H), 1.88 (dddd, JZ15 Hz, J Z10 Hz, JZ4.5 Hz, JZ
HF
2 3 3 3
Hz, 1H), 1.48 (qd, JZ JZ JZ13.5 Hz, JZ5 Hz, 1H),
.35 (d, JHFZ22 Hz, 3H, Me), 1.28 (m, 1H), 1.11 (m, 1H),
2
13
.99 (dddd, JZ15 Hz, JHFZ40 Hz, JZ10 Hz, JZ3 Hz,
overlapped); C NMR (100 MHz C D ) signals of both
6
6

11380
A. Solladi e´ -Cavallo et al. / Tetrahedron 60 (2004) 11375–11381
diastereomers not assigned d 207.8 (d, JZ25 Hz), 207.1 (d,
JZ25 Hz), 95.8 (d, JZ173 Hz), 95.6 (d, JZ173 Hz), 74.1,
distilled water (3.5 mL) is added dropwise over 8 h. During
addition of oxone, the pH is controlled and regulated (8.5–9)
by addition of 1.4 M solution of K CO . The reaction is
7
2
2
4.0, 68.5, 68.0, 46.4, 46.1, 40.3 (d, JZ2.5 Hz), 39.1 (d, JZ
.5 Hz), 38.6, 38.3, 22.3 (d, JZ2.5 Hz), 21.1 (d, JZ2.5 Hz),
0.3 (d, JZ24 Hz), 20.1 (d, JZ24 Hz), 20.2, 19.8. MS (m/z
2
3
quenched by addition of CH Cl (30 mL) and water
2
2
(10 mL). The mixture is extracted with CH Cl , dried
2
2
%
(
) 179 (4), 158 (17), 130 (10), 109 (42), 81 (12), 75 (31), 48
100).
over Na SO , and analysed by NMR.
2 4
In DME/CH CN/water. To a solution of 0.5 mmol of the
3
4
.1.4.
(2S,5R)-2-Fluoro-2-methyl-5-[(4R)-2,2,4-tri-
desired olefin and 0.15 mmol of the ketone in DME (6 mL)
methyl11,3-dioxolan-4-yl]cyclohexanone 10. To a
solution of 9 (381 mg, 2.016 mmol) in acetone (previously
distilled on K CO ) was added pTsOH (20 mg,
under stirring, a solution (7.5 mL) of a 0.05 M Na
buffer, 0.5 mL of tetrabutyl ammonium hydrogensulfate and
6 mL of CH CN are added. A solution of oxone (1.5 mmol)
2 4 7
B O
2
3
3
0
.105 mmol). Upon stirring under argon for 4 days at
in distilled water (4 mL) is added dropwise within 1 h to the
mixture at room temperature. During the addition of oxone,
the pH is controlled and regulated (8.5–9.0) by addition of a
room temperature, NEt3 (0.015 mL, 0.105 mmol) was
added. The reaction mixture was concentrated and purified
by flash chromatography (treated with 1% NEt ) to give
ketone 10 (440 mg, 95%) as a colorless oil in a 50:50 ratio of
diastereomers 10I/10II. Anal. calcd for C H FO : C,
1 M solution of K
addition of Et O (40 mL) and water (10 mL). After
extraction with CH Cl , the mixture is dried over Na SO
and analysed by NMR.
CO . The reaction is quenched by
3
2 3
2
1
3
21
3
2
2
2
4
63.91; H, 8.66. Found: C, 63.13; H, 8.11. Each diastereo-
mers was separated by repeated silica gel chromatography
2
0
(
hexane 9/ethyl acetate 1) 10I: [a] ZK0.5 (cZ4.15,
D
1
CHCl ); IR: 2990, 1727, 1269, 1239; H NMR (400 MHz
3
C D ) d 3.45 (d, JZ9.0 Hz, 1H), 3.28 (d, JZ9.0 Hz, 1H),
6
6
2
.53 (dt, JZJZ13.0 Hz, JZ6.5 Hz, 1H), 2.15 (bd, JZ
References and notes
1
3.0 Hz, 1H), 1.87 (m, 1H), 1.60 (m, 3H), 1.34 (s, 3H), 1.28
(
s, 3H), 1.26 (d, JZ22.0 Hz, 3H), 1.01 (m, 1H), 0.93 (s, 3H);
1. (a) Denmark, S. E.; Wu, Z. Synlett 1999, 847 and references
cited herein. (b) Frohn, M.; Shi, Y. Synthesis 2000, 1979 and
references cited herein. (c) Adam, W.; Saha-M o¨ ller, R.;
Ganeshpure, P. A. Chem. Rev. 2001, 101, 3499 and references
cited herein.
1
3
C NMR (100 MHz C D ) d 205.5 (d, JZ25 Hz), 109.4,
6
6
9
3
2
5.3 (d, JZ172.5 Hz), 82.2, 72.8, 48.2, 40.6 (d, JZ2.5 Hz),
8.2 (d, JZ23 Hz), 27.2 (d, JZ9.5 Hz), 21.9 (d, JZ
2
0
4.5 Hz), 21.6, 20.3, 20.1; 10II: [a] ZK2.8 (cZ3.40,
D
1
CHCl ); IR: 2990, 1727, 1269, 1239; H NMR (400 MHz
C D ) d 3.47 (d, JZ8.5 Hz, 1H), 3.32 (d, JZ8.5 Hz, 1H),
2
2. For references concerning asymmetric epoxidation of
cinnamates esters using dioxiranes, see also: (a) Seki, M.;
Furutani, T.; Imashiro, R.; Kuroda, T.; Yamanaka, T.; Harada,
N.; Arakawa, H.; Kusama, M.; Hashiyama, T. Tetrahedron
Lett. 2001, 42, 8201. (b) Wu, X.-Y.; She, X.; Shi, Y. J. Am.
Chem. Soc. 2002, 124, 8792.
3
6
6
.63 (m, 2H), 1.82 (m, 1H), 1.55 (m, 2H), 1.31 (d, JZ
2.5 Hz, 3H), 1.29 (s, 3H), 1.24 (s, 3H), 1.00 (m, 3H), 0.92
2
1
3
(
(
s, 3H), 0.89 (m, 1H); C NMR (100 MHz C D ) d 205.9
6 6
d, JZ25 Hz), 109.6, 95.7 (d, JZ173.5 Hz), 82.1, 72.9,
4
2
8.2, 39.8 (d, JZ2.5 Hz), 38.1 (d, JZ23 Hz), 27.5, 27.4,
2.7 (d, JZ31.5 Hz), 21.5, 20.2 (d, JZ31.5 Hz).
3. Denmark, S. E.; Wu, Z.; Crudden, M. C.; Matsuhashi, H.
J. Org. Chem. 1997, 62, 8288.
4
. Armstrong, A.; Hayter, B. Chem. Commun. 1998, 621.
4
.2. General procedure for the epoxidation of stilbene,
methyl p-methoxycinnamate and cinnamyl alcohol
5. (a) Armstrong, A.; Hayter, B.; Moss, W. O.; Reeves, J. R.;
Wailes, J. S. Tetrahedron: Asymmetry 2000, 11, 2057. (b) Klein,
S.; Roberts, S. M. J. Chem. Soc., Perkin Trans. 1 2002, 2686.
derivatives
6
. Tu, Y.; Wang, Z.-X.; Frohn, M.; He, M.; Yu, H.; Tang, Y.; Shi,
Y. J. Org. Chem. 1998, 63, 8475.
In dioxane/water. To a solution of 1 mmol of the desired
olefin and 0.3 mmol of the desired ketone in dioxane
7. Solladi e´ -Cavallo, A.; Bou e´ rat, L. Org. Lett. 2000, 2, 3531.
8. Solladi e´ -Cavallo, A.; Bou e´ rat, L.; Jierry, L. Eur. J. Org. Chem.
2001, 4557.
(
(
20 mL) are added successively and under stirring a solution
4 mL) of a buffer (made from addition of 0.5 mL of AcOH
in 100 mL of an aqueous solution of K CO , 0.1 M), and
2
then 6 mL of H O. The mixture is cooled to the desired
2
9. Solladi e´ -Cavallo, A.; Jierry, L.; Bou e´ rat, L.; Taillasson, P.
Tetrahedron: Asymmetry 2001, 12, 883.
3
temperature, and a solution of oxone (1.850 g, 3 mmol) in
distilled water (7 mL) is added dropwise over 6 h. During
addition of oxone, the pH is controlled and regulated (8.5–9)
by addition of a 1 M solution of K CO . The reaction is
10. Solladi e´ -Cavallo, A.; Jierry, L.; Bou e´ rat, L.; Schmitt, M.
Tetrahedron 2002, 58, 4195.
11. B u¨ chi, G.; W u¨ est, H. J. Org. Chem. 1979, 44, 546.
12. Adam, W.; Bialas, J.; Hadjiarapoglou, L. Chem. Ber. 1991,
124, 2377.
2
3
quenched by addition of CH Cl (30 mL) and water
2
2
(
over Na SO , and analysed by NMR.
10 mL). The mixture is extracted with CH Cl , dried
2
13. Van Rheenen, V.; Kelly, R. C.; Cha, D. Y. Tetrahedron Lett.
1976, 23, 1973.
2
2
4
1
4. For recent results on asymmetric oxidation of silyl enol ethers
using such a-fluoro cyclohexanones see: Solladi e´ -Cavallo, A.;
Lupattelli, P.; Jierry, L.; Bovicelli, P.; Angeli, F.; Antonioletti,
R.; Klein, A. Tetrahedron Lett. 2003, 44, 6523.
In DME/water. To a solution of 1 mmol of the desired olefin
and 0.3 mmol of the desired ketone in DME (10 mL) is
added under stirring a solution (6 mL) of a buffer (made
from addition of 0.5 mL of AcOH in 100 mL of an aqueous
solution of K CO , 0.1 M). The mixture is cooled to the
15. For assignment of the (K)-(S,S) configuration of the stilbene
oxide 17, see: Imuta, M.; Ziffer, H. J. Org. Chem. 1979, 44,
2505. For the assignment of (K)-(2R,3S) configuration to the
2
3
desired temperature, and a solution of oxone (1.4 mmol) in

A. Solladi e´ -Cavallo et al. / Tetrahedron 60 (2004) 11375–11381
11381
methyl p-methoxycinnamate epoxide 18, see: Matsuki, K.;
Sobukawa, M.; Kawai, A.; Inoue, H.; Takeda, M. Chem.
Pharm. Bull. 1993, 41, 643.For the assignment of (K)-(2S,3S)
configuration-3-phenylglycidol acetate 20, commercial
17. Baumstark, A. L.; McKloskey, C. J. Tetrahedron Lett. 1987,
28, 3311.
18. Yang, D.; Wang, X. C.; Wong, M. K.; Yip, Y. C.; Tang, M. W.
J. Am. Chem. Soc. 1996, 118, 11311.
(
K)-(2S,3S)-3-phenylglycidol has been acetylated (Ac
Pyr) and compared with 20.For the assignment of
K)-(2S,3S)-3-phenylglycidyl tert-butyldimethyl ether 21, it
2
O/
19. Adam, W.; Paredes, R.; Smerz, A. K.; Veloza, L. A. Liebigs
Ann. 1997, 547.
(
20. Jenson, C.; Liu, J.; Houk, K. N.; Jorgensen, W. L. J. Am.
Chem. Soc. 1997, 119, 12982.
has been desylilated (with CsF) and compared with
commercial (K)-(2S,3S)-3-phenylglycidol.
6. For type 6 ketones having an a-chlorine atom and for effect of
substitution at the isopropyl group see: Yang, D.; Yip, Y.-C.;
Chen, J.; Cheung, K.-K. J. Am. Chem. Soc. 1998, 120, 7659.
21. Armstrong, A.; Washington, I.; Houk, K. N. J. Am. Chem. Soc.
2000, 122, 6297.
22. Solladi e´ -Cavallo, A.; Jierry, L.; Norrousi-Arasi, H.;
Tahmassebi, D. J. Fluorine Chem. 2004, 125(9), 1371.
1