Regio- and stereoselective ring opening of epoxides. Enantioselective synthesis of 2,3,4-trisubstituted five-membered heterocycles

Article abstract of DOI:10.1016/S0957-4166(02)00160-X

By using the appropriate protecting groups, the opening of (2S,3S,4E)-5-benzenesulfonyl-2,3-epoxy-pent-4-en-1-ol (-)-2 could be controlled and used for the synthesis of the enantiomeric pyrrolidines (+)- and (-)-18 and the tetrahydrofuran analogs (+)- and (-)-19.

Full text of DOI:10.1016/S0957-4166(02)00160-X

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 13 (2002) 639–646
Regio- and stereoselective ring opening of epoxides.
Enantioselective synthesis of 2,3,4-trisubstituted five-membered
heterocycles†
David D´ıez,* M. Templo Beneitez, Isidro S. Marcos, N. M. Garrido, P. Basabe and
Julio G. Urones
Dpto. de Qu´ımica Orga´nica, Facultad de Ciencias Quimicas, Universidad de Salamanca, 37008 Salamanca, Spain
Received 18 March 2002; accepted 27 March 2002
Abstract—By using the appropriate protecting groups, the opening of (2S,3S,4E)-5-benzenesulfonyl-2,3-epoxy-pent-4-en-1-ol (−)-2
could be controlled and used for the synthesis of the enantiomeric pyrrolidines (+)- and (−)-18 and the tetrahydrofuran analogs
(+)- and (−)-19. © 2002 Elsevier Science Ltd. All rights reserved.
1. Introduction
2. Results and discussion
The discovery of the asymmetric epoxidation of allylic
epoxides by Sharpless1 was a milestone in asymmetric
synthesis and following on from this, the regio- and
stereoselective opening of chiral epoxides have been the
subject of many studies in recent years.2
In this work we wished to investigate the regio- and
stereoselective opening of chiral epoxides and disclose
the possibility of obtaining enantiomeric compounds by
the use of appropriate protecting groups (Scheme 2).
The starting material chosen for these studies was com-
Five-membered oxa and aza ring systems are widely
distributed in nature and have attracted the interest of
the scientific community, particularly in conjunction
with the total synthesis of polyether natural products,3
or pyrrolidines with glycosidase inhibiting activity.4
Our laboratory has been involved in a program seeking
to exploit the reactivity of 1-hydroxymethyl-4-sul-
fonylbutadienes for the synthesis of functionalized oxy-
gen and nitrogen five-membered heterocycles.
pound (−)-2, obtained by Sharpless epoxidation of 1
with
-(+)-DET,1c with e.e. of 95% (measured by Mosh-
L
er’s ester derivatization).6 Compound (−)-2 was pro-
tected with various groups under the usual conditions
(Scheme 3).
In a recent paper we reported the influence of several
protecting groups on the cyclization of d-hydroxyepox-
ides.7 In this paper, control of the opening of epoxides
The vinyl sulfone 1 has been transformed into an
isosorbide analogue exploiting its chemo- and enan-
tioselective epoxidation and the reactivity of the a
position of the vinyl sulfone towards electrophiles.5
Similarly, 1 has been transformed into a biologically
active 2,3,4-trisubstituted pyrrolidine (+)-18, and tetra-
hydrofuran (+)-19 using the regio- and stereoselective
opening of the corresponding epoxide (Scheme 1).
SO2Ph
HO
1
H
H
O
HO
OH
HO
OH
PhO2S
OH
O
N
H
H
H
O
HCl
Isosorbide analogue
(+)-18
(+)-19
* Corresponding author. Tel.: 34 923 294474; fax: 34 923 294574;
e-mail: ddm@usal.es
† In memoriam of Dr. B. del Rey.
Scheme 1.
0957-4166/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(02)00160-X

640
D. D´ıez et al. / Tetrahedron: Asymmetry 13 (2002) 639–646
The stereochemistry of these compounds was estab-
O
SO2Ph
PO
O
lished in the following way. The stereochemistry of
(+)-7 has been reported.5 Treatment of compounds
(+)-8 and (−)-9 under basic conditions gave the enan-
tiomeric tetrahydrofurans (+)-10 and (−)-10, respec-
tively, in a diastereoselective way. In order to establish
unequivocally the configuration of each molecule, both
were transformed into known compounds. Treatment
of (+)-10 and (−)-10 separately with n-BuLi in THF
and quenching with TsCl led to compounds (+)-7 and
(−)-7, respectively, in 60% yield with 20% starting mate-
rial recovered and 5% of the diastereoisomers of (+)-10
and (−)-10 at the C-2 center, compounds (+)-11 and
(−)-11, respectively. These derivatives, (+)-7 and (−)-7,
already demonstrate the stereochemistry of the parent
compounds, but due to the low value of the specific
rotation, were transformed to give the enantiomeric
pyrrolidines (+)-12 and (−)-12, respectively, by treat-
ment with benzylamine in methanol. No other
diastereomer was detected, confirming the stereochemi-
cal outcome of the epoxide ring-opening reaction
(Scheme 5).
O
O
O
PO
PO
SO2Ph
SO2Ph
HO
OH
HO
OH
X
X
Scheme 2.
The stereochemistry of (+)-6 remained to be estab-
lished. This was carried out as shown in Scheme 6.
Deprotection of (+)-6 with HCl/MeOH followed by
treatment under basic conditions, gave a 1:1 mixture of
diastereoisomers at C-2, (−)-13 and (−)-14. These com-
pounds were protected under the usual conditions,
without isolation, to give (−)-10 and (−)-11 in 80% yield
for the two steps. The specific rotation value and the
rest of the physical properties for (−)-10 and (−)-11
were concordant with compounds obtained before,
confirming the inversion at C-2 during the opening of
the epoxide in the reaction of (−)-2 with AlCl3 in
acetone. The stereochemical assignment was confirmed
by deprotection of (−)-10 and (−)-11 to give (−)-13 and
(−)-14 respectively, in excellent yield (Scheme 6).
Scheme 3. Reagents and conditions: (a) L
-(+)-DET, Ti(iPrO)4,
TBHP, CH2Cl2, −20°C, 12 h, 85%; (b) TsCl, Py, 80% or
CF3COCl, Py, 71%, or Ac2O, Py, 95%.
obtained from 1-hydroxymethyl-4-sulfonylbutadiene by
the use of different protecting groups is reported. Treat-
ment of compounds (−)-2, (−)-3, (−)-4 and (−)-5, with
AlCl3 in acetone8 gave only one compound for each
starting material as shown in Scheme 4.
As can be seen, the opening of the epoxide could be
controlled by choosing a suitable protecting group. If
there is no ‘internal nucleophile’ on C-1, as for (−)-3
and (−)-4, inversion at C-3 occurs, giving rise to com-
pounds (+)-7 and (+)-8, respectively. The existence of
an ‘internal nucleophile’ on C-1, as is the case for (−)-2
and (−)-5, produced opening on C-2 with inversion of
configuration in both cases, giving compounds (+)-6
and (−)-9, respectively (Scheme 4).
The regio- and stereoselective opening of these epoxides
could easily be rationalized. Compound (+)-6 would be
produced by Payne rearrangement1b and transforma-
tion of the corresponding epoxide into the acetal,9 while
compounds (+)-7 and (+)-8 would arise from nucleo-
philic opening at C-3 by acetone, as described by Sharf8
and Colvin.10 The result for (−)-9 could be understood
by the intervention of an acetoxonium cation and ace-
tone acting as nucleophile, as described by Rastetter
and Oppolzer.11
Scheme 4.

D. D´ıez et al. / Tetrahedron: Asymmetry 13 (2002) 639–646
641
(+)-8
(-)-9
a
a
O
5
O
3
O
O
[α]D20= + 18.0
1´
SO2Ph
2
[α]D20= - 17.8
O
O
(+)-10
SO2Ph
(-)-10
b
b
O
O
O
O
3
O
1
O
O
O
+
1
+
OTs
O
OTs
(-)-7
O
SO2Ph
SO2Ph
SO2Ph
SO2Ph
(+)-11
[α]D20= +13.8
(-)-11
(+)-7
[α]D20= - 3.2
[α]D20= + 3.8
[α]D20= - 14.0
c
c
O
O
O
O
3
2
5
1´
N
CH2Ph
N
SO2Ph
SO2Ph
CH2Ph
1´´
[α]D20= - 37.3
(+)-12 [α]D20= + 40.2
(-)-12
Scheme 5. Reagents and conditions: (a) K2CO3, MeOH, quantitative; (b) 1. n-BuLi, THF, −78°C, 2. TsCl, THF, 60%; (c) BnNH2,
MeOH, Et3N, 78%.
HO
OH
conditions to produce (+)-16 in 77% yield. Compound
(+)-16 was then debenzylated under the same condi-
tions as before to produce (+)-17. Without isolation,
(+)-17 was subjected to treatment with 6 M HCl to give
pyrrolidine (+)-18 in an excellent yield (80%) as its
hydrochloride salt, over two steps. This compound
shows the same physical properties as described in the
literature.4d
(-)-13
a
80%
O
(-)-10
+
(-)-13
SO2Ph
b
a
Ratio (-)-10 : (-)-11 = 1:1
+
(+)-6
90%
80%
HO
OH
(-)-11
70%
a
The versatility of this procedure for obtaining enan-
tiomeric compounds could be seen as compound (−)-7
having been transformed above into (−)-12. This com-
pound could easily be transformed into the enantiomer
of pyrrolidine (+)-18, following an identical procedure.
(-)-14
O
SO2Ph
(-)-14
Scheme 6. Reagents and conditions: (a) 1. 2 M HCl, MeOH;
2. Na2CO3, MeOH; (b) p-TsOH, acetone.
The synthesis of the tetrahydrofuran analogues was
straightforward. Tetrahydrofuran (+)-10 was trans-
formed into diol (+)-19, as shown in Scheme 8. Depro-
tection of the acetal under acidic conditions gave diol
(+)-13, confirming the assignment of (−)-13 made
above. Desulfonylation of (+)-13 as before gave the
oxygen analogue of pyrrolidine (+)-18, the tetra-
hydrofuran (+)-19. The enantiomeric tetrahydrofuran
(−)-19 could be obtained starting from (−)-10 following
the same procedure.
Having determined the stereochemical outcome of the
epoxide ring-opening reactions, we then synthesized the
corresponding heterocycles. Compound (+)-12 was
transformed into pyrrolidine (+)-18 as shown in Scheme
7.
Deprotection of (+)-12 with H2, Pd/C led to (+)-15 in a
95% yield. The stereochemistry of this compound was
1
assigned by H NMR and NOE experiments.5 Desul-
Thus, using different protecting groups, the regio- and
stereoselectivity of the epoxide ring-opening reaction of
(2S,3S,4E)-5-benzenesulfonyl-2,3-epoxy-pent-4-en-1-ol
fonation of (+)-15 proceed in low yield, so (+)-12 was
first treated with sodium amalgam under the usual

642
D. D´ıez et al. / Tetrahedron: Asymmetry 13 (2002) 639–646
3. Experimental
O
O
3
O
O
3
3.1. General
a
SO2Ph
1´
SO2Ph
1´
1
1
N
Unless otherwise stated, all chemicals were purchased
as the highest purity commercially available and were
used without further purification. Melting points were
determined with a Kofler hot stage melting point
apparatus and are uncorrected. IR spectra were
recorded on a BOMEM 100 FT-IR spectrophotometer.
1H and 13C NMR spectra were performed in deutero-
chloroform and referenced to the residual peak of
CHCl3 at l 7.26 and l 77.0 ppm for 1H and 13C,
respectively, in a Bruker WP-200 SY and a BRUKER
DRX 400 MHz. Chemical shifts are reported in l, ppm
and coupling constants (J) are given in Hz. MS were
performed in a VG-TS 250 spectrometer at 70 eV
ionizing voltage. Mass spectra are presented as m/z (%
rel. int.). HRMS were recorded on a VG Platform
spectrometer using Electronic Impact (EI) or Fast
Atom Bombardment (FAB) technique. Optical rota-
tions were determined in a Perkin–Elmer 241 polarime-
ter in 1 dm cells. Diethyl ether, THF and benzene were
N
(+)-12
H
(+)-15
Bn
b
O
O
3
HO
OH
3
O
O
3
a
c
1´
1´
1
1
N
N
1´
HCl
1
N
H
H
Bn
(+)-16
(+)-18
(+)-17
Scheme 7. Reagents and conditions: (a) H2, Pd/C, MeOH,
90%; (b) Na(Hg), MeOH, 77%; (c) 6 M HCl, MeOH, 80%.
HO
5
OH
3
HO
5
OH
O
5
O
3
b
a
3
2
2
distilled
from
sodium,
and
pyridine
and
1´
1´
O
1´
SO2Ph
O
dichloromethane were distilled under argon from CaH2.
O
SO2Ph
(+)-10
(+)-13
(+)-19
3.2. (2S,3S,4E)-5-Benzenesulfonyl-2,3-epoxy-pent-4-en-
1-ol (−)-2
Scheme 8. Reagents and conditions: (a) 6 M HCl, MeOH,
80%; (b) Raney-Ni, MeOH, 77%.
To a solution of
L
-(+)-DET (460 mg, 2.23 mmol) in
could be controlled to give enantiomeric pyrrolidine
and tetrahydrofuran analogues. Compounds with tosyl-
ate or trifluoroacetate groups at C(1) undergo ring-
opening under the above conditions with inversion at
C-3, while compounds with no protecting group or an
acetate group at C-1 undergo inversion at the C-2
center. Thus, employing only natural -(+)-DET in the
Sharpless epoxidation can be used in combination with
this methodology to obtain both enantiomeric series.
CH2Cl2 (10 mL) cooled at −23°C was added titanium
isopropoxide (0.61 mL, 2.23 mmol). The mixture was
stirred for 15 min before the addition of a solution of
compound 1 (500 mg, 2.23 mmol) in CH2Cl2 (12 mL)
and finally a solution of t-butyl hydroperoxide (5.5 M
in decane, 0.80 mL, 4.46 mmol) was added. The result-
ing mixture was then stored (ꢀ48 h) in the freezer at
ꢀ20°C. Then the flask was placed in a bath at −23°C
and 10% aqueous tartaric acid solution (7 mL) was
added. After 30 min the cooling bath was removed and
stirring was continued at room temperature for 1 h
until the aqueous layer became clear. The organic layer
was washed once with water. The resulting solution was
cooled in an ice bath and then 1N sodium hydroxide
solution (8 mL) was added and the mixture was stirred
for 30 min. The organic layer was washed with water
and brine, dried with sodium sulfate and concentrated
to give a yellow oil. It was purified by flash chromatog-
raphy (n-hexane/EtOAc, 7:3) to give (−)-2 (454 mg,
85%) as a white oil: [h]2D0=−11.7 (c=1.90, CHCl3), IR
L
The fact that both enantiomeric series can be obtained
by the use of either isomer of DET in the Sharpless
epoxidation reaction opens interesting possibilities.
Either the route from epoxide to heterocycle with the
best yield can be selected, or, where additional stereo-
centers are present in the starting material, it should be
possible to use the enantiomer of DET that gives the
best selectivity and yield in the Sharpless oxidation step,
adjusting the subsequent chemistry to give the desired
stereochemistry at the three centers in the heterocycles
produced using the method described here.
(film) w (cm−1): 3600, 1447, 1308, 1148, 1086; H NMR
1
(CDCl3, 200 MHz) l: 7.90–7.51 (5H, m, Ar), 6.77 (1H,
dd, J=15.0, and 5.9, H-4), 6.67 (1H, d, J=15.0, H-5),
3.93 (1H, d, J=13.0, Ha-1), 3.71 (1H, d, J=13.0, Hb-1),
3.57 (1H, dd, J=5.9 and 1.8, H-3), 3.09 (1H, d, J=1.8,
H-2); 13C NMR (CDCl3, 50.3 MHz) 142.0 (CH-4),
139.8 (C-ipso), 133.7 (CH-para), 132.9 (CH-5), 129.4
(2CH-meta), 127.7 (2CH-ortho), 61.4 (CH-3), 60.5
(CH2-1), 52.2 (CH-2); EIMS m/z (%) 241 (M++1, 3) 197
(30), 125 (45), 77 (100) 64 (15), HRMS (EI) m/z calcd
for C11H12O4S 240.0456; found 241.0453 (M++1).
In this paper, we have also reported the transformation
of compound (−)-2 into a 2,3,4-trisubstituted pyrro-
lidine, which has glycosidase inhibiting activity,5 its
tetrahydrofuran analogue and a route to synthesize the
enantiomers of both compounds. Tetrahydrofurans
with an extra side chain are used in the synthesis of
amphiphilic structures11 so this methodology opens new
ways to obtain derivatives of these compounds easily in
both enantiomeric forms.

D. D´ıez et al. / Tetrahedron: Asymmetry 13 (2002) 639–646
643
3.3. (2S,3S,4E)-5-Benzenesulfonyl-2,3-epoxy-pent-4-en-
1-yl tosylate (−)-3
on silica gel (n-hexane/EtOAc, 8:2) gave (−)-5 (318
mg, 95%): [h]2D0=−40.6 (c=1.17, CHCl3), IR (film) w
1
(cm−1): 3055, 1744, 1148; H NMR (CDCl3, 200 MHz)
To a solution of (−)-2 (400 mg, 1.67 mmol) in pyridine
(4 mL) was added TsCl (476 mg, 2.50 mmol) at 0°C.
The mixture was stirred for 8 h and ice was added.
The mixture was stirred for 30 min and then extracted
with EtOAc. The combined organic extracts were
washed with aqueous HCl (2N), NaHCO3 (5%) and
brine. After drying and concentration the residue was
purified by flash chromatography (n-hexane/EtOAc,
8:2) to gave (−)-3 (526 mg, 80%): [h]2D0=−12.2 (c=
0.78, CHCl3), IR (film) w (cm−1): 1362, 1177, 1150,
l: 7.91–7.53 (5H, m, Ar), 6.78 (1H, dd, J=15.0, and
5.6, H-4), 6.69 (1H, d, J=15.0, H-5), 4.40 (1H, dd,
J=12.6 and 3.4, Ha-1), 4.06 (1H, dd, J=12.6 and 5.0,
Hb-1), 3.46 (1H, dd, J=5.6, and 1.8, H-3), 3.18 (1H,
m, H-2), 2.09 (3H, s, CH3-Ac); 13C NMR (CDCl3,
50.3 MHz): 170.7 (CO-Ac), 140.9 (CH-4), 139.8 (C-
ipso), 134.0 (CH-5), 133.8 (CH-para), 129.7 (2CH-
meta), 128.1 (2CH-ortho), 63.2 (CH2-1), 58.4 (CH-3),
53.3 (CH-2), 20.9 (CH3-Ac).
1
1086, 966; H NMR (CDCl3, 200 MHz) l 8.01–7.30
3.6. (2R,3S,4E)-5-Benzenesulfonyl-1,2-isopropylidene-
dioxy-pent-4-en-3-ol (+)-6
(9H, m, Ar), 6.68 (1H, dd, J=15.0, and 5.2, H-4),
6.64 (1H, d, J=15.0, H-5), 4.20 (1H, dd, J=12.2 and
3.8, Ha-1), 4.10 (1H, dd, J=12.2 and 4.6, Hb-1), 3.40
(1H, dd, J=5.2, and 1.8, H-3), 3.13 (1H, m, H-2),
2.44 (3H, s, CH3-Ts); 13C NMR (CDCl3, 50.3 MHz)
145.4 (C-ipso, -Ts), 140.1 (CH-4), 139.6 (C-ipso,
SO2Ph), 134.1 (CH-5), 133.8 (CH-para, SO2Ph), 132.6
(C-para, -Ts), 130.0 (2CH-meta, -Ts), 129.4 (2CH-
meta, -SO2Ph), 127.9 (2CH-ortho, -Ts), 127.8 (2CH-
ortho, -SO2Ph), 68.1 (CH2-1), 57.6 (CH-3), 52.9
(CH-2), 21.9 (CH3-Ts); EIMS m/z (%) 394 (M+, 5) 351
(5), 155 (42), 125 (55), 91 (100), HRMS (EI) m/z calcd
for C18H18O6S2 394.0545; found 394.0546.
To a solution of (−)-2 (350 mg, 1.04 mmol) in acetone
(10 mL) was added a catalytic amount of AlCl3. The
mixture was stirred for 24 h then neutralized with a
solution of NaHCO3 (5%) and extracted with EtOAc.
The combined organic layers washed with water and
brine. The residue was purified by flash chromatogra-
phy (n-hexane/EtOAc, 8.5:1.5) to give (+)-6 (254 mg,
82%): [h]2D0=+11.3 (c=0.60, CHCl3), IR (film) w
1
(cm−1): 2928, 1308, 1148, 1071, 843; H NMR (CDCl3,
200 MHz) l: 7.90–7.50 (5H, m, Ar), 6.95 (1H, dd,
J=15.0, and 3.4, H-4), 6.69 (1H, dd, J=15.0 and 2.2,
H-5), 4.52 (1H, brs, H-3), 4.13 (1H, m, H-2), 3.92 (1H,
dd, J=8.4, and 6.6, Ha-1), 3.84 (1H, dd, J=8.4, and
6.0, Hb-1), 1.42 (3H, s, CH3), 1.35 (3H, s, CH3); 13C
NMR (CDCl3, 50.3 MHz) 143.1 (CH-4), 140.3 (C-
ipso), 133.7 (CH-para), 131.9 (CH-5), 129.6 (2CH-
meta), 127.9 (2CH-ortho), 110.3 (C-acetonide), 77.1
(CH-2), 70.3 (CH-3), 64.8 (CH2-1), 26.6 (CH3 -ace-
tonide), 25.1 (CH3-acetonide); MS (FAB) m/z (%) 299
(M++1, 10), 241 (10), 136 (100), 91 (42), 69 (57);
HRMS (FAB) m/z calcd for C14H19O5S 299.0953;
found 299.0958.
3.4. (2S,3S,4E)-5-Benzenesulfonyl-2,3-epoxy-pent-4-en-
1-yl trifluoroacetate (−)-4
To a solution of (−)-2 (300 mg, 1.25 mmol) in pyridine
(4 mL) was added trifluoracetic anhydride (0.30 mL,
1.87 mmol) at 0°C. The mixture was stirred for 6 h
and quenched with water. The organic layer was sepa-
rated, washed with water and brine and dried over
Na2SO4. The residue obtained by filtration was
purified by flash chromatography (n-hexane/EtOAc,
8:2) to give (−)-4 (300 mg, 71%): [h]2D0=−20.5 (c=0.92,
CHCl3), IR (film) w (cm−1): 1790, 1449, 1319, 1150,
1
1086; H NMR (CDCl3, 200 MHz) l: 7.91–7.53 (5H,
3.7. (2S,3R,4E)-5-Benzenesulfonyl-2,3-isopropylidene-
dioxy-pent-4-en-1-yl tosylate (+)-7
m, Ar), 6.77 (1H, dd, J=15.0, and 5.2, H-4), 6.71
(1H, d, J=15.0, H-5), 4.70 (1H, dd, J=12.0 and 2.8,
Ha-1), 4.34 (1H, dd, J=12.0 and 5.0, Hb-1), 3.50 (1H,
dd, J=5.2, and 1.8, H-3), 3.26 (1H, m, H-2); 13C
NMR (CDCl3, 50.3 MHz): 171.0 (CO-CF3), 139.4
(CH-4), 139.8 (C-ipso), 134.5 (CH-5), 134.1 (CH-
para), 129.7 (2CH-meta), 128.1 (2CH-ortho), 65.9
(CH2-1), 57.2 (CH-3), 52.9 (CH-2); EIMS m/z (%):
336 (M+, 12), 197 (35), 163 (100), 125 (100), 77 (92);
HRMS (EI) m/z calcd for C13H11O5F3S 336.0279;
found 336.0285.
Starting from (−)-3 (90 mg, 0.23 mmol) and following
an identical procedure to that described for the prepa-
ration of (+)-6 compound, (+)-7 (67 mg, 65%) was
obtained: [h]2D0=+3.8 (c=1.05, CHCl3), IR (film) w
1
(cm−1): 2990, 1368, 1177, 1150, 980; H NMR (CDCl3,
200 MHz) l: 7.91–7.39 (9H, m, Ar), 6.91 (1H, dd,
J=15.0, and 3.8, H-4), 6.63 (1H, dd, J=15.0 and 1.4,
H-5), 4.85 (1H, m, H-3), 4.44 (1H, q, J=6.6, H-2),
3.93 (1H, dd, J=10.3 and 6.6, Ha-1), 3.79 (1H, dd,
J=10.3 and 6.6, Hb-1), 2.46 (3H, s, CH3-Ts) 1.37 (3H,
s, CH3-acetonide), 1.31 (3H, s, CH3-acetonide); 13C
NMR (CDCl3, 50.3 MHz), l: 145.2 (C-ipso-Ts), 139.8
(C-ipso-SO2Ph), 138.6 (CH-4), 133.6 (CH-para-
SO2Ph), 133.1 (CH-5), 132.4 (C-para-Ts) 130.0 (2CH-
3.5. (2S,3S,4E)-5-Benzenesulfonyl-2,3-epoxy-pent-4-en-
1-yl acetate (−)-5
To a solution of (−)-2 (300 mg, 1.25 mmol) in pyridine
(5 mL) was added acetic anhydride (1 mL). The solu-
tion was stirred for 30 min and quenched with ice.
After 15 min ethyl acetate (15 mL) was added. The
organic layer was separated, washed with aqueous 2N
HCl, NaHCO3 (5%), water and brine and dried over
Na2SO4. Concentration followed by chromatography
meta-Ts),
129.4
(2CH-meta,
-SO2Ph),
128.0
(2CH-ortho-SO2Ph), 127.9 (2CH-ortho, -Ts) 110.3 (C-
acetonide), 75.0 (2CH-2,3), 67.0 (CH2-1); 27.3 (CH3-
acetonide), 25.3 (CH3-acetonide), 21.6 (CH3-Ts); EIMS
m/z (%) 452 (M+, 28), 426 (55), 414 (100); HRMS (EI)
m/z calcd for C21H24O7S2 452.0963; found 452.0965.

644
D. D´ıez et al. / Tetrahedron: Asymmetry 13 (2002) 639–646
3.8. (2S,3R,4E)-5-Benzenesulfonyl-2,3-isopropylidene-
dioxy-pent-4-en-1-yl trifluoroacetate (+)-8
3.11. (2S,3S,4R)-2-Benzenesulfonylmethyl-3,4-isopropyl-
idenedioxy-tetrahydrofuran (−)-10
Starting from (−)-4 (65 mg, 0.9 mmol) and following an
identical procedure to that described for the prepara-
tion of (+)-6, compound (+)-8 (47 mg, 63%) was
obtained: [h]2D0=+4.3 (c=0.15, CHCl3), IR (film) w
Compound (−)-9 (70 mg, 0.20 mmol) was dissolved in a
solution of K2CO3 in MeOH (3%) (2 mL). The mixture
was stirred for 2 h, neutralized with 2 M HCl and
extracted with EtOAc. The combined organic layers
washed with water and brine. The residue was purified
by flash chromatography (n-hexane/EtOAc, 7.5:2.5) to
give (−)-10 (54 mg, 90%): [h]2D0=−17.8 (c 0.67, CHCl3)
1
(cm−1): 2938, 1790, 1221, 1148, 1086; H NMR (CDCl3,
200 MHz) l: 7.90–7.50 (5H, m, Ar), 6.98 (1H, dd,
J=15.0, and 3.8, H-4), 6.70 (1H, d, J=15.0, H-5), 4.90
(1H, m, H-3), 4.54 (1H, q, J=4.4, H-2), 4.20 (2H, d,
J=4.4, H-1), 1.47 (3H, s, CH3-acetonide), 1.37 (3H, s,
CH3-acetonide); 13C NMR (CDCl3, 50.3 MHz) 170.3
(CO-CF3), 138.0 (CH-4), 137.0 (C-ipso), 134.0 (CH-5),
133.7 (CH-para), 129.8 (2CH-meta), 128.0 (2CH-
ortho), 110.3 (C-acetonide), 74.9 (CH-3), 74.6 (CH-2),
65.7 (CH2-1), 27.4 (CH3-acetonide), 25.3 (CH3-
acetonide).
3.12. (2S,3R,4E)-5-Benzenesulfonyl-2,3-isopropylidene-
dioxy-pent-4-en-1-yl tosylate (+)-7 and (2S,3R,4S)-2-
benzenesulfonylmethyl-3,4-isopropylidenedioxy-tetra-
hydrofuran (+)-11
To a solution of (+)-10 (100 mg, 0.33 mmol) in THF
(3.5 mL) was added n-BuLi (0.2 mL, 0.33 mmol) at
−78°C. The mixture was stirred for 5 min and then a
solution of TsCl (314 mg, 1.65 mmol) in THF (4 mL)
was added via cannula. The mixture was allowed to
warm to room temperature and then quenched with
saturated aqueous ammonium chloride. The organic
layer was separated, washed with water and brine, dried
over Na2SO4. Concentration followed by flash chro-
matography on silica gel (n-hexane/EtOAc, 8.5:1.5)
gave (+)-7 (88 mg, 60%), starting material (+)-10 (20
mg, 20%) and (+)-11 (5 mg, 5%): [h]2D0=+13.8 (c 0.30,
3.9. (2R,3S,4E)-5-Benzenesulfonyl-2,3-isopropylidene-
dioxy-pent-4-en-1-yl acetate (−)-9
Starting from (−)-5 (88 mg, 0.31 mmol) and following
an identical procedure to that described for the prepa-
ration of (+)-6, compound (−)-9 (84 mg, 80%) was
obtained: [h]2D0=−5.0 (c=0.42, CHCl3), IR (film) w
1
(cm−1): 2926, 1740, 1229, 1148; H NMR (CDCl3, 200
MHz) l: 7.90–7.50 (5H, m, Ar), 6.98 (1H, dd, J=15.0
and 4.0, H-4), 6.72 (1H, dd, J=15.0 and 1.4, H-5), 4.87
(1H, m, H-3), 4.47 (1H, q, J=6.2, H-2), 3.94 (2H, dd,
J=6.2, and 2.6, H-1), 2.06 (3H, s, CH3-Ac), 1.47 (3H,
s, CH3-acetonide), 1.36 (3H, s, CH3-acetonide); 13C
NMR (CDCl3, 50.3 MHz) 170.5 (CO-Ac), 139.8 (C-
ipso), 139.7 (CH-4), 133.8 (CH-para), 132.5 (CH-5),
129.6 (2CH-meta), 127.9 (2CH-ortho), 110.3 (C-ace-
tonide), 75.5 (CH-3), 75.3 (CH-2), 62.6 (CH2-1); 27.7
(CH3-acetonide), 25.3 (CH3-acetonide), 20.9 (CH3-Ac).
1
CHCl3); IR (film) w (cm−1): 2932, 1308, 1144, 1080; H
NMR (CDCl3, 200 MHz) l: 7.96–7.19 (5H, m, -Ar),
4.77 (1H, m, H-4), 4.68 (1H, dd, J=6.2 and 1.6 Hz,
H-3), 4.39 (1H, dt, J=6.6 and 1.6 Hz, H-2), 3.86 (1H,
d, J=10.9 Hz, Ha-5), 3.65 (1H, dd, J=10.9 and 4.3 Hz,
Hb-5), 3.28 (1H, dd, J=14.4 and 6.8 Hz, Ha-1%), 3.20
(1H, dd, J=14.4 and 6.6 Hz, Hb-1%), 1.41 (3H, s,
Me-acetonide), 1.28 (3H, s, Me-acetonide); 13C NMR
(CDCl3, 50.3 MHz), l: 139.4 (C-ipso), 133.9 (CH-
para), 129.2 (2CH-meta), 128.2 (2CH-ortho), 113.3 (C-
acetonide), 84.3 (CH-2), 80.4 (CH-3), 79.0 (CH-4), 72.2
(CH2-5), 56.5 (CH2-1%), 26.1 (Me-acetonide), 24.9 (Me-
acetonide); MS (FAB) m/z (%) 299 (M++1, 5), 154
(100), 107 (22), 69 (28); HRMS (FAB) m/z calcd for
C14H19O5S 299.0953; found 299.0958.
3.10. (2R,3R,4S)-2-Benzenesulfonylmethyl-3,4-isopropyl-
idenedioxy-tetrahydrofuran (+)-10
To a solution of (+)-8 (60 mg, 0.15 mmol) in MeOH (3
mL) was added a solution of Na2CO3 (10%) (0.5 mL).
The mixture was stirred for 2 h, neutralized with 2N
HCl and extracted with EtOAc. The combined organic
layers washed with water and brine. The residue was
purified by flash chromatography (n-hexane/EtOAc,
7.5:2.5) to give (+)-10 (40 mg, 88%): [h]2D0=+18.0 (c
0.25, CHCl3); IR (film) w (cm−1): 2932, 1308, 1148,
3.13. (2R,3S,4E)-5-Benzenesulfonyl-2,3-isopropylidene-
dioxy-penta-4-en-1-yl tosylate (−)-7 and (2R,3S,4R)-2-
benzenesulfonylmethyl-3,4-isopropylidenedioxy-tetra-
hydrofuran (−)-11
1
1086; H NMR (CDCl3, 400 MHz) l: 7.96–7.19 (5H,
Starting from (−)-10 (60 mg, 0.20 mmol) and following
an identical procedure to that described for the prepa-
ration of (+)-7 and (+)-11, compounds (−)-7 (53 mg,
60%): [h]2D0=−3.2 (c 0.21, CHCl3) and (−)-11 (3 mg,
5%): [h]2D0=−14.0 (c 0.26, CHCl3) were obtained.
m, -Ar), 4.73 (1H, dd, J=5.8 and 3.2 Hz, H-4), 4.60
(1H, dd, J=5.8 and 3.6 Hz, H-3), 3.97 (1H, m, H-2),
3.95 (1H, d, J=11.0 Hz, Ha-5), 3.60 (1H, dd, J=14.8
and 4.8 Hz Ha-1%), 3.46 (1H, d, J=14.8 Hz, Hb-1%), 3.44
(1H, dd, J=11.0 and 3.2 Hz, Hb-5), 1.41 (3H, s,
Me-acetonide), 1.28 (3H, s, Me-acetonide); 13C NMR
(CDCl3, 50.3 MHz). 140.0 (C-ipso), 133.9 (CH-para),
129.4 (2CH-meta), 128.3 (2CH-ortho), 111.7 (C-acet-
onide), 81.3 (CH-3), 80.9 (CH-4), 72.2 (CH-2), 73.2
(CH2-5), 56.1 (CH2-1%), 26.1 (Me-acetonide), 24.9 (Me-
acetonide); MS (FAB) m/z (%) 299 (M++1, 5), 154
(100), 107 (22), 69 (28); HRMS (FAB) m/z calcd for
C14H19O5S 299, 0953; found 299.0958.
3.14. (2R,3R,4S)-N-Benzyl-2-benzenesulfonylmethyl-
3,4-isopropylidenedioxypyrrolidine (+)-12
To a solution of (+)-7 (70 mg, 0.15 mmol) in MeOH (2
mL) was added BnNH2 (66 mL, 0.60 mmol) and Et3N
(30 mL, 0.22 mmol). The mixture was heated under
reflux for 12 h and was then allowed to cool at room
temperature. The mixture was diluted with EtOAc (15

D. D´ıez et al. / Tetrahedron: Asymmetry 13 (2002) 639–646
645
mL), the organic layer was separated, washed with
water and dried over Na2SO4. Filtration and concentra-
tion gave a yellow oil which was flash chromatographed
(n-hexane/EtOAc, 85:15) to give (+)-12 (45 mg, 78%):
[h]2D0=+40.2 (c 0.94, CHCl3); IR (film) w (cm−1): 2938,
(CDCl3, 200 MHz) l: 8.0–7.4 (5H, m, Ar), 4.32 (2H, m,
H-3, H-4), 3.83 (1H, dd, J=9.4 and 5.8, Ha-5), 3.76
(1H, dd, J=14.0 and 7.2, Ha-1%), 3.73 (1H, dd, J=9.4
and 5.2, Hb-5), 3.66 (1H, m, H-2), 3.47 (1H, dd, J=
14.0 and 5.2, Hb-1%); 13C NMR (CDCl3, 50.3 MHz), l:
139.4 (C-ipso), 134.2 (CH-para), 129.6 (2CH-meta),
128.1 (2CH-ortho), 75.4 (CH-2) 72.2 ( CH2-5), 71.7
(2CH, CH-3, 4), 56.4 (CH2-1%).
1
2805, 1447, 1306, 1150, 1086; H NMR (CDCl3, 400
MHz) l: 7.96–7.19 (10H, m, -Ar), 4.57 (1H, dd, J=
10.8 and 4.4 Hz, H-4), 4.53 (1H, dd, J=10.8 and 5.1
Hz, H-3), 3.88 (1H, d, J=13.9, Ha-1%%), 3.87 (1H, dd,
J=14.5 and 8.6 Hz, Hb-1%), 3.20 (1H, d, J=14.5, Ha-
1%), 3.13 (1H, d, J=13.9 Hz, Hb-1%%), 3.01 (1H, d,
J=11.2, Ha-5), 2.77 (1H, m, H-2), 2.03 (1H, dd, J=
11.2 and 4.4, Hb-5); 1.45 (3H, s, Me-acetonide), 1.26
(3H, s, Me-acetonide). 13C NMR (CDCl3, 100 MHz),
l: 139.8 (C-ipso, SO2Ph), 137.7 (C-ipso, Bn), 133.6
(CH-para, SO2Ph), 129.1 (2CH-meta, SO2Ph), 128.3
(4CH-2ortho, SO2Ph, 2meta, Bn), 128.0 (2CH-ortho,
Bn), 127.0 (CH-para, Bn), 111.4 (C-acetonide), 79.8
(CH-3), 77.8 (CH-4), 62.1 (CH-2), 58.7 (CH2-5), 56.5
(CH2-1%%), 53.7 (CH2-1%); 26.1 (Me-acetonide), 25.3 (Me-
acetonide); MS (FAB) m/z (%) 388 (M++1, 21), 376
(100), 370 (30), 364 (25); HRMS (FAB) m/z calcd for
C21H26O4SN 388.1582; found 388.1588.
3.18. (2R,3R,4R)-2-Benzenesulfonylmethyl-tetrahydro-
furan-3,4-diol (−)-14
To a solution of (−)-11 (10 mg, 0.03 mmol) in 1 mL of
MeOH was added two drops of 6 M HCl. The reaction
was stirred at room temperature for 12 h, neutralized
with NaHCO3 (5%) and extracted with EtOAc. The
combined organic layers washed with water then dried
over Na2SO4 before concentration to give (−)-14 (5.1
mg, 70%): [h]2D0=−5.6 (c=0.16, CHCl3); IR (film) w
1
(cm−1): 3445, 1304, 1146, 1088, 1034; H NMR (CDCl3,
200 MHz) l: 8.00–7.50 (5H, m, Ar), 4.29 (1H, m, H-4),
4.07 (3H, m, H-2, H-3, Ha-5), 3.79 (1H, dd, J=10.2
and 2.2, Hb-5), 3.52 (1H, dd, J=14.0 and 4.8, Ha-1%),
3.41 (1H, dd, J=14.0 and 7.0, Hb-1%); 13C NMR
(CDCl3, 50.3 MHz), l: 140.0 (C-ipso), 134.4 (CH-
para), 129.7 (2CH-meta), 128.3 (2CH-ortho), 76.3 (CH-
3), 75.7 (CH-2), 73.5 (CH2-5), 71.3 (CH-4), 59.9
(CH2-1%).
3.15. (2S,3S,4R)-N-Benzyl-2-benzenesulfonylmethyl-3,4-
isopropylidenedioxypyrrolidine (−)-12
Starting from (−)-7 (50 mg, 0.11 mmol) and following
an identical procedure to that described for the prepa-
ration of (+)-12, compound (−)-12 was obtained (25
mg, 78%): [h]2D0=−37.3 (c 0.32, CHCl3).
3.19. (2R,3R,4S)-2-Benzenesulfonylmethyl-3,4-isopropyl-
idenedioxypyrrolidine (+)-15
3.16. Deprotection of (+)-6
Compound (+)-12 (40 mg, 0.10 mmol) was dissolved in
MeOH (2 mL) and a catalytic amount of Pd/C was
added. After being flushed and stirred under hydrogen
for 24 h, the mixture was filtered over Celite and after
concentration was obtained (+)-15 (29 mg, 97%). For
physical properties, see Ref. 5.
Compound (+)-6 (40 mg, 0.13 mmol) was dissolved in
MeOH (1.5 mL) and three drops of aqueous 6 M HCl
were added and stirred overnight. Then, aqueous
Na2CO3 (10%) was added until the pH became basic.
The mixture was stirred for 2 h, neutralized with
aqueous 2 M HCl and extracted with EtOAc. The
combined organic layers were washed with water and
brine and dried over Na2SO4. After evaporation of the
solvent a mixture of compounds (−)-13 and (−)-14 in a
1:1 ratio was obtained (29 mg, 90%). This mixture was
dissolved in acetone (2 mL) and a catalytic amount of
p-TsOH was added and stirred for 6 h. The reaction
was quenched with NaHCO3 (5%) and extracted with
EtOAc. The combined organic layers washed with
water and brine and dried with Na2SO4. The crude
mixture was chromatographed on silica gel flash to give
(−)-10 (13 mg, 33%) and (−)-11 (10 mg, 25%).
3.20. (2S,3R,4S)-N-Benzyl-3,4-isopropylidenedioxy-2-
methylpyrrolidine (+)-16
Compound (+)-12 (40 mg, 0.10 mmol) was dissolved in
MeOH (1.5 mL) and the solution was cannulated into a
flask containing Na(Hg) 2% (100 mg). The mixture was
stirred for 3 h and concentrated. The residue was
dissolved in EtOAc (15 mL) and the organic layer was
separated and washed with water and brine. After
drying (Na2SO4) and concentration, the residue was
flash chromatographed on silica gel (n-hexane/EtOAc,
7.5:3.5) to give (+)-16 (19 mg, 77%): [h]2D0=+33.4 (c=
0.70, CHCl3); IR (film) w (cm−1): 2934, 1377, 1208,
1
3.17. (2S,3R,4R)-2-Benzenesulfonylmethyl-tetrahydro-
furan-3,4-diol (−)-13
1119, 1005; H NMR (CDCl3, 200 MHz) l: 7.32 –7.25
(5H, m, -Ar), 4.58 (1H, dd, J=6.6 and 4.4 Hz, H-4),
4.50 (1H, dd, J=6.2 and 4.4 Hz, H-3), 4.00 (1H, d,
J=13.4, Ha-1%%), 3.06 (1H, d, J=13.4, Hb-1%%), 2.99 (1H,
d, J=11.4 Hz, Ha-5), 2.20 (1H, m, H-2), 1.96 (1H, dd,
J=11.4 and 4.4 Hz, Hb-5), 1.56 (3H, s, Me-acetonide),
1.33 (3H, s, Me-acetonide), 1.22 (3H, d, J=6.6, CH3-
1%). 13C NMR (CDCl3, 50.3 MHz), l: 139.8 (C-ipso),
128.8 (2CH-meta), 128.4 (2CH-ortho), 126.9 (CH-
para), 111.3 (C-acetonide), 82.7 (CH-3), 78.3 (CH-4),
63.0 (CH-2), 59.7 (CH2-5), 56.8 (CH2-1%%), 26.6 (Me-ace-
To a solution of (−)-10 (100 mg, 0.33 mmol) in 5 mL of
MeOH was added five drops of 6N HCl. The reaction
was stirred at room temperature for 12 h, neutralized
with NaHCO3 (5%) and extracted with EtOAc. The
combined organic layers washed with water then dried
over Na2SO4 before concentration to give (−)-13 (74
mg, 80%): [h]2D0=−2.1 (c 0.68, CHCl3); IR (film) w
(cm−1): 3445, 1304, 1146, 1088, 1034, 822; 1H NMR

646
D. D´ıez et al. / Tetrahedron: Asymmetry 13 (2002) 639–646
tonide), 26.0 (Me-acetonide), 12.8 (Me-1%); EIMS m/z
(%) 247 (M+, 60), 219 (72) 232 (100); HRMS (EI) m/z
calcd for C15H21NO2 247.1572 found 247.1560.
References
1. (a) Katsuki, T.; Sharpless, K. B. J. Am. Chem. Soc. 1980,
102, 5974–5976; (b) Sharpless, K. B.; Behrens, C. H.;
Katsuki, T.; Lee, A. W. M.; Martin, V. S.; Takatani, M.;
Viti, S. V.; Walker, F. J.; Woodard, S. S. Pure Appl. Chem.
1983, 55, 589–604; (c) For leading references, see: Katsuki,
T.; Martin, V. S. Org. React. 1996, 48, 1–300.
2. (a) Brandes, B. D.; Jacobsen, E. N. Synlett 2001, 1013–
1015; (b) Sasaki, M.; Tanino, K.; Miyashita, M. J. Org.
Chem. 2001, 66, 5388–5394; (c) Righi, G.; Pescatore, G.;
Bonadies, F.; Bonini, C. Tetrahedron 2001, 57, 5649–5656;
(d) Hayakawa, H.; Okada, N.; Miyazawa, M.; Miyashita,
M. Tetrahedron Lett. 1999, 40, 4589–4592; (e) Righi, G.;
Rumboldt, G.; Bonini, C. Tetrahedron 1995, 51, 13401–
13408.
3.21. (2S,3R,4S)-2-Methylpyrrolidine-3,4-diol hydro-
chloride (+)-18
Compound (+)-16 (30 mg, 0.12 mmol) was dissolved in
MeOH and a catalytic amount of Pd/C was added.
After being flushed and stirred under hydrogen for 24 h
the mixture was filtered over Celite. After concentration
the crude was dissolved in MeOH (2 mL) and treated
with four drops of 6 M HCl. The reaction was stirred at
room temperature for 12 h and after concentration
afforded a white solid of (+)-18 (11 mg, 80%). For
physical properties, see Refs. 4d and 5.
3. Shi, H.; Liu, H.; Bloch, R.; Mandville, G. Tetrahedron
2001, 57, 9335–9341.
3.22. (2R,3S,4S)-2-Benzenesulfonylmethyl-tetra-
hydrofuran-3,4-diol (+)-13
4. (a) Robina, I.; Moreno-Vargas, A. M.; Fernandez-
Bolan˜os, J. G.; Fuentes, J.; Demange, R.; Vogel, P. Bioorg.
Med. Chem. Lett. 2001, 11, 2489–2493 and references cited
therein; (b) Wong, C.-H.; Provencher, L.; Porco, J. A., Jr.;
Jung, S.-H.; Wang, Y.-F.; Chen, L.; Wang, R.; Steensma,
D. H. J. Org. Chem. 1995, 60, 1492–1501; (c) Arribas, C.;
Carren˜o, M. C.; Garcia Ruano, J. L.; Rodriguez, J. F.;
Santos, M.; Sanz-Tejedor, M. A. Org. Lett. 2000, 2,
3165–3168; (d) Joubert, M.; Defoin, A.; Tarnus, C.; Streith,
J. Synlett 2000, 1366–1368; (e) O’Neil, I. A.; Cleator, E.;
Hone, N.; Southern, J. M.; Tapolczay, D. J. Synlett 2000,
1408–1410.
5. D´ıez Mart´ın, D.; Beneitez, M. T.; Marcos, I. S.; Garrido,
N. M.; Basabe, P.; Urones, J. G. Synlett 2001, 655–657.
6. Dale, J. A.; Dull, D. L.; Mosher, H. S. J. Org. Chem. 1969,
34, 2543–2546. The e.e. of epoxides was controlled by
comparison of Mosher’s ester of the Sharpless products
with those of the racemic epoxides obtained with m-CPBA.
7. (a) D´ıez Mart´ın, D.; Moro, R. F.; Lumeras, W.; Rodriguez,
L.; Marcos, I. S.; Basabe, P.; Escarcena, R.; Urones, J. G.
Synlett 2001, 1335–1337; (b) D´ıez Mart´ın, D.; Moro, R. F.;
Lumeras, W.; Rodriguez, L.; Marcos, I. S.; Basabe, P.;
Escarcena, R.; Urones, J. G. Synthesis 2002, 175–184.
8. Wershofen, S.; Scharf, H.-D. Synthesis 1988, 854–858.
9. Meskens, F. A. J. Synthesis 1981, 501–522.
Starting from (+)-10 (52 mg, 0.18 mmol) and following
an identical procedure to that described for the prepa-
ration of (−)-13, compound (+)-13 (37 mg, 80%) was
obtained: [h]2D0=+1.5 (c=0.68, CHCl3)
3.23. (2S,3S,4S)-2-Methyl-tetrahydrofuran-3,4-diol (+)-
19
To a solution of (+)-13 (70 mg, 0.29 mmol) in MeOH (3
mL) was added Raney-Ni. The mixture was heated
under reflux with vigorous agitation for 16 h and then
filtered over Celite to give after concentration (+)-19 (27
mg, 93%): [h]2D0=+8.0 (c=0.50, CHCl3); IR (film) w
1
(cm−1): 3500, 1117, 1080, 1024; H NMR (CDCl3, 200
MHz) l: 4.40 (1H, m, H-4), 4.01 (1H, m, H-3), 3.80
(3H, m, H-2, 2H-5), 1.30 (3H, d, J=6.6, Me); 13C
NMR (CDCl3, 50.3 MHz), l: 77.7 (CH-2), 72.8 (CH-
3), 72.7 (CH-4), 72.6 (CH2-5), 14.5 (CH3-1%); HRMS
(EI) m/z calcd for C5H10O3 118.0630; found 118.0633.
Acknowledgements
10. (a) Colvin, E. W.; Robertson, A. D.; Wakharkar, S. J.
Chem. Soc., Chem. Commun. 1983, 312–314; (b) Rastetter,
W. H.; Adams, J. Tetrahedron Lett. 1982, 23, 1319–1322;
(c) Oppolzer, W.; Radinov, R. N.; De Brabander, J.
Tetrahedron Lett. 1995, 36, 2607–2610.
The authors thank the CICYT (BQU2001-1034) and
Junta de Castilla y Leo´n (SA13-00B) for financial sup-
port and the Spanish Ministerio de Educacio´n y Cien-
cia for a doctoral fellowship to M.T.B.
11. Ejiyar, S.; Saluzzo, C.; Massoui, M.; Amouroux, R.; Terry,
N.; Coleman, A. W. J. Phys. Org. Chem. 2001, 14, 1–10.