Reactivity of polyhydroxyalkyl-heterocycles towards Lewis acids

Article abstract of DOI:10.1016/S0957-4166(01)00568-7

We report the reactivity of different polyhydroxyalkyl-heterocycles towards ceric ammonium nitrate (CAN) and ferric chloride. The behaviour of 2-methyl-5-(tetritol-1-yl)-pyrroles and -furans is different towards CAN oxidation. Pyrroles afford 2,5-diformylheterocycles, while furans give access to 1,4-dicarbonyl compounds containing three stereogenic centres. Ferric chloride promotes an intramolecular C-arylation reaction on O-benzylated-polyhydroxyalkyl furans, yielding an isochroman moiety, which is the basic skeleton of a variety of natural products.

Full text of DOI:10.1016/S0957-4166(01)00568-7

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 12 (2001) 3257–3266
Reactivity of polyhydroxyalkyl-heterocycles towards Lewis acids
A. J. Moreno-Vargas, J. G. Ferna´ndez-Bolan˜os, J. Fuentes and I. Robina*
Departamento de Qu´ımica Orga´nica, Facultad de Qu´ımica, Universidad de Sevilla, Apartado 553, E-41071 Sevilla, Spain
Received 14 November 2001; accepted 14 December 2001
Abstract—We report the reactivity of different polyhydroxyalkyl-heterocycles towards ceric ammonium nitrate (CAN) and ferric
chloride. The behaviour of 2-methyl-5-(tetritol-1-yl)-pyrroles and -furans is different towards CAN oxidation. Pyrroles afford
2,5-diformylheterocycles, while furans give access to 1,4-dicarbonyl compounds containing three stereogenic centres. Ferric
chloride promotes an intramolecular C-arylation reaction on O-benzylated-polyhydroxyalkyl furans, yielding an isochroman
moiety, which is the basic skeleton of a variety of natural products. © 2002 Elsevier Science Ltd. All rights reserved.
1. Introduction
were necessary.15 In 1988, the preparation of these
compounds by oxidation of 2,5-dimethyl derivatives
with Pb(OAc)4–PbO2, was reported16 and recently, a
one-step procedure starting from pyrrole-2-carboxylic
acids has been described.17
Five-membered heteroaromatic rings are interesting
intermediates in organic syntheses.1 Among them, poly-
hydroxyalkyl-heterocycles—particularly
tetritol-1-yl
derivatives, a class of acyclic C-nucleoside that can be
easily obtained from inexpensive starting materials,
Other five-membered hetaryl-dicarbaldehydes are also
interesting. Thiophene derivatives, for example, are
used in the synthesis of tetrathiafulvalene, an organic
semi-conductor18 and the preparation of many macro-
cycles containing 2,5-furylene rings in their structure
has been described.18,19 The oxidation of different furan
derivatives by both chemical1,20 and photocatalytic20
methods has been studied. These oxidations, depending
on the reagents, conditions and starting materials,
effect either oxidation of benzylic positions or opening
of the furan ring.1,21,22
such as
D
-glucosamine,
D
-glucose, b-dicarbonyl
compounds2 and alkyl(aryl)isothiocyanates—have been
transformed into different products. Thus, the corre-
sponding transformations into C-erythrofuranosyl het-
erocycles,3 into heterocycle monocarbaldehydes,4
nitropyrroles,5 a-furfurylamides6 and benzimidazoles
without a polyhydroxylic chain7 have been studied.
Many of these transformations involve a decrease in the
number of stereogenic centres, but the yields and the
low price of the starting materials give them synthetic
interest. O-Benzyl substituted sugars can undergo
intramolecular C-arylation reactions when activated
with protic8 or Lewis acids.9 The bibliographic data on
this C-arylation process in benzylated polyhydroxy-
alkyl-heterocycles are scarce.
Ceric ammonium nitrate (CAN) is a versatile reagent
for the oxidation of numerous functional groups in
organic synthesis.22 This reagent has been applied to
the oxidations of carbon atoms in benzylic positions of
arenes.22b However, the use of CAN in heterocyclic
chemistry is limited, and, as far as we are aware, only
the oxidations of furoin23 and polyhydroxyalkyltria-
zoles,24 with formation of the corresponding carboxylic
acids, have been described. More recently, Lightner et
al.25 and Moranta et al.26 have reported the oxidation
of a-benzyl and a-methylpyrroles to the corresponding
hydroxy- and formyl-derivatives.
At the same time, pyrrole 2,5-dicarbaldehydes are inter-
esting precursors in the preparation of bioactive com-
pounds
having
in
many
cases
macrocyclic
structures.1,10,11 Of these compounds, the b-alkylsubsti-
tuted porphyrins are the most widely studied, because
of their conformational12 and therapeutic properties.13
To date, only a few procedures for the preparation of
3,4-disubstituted pyrrole 2,5-dicarbaldehydes have been
reported,14 and in some cases long multistep sequences
In a previous communication,27 we have reported
preliminary results on the oxidation of poly-
hydroxyalkyl-heterocycles, which, in the case of
* Corresponding author. Fax: +34954624960; e-mail: robina@us.es
0957-4166/01/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(01)00568-7

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A. J. Moreno-Vargas et al. / Tetrahedron: Asymmetry 12 (2001) 3257–3266
2-methyl-5-(tetritol-1-yl)pyrroles, gave access to
pyrrole-2,5-dicarbaldehydes.
Compound 2 was also obtained from aldehyde 3 after
treatment with 6 equiv. of CAN. Alcohol 4, an interme-
diate in the oxidation, was obtained after treatment of
3 with 4.2 equiv. of CAN, indicating that oxidative
cleavage of the polyol chain takes place first, followed
by oxidation of the 2-methyl group.
O-Benzyl protection is a standard strategy in syntheses
of carbohydrate derivatives.28 The O-benzyl groups can
be removed in several ways, one of which is acetolysis
in the presence of a protic or Lewis acid and mild
conditions. Recently, it has been observed8,9 that O-
debenzylation in the mentioned conditions can produce
internal electrophilic aromatic substitution.
When the same reaction conditions were applied to
furan 5, different behaviour was observed. Thus, the
reaction of 5 with 11 equiv. of CAN, in a slow addition
(1 equiv. each 15 min), gave compound 6 that was
isolated in 48% yield. Further addition of CAN, did not
effect oxidation of the methyl group. Compound 6 is
totally unreactive to further oxidation. Nevertheless,
the rapid addition of all the reagent to compound 5
gave a complex mixture of decomposition products.
The same treatment applied to commercially available
compounds such as 2,5-dimethylpyrrole and 2,5-
dimethylfuran gave a complex mixture of decomposi-
tion products.
Herein, we report on the oxidation of 2-methyl-5-(tetri-
tol-1-yl)-pyrroles and -furans with CAN. These com-
pounds exhibit a wide range of behaviours towards this
reagent that strongly depend on the heterocycle, the
substituents on the heterocyclic ring, the equivalents of
the reagent and the form of its addition. We also report
the behaviour of different furan tetra-O-benzyl deriva-
tives in the acetolysis of O-benzyl groups in the pres-
ence of ferric chloride.
The differing behaviour of furan 6 and pyrrole 3 indi-
cates that the oxidation must be strongly dependent on
the p-electron density of the heterocyclic ring; lower
p-electron density of the heterocyclic ring makes oxida-
tion of the 2-methyl group more difficult.
2. Results and discussion
The reactivity of 3-ethoxycarbonyl-2-methyl-5-D-ara-
bino-tetritol-1-ylpyrrol 14 towards CAN is depicted in
Scheme 1. The slow addition of 11 equiv. of CAN over
165 min (1 equiv. each 15 min), gave dicarbaldehyde 2
in 66% isolated yield, whereas rapid addition of the
reagent to compound 14 gave a complex mixture of
products from which 2 was isolated in only 10% yield.
This different behaviour is probably due to the action
of CAN as a Lewis acid in high initial concentration.
With the aim of avoiding the oxidative cleavage of the
5-polyolic chain to an electron-withdrawing group such
as a formyl group, and thus favouring the oxidation of
the 2-methyl furan in 5, we envisaged the oxidation of
the tetra-O-benzyl derivative 7 obtained after conven-
tional benzylation of 5. For compound 7 (Scheme 2)
O
O
OH
OEt
Me
OEt
(i)
HO
OHC
CHO
N
N
H
2
66%
H
OH
OH
1
(iii)
(iv)
(ii)
91%
58%
O
O
OEt
OEt
OH
+
2 (40%)
OHC
CH3
O
OHC
N
H
3
N
H
4 (23%)
O
OEt
Me
OH
(i)
OEt
OHC
O
6
HO
48%
Me
O
5
OH
OH
(i)
complex mixture
H3C
CH3
X
X = NH, O
Scheme 1. Reaction conditions: (i) 11 equiv. of CAN, MeCN–H2O (5:1), 165 min; (ii) NaIO4, MeOH–H2O; (iii) 6.6 equiv. of CAN,
MeCN–H2O (9:1), 15 min; (iv) 4.2 equiv. of CAN, MeCN–H2O (9:1), 15 min.

A. J. Moreno-Vargas et al. / Tetrahedron: Asymmetry 12 (2001) 3257–3266
3259
O
OBn
OBn
O
COOEt
O
OEt
Me
(i)
(ii)
BnO
5
BnO
O
34%
77%
OBn
OBn
OBn
OBn
7
8a and 8b
Scheme 2. Reaction conditions: (i) BnBr, NaH, DMF; (ii) 5 equiv. of CAN, MeCN–H2O (9:1), 75 min.
with an ester group in position 3, both slow and rapid
addition of 5 equiv. of CAN in MeCN–H2O effected
oxidative opening of the furan ring and a mixture of
two compounds 8a and 8b in a 1:1.3 ratio was isolated
in 34% yield. No formyl group was observed, and the
exact configuration of each compound was not
determined.
acidic medium and under such conditions, oxidative
opening of the furan ring produces (E)-2-ene-1,4-
diones.
In the case of compound 9 (Scheme 3) with a hydroxy-
methyl group at position 3, formed by the reduction of
7 with LiAlH4/THF, the reaction with slow addition of
2 equiv. of CAN gave 10 in 45% yield as a result of
oxidative ring opening, and compound 11 in 18% yield
as a result of the oxidation of the 2-methyl group into
a hydroxymethyl group. Compound 10, presented
IR bands at 3468 cm−1 (OH) and 1696 cm−1 (CꢀO). In
The opening of the furan ring is clearly demonstrated
by the appearance of two IR bands at 1707 and 1732
cm−1 corresponding to wmax of CO of ketone and ester,
respectively. The 1H NMR spectra indicate the
deshielding of the C(4) proton of the furan ring from
6.54 ppm to 7.2–7.4 ppm. It is worth noting the appear-
ance of signals at 201.1 (2C), 200.9 and 194.2 corre-
sponding to C(2) and C(5) of each isomer.
1
the H NMR spectrum the C(4)H signal appeared at
6.56 ppm as a triplet with two allylic coupling constants
(1.9 Hz) with the methylene protons of the CH2OH
group. The CO groups (C(2) and C(5)) resonated at
205.5 and 200.6 ppm, as corresponds to a,b-unsatu-
rated ketones. The presence of two hydroxymethyl
groups in compound 11 was deduced from the IR band
The configuration of the CꢀC bond cannot be deduced
from the spectroscopic data. Nevertheless, we tenta-
tively assigned (E)-configuration to the major com-
pound based on reported data1,18b as the oxidation
reaction has previously been conducted in a slightly
1
at 3420 cm−1 (OH), and from two H NMR resonances
at 4.50 and 4.54 ppm for the methylene protons. The
resonance of the C(4) proton of the furan ring in 11
O
OBn
OEt
BnO
Me
O
OBn
OBn
7
87% LiAlH4 / THF
OH
Me
OBn
BnO
O
BnO
OBn
9
CAN (2 eq.)
CAN (5 eq.)
slow addition
rapid addition
CAN (3 eq.)
slow addition
OH
10 (37%)
10 (45%)
+
OBn
O
BnO
+
OBn
OBn
O
10 (50%)
OH
OH
OH
Me
OBn
OBn
BnO
BnO
O
O
BnO
OBn
BnO
O
* In all cases the reaction
solvent was MeCN-H2O (9:1)
12 (25%)
11 (18%)
Scheme 3.

3260
A. J. Moreno-Vargas et al. / Tetrahedron: Asymmetry 12 (2001) 3257–3266
(7.44–7.12 ppm) and C(4) (121.6 ppm) also confirmed
the proposed structure.
appeared at 6.24 ppm, which is very close to the
corresponding signal in 9.
Treatment of 7 and 9 with CAN under the above
conditions gives access to 1,4-dicarbonyl compounds
bearing three stereogenic centres.
With 3 equiv. of CAN and slow addition of the reagent,
only 10 was isolated in 50% yield. Using 5 equiv. of
CAN and a rapid addition, the oxidation of the 1%-ben-
zylic position was observed and compound 12 was
isolated in 25% yield together with the ring-opened
compound 10 in 37% yield. In neither of these experi-
ments was any aldehyde detected. Compound 12 had
IR bands at 3420 cm−1 (OH) and 1704 cm−1 (CO). The
1H and 13C NMR spectra showed the disappearance of
the signal of C(1%) and a signal at 186.8 ppm for C(1%)
indicates a carbonyl group. The signal of C(2%)H is
deshielded to 4.6 ppm and appears as a doublet with
J2%,3%=6.6 Hz. The resonances for only one hydroxy-
methyl group (4.41 ppm for CH2OH and 55.9 for
CH2OH), the methyl group (2.36 ppm for CH3 and
12.2 ppm for CH3), and the deshielded signal for C(4)H
It is worth pointing out the formation of (Z)- and
(E)-geometric isomers of 8, in almost equimolar ratio
from the oxidation of 7 and the appearance of only one
(E)-isomer for 10 as the major product in all of the
CAN oxidations of 9 (Scheme 3). Taking into account
steric and electronic effects, the most probable struc-
tures for isomers 8 and 10 are indicated in Fig. 1.
In order to confirm a possible intramolecular hydrogen
bond in compound 10 (structures 10 (I) and 10 (II)), we
have performed the CAN oxidation of 13 where the
hydroxymethyl
group
is
protected
as
tert-
butyldiphenylsilyl ether (Scheme 4). The rapid addition
O
OEt
O
O
O
O
R
OEt
R
8 (Z)
O
8 (E)
OH
O
O
O
O
H
O
O
H
R
O
O
R
R
10 (III)
10 (II)
10 (I)
Figure 1.
9
TBDPSCl, DMAP (cat.)
CH2Cl2-Py (5:1)
83%
Ph
Si But
O
OBn
Ph
BnO
Me
O
BnO
OBn
13
CAN (5 eq.)
CAN (5 eq.)
slow addition
MeCN-H2O
(9:1)
rapid addition
MeCN-H2O
(9:1)
Ph
Si But
O
14 (25%)
OBn
Ph
+
BnO
CHO
O
Ph
Si But
BnO
OBn
O
OBn
O
Ph
14 (15%)
BnO
+
OBn
OBn
O
15 (35%)
15 (24%)
Scheme 4.

A. J. Moreno-Vargas et al. / Tetrahedron: Asymmetry 12 (2001) 3257–3266
3261
of 5 equiv. of CAN yielded a 1:1 mixture of the
aldehyde 14 and the ring-opened compound 15 in 25
and 24% yield, respectively. However, with a slow
addition of 5 equiv. of CAN, the ring-opened com-
pound 15 was isolated in 35% yield, and only 15% of
the aldehyde (1H and 13C NMR of CHO at 9.60 ppm,
178.4 ppm) was formed. The spectroscopic data for 15
were very close to that for 10. C(4) resonated as a
triplet (4J=1.8 Hz) and the resonances of the CO
groups appeared at 205.5 and 200.6 ppm.
perature and at 0°C. Reaction of alcohol 9 with ferric
chloride in acetic anhydride and dichloromethane at
room temperature and at 0°C effected decomposition of
the products. However, when the reaction was carried
out on the ester 7, a mixture of the two 4-furyl-3,4-
dihydro-1H-benzo[c]pyrans 16 and 17 was formed. The
reaction takes place by intramolecular alkylation of the
benzyl group at C(2%) and leads to isochromane, the
basic skeleton of a variety of natural products.31 The
easily formed carbocation at C(1%) reacts with the ben-
zyl group at C(2%) through Friedel–Crafts-type reaction
in a poorly stereoselective process giving the mixture of
epimers 16 and 17. The results are summarised in
Scheme 5. A mixture of 16 and 17 was isolated in each
case (same Rf in chromatography) and the ratio deter-
The existence of an intramolecular hydrogen bond in 10
must produce a deshielding of 3–4 ppm in the chemical
shift of C(2) due to the local diamagnetic effect.29 The
similarity between the 1H and 13C NMR spectra of
compounds 10 and 15 (see Section 4) rules out the
intramolecular hydrogen bonding and hence the (E)-
configuration (III, Fig. 1) is proposed for 10 and 15.
The absence of any NOE in 10 for C(4)H/-CH2O- or
CH3 (Fig. 2) confirms the assignment which is also in
accordance with published data.20c
1
mined by H NMR. It is observed that with 2, 4 and 10
equiv., the ratio is the same, although the optimal yield
is obtained with 2 equiv. of ferric chloride. With 1
equiv. of reagent, compound 18 that still has a benzyl
group at position 1¦, was easily isolated by chromatog-
raphy in 11% yield.
Ferric chloride is a reagent that has been successfully
used30 in natural product chemistry, in particular
oligosaccharide chemistry, showing itself to be a highly
efficient reagent for debenzylation both at room tem-
The structure of compounds 16, 17 and 18 is supported
on 1H and 13C NMR data. In the case of compounds 16
and 17, the appearance of two acetyl groups (2.04 and
1.97 ppm) and the deshielding of the corresponding
protons of the polyol chain (H(1¦), H(2¦a) and H(2¦b),
Scheme 5, see Section 4) is observed. Resonances for
two benzyl-type methylenic protons (H-1a, H-1b)
appeared for each compound. The configuration of the
newly-formed stereogenic centre C(4) is based on the
coupling constant J3,4, that indicates an anti-relation-
OH
O
CH3
R
H
O
10 (III)
ship (J3,4=7.2 Hz) in 16 and a syn-relationship (J3,4
=
2.9 Hz) in 17. Additionally, NOEs between pairs
Figure 2.
H-4/H-3 (2%) in 17 confirm the assignment. It is worth
OH
Me
anh. FeCl3, Ac2O
r.t. and 0 ºC
OBn
BnO
BnO
O
O
decomposition
OBn OBn
9
1
COOEt
Me
O
O
3
anh. FeCl3, Ac2O
r.t., 30 min-2 h
OBn
1''
4
+
3'
1'
AcO
AcO
4'
2''
2'
5'
4'
H
AcO
H
AcO
OBn OBn
7
O
COOEt
O
2'
COOEt
3'
17
16
Me
Me
yield
FeCl3
ratio
(equiv.)
16 + 17
18
16 : 17
O
1
44%
11%
1.8 : 1
AcO
2
63%
52%
47%
---
---
---
1.1 : 1
1.1 : 1
1.1 : 1
H
BnO
O
COOEt
4
18
Me
10
Scheme 5.

3262
A. J. Moreno-Vargas et al. / Tetrahedron: Asymmetry 12 (2001) 3257–3266
noting the chemical shifts of C(4) at 38.3 and 39.4 ppm
for 16 and 17, respectively, that are consistent with the
absence of oxygen at this carbon and with carbon
attached to two aromatic moieties [C-CH(Ar)2], which
is in accordance with bibliographic data.9 The presence
of one acetyl group signal and J3,4=2.5 Hz in 18
confirms the assigned structure.
J
H,H=7.1, CH2CH3); 13C NMR (75.4 MHz): l 183.9,
180.7 (2CHO), 162.5 (COOEt), 135.1, 133.3 (C-2, C-5),
120.9 (C-4), 112.6 (C-3), 61.2 (CH2CH3), 14.2
(CH2CH3).
4.2. 3-Ethoxycarbonyl-5-formyl-2-hydroxymethylpyrrole
4
To a stirred solution of 3-ethoxycarbonyl-5-formyl-2-
methylpyrrole4 3 (150 mg, 0.83 mmol) in MeCN–H2O,
9:1 (6 mL) at rt, CAN (1.9 g, 3.48 mmol, 4.2 mol
equiv.) was added and the mixture was stirred for 15
min at rt. The reaction mixture was diluted with
dichloromethane, washed with water (3×50 mL), dried
(Na2SO4), evaporated and the residue was purified by
column chromatography (dichloromethane–acetone,
40:1“10:1). Eluted first 2 (64 mg, 40%). Eluted second
3 (37 mg, 23%) that crystallised from EtOH–H2O, 1:8;
3. Conclusion
In conclusion, the different behaviour of polyhydroxy-
alkyl-pyrroles and furans towards CAN oxidation is
demonstrated. With an unprotected polyolic chain, oxi-
dative degradation is observed in both cases. The oxi-
dation of the 2-methyl moiety to a formyl group only
takes place on pyrroles bearing electron-withdrawing
groups. For (tetra-O-benzylated-tetritol-1-yl)-3-ethoxy-
carbonylfurans, oxidative opening of the furan ring is
observed, giving access to 1,4-dicarbonyl compounds
that bear three stereogenic centres. Finally, an
intramolecular C-arylation reaction of benzylated poly-
hydroxyalkyl-furans is carried out leading to new com-
pounds containing the isochroman moiety, which is the
basic skeleton of a variety of natural products.32
1
mp 136–138°C, lit.4 138–139.5°C; H NMR (300 MHz,
CDCl3): l 10.22 (bs, 1H, NH), 9.49 (s, 1H, CHO), 7.37
(d, 1H, J4,CHO=2.7, H-4), 5.03 (d, 2H, JH,OH=5.3,
CH2), 4.33 (q, 2H, JH,H=7.1, CH2CH3), 3.73 (bs, 1H,
OH), 1.37 (t, 3H, JH,H=7.1, CH2CH3); 13C NMR (75.4
MHz): l 179.5 (CHO), 164.2 (COOEt), 145.3 (C-5),
130.5 (C-2), 123.5 (C-4), 114.4 (C-3), 60.4 (CH2CH3),
14.3 (CH2CH3).
4. Experimental
4.3. 3-Ethoxycarbonyl-5-formyl-2-methylfuran 6
Melting points are uncorrected. Optical rotations were
measured at 25 1°C for solutions in dichloromethane.
1H NMR spectra (300 and 500 MHz) were obtained for
solutions in CDCl3, J values are given in Hz and l in
ppm. The FABMS spectra were measured with a
KRATOS MS-80RFA instrument. Ions were produced
by a beam of xenon atoms (6–7 keV) using a matrix
consisting of glycerol or thioglycerol and NaI as salt,
(CsI)37Cs was used as reference. TLC was performed on
Silica Gel HF254 (Merck), with detection by UV light or
charring with H2SO4. Silica Gel 60 (Merck, 230 mesh)
was used for preparative chromatography.
4.3.1. Procedure a. To a stirred solution of 3-ethoxycar-
bonyl-2-methyl-5-(
-arabino-tetritol-1-yl)furan4 5 (57.5
D
mg, 0.21 mmol) in MeCN–H2O, 9:1 (5 mL) at rt, CAN
(575 mg, 1.05 mmol, 5 equiv.) was added over 1 h (by
adding 115 mg, 0.21 mmol, each 15 min). After 75 min
(total reaction time) the reaction mixture was diluted
with ether, washed with water (3×20 mL), dried
(Na2SO4) and evaporated to give 6 as a solid (15 mg,
38%) which crystallised from EtOH–H2O, 1:1; mp 56–
58°C, lit.4 mp 57°C; 13C NMR (75.5 MHz, CDCl3): l
176.9 (CHO), 164.5 (COOEt), 162.4, 150.2 (C-2, C-5),
122.3 (C-4), 116.4 (C-3), 60.7 (CH2CH3), 14.1 (2C,
CH2CH3, CH3).
4.1. 3-Ethoxycarbonyl-2,5-diformylpyrrole 2
4.3.2. Procedure b. To a stirred solution of 5 (57.5 mg,
0.21 mmol) in MeCN–H2O, 9:1 (5 mL) at rt, CAN
(1.27 g, 2.31 mmol, 11.0 mol equiv.) was added over
165 min (by adding 115 mg, 0.21 mmol, each 15 min).
After stirring the mixture for 3 h (total reaction time),
the reaction mixture was elaborated as described above
to give 6 (18.5 mg, 48%).
4.1.1. Procedure a. To a stirred solution of 3-ethoxycar-
bonyl-2-methyl-5-(
-arabino-tetritol-1-yl)pyrrole4 1 (50
D
mg, 0.18 mmol) in MeCN–H2O, 5:1 (6 mL) at rt, CAN
(1.10 g, 1.98 mmol, 11.0 equiv.) was added over 165
min (by adding 100 mg, 0.18 mmol, each 15 min). After
3 h (total reaction time) the reaction mixture was
diluted with ether, washed with water (3×20 mL), dried
(Na2SO4) and evaporated to give 2 as a solid (23 mg,
66%).
4.4. 3-Ethoxycarbonyl-2-methyl-5-(1%,2%,3%,4%-tetra-O-
benzyl- -arabino-tetritol-1-yl)furan 7
D
4.1.2. Procedure b. To a stirred solution of 3 (142 mg,
0.78 mmol) in MeCN–H2O, 9:1 (6 mL) at rt, CAN (2.8
g, 5.13 mmol, 6.6 equiv.) was added and the mixture
was stirred for 15 min at rt. Work-up of the residue as
described above gave 2 as a solid (86 mg, 58%) that
crystallised from EtOH–H2O, 1:1; mp 130–132°C, lit.4
128–129°C; H NMR (300 MHz, CDCl3): l 10.17 (s,
1H, NH), 10.40, 9.76 (2s, 2H, 2CHO), 7.40 (s, 1H,
H-4), 4.41 (q, 2H, JH,H=7.1, CH2CH3), 1.41 (t, 3H,
To a stirred solution of 3-ethoxycarbonyl-2-methyl-5-
-arabino-tetritol-1-yl)furan 1a (1.28 g, 4.7 mmol) in
(D
dry DMF (6 mL), NaH (1.8 g, 74.74 mmol) and benzyl
bromide (9 mL, 74.7 mmol) were added at 0°C. The
reaction mixture was stirred for 2 h at rt. Excess NaH
and benzyl bromide were removed by addition of
methanol and Et3N. The reaction mixture was evapo-
rated, diluted with dichloromethane, washed with water
(3×100 mL), dried (Na2SO4) and evaporated. Column
1

A. J. Moreno-Vargas et al. / Tetrahedron: Asymmetry 12 (2001) 3257–3266
3263
chromatography (ether–petroleum ether, 1:3“1:1) gave
7 as a syrup (2.28 g, 77%); [h]D −30.9 (c 1.0, CH2Cl2);
1H, J1%,2%=5.8, J2%,3%=4.8, H-2%), 3.72–3.60 (m, 3H, H-3%,
H-4%a, H-4%b), 2.25 (s, 3H, CH3); 13C NMR (75.5 MHz,
CDCl3): l 149.7, 149.0 (C-2, C-5), 138.5, 138.5, 138.2,
138.0 (C-1 of Ph), 127.3–128.2 (20C, Ph), 119.4 (C-3),
110.4 (C-4), 80.8 (C-2%), 78.2 (C-3%), 75.0, 74.7 (C-1%,
CH2Ph), 73.1, 71.8, 71.0 (CH2Ph), 69.3 (C-4%), 56.5
(CH2CH3), 11.6 (CH3); FABMS: m/z 615 [100%, (M+
Na)+]. Anal. calcd for C38H40O6: C, 77.00; H, 6.80.
Found: C, 76.75; H, 6.46%.
1
IR: 1717 cm−1 (CꢀO); H NMR (300 MHz, CDCl3): l
7.20–7.34 (m, 20H, arom.), 6.54 (s, 1H, H-4), 4.64 (d,
2
1H, J1%,2%=5.3, H-1%), 4.59, 4.52 (2d, 1H each, JH,H
=
11.2, CH2Ph),), 4.57, 4.32 (2d, 1H each, 2JH,H=11.8
Hz, CH2Ph),), 4.53, 4.35 (2d, 1H each, 2JH,H=11.7,
CH2Ph),), 4.49, 4.42 (2d, 1H each, 2JH,H=12.1 Hz,
CH2Ph), 4.29 (q, 2H, JH,H=7.1, CH2CH3), 4.02 (t, 1H,
J2%,3%=5.30, H-2%), 3.58–3.70 (m, 3H, H-3%, H-4%a, H-
4%b), 2.50 (s, 3H, CH3), 1.35 (t, 3H, JH,H=7.1,
CH2CH3); 13C NMR (75.4 MHz): l 163.9 (COOEt),
159.0, 149.8 (C-2, C-5), 138.3, 138.3, 138.2, 137.7 (C-1
of Ph), 128.2–127.4 (20C, Ph), 114.1 (C-3), 109.9 (C-4),
80.5 (C-2%), 78.0 (C-3%), 74.5 (C-1%), 74.8, 73.2, 71.8, 71.1
(CH2Ph), 68.9 (C-4%), 60.0 (CH2CH3), 14.3 (CH3), 13.8
(CH2CH3); FABMS: m/z 657 [100%, (M+Na)+];
HRFABMS: Found (M+Na)+ 657.2865. C40H42NaO7
requires 657.2828. Anal. calcd for C40H42O7: C, 75.68;
H, 6.67. Found: C, 75.99; H, 6.35%.
4.7. Oxidation of 3-hydroxymethyl-2-methyl-5-
(1%,2%,3%,4%-tetra-O-benzyl- -arabino-tetritol-1-yl)furan 9
D
4.7.1. Procedure a. To a stirred solution of 9 (64 mg,
0.108 mmol) in MeCN–H2O, 9:1 (5 mL) at rt, CAN
(128 mg, 0.218 mmol, 2 equiv.) was added over 30 min
(by adding 64 mg, 0.108 mmol, each 15 min). After the
first addition, the initial red–orange colour had faded to
colourless. Further CAN was added and the mixture
was stirred for 15 min. The reaction mixture was
diluted with dichloromethane and washed successively
with brine and water (3×25 mL), dried (Na2SO4), and
evaporated. The residue was purified by column chro-
matography (ether–petroleum ether, 1:3“1:1). Eluted
first (E)-(6S,7R,8R)-6,7,8,9-tetrabenzyloxy-3-hydroxy-
methylnon-3-ene-2,5-dione 10 (30 mg, 45%) as a
colourless oil; [h]D −34.6 (c 1, CH2Cl2); IR: 3468 cm−1
4.5. (Z,E)-(6S,7R,8R)-6,7,8,9-Tetrabenzyloxy-3-ethoxy-
carbonylnon-3-ene-2,5-dione 8
To a stirred solution of 7 (81 mg, 0.127 mmol) in
MeCN–H2O, 9:1 (7.5 mL) at rt, CAN (348 mg, 0.638
mmol, 5 mol equiv.) was added and the resulting mix-
ture was stirred for 15 min at rt. Work-up of the
residue as described above and purification by column
chromatography (ether–petroleum ether, 1:5“1:1)
gave, as syrups, a mixture of two compounds 8 in a
ratio of 1:1.3 (28 mg, 34%); [h]D −31.8 (c 1.0, CH2Cl2);
IR: 1732, 1704 cm−1 (CꢀO); 13C NMR (125.7 MHz,
CDCl3), 201.1 (2C), 200.9, 194.7 (4CꢀO), 165.7, 163.0
(2COOEt), 144.0, 141.1 (2C-3), 138.1 (2C), 138.0,
138.0, 137.5, 137.4, 136.8, 136.7 (8C-1 of Ph), 132.2,
131.9 (2C-3), 128.4–127.5 (40C, Ph), 85.5, 85.1 (2C-6),
80.1, 79.8 (2C-7), 77.6, 77.4 (2C-8), 74.7, 74.5, 73.5
(2C), 73.3 (2C), 71.7, 71.6 (8CH2Ph), 68.1, 67.9 (2C-9),
61.9, 61.7 (2CH2CH3), 29.8, 27.3 (2C-1), 13.9, 13.8
(2CH2CH3); FABMS: m/z 673 [100%, (M+Na)+];
HRFABMS: Found (M+Na)+ 673.2781. C40H42NaO8
requires 673.2777.
1
(OH), 1696 (CꢀO), 1625 (CꢀC); H NMR (500 MHz,
CDCl3): l 7.32–7.24 (m, 20H, arom.), 6.56 (t, 1H,
2
4J4,CHOH=1.9, H-4), 4.62, 4.34 (2d, 1H each, JH,H
=
11.6, CH2Ph), 4.56, 4.41 (2d, 1H each, 2JH,H=11.6,
CH2Ph),), 4.55, 4.40 (2d, 1H each, 2JH,H=11.1,
CH2Ph), 4.52 (s, 2H, CH2Ph), 4.22 (d, 1H, J6,7=3.4,
H-6), 4.12 (bs, 2H, CH2OH), 4.06 (dd, 1H, J7,8=8.2,
H-7), 3.84 (m, 1H, H-8), 3.80 (dd, 1H, J8,9a=2.4,
J9a,9b=10.7 Hz, H-9a), 3.68 (dd, 1H, J8,9b=3.9, H-9b),
2.21 (s, 3H, CH3); 13C NMR (125.7 MHz, CDCl3): l
205.5 (C-2), 200.6 (C-5), 157.9 (C-3), 138.2, 138.0,
137.7, 137.1 (C-1 of Ph), 128.3–127.5 (20C of Ph), 120.1
(C-4), 84.8 (C-6), 79.8 (C-7), 77.5 (C-8), 74.4, 73.4, 71.3,
71.7 (CH2Ph), 68.1 (C-9), 63.0 (CH2OH), 29.5 (C-1).
FABMS: m/z 631 [100%, (M+Na)+]; HRFABMS:
Found (M+Na)+ 631.2644. C38H40NaO7 requires
631.2671. Anal. calcd for C38H40O7: C, 75.00; H, 6.62.
Found: C, 75.53; H, 6.55%.
4.6. 3-Hydroxymethyl-2-methyl-5-(1%,2%,3%,4%-tetra-O-
benzyl- -arabino-tetritol-1-yl)furan 9
D
Eluted second 2,3-dihydroxymethyl-5-(1%,2%,3%,4%-tetra-
To a stirred solution of lithium aluminium hydride (46
mg, 1.15 mmol) in dry THF (2 mL), a solution of
compound 7 (371 mg, 0.6 mmol) in dry THF (4 mL)
was added. After 30 min, aqueous sodium sulphate was
added to destroy excess sodium hydride. The reaction
mixture was diluted with ether, filtered and the solvents
removed in vacuo. The residue was diluted with
dichloromethane, washed with water (50 mL), dried
and evaporated to give pure 9 as a syrup (281 mg,
81%); [h]D −26.1 (c 12.8, CH2Cl2); IR: 3452 cm−1 (OH);
1H NMR (300 MHz, CDCl3): l 7.37–7.23 (m, 20H,
Ph), 6.24 (s, 1H, H-4), 4.63 (d, 1H, J1%,2%=5.8, H-1%),
4.64, 4.60 (2d, 1H each, 2JH,H=11.2, CH2Ph), 4.50, 4.44
O-benzyl-D-arabino-tetritol-1-yl)furan 11 (12 mg, 18%)
as a colourless oil; [h]D −28.3 (c 1, CH2Cl2); IR: 3420
1
cm−1 (OH); H NMR (500 MHz, CDCl3): l 7.23–7.29
(m, 20H, Ph), 6.24 (s, 1H, H-4), 4.67 (d, 1H, J1%,2%=5.4,
2
H-1%), 4.60, 4.53 (2d, 1H each, JH,H=11.3, CH2Ph),),
2
4.58, 4.36 (2d, 1H each, JH,H=11.8, CH2Ph),), 4.57,
2
4.40 (2d, 1H each, JH,H=11.9, CH2Ph), 4.54, 4.50 (2s,
2
2H each, CH2OH), 4.49, 4.44 (2d, 1H each, JH,H
=
12.1, CH2Ph), 4.04 (t, 1H, J2%,3%=5.44, H-2%), 3.71 (td,
1H, J3%,4%a=3.1, J3%,4%b=5.4, H-3%), 3.66 (dd, 1H, J4%a,4%b
=
10.6, H-4%a), 3.61 (dd, 1H, H-4%b); 13C NMR (125.7
MHz, CDCl3): l 151.3, 150.8 (C-2, C-5), 138.6, 138.5,
138.2, 138.0 (4C-1 of Ph), 128.2–127.3 (20C, Ph), 122.5
(C-3), 110.4 (C-4), 80.9 (C-2%), 78.3 (C-3%), 75.1 (C-1%),
74.6, 73.3, 71.9, 71.4 (CH2Ph), 69.4 (C-4%), 56.6, 55.9
(CH2OH); FABMS: m/z 631 [100%, (M+Na)+];
2
(2d, 1H each, JH,H=11.9 Hz, CH2Ph),), 4.57, 4.42 (2d,
2
1H each, JH,H=11.6, CH2Ph), 4.41 (s, 2H, CH2OH),
2
4.60, 4.38 (2d, 1H each, JH,H=12.0, CH2Ph), 4.09 (dd,

3264
A. J. Moreno-Vargas et al. / Tetrahedron: Asymmetry 12 (2001) 3257–3266
HRFABMS: Found (M+Na)+ 631.2671. C38H40NaO7
requires 631.2672.
Na)+]; HRFABMS: Found (M+Na)+ 853.3933.
C54H58NaO6Si requires 853.3900.
4.7.2. Procedure b. As described above but by adding
CAN (180 mg, 0.327 mmol, 3 mol equiv.) over 45
min (by adding 64 mg, 0.108 mmol, each 15 min).
Work-up of the residue and column chromatography
(ether–petroleum ether, 1:3“1:1) gave 10 (50 mg,
50%).
4.9. Oxidation of 3-(tert-butyldiphenylsilyloxymethyl)-
2-methyl-5-(1%,2%,3%,4%-tetra-O-benzyl- -arabino-tetritol-
D
1-yl)furan 13
4.9.1. Procedure a. To a stirred solution of 13 (122
mg, 0.147 mmol) in MeCN–H2O, 9:1 (15 mL) at rt,
CAN (403 mg, 0.73 mmol) was added and the mix-
ture was stirred for 15 min until TLC (ether–
petroleum ether, 2:1) indicated total consumption of
the starting material. The reaction mixture was evap-
orated, diluted with CH2Cl2 and washed successively
with brine (30 mL) and water (2×30 mL), dried
(Na2SO4), and evaporated. Column chromatography
of the residue (ether–petroleum ether, 1:3“1:1) eluted
4.7.3. Procedure c. To a stirred solution of 9 (98 mg,
0.16 mmol) in MeCN–H2O, 9:1 (10 mL) at rt, CAN
(438 mg, 0.80 mmol, 5 mol equiv.) was added and
the mixture was stirred for 15 min until TLC indi-
cated total consumption of the starting material
(ether–petroleum ether 3:1). The residue was diluted
with ether, treated as described above, and purified
by column chromatography (ether–petroleum ether,
1:3“1:1). Eluted first 10 (36 mg, 37%). Eluted second
first
3-(tert-butyldiphenylsilyloxymethyl)-2-formyl-5-
-arabino-tetritol-1-yl)furan
(1%,2%,3%,4%-tetra-O-benzyl-
D
3-hydroxymethyl-2-methyl-5-(2%,3%,4%-tri-O-benzyl-D-
14 (31 mg, 25%) as a colourless oil; [h]D −26.4 (c 2.5,
erythro-butanoyl)furan 12 (20 mg, 20%) as a colour-
CH2Cl2); IR: 2936, 2864 cm−1 (CH), 1680 cm−1
1
less oil; IR: 3420 cm−1 (OH), 1704 (CꢀO); H NMR
1
(CHO); H NMR (300 MHz, CDCl3): l 9.60 (s, 1H,
(300 MHz, CDCl3): l 7.44–7.12 (m, 21H, Ph and
CHO), 7.69–7.19 (m, 30H, Ph), 6.66 (s, 1H, H-4),
4.90 (s, 2H, CH2OSi), 4.88 (d, 1H, J1%,2%=3.7, H-1%),
4.61, 4.36 (2d, 1H each, 2JH,H=11.6, CH2Ph), 4.60,
4.32 (2d, 1H each, 2JH,H=11.7 Hz, CH2Ph), 4.53,
4.48 (2d, 1H each, 2JH,H=12.1, CH2Ph), 4.52, 4.48
(2d, 1H each, 2JH,H=12.1, CH2Ph), 4.07 (dd, 1H,
J2%,3%=7.2, H-2%), 3.82 (m, 1H, H-3%), 3.78 (dd, 1H,
H-4), 4.66, 4.49 (2d, 1H each, 2JH,H=11.8, CH2Ph),
2
4.64, 4.45 (2d, 1H each, JH,H=11.7, CH2Ph), 4.62 (d,
2
1H, J2%,3%=6.6, H-2%), 4.55, 4.50 (2d, 1H each, JH,H
=
12.1, CH2Ph), 4.41 (s, 2H, CH2OH), 4.06–4.00 (m,
1H, H-3%), 3.83–3.68 (m, 2H, H-4%a, H-4%b), 2.36 (s,
3H, CH3); 13C NMR (125.7 MHz, CDCl3): l 186.8
(C-1%), 155.5, 149.8 (C-2, C-5), 138.1, 137.9, 137.2 (C-
1 of Ph), 128.2–127.0 (15C, Ph), 122.2 (C-3), 121.6
(C-4), 80.1 (C-2%), 79.0 (C-3%), 73.2, 72.5, 72.4
(CH2Ph), 69.3 (C-4%), 55.9 (CH2OH), 12.2 (CH3);
FABMS: m/z 523 [100%, (M+Na)+].
J3%,4%a=2.8, J4%a,4%b=11.7, H-4%a), 3.66 (dd, 1H, J3%,4%b=
4.2 Hz, H-4%b), 1.10 (s, 9H, (CH3)3C); 13C NMR
(75.4 MHz, CDCl3): l 178.4 (CꢀO), 158.9, 146.6 (C-2,
C-5), 138.2 (3C), 138.0, 137.6, 137.2 (C-1 of Ph),
135.4, 132.7, 129.8, 128.2–127.4 (31C, Ph and C-3),
111.3 (C-4), 79.6 (C-2%), 77.5 (C-3%), 74.9 (C-1%), 74.5,
73.2, 72.2, 71.7 (CH2Ph), 69.2 (C-4%), 58.3 (CH2OSi),
29.6 ((CH3)3C), 26.7 (3C, (CH3)3C); FABMS: m/z
867 [100%, (M+Na)+]; HRFABMS: Found (M+Na)+
867.3742. C54H56NaO7Si requires 867.3693. Eluted
second (E)-(6S,7R,8R)-6,7,8,9-tetrabenzyloxy-3-(tert-
butyldiphenylsilyloxymethylnon)-3-ene-2,5-dione (15)
(30 mg, 24%) as a colourless oil; [h]D −14.1 (c 2.2,
4.8. 3-(tert-Butyldiphenylsilyloxymethyl)-2-methyl-5-
(1%,2%,3%,4%-tetra-O-benzyl-
D
-arabino-tetritol-1-yl)furan
13
To a stirred solution of 9 (80 mg, 0.304 mmol) and
2,6-dimethylaminopyridine (15 mg) in CH2Cl2–pyri-
dine, 5:1 (3 mL), TBDPSCl (0.155 mL, 0.608 mmol)
at 0°C was added. The mixture was stirred for 2 h at
rt and then evaporated in vacuo. Column chromatog-
raphy (ether–petroleum ether, 1:30“1:20) gave 13 as
a syrup (208 mg, 82%); [h]D −25.8 (c 1.2, CH2Cl2);
1H NMR (300 MHz, CDCl3): l 7.89–7.24 (m, 30H,
Ph), 6.25 (s, 1H, H-4), 4.62 (d, 1H, J1%,2%=5.5, H-1%),
4.60, 4.56 (2d, 1H each, 2JH,H=11.3, CH2Ph), 4.60,
4.35 (2d, 1H each, 2JH,H=12.1, CH2Ph), 4.55, 4.41
(2d, 1H each, 2JH,H=11.8, CH2Ph), 4.50 (s, 2H,
CH2OSi), 4.48, 4.40 (2d, 1H each, 2JH,H=12.1,
CH2Ph), 4.06 (t, 1H, J2%,3%=5.5, H-2%), 3.70 (m, 1H,
H-3%), 3.67 (dd, 1H, J3%,4%a=3.0, J4%a,4%b=10.5, H-4%a),
3.61 (dd, 1H, J3%,4%b=5.8, H-4%b), 2.04 (s, 3H, CH3),
1.05 (s, 9H, (CH3)3C); 13C NMR (75.4 MHz, CDCl3):
l 149.2, 148.0 (C-2, C-5), 138.6 (2C), 138.3, 138.1,
135.5, 133.5 (4C-1 of Ph), 129.5, 128.1–127.2 (30C,
Ph), 119.5 (C-3), 110.7 (C-4), 80.8 (C-2%), 78.3 (C-3%),
74.8. 74.7 (C-1%, CH2Ph), 73.2, 71.9, 70.8 (CH2Ph),
69.4 (C-4%), 57.9 (CH2OSi), 29.6 ((CH3)3C), 26.7 (3C,
(CH3)3C), 11.6 (CH3); FABMS: m/z 853 [100%, (M+
1
CH2Cl2); IR: 1704 cm−1 (CꢀO), 1625 cm−1 (CꢀC); H
NMR (300 MHz, CDCl3): l 7.63–7.18 (m, 30H, Ph),
4
6.78 (t, 1H, J4,H=1.8, H-4), 4.66, 4.40 (2d, 1H each,
2
2JH,H=11.6, CH2Ph), 4.62, 4.34 (2d, 1H each, JH,H
=
11.7, CH2Ph), 4.52 (s, 2H, CH2Ph), 4.27 (d, 1H,
6,7=3.2, H-6), 4.26 (d, 2H, CH2OSi), 4.52, 4.47 (2d,
1H each, 2JH,H=11.1, CH2Ph), 4.09 (dd, 1H, J7.8
8.1, H-7), 3.84 (m, 1H, H-8), 3.78 (dd, 1H, J8,9a=2.5,
9a,9b=10.6, H-9a), 3.67 (dd, 1H, J8,9b=4.1, H-9b),
J
=
J
2.23 (s, 3H, CH3), 1.04 (s, 9H, ((CH3)3C-); 13C NMR
(125.7 MHz, CDCl3): l 205.2, 200.9 (C-2, C-5), 158.3
(C-3), 138.2, 138.0, 137.6, 137.1 (C-1 of Ph), 135.3,
132.2, 129.9, 128.3–127.3 (32C, Ph), 119.2 (C-4), 84.6
(C-6), 79.6 (C-7), 77.4 (C-8), 74.4, 73.4 (2C), 71.7
(CH2Ph), 68.2 (C-9), 64.3 (CH2OSi), 29.7 (C-1), 29.6
((CH3)3C-), 26.5 (3C, (CH3)3C-); FABMS: m/z 869
[100%, (M+Na)+]; HRFABMS: Found (M+Na)+
869.3884. C54H58NaO7Si requires 869.3849. Anal.
calcd for C54H58O7Si: C, 76.56; H, 6.90. Found: C,
76.33; H, 7.05%.

A. J. Moreno-Vargas et al. / Tetrahedron: Asymmetry 12 (2001) 3257–3266
3265
4.9.2. Procedure b. To a stirred solution of 13 (96 mg,
0.115 mmol) in MeCN–H2O, 9:1 (12 mL) at rt, CAN
(320 mg, 0.583 mmol, 5 equiv.) was added over 75 min
(by adding 64 mg, 0.116 mmol, each 15 min). After 90
min (total reaction time) the reaction mixture was
elaborated as described above to yield 14 (15 mg, 15%)
and 15 (34 mg, 35%).
9.6, J1¦,2¦a=2.4, J1¦,2¦b=3.9, H-1¦), 4.47 (dd, 1H,
J
2¦a,2¦b=12.3, H-2¦a), 4.26 (dd, 1H, H-2¦b), 4.22–4.15
(m, 2H, CH2CH3), 4.14 (d, 1H, J3,4=2.9, H-4), 4.05
(dd, 1H, H-3), 2.49 (s, 3H, CH3), 2.16, 2.05 (2s, 3H
3
each, 2CH3CO), 1.27 (t, 3H, JH,H=7.1, CH2CH3); 13C
NMR (75.4 MHz, CDCl3): l 170.6, 169.4 (2CH3CO),
163.8 (COOEt), 158.0, 152.1 (C-2%, C-5%), 133.0, 132.7,
129.9–124.0 (6C, arom.), 114.2 (C-3%), 109.8 (C-4%), 76.4
(C-3), 70.8 (C-1¦), 68.3 (C-1), 62.1 (CH2CH3), 59.8
(C-2¦), 39.4 (C-4), 20.9, 20.6 (2CH3CO), 14.2
(CH2CH3), 13.4 (CH3).
4.10. Treatment with FeCl3 of 3-ethoxycarbonyl-2-
methyl-5-(1%,2%,3%,4%-tetra-O-benzyl- -arabino-tetritol-1-
D
yl)furan 7
+
’
To a suspension of anhydrous FeCl3 (x equiv., see
Scheme 5) in freshly distilled Ac2O (1 mL/mmol), a
solution of 1a (y mmol, see Scheme 5) in Ac2O (3
mL/mmol) was added under an argon atmosphere. The
reaction mixture was stirred at rt for 30 min to 2 h,
then diluted with dichloromethane and washed succes-
sively with saturated solution of NaHCO3 and water.
The organic layer was dried (Na2SO4), evaporated and
the residue was purified by column chromatography
(ether–petroleum ether, 1:20“1:5). Eluted first
(4R,3S,1¦R)-3-(2-acetoxy-1-benzyloxyethyl)-4-(3-ethoxy-
carbonyl-2-methylfur-5-yl)-3,4-dihydro-1H-benzo[c]-
pyran 18 as a colourless oil; [h]D −84 (c 1.4, CH2Cl2);
1H NMR (300 MHz, CDCl3): l 7.43–7.04 (m, 9H,
arom.), 6.17 (s, 1H, H-4%), 5.00, 4.87 (2d, 1H each,
2JH,H=15.2, H-1a, H-1b), 4.72, 4.37 (2d, 1H each,
Data for 16 and 17: FABMS: m/z 453 [100%, (M+Na) ];
HRFABMS: Found (M+Na)+ 453.1539, C23H26O8+Na
requires 453.1525. Anal. calcd for C38H40O6: C, 64.17;
H, 6.09. Found: C, 63.68; H, 6.07%.
Acknowledgements
We thank the Direccio´n General de Investigacio´n Cien-
t´ıfica y Te´cnica of Spain (Grant number PB 97-0730)
and Junta de Andaluc´ıa (FQM 134) for financial sup-
port, and the University of Seville for a fellowship to
A.J.M.-V. This work is part of the European COST
D13/0001/99.
2JH,H=15.2, CH2Ph), 4.72 (dd, 1H,
2¦a,2¦b=12.0, H-2¦a), 4.33 (d, 1H, J3,4=2.5, H-4), 4.24
J1¦,2¦a=2.6,
J
3
(q, 2H, JH,H=7.1, CH2CH3), 4.26 (dd, 1H, J1¦,2¦b=3.8,
H-2¦b), 3.94 (dd, 1H, J1¦,3=9.5, H-3), 3.47 (ddd, 1H,
H-1¦), 2.54 (s, 3H, CH3), 2.07 (s, 3H, CH3CO), 1.31 (t,
3H, CH2CH3); 13C NMR (75.4 MHz, CDCl3): l 170.8
(CH3CO), 164.0 (COOEt), 157.7, 153.0 (C-2%, C-5%),
137.8, 134.0, 133.7, 130.3–125.9 (12C, arom.), 114.2
(C-3%), 109.1 (C-4%), 77.0 (C-1¦), 75.3 (C-3), 72.1
(CH2Ph), 68.4 (C-1), 62.2 (CH2CH3), 59.9 (C-2¦), 38.4
(C-4), 20.8 (CH3CO), 14.2 (CH2CH3), 13.7 (CH3);
FABMS: m/z 501 [100%, (M+Na)+]; CIMS: m/z 479
[100%, (M+H)+]; HRCIMS: Found (M+H)+ 479.2043,
C28H30O7+H requires 479.2069. Eluted second a mix-
ture of (4R and 4S,3S,1¦R)-3-(1,2-diacetoxyethyl)-4-(3-
ethoxycarbonyl-2-methylfur-5-yl)-3,4-dihydro-1H-benzo
[c]pyran 16 and 17 as a colourless oil.
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Data for 16: H NMR (500 MHz, CDCl3): l 7.92–7.25
(m, 4H, arom.), 6.47 (s, 1H, H-4%), 5.20 (ddd, 1H,
J
1¦,3=7.1, J1¦,2¦a=3.2, J1¦,2¦b=4.5, H-1¦), 4.88 (s, 2H,
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