Experimental Section
4.42 (dd, J ) 18.6, 4.3 Hz), 3.98 (d, J ) 9.2 Hz, 1H), 2.20 (s,
1
3
3
1
2
H), 1.52 (s, 3H), 1.38 (s, 3H); C NMR (100 MHz, CDCl
82.1, 168.0, 140.9, 133.5, 113.7, 102.9, 70.8, 59.9, 26.5, 25.6,
0.2; HRMS calcd for C11 265.0688, Found 265.0685. Anal.
: C, 54.54; H, 5.83. Found C, 54.20; H, 6.07.
,5-Di-O-acetyl-3-hydroxy-1,2-O-isopropylidene-D-fruc-
3
) δ
Optimized Conditions for the Preparation of 4,5-Di-O-
acetyl-1,2-O-isopropylidene-D-erythro-hexos-2,3-diulo-2,6-
pyranose, 3. (a) Oxidation. Compound 4 (10.0 g, 38.42 mmol),
4 6
H O
Calcd for C11
4 6
H O
Et
2
3
BzNCl (442 mg, 1.92 mmol), NaIO
CO (826 mg, 5.92 mmol) were vigorously stirred in a mixture
of 33 mL of CHCl and 33 mL of H O. RuCl monohydrate (303
4
(12.4 g, 57.24 mmol), and
4
K
3
topyranose, 7. Oxidation, selective deketalization, and acety-
lation were carried out as described for 3 starting from compound
3
2
3
mg, 1.34 mmol) were added, and the reaction mixture was
heated at 70 °C. 2-Propanol (11 mL) was added after 2 h, and
the suspension was further stirred for 5 h. The reaction mixture
was filtered through a Celite pad, and this material was washed
4
(10.0 g, 38.42 mmol). Ice (20.0 g) was added to the reaction
mixture once the acetylation was complete (3 h stirring at room
temperature). The precipitate was filtered off the solution,
washed with ice-water (2 × 15 mL), and lyophilized to give 7
with CH
filtrate, the organic layer was separated, and the aqueous layer
was extracted with CH Cl
(2 × 20 mL). The combined organic
extracts were washed with saturated Na SO (130 mL), brine
Cl
2 2
(2 × 35 mL). This solution was mixed with the
as a white solid (5.14 g, 41% overall yield). [R]D25 -116 (c 0.98,
-1
1
CHCl
500 MHz, D
Hz, 1H), 4.39 (d, J ) 9.5 Hz, 1H), 4.24 (dd, J ) 13.6, 1.8 Hz),
3
); mp 91.1-93.7 °C; IR (ATR) 3467, 1735 cm ; H NMR
2
2
(
O) δ 5.34 (dd, J ) 4.1, 1.8 Hz, 1H), 5.17 (d, J ) 4.1
2
2
3
(
100 mL), and water (100 mL). The solid, which was obtained
4
3
.06 (d, J ) 9.5 Hz, 1H), 3.85 (dd, J ) 13.6, 1.8 Hz, 1H), 2.16 (s,
after drying and evaporating the solvents, was not purified
13
H), 2.13 (s, 3H), 1.55 (s, 3H), 1.47 (s, 3H); C NMR (125 MHz,
O) δ 173.5, 172.7, 113.9, 106.7, 91.2, 70.3, 69.7, 68.7, 61.4,
6.0, 24.9, 20.3, 20.1; HRMS calcd for C13 Na 343.1005,
: C, 49.00; H, 6.51.
1
further. H NMR data were in agreement with the described
ones. (b) Selective deketalization. AcOH (80 mL) and water (20
D
2
9
2
20 9
H O
mL) were added at once to the oxidation raw material from the
previous step (8.77 g, 38.42 mmol referred to starting material
Found 343.1008. Anal. Calcd for C13
20 9
H O
Found C, 48.75; H, 6.29.
4
). The resulting solution was stirred for 12 h at room temper-
ature. The solvents were removed in vacuo at room temperature,
and the residue was dissolved in CH Cl (50 mL). The solid,
which was obtained after drying (an. NaSO ) and evaporating
General Procedure for the Epoxidation of Alkenes.
Alkene (2.22 mmol) and the required amount of catalyst 3 or 7
2
2
(
8-30 molar %) were dissolved in acetonitrile/dimethoxymethane
44 mL, 1:2 v/v). A pH ) 6 buffer solution (8 mL) and tetra-
4
(
1
13
the CH
data were in agreement with the described ones.
lation. ZnCl (132 mg, 0.96 mmol) was added to a suspension of
diol 5 arising from part b (8.56 g, 38.42 mmol referred to starting
material 4) in Ac O (19.4 mL, 153.95 mmol), and the mixture
was stirred under N at room temperature for 3 h. The reaction
mixture was diluted with AcOEt (20 mL), and the solution was
passed through a neutral silica gel pad (15 g). SiO was washed
2 2
Cl , was not purified further. H NMR and C NMR
butylammonium hydrogen sulfate (35 mg, 0.10 mmol) were
slowly added with stirring, and the mixture was cooled to the
desired temperature. The flask was equipped with two syringe
pumps; one of them was filled with a solution of oxone (2.23 g,
5
j,15
(c) Acety-
2
2
3
.62 mmol) in the pH ) 6 buffer (14 mL), and the other one
2
with a solution of K CO (744 mg, 5.33 mmol) in water (14 mL).
2
3
The two solutions were added dropwise over a 2 h period (syringe
pump). The solution was stirred at the desired temperature for
the corresponding reaction time. The crude was quenched by
addition of water (40 mL) and pentane (10 mL). The reaction
mixture was extracted with an organic solvent (9a and 9e:
hexane, 4 × 40 mL; 9b-d: 4 × 40 mL DCM). The combined
organic extracts were washed with brine (50 mL), dried over
sodium sulfate, filtered, and concentrated under reduced pres-
sure. The crude material was purified by flash chromatography
on silica gel.
2
with AcOEt (100 mL), the combined organic solutions were
gathered, AcOEt was removed in vacuo, and the resulting oil
was chromatographed (75 g neutral SiO
from 1:0 to 7:3) mixtures as the eluent. The oil, which was
2
) using hexane/EtOAc
(
obtained after drying and evaporating the solvents, was used
as the catalyst for the epoxidation of alkenes without any further
purification (7.71 g, 66% overall yield). Physical and spectro-
5
j
D
scopic data were in agreement with the described ones. [R] 25
5
j
D
-
104 (c 0.95, CHCl
3 3
) [lit. [R] 25 -103 (c 0.98, CHCl )]; Anal.
The ee’s were determined by chiral chromatography, and the
configuration of the epoxides were established by comparison
with either reported retention times or optical rotations (9a:
Calcd for C13 : C, 51.65; H, 6.00. Found C, 51.36; H, 6.10.
18 8
H O
Optimization of the Acetylation Conditions (Experi-
ments Described in Table 1). A quantity of 510 mg of raw
material 5 obtained as indicated in part b above (2.29 mmol
referred to starting material 4) and the catalyst were dissolved
16
chiralpak AD, (R,R)-9a Rt 5.6 min, (S,S)-9a Rt 8.6 min; 9b:
4i
chiralcel OD, (S,S)-9b Rt 19.3 min, (R,R)-9b Rt 21.9 min; 9c:
4i
chiralcel OD, (S,S)-9c Rt 7.6 min, (R,R)-9c Rt 9.1 min; 9d:
in the corresponding Ac
2
O amount, and the mixture was stirred
Alphadex, (S,S)-9d Rt 26.9 min, (R,R)-9d Rt 27.4 min, (+)-(R,R)-
under N at the given temperature for the given time in each
2
4i
4c
9
d; 9e: chiralpak OD, (S)-9e Rt 10.6 min, (R)-9e Rt 17.4 min,
case. The experiments under microwave irradiation were carried
out in a CEM discover microwave reactor (temperature is
automatically controlled by a noncontact infrared sensor that
monitors and controls the temperature conditions of the reaction
vessel). The reaction mixture was filtered through a short silica
17
(
-)-(R)-9e.
Acknowledgment. A.V.-F. thanks the ICIQ and
“
Ram o´ n Areces” Foundations for financial support. N.N.
and P.M. thank the “Programa Torres Quevedo”.
2
gel pad (5.0 g neutral SiO ) eluting with a mixture of hexane/
AcOEt, 1:1 v/v. The ratio between 3 and 6 was measured by
Supporting Information Available: 1H and 13C NMR
spectra for 2-7 and CIF data for 6 and 7. This material is
available free of charge via the Internet at http://pubs.acs.org.
1
integration of appropriated signals in the H NMR spectra of
the mixture after the chromatographic purification.
(
5S)-9-Acetoyloxy-2,2-dimethyl-1,3,6-trioxaspiro[4.5]dec-
8
-en-10-one, 6. DMAP (940 mg, 7.68 mmol) and Ac
2
O (14.5 mL,
JO051682H
1
15.49 mmol) were added to a solution of 5 (8.87 g, 38.42 mmol
referred to starting material 4, prepared as described in part b
(
14) ESI mass spectra of compounds 3 indicated that an equilibra-
of the recipe for the preparation of 3) under N
CH Cl at room temperature. The reaction mixture was filtered
through a short SiO gel column. The filtrate was concentrated,
and the residue was chromatographed using hexane/AcOEt
2
in 200 mL of
tion between the two species was taking place in hydroorganic solution,
as the peak corresponding to the hydrate 7 could be observed in a pure
sample of 3. On the other hand, no peak corresponding to ketone 3
was observed in a sample of 7.
2
2
2
(
from 1:0 to 3:2) mixtures as the eluent to give 6 as an oil (4.26
(15) Lichtenthaler, F. W.; Doleschal, W.; Hahn, S. Liebigs Ann.
Chem. 1985, 2454-2464.
(16) Roberts, S. M.; Poignant, G. Catalysts for Fine Chemical
Synthesis. Hydrolysis, Oxidation and Reduction; 1st ed.; John Wiley
g, 17.59 mmol, 46% yield). This oil was recrystallized in hexane
to get a white solid (3.37 g, 13.91 mmol, 36% overall yield). [R]D25
-
129 (c 0.90, CHCl
3
); mp 63.7-64.4 °C; IR (ATR) 1764, 1702
) δ 6.68 (dd, J ) 4.3, 1.9 Hz,
H), 4.79 (dd, J ) 18.6, 1.8 Hz, 1H), 4.59 (d, J ) 9.2 Hz, 1H),
&
Sons: Chichester, 2002; pp 94-98.
-
1 1
cm ; H NMR (400 MHz, CDCl
3
(17) Brandes, B. D.; Jacobsen, E. N. J. Org. Chem. 1994, 59, 4378-
1
4380.
10146 J. Org. Chem., Vol. 70, No. 24, 2005