Base- and Co(II)-catalyzed ring-opening reactions of perhydrooxireno[2,3-d][1,2]dioxines: An efficient route to 4-hydroxy-2,3-epoxy-ketones

Article abstract of DOI:10.1021/jo0300845

A series of 3,4,6-substituted 3,6-dihydro-1,2-dioxines were epoxidized with m-chloroperbenzoic acid to furnish perhydrooxireno[2,3-d][1,2]dioxines (epoxy-1,2-dioxines) in yields ranging from 51% to 93% with de's from 26% to 100%. Unsymmetrical epoxy-1,2-d

Full text of DOI:10.1021/jo0300845

Ba se- a n d Co(II)-Ca ta lyzed Rin g-Op en in g Rea ction s of
P er h yd r ooxir en o[2,3-d ][1,2]d ioxin es: An Efficien t Rou te to
4-Hyd r oxy-2,3-ep oxy-k eton es
Ben W. Greatrex,† Natalie F. J enkins,† Dennis K. Taylor,*,† and Edward R. T. Tiekink‡
Departments of Chemistry, The University of Adelaide, South Australia 5004 and
National University of Singapore, Singapore 117543
dennis.taylor@adelaide.edu.au
Received March 10, 2003
A series of 3,4,6-substituted 3,6-dihydro-1,2-dioxines were epoxidized with m-chloroperbenzoic acid
to furnish perhydrooxireno[2,3-d][1,2]dioxines (epoxy-1,2-dioxines) in yields ranging from 51% to
93% with de’s from 26% to 100%. Unsymmetrical epoxy-1,2-dioxines were ring-opened using
triethylamine to yield 4-hydroxy-2,3-epoxy-ketones quantitatively, and meso-epoxy-1,2-dioxines were
ring-opened using Co(II) salen complexes to afford 4-hydroxy-2,3-epoxy-ketones in 77-98% yield.
The first reported examples of the catalytic asymmetric ring-opening of meso-epoxy-1,2-dioxines
using a range of chiral Co(II) salen and â-ketoiminato complexes to afford highly enantio-enriched
4-hydroxy-2,3-epoxy-ketones are also presented.
In tr od u ction
chiral Co(II) salen or â-ketoiminato complexes to furnish
cis-γ-hydroxyenones with high enantiomeric excesses.7 To
increase the scope of this asymmetric ring-opening reac-
tion we decided to examine 1,2-dioxines where the double
bond had been either modified or removed. This led us
to consider epoxidation of the parent meso-3,6-dihydro-
1,2-dioxines 1, as the products from the reaction would
again be meso. Although many tricyclic perhydrooxireno-
[2,3-d][1,2]dioxines (epoxy-1,2-dioxines) have been previ-
ously synthesized, few examples of bicyclic epoxy-1,2-
dioxines 2 exist, and none of the products from the
reaction with transition metals have been characterized.8
Moreover, a unique opportunity exists for an examination
of the selectivity of the transition-metal-catalyzed ring-
opening reaction of epoxy-1,2-dioxines 2. Application of
the asymmetric version of the ring-opening could then
be applied with the aim of generating useful chiral
synthons. Nonsymmetrical epoxy-1,2-dioxines could simi-
larly yield substituted 4-hydroxy-2,3-epoxy-ketones if
ring-opened with an appropriate base. The current report
describes the preparation of epoxy-1,2-dioxines 2, their
ring-opening reactions, and the characterization of the
product 4-hydroxy-2,3-epoxy-ketones.
3,6-Dihydro-1,2-dioxines 1 (endoperoxides) are an im-
portant class of organic peroxides because of their
versatility in organic synthesis.1 1,2-Dioxines may be
homolytically or heterolytically ring-opened as a result
of their weak O-O bond to yield bis-epoxides or reactive
cis-γ-hydroxy enones, which may then undergo further
reaction.2 The transition-metal-catalyzed (homolytic) ring-
opening of 3,6-dihydro-1,2-dioxines of type 1 may be
effected by complexes of Fe(II), Ru(II), and Co(II).3-5 The
base-induced ring-opening proceeds readily with neutral
amine bases in high yield.6 Furthermore, we have
reported that meso-1,2-dioxines may be ring-opened using
* To whom correspondence should be addressed. Tel. (+61) 8 8303
5495. Fax. (+61) 8 8303 4358.
† The University of Adelaide.
‡ National University of Singapore.
(1) For examples of the use of 1,2-dioxines in furan synthesis, see:
(a) Harirchian, B.; Magnus, P. D. Synth. Commun. 1977, 7, 119. For
1,4-diketone synthesis, see: (b) Sengu¨l, M. E.; Ceylan, Z.; Balci, M.
Tetrahedron 1997, 53, 10401. For pyrrole synthesis, see: (c) Hewton,
C. E.; Kimber, M. C.; Taylor, D. K. Tetrahedron Lett. 2002, 43, 3199.
For 1,4-diol synthesis, see: (d) Mueller, P.; Rodriguez, D. Helv. Chim.
Acta 1985, 68, 975. Henninger, T. C.; Sabat, M.; Sundberg, R. J .
Tetrahedron 1996, 52, 14403.
(2) (a) Avery, T. D.; Taylor, D. K.; Tiekink, E. R. T. J . Org. Chem.
2000, 65, 5531. (b) Avery, T. D.; Fallon, G.; Greatrex, B. W.; Pyke, S.
M.; Taylor, D. K.; Tiekink, E. R. T. J . Org. Chem. 2001, 66, 7955. (c)
Greatrex, B. W.; Kimber, M. C.; Taylor, D. K.; Fallon, G.; Tiekink, E.
R. T. J . Org. Chem. 2002, 67, 5307.
(3) (a) Herz, W.; Ligon, R. C.; Turner, J . A.; Blount, J . F. J . Org.
Chem. 1977, 42, 1885. (b) Turner, J . A.; Herz, W. J . Org. Chem. 1977,
42, 1895. (c) Turner, J . A.; Herz, W. J . Org. Chem. 1977, 42, 1900.
(4) Suzuki, M.; Ohtake, H.; Kameya, Y.; Hamanaka, N.; Noyori, R.
J . Org. Chem. 1989, 54, 5292.
(5) (a) Boyd, J . D.; Foote, C. S.; Imagawa, D. K. J . Am. Chem. Soc.
1980, 102, 2, 3641. (b) Balci, M.; Su¨tbeyaz, Y. Tetrahedron Lett. 1983,
24, 4135. (c) Balci, M.; Akbulut, N. Tetrahedron 1985, 41, 1315. (d)
O’Shea, K. E.; Foote, C. S. J . Org Chem. 1989, 54, 3475. (e) Harter,
R.; Weymuth, C.; Scheffold, R.; Engel, P.; Linden, A. Helv. Chim. Acta
1993, 76, 353. (f) Sengu¨l, M. E.; Simsek, N.; Balci, M. Eur. J . Chem.
2000, 1359.
Resu lts a n d Discu ssion
P r ep a r a t ion of E p oxy-1,2-d ioxin es. 1,2-Dioxines
1a -g used in this study were prepared by the Rose
(6) (a) Kornblum, N.; De La Mare, H. E. J . Am. Chem. Soc. 1951,
73, 880. (b) Zagorski, M. G.; Salomon, R. G. J . Am. Chem. Soc. 1980,
102, 2501. (c) Akbulut, N.; Balci, M. J . Org. Chem. 1988, 53, 3338.
(7) Avery, T. D.; J enkins, N. F.; Kimber, M. C.; Lupton, D. W.;
Taylor, D. K. Chem. Commun. 2002, 28.
(8) (a) Burns, P.; Foote, C. S. J . Org. Chem. 1976, 41, 908. (b)
Sasaoka, M.; Hart, H. J . Org. Chem. 1979, 44, 368. (c) Bascetta, E.;
Gunstone, F. D.; Scrimgeour, C. M. J . Chem. Soc., Perkin Trans. 1
1984, 2199. (d) Secan, H.; Sutbeyaz, Y.; Balci, M. Tetrahedron Lett.
1990, 31, 1323.
10.1021/jo0300845 CCC: $25.00 © 2003 American Chemical Society
Published on Web 06/03/2003
J . Org. Chem. 2003, 68, 5205-5210
5205

Greatrex et al.
TABLE 1. Oxid a tion of 3,6-Dih yd r o-1,2-d ioxin es Usin g
m -CP BA
SCHEME 2
entrya
1,2-dioxine
time (d)
2:3
yieldb
1
2
3
1a
1b
1c
1d
1e
1f
14c
7
10
1
1
3
100:0
84:16
84:16
63:37
77:23
69:31
93:7
83
93
74
85
84
51
92
4
5d
6
7
1g
2
a
Reactions were typically performed on a 1 mmol scale with
b
1.2 equiv of m-CPBA in CH2Cl2 (5 mL). Combined isolated yield.
c 94% complete by 1H NMR. 1.8 equiv of m-CPBA was used.
d
SCHEME 1
TABLE 2. Rin g-Op en in g of 2 or 3 Usin g NEt 3 (Meth od
a ) or Co(II) Sa len (Meth od b) Affor d in g
2,3-Ep oxy-k eton es 4 a n d 5
entrya
dioxine
method
product
yieldb
1
2
3
4
5
6
7
8
9
2a
2a
2b
2c
2d
2e
2f
2g
3b
3e
a
b
a
a
b
b
b
a
a
b
4a
4a
4b
4c
4d
4e
4f
4g
5b
5e
100
98
100
86
96
95
89
84
83
77
Bengal sensitized addition of singlet oxygen to the
corresponding 1,3-butadiene as previously reported.2a,9
The epoxidation of the 1,2-dioxines was carried out in a
procedure analogous to that reported by Herz.3b Thus,
when 1 was allowed to react with m-CPBA, the sole
isolable products were epoxy-1,2-dioxines 2 and 3 with
moderate to good diastereoselectivity in excellent yield,
Table 1, Scheme 1. Diastereoselectivity was greatest for
the 3,6-diphenyl dioxine 1a where none of the all-cis
10
a
Reactions were typically performed on a 40 mg scale with 1
equiv of triethylamine or 2.5% w/w of N,N′-bis(salicylidene)eth-
ylenediaminocobalt(II). Isolated yield by silica gel chromatogra-
phy.
b
1
isomer was detectable by H NMR or TLC, although the
reaction proceeded only sluggishly, entry 1. Substitution
at the 4-position in the parent 1,2-dioxine 1g was found
to increase the observed diastereoselectivity; compare
entries 3 and 7.
epoxy-1,2-dioxines (2 or 3) are analogous to the ring-
opening reactions of 3,6-dihydro-1,2-dioxines. Thus, in
the case of Co(II) catalysis, single electron transfer from
the cobalt to oxygen affords an oxygen-centered radical
that then undergoes a 1,5-hydrogen atom abstraction,
regenerating the Co(II) catalyst, Scheme 3.7,10 The out-
come of the Co(II)-catalyzed ring-opening does not rely
on the acidity of the proton(s) R to the O-O linkage but
does, however, depend on the steric size of the attached
R-groupings. This reaction was only applied to the use
of symmetrical epoxy-1,2-dioxines to avoid formation of
regioisomers. Base catalysis involves the removal of the
most acidic proton R to the O-O linkage and then
rearrangement through cleavage of the O-O linkage to
afford the 4-hydroxy-2,3-epoxy-ketones.6 The presence of
an R-phenyl grouping significantly increases the acidity
of the R-proton, causing the ring-opening to proceed
regioselectively.
The identity of the major trans-isomer 2 was deter-
mined by 1H NMR. Typically, the protons attached to C1a
and C2 showed no or very little coupling as a result of
an approximate 90° dihedral angle and therefore ap-
peared as broadened singlets as in 2a or doublets where
not symmetrical, 2b,c. The minor isomer 3 with all
groups cis typically showed a larger coupling between the
C1a and C2 protons, causing the signals to appear as non-
first-order multiplets. Both isomers were considerably
more stable than their 3,6-dihydro counterparts 1 and
could be stored neat at room temperature for several
months without decomposition.
We next examined the ring-opening of epoxy-1,2-
dioxines 2 and 3 using either a mild amine base or
transition metal catalyst, the results of which are sum-
marized in Scheme 2 and Table 2. Exploiting either
method resulted in the corresponding 4-hydroxy 2,3-
epoxy-ketones 4 or 5 being formed in excellent yields. The
proposed mechanisms for the ring-openings of these
(10) The synthesis of catalysts 10a -e and 11a -d will be reported
elsewhere. (a) For general syntheses of â-ketoiminato catalysts, see:
Nagata, T.; Imagawa, K.; Yamada, T. Inorg. Chim. Acta 1994, 220,
283. Sugi, K. D.; Nagata, T.; Imagawa, K.; Yamada, T.; Mukaiyama,
T. Chem. Lett. 1994, 1259. (b) For the syntheses of cobalt salen
catalysts, see: Fukuda, T.; Katsuki, T. Tetrahedron 1997, 53, 7201.
Irie, R.; Noda, K.; Ito, Y.; Matsumoto, N.; Katsuki, T. Tetrahedron:
Asymmetry 1991, 2, 481.
(9) Clennan, E. L. Tetrahedron 1991, 47, 1343.
5206 J . Org. Chem., Vol. 68, No. 13, 2003

Efficient Route to 4-Hydroxy-2,3-epoxy-ketones
TABLE 3. Isom er ic Ra tios of
4-Hyd r oxy-2,3-ep oxy-k eton es Mea su r ed Wh en Nea t a n d
Dissolved in CDCl3
SCHEME 3
entry
ketone
neata
ratiob 4:(6:7)
1
2
4a
4b
4b
4c
4d
4e
4f
4g
5b
5e
4a
4b
57:(37:6)
41:(51:8)
27:(68:5)
39:(55:6)
0:(79:21)
0:(78:22)
0:(70:30)
34:(57:9)
26:(61:13)e
0:(77:23)e
3c
4
oild
5
6
7
8
9
10
6d /7d
6e/7e
6f/7f
6g/7g
5b
8e/9e
a
SCHEME 4
Refers to which isomeric form the 4-hydroxy-2,3-epoxy-ketone
b
1
exists in when neat. Determined by IR. Ratio determined by H
NMR by dissolving sample in CDCl3 and allowing it to equilibrate
for 1 h before integrating peak height. Anomers 6 and 7 could not
be unambiguously assigned. c Measured in the presence of 0.5
equiv of DABCO. Could not be determined. e Ratio of 5 : 8: 9.
d
The characterization of the product hydroxy ketones
by NMR was complicated as the products existed in both
their acyclic and cis and trans cyclic furanol forms,
1
Scheme 4. 2D H and 13C NMR was used to assign the
resonances in the 1D 1H spectra from which isomeric
ratios could be determined. The furanol forms showed
resonances at ca. δ 100 ppm in their 13C NMR spectra,
consistent with a hemiketal carbon, whereas phenyl-
substituted hydroxy ketones showed resonances at ca. δ
F IGURE 1. Catalysts for the asymmetric ring-opening of
meso-epoxy-1,2-dioxines.
TABLE 4. Asym m etr ic Rin g-Op en in g of
m eso-1,2-Dioxin es 2a or 2f
1
200 ppm for the aryl ketone. Long range H-13C correla-
entrya
dioxine
catalyst
mol %
temp
ratiob (ee)
tion spectroscopy (HMBC) was used to link resonances
1
in the 1D H with the identifying 13C signals. It was not
1
2
3
4
5
6
7
8
9
10
11c
12
13
14
15
16
17
2a
10a
10b
10c
10d
10e
10e
10e
10e
10e
10e
10e
11a
11b
11c
11d
10a
10e
5
5
5
5
2.5
5
7.5
5
5
7.5
5
5
5
5
5
5
5
20
20
20
20
20
20
20
0
70:30 (40)
12:88 (76)
79:21 (58)
16:84 (68)
85:15 (70)
84:16 (68)
92:8 (84)
89:11 (78)
89:11 (78)
92:8 (84)
86:14 (72)
17:83 (66)
16:84 (68)
20:80 (60)
35:65 (30)
67:33 (34)
82:18 (64)
possible to assign all aromatic peaks in the 13C spectra
to a specific anomer for all furanols. A lack of through-
1
space interactions in the 2D H NMR of the furanols 6/7
and 8/9 made assignment of the anomeric carbon dif-
ficult, and thus although all signals could be assigned to
an anomer, the relative configuration of the anomers
could not be determined.
-15
0
The Nujol mull IR spectra of the 4-hydroxy-2,3-epoxy-
ketones were used to determine whether the epoxy-
ketone existed in its cyclic or acyclic form in the solid
state. Typically, phenyl-substituted epoxy-ketones existed
in their acyclic form when in the solid state, as they
showed an aryl-carbonyl stretching adsorption at 1670-
1680 cm-1. The alkyl-substituted epoxy-ketones existed
solely in their cyclic forms both in the solid state and in
solution, as could be seen by an absence of the carbonyl
absorption. Specific population ratios for each of the
epoxy-ketones are given in Table 3. X-ray crystallography
was used to confirm the identity of the epoxy-ketone 4b,
validating the assignment of structure in the solid state
for the series of epoxy-ketones 4 and the trans relation-
ship between the epoxidic oxygen and R-groups in the
parent epoxy-1,2-dioxine 2b.
20
20
20
20
20
20
20
2f
a
Reactions were performed in THF (1 mL) on a 20 mg scale by
dissolving catalyst in solvent and allowing it to equilibrate for 1
b
h before addition of 1,2-dioxine. Ratio determined by chiral shift
NMR using europium tris[3-(heptafluoropropylhydroxymethylene)]-
(+)-camphorate in CDCl3. c Reaction performed in CH2Cl2.
ring-opening of the meso-1,2-dioxines generated in this
study. Thus, 1,2-dioxines 2a and 2f were treated with a
range of chiral Co(II) complexes 10a -e and 11a -d
(Figure 1)to afford the hydroxy-ketones 4a and 4f as the
sole products, the results of which are summarized in
Table 4.10
The trends observed were similar to those observed for
the 3,6-dihydro-1,2-dioxines 1; however, ee’s were slightly
improved in the two systems tested here. Best results
Asym m etr ic Rin g-Op en in g of m eso-1,2-Dioxin es.
We have recently shown that meso-3,6-dihydro-1,2-diox-
ines 1 may be ring-opened with high enantioselectivity
using chiral Schiff base complexes of Co(II).7 We antici-
pated that this methodology could also be applied to the
J . Org. Chem, Vol. 68, No. 13, 2003 5207

Greatrex et al.
127.9, 128.8, 129.2, 135.5; MS (EI) m/z (%) 178 (M+, 20), 131
(30), 105 (100); HRMS of 2c C10H10O3 calcd 178.0629, found
178.0628.
obtained for the diaryl 1,2-dioxine 2a were from 10e at
a catalyst concentration of 7.5%. Menthyl ester catalysts
10d and 10e with R,R and S,S backbone stereochemistry,
respectively, gave equal and opposite enantiomeric ratios
as expected. The dialkyl 1,2-dioxine 2f gave ee’s slightly
lower than the diaryl 1,2-dioxine 2a , entries 1, 5, and
16-17, a result analogous to that found when starting
with 1. Higher ee’s were also seen from the bis-iminato
complexes as compared to the salen type complexes. Over
the range studied, no great changes in ratio due to
temperature were observed, however, a slight increase
in ee was seen with increasing catalyst concentrations.
This also agrees with the results obtained for the ring-
opening of 1a . The absolute stereochemistry of the cis-
γ-hydroxyenone obtained from the reaction of 1 has been
previously determined unambiguously by several
methods.2c,7,11 Although the expected selectivity for the
epoxy-1,2-dioxines is the same, the assignment of the
absolute stereochemistry of the product epoxy-ketone 4
obtained from 2 is not yet confirmed and will be made in
an upcoming natural product synthesis.
In summary, epoxy-1,2-dioxines 2 can be readily
prepared from 3,6-dihydro-1,2-dioxines 1 in high yield
and good to excellent de. Exposure of these epoxy-1,2-
dioxines to either triethylamine or Co(II) complexes
allowed for the preparation of 4-hydroxy-2,3-epoxy-
ketones 4/5 in excellent yields. The use of chiral Co(II)
complexes allowed for the asymmetric ring-opening of
meso-epoxy-1,2-dioxines in a highly enantioselective man-
ner, again affording these useful synthons 4/5.
(()-(1a R,2S,5R,5a S)-2,5-Dip r op ylp er h yd r ooxir en o[2,3-
d ][1,2]d ioxin e 2d . Colorless oil; Rf 0.31 (1:1 hexane/CH2Cl2);
IR (neat) 2961, 2874, 1465, 1380, 1068, 1005, 802 cm-1 1H
;
NMR (300 MHz) δ 0.96 (t, J ) 6.9 Hz, 6H), 1.44-1.57 (m, 6H),
1.60-1.82 (m, 2H), 3.19 (d, J ) 0.6 Hz, 2H), 4.24 (dd, J ) 7.8,
4.2 Hz, 2H); 13C NMR (75 MHz) δ 13.8, 18.4, 32.3, 52.3, 77.8;
MS (EI) m/z (%) 186 (M+, 20), 154 (50), 125 (70), 57 (60), 43
(100); HRMS of 2d C10H18O3 calcd 186.1255, found 186.1250.
(()-(1aR,2S,5R,5a S)-2,5-Dicycloh exylp er h yd r ooxir en o-
[2,3-d ][1,2]d ioxin e 2e. Colorless solid; mp 61.5-63 °C; Rf 0.21
(1:1 hexane/CH2Cl2); IR (Nujol) 1450, 1100, 1013, 845 cm-1
;
1H NMR (300 MHz) δ 1.13-1.29 (m, 10H), 1.64-1.91 (m, 12H),
3.32 (s, 2H), 3.96 (d, J ) 6.9 Hz, 2H); 13C NMR (75 MHz) δ
25.7, 25.8, 26.1, 28.3, 29.0, 39.1, 51.3, 81.7; MS (EI) m/z (%)
266 (M+, 20), 249 (15), 234 (10), 83 (100). Anal. Calcd for
C
16H26O3: C, 72.14; H, 9.83. Found: C, 72.37; H, 9.86.
(()-(1a R,2S,5R,5a S)-2,5-Diisop r op ylp er h yd r ooxir en o-
[2,3-d ][1,2]d ioxin e 2f. Colorless oil; Rf 0.15 (1:1 hexane/CH2-
Cl2); IR (neat) 2964, 1469, 1389, 1370, 991 cm-1; 1H NMR (300
MHz) δ 1.03 (d, J ) 6.9 Hz, 6H), 1.03 (d, J ) 6.9 Hz, 6H), 2.02
(oct, J ) 6.9 Hz, 2H), 3.30 (d, J ) 0.9 Hz, 2H), 3.91 (d, J ) 6.9
Hz, 2H); 13C NMR (75 MHz) δ 18.4, 18.6, 29.4, 51.2, 82.4; MS
(EI) m/z (%) 186 (M+, 5), 101 (30), 71 (70), 43 (100); HRMS of
2f C10H18O3 calcd 186.1255, found 186.1247.
(()-(1a S,5R,5a R)-1a -Meth yl-5-p h en ylp er h yd r ooxir en o-
[2,3-d ][1,2]d ioxin e 2g. Colorless solid; mp 61.5-63 °C; Rf 0.43
1
(CH2Cl2); IR (Nujol) cm-1; H NMR (300 MHz) δ 1.48 (s, 3H),
3.39 (s, 1H), 4.21 (d, J ) 13.2 Hz, 1H), 4.43 (d, J ) 13.2 Hz,
1H), 5.37 (s, 1H), 7.35-7.42 (m, 5H); 13C NMR (75 MHz) δ
18.0, 54.5, 60.6, 72.4, 81.4, 127.9, 128.8, 129.2, 135.5; MS (EI)
m/z (%) 192 (M+, 20), 160 (95), 105 (90), 43 (100). Anal. Calcd
for C11H12O3: C, 68.73; H, 6.29. Found: C, 68.75; H, 6.51.
(()-(1aS,2S,5R,5aR)-2-Meth yl-5-ph en ylper h ydr ooxir en o-
[2,3-d ][1,2]d ioxin e 3b. Colorless oil; Rf 0.28 (1:1 hexane/CH2-
Exp er im en ta l Section
Cl2); IR (neat) 2996, 2932, 1496, 1454, 1371, 1024, 700 cm-1
;
Gen er a l P r oced u r e for th e Ep oxid a tion of 3,6-Dih y-
d r o-1,2-d ioxin es. To a stirred solution of 1,2-dioxine (1 mmol)
in CH2Cl2 (5 mL) was added 70% m-chloroperbenzoic acid (295
mg, 1.2 mmol), and the reaction was left to stir at ambient
temperature until complete by TLC. The solvent was removed
under reduced pressure, and the products were purified by
flash chromatography.
1H NMR (300 MHz) δ 1.75 (d, J ) 6.6 Hz, 3H), 3.79 (dd, J )
4.4, 4.4 Hz, 1H), 3.84 (dd, J ) 4.4, 1.6 Hz, 1H), 4.77 (dq, J )
6.6, 3.6 Hz, 1H), 5.55 (d, J ) 1.6 Hz, 1H), 7.51-7.67 (m, 3H),
7.77-7.82 (m, 2H); 13C NMR (50 MHz) δ 14.9, 52.1, 53.7, 73.4,
79.1, 128.2, 128.7, 128.9, 135.5; MS (EI) m/z (%) 192 (M+, 100),
160 (50), 131 (70), 105 (65); HRMS of 3b C11H12O3 calcd
192.0786, found 192.0778.
(()-(1a R,2S,5R,5a S)-2,5-Dip h en ylp er h yd r ooxir en o[2,3-
d ][1,2]d ioxin e 2a . Colorless solid; mp 97-99 °C; Rf 0.25 (90:
(()-(1aR,2R,5a R)-2-P h en ylp er h yd r ooxir en o[2,3-d ][1,2]-
d ioxin e 3c. Colorless oil; Rf 0.40 (1:1 hexane/CH2Cl2); IR (neat)
2917, 1494, 1454, 1423, 1030 cm-1; 1H NMR (300 MHz) δ 3.53
(ddd, J ) 4.5, 0.9, 0.6 Hz, 1H), 3.66 (ddd, J ) 4.5, 4.5, 1.2 Hz,
1H), 4.38 (dd, J ) 13.5, 4.5 Hz, 1H), 4.60 (ddd, J ) 13.5, 1.2,
0.6 Hz, 1H), 5.37 (d, J ) 0.9 Hz, 1H), 7.39-7.42 (m, 5H); 13C
NMR (150 MHz) δ 50.5, 51.0, 70.1, 79.8, 128.6, 128.6, 129.3,
134.8; MS (EI) m/z (%) 178 (M+, 60), 131 (90), 105 (100); HRMS
of 3c C10H10O3 calcd 178.0629, found 178.0634.
(()-(1a R,2R,5S,5a S)-2,5-Dip r op ylp er h yd r ooxir en o[2,3-
d ][1,2]d ioxin e 3d . Colorless oil; Rf 0.48 (1:1 hexane/CH2Cl2);
IR (neat) 2961, 2874, 1465, 1379, 1253, 913, 668 cm-1; 1H NMR
(300 MHz) δ 0.96 (t, J ) 7.2 Hz, 6H), 1.43-1.78 (m, 8H), 3.37-
3.38 (m, 2H), 4.21-4.26 (m, 2H); 13C NMR (75 MHz) δ 13.9,
18.5, 31.3, 52.3, 77.2; MS (EI) m/z (%) 186 (M+, 5), 154 (30),
1
10 hexane/ethyl acetate); IR (Nujol) 1492, 740, 695 cm-1; H
NMR (300 MHz) δ 3.73 (s, 2H), 5.43 (s, 2H), 7.38-7.49 (m,
10H); 13C NMR (75 MHz) δ 52.8, 80.1, 127.8, 128.8, 128.9,
136.0; MS (EI) m/z (%) 254 (M+, 10), 222 (95), 193 (70),131
(50), 77 (100). Anal. Calcd for C16H14O3: C, 75.57; H, 5.54.
Found: C, 75.8; H, 5.58.
(()-(1aR,2S,5R,5aS)-2-Meth yl-5-ph en ylper h ydr ooxir en o-
[2,3-d ][1,2]d ioxin e 2b. Colorless solid; mp 72-72 °C; Rf 0.20
(1:1 hexane/CH2Cl2); IR (Nujol) 1492, 1042, 749, 696 cm-1; 1H
NMR (300 MHz) δ 1.48 (d, J ) 6.6 Hz, 3H), 3.33 (d, J ) 4.2
Hz, 1H), 3.55 (d, J ) 4.2 Hz, 1H), 4.54 (q, J ) 6.6 Hz, 1H),
5.30 (s, 1H), 7.38-7.44 (m, 5H); 13C NMR (150 MHz) δ 15.9,
52.6, 52.9, 74.2, 80.1, 127.9, 128.7, 128.9, 136.0; MS (EI) m/z
(%) 192 (M+, 60), 160 (90), 131 (100), 105 (90). Anal. Calcd for
125 (30), 71 (50), 43 (100); HRMS of 3d
C10H18O3 calcd
C
11H12O3: C, 68.73; H, 6.29. Found: C, 68.76; H, 6.50.
186.1255, found 186.1249.
(()-(1a S,2R,5a S)-2-P h en ylp er h yd r ooxir en o[2,3-d ][1,2]-
(()-(1aR,2R,5S,5a S)-2,5-Dicycloh exylp er h yd r ooxir en o-
[2,3-d ][1,2]d ioxin e 3e. Colorless oil; Rf 0.54 (1:1 hexane/CH2-
Cl2); IR (neat) 2925, 2852, 1449, 1254, 983, 911 cm-1; 1H NMR
(300 MHz) δ 0.96-1.36 (m, 10H), 1.67-2.00 (m, 12H), 3.42-
3.43 (m, 2H), 3.89 (br d, J ) 8.7 Hz, 2H); 13C NMR (75 MHz)
δ 25.4, 25.7, 26.3, 28.4, 29.5, 37.4, 51.1, 81.8; MS (EI) m/z (%)
266 (M+, trace), 249 (10), 234 (10), 216 (20), 83 (100); HRMS
of 3e C16H26O3 calcd 266.1881, found 266.1871.
d ioxin e 2c. Colorless oil; Rf 0.37 (1:1 hexane/CH2Cl2); IR (neat)
3033, 2913, 1494, 1455, 1036 cm-1; 1H NMR (300 MHz) δ 3.51
(br d, J ) 4.5 Hz, 1H), 3.59 (dd, J ) 4.5, 0.6 Hz, 1H), 4.42 (d,
J ) 13.5 Hz, 1H), 4.58 (dd, J ) 13.5, 1.2 Hz, 1H), 5.38 (s, 1H),
7.39-7.42 (m, 5H); 13C NMR (50 MHz) δ 48.6, 53.4, 69.2, 81.3,
(11) The backbone (diamine portion) stereochemistry is responsible
for the sign of the induction. R,R backbone stereochemistry in the
catalyst gives S absolute stereochemistry in the product obtained from
1a ; S,S backbone stereochemistry yields R absolute stereochemistry.
(()-(1a R,2R,5S,5a S)-2,5-Diisop r op ylp er h yd r ooxir en o-
[2,3-d ][1,2]d ioxin e 3f. Colorless oil; Rf 0.42 (1:1 hexane/CH2-
5208 J . Org. Chem., Vol. 68, No. 13, 2003

Efficient Route to 4-Hydroxy-2,3-epoxy-ketones
Cl2); IR (neat) 2961, 2874, 1465, 1379, 1253, 913 cm-1
;
1H
(()-(1a S,4a R)-2-P h en yltetr a h yd r ooxir en o[2,3-c]fu r a n -
2-ol 6c/7c. Major anomer: 1H NMR (600 MHz) δ 3.76 (d, J )
3.0 Hz, 1H), 3.84 (dd, J ) 3.0, 0.6 Hz, 1H), 4.02 (dd, J ) 10.8,
NMR (300 MHz) δ 1.02 (d, J ) 6.6 Hz, 6H), 1.06 (d, J ) 6.6
Hz, 6H), 2.11 (dsept, J ) 9.0, 6.6 Hz, 2H), 3.43-3.46 (m, 2H),
3.78-3.82 (m, 2H); 13C NMR (75 MHz) δ 18.3, 19.3, 28.3, 51.3,
82.8; MS (EI) m/z (%) 186 (M+, trace), 139 (30), 71 (60), 43
(100); HRMS of 3f C10H18O3 calcd 186.1255, found 186.1256.
(()-(1a R,5R,5a S)-1a -Meth yl-5-p h en ylp er h yd r ooxir en o-
[2,3-d ][1,2]d ioxin e 3g. Colorless oil; Rf 0.53 (CH2Cl2); IR
0.6 Hz, 1H), 4.20 (d, J ) 10.8 Hz, 1H), 7.34-7.62 (m, 5H); 13
C
NMR (150 MHz) δ 54.8, 60.0, 66.7, 102.0, 125.7-128.9 (4 Aryl
13C).
(()-(1aS,4S,4a R)-2,4-Dip r op yltetr a h yd r ooxir en o[2,3-c]-
fu r a n -2-ol 6d /7d . Major anomer: colorless oil; Rf 0.50 (70:30
hexane/ethyl acetate); IR (neat) 3422, 2961, 1456, 1423, 1380,
1
(neat) 2915, 1495, 1454, 1267, 1004, 734, 698 cm-1; H NMR
1
(200 MHz) δ 1.51 (s, 3H), 3.39 (s, 1H), 4.20 (d, J ) 13.6 Hz,
1H), 4.50 (dd, J ) 13.6, 0.4 Hz, 1H), 5.35 (m, 1H), 7.36-7.41
(m, 3H), 7.50-7.54 (m, 2H); 13C NMR (75 MHz) δ 20.0, 57.3,
57.6, 73.6, 79.5, 128.3, 128.5, 129.1, 135.0; MS (EI) m/z (%)
192 (M+, 20), 145 (70), 131 (80), 105 (100); HRMS of 3g
1237, 1146, 1009; H NMR (300 MHz) δ 0.93-0.99 (m, 6H),
1.35-1.85 (m, 8H), 2.28 (s, 1H), 3.61 (d, J ) 3.0 Hz, 1H), 3.62
(d, J ) 3.0 Hz, 1H), 4.09 (dd, J ) 8.4, 5.7 Hz, 1H); 13C NMR
(75 MHz) δ 13.9, 14.2, 17.3, 19.0, 35.4, 38.8, 57.8, 58.4, 78.5,
103.3; MS (LSIMS) m/z (%) 187 (MH+, 25), 169 (100); HRMS
of 6d /7d + H C10H19O3 calcd 187.1334; found, 187.1332. Minor
anomer: 1H NMR (300 MHz) δ 0.93-0.99 (m, 6H), 1.35-1.85
(m, 8H), 3.22 (s, 1H), 3.62 (d, J ) 3.0 Hz, 1H), 3.66 (d, J ) 3.0
Hz, 1H), 4.20-4.24 (m, 1H); 13C NMR (75 MHz) δ 13.8, 14.4,
16.4, 18.6, 35.1, 39.7, 60.7, 61.4, 77.9, 103.3.
C
11H12O3 calcd 192.0786, found 192.0790.
Gen er a l P r oced u r e for th e Rin g-Op en in g of P er h y-
d r ooxir en o[2,3-d ][1,2]d ioxin es u sin g Co(II) Sa len . To a
stirred solution of N,N′-bis(salicylidene)ethylenediaminocobalt-
(II) (10 mg, 0.03 mol) in CH2Cl2 (5 mL) at ambient temperature
was added 1,2-dioxine (1 mmol), and the reaction left to stir
until complete by TLC (3-16 h). All volatiles were then
removed in vacuo, and the product purified by flash chroma-
tography.
(()-(1a S,4S,4a R)-2,4-Dicycloh exyltetr a h yd r ooxir en o-
[2,3-c]fu r a n -2-ol 6e/7e. Major anomer: colorless solid; mp
81-83 °C; Rf 0.38 (80:20 hexane/ethyl acetate); IR (Nujol) 3400,
1
1304, 1241, 1021, 866 cm-1; H NMR (600 MHz) δ 0.95-1.95
(()-{(2S,3S)-3-[(1S)-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 148-150
°C; Rf 0.50 (60:40 hexane/ethyl acetate); IR (Nujol) 3408, 1673,
(m, 22H), 2.16 (s, 1H), 3.62 (d, J ) 3.0 Hz, 1H), 3.68 (d, J )
3.0 Hz, 1H), 3.73 (d, J ) 9.6 Hz, 1H); 13C NMR (150 MHz) δ
25.5, 25.6, 25.9, 26.0, 26.2, 26.2, 26.3, 28.2, 29.3, 29.6, 40.6,
43.9, 56.2, 58.0, 83.4, 104.6; MS (EI) m/z (%) 266 (M+, 10), 248
(30), 230 (40), 83 (90), 55 (100). Anal. Calcd for C16H26O3: C,
72.14; H, 9.83. Found: C, 71.85; H, 9.83. Minor anomer:1H
NMR (600 MHz) δ 0.95-1.95 (m, 22H), 3.14 (s, 1H), 3.72 (d, J
) 3.0 Hz, 1H), 3.75 (d, J ) 3.0 Hz, 1H), 3.89 (d, J ) 9.0 Hz,
1H); 13C NMR (150 MHz, partial) δ 26.1, 26.3, 27.2, 28.8, 29.1,
40.3, 44.3, 60.9, 82.9, 104.5
1
1595, 1252, 1103, 977 cm-1; H NMR (600 MHz) δ 2.34 (br d,
J ) 3.0 Hz, 1H), 3.59 (dd, J ) 6.6, 4.5 Hz, 1H), 4.26 (d, J )
4.5 Hz, 1H), 4.57 (dd, J ) 6.6, 3.0 Hz, 1H), 7.30-7.68 (m, 8H),
8.01-8.09 (m, 2H); 13C NMR (150 MHz) δ 57.6, 61.5, 71.2,
126.0-140.0 (8 13C signals), 193.9; MS (EI) m/z (%) 335 (MH+
- H2O, 8), 316 (15), 290 (20),105 (100). Anal. Calcd for
C
16H14O3: C, 75.57; H, 5.54. Found: C, 75.31; H, 5.41.
(()-(1a S,4S,4a R)-2,4-Dip h en ylt et r a h yd r ooxir en o[2,3-
(()-(1a S,4S,4a R)-2,4-Diisop r op ylt et r a h yd r ooxir en o-
[2,3-c]fu r a n -2-ol 6f/7f. Major anomer: colorless solid; mp 66-
68 °C; Rf 0.52 (60:40 hexane/ethyl acetate); IR (Nujol) 3363,
c]fu r a n -2-ol 6a /7a . Major anomer: 1H NMR (600 MHz) δ 3.05
(br s, 1H), 3.98 (s, 2H), 5.42 (s, 1H), 7.29-7.69 (m, 10H); 13C
NMR (150 MHz) δ 59.9, 62.0, 81.8, 103.0, 126.0-140.0 (8 13C
signals). Minor anomer: 1H NMR (600 MHz) δ 3.83 (br s, 1H),
4.06 (d, J ) 2.4 Hz, 1H), 4.17 (d, J ) 2.4 Hz, 1H), 5.48 (s, 1H),
7.29-7.69 (m, 10H).
1
1414, 1211, 1060, 1010, 868 cm-1; H NMR (600 MHz) δ 1.0
(d, J ) 6.6 Hz, 6H), 1.05 (d, J ) 6.6 Hz, 6H), 1.81 (d sept, J )
9.0, 6.6 Hz, 1H), 2.04 (sept, J ) 6.6 Hz, 1H), 2.11 (s, 1H), 3.63
(d, J ) 3.0 Hz, 1H), 3.67 (d, J ) 3.0 Hz, 1H), 3.68 (d, J ) 9.0
Hz, 1H); 13C NMR (150 MHz) δ 18.0, 19.4, 31.9, 33.8, 56.5,
58.2, 84.7, 105.0; MS (EI) m/z (%) 187 (M+ + H, 10), 169 (100),
97 (40), 71 (70). Anal. Calcd for C10H18O3: C, 64.48; H, 9.74.
Found: C, 64.24; H, 9.96. Minor anomer: 1H NMR (600 MHz)
δ 0.96 (d, J ) 6.6 Hz, 6H), 1.04 (d, J ) 6.6 Hz, 6H), 1.63 (d
sept, J ) 9.3, 6.6 Hz, 1H), 1.93 (sept, J ) 6.6 Hz, 1H), 3.12 (s,
1H), 3.72 (d, J ) 3.0 Hz, 1H), 3.76 (d, J ) 3.0 Hz, 1H), 3.84 (d,
J ) 9.3 Hz, 1H); 13C NMR (150 MHz) δ 15.6, 18.7, 30.8, 34.3,
61.5, 60.9, 84.0, 105.1.
(()-{(2S ,3S )-3-[(1S )-1-H y d r o x y e t h y l]o x ir a n -2-y l}-
(p h en yl)m eth a n on e 4b. Colorless solid; mp 90-92 °C; Rf
0.50 (60:40 hexane/ethyl acetate); IR (Nujol) 3448, 2924, 2854,
1677, 1597, 1450, 1274, 1234, 1065, 982, 964, 705 cm-1 1H
;
NMR (600 MHz) δ 1.31 (d, J ) 6.6 Hz, 3H), 3.29 (dd, J ) 6.6,
4.8 Hz, 1H), 3.57 (dq, J ) 6.6, 6.6 Hz, 1H), 4.16 (d, J ) 4.8 Hz,
1H), 7.49-7.53 (m, 2H), 7.59-7.61 (m, 1H), 8.04-8.06 (m, 2H);
13C NMR (150 MHz) δ 20.5, 57.4, 61.6, 64.7, 128.5, 128.6, 133.8,
135.5, 193.9; MS (EI) m/z (%) 192 (M+, 4), 149 (10), 123 (20),
105 (90), 86 (100). Anal. Calcd for C11H12O3: C, 68.73; H, 6.29.
Found: C, 68.85; H, 6.40.
(()-(1a S,4S,4a R)-2-Meth yl-4-ph en yltetr a h yd r ooxir en o-
[2,3-c]fu r a n -2-ol 6b/7b. Major anomer: 1H NMR (600 MHz)
δ 1.38 (d, J ) 7.2 Hz, 3H), 3.64 (d, J ) 3.0 Hz, 1H), 3.72 (d, J
) 3.0 Hz, 1H), 4.45 (q, J ) 7.2 Hz, 1H), 7.27-7.34 (m, 3H),
7.53-7.55 (m, 2H); 13C NMR (150 MHz) δ 19.0, 59.1, 61.1, 75.0,
101.9, 126.4, 127.8, 128.1, 140.8. Minor anomer: 1H NMR (600
MHz) δ 1.25 (d, J ) 6.6 Hz, 3H), 3.63 (d, J ) 3.0 Hz, 1H), 3.93
(d, J ) 3.0 Hz, 1H), 4.58 (q, J ) 6.6 Hz, 1H), 7.27-7.34 (m,
3H), 7.53-7.55 (m, 2H).
(()-[(2S,3S)-3-(Hyd r oxym eth yl)-3-m eth yloxir a n -2-yl]-
1
(p h en yl)m eth a n on e 4g. H NMR (300 MHz) δ 1.63 (s, 3H),
1.70-1.80 (br s, 1H), 3.63 (br s, 2H), 4.02 (s, 1H), 7.35-7.63
(m, 3H), 7.98-8.01 (m, 2H); 13C NMR (150 MHz, partial) δ
19.3, 63.4, 63.8, 193.1
(()-(1a S,4a S)-4a -Met h yl-2-p h en ylt et r a h yd r ooxir en o-
[2,3-c]fu r a n -2-ol 6g/7g. Major anomer: colorless solid; mp
78-81 °C; Rf 0.45 (60:40 hexane/ethyl acetate); IR (Nujol) 3352,
1
1262, 1105, 1022, 1002, 763 cm-1; H NMR (300 MHz) δ 1.61
(s, 3H), 2.82 (br s, 1H), 3.58 (s, 1H), 3.99 (d, J ) 9.9 Hz, 1H),
4.08 (d, J ) 9.9 Hz, 1H), 7.35-7.63 (m, 5H); 13C NMR (150
MHz, partial) δ 13.6, 69.4, 65.5, 102.8; MS (EI) m/z (%) 174
(M+ - H2O, 5), 161 (60), 123 (20), 105 (100). Anal. Calcd for
(()-[(2S,3S)-3-(H yd r oxym et h yl)oxir a n -2-yl](p h en yl)-
m eth a n on e 4c.12 Colorless oil that decomposed over a period
of several days; Rf 0.43 (60:40 hexane/ethyl acetate); IR (neat)
C
11H12O3: C, 68.73; H, 6.29. Found: C, 69.00; H, 6.41. Minor
1
3430, 1688, 1597, 1450, 1229, 1042, 701 cm-1; H NMR (600
anomer: 1H NMR (300 MHz) δ 1.53 (s, 3H), 3.51 (br s, 1H),
3.65 (s, 1H), 3.87 (d, J ) 10.5 Hz, 1H), 4.25 (d, J ) 10.5 Hz,
1H), 7.35-7.63 (m, 5H).
MHz) δ 3.61 (dt, J ) 5.4, 4.2 Hz, 1H), 3.67 (br dd, J ) 12.6,
5.4 Hz, 1H), 3.71 (br dd, J ) 12.6, 5.4 Hz, 1H), 4.23 (d, J ) 4.2
Hz, 1H), 7.34-7.62 (m, 3H), 8.00-8.02 (m, 2H); 13C NMR (150
MHz) δ 56.8, 58.0, 59.9, 125.7-128.9 (4 Aryl 13C), 193.5; MS
(EI) m/z (%) 178 (M+, 10), 161 (30), 147 (20), 105 (100).
(()-{(2R ,3R )-3-[(1S )-1-H y d r o x y e t h y l]o x ir a n -2-y l}-
(p h en yl)m eth a n on e 5b. Colorless solid; mp 69-71 °C; Rf
0.50 (60:40 hexane/ethyl acetate); IR (Nujol) 3400, 1690, 1597,
1
1226, 1093, 1038, 984, 707 cm-1; H NMR (600 MHz) δ 1.13
(12) Boeckman, R. K., J r.; Thomas, E. W. J . Am. Chem. Soc. 1979,
101, 987. Boeckman, R. K., J r.; Thomas, E. W. Tetrahedron Lett. 1976,
17, 4045.
(d, J ) 6.6 Hz, 3H), 2.31 (br d, J ) 3.0 Hz, 1H), 3.38 (dd, J )
7.2, 4.8 Hz, 1H), 3.56 (ddq, J ) 6.6, 6.6, 3.0 Hz, 1H), 4.28 (d,
J . Org. Chem, Vol. 68, No. 13, 2003 5209

Greatrex et al.
J ) 4.8 Hz, 1H), 7.33-7.65 (m, 3H), 7.99-8.01 (m, 2H); 13C
NMR (150 MHz) δ 19.0,57.5, 67.4, 65.4, 125.7-139.1 (4 aryl
13C), 193.1; MS (EI) m/z (%) 193 (MH+, 15), 175 (40), 154 (100),
137 (80); HRMS of 7b C11H13O3 (MH+) calcd 193.0864, found
193.0864.
(()-(1a R,4S,4a S)-2-Meth yl-4-p h en yltetr a h yd r ooxir en o-
[2,3-c]fu r a n -2-ol 8b/9b. Major anomer: 1H NMR (600 MHz)
δ 1.42 (d, J ) 6.0 Hz, 3H), 3.21 (br s, 1H), 3.67 (dd, J ) 3.0,
0.6 Hz, 1H), 3.70 (d, J ) 3.0 Hz, 1H), 4.32 (dq, J ) 6.0, 0.6 Hz,
1H), 7.33-7.60 (m, 5H); 13C NMR (150 MHz) δ 15.2, 57.7, 60.7,
72.9, 102.2, 125.7-139.1 (4 aryl 13C). Minor anomer: 1H NMR
(600 MHz) δ 1.43 (d, J ) 6.6 Hz, 3H), 3.71 (dd, J ) 3.0, 0.6
Hz, 1H), 3.80 (d, J ) 3.0 Hz, 1H), 4.24 (dq, J ) 6.6, 0.6 Hz,
1H), 7.33-7.60 (m, 5H); 13C NMR (150 MHz) δ 16.3, 60.1, 61.6,
74.0 104.0, 125.7-139.1 (4 aryl 13C).
(150 MHz,) δ 25.7, 25.8, 26.0, 26.0, 26.3, 26.4, 26.4, 27.9, 29.2,
30.1, 38.7, 43.6, 54.3, 57.1, 80.8, 104.2; MS (EI) m/z (%) 266
(M+, 4), 248 (15), 230 (30), 83 (100); HRMS of 8e/9e C16H26O3
calcd 266.1887, found 266.1881. Minor anomer: 1H NMR (600
MHz) δ 0.97-1.32 (m, 10H), 1.58-1.96 (m, 12H), 2.93 (s, 1H),
3.54 (dd, J ) 7.8, 1.2 Hz, 1H), 3.65 (d, J ) 3.0 Hz, 1H), 3.73
(dd, J ) 3.0, 1.2 Hz, 1H); 13C NMR (150 MHz, partial) δ 25.7,
26.0, 26.2, 26.3, 26.3, 26.8, 39.9, 44.2, 58.5, 59.2, 82.6, 104.7.
Ack n ow led gm en t. B.W.G. thanks the Faculty of
Science, University of Adelaide and N.F.J . thanks the
Australian Postgraduate Award Scheme for financial
support in the form of scholarships. We also thank the
Australian Research Council for funding.
(()-(1a R,4S,4a S)-2,4-Dicycloh exyltetr a h yd r ooxir en o-
[2,3-c]fu r a n -2-ol 8e/9e. Major anomer: colorless solid; mp
94-95 °C; Rf 0.19 (CH2Cl2); IR (Nujol) 3400, 1304, 1241, 1021,
Su p p or tin g In for m a tion Ava ila ble: Ortep representa-
1
tion of 4b and H NMR of 1,2-dioxines 2c,d ,f and 3b-g. This
material is available free of charge via the Internet at
http://pubs.acs.org.
1
866 cm-1; H NMR (600 MHz) δ 0.97-1.32 (m, 10H), 1.58-
1.96 (m, 12H), 2.20 (s, 1H), 3.58 (d, J ) 3.0 Hz, 1H), 3.63 (dd,
J ) 3.0, 0.6 Hz, 1H), 3.70 (br d, J ) 8.4 Hz, 1H); 13C NMR
J O0300845
5210 J . Org. Chem., Vol. 68, No. 13, 2003