Structural modification of carbohydrates via functionalised organolithium intermediates: EPC preparation of branched-chain functionalised sugars

Article abstract of DOI:10.1016/S0957-4166(99)00488-7

The reductive opening of epoxides 1, 9, 13 derived from D-glucose and 18 derived from D-fructose using lithium and a catalytic amount of 4,4'-di-tert-butylbiphenyl (DTBB) in THF at -78°C allows the formation of β-oxido organolithium derivatives (2, 10, 14 and 19), which, by reaction with different electrophiles [H₂O, D₂O, Me₃SiCl, PhCHO, Me₂CO, Et₂CO, (CH₂)₅CO, CO₂] at the same temperature yields, after hydrolysis with water, the expected branched-chain functionalised carbohydrates. An alternative route for compound 11, derived from the epoxide 9, consists of the deprotonation of the chlorohydrin 12 followed by the same protocol of lithiation-reaction with an electrophile. The application of this methodology to the oxetane 4 allows compound 6 to be obtained through the corresponding γ-functionalised organolithium intermediates 5. Finally, the addition of the dianions 25 (resulting from the DTBB-catalysed lithiation of phthalan and isochroman) to the ketones 8 and 23, derived from D-glucose and D-fructose, respectively, allowed the stereoselective functionalisation at the 3-position of the sugars, giving the corresponding diols 26 and 27, which can cyclise to the corresponding heterocycles 28 and 29, respectively, under Mitsunobu reaction conditions. Copyright (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0957-4166(99)00488-7

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 11 (2000) 493–517
Structural modification of carbohydrates via functionalised
organolithium intermediates: EPC preparation of branched-chain
functionalised sugars
Tatiana Soler,a Abderrazak Bachki,a Larry R. Falvello,b,† Francisco Foubelo a and
Miguel Yus a,∗
aDepartamento de Química Orgánica, Facultad de Ciencias, Universidad de Alicante, Apdo 99, 03080 Alicante, Spain
bDepartamento de Química Inorgánica, Instituto de Ciencias de los Materiales de Aragón, Facultad de Ciencias, Universidad
de Zaragoza-CSIC, 50009 Zaragoza, Spain
Received 19 October 1999; accepted 3 November 1999
Abstract
The reductive opening of epoxides 1, 9, 13 derived from D-glucose and 18 derived from D-fructose using lithium
and a catalytic amount of 4,40-di-tert-butylbiphenyl (DTBB) in THF at −78°C allows the formation of β-oxido
organolithium derivatives (2, 10, 14 and 19), which, by reaction with different electrophiles [H2O, D2O, Me3SiCl,
PhCHO, Me2CO, Et2CO, (CH2)5CO, CO2] at the same temperature yields, after hydrolysis with water, the expected
branched-chain functionalised carbohydrates. An alternative route for compound 11, derived from the epoxide 9,
consists of the deprotonation of the chlorohydrin 12 followed by the same protocol of lithiation-reaction with an
electrophile. The application of this methodology to the oxetane 4 allows compound 6 to be obtained through the
corresponding γ-functionalised organolithium intermediates 5. Finally, the addition of the dianions 25 (resulting
from the DTBB-catalysed lithiation of phthalan and isochroman) to the ketones 8 and 23, derived from D-glucose
and D-fructose, respectively, allowed the stereoselective functionalisation at the 3-position of the sugars, giving the
corresponding diols 26 and 27, which can cyclise to the corresponding heterocycles 28 and 29, respectively, under
Mitsunobu reaction conditions. © 2000 Elsevier Science Ltd. All rights reserved.
1. Introduction
Carbohydrates are the most abundant organic compounds in nature.1 Considering their biological
activity, they play an important role in molecular recognition, cell signalling, biomolecular transport,
the immune system and, in fact, in virtually every essential biological process.2 From a chemical point of
∗
†
Corresponding author. Fax: 34 965903549; e-mail: yus@ua.es
To whom the correspondence on X-ray structure should be addressed.
0957-4166/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(99)00488-7
tetasy 3124

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T. Soler et al. / Tetrahedron: Asymmetry 11 (2000) 493–517
view, carbohydrates constitute one of the most important families of the chiral pool of natural products,
which can be used for the preparation of enantiopure molecules.3 In particular, naturally occurring D-
glucose is one of the molecules most used in the so-called EPC (enantiomerically pure compounds)
synthesis, which uses natural products as starting materials and a source of chirality.4 In recent years
much effort has been focused on the preparation of branched-chain functionalised carbohydrates, bearing
mainly an alcohol functionality at the branching carbon atom, due to their presence as glycosidic
components of many antibiotics.5 On the other hand, during the last decade we have developed a new
methodology for the preparation of organolithium compounds consisting of the use of lithium powder
and a catalytic amount of an arene, naphthalene or 4,40-di-tert-butylbiphenyl (DTBB) being the most
commonly used.6–9 This methodology has allowed us to generate organolithium reagents starting from
non-halogenated materials,10 functionalised organolithium intermediates11 (starting from chlorinated
precursors,12 ethers,13 thioethers,14sulfones15 and saturated heterocycles16) and polylithiated synthons.17
Among the different methods for generating functionalised organolithium compounds, the reductive
opening of epoxides using lithium and a stoichiometric18 or catalytic19 amount of an arene has been
shown to be effective for the generation of β-oxido-functionalised organolithium derivatives. In this
paper, we describe the application of the aforementioned arene-catalysed lithiation of epoxides derived
from carbohydrates such as glucose or fructose derivatives.20
2. Results and discussion
The reaction of the protected epoxy D-glucose 1 with an excess of lithium (1:14 molar ratio) and
a catalytic amount of DTBB (1:0.1 molar ratio, 5 mol%) in THF at −78°C for 2 h followed by
treatment with different electrophiles [E+=H2O, D2O, Me3SiCl, PhCHO, Me2CO, (CH2)5CO] at the
same temperature for 10 min afforded, after hydrolysis with water, the expected products 3a–f, the
corresponding intermediate 2 probably being involved in the process (Scheme 1 and Table 1). In the
case of prochiral carbonyl compounds, such as benzaldehyde, a 2:3 diastereomeric mixture was isolated
(Table 1, entry 4), which was separated by chromatography (neutral silica gel, hexane:ethyl acetate),
giving the corresponding pure diastereomers. The unequivocal assignment of the stereochemistry of both
formed stereocentres in diols 3d and 3d0 was performed by single-crystal analysis of compound 3d0 (Fig.
1).21
Scheme 1. Reagents and conditions: (i) Li, DTBB (5%), THF, −78°C, 2 h; (ii) E+=H2O, D2O, Me3SiCl, PhCHO, Me2CO,
(CH2)5CO, −78°C, 10 min; (iii) H2O, –78 to 20°C
Since oxetanes can be reductively opened using lithium and a catalytic amount of DTBB,22 we applied
the above-mentioned methodology to the oxetane derivative 4, but performing the lithiation step at
−40°C. In this case, the reaction with different electrophiles [H2O, D2O, PhCHO, Me2CO, (CH2)5CO]
always gave the ‘reduced’ product 6a (E=H; >95% yield) except for the deuterolysis in which a 98% yield
of compound 6b was obtained with only 55% of deuterium incorporation (MS) (Scheme 2). It seems that,
under these reaction conditions, the intermediate 5 partially decomposed by abstracting a proton from the

T. Soler et al. / Tetrahedron: Asymmetry 11 (2000) 493–517
495
Table 1
Preparation of compounds 3 from the epoxide 1
Fig. 1.
reaction medium, probably from the THF, thus giving the corresponding product 6a instead of reacting
with the electrophile, except in the case of deuterium oxide.

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T. Soler et al. / Tetrahedron: Asymmetry 11 (2000) 493–517
Scheme 2. Reagents and conditions: (i) Li, DTBB (5%), THF, −40°C, 3 h; (ii) E+=H2O, D2O, –40°C, 10 min; (iii) H2O, –40 to
20°C
Starting materials 1 and 4 were prepared from commercially available compound 7, which was
oxidised with pyridinium chlorochromate (PCC) in CH2Cl2 to give the ketone 8, followed by treatment
with a stoichiometric amount or an excess of trimethylsulfoxonium iodide in 80–85% yield (Scheme
3).22d
Scheme 3. Reagents and conditions: (i) PCC, Ac2O, CH2Cl2, 20°C, 30 min; (ii) KOBut (1 equiv.), Me3SOI (1 equiv.), ButOH,
50°C, 2.5 h; (iii) KOBut (4 equiv.), Me3SOI (4 equiv.), ButOH, 50°C, 1.5 h
When the epimeric epoxide 9 was submitted to the same procedure as shown in Scheme 1 and using
various electrophiles [H2O, D2O, PhCHO, Et2CO, (CH2)5CO] we always isolated the same product 11a
resulting from a lithium/hydrogen exchange. In this case, the corresponding dianion 10 seemed to be
very unstable and decomposed during the lithiation time (2 h), under the reaction conditions employed,
by abstraction of a proton from the reaction medium (Scheme 4).23
In order to avoid the former problem we lithiated the chlorohydrin 12, previously deprotonated with
BunLi in THF at −78°C, using the same procedure as above, so that the corresponding intermediate
10 was formed in only 30 min, and its decomposition could be avoided and compounds 11 could be
isolated, after reaction with D2O, (CH2)5CO and compound 8 (Scheme 5 and Table 2). In the last case, the
stereochemistry of compound 11d is that corresponding to the attack of intermediate 10 to the upper face
of the ketone 8.24 A definitive proof of the C2 symmetry in compound 11d is observed in its NMR spectra

T. Soler et al. / Tetrahedron: Asymmetry 11 (2000) 493–517
497
Scheme 4. Reagents and conditions: (i) Li, DTBB (5%), THF, −78°C, 2 h; (ii) E+=H2O, D2O, PhCHO, Et2CO, (CH2)5CO,
−78°C; (iii) H2O
(see the Experimental part). The stereochemistry of compound 11a was confirmed by its preparation by
reaction of ketone 8 with methyllithium.
Scheme 5. Reagents and conditions: (i) BunLi, THF, −78°C; (ii) Li, DTBB (5%), THF, −78°C, 30 min; (iii) E+=D2O,
(CH2)5CO, 8, –78 to 0°C; (iv) H2O
Table 2
Preparation of compounds 11 from the chlorohydrin 12
Starting materials 9 and 12 were prepared from ketone 8 by reaction with in situ generated chloro-
methyllithium (from chloroiodomethane and BunLi), the only difference being the reaction temperature
for the hydrolysis: at low temperature the chlorohydrin 12 did not cyclise to the epoxide 9, but at room
temperature this was the reaction product formed (Scheme 6).

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Scheme 6. Reagents and conditions: (i) ClCH2I, LiBr, THF, 10 min; (ii) BunLi, THF, −78 to 20°C; (iii) as (ii) but at −78°C and
then H2O, −78 to 0°C; (iv) H2O
Another epoxide derived from D-glucose is compound 13, which was lithiated and reacted with
electrophiles [H2O, D2O, PhCHO, Me2CO, (CH2)5CO, CO2] using the same procedure shown in
Scheme 1. Thus, the expected compounds 15 were isolated, dianion 14 probably being involved as an
intermediate (Scheme 7 and Table 3). Also in this case, when benzaldehyde was used as electrophile, a
3:1 diastereomeric mixture of compounds 15c and 15c0 was obtained (Table 3, entry 3).
Scheme 7. Reagents and conditions: (i) Li, DTBB (5%), THF, −78°C, 2.5 h; (ii) E+=H2O, D2O, PhCHO, Me2CO, (CH2)5CO,
CO2, −78°C, 10 min; (iii) H2O, −78 to 20°C
Table 3
Preparation of compounds 15 from the epoxide 13
The preparation of the starting epoxide 13 was carried out starting from the commercially available
triol 16, which was treated with diisopropyl azodicarboxylate (DIAD) and triphenylphosphine in benzene
at reflux, to give the epoxide 17.25 This epoxide was finally protected with chloromethyl ethyl ether to
give 13 (Scheme 8).
In order to establish the scope of the methodology described in this paper, we applied this procedure to
the epoxide 18 derived from D-fructose. This compound was used as a 4:1 diastereomeric mixture, which
could not be separated chromatographically, the major compound being the structure 18. After lithiation

T. Soler et al. / Tetrahedron: Asymmetry 11 (2000) 493–517
499
Scheme 8. Reagents and conditions: (i) PPh3, DIAD, PhH reflux, 2.5 h; (ii) BunLi, ClCH2OEt, THF, −78 to 20°C
and reaction with different electrophiles, compounds 20 were isolated resulting from the reaction of the
major diasteroisomer, except for compound 20 with E=D, in which the same 4:1 mixture (20b and 20b0)
was obtained and separated chromatographically (Scheme 9 and Table 4). Also in this case, a dimer 20f
was prepared in poor yield when the ketone 23 was used as electrophilic component (Table 4, entry 6).
Also for compound 20f a C2 symmetry was observed in the NMR spectra (compare to compound 11d; see
the Experimental part). The stereochemistry of compounds 18 and 20 was also confirmed by preparation
of 20a by reaction of ketone 23 with methyllithium (62% isolated yield).24 The use of benzaldehyde
afforded an 8:1 mixture of diastereomers 20c and 20c0, resulting from the major intermediate 19.
Scheme 9. Reagents and conditions: (i) Li, DTBB (5%), THF, −78°C, 2 h; (ii) E+=H2O, D2O, PhCHO, Et2CO, (CH2)5CO, 23,
−78°C, 10 min; (iii) H2O, −78 to 20°C
Table 4
Preparation of compounds 20 from the epoxide 18
The mentioned 4:1 diastereomeric mixture of epoxides 18 and 180 was prepared starting from the
commercially available D-fructose 21, which was converted into the compound 22 by reaction with 2,2-
dimethoxypropane in acetone under perchloric acid catalysis. Compound 22 was oxidised with PCC in

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T. Soler et al. / Tetrahedron: Asymmetry 11 (2000) 493–517
CH2Cl2 and acetic anhydride to give the ketone 23, which finally afforded the epoxides 18 and 180 using
the same methodology as for epoxide 1 (Scheme 10).
Scheme 10. Reagents and conditions: (i) Me2C(OMe)2, HClO4 cat., Me2CO, 0°C, 6 h; (ii) PCC, Ac2O, CH2Cl2, 30 min; (iii)
KOBut (1 equiv.), Me3SOI (1 equiv.), ButOH, 50°C, 2.5 h
In the final part of this study we use a different approach to prepare the branched-chain functionalised
sugars, which consisted of adding functionalised organolithium compounds to ketone 8 or 23 in a
stereoselective manner. As organolithium component we used dianions 25a and 25b, easily accessible
by DTBB-catalysed lithiation of phthalan 24a26 and isochroman 24b,27 respectively. Once intermediates
25 were generated, the reaction with ketone 8 or 23 at −78°C for 10 min afforded, after hydrolysis,
the expected compounds 26 or 27, respectively (Scheme 11). These diols can be easily cyclised under
Mitsunobu-type reaction conditions to yield heterocycles 28 or 29, respectively (Scheme 11).
Scheme 11. Reagents and conditions: (i) Li, DTBB (2.5%), THF, −78 to 20°C, 30 min; (ii) 8, −78°C, 10 min; (iii) H2O, −78
to 20°C; (iv) 23, −78°C, 10 min; (v) PPh3, DIAD, PhH reflux, 3 h
In conclusion, we have reported here a new way to prepare branched-chain functionalised carbohy-
drates involving functionalised organolithium compounds derived from the carbohydrate or by using an
external organolithium derivative and a ketone, derived from a sugar, as the chiral source.

T. Soler et al. / Tetrahedron: Asymmetry 11 (2000) 493–517
501
3. Experimental
3.1. General
Melting points were obtained with a Reichert Thermovar apparatus. FT-IR spectra were obtained on a
Nicolet Impact 400D spectrophotometer. NMR spectra were recorded on a Bruker AC-300 (300 MHz for
1H and 75 MHz for 13C) using CDCl3 as solvent and TMS as internal standard; chemical shifts are given
in δ (ppm) and coupling constants (J) are given in hertz. 13C NMR assignments were made on the basis
of DEPT experiments. Mass spectra (EI) were obtained at 70 eV on a Shimadzu QP-5000 spectrometer,
fragment ions in m/z with relative intensities (%) in parentheses. Elemental analyses were performed by
the Microanalyses Service at the University of Alicante. High resolution mass spectra were performed by
the corresponding service at the University of Alicante using a Finnigan MAT 95 S apparatus. The purity
of volatile products and the chromatographic analyses (GLC) were determined with a Hewlett–Packard
HP-5890 instrument equipped with a flame ionisation detector and a 12 m capillary column (0.2 mm
diam., 0.33 mm film thickness), using nitrogen (2 ml/min) as carrier gas, Tinjector=275°C, Tcolumn=60°C
(3 min) and 60–270°C (15°C/min). Thin layer chromatography (TLC) was carried out on Schleicher
& Schuell F1500/LS 254 plates coated with a 0.2 mm layer of silica gel; Rf values are given under
these conditions. Column chromatography was performed using silica gel 60 of 35–70 mesh. All starting
materials were commercially available (Acros, Aldrich, Fluka) of the best grade and were used without
further purification. THF was dried over benzophenone ketyl under an argon atmosphere and distilled
before use.
3.2. Preparation of compound 8
To a dichloromethane solution (70 ml) of commercially available D-glucose derivative 7 (5.2 g, 20
mmol) was added acetic anhydride (8 ml, 84.6 mmol) and PCC (13 g, 60 mmol) and the mixture
was stirred at 25°C for 30 min. Then the resulting mixture was filtrated and evaporated (15 mmHg).
The resulting residue was purified by column chromatography (silica gel, hexane:ethyl acetate) to give
1,2;5,6-di-O-isopropylidene-α-D-glucofuranos-3-ulose 8:28 (83% yield) Rf 0.31 (hexane:ethyl acetate,
4;1); ν (film) 1774 (C_O), 1215 cm−1 (CO); δH 1.34 (6H, s, 2×CH3), 1.44 (3H, s, CH3), 1.46
(3H, s, CH3), 4.02–4.05 (2H, m, CHCHH), 4.35–4.40 (2H, m, CHCHCHH), 4.36 (1H, d, J=4.6,
CHCHO2), 6.14 (1H, d, J=4.6, OCHO); δC 25.3, 25.9, 27.1, 27.5 (4×CH3), 64.3 (CH2O), 76.3 (CHCH2),
77.2 (CH2CHCH), 78.9 (CHCHO2), 103.1 (OCHO), 110.4, 114.3 [2×C(CH3)2], 176.2 (CO); m/z 243
[M+−(CH3), 5.5%], 101 (56), 85 (17), 71 (10), 59 (12), 43 (100) [found: M+−(CH3), 243.0825;
C11H15O6 requires: M, 243.0869]; [α]D20=+131.5 [c 1.27 (CH2Cl2)] {lit.28b [α]D20=+107 (CHCl3)}.
3.3. Preparation of epoxide 1
To a tert-butanol solution (30 ml) of trimethylsulfoxonium iodide (3.30 g, 15 mmol) was added a tert-
butanol solution (30 ml) of potassium tert-butoxide (1.80 g, 16 mmol) at 50°C under argon. After 30 min
at this temperature, a new tert-butanol solution (15 ml) of ketone 8 (3.77 g, 14.6 mmol) was added and
stirring was continued for 3 h. Then the resulting mixture was evaporated (15 mmHg) and the resulting
residue was hydrolysed with water (30 ml) and extracted with ethyl acetate (3×40 ml). The organic layer
was dried over anhydrous sodium sulfate and evaporated (15 mmHg). The resulting residue was purified
by column chromatography (silica gel, hexane:ethyl acetate) to give 3,30-anhydro-3-C-hydroxymethyl-
1,2;5,6-di-O-isopropylidene-α-D-glucofuranose 1:29 (82% yield) Rf 0.48 (hexane:ethyl acetate, 4:1); ν

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T. Soler et al. / Tetrahedron: Asymmetry 11 (2000) 493–517
(film) 1213, 1166 cm−1 (CO); δH 1.27 (3H, s, CH3), 1.32 (3H, s, CH3), 1.34 (3H, s, CH3), 1.40 (3H,
s, CH3), 3.09 (1H, d, J=4.9, OCHHC), 3.17 (1H, d, J=4.9, OCHHC), 4.00–4.04 (3H, m, CH2CH), 4.29
(1H, d, J=3.7, CHCHO2), 4.37 (1H, d, J=6.7, CHCHCH2), 5.95 (1H, d, J=3.7, OCHO); δC 25.2, 26.4,
26.8, 26.9 (4×CH3), 46.3 (CH2C), 65.05 (CH2C), 66.9 (CH2CH), 72.9 (CHCHCH2), 76.4 (CHCH2),
84.5 (CHCHO2), 104.2 (OCHO), 109.5, 112.6 [2×C(CH3)2]; m/z 257 [M+−(CH3), 4.3%], 101 (26), 59
(12), 43 (100) [found: M+−(CH3), 257.1029; C12H17O6 requires: M, 257.1025]; [α]D20=+55.5 [c 1.08
(CH2Cl2)] {lit.29 [α]D20=+55 [c 1.7 (MeOH)]}.
3.4. Preparation of oxetane 4
To a tert-butanol solution (30 ml) of trimethylsulfoxonium iodide (8.80 g, 40 mmol) was added a tert-
butanol solution (30 ml) of potassium tert-butoxide (4.48 g, 40 mmol) at 50°C under argon. After 30 min
at this temperature, a new tert-butanol solution (10 ml) of ketone 8 (2.58 g, 10 mmol) was added and
stirring was continued for 3 h. Then the resulting mixture was evaporated (15 mmHg) and the resulting
residue was hydrolysed with water (30 ml) and extracted with ethyl acetate (3×40 ml). The organic layer
was dried over anhydrous sodium sulfate and evaporated (15 mmHg). The resulting residue was purified
by column chromatography (silica gel, hexane:ethyl acetate) to give 3,30-anhydro-3-C-(3-hydroxyethyl)-
1,2;5,6-di-O-isopropylidene-α-D-glucofuranose 4: (83% yield) Rf 0.46 (hexane:ethyl acetate, 4:1); ν
(film) 1215, 1076 cm−1 (CO); δH 1.34 (3H, s, CH3), 1.41 (3H, s, CH3), 1.48 (6H, s, 2×CH3), 2.77–2.86
(2H, m, CH2CH2O), 3.89 (1H, d, J=7.6, CHCHCH2), 4.02 (1H, dd, J=8.5, 5.8, CHCHH), 4.14 (1H, dd,
J=8.5, 6.4, CHCHH), 4.48–4.56 (1H, m, CHCH2), 4.57–4.61 (2H, m, OCH2CH2), 4.67 (1H, d, J=3.5,
CHCHO2), 5.79 (1H, d, J=3.5, OCHO); δC 23.7, 25.4, 26.4, 26.9 (4×CH3), 31.2 (OCH2CH2), 67.5
(OCH2CH2), 73.2 (CH2CO), 77.2 (CH2CH), 82.05 (CHCHCH2), 85.5 (CHCHCH2), 90.9 (CHCHO2),
104.05 (OCHO), 109.3, 112.1 [2×C(CH3)2]; m/z 272 [M+−(CH3), 2.0%], 271 (13), 111 (11), 101 (90),
99 (20), 97 (19), 95 (13), 85 (12), 83 (16), 73 (16), 72 (19), 71 (13), 69 (11), 59 (24), 55 (20), 43 (100), 42
(21) [found: M+−(CH3), 217.1176; C13H19O6 requires: M, 271.1181]; [α]D20=+27.9 [c 0.98 (CH2Cl2)].
3.5. Preparation of epoxide 9
To a suspension of lithium bromide (0.79 g, 9.1 mmol) in THF (15 ml) were added chloroiodomethane
(0.66 ml, 9.1 mmol) and ketone 8 (1.7 g, 6.5 mmol) at 25°C under argon. The reaction mixture was cooled
down to −78°C and 1.6 M n-butyllithium hexane solution (4.5 ml, 7.8 mmol) was added dropwise. The
reaction mixture was allowed to get to 25°C overnight and was hydrolysed with water (30 ml) and
extracted with ethyl acetate (3×30 ml). The organic layer was dried over anhydrous sodium sulfate
and evaporated (15 mmHg). The resulting residue was purified by column chromatography (silica
gel, hexane:ethyl acetate) to give 3,30-anhydro-3-C-hydroxymethyl-1,2;5,6-di-O-isopropylidene-α-D-
allofuranose 9:28a (30% yield) Rf 0.15 (hexane:ethyl acetate, 4:1); ν (film) 1074, 1020 cm−1 (CO); δH
1.32 (3H, s, CH3), 1.37 (3H, s, CH3), 1.40 (3H, s, CH3), 1.63 (3H, s, CH3), 2.99 (1H, d, J=5.2, OCHHC),
3.39 (1H, d, J=5.2 OCHHC), 3.91 (1H, dd, J=7.3, 4.9, CHCHH), 3.96–4.08 (2H, m, CHCHH), 4.25 (1H,
d, J=6.7, CHCHCH2), 4.43 (1H, d, J=3.7, CHCHO2), 5.87 (1H, d, J=4.3, OCHO); δC 25.2 (CH3), 26.5
(2×CH3), 26.8 (CH3), 26.9 (CH2), 64.3 (CH2), 67.0 (CHCH2), 75.1 (CHCH2), 75.7 (CHCHCH2), 80.5
(CHCHO2), 103.8 (OCHO), 109.9, 113.6 [2×C(CH3)2]; m/z 257 [M+−(CH3), 0.4%], 101 (17), 59 (20),
55 (18), 44 (12), 43 (100), 41 (16); [α]D20=+85.6 [c 1.20 (CH2Cl2)].

T. Soler et al. / Tetrahedron: Asymmetry 11 (2000) 493–517
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3.6. Preparation of chlorohydrin 12
To a suspension of lithium bromide (1.31 g, 14.7 mmol) in THF (20 ml) were added chloroiodo-
methane (1.08 ml, 15.6 mmol) and ketone 8 (2.7 g, 10.5 mmol) at 25°C under argon. The reaction
mixure was cooled down to −78°C and a 1.6 M n-butyllithium hexane solution (9.3 ml, 14.9 mmol)
was added dropwise. The reaction mixture was stirred at the same temperature for 30 min and hy-
drolysed with water (30 ml). After that, it was extracted with ethyl acetate (3×30 ml). The organic
layer was dried over anhydrous sodium sulfate and evaporated (15 mmHg). The resulting residue was
purified by column chromatography (silica gel, hexane:ethyl acetate) to give 3-C-chloromethyl-1,2;5,6-
di-O-isopropylidene-α-D-allofuranose 12: (20%) Rf 0.30 (hexane:ethyl acetate, 4:1); m.p. 122–123°C
(dichloromethane/pentane); ν (KBr) 3675–3028 (OH), 1210, 1081, 1016 (CO), 800–600 cm−1 (CCl);
δH 1.36 (3H, s, CH3), 1.39 (3H, s, CH3), 1.46 (3H, s, CH3), 1.61 (3H, s, CH3), 3.01 (1H, s, OH), 3.60
(1H, d, J=12.2, CHHCl), 3.89–3.97 (3H, m, CHHCl, CHCHCH2), 4.09–4.16 (2H, m, CHCH2), 4.64 (1H,
d, J=3.7, CHCHO2), 5.80 (1H, d, J=3.7, OCHO); δC 25.1, 26.5, 26.6, 26.65 (4×CH3), 45.5 (CH2Cl),
67.9 (CHCH2O), 73.0 (CHCH2O), 79.2 (COH), 80.9 (CHCHCH2), 82.1 (CHCHO2), 103.8 (OCHO),
110.0, 112.9 [2×C(CH3)]; m/z 293 [M+−(CH3), 7.0%], 101 (33), 72 (12), 59 (46), 55 (19), 43 (100),
41 (14). Anal. calcd for C13H21ClO6: C, 50.57; H, 6.85; found: C, 50.36; H, 6.63. [α]D20=+23.4 [c 1.20
(CH2Cl2)].
3.7. Preparation of epoxide 17
To a benzene solution (40 ml) of commercially available D-glucose derivative 16 (1.0 g, 4.54 mmol)
and triphenylphosphine (1.31 g, 4.98 mmol) in the presence of 4 Å molecular sieves under argon was
added dropwise diisopropyl azodicarboxylate (0.97 ml, 4.98 mmol) at 25°C. The reaction mixture was
heated at 80°C for 2.5 h. Then the resulting mixture was evaporated (15 mmHg) and the resulting residue
was hydrolysed with water (30 ml) and extracted with ethyl acetate (3×40 ml). The organic layer was
dried over anhydrous sodium sulfate and evaporated (15 mmHg). The resulting residue was purified
by column chromatography (silica gel, hexane:ethyl acetate) to give 5,6-anhydro-1,2-O-isopropylidene-
α-D-glucofuranose 17:30 (80% yield) Rf 0.28 (hexane:ethyl acetate, 3:2); ν (film) 3538–3140 (OH),
1083, 1065 cm−1 (CO); δH 1.32 (3H, s, CH3), 1.48 (3H, s, CH3), 2.87 (1H, dd, J=4.6, 2.7, OCHH),
2.97–3.00 (1H, m, OCHH), 3.30 (1H, br s, OH), 3.40–3.43 (1H, m, CHCH2), 4.00–4.03 (1H, m,
CHCHCH2), 4.24–4.29 (1H, m, CHOH), 4.52 (1H, d, J=3.7, CHCHO2), 5.98 (1H, d, J=3.7, OCHO);
δC 26.1, 26.7 (2×CH3), 45.9 (CH2O), 50.3 (CHCH2), 75.2 (COH), 79.2 (CHCHCH2), 85.0 (CHCHO2),
104.9 [C(CH3)2], 111.8 (OCHO); m/z 187 [M+−(CH3), 12.2%], 59 (82), 57 (13), 55 (15), 43 (100);
[α]D20=−25.0 [c 1.00 (CHCl3)] {lit.30 [α]D20=−25 [c 1 (CHCl3)]}.
3.8. Preparation of epoxide 13
To a THF solution (40 ml) of epoxide 17 (0.91 g, 4.56 mmol) at −78°C under argon was added
dropwise a 1.6 M n-butyllithium hexane solution (3.64 ml, 5.47 mmol). After 5 min at the same
temperature, chloromethyl ethyl ether (0.92 ml, 5.47 mmol) was added and the reaction mixture was
allowed to rise to 25°C overnight and then hydrolysed with water (30 ml) and extracted with ethyl acetate
(3×40 ml). The organic layer was dried over anhydrous sodium sulfate and evaporated (15 mmHg).
The resulting residue was purified by column chromatography (silica gel, hexane:ethyl acetate) to
give 5,6-anhydro-3-O-ethoxymethyl-1,2-O-isopropylidene-α-D-glucofuranose 13: (79% yield) Rf 0.60
(hexane:ethyl acetate, 3:2); ν (film) 1088, 1031 cm−1 (CO); δH 1.24 (3H, t, J=6.9, CH2CH3), 1.47 (3H,

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T. Soler et al. / Tetrahedron: Asymmetry 11 (2000) 493–517
s, CH3), 1.49 (3H, s, CH3), 2.76–2.78 (1H, m, CHCHH), 2.87–2.92 (1H, m, CHCHH), 3.20–3.24 (1H,
m, CHCH2), 3.60–3.71 (2H, m, CH2CH3), 3.76 (1H, dd, J=7.0, 3.0, CHCHCH2), 4.31 (1H, d, J=3.0,
CHOCH2O), 4.62 (1H, d, J=3.5, CHCHO2), 4.77–4.83 (2H, m, OCH2O), 5.92–5.98 (1H, m, OCHO);
δC 14.9 (CH2CH3), 26.1, 26.7 (2×CH3), 46.8 (CHCHCH2), 48.1 (CHCHCH2), 63.8 (CH2CH3), 79.4
(CHOCH2O), 81.4 (CHCHCH2), 83.1 (CHCHO2), 94.3 (OCH2O), 105.2 (OCHO), 111.9 (OCO); m/z
245 [M+−(CH3), 5.5%], 129 (30), 117 (16), 85 (25), 73 (12), 69 (12), 59 (100), 57 (15), 55 (36) 43 (84)
[found: M+, 260.1251; C12H20O6 requires: M, 260.1259]; [α]D20=−38.8 [c 1.44 (CH2Cl2)].
3.9. Preparation of ketone 23
To a suspension of D-fructose (18.42 g, 100 mmol) and 2,2-dimethoxypropane (7.4 ml, 60 mmol) in
acetone (370 ml) was added perchloric acid (4.3 ml, 70%) at 0°C. The reaction mixture was stirred at
the same temperature for 6 h. After that, a saturated ammonium hydroxide aqueous solution (5 ml) was
added. Then the resulting mixture was evaporated (15 mmHg) and the resulting residue was hydrolysed
with water (30 ml) and extracted with dichloromethane (3×40 ml). The organic layer was dried over
anhydrous sodium sulfate and evaporated (15 mmHg). The resulting residue was compound 22 and was
used for the preparation of ketone 23 without further purification. To a dichloromethane solution (80
ml) of D-fructose derivative 22 (7.74 g, 30 mmol) were added acetic anhydride (12 ml, 126.9 mmol)
and PCC (19.5 g, 90 mmol) and the mixture was stirred at 25°C for 30 min. Then the resulting mixture
was filtrated and evaporated (15 mmHg). The resulting residue was purified by column chromatography
(silica gel, hexane:ethyl acetate) to give 1,2;4,5-di-O-isopropylidene-β-D-fructopyranos-3-ulose 23:31
(91% yield) Rf 0.23 (hexane:ethyl acetate, 4:1); m.p. 96–97°C (dichloromethane/pentane) (lit.31b m.p.
102–103°C); ν (KBr) 1748 (C_O), 1229, 1099 cm−1 (CO); δH 1.40 (6H, s, 2×CH3), 1.46 (3H, s, CH3),
1.55 (3H, s, CH3), 3.99 (1H, d, J=9.5, CCHHO), 4.12 (1H, d, J=13.4, CHCHHO), 4.39 (1H, dd, J=13.4,
1.8, CHCHHO), 4.55 (1H, dd, J=5.5, 1.2, CHCHCO), 4.61 (1H, d, J=9.5, CCHHO), 4.73 (1H, d, J=5.5,
CHCO); δC 26.0 (2×CH3), 26.5 (CH3), 27.1 (CH3), 60.1 (CHCH2O), 70.0 (CHCH2O), 75.8 (CCH2O),
77.9 (CHCO), 104.1 (CCH2O), 110.6, 113.8 [2×C(CH3)2], 196.9 (CO); m/z 243 [M+−(CH3), 9.0%],
117 (33), 114 (36), 85 (36), 72 (11), 59 (72), 58 (10), 56 (14), 43 (100), 42 (47), 41 (23); [α]D20=−100.9
[c 1.35 (CH2Cl2)].
3.10. Preparation of epoxide 18
To a tert-butanol solution (50 ml) of trimethylsulfoxonium iodide (4.58 g, 20.8 mmol) was added a
tert-butanol solution (50 ml) of potassium tert-butoxide (2.33 g, 20.8 mmol) at 50°C under argon. After
30 min at this temperature, a new tert-butanol solution (50 ml) of ketone 22 (5.38 g, 20.8 mmol) was
added and stirring was continued for 3 h. Then the resulting mixture was evaporated (15 mmHg) and
the resulting residue was hydrolysed with water (30 ml) and extracted with ethyl acetate (3×40 ml).
The organic layer was dried over anhydrous sodium sulfate and evaporated (15 mmHg). The resulting
residue was purified by column chromatography (silica gel, hexane:ethyl acetate) to give 3,30-anhydro-3-
C-hydroxymethyl-1,2;4,5-di-O-isopropylidene-β-D-psicopyranose 18: (83% yield) Rf 0.55 (hexane:ethyl
acetate, 3:2); ν (film) 1096, 1021 cm−1 (CO); δH 1.32 (3H, s, CH3), 1.33 (3H, s, CH3), 1.48 (3H, s, CH3),
1.54 (3H, s, CH3), 2.68 (1H, d, J=5.5, CHCCHHO), 3.22 (1H, d, J=5.5, CHCCHHO), 3.83–3.84 (1H, m,
CHCHHO), 4.01–4.08 (3H, m, CHCHHO, CHCH2O, CCHHO), 4.23 (1H, d, J=9.1, CCHHO), 4.39 (1H,
d, J=7.3, CHCHCH2); δC 25.1 (CH3), 25.9 (CH3), 26.1 (2×CH3), 48.6 (CHCCH2O), 63.8 (CHCCH2O,
CHCH2O), 73.5 (CCCH2O), 75.0 (CHCH2O), 75.8 (CHCHCH2O), 110.4 (2×CCH3), 110.8 (CCCH2O);

T. Soler et al. / Tetrahedron: Asymmetry 11 (2000) 493–517
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m/z 257 [M+−(CH3), 15%], 139 (14), 72 (29), 59 (15), 55 (12), 43 (100), 42 (25), 41 (15) (found: M+,
272.1280; C13H20O6 requires: M, 272.1260); [α]D20=−120.1 [c 1.20 (CH2Cl2)].
3.11. DTBB-catalysed lithiation of epoxides 1, 9, 13 and 18, and reaction with electrophiles. Isolation
of compounds 3, 11, 15 and 20. General procedure
To a cooled (−78°C) blue suspension of lithium powder (0.10 g, 14.0 mmol) and a catalytic amount of
4,40-di-tert-butylbiphenyl (0.04 g, 0.15 mmol) in THF (5 ml) was added the corresponding epoxide (1.0
mmol) uner argon and the mixture was stirred at the same temperature for 2 h in the case of compounds
1, 9 and 18 and 2.5 h in the case of compounds 13. Then the corresponding electrophile (1.2 mmol; 0.5
ml in the case of water and deuterium oxide; CO2 was bubbled for 30 min) was added at −78°C and
the temperature was allowed to rise to 20°C overnight. The resulting mixture was hydrolysed with water
(20 ml) and extracted with ethyl acetate (3×20 ml). The organic layer was dried over anhydrous sodium
sulfate and evaporated (15 mmHg). The resulting residue was purified by column chromatography (silica
gel, hexane:ethyl acetate) and/or recrystallised to yield pure products 3, 11, 15 and 20. Yields are included
in Tables 1, 3 and 4. Physical, spectroscopic and analytical data follow.
3.11.1. 1,2;5,6-Di-O-isopropylidene-3-C-methyl-α-D-glucofuranose 3a29
Rf 0.31 (hexane:ethyl acetate, 4:1); ν (film) 3664–3061 (OH), 1215, 1076 cm−1 (CO); δH 1.32 (3H,
s, CH3), 1.35 (3H, s, CH3), 1.44 (3H, s, CH3), 1.47 (3H, s, CH3), 1.51 (3H, s, CH3), 2.14 (1H, br s,
OH), 3.80 (1H, d, J=7.6, CHCHCH2), 3.97–4.02 (1H, m, OCHH), 4.12–4.17 (1H, m, OCHH), 4.23
(1H, d, J=3.5, CHCHO2), 4.25–4.30 (1H, m, CHCH2), 5.86 (1H, d, J=3.5, OCHO); δC 20.0, 25.2, 26.4,
26.7, 27.1 (5×CH3), 67.7 (CHCH2), 73.6 (CHCH2), 80.05 (CHCHCH2), 83.1 (CHCHO2), 87.65 (COH),
104.6 (OCHO), 109.6, 112.3 [2×C(CH3)2]; m/z 259 [M+−(CH3), 16.6%], 159 (16), 101 (48), 100 (44),
99 (11), 85 (30), 83 (19), 73 (11), 72 (13), 71 (13), 59 (67), 55 (14), 43 (100), 42 (16) [found: M+−(CH3),
259.1158; C12H19O6 requires: M, 259.1182]; [α]D20=+21.1 [c 0.72 (CH2Cl2)] {lit.29 [α]D20=+23 [c 1.0
(Me2CO)]}.
3.11.2. 3-C-Deuteriomethyl-1,2;5,6-di-O-isopropylidene-α-D-glucofuranose 3b
Rf 0.31 (hexane:ethyl acetate, 4:1); ν (film) 3664–3061 (OH), 1215, 1076 cm−1 (CO); δH 1.32 (3H,
s, CH3), 1.36 (3H, s, CH3), 1.44 (3H, s, CH3), 1.47 (2H, s, CH2D), 1.51 (3H, s, CH3), 2.35 (1H,
br s, OH), 3.80 (1H, d, J=7.6, CHCHCH2), 3.98–4.02 (1H, m, OCHH), 4.11–4.16 (1H, m, OCHH),
4.23 (1H, d, J=3.5, CHCHO2), 4.25–4.32 (1H, m, CHCH2), 5.86 (1H, d, J=3.5, OCHO); δC 19.6 (t,
JCD=19.5, CH2D), 25.2, 26.4, 26.65, 27.1 (4×CH3), 67.7 (CHCH2), 73.5 (CHCH2), 79.9 (CHCHCH2),
83.0 (CHCHO2), 87.6 (COH), 104.5 (OCHO), 109.5, 112.2 [2×C(CH3)2]; m/z 260 [M+−(CH3), 9.3%],
101 (39), 100 (40), 85 (23), 84 (10), 72 (14), 59 (63), 55 (10), 44 (63), 43 (100), 42 (16) [found:
M+−(CH3), 260.1247; C12H18DO6 requires: M, 260.1244]; [α]D20=+22.9 [c 1.25 (CH2Cl2)].
3.11.3. 1,2;5,6-Di-O-isopropylidene-3-C-(trimethylsilylmethyl)-α-D-glucofuranose 3c
Rf 0.27 (hexane:ethyl acetate, 4:1); ν (film) 3643–3117 (OH), 1069, 1013 cm−1 (CO); δH 0.18 [9H,
s, Si(CH3)3], 1.21 (2H, s, CH2Si), 1.31 (3H, s, CH3), 1.36 (3H, s, CH3), 1.45 (3H, s, CH3), 1.50 (3H, s,
CH3), 1.95 (1H, br s, OH), 3.81 (1H, d, J=6.7, CHCHCH2), 3.96–4.01 (1H, m, OCHH), 4.11–4.16 (1H,
m, OCHH), 4.25 (1H, d, J=3.7, CHCHO2), 4.25–4.29 (1H, m, CHCH2), 5.83 (1H, d, J=3.7, OCHO);
δC 0.3 [Si(CH3)3], 21.5 (CH2Si), 25.2, 26.2, 26.6, 27.1 (4×CH3), 67.7 (COH), 74.1 (CH2O), 82.7
(CHCH2O), 84.5 (CHCHCH2), 86.1 (CHCHO2), 104.6 (OCHO), 109.6, 112.0 [2×C(CH3)2]; m/z 331
[M+−(CH3), 0.1%], 115 (45), 101 (19), 100 (47), 85 (26), 75 (34), 73 (76), 59 (25), 55 (10), 45 (19), 44

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T. Soler et al. / Tetrahedron: Asymmetry 11 (2000) 493–517
(27), 43 (100) [found: M+−(CH3), 331.1585; C15H27O6Si requires: M, 331.1577]; [α]D20=+27.8 [c 1.18
(CH2Cl2)].
3.11.4. (20R)-3-C-(2-Hydroxy-2-phenylmethyl)-1,2;5,6-di-O-isopropylidene-α-D-glucofuranose 3d
Minor isomer: Rf 0.29 (hexane:ethyl acetate, 4:1); ν (film) 3691–3107 (OH), 3033 (ArCH), 1065 cm−1
(CO); δH 1.34 (3H, s, CH3), 1.37 (6H, s, 2×CH3), 1.51 (3H, s, CH3), 2.02–2.07 (1H, m, COHCHH),
2.25–2.33 (1H, m, COHCHH), 2.66 (1H, br s, OH), 2.88 (1H, br s, OH), 3.83 (1H, d, J=6.7, CHCHCH2),
4.00–4.13 (2H, m, OCHCH2), 4.38–4.42 (1H, m, OCHCH2), 4.60 (1H, d, J=3.4, CHCHO2), 5.19–5.23
(1H, m, CHOH), 5.93 (1H, d, J=3.4, OCHO), 7.12–7.40 (5H, m, ArH); δC 25.3, 26.6, 26.7, 27.2
(4×CH3), 39.5 (CH2COH), 67.2 (CH2COH), 73.0 (CH2CHOH), 73.7 (CH2O), 82.1 (CHCH2O), 83.6
(CHCHCH2), 85.9 (CHCHO2), 104.8 (OCHO), 109.1, 112.4 [2×C(CH3)2], 125.6, 128.1, 128.7 (ArCH),
144.0 (ArC); m/z 289 [M+−(PhCH2), 1.6%], 105 (13), 104 (13), 101 (18), 100 (20), 85 (13), 59 (12), 58
(14), 44 (32), 43 (100), 42 (11) [found: M+−(CH3, CH3COCH3, H2O), 289.1081; C16H17O5 requires:
M, 289.1076]; [α]D20=+33.3 [c 1.11 (CH2Cl2)].
3.11.5. (20S)-3-C-(2-Hydroxy-2-phenylmethyl)-1,2;5,6-di-O-isopropylidene-α-D-glucofuranose 3d0
Major isomer:21 Rf 0.24 (hexane:ethyl acetate, 4:1); m.p. 94–95°C (dichloromethane/pentane); ν
(KBr) 3708–3118 (OH), 3061, 3036 (ArCH), 1222, 1063 cm−1 (CO); δH 1.28 (3H, s, CH3), 1.36 (3H,
s, CH3), 1.41 (3H, s, CH3), 1.49 (3H, s, CH3), 2.25–2.28 (2H, m, COHCH2), 3.00 (1H, br s, OH), 3.70
(1H, br s, OH), 3.88 (1H, d, J=7.3, CHCHCH2), 4.00 (1H, dd, J=8.5, 6.1, CHCHH), 4.14 (1H, dd, J=8.5,
6.1, CHCHH), 4.35–4.41 (2H, m, OCHCH2, CHCHO2), 5.23–5.29 (1H, m, CHOH), 5.82 (1H, d, J=3.4,
OCHO), 7.11–7.37 (5H, m, ArH); δC 25.4, 26.4, 26.6, 27.1 (4×CH3), 40.4 (CH2COH), 67.8 (CH2COH),
71.2 (CH2CHOH), 72.9 (CH2O), 81.2 (CHCH2O), 84.1 (CHCHCH2), 87.4 (CHCHO2), 104.3 (OCHO),
109.5, 112.2 [2×C(CH3)2], 125.6, 127.6, 128.5 (ArCH), 144.4 (ArC); m/z 322 [M+−(2×CH3, H2O),
0.6%], 105 (14), 104 (15), 101 (14), 100 (21), 85 (14), 59 (13), 58 (15), 44 (18), 43 (100), 42 (10) [found:
M+−(CH3), 369.1605; C19H25O7 requires: M, 365.1600]; [α]D20=+19.5 [c 1.12 (CH2Cl2)].
3.11.6. 3-C-(2-Hydroxy-2-methylpropyl)-1,2;5,6-di-O-isopropylidene-α-D-glucofuranose 3e
Rf 0.27 (hexane:ethyl acetate, 4:1); ν (film) 3670–3074 (OH), 1165, 1069 cm−1 (CO); δH 1.32 (3H,
s, CH3), 1.35 (3H, s, CH3), 1.37 (3H, s, CH3), 1.44 (3H, s, CH3), 1.47 (3H, s, CH3), 1.49 (3H, s,
CH3), 1.95 (1H, d, J=14.9, CHHCOH), 2.16 (1H, d, J=14.9, CHHCOH), 2.37 (1H, br s, OH), 3.77
(1H, d, J=6.4, CHCHCH2), 4.03–4.13 (2H, m, CHCH2), 4.34–4.41 (1H, m, CHCH2), 4.50 (1H, d, J=3.4,
CHCHO2), 5.11 (1H, br s, OH), 5.87 (1H, d, J=3.4, OCHO); δC 25.45, 26.5, 26.7, 27.2 (4×CH3), 28.9,
33.7 [COH(CH3)2], 40.0 (CH2C), 67.4 [COH(CH3)2], 73.1 (COHCH2), 77.2 (CH2O), 81.5 (CHCH2),
84.2 (CHCHCH2), 86.2 (CHCHO2), 105.0 (OCHO), 109.1, 112.0 [2×C(CH3)2]; m/z 299 [M+−(CH3,
H2O), 1.6%], 241 (12), 143 (35), 111 (11), 101 (55), 100 (68), 97 (10), 85 (55), 83 (29), 73 (11), 72
(15), 71 (31), 59 (76), 58 (12), 57 (17), 56 (13), 55 (33), 44 (10), 43 (100), 42 (18) [found: M+−(CH3),
317.1555; C15H25O7 requires: M, 317.1600]; [α]D20=+27.8 [c 1.50 (CH2Cl2)].
3.11.7. 3-C-(1-Hydroxycyclohexylmethyl)-1,2;5,6-di-O-isopropylidene-α-D-glucofuranose 3f32
Rf 0.34 (hexane:ethyl acetate, 4:1); m.p. 108–109°C (dichloromethane/pentane); ν (KBr) 3689–3093
(OH), 1222, 1158 cm−1 (CO); δH 1.32 (3H, s, CH3), 1.37 (3H, s, CH3), 1.44 (3H, s, CH3), 1.50 (3H,
s, CH3), 1.30–1.96 [10H, m, (CH2)5], 2.00–2.08 (2H, m, COHCH2), 2.47 (2H, br s, 2×OH), 3.78 (1H,
d, J=7.3, CHCHCH2), 4.01–4.13 (2H, m, CHCH2), 4.34–4.41 (1H, m, CHCH2), 4.46 (1H, d, J=3.1,
CHCHO2), 5.85 (1H, d, J=3.1, OCHO); δC 21.8, 21.9, 25.3 (3×CH2), 25.45, 26.5, 26.7, 27.25 (4×CH3),
36.6, 39.15, 41.15 (3×CH2), 67.3 [COH(CH2)5], 73.1 (COHCH), 74.0 (CH2O), 81.3 (CHCH2), 84.2

T. Soler et al. / Tetrahedron: Asymmetry 11 (2000) 493–517
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(CHCHCH2), 86.4 (CHCHO2), 105.0 (OCHO), 109.0, 111.9 [2×C(CH3)2]; m/z 357 [M+−(CH3), 0.6%],
281 (23), 183 (21), 143 (52), 101 (83), 100 (100), 99 (36), 95 (35), 85 (71), 81 (43), 71 (38), 67 (21), 59
(62), 57 (21), 55 (63), 43 (98), 42 (28); [α]D20=+30.1 [c 1.79 (CH2Cl2)].
3.11.8. 1,2;5,6-Di-O-isopropylidene-3-C-methyl-α-D-allofuranose 11a28a
Rf 0.13 (hexane:ethyl acetate, 4:1) (48% yield); ν (film) 3637–3107 (OH), 1076, 1008 cm−1 (CO); δH
1.28 (3H, s, CH3), 1.35 (3H, s, CH3), 1.36 (3H, s, CH3), 1.45 (3H, s, CH3), 1.59 (3H, s, CH3), 2.68 (1H, br
s, OH), 3.78 (1H, d, J=7.3, CHCHCH2), 3.98 (1H, dd, J=11.1, 8.1, CHH), 4.07–4.13 (2H, m, CHCHH),
4.17 (1H, d, J=3.7, CHCHO2), 5.7 (1H, d, J=3.7, OCHO); δC 19.5, 25.2, 26.4, 26.6, 26.7 (5×CH3),
67.7 (CHCH2), 73.7 (CHCH2), 77.4 (CHCHCH2), 81.4 (CHCHO2), 84.7 (COH), 103.6 (OCHO), 109.5,
112.8 [2×C(CH3)2]; m/z 259 [M+−(CH3), 6.4%], 101 (16), 100 (24), 85 (13), 59 (39), 55 (14), 44
(13), 43 (100) [found: M+−(CH3), 259.1176; C12H19O6 requires: M, 259.1182]; [α]D20=+23.7 [c 1.26
(CH2Cl2)].
3.11.9. 6-Deoxy-3-O-ethoxymethyl-1,2-O-isopropylidene-α-D-glucofuranose 15a
Rf 0.38 (hexane:ethyl acetate, 3:2); ν (film) 3645–3106 (OH), 1082, 1025 cm−1 (CO); δH 1.24 (3H, t,
J=7.0, CH2CH3), 1.34 (3H, d, J=6.1, CHCH3), 1.50 (3H, s, CH3), 1.56 (3H, s, CH3), 3.06 (1H, d, J=4.6,
OH), 3.56–3.71 (2H, m, CH2CH3), 3.93 (1H, dd, J=8.2, 2.7, CHCHOH), 3.98–4.02 (1H, m, CHOH),
4.22 (1H, d, J=2.7, CHCHCHOH), 4.56 (1H, d, J=3.7, CHCHO2), 4.75 (1H, d, J=6.4, OCHHO), 4.80
(1H, d, J=6.4, OCHHO), 5.92 (1H, d, J=3.7, OCHO); δC 14.9 (CH2CH3), 20.4 (CHOHCH3), 26.3,
26.8 (2×CH3), 64.4 (CH2CH3), 64.9 (CHOCH2O), 81.7 (CHOH), 83.6 (CHCHOH), 84.1 (CHCHO2),
95.6 (OCH2O), 105.1 (OCHO), 111.8 (OCO); m/z 247 [M+−(CH3), 0.5%], 113 (32), 85 (13), 59 (100),
55 (11), 45 (21), 44 (11), 43 (72) [found: M+−(CH3), 247.1176; C11H19O6 requires: M, 247.1182];
[α]D20=−48.2 [c 1.10 (CH2Cl2)].
3.11.10. 6-Deoxy-6-deuterio-3-O-ethoxymethyl-1,2-O-isopropylidene-α-D-glucofuranose 15b
Rf 0.38 (hexane:ethyl acetate, 3:2); ν (film) 3645–3106 (OH), 1082, 1025 cm−1 (CO); δH 1.26 (3H, t,
J=3.6, CH2CH3), 1.31 (6H, s, 2×CH3), 1.32–1.35 (2H, m, CH2D), 3.10 (1H, d, J=4.9, OH), 3.56–3.74
(2H, m, CH2CH3), 3.93 (1H, dd, J=8.1, 2.9, CHCHOH), 3.99–4.10 (1H, m, CHOH), 4.23 (1H, d, J=3.0,
CHOCH2O), 4.56 (1H, d, J=3.8, CHCHO2), 4.75 (1H, d, J=6.4, OCHHO), 4.80 (1H, d, J=6.4, OCHHO),
5.90 (1H, d, J=3.8, OCHO); δC 14.9 (CH2CH3), 20.1 (t, JCD=20.1, CH2D), 26.2, 26.7 (2×CH3), 64.4
(CH2CH3), 64.8 (CHOCH2O), 81.7 (CHOH), 83.6 (CHCHOH), 84.0 (CHCHO2), 95.5 (OCH2O), 105.1
(OCHO), 111.8 (OCO); m/z 248 [M+−(CH3), 0.3%], 113 (38), 85 (20), 84 (11), 71 (11), 60 (11), 59
(100), 55 (17), 46 (16), 45 (14), 44 (21), 43 (82), 41 (32) [found: M+, 263.1475; C12H21DO6 requires:
M, 263.1479]; [α]D20=−41.3 [c 1.46 (CH2Cl2)].
3.11.11. (10S)-6-Deoxy-3-O-ethoxymethyl-6-C-(hydroxyphenylmethyl)-1,2-O-isopropylidene-α-D-
glucofuranose 15c
Major isomer: Rf 0.27 (hexane:ethyl acetate, 3:2); ν (film) 3682–3085 (OH), 3024 (ArH), 1085,
1031 cm−1 (CO); δH 1.22 (3H, t, J=7.0, CH2CH3), 1.30 (3H, s, CH3), 1.49 (3H, s, CH3), 2.00–2.10
(1H, m, CHOHCHH), 2.20 (1H, dd, J=14.6, 7.9, CHOHCHH), 3.24 (1H, br s, OH), 3.51–3.70 (2H,
m, CH2CH3), 3.78 (1H, br s, OH), 4.10 (2H, m, CHCHOH), 4.20 (1H, m, CHCHCHOH), 4.53 (1H,
d, J=3.7, CHCHO2), 4.72 (1H, d, J=6.7, OCHHO), 5.08–5.11 (1H, m, CHPh), 4.77 (1H, d, J=6.7,
OCHHO), 5.88 (1H, d, J=3.7, OCHO), 7.22–7.40 (5H, m, ArH); δC 14.9 (CH2CH3), 26.3, 26.8
(2×CH3), 41.7 (CHOHCH2), 64.6 (CH2CH3), 66.3 (CHOCH2O), 71.5 (CHCHOH), 82.0 (PhCHOH),
82.2 (CHCHOH), 83.6 (CHCHO2), 95.9 (OCH2O), 105.1 (OCHO), 111.9 (OCO), 125.6, 127.1, 128.3

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T. Soler et al. / Tetrahedron: Asymmetry 11 (2000) 493–517
(ArCH), 144.5 (ArC); m/z 335 [M+−(CH3, H2O), 0.2%], 113 (31), 105 (16), 77 (10), 59 (100), 43 (36)
[found: M+−(2H2O, CH3COCH3), 274.1208; C16H18O4 requires: M, 274.1205]; [α]D20=−18.2 [c 1.00
(CH2Cl2)].
3.11.12. (10R)-6-Deoxy-3-O-ethoxymethyl-6-C-(hydroxyphenylmethyl)-1,2-O-isopropylidene-α-D-
glucofuranose 15c0
Minor isomer: Rf 0.34 (hexane:ethyl acetate, 3:2); ν (film) 3658–3113 (OH), 3058, 3054 (ArH), 1085,
1024 cm−1 (CO); δH 1.25 (3H, t, J=3.7, CH2CH3), 1.30 (3H, s, CH3), 1.46 (3H, s, CH3), 1.84–1.96
(1H, m, CHOHCHH), 2.15–2.20 (1H, m, CHOHCHH), 3.57–3.79 (2H, m, CH2CH3), 3.82 (1H, br
s, OH), 3.98 (1H, dd, J=8.2, 2.7, CHCHOH), 4.16 (1H, m, CHOH), 4.19 (1H, br s, OH), 4.21 (1H,
d, J=3.0, CHCHCHOH), 4.55 (1H, d, J=3.7, CHCHO2), 4.76 (1H, d, J=6.7, OCHHO), 4.84 (1H, d,
J=6.7, OCHHO), 5.00–5.03 (1H, m, CHPh), 5.89 (1H, d, J=3.7, OCHO), 7.24–7.40 (5H, m, ArH);
δC 14.9 (CH2CH3), 26.3, 26.7 (2×CH3), 42.8 (CHOHCH2), 64.5 (CH2CH3), 69.7 (CHOCH2O), 75.0
(CHCHOH), 81.5 (PhCHOH), 82.7 (CHCHOH), 83.6 (CHCHO2), 95.8 (OCH2O), 105.1 (OCHO), 112.0
(OCO), 125.6, 127.4, 128.3 (ArCH), 144.4 (ArC); m/z 321 [M+−(CH2CH3, H2O), 0.6%], 113 (16), 105
(15), 77 (10), 59 (100), 43 (39) [found: M+−(2H2O, CH3COCH3), 274.1208; C16H18O4 requires: M,
274.1205]; [α]D20=−38.3 [c 1.15 (CH2Cl2)].
3.11.13. 6-Deoxy-3-O-ethoxymethyl-6-C-[(1-hydroxy-1-methyl)ethyl]-1,2-O-isopropylidene-α-D-
glucofuranose 15d32
Rf 0.34 (hexane:ethyl acetate, 3:2); ν (film) 3670–3087 (OH), 1083, 1033 cm−1 (CO); δH 1.26 (3H, t,
J=7.0, CH2CH3), 1.27 (3H, s, CH3), 1.31 (3H, s, CH3), 1.33 (3H, s, CH3), 1.49 (3H, s, CH3), 1.73 (1H,
dd, J=14.6, 11.0, CHOHCHH), 1.78 (1H, dd, J=14.6, 2.4, CHOHCHH), 3.42 (1H, br s, OH), 3.59–3.77
(2H, m, CH2CH3), 3.97 (1H, dd, J=8.5, 3.0, CHOHCH), 4.08 (1H, br s, OH), 4.22–4.27 (2H, m, CHOH,
CHOCH2O), 4.56 (1H, d, J=3.7, CHCHO2), 4.77 (1H, d, J=6.1, OCHHO), 4.84 (1H, d, J=6.1, OCHHO),
5.90 (1H, d, J=3.7, OCHO); δC 14.9 (CH2CH3), 26.3, 26.8 (2×CH3), 27.9, 31.6 (2×COHCH3), 45.2
(CHOHCH2), 64.4 (CH2CH3), 66.8 (CHOCH2O), 71.3 (COH), 81.5 (CHOH), 83.6 (CHCHOH), 95.8
(OCH2O), 105.0 (OCHO), 111.9 (OCO); m/z 305 [M+−(CH3), 0.4%], 59 (100), 43 (71); [α]D20=−17.0
[c 1.15 (CH2Cl2)].
3.11.14. 6-Deoxy-3-O-ethoxymethyl-6-C-(1-hydroxycyclohexyl)-1,2-O-isopropylidene-α-D-glucofura-
nose 15e
Rf 0.34 (hexane:ethyl acetate, 3:2); ν (film) 3648–3115 (OH), 1086, 1024 cm−1 (CO); δH 1.22–1.25
(3H, m, CH2CH3), 1.31 (3H, s, CH3), 1.49 (3H, s, CH3), 1.55–1.71 [12H, m, (CH2)5, CH2COH], 3.23
(1H, br s, OH), 3.59–3.75 (2H, m, CH2CH3), 3.96 (1H, dd, J=8.4, 2.7, CHCHOH), 4.06 (1H, br s, OH),
4.22 (1H, d, J=2.7, CH2OCH), 4.22–4.26 (1H, m, CHOH), 4.56 (1H, d, J=3.7, CHCHO2), 4.75 (1H,
d, J=6.4, OCHHO), 4.83 (1H, d, J=6.4, OCHHO), 5.90 (1H, d, J=3.7, OCHO); δC 14.9 (CH2CH3),
22.1, 22.3, 25.8 (3×CH2), 26.3, 26.8 (2×CH3), 36.1, 40.1 (2×CH2), 43.5 (CHOHCH2), 64.4 (CH2CH3),
66.0 (CHOH), 72.2 (COH), 81.3 (CH2OCH), 83.1 (CHOHCH), 83.6 (CHCHO2), 95.7 (OCH2O), 105.1
(OCHO), 111.9 (OCO); m/z 314 [M+−(CH3CH2OH), 0.1%], 113 (38), 85 (13), 81 (15), 71 (12), 59 (100),
57 (19), 55 (33), 44 (21), 43 (65), 42 (10) [found: M+−(CH3CH2OH), 314.1707; C16H26O6 requires: M,
314.1729]; [α]D20=−23.5 [c 1.35 (CH2Cl2)].
3.11.15. 6-C-Carboxy-6-deoxy-3-O-ethoxymethyl-1,2-O-isopropylidene-α-D-glucofuranose 15f32
Rf 0.12 (hexane:ethyl acetate, 3:2); ν (film) 3694–3043 (OH), 1723 (C_O), 1084, 1029 cm−1 (CO);
δH 1.24 (3H, t, J=7.1, CH2CH3), 1.31 (3H, s, CH3), 1.49 (3H, s, CH3), 2.58 (1H, dd, J=16.5, 9.5,

T. Soler et al. / Tetrahedron: Asymmetry 11 (2000) 493–517
509
CHOHCHH), 2.88 (1H, dd, J=16.5, 2.4, CHOHCHH), 3.56–3.76 (2H, m, CH2CH3), 4.06 (1H, dd,
J=8.8, 2.7, CHCHOH), 4.23 (1H, d, J=2.7, CHCHCHOH), 4.24–4.33 (1H, m, CHOH), 4.57 (1H, d,
J=3.4, CHCHO2), 4.76 (1H, d, J=6.7, OCHHO), 4.81 (1H, d, J=6.7, OCHHO), 5.88 (1H, d, J=3.4,
OCHO); δC 14.8 (CH2CH3), 26.2, 26.8 (2×CH3), 38.6 (CHOHCH2), 64.4 (CH2CH3), 65.1 (CHOH),
81.1 (CHOCH2), 81.8 (CHCHOH), 83.6 (CHCHO2), 95.7 (OCH2O), 105.1 (OCHO), 112.0 (OCO),
177.2 (CO2H); [α]D20=−19.9 [c 0.89 (CH2Cl2)].
3.11.16. 1,2;4,5-Di-O-isopropylidene-3-C-methyl-β-D-psicopyranose 20a
Major isomer: Rf 0.62 (hexane:ethyl acetate, 3:2); ν (film) 3623–3122 (OH), 1215, 1044 cm−1 (CO);
δH 1.24 [3H, s, C(OH)CH3], 1.39 (3H, s, CH3), 1.42 (3H, s, CH3), 1.49 (3H, s, CH3), 1.60 (3H, s, CH3),
2.53 (1H, br s, OH), 3.97 (1H, d, J=9.8, CCHHO), 4.06 (1H, d, J=5.5, CHCHCH2), 4.10–4.18 (3H, m,
CHCH2), 4.30 (1H, d, J=9.8, CCHHO); δC 20.2 [C(OH)CH3], 25.5, 25.7, 25.8, 26.2 (4×CH3), 59.7
(CHCH2), 70.4 (COH), 71.6 (CCH2), 71.8 (CHCH2), 75.5 (CHCHCH2), 106.9, 108.9 [2×C(CH3)2],
112.3 (CCH2O); m/z 259 [M+−(CH3), 4.6%], 157 (10), 99 (20), 85 (12), 79 (11), 59 (36), 52 (11), 43
(100), 42 (11) [found: M+−(CH3), 259.1187; C12H19O6 requires: M, 259.1182]; [α]D20=−118.7 [c 1.10
(CH2Cl2)].
3.11.17. 3-C-Deuteriomethyl-1,2;4,5-di-O-isopropylidene-β-D-psicopyranose 20b
Major isomer: Rf 0.62 (hexane:ethyl acetate, 3:2); ν (film) 3645–3078 (OH), 1220, 1097, 1030 cm−1
(CO); δH 1.23 (2H, m, CH2D), 1.39, 1.42, 1.49, 1.60 (12H, s, 4×CH3), 2.51 (1H, br s, OH), 3.97 (1H,
d, J=9.5, CCHHO), 4.06 (1H, d, J=5.5, CHCHCH2), 4.14–4.21 (3H, m, CHCH2O), 4.30 (1H, d, J=9.5,
CCHHO); δC 19.5 (t, JCD=19.5, CH2D), 25.5, 25.7, 25.8, 26.2 (4×CH3), 59.7 (CHCH2O), 70.3 (COH),
71.6 (CCH2O), 71.8 (CHCH2O), 75.5 (CHCHCH2O), 106.9 (CCH2O), 108.9, 112.3 [2×C(CH3)2]; m/z
260 [M+−(CH3), 8.0%], 158 (18), 117 (14), 100 (36), 99 (15), 85 (23), 84 (16), 72 (13), 59 (64), 57
(16), 55 (10), 43 (100), 42 (29), 41 (18) [found: M+, 275.1440; C13H21DO6 requires: M, 275.1479];
[α]D20=−123.7 [c 1.30 (CH2Cl2)].
3.11.18. 3-C-Deuteriomethyl-1,2;4,5-di-O-isopropylidene-β-D-fructopyranose 20b0
Minor isomer: Rf 0.52 (hexane:ethyl acetate, 3:2); ν (film) 3645–3078 (OH), 1220, 1077, 1030 cm−1
(CO); δH 1.31 (2H, m, CH2D), 1.35, 1.44, 1.49, 1.51 (12H, s, 4×CH3), 2.53 (1H, br s, OH), 3.81
(1H, d, J=12.8, CHCHCH2), 3.90 (1H, d, J=9.8, CCHHO), 4.19–4.23 (3H, m, CHCHCHHO), 4.30
(1H, dd, J=7.3, 2.4, CCHHO); δC 21.8 (t, JCD=20.7, CH2D), 24.8, 25.7, 26.0, 26.4 (4×CH3), 62.6
(CHCH2O), 71.3 (COH), 72.3 (CCH2O), 73.0 (CHCH2O), 77.9 (CHCHCH2O), 105.9 (CCH2O), 109.0,
110.5 [2×C(CH3)2]; m/z 260 [M+−(CH3), 9.0%], 158 (16), 117 (13), 100 (31), 99 (13), 85 (20), 84 (14),
72 (19), 59 (51), 57 (14), 55 (10), 44 (100), 43 (53), 42 (27) [found: M+, 275.1440; C13H21DO6 requires:
M, 275.1479]; [α]D20=−89.6 [c 0.85 (CH2Cl2)].
3.11.19. (20R)-3-C-(2-Hydroxy-2-phenylethyl)-1,2;4,5-di-O-isopropylidene-β-D-psicopyranose 20c
Major isomer: m.p. 126–127°C (dichloromethane/pentane); Rf 0.40 (hexane:ethyl acetate, 3:2); ν
(KBr) 3606–3278 (OH), 3016, 3004 (ArH), 1217, 1089, 1040 cm−1 (CO); δH 1.36 (3H, s, CH3), 1.43
(3H, s, CH3), 1.46 (3H, s, CH3), 1.68 (3H, s, CH3), 1.93 (2H, d, J=5.5, COHCH2), 2.71 (2H, br s, 2×OH),
3.94 (1H, d, J=9.8, CCHHO), 4.17–4.38 (4H, m, CHCH2O, CCHHO), 4.62 (1H, d, J=1.8, CHCHCH2O),
5.13 (1H, m, CHOH), 7.24–7.41 (5H, m, ArH); δC 25.1 (CH3), 25.6 (CH3), 25.7 (CH3), 26.3 (CH3), 45.1
[C(OH)CH2], 59.6 (CHCH2O), 68.9 (CHOH), 71.7 (CCH2O), 72.3 (CHCH2O), 75.9 (CHCHCH2), 77.2
(COH), 107.5 (CCH2O), 109.3, 112.6 [2×C(CH3)2], 125.7, 126.9, 128.2 (ArCH), 144.9 (ArC); m/z 347
[M+−(H2O, CH3), 8%], 131 (12), 114 (23), 105 (20), 104 (24), 85 (14), 77 (11), 59 (15), 55 (11), 44

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T. Soler et al. / Tetrahedron: Asymmetry 11 (2000) 493–517
(10), 43 (100), 42 (21), 41 (12). Anal. calcd for C20H28O7: C, 63.14; H, 7.41; found: C, 63.07; H, 7.11.
[α]D20=−123.5 [c 0.98 (CH2Cl2)].
3.11.20. (20S)-3-C-(2-Hydroxy-2-phenylethyl)-1,2;4,5-di-O-isopropylidene-β-D-psicopyranose 20c0
Minor isomer: Rf 0.44 (hexane:ethyl acetate, 3:2); ν (film) 3670–3133 (OH), 3006, 3000 (ArH), 1225,
1069, 1026 cm−1 (CO); δH 1.37 (3H, s, CH3), 1.45 (3H, s, CH3), 1.46 (3H, s, CH3), 1.65 (3H, s, CH3),
2.96 (1H, d, J=16.2, COHCHH), 3.16 (1H, d, J=16.2, COHCHH), 3.46 (1H, d, J=9.8, CCHHO), 3.73
(1H, d, J=9.8, CCHHO), 4.03–4.18 (3H, m, CHCHCH2, OH), 4.24–4.28 (1H, m, PhCHOH), 4.67 (1H, d,
J=13.4, CHCHHO), 4.92 (1H, d, J=13.4, CHCHHO), 5.29 (1H, br s, OH), 7.09–7.28 (5H, m, ArH); δC
24.5 (CH3), 25.1 (CH3), 26.2 (CH3), 26.6 (CH3), 41.1 (COHCH2), 63.7 (CHCH2O), 70.7 (CHOH), 72.3
(CCH2O), 72.6 (CHCH2O), 73.6 (CHCHCH2), 73.9 (COH), 105.2 (CCH2O), 109.4, 110.2 [2×C(CH3)2],
125.8, 127.5, 128.4 (ArCH), 144.1 (ArC); m/z 347 [M+−(H2O, CH3), 13.5%], 131 (11), 105 (19), 104
(17), 59 (11), 55 (15), 44 (10), 43 (100), 42 (18), 41 (12) [found: M+−(H2O, CH3), 347.1521; C19H23O6
requires: M, 347.1495]; [α]D20=−57.7 [c 1.33 (CH2Cl2)].
3.11.21. 3-C-(2-Ethyl-2-hydroxybutyl)-1,2;4,5-di-O-isopropylidene-β-D-psicopyranose 20d
Rf 0.48 (hexane:ethyl acetate, 3:2); ν (film) 3555–3107 (OH), 1218, 1053 cm−1 (CO); δH 0.90 (6H,
dd, J=14.6, 7.3, 2×CH2CH3), 1.26–1.63 (4H, m, 2×CH2CH3), 1.34 (3H, s, CH3), 1.46 (3H, s, CH3), 1.49
(3H, s, CH3), 1.51 (3H, s, CH3), 1.81 [1H, d, J=15.0, C(OH)CHH], 1.96 [1H, d, J=15.0, C(OH)CHH],
2.82 (1H, br s, OH), 3.67 (1H, m, CHCHH), 3.87 (1H, d, J=10.1, CCHHO), 4.18 (1H, d, J=10.1,
CCHHO), 4.24–4.35 (3H, m, CHCHH, OH), 4.69 (1H, d, J=7.3, CHCHCH2); δC 7.5, 8.2 (2×CH2CH3),
24.4, 25.1, 26.3, 26.6 (4×CCH3), 31.9, 33.7 (2×CH2CH3), 36.1 (COHCH2), 64.0 (CHCH2O), 72.6
(CCH2O), 73.0 (CHCH2O), 74.3 (CH3CH2COH), 75.6 (CHCHCH2), 76.1 (CCCOH), 105.7, 109.1
[2×C(CH3)2], 109.6 (CCH2O); m/z 345 [M+−(CH3), 1.0%], 197 (18), 111 (13), 99 (13), 87 (12), 85
(22), 83 (23), 79 (11), 69 (11), 59 (38), 57 (59), 55 (26), 45 (15), 43 (100), 42 (15), 41 (25) [found:
M+−(CH3), 345.1912; C17H29O7 requires: M, 345.1913]; [α]D20=−46.2 [c 1.00 (CH2Cl2)].
3.11.22. 3-C-(1-Hydroxycyclohexylmethyl)-1,2;4,5-di-O-isopropylidene-β-D-psicopyranose 20e
Rf 0.56 (hexane:ethyl acetate, 3:2); ν (film) 3665–3101 (OH), 1214, 1067, 1012 cm−1 (CO); δH
1.32–1.70 (10H, m, 5×CH2), 1.35, 1.47, 1.48, 1.51 (12H, s, 4×CH3), 1.77 (1H, d, J=15.3, COHCHH),
2.02 (1H, m, COHCHH), 2.85 (1H, br s, OH), 3.68 (1H, dd, J=12.8, 1.8, CHCHHO), 3.88 (1H, d,
J=10.1, CCHHO), 4.18 (1H, d, J=10.1, CCHHO), 4.27–4.32 (3H, m, CHCHHO, OH), 4.68 (1H, d,
J=7.3, CHCHCH2); δC 22.1, 24.5, 25.1, 25.5, 26.2, 26.6 [4×CH3, 3×CH2, C(OH)CH2C(OH)], 38.5
[C(OH)CH2CH2], 40.2 [C(OH)CH2CH2], 41.0 [C(OH)CH2CH2], 63.8 (CHCH2O), 72.5 (CCH2O), 72.9
(CHCH2O), 74.3 [CHC(OH)C], 76.0 (CHCHCH2), 105.7 (OCCH2), 109.0, 109.7 [2×C(CH3)2]; m/z 354
[M+−(H2O), 0.4%], 339 [M+−(CH3, H2O), 5.0%], 123 (12), 117 (10), 95 (49), 94 (10), 85 (20), 81 (19),
79 (11), 67 (16), 59 (53), 57 (17), 55 (28), 43 (100), 42 (20), 41 (33) [found: M+−(CH3), 357.1907;
C18H29O7 requires: M, 357.1913]; [α]D20=−60.8 [c 1.30 (CH2Cl2)].
3.11.23. Compound 20f
M.p. 232–233°C (dichloromethane/pentane); Rf 0.49 (hexane:ethyl acetate, 3:2); ν (KBr) 3634–3150
(OH), 1220, 1079 cm−1 (CO); δH 1.39 (6H, s, 2×CH3), 1.47 (12H, s, 4×CH3), 1.61 (6H, s, 2×CH3),
1.94 (2H, s, CCH2C), 4.01 (2H, d, J=9.8, 2×CCHHO), 4.05–4.18 (4H, m, 2×CHCH2), 4.25–4.29 (2H,
m, 2×CHCH2), 4.35 (2H, d, J=6.1, 2×CHCHCH2), 4.44 (2H, d, J=9.8, 2×CCHHO), 4.58 (2H, br s,
2×OH); δC 24.9, 25.4, 26.2, 26.6 (8×CH3), 43.4 (CCH2C), 60.7 (2×CHCH2), 70.6 (2×CCH2), 71.0
(2×COH), 72.5 (2×CHCH2), 75.8 (2×CHCHCH2), 107.1, 109.2, 111.9 [4×C(CH3)2, (2×CCH2O)];

T. Soler et al. / Tetrahedron: Asymmetry 11 (2000) 493–517
511
m/z 317 [M+−(215), 0.2%], 85 (17), 59 (22), 43 (100), 42 (12), 41 (10). Anal. calcd for C25H40O12: C,
56.38; H, 7.57; found: C, 56.10; H, 7.57. [α]D20=−104.6 [c 1.00 (CH2Cl2)].
3.12. Preparation of compounds 11a and 20a by addition of methyllithium to ketones 8 and 23
A 1.6 M methyllithium diethyl ether solution (0.5 ml, 0.8 mmol) was added at −78°C to the
corresponding ketone (0.5 mmol) THF solution (5 ml) under argon at −78°C. After 10 min at this
temperature the reaction mixture was hydrolysed with water (15 ml), allowed to reach 25°C and extracted
with ethyl acetate (3×20 ml). The organic layer was dried over anhydrous sodium sulfate and evaporated
(15 mmHg). The resulting residue was purified by column chromatography (silica gel, hexane:ethyl
acetate) to yield the title compounds. Yields are given in the text. Physical and spectroscopic data are
given above.
3.13. DTBB-catalysed lithiation of the oxetane 4. Isolation of compounds 6. General procedure
To a cooled (–40°C) blue suspension of lithium powder (0.10 g, 14.0 mmol) and a catalytic amount
of 4,40-di-tert-butylbiphenyl (0.04 g, 0.15 mmol) in THF (6 ml) was added oxetane 4 (0.27 g, 1.0
mmol) under argon and the mixture was stirred at the same temperature for 3 h. Then the corresponding
electrophile (1.2 mmol; 0.5 ml in the case of water and deuterium oxide) was added at –40°C and the
temperature was allowed to rise to 20°C overnight. The resulting mixture was hydrolysed with water
(20 ml) and extracted with ethyl acetate (3×20 ml). The organic layer was dried over anhydrous sodium
sulfate and evaporated (15 mmHg). The resulting residue was purified by column chromatography (silica
gel, hexane:ethyl acetate) and/or recrystallised to yield pure products 6. Yields are given in the text.
Physical, spectroscopic and analytical data follow.
3.13.1. 3-C-Ethyl-1,2;5,6-di-O-isopropylidene-α-D-glucofuranose 6a
Rf 0.32 (hexane:ethyl acetate, 4:1); ν (film) 3670–3099 (OH), 1075 cm−1 (CO); δH 1.05 (3H, t, J=7.4,
CH2CH3), 1.32 (3H, s, CH3), 1.35 (3H, s, CH3), 1.42 (3H, s, CH3), 1.51 (3H, s, CH3), 1.81 (2H, q, J=7.4,
CH2CH3), 2.34 (1H, br s, OH), 3.81 (1H, d, J=7.6, CHCHCH2), 3.99 (1H, dd, J=8.5, 5.5, CHCHCHH),
4.12 (1H, dd, J=8.5, 6.4, CHCHCHH), 4.24–4.28 (1H, m, CHCHCH2), 4.31 (1H, d, J=3.4, CHCHO2),
5.85 (1H, d, J=3.4, OCHO); δC 7.9 (CH2CH3), 25.1 (CH2CH3), 25.6, 26.4, 26.6, 27.1 (4×CH3), 67.65
(OCH2), 73.45 (COH), 82.9 (CHCH2O), 83.5 (CHCHCH2), 85.2 (CHCHO2), 104.5 (OCHO), 109.4,
112.2 [2×C(CH3)2]; m/z 273 [M+−(CH3), 5.0%], 101 (37), 100 (30), 85 (19), 71 (12), 59 (34), 57 (40), 55
(12), 43 (100), 42 (10) [found: M+−(CH3), 273.1340; C13H21O6 requires: M, 273.1338]; [α]D20=+25.5
[c 0.69 (CH2Cl2)].
3.13.2. 3-C-(2-Deuterioethyl)-1,2;5,6-di-O-isopropylidene-α-D-glucofuranose 6b
Rf 0.32 (hexane:ethyl acetate, 4:1); ν (film) 3657–3112 (OH), 1074 cm−1 (CO); δH 1.05 (2H, t,
J=7.3, CH2D), 1.32 (3H, s, CH3), 1.35 (3H, s, CH3), 1.43 (3H, s, CH3), 1.51 (3H, s, CH3), 1.81 (2H,
t, J=7.3, CH2CH2D), 2.10 (1H, br s, OH), 3.81 (1H, d, J=7.6, CHCHCH2), 3.98 (1H, dd, J=8.5, 5.5,
CHCHCHH), 4.10–4.15 (1H, m, CHCHCHH), 4.24–4.28 (1H, m, CHCHCH2), 4.31 (1H, d, J=3.4,
CHCHO2), 5.85 (1H, d, J=3.4, OCHO); δC 7.7 (t, JCD=20.7, CH2D), 25.2 (CH3), 25.7 (CH2CH2D), 26.4,
26.6, 27.2 (3×CH3), 67.7 (OCH2), 73.6 (COH), 83.0 (CHCH2), 83.5 (CHCHCH2), 85.2 (CHCHO2),
104.6 (OCHO), 109.5, 112.3 [2×C(CH3)2]; m/z 274 [M+−(CH3), 4.0%], 101 (39), 100 (45), 85 (27), 72
(11), 71 (14), 59 (50), 58 (28), 57 (35), 55 (10), 44 (14), 43 (100), 42 (13) [found: M+−(CH3), 274.1394;
C13H20DO6 requires: M, 274.1401]; [α]D20=+28.5 [c 1.26 (CH2Cl2)].

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3.14. Preparation of compounds 11 from the chlorohydrin 12. General procedure
A 1.6 M n-butyllithium hexane solution (0.69 ml, 1.1 mmol) was added to a chlorohydrin 12 (0.31 g,
1.0 mmol) THF solution (5 ml) under argon at −78°C. After 10 min at this temperature, the resulting
solution was transferred via cannula to a cooled (−78°C) blue suspension of lithium powder (0.10 g, 14.0
mmol) and a catalytic amount of 4,40-di-tert-butylbiphenyl (0.04 g, 0.15 mmol) in THF (5 ml) under
argon. The mixture was stirred at the same temperature for 30 min. Then the corresponding electrophile
(1.1 mmol; 0.5 ml in the case of deuterium oxide) was added at −78°C and the temperature was allowed
to rise to 20°C overnight. The resulting mixture was hydrolysed with water (20 ml) and extracted with
ethyl acetate (3×20 ml). The organic layer was dried over anhydrous sodium sulfate and evaporated (15
mmHg). The resulting residue was purified by column chromatography (silica gel, hexane:ethyl acetate)
and/or recrystallised to yield pure products 11. Yields are included in Table 2. Physical, spectroscopic
and analytical data follow.
3.14.1. 3-C-Deuteriomethyl-1,2;5,6-di-O-isopropylidene-α-D-allofuranose 11b
M.p. 123–124°C (dichloromethane/pentane); Rf 0.19 (hexane:ethyl acetate, 4:1); ν (KBr) 3625–3113
(OH), 1267, 1076, 1014 cm−1 (CO); δH 1.27 (2H, s, CH2D), 1.35 (3H, s, CH3), 1.36 (3H, s, CH3),
1.45 (3H, s, CH3), 1.59 (3H, s, CH3), 2.68 (1H, s, OH), 3.78 (1H, d, J=6.7, CHCHCH2), 3.90–3.96
(1H, m, CHCHH), 4.07–4.13 (2H, m, CHCHH), 4.17 (1H, d, J=3.7, CHCHO2), 5.7 (1H, d, J=3.7,
OCHO); δC 18.9 (t, JCD=20.1, CH2D), 25.2, 26.4, 26.6, 26.7 (4×CH3), 67.7 (CHCH2), 73.7 (CHCH2),
77.3 (CHCHCH2), 81.4 (CHCHO2), 84.7 (COH), 103.5 (OCHO), 109.5, 112.8 [2×C(CH3)2]; m/z 260
[M+−(CH3), 6.7%], 101 (19), 100 (26), 85 (11), 72 (11), 59 (48), 55 (15), 44 (53), 43 (100), 42 (14),
41 (13). Anal. calcd for C13H21DO6: C, 56.71; H, 8.42; found: C, 5.79; H, 8.86. [α]D20=+26.2 [c 1.35
(CH2Cl2)].
3.14.2. 3-C-(1-Hydroxycyclohexylmethyl)-1,2;5,6-di-O-isopropylidene-α-D-allofuranose 11c
M.p. 122–123°C (dichloromethane/pentane); Rf 0.22 (hexane:ethyl acetate, 4:1); ν (KBr) 3665–3083
(OH), 1214, 1085, 1018 cm−1 (CO); δH 1.36 (6H, s, 2×CH3), 1.44 (3H, s, CH3), 1.58 (3H, s, CH3),
1.24–1.68 (10H, m, 5×CH2), 1.73–1.77 (1H, m, COHCHH), 2.00 (1H, d, J=15.3, COHCHH), 2.82 (1H,
br s, OH), 3.08 (1H, br s, OH), 3.76 (1H, d, J=7.3, CHCHCH2), 3.92 (1H, dd, J=7.9, 5.5, CHCHCHO),
4.07–4.18 (2H, m, CHCHHO), 4.94 (1H, d, J=3.7, CHCHO2), 5.71 (1H, d, J=3.7, OCHO); δC 21.9,
22.2 (2×CH2), 25.3, 25.6 (2×CH3), 26.6 (CH2), 26.7 (2×CH3), 39.7 (CH2), 40.8 (COHCH2), 67.6
(OCH2CH), 71.9 (COH), 73.3 (OCH2CH), 80.0 (COH), 81.5 (OCH2CHCH), 83.3 (CHCHO2), 103.7
(OCHO), 109.6, 112.5 [2×C(CH3)2]; m/z 357 [M+−(CH3), 0.12%], 101 (22), 100 (10), 95 (14), 85 (11),
73 (15), 71 (14), 67 (10), 59 (17), 55 (16), 44 (23), 43 (100), 42 (14), 41 (29). Anal. calcd for C19H32O7:
C, 61.27; H, 8.66; found: C, 61.19; H, 8.66. [α]D20=−7.5 [c 1.00 (CH2Cl2)].
3.14.3. Compound 11d
M.p. 169–170°C (dichloromethane/pentane); Rf 0.32 (hexane:ethyl acetate, 3:2); ν (KBr) 3691–3133
(OH), 1260, 1068, 1030 cm−1 (CO); δH 1.37 (12H, s, 4×CH3), 1.45 (6H, s, 2×CH3), 1.59 (6H, s,
2×CH3), 1.91 (2H, s, CCH2C), 2.81 (2H, br s, 2×OH), 3.78 (2H, dd, J=12.5, 7.5, 2×CHCHHO),
3.93–3.97 (2H, m, 2×CHCHHO), 4.07–4.12 (4H, m, 2×CHCHCH2), 5.26 (2H, d, J=3.4, 2×CHCHO2),
5.77 (2H, d, J=3.4, 2×OCHO); δC 25.3, 26.6, 26.7 (8×CH3), 32.9 (CCH2C), 67.8 (2×CHCH2O), 73.1
(2×CHCH2O), 79.6 (2×CHCHCH2), 80.5 (2×CHCHO2), 82.8 (2×COH), 103.8 (2×OCHO), 109.7,
112.5 [4×C(CH3)2]; m/z 515 [M+−(OH), 3.8%], 207 (11), 101 (15), 58 (10), 57 (18), 56 (10), 55 (12),

T. Soler et al. / Tetrahedron: Asymmetry 11 (2000) 493–517
513
44 (56), 43 (100), 42 (18), 41 (27). Anal. calcd for C25H40O12: C, 56.38; H, 7.57; found: C, 56.69; H,
7.50. [α]D20=+32.7 [c 1.05 (CH2Cl2)].
3.15. Reaction of intermediates 25 with ketones 8 and 25. Isolation of compounds 26 and 27. General
procedure
To a cooled (−78°C) blue suspension of lithium powder (0.10 g, 14.0 mmol) and a catalytic amount
of 4,40-di-tert-butylbiphenyl (0.04 g, 0.15 mmol) in THF (6 ml) was added phthalan or isochroman 24
(1.0 mmol) under argon and the mixture was allowed to reach 25°C in 30 min. After that, it was cooled
down to −78°C and a THF solution (0.5 ml) of ketones 8 or 23 (1.0 mmol) was added dropwise. Stirring
was continued at the same temperature for 10 min, hydrolysed with water (30 ml) and extracted with
ethyl acetate (3×20 ml). The organic layer was dried over anhydrous sodium sulfate and evaporated (15
mmHg). The resulting residue was purified by column chromatography (silica gel, hexane:ethyl acetate)
and/or recrystallised to yield pure products 26 and 27. Yields (based on the starting material 25), physical,
spectroscopic and analytical data follow.
3.15.1. 3-C-[2-(Hydroxymethyl)phenylmethyl]-1,2;5,6-di-O-isopropylidene-α-D-allofuranose 26a
M.p. 119–120°C (dichloromethane/pentane) (58% yield); Rf 0.39 (hexane:ethyl acetate, 3:2); ν (KBr)
3600–3106 (OH), 3000 (ArH), 1069, 1006 cm−1 (CO); δH 1.25 (3H, s, CH3), 1.41 (3H, s, CH3), 1.48
(3H, s, CH3), 1.54 (3H, s, CH3), 2.67 (1H, d, J=14.4, COHCHH), 3.44 (1H, d, J=14.4, COHCHH),
3.46–3.57 (2H, br s, 2×OH), 3.89 (1H, d, J=8.2, CHCHCH2), 3.96–4.00 (1H, m, CHCHH), 4.14–4.19
(1H, m, CHCHH), 4.26–4.31 (1H, m, CHCH2), 4.34 (1H, d, J=3.5, CHCHO2), 4.55 (1H, d, J=12.1,
CHHOH), 4.75 (1H, d, J=12.1, CHHOH), 5.85 (1H, d, J=3.5, OCHO), 7.14–7.43 (4H, m, ArH); δC 25.3
(CH3), 26.4 (CH3), 26.6 (2×CH3), 33.9 (PhCH2), 63.0 (CH2OH), 67.9 (CH2O), 73.2 (CHCH2O), 79.3
(CHCHCH2), 80.5 (COH), 82.6 (CHCHO2), 103.4 (OCHO), 109.7, 112.4 [2×C(CH3)2], 127.3, 127.7,
130.6, 131.9 (ArCH), 134.3, 140.9 (ArC); m/z 347 [M+−(CH3, H2O), 0.8%], 145 (12), 104 (25), 101
(17), 100 (11), 85 (11), 44 (24), 43 (100), 42 (10). Anal. calcd for C20H28O7: C, 63.14; H, 7.42; found:
C, 62.91; H, 7.12. [α]D20=+26.6 [c 0.98 (CH2Cl2)].
3.15.2. 3-C-[2-(2-Hydroxyethyl)phenylmethyl]-1,2;5,6-di-O-isopropylidene-α-D-allofuranose 26b
M.p. 112–113°C (dichloromethane/pentane) (67% yield); Rf 0.16 (hexane:ethyl acetate, 3:2); ν (KBr)
3680–3052 (OH), 3022 (ArH), 1071 cm−1 (CO); δH 1.26 (3H, s, CH3), 1.40 (3H s, CH3), 1.50 (3H,
s, CH3), 1.55 (3H, s, CH3), 2.72 (1H, d, J=14.8, PhCHHC), 2.85 (1H, br s, OH), 2.87–3.06 (2H,
m, PhCH2CH2), 3.31 (1H, d, J=14.8, PhCHHC), 3.38 (1H, br s, OH), 3.80–3.88 (3H, m, CH2OH,
CHCHCH2), 3.99 (1H, dd, J=8.2, 5.8, CHCHH), 4.17 (1H, dd, J=8.2, 6.2, CHCHH), 4.24 (1H, d, J=3.7,
CHCHO2), 4.28–4.35 (1H, m, CHCH2), 5.82 (1H, d, J=3.7, OCHO), 7.19–7.40 (4H, m, ArH); δC 25.4,
26.4, 26.6, 26.7 (4×CH3), 33.2 (PhCH2C), 35.9 (PhCH2CH2), 63.4 (CH2OH), 67.9 (CH2O), 73.2 (COH),
79.9 (CHCH2), 80.4 (CHCHCH2), 82.7 (CHCHO2), 103.6 (OCHO), 109.7, 112.5 [2×C(CH3)2], 126.4,
127.1, 129.8, 132.1 (ArCH), 134.7, 138.1 (ArC); m/z 379 [M+−(CH3), 0.15%], 117 (10), 101 (21), 100
(18), 85 (12), 71 (12), 59 (17), 54 (11), 44 (55), 43 (100), 42 (13). Anal. calcd for C21H30O7: C, 63.46;
H, 7.65; found: C, 63.46; H, 7.65. [α]D20=+32.2 [c 1.00 (CH2Cl2)].
3.15.3. 3-C-[2-(Hydroxymethyl)phenylmethyl]-1,2;4,5-di-O-isopropylidene-β-D-psicopyranose 27a
M.p. 181–182°C (dichloromethane/pentane) (80% yield); Rf 0.41 (hexane:ethyl acetate, 3:2); ν (KBr)
3498–3091 (OH), 3060, 3023 (ArCH), 1209, 1076 cm−1 (CO); δH 1.27 (3H, s, CH3), 1.39 (3H, s,
CH3), 1.53 (3H, s, CH3), 1.57 (3H, s, CH3), 3.03 (1H, d, J=14.6, PhCHH), 3.07 (1H, br s, OH),

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T. Soler et al. / Tetrahedron: Asymmetry 11 (2000) 493–517
3.14 (1H, d, J=14.6, PhCHH), 3.43 (1H, br s, OH), 3.96 (1H, d, J=9.8, CCHHO), 4.05–4.13 (1H, m,
CHCHHO), 4.20–4.25 (2H, m, CHCHHO, PhCHHOH), 4.35 (1H, d, J=5.5, PhCHHOH), 4.42 (1H,
d, J=9.8, CCHHO), 4.64–4.66 (2H, m, CHCHCH2O), 7.21–7.39 (4H, m, ArH); δC 25.2, 25.3, 25.8,
26.5 (4×CH3), 37.4 (PhCH2), 59.9 (CHCH2O), 63.3 (PhCH2OH), 71.5 (CCH2O), 72.3 (CHCH2O), 75.4
(CHCHCH2), 107.0 (CCH2O), 108.9, 112.4 [2×C(CH3)2], 127.0, 127.1 (ArCH), 127.4 (COH), 130.3,
132.5 (ArCH), 134.7, 140.5 (2ArC); m/z 362 [M+−(H2O), 2.5%], 145 (10), 129 (11), 117 (12), 115 (12),
105 (12), 104 (27), 103 (10), 91 (12), 85 (15), 59 (15), 58 (10), 55 (12), 44 (24), 43 (100), 42 (15),
41 (14). Anal. calcd for C20H28O7: C, 63.14; H, 7.42; found: C, 63.22; H, 7.31. [α]D20=−52.1 [c 1.10
(CH2Cl2)].
3.15.4. 3-C-[2−(2-Hydroxyethyl)phenylmethyl]-1,2;4,5-di-O-isopropylidene-β-D-psicopyranose 27b
Rf 0.27 (hexane:ethyl acetate, 3:2) (85% yield); ν (film) 3649–3112 (OH), 3071 (ArCH), 1213, 1078,
1060 cm−1 (CO); δH 1.25, 1.40, 1.53, 1.56 (12H, s, 4×CH3), 1.91 (1H, br s, OH), 2.88 (1H, br s, OH),
2.95 (1H, d, J=14.0, PhCHHC), 3.06–3.12 (3H, m, PhCHHO, PhCH2CH2), 3.91 (2H, m, PhCH2CH2),
3.96 (1H, d, J=9.5, CCHHO), 4.04–4.09 (1H, m, CHCHH), 4.16–4.21 (2H, m, CHCHH), 4.29 (1H, d,
J=6.1, CHCHCH2), 4.43 (1H, d, J=9.5, CCHHO), 7.13–7.36 (4H, m, ArH); δC 25.2, 25.3, 25.7, 26.5
(4×CH3), 35.4, 37.2 (2×PhCH2), 60.0 (CH2OH), 63.2 (CHCH2O), 71.5 (CCH2O), 72.4 (CHCH2O),
72.6 (COH), 75.2 (CHCHCH2), 107.1 (CCH2O), 108.8, 112.3 [2×C(CH3)2], 125.7, 126.8, 129.1, 132.5
(ArCH), 135.5, 138.1 (ArC); m/z 379 [M+−(CH3), 0.5%], 201 (14), 129 (10), 118 (12), 117 (31), 115
(14), 105 (10), 91 (11), 85 (16), 59 (41), 57 (12), 55 (11), 43 (100), 42 (14), 41 (16), 40 (10) [found:
M+−(CH3), 379.1776; C20H27O7 requires: M, 379.1757]; [α]D20=−74.6 [c 1.00 (CH2Cl2)].
3.16. Cyclisation of compounds 26 and 27. Isolation of compounds 28 and 29. General procedure
To a benzene solution (5 ml) of diols 26 or 27 (0.25 mmol) and triphenylphosphine (0.16 g, 0.6
mmol) in the presence of 4 Å molecular sieves (0.5 g) under argon was added dropwise diisopropyl
azodicarboxylate (0.12 ml, 0.6 mmol) at 25°C. The reaction mixture was heated at 80°C for 3 h. Then
the resulting mixture was evaporated (15 mmHg) and the resulting residue was hydrolysed with water
(10 ml) and extracted with ethyl acetate (3×20 ml). The organic layer was dried over anhydrous sodium
sulfate and evaporated (15 mmHg). The resulting residue was purified by column chromatography (silica
gel, hexane:ethyl acetate) to give compounds 28 and 29. Yields (based on the starting materials 26 and
27), physical, spectroscopic and analytical data follow.
3.16.1. Compound 28a
M.p. 123–124°C (dichloromethane/pentane) (50% yield); Rf 0.31 (hexane:ethyl acetate, 4:1); ν (KBr)
3035, 3023 (ArH), 1076, 1039 cm−1 (CO); δH 1.27 (3H, s, CH3), 1.32 (3H, s, CH3), 1.46 (3H, s, CH3),
1.61 (3H, s, CH3), 2.44 (1H, d, J=15.9, CCHHPh), 3.25 (1H, d, J=15.9, CCHHPh), 3.99 (1H, dd, J=8.1,
5.0, CHCHHO), 4.11 (1H, d, J=5.8, CHCHCH2), 4.12–4.24 (2H, m, CHCH2, CHCHH), 4.19 (1H, d,
J=3.7, CHCHO2), 4.90 (1H, d, J=15.3, OCHHPh), 5.01 (1H, d, J=15.3, OCHHPh), 5.69 (1H, d, J=3.7,
OCHO), 7.04–7.23 (4H, m, ArH); δC 25.3, 26.5, 26.6, 26.9 (4×CH3), 30.0 (CCH2Ph), 65.2 (CHCH2),
67.6 (OCH2Ph), 73.5 (CHCHCH2), 80.8 (CHCH2), 81.1 (CCH2Ph), 81.9 (CHCHO2), 103.6 (OCHO),
109.6, 113.0 [2×C(CH3)2], 124.3, 126.4, 126.6, 128.9 (ArCH), 130.8, 135.1 (ArC); m/z 347 [M+−(CH3),
1.8%], 145 (18), 117 (13), 104 (21), 101 (24), 100 (23), 85 (23), 72 (10), 59 (10), 55 (12), 44 (12), 43
(100), 42 (12) [found: M+−(CH3), 347.1495; C19H23O6 requires: M, 347.1496]; [α]D20=+128.0 [c 1.00
(CH2Cl2)].

T. Soler et al. / Tetrahedron: Asymmetry 11 (2000) 493–517
515
3.16.2. Compound 28b
Rf 0.37 (hexane:ethyl acetate, 4:1) (70% yield); ν (film) 3053 (ArCH), 1083 cm−1 (CO); δH 1.20 (3H,
s, CH3), 1.38 (3H, s, CH3), 1.47 (3H, s, CH3), 1.56 (3H, s, CH3), 2.61 (1H, d, J=15.1, CCHHPh), 2.74
(1H, dd, J=15.6, 4.9, CH2CHHPh), 3.31–3.39 (1H, m, CH2CHHPh), 3.51 (1H, d, J=15.1, CCHHPh),
3.75 (1H, m, CHHCH2Ph), 4.02–4.04 (1H, m, CHCHH), 4.07–4.18 (4H, m, CHCHCHH, CHCHO2),
4.25–4.31 (1H, m, CHHCH2Ph), 5.66 (1H, d, J=3.7, OCHO), 7.02–7.26 (4H, m, ArH); δC 25.5,
26.5, 26.6, 27.1 (4×CH3), 38.7 (CCH2Ph), 39.7 (CH2CH2Ph), 66.0 (CH2CH2Ph), 67.2 (CHCH2),
73.3 (CHCHCH2), 79.7 (CHCH2), 81.8 (CCH2Ph), 82.7 (CHCHO2), 103.4 (OCHO), 109.4, 112.8
[2×C(CH3)2], 126.6, 127.1, 129.4, 130.2 (ArCH), 136.6, 141.4 (2×ArC); m/z 361 [M+−(CH3), 1.7%],
118 (18), 117 (22), 115 (11), 101 (23), 100 (23), 91 (11), 85 (20), 71 (11), 59 (10), 55 (15), 44 (12), 43
(100), 42 (11) [found: M+−(CH3), 361.1651; C20H25O6 requires: M, 361.1651]; [α]D20=+41.8 [c 1.00
(CH2Cl2)].
3.16.3. Compound 29a
Rf 0.64 (hexane:ethyl acetate, 3:2) (45% yield); ν (film) 3029 (ArCH), 1262, 1092, 1025 cm−1 (CO);
δH 1.37 (3H, s, CH3), 1.45 (6H, s, 2×CH3), 1.46 (3H, s, CH3), 2.97 (1H, d, J=16.2, PhCHH), 3.16
(1H, d, J=16.2, PhCHH), 3.47 (1H, d, J=9.8, CCHHO), 3.73 (1H, d, J=9.8, CCHHO), 4.06 (1H, dd,
J=13.1, 2.1, CHCHHO), 4.14–4.18 (2H, m, CHCHCHHO), 4.24–4.28 (1H, m, CHCH2O), 4.67 (1H, d,
J=13.4, PhCHHO), 4.92 (1H, d, J=13.4, PhCHHO), 7.09–7.26 (4H, m, ArH); δC 25.8, 26.0, 26.3, 26.5
(4×CH3), 32.1 (PHCH2C), 60.9 (CHCH2O), 66.8 (PhCH2O), 71.3 (CHCH2O), 71.4 (CCH2O), 73.7
(CHCHCH2O), 77.7 (CCHCHCH2), 106.6, 109.5 [2×C(CH3)2], 111.6 (CCH2O), 124.4, 126.3, 127.2,
127.8 (ArCH), 134.1, 136.7 (ArC); m/z 362 (M+, 5.5%), 173 (14), 145 (15), 144 (15), 129 (11), 117 (16),
116 (13), 115 (13), 105 (14), 104 (27), 100 (12), 85 (20), 59 (19), 55 (14), 44 (16), 43 (100), 42 (18), 41
(17) [found: M+, 362.1740; C20H26O6 requires: M, 362.1729]; [α]D20=−83.3 [c 0.94 (CH2Cl2)].
3.16.4. Compound 29b
Rf 0.66 (hexane:ethyl acetate, 3:2) (40% yield); ν (film) 3067 (ArH), 1247, 1215, 1053 cm−1 (CO); δH
1.16 (3H, s, CH3), 1.46 (3H, s, CH3), 1.50 (3H, s, CH3), 1.53 (3H, s, CH3), 2.82 (1H, m, PhCHHCH2),
3.12 (1H, d, J=15.9, PhCHHC), 3.28 (1H, m, PhCHHCH2), 3.65 (1H, dd, J=12.8, 7.3, CHCHHO),
3.68 (1H, d, J=15.9, PhCHHC), 3.91–4.19 (5H, m, CHCHCHHO, PhCH2CH2O), 4.20 (1H, d, J=9.8,
CCHHO), 4.39 (1H, d, J=9.8, CCHHO), 7.04–7.26 (4H, m, ArH); δC 25.85 (2×CH3), 26.8, 27.9
(2×CH3), 38.1 (PhCH2C), 39.2 (PhCH2CH2), 62.6 (CHCH2O), 63.9 (CCH2O), 67.55 (PhCH2CH2),
70.1 (CHCH2O), 74.5 (PhCH2C), 74.9 (CHCHCH2O), 106.6, 109.9 [2×C(CH3)2], 110.3 [CCH2O],
126.6, 126.9, 129.3, 130.1 (ArCH), 136.5, 139.6 (ArC); m/z 376 (M+, 2.6%), 176 (11), 118 (13), 117
(25), 115 (13), 100 (15), 91 (11), 85 (15), 59 (16), 55 (11), 44 (24), 43 (100), 42 (16), 41 (17) [found:
M+, 376.1926; C21H28O6 requires: M, 376.1886]; [α]D20=−19.4 [c 1.45 (CH2Cl2)].
Acknowledgements
This work was financially supported by the DGES (grant no. PB97-0133) from the Spanish Ministerio
de Educación y Culura (MEC). T.S. thanks the Generalitat Valenciana for a predoctoral fellowship.
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;
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2
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32. For compounds 3f, 15d and 15f it was not possible to get accurate HRMS or microanalysis.