A Domino Ring-Opening/Epoxidation of 1,2-Dioxines

Article abstract of DOI:10.1021/jo0303315

When allowed to react with alkaline hydrogen peroxide, monocyclic 1,2-dioxines ring-open to their isomeric γ-hydroxyenone intermediates which are rapidly epoxidized to afford trans-4-hydroxy-2,3-epoxyketones in 21-81% yield. In the case of meso-1,2-dioxin

Full text of DOI:10.1021/jo0303315

SCHEME 1
A Dom in o Rin g-Op en in g/Ep oxid a tion of
1,2-Dioxin es
Ben W. Greatrex,† Dennis K. Taylor,*,† and
Edward R. T. Tiekink‡
Department of Chemistry, University of Adelaide, South
Australia 5005, Australia, and Department of Chemistry,
National University of Singapore, Singapore 117543
dennis.taylor@adelaide.edu.au
Received October 28, 2003
Abstr a ct: When allowed to react with alkaline hydrogen
peroxide, monocyclic 1,2-dioxines ring-open to their isomeric
γ-hydroxyenone intermediates which are rapidly epoxidized
to afford trans-4-hydroxy-2,3-epoxyketones in 21-81% yield.
In the case of meso-1,2-dioxines, Co(II) complex catalyzed
asymmetric ring-opening of the 1,2-dioxine may be employed
to furnish enantioenriched epoxides
TABLE 1. Rea ction of 1,2-Dioxin es w ith Hyd r ogen
P er oxid e a n d Ba se
entrya dioxine solvent base time (h) yieldb (%) ratioc of 3/4
1
2
3
4
5
6
7
8
9
1a
1a
1a
1a
1b
1c
1c
1d
1e
1e
1f
CH2Cl2 LiOH
THF LiOH
MeOH LiOH
16
16
0.5
16
3
72
16
16
48
78
81
79
d
75
64
d
70
73
76
72
21
60:40
64:36
49:51
46:54
57:43
65:35
60:40
57:43
THF
THF
THF
KOH
LiOH
LiOH
1,2-Dioxines 1 undergo a base catalyzed rearrangement
to cis-γ-hydroxyenones 2 known as the Kornblum/
DeLaMare rearrangement in the presence of bases such
as triethylamine, lithium hydroxide, and phosphorus
ylides.1-5 Nucleophiles capture these sensitive γ-hydroxy-
enones stereospecifically allowing for the synthesis of a
range of organic functionalities including tetrahydro-
furans, γ-lactones, and cyclopropanes.2,5-7 We have also
developed a procedure for the asymmetric ring-opening
of meso-1,2-dioxines, and our interest now lies in broad-
ening the scope of nucleophiles that can add to these
γ-hydroxyenones.8
MeOH LiOH
THFe
THF
LiOH
LiOH
10
11
12
MeOH LiOH
MeOH LiOH
MeOH LiOH
0.5
1
16
1g
a
Reactions were conducted at ambient temperature with 1.0
b
equiv of base and 4.0 equiv of hydrogen peroxide. Refers to
combined isolated yield. c Ratio determined by 1H NMR on the
crude reaction mixture. Yield not determined. e 7:1 mixture of
d
THF/MeOH employed as solvent.
Weakly basic nucleophiles that can rearrange the 1,2-
dioxine and then undergo proton exchange with the
γ-hydroxyenone are ideal reagents for reactions with 1,2-
dioxines as they allow for one-pot ring-opening/nucleo-
philic addition reactions. This is highly desirable as the
acyclic γ-hydroxyenone motif is unstable as it can dehy-
drate to furan9-12 or rearrange to 1,4-diketone5,13 under
acidic or basic conditions, respectively. The hydrogen
peroxide anion is a reagent that falls into this category
of nucleophile and when allowed to react with R,â-
unsaturated ketones gives R,â-epoxyketones by a nucleo-
philic addition/SN2 displacement sequence.14-17 The re-
action of 1,2-dioxines with alkaline hydrogen peroxide
was therefore hypothesized to give 4-hydroxy-2,3-ep-
oxyketones by a two-step ring-opening/epoxidation one-
pot reaction. We have recently synthesized a range of
compounds containing this functionality and it was of
interest to compare the stereoselectivity that would result
from this approach with our earlier procedure.18
1,2-Dioxines 1a -f were prepared by the Rose Bengal
sensitized addition of singlet oxygen to the corresponding
1,3-butadienes.19,20 When 1,2-dioxines 1a -f were allowed
to react with alkaline hydrogen peroxide, smooth trans-
formation of the 1,2-dioxine into the trans-substituted
epoxides 3 and 4 was observed, Scheme 1 and Table 1.
An excess of hydrogen peroxide was employed to suppress
dimerization of the γ-hydroxyenone which occurs in the
† University of Adelaide, Australia.
‡ National University of Singapore.
(1) Kornblum, N.; DeLaMare, H. E. J . Am. Chem. Soc. 1951, 73,
880.
(2) Greatrex, B. W.; Kimber, M. C.; Taylor, D. K.; Tiekink, E. R. T.
J . Org. Chem. 2003, 68, 4239.
(3) Zagorski, M. G.; Saloman, R. G. J . Am. Chem. Soc. 1980, 102,
2501.
(4) Akbulut, N.; Balci, M. J . Org. Chem. 1988, 53, 3338.
(5) Avery, T. D.; Taylor, D. K.; Tiekink, E. R. T. J . Org. Chem. 2000,
65, 5531.
(6) Avery, T. D.; Fallon, G.; Greatrex, B. W.; Pyke, S. M.; Taylor, D.
K.; Tiekink, E. R. T. J . Org. Chem. 2001, 66, 7955.
(7) Greatrex, B. W.; Kimber, M. C.; Taylor, D. K.; Fallon, G.; Tiekink,
E. R. T. J . Org. Chem. 2002, 67, 5307.
(8) Avery, T. D.; J enkins, N. F.; Kimber, M. C.; Lupton, D. W.;
Taylor, D. K. Chem. Commun. 2002, 28.
(14) Bailey, M.; Marko´, I. E.; Ollis, W. D.; Rasmussen, P. R.
Tetrahedron Lett. 1990, 31, 4509.
(15) Bailey, M.; Marko´, I. E.; Ollis, W. D. Tetrahedron Lett. 1991,
32, 2687.
(16) Castedo, L.; Mascaren˜as, J . L.; Mourin˜o, A. Tetrahedron Lett.
1987, 28, 2099.
(9) Nguyen, V.; Hishino, H.; Kurosawa, K. Synthesis 1997, 899.
(10) Sammond, D. M.; Sammakia, T. Tetrahedron Lett. 1996, 37,
6065.
(11) Nishio, T.; Omote, Y. Chem. Lett. 1976, 103.
(12) Suzuki, M.; Ohtake, H.; Kameya, Y.; Hamanaka, N.; Noyori,
R. J . Org. Chem. 1990, 54, 3475.
(17) Allen, J . V.; Bergeron, S.; Griffiths, M. G.; Mukherjee, S.;
Roberts, S. M.; Williamson, N. M.; Wu, W. J . Chem. Soc., Perkin Trans.
1 1998, 3171.
(18) Greatrex, B. W.; J enkins, N. F.; Taylor, D. K.; Tiekink, E. R.
T. J . Org. Chem. 2003, 68, 5205.
(19) Hewton, C. E.; Kimber, M. C.; Taylor, D. K. Tetrahedron Lett.
2002, 43, 3199.
(20) Clennan, E. L. Tetrahedron 1991, 47, 1343.
(13) Sengul, M. E.; Ceylan, Z.; Balci, M. Tetrahedron 1997, 53,
10401.
10.1021/jo0303315 CCC: $27.50 © 2004 American Chemical Society
Published on Web 02/28/2004
2580
J . Org. Chem. 2004, 69, 2580-2583

presence of hydroxide and alkoxide bases.2 Initially, the
reaction was quenched with the addition of thiosulfate
solution; however, the manganese dioxide catalyzed
decomposition of the excess hydrogen peroxide gave
greater yields of the epoxidation products.
SCHEME 2
The reaction afforded two products from 3,6-disubsti-
tuted-1,2-dioxines 1a -d and only a single product from
3-substituted 1,2-dioxines 1e,f. The reaction was slightly
more selective for 3 in THF than methanol; however, a
greater rate of reaction was seen in methanol attributed
to a faster ring-opening of the parent 1,2-dioxine. The
products 3 and 4 were assigned as having trans-geometry
about the epoxide ring based upon a ∼2 Hz coupling
constant between protons on the ring. The X-ray crystal
structure obtained for 3a was used to determine the
stereochemistry of the hydroxyl center for 3a and 4a and,
with the X-ray structure of 3e,21 further confirmed the
trans-assignment for the epoxide. A conserved 4J coupling
of ∼0.5 Hz was seen between protons on C2 and C4 for
3a -d and together with the X-ray structure obtained for
3a was the basis for the stereochemical assignment of
the C4 hydroxyl center. The separation of the isomers
3c and 4c was more readily achieved by chromatography
after acetylation of the hydroxyl group and consequently
were characterized as the acetates.
TABLE 2. Ep oxid a tion Rea ction s of Op tica lly En r ich ed
tr a n s-En on e 8a P r ep a r ed fr om 1,2-Dioxin e, Co(II)
Ca ta lyst, a n d Tr ip h en ylp h osp h in e
ratio (R/S)c
entrya
catalyst
yieldb (%)
3a
4a
1
2
7a
7b
69
58
44 (86:14)
40 (14:86)
56 (88:12)
60 (15:85)
The reaction regioselectivity was directed by the acidity
of the protons at the 3- and 6-position of the 1,2-dioxine.
The presence of an aromatic ring at the 3-position
significantly increased the acidity of the C3-proton and
directed the rearrangement of the 1,2-dioxine. p-Bromo
substitution on the aromatic ring of 1b sufficiently
increased the acidity of the C3-proton and gave only
products from the collapse of the 1,2-dioxine initiated by
removal of the C3-proton. It was envisaged that the ring-
opening/epoxidation could also be applied to 1,2-dioxines
that did not contain a group directing the removal of the
3- or 6-substituted proton in the 1,2-dioxine. For example,
exposure of cyclohexyl substituted 1g to the reaction
conditions gave a mixture of products including several
aldehydes; however, the major component was still 3g.
There appeared to be little facial selectivity in the
addition of hydrogen peroxide anion to the γ-hydroxy-
enone and thus both isomers 3 and 4 were formed in the
reaction. The use of a more bulky peroxide nucleophile
to increase the observed diastereoselectivity did not
afford high yields of epoxide. The reaction of 1a with
TBHP/LiOH resulted in significant 1,4-diketone forma-
tion via base induced rearrangement of the cis-γ-hy-
droxyenone.13,19 The low selectivity seen in the reaction
can be rationalized when the ability of the γ-hydroxy-
enone to undergo cis/trans isomerization is considered.
After initial rearrangement of the 1,2-dioxine, the cis-γ-
hydroxyenone is formed exclusively. Under basic condi-
tions or in the presence of nucleophiles such as triphen-
ylphosphine, equilibrium is established between the cis-
and trans-γ-hydroxyenones, Scheme 2.2,5 The hydrogen
peroxide anion can presumably add to either the cis or
trans enone, both of which can afford 3 or 4.
a
Reactions were performed on a 1 mmol scale in THF (5 mL)
b
at ambient temperature. Combined isolated yield based upon
amount of starting 1,2-dioxine. c Enantiomeric ratio measured by
converting to the Mosher ester derivative (DCC/Mosher acid/
DMAP) and integrating peak height in the crude 1H NMR. R and
S refer to the stereochemistry of the C4 hydroxyl center. Assign-
ment of the absolute stereochemistry is based on the previously
observed selectivity; see ref 7.
for the asymmetric ring-opening of 1a to give the optically
enriched cis-enone which was converted to the trans-
isomer 8a by isomerization with triphenylphosphine,
Scheme 2.8
The reaction of 8a with hydrogen peroxide gave both
3a and 4a ; however, the reaction from the trans-enone
8a was more selective for 4a than when starting from
1,2-dioxine (cis-enone), compare Tables 1 and 2. There-
fore, the opposing selectivity observed for the epoxidation
in the cis and trans isomers may be responsible for the
low diastereoselectivity seen in the reactions of 1,2-
dioxines.
The ee’s for both the epoxidic products 3a and 4a were
determined by conversion of the alcohol to the Moshers
ester derivative and measuring the de by 1H NMR. Both
isomers had ee’s within 5% of one another as was
expected. The magnitude of the ee’s obtained from 1a
utilizing catalysts 7a and 7b are in agreement with those
found for other reactions of 1,2-dioxines catalyzed by 7a
and 7b; however, this represents the first reported use
of catalyst 7 for the asymmetric synthesis of a trans-γ-
hydroxyenone.5,8
The ring-opening/epoxidation reaction described is an
efficient route to trans-epoxides such as 3 and 4. It is a
useful adjunct to our previously described methodology
for the synthesis of 4-hydroxy-2,3-epoxy ketones as the
products have opposite stereochemistry about the epoxide
ring.
To elucidate the stereoselectivity of the reaction when
starting from the trans-enone, compound 8a was syn-
thesized. Use of chiral Co(II) catalyst 7a and 7b allowed
(21) Greatrex, B. W.; Taylor, D. K.; Tiekink, E. R. Z. Kristallogr.
2003, submitted for publication.
J . Org. Chem, Vol. 69, No. 7, 2004 2581

300) δ 1.06-1.29 (m, 5H), 1.55-1.77 (m, 6H), 1.94 (d, J ) 12.3
Hz, 1H), 3.32 (dd, J ) 3.0, 2.1 Hz, 1H), 3.56 (dd, J ) 5.7, 3.0,
1H), 4.32 (d, J ) 2.1 Hz, 1H), 7.48-7.54 (m, 2H), 7.60-7.63 (m,
1H), 8.01-8.05 (m, 2H); 13C NMR (CDCl3, 75) δ 25.8, 25.9, 26.2,
28.3, 28.8, 42.6, 54.4, 60.6, 73.4, 128.3, 128.8, 133.9, 135.4, 194.1.
Gen er a l P r oced u r e for th e Ep oxid a tion of 1,2-Dioxin es
1d -f. To a stirred solution of 1,2-dioxine (1 mmol) in THF (5
mL) was added 30% aqueous hydrogen peroxide (453 mg, 4
mmol) followed by lithium hydroxide (23 mg, 1 mmol). The
resulting suspension was stirred vigorously until complete (TLC,
16-48 h). A small portion (1-2 mg) of manganese dioxide was
then added to the mixture and allowed to stir until evolution of
gas had ceased. The solution was then diluted with water (15
mL) and extracted with CH2Cl2 (2 × 20 mL). The combined
organic extracts were dried and evaporated affording the trans-
epoxides, which were separable by flash chromatography and/
or recrystallization.
Exp er im en ta l Section
Gen er a l P r oced u r e for th e Ep oxid a tion of 1,2-Dioxin es
1a -c. To a stirred solution of 1,2-dioxine (1 mmol) in THF (5
mL) was added 30% aqueous hydrogen peroxide (453 mg, 4
mmol) followed by lithium hydroxide (23 mg, 1 mmol). The
resulting suspension was stirred vigorously until all starting
material had been consumed (TLC, 16-48 h). Sodium thiosulfate
solution (10%, 20 mL) was then added, and the reaction was
stirred for 15 min before being diluted with CH2Cl2 (40 mL).
The organic layer was separated and the aqueous layer extracted
with CH2Cl2 (30 mL). The combined organic extracts were
washed with brine (10 mL), dried, and concentrated in vacuo
affording the trans-epoxides which were separable by flash
chromatography and/or recrystallization.
(()-{(2R,3S)-3-[(S)-1-Hyd r oxy-1-p h en ylm eth yl]oxir a n -2-
yl}(p h en yl)m eth a n on e 3a : colorless solid; mp 106-107 °C
(CH2Cl2/hexane); Rf 0.50 (60:40 hexane/ethyl acetate); IR (Nujol)
3420, 1666, 1233, 1048, 696 cm-1; 1H NMR (CDCl3, 300) δ 2.10-
2.70 (br s, 1H), 3.35 (dd, J ) 2.7, 2.1 Hz, 1H), 4.47 (dd, J ) 2.1,
0.6 Hz, 1H), 5.12 (d, J ) 2.7, 0.6 Hz, 1H), 7.34-7.56 (m, 8H),
7.81-7.84 (m, 2H); 13C NMR (CDCl3, 75) δ 53.5, 61.9, 70.1, 125.9,
128.2, 128.5, 128.7, 128.8, 133.8, 135.2, 138.6, 193.8; EIMS m/z
255 (MH+, 10), 237 (100), 209 (20), 105 (55). Anal. Calcd for
(()-{(2R,3S)-3-[(1R)-1-Hydr oxyeth yl]oxir an -2-yl}(ph en yl)-
m eth a n on e 3d : colorless oil; Rf 0.24 (60:40 hexane/ethyl
acetate); IR (neat) 3460, 2977, 1689, 1598, 1450, 1232, 696 cm-1
;
1H NMR (CDCl3, 300) δ 1.36 (d, J ) 6.3 Hz, 3H), 2.34 (br s, 1H),
3.24 (dd, J ) 2.5, 2.2 Hz, 1H), 4.19 (ddq, J ) 6.3, 2.5, 0.5 Hz,
1H), 4.41 (dd, J ) 2.2, 0.5 Hz, 1H), 7.44-7.66 (m, 3H), 8.02-
8.11 (m, 2H); 13C NMR (CDCl3, 75) δ 18.6, 53.2, 62.5, 64.3, 128.2,
128.7, 133.9, 135.4, 194.1; EIMS m/z 193 (MH+, 95), 147 (50),
105 (100); HRMS calcd for (MH+) C11H13O3 193.0864, found
193.0866.
C
16H14O3: C, 75.57; H, 5.54. Found: C, 74.94; H, 5.31.
(()-{(2R,3S)-3-[(R)-1-Hyd r oxy-1-p h en ylm eth yl]oxir a n -2-
yl}(p h en yl)m eth a n on e 4a : colorless solid; mp 78-80 °C (CH2-
Cl2/hexane); Rf 0.38 (60:40 hexane/ethyl acetate); IR (Nujol)
3486, 1677, 1230, 1061, 685 cm-1; 1H NMR (CDCl3, 300) δ 2.31
(br s, 1H), 3.49 (dd, J ) 3.9, 2.4 Hz, 1H), 4.34 (d, J ) 2.4 Hz,
1H), 4.81 (d, J ) 3.9 Hz, 1H), 7.35-7.62 (m, 8H), 7.87-7.90 (m,
2H); 13C NMR (CDCl3, 75) δ 55.0, 62.1, 72.7, 126.5, 128.3, 128.6,
128.7, 128.9, 133.9, 135.2, 139.5, 193.6; EIMS m/z 254 (M+, 3),
236 (30), 208 (30), 147 (80), 105 (100). Anal. Calcd for C16H14O3:
C, 75.57; H, 5.54. Found: C, 75.53; H, 5.60.
(()-{(2R,3S)-3-[(1S)-1-Hydr oxyeth yl]oxir an -2-yl}(ph en yl)-
m eth a n on e 4d : colorless solid; mp 106-108 °C; Rf 0.21 (60:40
hexane/ethyl acetate); IR (neat) 3378, 2922, 1694, 1598, 1453,
1338, 1231, 901, 700 cm-1; 1H NMR (CDCl3, 300) δ 1.41 (d, J )
6.4 Hz, 3H), 1.71 (br s, 1H), 3.23 (dd, J ) 3.4, 2.0 Hz, 1H), 4.00
(dq, J ) 6.4, 3.4 Hz, 1H), 4.34 (d, J ) 2.0 Hz, 1H), 7.47-7.64
(m, 3H), 8.00-8.05 (m, 2H); 13C NMR (CDCl3, 75) δ 20.3, 54.8,
62.7, 65.9, 128.3, 128.8, 133.9, 135.4, 193.9; EIMS m/z 193 (MH+,
20), 175 (10), 147 (40), 105 (100). Anal. Calcd for C11H12O3: C,
68.72; H, 6.29. Found: C, 68.83; H, 6.34.
(()-(4-Br om op h en yl){(2R,3S)-3-[(S)-1-h yd r oxy-1-p h en yl-
m eth yl]oxir a n -2-yl}m eth a n on e 3b: colorless solid; mp 138-
140 °C (CH2Cl2/hexane); Rf 0.26 (70:30 hexane/ethyl acetate);
IR (Nujol) 3426, 2923, 1666, 1583, 1455, 1250, 1070, 1045, 1007,
(()-[(2R,3S)-3-(Hydr oxym eth yl)oxir an -2-yl](ph en yl)m eth -
a n on e 3e: colorless oil which crystallized at -15 °C; mp 60-62
°C; Rf 0.27 (1:1 hexane/ethyl acetate); IR (neat) 3445, 1686, 1597,
765, 698 cm-1 1H NMR (CDCl3, 300) δ 1.40-1.80 (br s, 1H),
;
1
1450, 1233, 1063, 697 cm-1; H NMR (CDCl3, 200) δ 2.64 (br s,
3.45 (dd, J ) 2.7, 2.1 Hz, 1H), 4.40 (dd, J ) 2.1, 0.6 Hz, 1H),
5.13 (d, J ) 2.7, 0.6 Hz, 1H), 7.36-7.47 (m, 5H), 7.52-7.58 (m,
2H), 7.66-7.68 (m, 2H); 13C NMR (CDCl3, 75) δ 53.5, 61.9, 70.0,
125.9, 128.6, 128.9, 129.2, 129.7, 132.1, 133.8, 138.4, 192.9; EIMS
m/z 334 (M+, 81Br, 10), 332 (M+, 79Br, 10), 227 (81Br, 50), 225
1H), 3.37 (ddd, J ) 3.0, 2.2, 2.0 Hz, 1H), 3.90 (dd, J ) 13.2, 3.0
Hz, 1H), 4.09 (dd, J ) 13.2, 2.0 Hz, 1H), 4.42 (d, J ) 2.2 Hz,
1H), 7.45-7.67 (m, 3H), 8.00-8.05 (m, 2H); 13C NMR (CDCl3,
50) δ 53.8, 59.3, 60.0, 128.3, 128.7, 133.9, 135.2, 194.3; EIMS
m/z 178 (M+, 5), 160 (25), 147 (25), 105 (100). Anal. Calcd for
C10H10O3: C, 67.41; H, 5.66. Found: C, 67.29; H, 5.66.
(()-(4-Br om op h en yl)[(2R,3S)-3-(h yd r oxym eth yl)oxir a n -
2-yl]m eth a n on e 3f: colorless solid; mp 78-80 °C; Rf 0.30 (1:1
hexane/ethyl acetate); IR (neat) 3500, 3291, 1682, 1586, 1232,
1071 cm-1; 1H NMR (CDCl3, 300) δ 1.67 (br s, 1H), 3.38 (ddd, J
) 2.7, 2.4, 2.1 Hz, 1H), 3.91 (dd, J ) 17.2, 2.7 Hz, 1H), 4.10 (dd,
J ) 17.2, 2.4 Hz, 1H), 4.33 (d, J ) 2.1 Hz, 1H), 7.64-7.67 (m,
2H), 7.89-7.92 (m, 2H); 13C NMR (CDCl3, 50) δ 53.7, 59.1, 59.8,
129.4, 129.5, 132.2, 133.9, 193.3; EIMS m/z 258 (M+, 81Br, 5),
256 (M+, 79Br, 6), 224 (30, 79Br), 222 (30, 81Br), 185 (100). Anal.
Calcd for C10H9O3Br1: C, 46.72; H, 3.53. Found: C, 46.41; H,
3.36.
(
79Br, 45), 107 (100). Anal. Calcd for C16H13O3Br1: C, 57.68; H,
3.93. Found: C, 57.76; H, 3.81.
(()-(4-Br om op h en yl){(2R,3S)-3-[(R)-1-h yd r oxy-1-p h en yl-
m eth yl]oxir a n -2-yl}m eth a n on e 4b: colorless solid; mp 121-
122 °C (CDCl3/hexane); Rf 0.20 (70:30 hexane/ethyl acetate); IR
(Nujol) 3446, 1697, 1586, 1229, 1071, 1008, 698; 1H NMR (CDCl3,
200) δ 2.33 (br s, 1H), 3.48 (dd, J ) 4.2, 2.2 Hz, 1H), 4.27 (d, J
) 2.2 Hz, 1H), 4.81 (d, J ) 4.2 Hz, 1H), 7.36-7.49 (m, 5H), 7.56-
7.61 (m, 2H), 7.72-7.77 (m, 2H); 13C NMR (CDCl3, 50) δ 55.0,
62.0, 72.8, 126.5, 128.3, 129.0, 129.3, 129.7, 132.1, 133.8, 139.4,
192.8; EIMS m/z 334 (M+, 81Br, 10), 332 (M+, 79Br, 10), 317 (10),
316 (10), 315 (10), 314 (10), 185 (90), 183 (90), 105 (100); HRMS
calcd for (ESI, M + Na+) C16H15O3Br1Na1 354.9945, found
354.9946.
(()-[(2R,3S)-3-(Hyd r oxym eth yl)oxir a n -2-yl](cycloh exyl)-
m eth a n on e 3g: colorless oil; Rf 0.50 (1:1 hexane/ethyl acetate);
(()-{(2R,3S)-3-[(S)-1-Cycloh exyl-1-h ydr oxym eth yl]oxir an -
2-yl}(p h en yl)m eth a n on e 3c: colorless solid; mp 128-130 °C
(CH2Cl2/hexane); Rf 0.39 (70:30 hexane/ethyl acetate); IR (Nujol)
IR (neat) 3443, 2930, 2855, 1704, 1450, 1064 cm-1 1H NMR
;
(CDCl3, 300) δ 1.18-1.47 (m, 5H), 1.68-1.92 (m, 6H), 2.51 (dddd,
J ) 11.1, 11.1, 3.3, 3.3 Hz, 1H), 3.22 (ddd, J ) 3.3, 2.4, 2.4 Hz,
1H), 3.63 (d, J ) 2.4 Hz, 1H), 3.76 (dd, J ) 12.9, 3.3 Hz, 1H),
4.01 (dd, J ) 12.9, 2.4, 1H); 13C NMR (CDCl3, 50) δ 25.2, 25.6,
25.6, 27.5, 28.3, 46.6, 54.9, 58.0, 60.4, 208.9; EIMS m/z 185 (MH+,
90), 111 (50), 83 (100); HRMS calcd for C10H16O3Na (M + Na+)
207.0997, found 207.0993.
P r oced u r e for th e Syn th esis of Op tica lly En r ich ed
Ep oxid es 3a a n d 4a . To a stirred degassed solution of THF (5
mL) cooled to -10 to -15 °C was added Co(II) catalyst 7a (54
mg, 0.075 mmol). After the solution was stirred for 30 min, 3,6-
diphenyl-3,6-dihydro-1,2-dioxine 1a (238 mg, 1 mmol) was added
and the solution allowed to stir at -10 °C for 3 h or until all
3471, 1670, 1596, 1242, 1043, 703 cm-1; H NMR (CDCl3, 300)
1
δ 1.15-1.28 (m, 6H), 1.60-1.87 (m, 6H), 3.30 (dd, J ) 2.7, 2.1
Hz, 1H), 3.76 (br dd, J ) 6.0, 2.7 Hz, 1H), 4.41 (dd, J ) 2.1, 0.3
Hz, 1H), 7.48-7.54 (m, 2H), 7.61-7.66 (m, 1H), 8.04-8.08 (m,
2H); 13C NMR (CDCl3, 75) δ 25.8, 25.9, 26.2, 28.2, 28.7, 41.7,
53.3, 60.9, 72.3, 128.3, 128.8, 133.9, 135.4, 194.2; EIMS m/z 261
(MH+, 20), 243 (40), 147 (70), 105 (100). Anal. Calcd for
C
16H20O3: C, 73.82; H, 7.74. Found: C, 73.39; H, 7.59.
(()-{(2R,3S)-3-[(R)-1-Cycloh exyl-1-h ydr oxym eth yl]oxir an -
2-yl}(p h en yl)m eth a n on e 4c: colorless solid isolated as a
mixture with 3c; Rf 0.35 (70:30 hexane/ethyl acetate); IR (Nujol)
3478, 2925, 2852, 1669, 1597, 1449, 1238 cm-1; 1H NMR (CDCl3,
2582 J . Org. Chem., Vol. 69, No. 7, 2004

1,2-dioxine had been consumed (TLC). Triphenylphosphine (136
mg, 0.50 mmol) was then added and the reaction left to stir for
a further 30 min. The reaction was concentrated in vacuo and
the trans-enone intermediate isolated immediately by column
chromatography (Florisil, 60:40 hexane/ethyl acetate) (Rf 0.50).
The trans-enone was epoxidized immediately using the above
procedure as for 1d -f.
(R-143-00-139-112) for financial support. B.G. thanks
the faculty of Science for a scholarship.
Su p p or tin g In for m a tion Ava ila ble: Characterization
data for 5c and 6c. ORTEP representation and X-ray data for
epoxide 3a . 13C NMR spectra for 3a ,c,d and 4b. This material
is available free of charge via the Internet at http://pubs.acs.org.
Ack n ow led gm en t. We thank the Australian Re-
search Council and the National University of Singapore
J O0303315
J . Org. Chem, Vol. 69, No. 7, 2004 2583