Stereoselective preparation of O-alkoxy D-tetrose, D-pentose, 2-deoxy- D-glycero tetrose and 2,3-dideoxy-D-erythro pentose derivatives by an iterative elongation of 2,3-O-isopropylidene-D-glyceraldehyde

Article abstract of DOI:10.1016/S0957-4166(99)00072-5

All D-pentoses are synthesized by one-carbon chain elongation commencing with the addition of the lithium salt of ethyl ethylthiomethyl sulfoxide to 2-O-(t-butyldimethylsilyl)-3,4-O-isopropylidene-D-erythrose and D-threose, 16 and 17. The addition of the

Full text of DOI:10.1016/S0957-4166(99)00072-5

Pergamon
Tetrahedron: Asymmetry 10 (1999) 973–990
Stereoselective preparation of O-alkoxy D-tetrose, D-pentose,
2-deoxy-D-glycero tetrose and 2,3-dideoxy-D-erythro pentose
derivatives by an iterative elongation of 2,3-O-isopropylidene-
D-glyceraldehyde
Y. Arroyo-Gómez, J. A. López-Sastre, J. F. Rodríguez-Amo, M. Santos-García and
M. A. Sanz-Tejedor ∗
Departamento de Química Organica (E.T.S.I.I.), Universidad de Valladolid, Paseo del Cauce s/n, 47011, Valladolid, Spain
Received 10 February 1999; accepted 25 February 1999
Abstract
All D-pentoses are synthesized by one-carbon chain elongation commencing with the addition of the lithium salt
of ethyl ethylthiomethyl sulfoxide to 2-O-(t-butyldimethylsilyl)-3,4-O-isopropylidene-D-erythrose and D-threose,
16 and 17. The addition of the above-mentioned nucleophile to 2-deoxy-3,4-O-isopropylidene-D-glycero tetrose,
19, gave rise to 2,3-dideoxy-D-glycero pentose. The starting aldehydes, 16, 17 and 19, are easily available from
2,3-O-isopropylidene-D-glyceraldehyde, 1, and ethyl ethylthiomethyl sulfoxide. © 1999 Elsevier Science Ltd. All
rights reserved.
1. Introduction
One of the goals in organic chemistry is the preparation of chiral molecules, in high chemical yields and
enantiomeric excess, so that they can be used as chiral starting materials in the synthesis of more elaborate
molecules.1 In this sense, monosaccharides as well as their three- to five-carbon derivatives are especially
interesting, since starting from them, a large variety of biologically interesting compounds, such as
natural and non-natural sugars, antibiotics, and nucleosides, amongst many others, can be synthesized.2
This explains the importance of finding new methodologies enabling the stereocontrolled building of 1,2-
and 1,3-diols with the desired stereochemical arrangement. Synthesis of this kind of chemical structure
has often been performed by transforming naturally occurring chiral compounds,3–5 which has led to a
wide range of carbohydrates. Nevertheless, this procedure does not always enable certain compounds
to be obtained, either because the suitable starting material is not available or because a large number
∗
Corresponding author.
0957-4166/99/$ - see front matter © 1999 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(99)00072-5

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of synthetic steps is needed to reach them. Therefore, it is more convenient to design an asymmetric
synthesis enabling the stereocontrolled building of the polyhydroxylated chain existing in the desired
monosaccharide.
The methods of asymmetric synthesis which have led to the best results in monosaccharide synthesis
have been the use of chiral catalysts (asymmetric epoxidation,6–9 asymmetric dihydroxylation,10 and
enzymatic catalysis11), the use of chiral auxiliaries as asymmetric inductors (a chiral sulfinyl group12
or norephedrine derivative13), and the use of enantiomerically pure chiral precursors,14 controlling the
formation of a new stereogenic center. Closely related to the latter category, one of the most used chiral
substrates for the synthesis of monosaccharides is 2,3-O-isopropylidene-D-glyceraldehyde 1, which has
been reacted with a wide range of nucleophiles with the aim of elongating its hydrocarbon chain by one,15
two,16 or more carbon atoms,17 which leads to tetroses, pentoses, hexoses and higher monosaccharides.
2. Results and discussion
In this paper we report the stereoselective synthesis of four- and five-carbon polyalkoxyaldehydes,
by means of the consecutive one-carbon chain elongation of 2,3-O-isopropylidene-D-glyceraldehyde, by
using commercially available ethyl ethylthiomethyl sulfoxide (EETMS) as the nucleophilic reagent.
The first reaction cycle begins with addition of the lithium salt of EETMS onto aldehyde 1, following
our previously described procedure.18 The reaction shows a high anti-diastereoselectivity, giving rise
to D-threo and D-erythro alcohols in a 4:96 ratio, which enables a straightforward route to D-erythrose
(Scheme 1). This reaction has been performed starting from 0.1 mol of aldehyde 1, and 23 g (0.08 mol) of
the diastereoisomeric mixture of D-erythro alcohols 2–5 have been easily obtained, which demonstrates
that it can be scaled up as required in synthetic processes.
In order to widen the scope of this methodology to the synthesis of five-carbon polyalkoxyaldehydes,
we have investigated the protection of the newly generated hydroxyl group with a variety of reagents, as
well as the removal of the protecting group of the aldehyde.
The reactions aiming at the protection of the hydroxyl group, starting from α-hydroxydithioacetal
mono-S-oxides 2–5 in the presence of benzylbromide, 3,4-dihydro-2H-pyran and t-butyldimethylsilyl
chloride, did not give rise to the desired products. The use of the two latter protection reagents led to the
recovery of the unaltered starting material after several days under reaction conditions. The reaction with
BnBr afforded the corresponding ketene dithioacetal mono-S-oxide 32, resulting from dehydration.
Therefore we decided to first reduce the sulfinyl moiety of diastereoisomers 2–5 with LiAlH4, which
gave dithioacetal 6 as the major reaction product (THF reflux) or α-hydroxydithioacetals 7 and 8 (Et2O
reflux or THF at 45°C) depending on the reaction conditions used.19 α-Hydroxydithioacetal 7, with
the threo configuration, has been protected as its corresponding O-acetyl, O-tetrahydropyranyl, and O-
t-butyldimethylsilyl derivative (compounds 9, 10 and 11, see Table 1). So far as its epimer 8, with the
erythro configuration, is concerned, it has been treated under the same conditions leading to acetylation
and formation of THP, TBDMS and benzyl ethers (compounds 12–15, respectively, see Table 1). The
protection reactions took place, in all the cases that we investigated, with excellent chemical yields
(quantitative for THP and TBDMS derivatives). All these results demonstrate that this procedure enables
the preparation of aldose derivatives bearing differently protected hydroxyl groups, which should be
required for further stereoselective synthetic transformations.
Following our research project, we carried out the hydrolysis of the dithioacetal moiety in order to
recover the free aldehyde, and through a second chain enlongation, attain five-carbon monosaccharides.
Hydrolysis reactions of diethyldithioacetals 6, 11, 14 and 15 with HgO–HgCl2 in acetone, gave rise to

Y. Arroyo-Gómez et al. / Tetrahedron: Asymmetry 10 (1999) 973–990
975
Scheme 1.
the corresponding aldehydes (19, 16, 17 and 18, respectively, see Table 1), in almost quantitative yields
in all the cases considered.
As the starting materials to perform the chain elongation, we chose the O-silyl derivatives 16 and 17,
since they have a bulky protecting group, and therefore, the diastereoselectivity of the hydroxylation
reaction should be presumably higher. We also used the 2-deoxy derivative 19, aiming at the synthesis
of the corresponding 3-deoxypentoses. Subsequent reaction of the aldehyde 17, exhibiting D-erythro
configuration, with the lithium salt of EETMS yielded a mixture of diastereoisomeric alcohols, which
without further purification, was treated with the reducing agent LiAlH4 to obtain the corresponding die-
thyldithioacetals with D-ribo 20 and D-arabino 21 configurations, in 88:12 ratio. The major stereoisomer
20 could be easily isolated.
In the reduction of the sulfinyl group, we observed concomitant desilylation. Hence, the next step
involved the protection of hydroxyl groups with DMP under acidic conditions to reach the corresponding
di-O-isopropylidene derivatives 22 and 23 (Scheme 2). We have chosen this protecting group because
the di-O-isopropylidene derivative 22 is the precursor of its epimer 23, produced through isomerization
under basic conditions (following the procedure reported by Sharpless et al.8). The absolute configuration

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Y. Arroyo-Gómez et al. / Tetrahedron: Asymmetry 10 (1999) 973–990
Table 1
Reactions of protection of the hydroxyl group and hydrolysis of the dithioacetal
of epimers 22 and 23, and therefore, that of compounds 20 and 21, was elucidated by comparison with
the products synthesized from natural D-ribose and D-arabinose following literature procedures.20 1H and
13C NMR spectra of these compounds were superimposable, and their specific rotations were similar in
sign and magnitude.
Scheme 2.
So far as it is concerned with the chain elongation of the D-threo configured aldehyde 16, the procedure

Y. Arroyo-Gómez et al. / Tetrahedron: Asymmetry 10 (1999) 973–990
977
follows the same reaction sequence as described for compound 17. In this case the reduction of the
sulfinyl group led to diethyldithioacetals showing D-lyxo 25 and D-xylo 26 configurations, in a 70:30
ratio, as well as trace amounts of the corresponding 2-deoxyderivative 24 (Scheme 3). In this case, the
diastereoselectivity of the process is only moderate, nevertheless both epimers can be easily separated
and purified. The configuration of epimers 25 and 26 has been establised by their transformation into
the corresponding di-O-isopropylidene derivatives, 27 and 28, and their comparison with the products
1
synthesized starting from the natural sugars, D-lyxose and D-xylose, respectively.20 Their H and 13C
NMR spectra were superimposable, and their specific rotations were similar in sign and magnitude. As
in the previous case the di-O-isopropylidene derivative 25, can be transformed into the corresponding
aldose with D-xylo configuration.8
Scheme 3.
The usefulness of the di-O-isopropylidene derivatives 22 (D-ribo) and 27 (D-lyxo), obtained as
the major products from the addition of EETMS to the aldehydes 17 (D-erythro) and 16 (D-threo),
respectively, is even greater if we bear in mind that these compounds are precursors of the corresponding
2-deoxypentoses following the method described by Gray et al.21
Accordingly, in order to synthesize 3-deoxypentoses, we carried out the chain elongation of aldehyde
19, with the lithium salt of EETMS and further reduction of the crude with LiAlH4 in THF at 45°C.
After this two-step sequence, the corresponding 3-deoxypentoses 30 and 31 were isolated only in
small amounts, and, surprisingly, 2,3-dideoxypentose 29 was obtained as the major product. In another
experiment carried out in refluxing THF, the compound 29 was obtained as the only product (Scheme 4).
This result is a new 2,3-dideoxy-D-pentose22 synthesis, which is a useful intermediate for the preparation
of dideoxycytidine.23
1H NMR data of the obtained diethyldithioacetal tetrose and pentose derivatives allowed us to establish
a correlation between vicinal coupling constants (Jvic) and relative configuration (erythro or threo) for
each compound. This correlation between configuration and conformation in diethyldithioacetals of aldi-
tols has been previously used to predict the most favored conformations so as to assign configurations.24
We observed that, in D-tetrose derivatives, the J2,3 value is larger for compounds exhibiting erythro

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Y. Arroyo-Gómez et al. / Tetrahedron: Asymmetry 10 (1999) 973–990
Scheme 4.
Table 2
Vicinal coupling constants (Hz) of diethyldithioacetal of D-tetrose and D-pentose derivatives
configuration (≥7 Hz for compounds 8, 12, 13 and 15, see Table 2) than for compounds with threo
configuration (≤4.2 Hz for compounds 7, 9 and 10).
In the case of D-pentose derivatives, we observed that compounds bearing hydrogens H-C3/H-C4 with
erythro configuration show larger values of J3,4 (≥7.3 Hz for compounds 20, 22 and 23) than those of their
isomers bearing such hydrogens with threo configuration (≤5.1 Hz for compounds 25–28). Concerning
the values of J2,3, this correlation can be established only for hydroxy derivatives, where the values of J2,3
are larger for an erythro configuration (≥7.1 Hz for compounds 20 and 25) than for a threo configuration
(≤1.5 Hz for compound 26, see Table 2).
Bearing in mind the dependence existing between the Jvic value and the dihedral angle formed by the
implied hydrogen atoms, a preferential syn or anti arrangement of such hydrogens may be inferred, which
would be related to a relative threo or erythro configuration, respectively. The observed deviation from
the Jvic values of some of these derivatives may be due to the presence of bulky substituents (11 and 14,

Y. Arroyo-Gómez et al. / Tetrahedron: Asymmetry 10 (1999) 973–990
979
see experimental section) or to the restrictions in the free bond rotation as a consequence of being part of
a cycle (J2,3 for compounds 22, 23, 27 and 28).
A similar correlation was observed in the case of deoxy derivatives 6, 30 and 31, where a syn or anti
relationship can also be inferred between vicinal hydrogens from the values of the coupling constants
between such hydrogens. As shown in Scheme 5, isomer 30 has a Jvic=8.1 Hz at H-3, so a preferential
anti arrangement of its vicinal hydrogens may be inferred. On the other hand, the geminal protons have a
J≤4.6 Hz, which would be correct for a preferential syn disposition. From all these data we have assigned
the R* absolute configuration at C-2 for this compound. In contrast, isomer 31 possesses one Jvic≥8 Hz
and another Jvic≤4.5 Hz at both hydrogens (3 and 30), in accordance with an anti and syn geometry in
relation to their vicinal hydrogens, which would be suitable for an S* absolute configuration at C-2.
Scheme 5.
In summary, D-erythrose 8, and D-threose 7, α-hydroxydithioacetal derivatives (derived from 2,3-
O-isopropylidene-D-glyceraldehyde 1 and EETMS) are stable intermediates which can be differently
protected and easily converted into aldehydes with the aim of using them in subsequent synthetic
transformations. Hydroxyalkylation of D-erythrose and D-threose derivatives, 16 and 17, resulted in the
total transformation of the starting product, so that the four stereoisomer D-pentoses can be obtained
by this procedure. The same reaction sequence carried out on 2-deoxy-D-glycero tetrose gave rise to a
2,3-dideoxy-D-glycero pentose derivative 29, in high yield. Additionally, the vicinal coupling constant
values of the obtained diethyldithioacetals D-tetrose and D-pentose derivatives, enable the assignment of
an anti or a syn relationship between vicinal hydrogens, which is related to their relative erythro or threo
configuration, respectively.
3. Experimental
3.1. General methods
Dry solvents and liquid reagents were distilled under argon just prior to use: THF and diethyl ether
were distilled from sodium and benzophenone ketyl; EETMS was distilled at reduced pressure. NaH
(60% mineral oil) was activated by repeated treatment with hexane, and further removing the solvent at
reduced pressure. All reactions vessels, after being flame-dried, were kept under argon. Organic solutions
were dried over anhydrous sodium or magnesium sulfate, and the solvent was evaporated at reduced
pressure below 40°C.
TLC was performed on glass plates coated with silica gel G (Merck) or SI-F-254 (Scharlau), spots
being developed either with sulfuric acid in ethanol (10%) or with phosphomolybdic acid in ethanol.

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Column chromatographic separations were determined by using silica gel Merck 60 (70–230 mesh,
ASTM, for gravity chromatography) or 230–400 mesh (for flash chromatography).
Optical rotations were measured with a 141 Perkin–Elmer polarimeter. Specific rotations are given in
units of 10−1 deg cm2 g−1.
1H NMR spectra (300 MHz, CDCl3) and 13C NMR (80 MHz, CDCl3) were determined with a Bruker
AC-300 spectrometer. Chemical shifts were measured in ppm (δ), relative to SiMe4 as the internal
reference; signal multiplicities are quoted as s, singlet; d, doublet; dd, double doublet; ddd, doubled
double doublet; dddd, double double doublet; dq, double quartet; t, triplet; q, quartet, and m, multiplet.
J values are given in hertz. Diastereoisomeric ratios were determined by integration of well separated
signals of 1H NMR spectra. IR spectra were measured using a Nicolet FTIR-20-SX spectrometer. Mass
spectra were recorded by the direct insertion technique by electronic impact (EI), using an HP-588-A
spectrometer at 230 eV with a source temperature of 200°C. Elemental analyses were determined with a
Carlo Erba elemental analyzer 1106.
2,3-O-Isopropylidene-D-glyceraldehyde 1, was synthesized from 1,2:5,6-di-O-isopropylidene-D-
mannitol by oxidation with sodium periodate.5b 2-Deoxi-3,4-O-isopropylidene-D-glycero-tetrose 6,
3,4-O-isopropylidene-D-threose 7, 3,4-O-isopropylidene-D-erythrose-8 diethyldithioacetals,19 and their
O-acetyl derivatives18b 9 and 12, were prepared as previously described.
3.2. General method for protection with 3,4-dihydro-2H-pyran25
3.2.1. Of alcohol 7
To a solution of compound 7 (250 mg, 0.94 mmol) and 3,4-dihydro-2H-pyran (395 mg, 4.7 mmol),
in CH2Cl2 (4 ml), at 20°C, PTSA (9 mg, 10−3 mmol) was added. The mixture was stirred for 2 h at
the same temperature, poured into Et2O (6 ml) and washed with saturated aqueous solution of NaHCO3
(6 ml), and NaCl (6 ml), and extracted with ether (3×6 ml). The combined ethereal layers were dried
over MgSO4, the solvent was removed under reduced pressure, and the residue was purified by column
chromatography (hexane:Et2O, 25:1) to give compound 10 (320 mg, 0.92 mmol, 98%) as a colorless oil.
3.2.1.1. 2-O-Tetrahydropyranyl-3,4-O-isopropylidene-D-threose diethyldithioacetal 10. Rf=0.52
1
(hexane:Et2O, 2:1); [α]D20=+19.1 (c 0.1, CHCl3); H NMR δ 1.19–1.48 (m, 12H, (CH3CH2S)2- and
C(CH3)2), 1.50–1.65 (m, 4H, H–C40 and H–C50), 1.68–1.91 (m, 2H, H–C60), 2.71–2.78 (m, 4H,
(CH3CH2S)2-), 3.45–3.92 (m, 2H, H–C30), 4.04 (dd, 1H, J3,4 6.9, Jgem 8.2, H–C4), 4.10 (d, 1H, J1,2
3.0, H–C1), 4.11 (dd, 1H, J3,4 6.6, Jgem 8.2, H0–C4), 4.25 (dd, 1H, J2,1 3.0, J2,3 3.5, H–C2), 4.42
0
(ddd, 1H, J3,2 3.5, J3,4 6.9, J3,4 6.6, H–C3), 4.83 (dd, 1H, J1 ,6 a 2.8, J1 ,6 b 4.8, H–C10); 13C NMR δ
14.1 and 14.5 ((CH3CH2S)2-), 19.8, 25.1, 25.4, 26.2, 30.7 ((CH3CH2S)2-, C-40, C-50, C-60), 25.1 and
26.6 (C(CH3)2), 53.0 (C-1), 62.9 and 65.3 (C-30, C-4), 76.6 and 80.8 (C-2, C-3), 100.7 (C-10), 107.9
(C(CH3)2); IR (KBr, liquid film): 3000, 1455, 1385, 1375, 1260, 1210, 1160, 1130, 1060, 975, 870, 815
cm−1; MS (m/e) (relative intensity): 350 (0.2, M+), 335 (0.3, M+−CH3), 289 (0.2, M+−C2H5S), 248 (4,
0
0
0
0
0
+
+
+
C11H20O2S2 ), 135 (40, C5H11S2 ), 101 (33, C5H9O2 ), 85 (100, C5H9O+), 43 (26, C2H3O+). Anal.
calcd for C16H30O4S2: C, 54.82; H, 8.63. Found: C, 54.75; H, 8.60.
3.2.2. Of alcohol 8
Following the same above-described procedure, starting from compound 8 (240 mg, 0.9 mmol) in
CH2Cl2 (4 ml), 3,4-dihydro-2H-pyran (379 mg, 4.5 mmol) and PTSA (1.72 mg, 9.05×10−3 mmol),
compound 13 (310 mg, 0.88 mmol, 98%) was obtained as a colorless oil after column chromatography
(hexane:Et2O, 20:1).

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981
3.2.2.1. 2-O-Tetrahydropyranyl-3,4-O-isopropylidene-D-erythrose diethyldithioacetal 13. Rf=0.64
(hexane:Et2O, 2:1); [α]D20=+77.9 (c 0.52, CHCl3); H NMR δ 1.27 and 1.29 (2t, each 3H, Jvic 7.4,
1
(CH3CH2S)2-), 1.35 and 1.41 (2s, each 3H, C(CH3)2), 1.52–1.80 (m, 6H, H-C40, H-C50, and H-C60),
2.67 and 2.74 (2c, each 2H, Jvic 7.4, (CH3CH2S)2-), 3.46–3.93 (m, 2H, H-C30), 3.98 (dd, 1H, J2,1 1.5,
0
J2,3 8.3, H–C2), 4.10 (dd, 1H, J4,3 6.3, Jgem 8.6, H–C4), 4.15 (d, 1H, J1,2 1.5, H–C1), 4.20 (dd, 1H, J4 ,3
5.0, Jgem 8.6, H–C4), 4.34 (ddd, 1H, J3,2 8.3, J3,4 6.3, J3,4 5.0, H–C3), 4.95–4.97 (m, 1H, H–C10); 13
C
0
NMR δ 14.5 and 14.6 ((CH3CH2S)2-), 20.2, 25.2, 25.4, 26.3, 30.7 ((CH3CH2S)2-, C-40, C-50, C-60),
25.2 and 26.9 (C(CH3)2), 53.3 (C-1), 63.7 and (C-30, C-4), 75.2 and 81.5 (C-2, C-3), 100.6 (C-10), 109.2
(C(CH3)2); IR (KBr, liquid film): 3000, 1455, 1385, 1375, 1260, 1220, 1160, 1130, 975, 855, 790 cm−1;
MS (m/e) (relative intensity): 350 (1%, M+), 289 (0.5, M+−C2H5S), 248 (5, C11H20O2S2 ), 220 (14,
+
C9H16O2S2 ), 135 (55, C5H11S2 ), 101 (32, C5H9O2 ), 85 (100, C5H9O+), 43 (19, C2H3O+). Anal.
calcd for C16H30O4S2: C, 54.82; H, 8.63. Found: C, 54.75; H, 8.60.
+
+
+
3.3. General method for O-silylation15c
3.3.1. Of alcohol 7
To a solution of compound 7 (798 mg, 3 mmol) in DMF (2 ml), imidazole (408 mg, 6 mmol) and
t-BuMe2SiCl (1.3 g, 6 mmol) were added. The solution was stirred at 70°C for 50 h, cooled to rt,
poured into water (100 ml), and extracted with Et2O (2×45 ml). The combined ethereal layers were dried
over Na2SO4, the solvent was removed under reduced pressure, and the residue was purified by column
chromatography (hexane:Et2O, 20:1) to give compound 11 (1.12 g, 2.94 mmol, 98%) as a colorless oil.
3.3.1.1. 2-O-(t-Butyldimethylsilyl)-3,4-O-isopropylidene-D-threose diethyldithioacetal 11. Rf=0.81
(hexane:Et2O, 2:1); [α]D20=−29.3 (c 0.52, CHCl3); 1H NMR δ 0.12 and 0.15 (2s, each 3H, (CH3)2Si-),
0.92 (s, 9H, (CH3)3CSi-), 1.25 and 1.26 (2t, each 3H, Jvic 7.4, Jvic 7.5, (CH3CH2S)2-), 1.35 and 1.40 (2s,
each 3H, C(CH3)2), 2.63 and 2.78 (2c, each 2H, Jvic 7.5, (CH3CH2S)2-), 3.66 (d, 1H, J1,2 2.2, H–C1),
0
3.71 (dd, 1H, J4,3=Jgem 8.0, H–C4), 3.99 (dd, 1H, J2,1 2.2, J2,3 7.2, H–C2), 4.05 (dd, 1H, J4 ,3 6.2, Jgem
8.0, H0–C4), 4.29–4.36 (m, 1H, H-3); 13C NMR δ −4.1 and −4.7 ((CH3)2Si-), 14.5 ((CH3CH2S)2-),
18.5 ((CH3)3CSi-), 24.9 and 26.1 ((CH3CH2S)2-), 25.5 and 26.6 (C(CH3)2), 26.0 ((CH3)3CSi-), 26.1
(CH3CH2S-), 26.6 (C(CH3)2), 54.4 (C-1), 65.8 (C-4), 78.5 and 78.8 (C-2 and C-3), 108.9 (C(CH3)2);
IR (KBr, liquid film): 2995, 1470, 1460, 1385, 1375, 1260, 1220, 1130, 1075, 840, 780 cm−1; MS (m/e)
(relative intensity): 380 (0.2%, M+), 365 (2, M+−Me), 323 (10, M+−t-Bu), 305 (4, C14H29O3SSi+), 265
+
+
+
+
(50, C11H21O3S2 ), 161 (26, C6H9O3S+), 135 (38, C5H11S2 ), 101 (100, C5H9O2 ), 73 (84, C3H5O2 ),
59 (29, C3H7O+), 43 (49, C2H3O+). Anal. calcd for C17H36O3S2Si: C, 53.64; H, 9.53. Found: C, 53.68;
H, 8.95.
3.3.2. Of alcohol 8
Following the above-described procedure for the silylation of compound 7, starting from compound
8 (1.46 g, 5.49 mmol) in DMF (4 ml), imidazole (747 mg, 10.98 mmol) and t-BuMe2SiCl (1.7 g,
11.35 mmol), compound 14 (2.05 g, 5.40 mmol, 98% yield) was obtained as a colorless oil after
chromatographic purification (hexane:Et2O, 20:1).
3.3.2.1. 2-O-(t-Butyldimethylsilyl)-3,4-O-isopropylidene-D-erythrose diethyldithioacetal 14. Rf=0.78
(hexane:Et2O, 2:1); [α]D20=+17.2 (c 0.52, CHCl3); 1H NMR δ 0.12 and 0.20 (2s, each 3H, (CH3)2Si-),
0.89 (s, 9H, (CH3)3CSi-), 1.27 (t, 6H, Jvic 7.4, (CH3CH2S)2-), 1.33 and 1.40 (2s, each 3H, C(CH3)2),

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2.60–2.77 (m, 4H, (CH3CH2)2S-), 3.90 (dd, 1H, J4,3 6.1, Jgem 8.3, H–C4), 3.99 (d, 1H, J1,2 1.8, H–C1),
4.01 (dd, 1H, J2,1 1.8, J2,3 6.1, H–C2), 4.08 (dd, 1H, J4 ,3 6.4, Jgem 8.3, H0–C4), 4.30 (ddd, 1H, J3,2=J3,4
0
6.1, J3,4 6.4, H–C3); 13C NMR δ −3.6 and −4.5 ((CH3)2Si-), 14.5 and 14.6 ((CH3CH2S)2-), 18.3
0
((CH3)3CSi-), 25.0 and 26.6 (C(CH3)2), 25.8 and 26.6 ((CH3CH2S)2), 25.9 ((CH3)3CSi-), 54.7 (C-1),
66.6 (C-4), 76.5 and 77.2 (C-2, C-3), 108.6 (C(CH3)2); IR (KBr, liquid film): 2995, 1475, 1465, 1385,
1375, 1260, 1220, 1130, 1075, 835, 780 cm−1; MS (m/e) (relative intensity): 380 (0.2%, M+), 365 (0.6,
M+−Me), 323 (6, M+−t-Bu), 305 (1, C14H29O3SSi+), 265 (8, C11H21O3S2 ), 161 (34, C6H9O3S+), 135
+
(45, C5H11S2 ), 101 (100, C5H9O2 ), 73 (63, C3H5O2 ), 59 (20, C3H7O+), 43 (35, C2H3O+). Anal. calcd
for C17H36O3S2Si: C, 53.64; H, 9.53. Found: C, 53.68; H, 8.95.
+
+
+
3.4. General method for O-benzylation15c
3.4.1. Of alcohol 8
To a solution of compound 8 (1.34 g, 5.04 mmol) in THF (60 ml), a 60% suspension of NaH (129 mg,
5.36 mmol) in mineral oil was added at rt. The mixture was stirred at reflux for 30 min, cooled at rt and
then t-Bu4NI (157 mg, 0.43 mmol) and benzylbromide (0.64 ml, 5.36 mmol) were successively added.
The solution was stirred for 2 h at rt, the solvent was removed in vacuo and the residue was treated with
a saturated aqueous solution of NaHCO3 (50 ml) and extracted with CH2Cl2 (2×30 ml). The combined
organic extracts were dried (Na2SO4), the solvent was removed under reduced pressure, and the residue
was purified by flash chromatography (hexane:Et2O, 4:1) to yield compound 15 (1.26 g, 3.53 mmol,
70%) as a colorless oil.
3.4.1.1. 2-O-Benzyl-3,4-O-isopropylidene-D-erythrose diethyldithioacetal 15. Rf=0.64 (hexane:Et2O,
1
1:1); [α]D20=+39.6 (c 1.06, CHCl3); H NMR δ 1.25 and 1.29 (2t, each 3H, Jvic 7.4, (CH3CH2S)2-),
1.34 and 1.40 (2s, each 3H, C(CH3)2), 2.66–2.76 (m, 4H, (CH3CH2S)2-), 3.86 (dd, 1H, J2,1 2.3, J2,3
6.8, H–C2), 3.89 (dd, 1H, J4,3 5.7, Jgem 8.6, H–C4), 4.08 (dd, 1H, J4 ,3 6.4, Jgem 8.6, H0–C4), 4.09 (d,
0
0
1H, J1,2 2.3, H–C1), 4.37 (ddd, 1H, J3,2 6.8, J3,4 5.7, J3,4 6.4, H–C3), 4.72 and 4.92 (AB system, 2H,
J 11.3, PhCH2-), 7.26–7.38 (m, 5H, C6H5-); 13C NMR δ 14.4 and 14.5 ((CH3CH2S)2-), 25.1 and 26.7
(C(CH3)2), 25.5 and 26.3 ((CH3CH2S)2-), 53.2 (C-1), 66.5 (C-4), 74.7 (PhCH2), 75.9 and 83.0 (C-2,
C-3), 108.8 (C(CH3)2), 127.7, 127.9 and 128.2 (C6H5), 137.93 (CPh–CH2); IR (KBr, liquid film): 3050,
3000, 1460, 1385, 1375, 1270, 1220, 1170, 1060, 855, 750 cm−1; MS (m/e) (relative intensity): 356 (2%,
+
+
M+), 295 (2, M+−C2H5S), 248 (3, C11H20O2S2 ), 188 (4, C9H16O2S+), 135 (84, C5H11S2 ), 101 (30,
+
+
C5H9O2 ), 91 (100, C7H7 ), 43 (53, C2H30+). Anal. calcd for C18H28O3S2: C, 60.63; H, 7.92. Found: C,
60.75; H, 7.93.
3.4.2. Of alcohols 2 and 3
Following the above-described procedure for the benzylation of compound 8, starting from the
diastereoisomeric alcohols26 2 and 3 (1.13 g, 4 mmol) in THF (50 ml), NaH (170 mg, 4.25 mmol),
t-BuNI (148 mg, 0.4 mmol) and benzylbromide (0.5 ml, 4.25 mmol), 32 (726 mg, 2.8 mmol, 70%,
reaction time 4 h) was isolated as a colorless oil by flash chromatography (hexane:Et2O, 1:1).
3.4.2.1. (1S)-1-Ethylsulfinyl-1-ethylthio-2-deoxy-3,4-O-isopropylidene-D-glycero-tetra-1-enose
32.
1
Rf=0.55 (Et2O); [α]D20=+127.4 (c 0.5, CHCl3); H NMR δ 1.19 (t, 3H, Jvic 7.3, CH3CH2S-), 1.30
(t, 3H, Jvic 7.3, CH3CH2SO), 1.42 and 1.45 (2s, each 3H, C(CH3)2), 2.67–3.20 (m, 4H, CH3CH2S-,
CH3CH2SO-), 3.64 (dd, 1H, J4,3 6.9, Jgem 8.2, H–C4), 4.18 (dd, 1H, J4 ,3 6.9, Jgem 8.2, H0–C4), 5.24
0

Y. Arroyo-Gómez et al. / Tetrahedron: Asymmetry 10 (1999) 973–990
983
(ddd, 1H, J3,2 8.2, J3,4=J3,4 6.9, H–C3), 6.90 (d, 1H, J2,3 8.2, H–C2); 13C NMR δ 14.8 and 15.0
(CH3CH2S, CH3CH2SO), 25.8 and 26.5 (C(CH3)2), 29.6 (CH3CH2S-), 44.7 (CH3CH2SO), 68.9 (C-4),
73.3 (C-3), 110.2 (C(CH3)2), 139.8 (C-1), 141.2 (C-2); IR (KBr, liquid film): 3000, 1610, 1460, 1385,
1375, 1250, 1220, 1160, 1065, 970, 840, 760 cm−1; MS (m/e) (relative intensity): 264 (1%, M+), 239
0
+
+
+
(3, M+−Me), 189 (2, C9H17O2S+), 161 (12, C6H9OS2 ), 145 (3, C6H9S2 ), 101 (37, C5H9O2 ), 59 (34,
C3H7O+), 43 (100, C2H30+). Anal. calcd for C11H20O3S2: C, 49.98; H, 7.62. Found: C, 50.03; H, 7.59.
3.5. General method for dithioacetals hydrolysis18a
3.5.1. Of dithioacetal 11
Compound 11 (740 mg, 1.95 mmol) in a mixture of acetone (6 ml) and water (0.5 ml) was treated with
HgCl2 (1.25 g, 4.6 mmol) and HgO (1.25 g, 5.78 mmol). The reaction mixture was stirred for 2 h at rt.
The solvent was removed in vacuo, CHCl3 was added and then the mixture was filtered through a Celite
pad and washed with the same solvent. The filtrate was treated with saturated aqueous solution of KI and
water. The organic layer was dried (MgSO4), and the solvent was removed under reduced pressure to
give pure 16 (535 mg, quantitative yield) as a colorless oil.
3.5.1.1. 2-O-(t-Butyldimethylsilyl)-3,4-O-isopropylidene-D-threose 16. Rf=0.57 (hexane:Et2O, 2:1);
[α]D20=+182.3 (c 0.85, CHCl3); spectroscopic data for compound 16 are coincident with those
reported:15c 1H NMR δ 0.08 and 0.10 (2s, each 3H, (CH3)2Si-), 0.92 (s, 9H, (CH3)3CSi-), 1.33 and
1.41 (2s, each 3H, C(CH3)2), 3.93 (dd, 1H, J4,3 6.1, Jgem 8.8, H–C4), 4.04 (dd, 1H, J2,1 1.3, J2,3 4.9,
H–C2), 4.06 (dd, 1H, J4 ,3 6.6, Jgem 8.8, H0–C4), 4.30 (ddd, 1H, J3,2 4.9, J3,4 6.1, J3,4 6.6, H–C3), 9.68
(d, 1H, J1,2 1.3, H–C1).
0
0
3.5.2. Of dithioacetal 14
Following the above-described hydrolysis procedure, starting from compound 14 (1.98 g, 5.21 mmol)
in acetone–water (16 ml), HgCl2 (3.34 g, 12.3 mmol) and HgO (3.34 g, 15.4 mmol), pure 17 (1.5 g,
quantitative yield) was obtained as a colorless oil.
3.5.2.1. 2-O-(t-Butyldimethylsilyl)-3,4-O-isopropylidene-D-erythrose 17. Rf=0.6 (hexane:Et2O, 2:1);
[α]D20=−1.2 (c 1.0, CHCl3); spectroscopic data of 17 are coincident with those reported:15c 1H NMR δ
0.08 and 0.10 (2s, each 3H, (CH3)2Si-), 0.91 (s, 9H, (CH3)3CSi-), 1.34 and 1.43 (2s, each 3H, C(CH3)2),
3.92 (dd, 1H, J4,3 5.9, Jgem 8.4, H–C4), 4.02 (dd, 1H, J4 ,3 6.1, Jgem 8.4, H0–C4), 4.05 (dd, 1H, J2,1 1.6,
0
J2,3 6.1, H–C2), 4.24 (m, 1H, H–C3), 9.65 (1H, d, J1,2 1.6, H–C1).
3.5.3. Of dithioacetal 15
Following the above-described hydrolysis procedure, starting from compound 15 (1.98 g, 5.21 mmol)
in acetone–water (16 ml), HgCl2 (3.34 g, 12.3 mmol) and HgO (3.34 g, 15.4 mmol), pure 18 (1.5 g,
quantitative yield) was achieved as a colorless oil.
3.5.3.1. 2-O-(Benzyl)-3,4-O-isopropylidene-D-erythrose 18. Rf=0.4 (hexane:Et2O, 1:2); [α]D20=+28.7
(c 1.2, CHCl3); spectroscopic data of compound 18 are coincident with those previously reported:15c 1
H
NMR δ 1.34 and 1.43 (2s, each 3H, C(CH3)2), 3.82 (dd, 1H, J1,2 2.0, J2,3 6.1, H–C2), 3.92 (dd, 1H, J4,3
5.5, Jgem 8.6, H–C4), 4.07 (dd, 1H, J4 ,3 6.3, Jgem 8.6, H0–C4), 4.35 (ddd, 1H, J3,4 5.5, J3,2 6.1, J3,4 6.3,
H–C3), 4.73 (AB system, 2H, Jgem 11.6, PhCH2-), 7.35 (d, 1H, J1,2 2.0, H–C1).
0
0

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Y. Arroyo-Gómez et al. / Tetrahedron: Asymmetry 10 (1999) 973–990
3.5.4. Of dithioacetal 6
Following the above-mentioned procedure for the hydrolysis of compound 11, starting from compound
6 (355 mg, 1.42 mmol) in acetone–water (5 ml), HgCl2 (908 mg, 3.34 mmol), and HgO (908 mg, 4.19
mmol), pure 19 (184 mg, 90%) was obtained as a colorless oil.
3.5.4.1. 2-Deoxy-3,4-O-isopropylidene-D-glycero tetrose 19. Rf=0.23 (hexane:isopropanol, 25:1);
[α]D20=+17.5 (c 0.6, CHCl3); 1H NMR δ 1.37 and 1.42 (2s, each 3H, C(CH3)2), 2.65 (ddd, 1H, J2,1 1.2,
J2,3 6.1, Jgem 17.3, H–C2), 2.85 (ddd, 1H, J2 ,1 1.8, J2 ,3 6.7, Jgem 17.3, H0–C2), 3.59 (dd, 1H, J4,3 6.7,
0
0
Jgem 8.3, H–C4), 4.19 (dd, 1H, J4 ,3 6.1, Jgem 8.3, H0–C4), 4.54 (dddd, 1H, J3,2=J3,4 6.1, J3,2 =J3,4 6.7,
0
0
0
H–C3), 9.81 (dd, 1H, J1,2 1.2, J1,2 1.8, H–C1); 13C NMR δ 25.5 and 26.8 (C(CH3)2), 47.8 (C-2), 69.1
0
(C-4), 70.6 (C-3), 109.3 (C(CH3)2), 200.1 (C-1); IR (KBr, liquid film): 3000, 2750, 1730, 1460, 1385,
1375, 1230, 1160, 1070 cm−1; MS (m/e) (relative intensity): 129 (7%, M+−CH3), 116 (1, M+−CO),
114 (1, C6H10O2 ), 101 (3, C5H9O2 ), 85 (7, C4H5O2 ), 69 (100, C4H5O+), 59 (17, C3H7O+), 43 (3,
+
+
+
C2H3O+). Anal. calcd for C7H12O3: C, 58.32; H, 8.39. Found: C, 58.21; H, 8.43.
3.6. Addition of EETMS to aldehydes. General procedure18
3.6.1. To aldehyde 17
1.6 M n-BuLi (4 ml, 6.45 mmol) was added dropwise to a solution of EETMS (784 mg, 5.16 mmol)
in dry THF (3 ml) at −20°C. The solution was warmed to 0°C and stirred for 30 min. Aldehyde 17
(1.4 g, 5.16 mmol) in THF (2 ml) was slowly added at −50°C and the reaction mixture was allowed
to reach room temperature (for ca. 90 min), then quenched with saturated aqueous NH4Cl solution and
extracted with dichloromethane (2×3 ml) and ethyl acetate (3 ml). The combined organic extracts were
dried (Na2SO4) and the solvent was removed in vacuo. The crude reaction (2.3 g; quantitative yield by
1H NMR spectrum) was dissolved in THF (15 ml), and without further purification, treated with LiAlH4
(600 mg, 15.8 mmol). The reaction mixture was warmed at 45°C and stirred for 4 h. The above-described
work-up yielded a residue, which was purified by flash chromatography (hexane:Et2O, 5:1) affording the
product 20 (1.02 g, 3.44 mmol, 67% yield) and a mixture of 20 and 21 (237 mg, 0.8 mmol, 16% yield).
Successive flash chromatography (hexane:Et2O, 20:1) did not allow isolation of stereoisomer 21 as a
pure form.
The diastereomeric ratio (88:12) was determined by integration of well separated signals (H–C5) of the
1H NMR spectrum by further transformation of an aliquot of the reaction mixture into the corresponding
di-O-isopropylidene derivatives, 22 and 23.
3.6.1.1. 4,5-O-Isopropylidene-D-ribose diethyldithioacetal 20. Rf=0.30 (hexane:Et2O, 1:1);
[α]D20=+9.4 (c 2.03, CHCl3); H NMR δ 1.29 (t, 6H, Jvic 7.4, (CH3CH2S)2-), 1.37 and 1.45 (2s,
1
each 3H, C(CH3)2), 2.66–2.78 (m, 5H, (CH3CH2S)2-, HO–C3), 3.15 (d, 1H, JOH,2 3.6, HO–C2,
exchangeable with D2O), 3.75 (ddd, 1H, J2,1 4.1, J2,OH 3.6, J2,3 7.1, H–C2, the signal turned into dd on
addition of D2O, J2,1 4.1, J2,3 7.1), 3.98 (m, 1H, H–C3, the signal turned into dd on addition of D2O, J3,2
0
7.1, J3,4 8.2), 4.05–4.11 (m, 2H, H–C4 and H–C5), 4.22 (d, 1H, J1,2 4.1, H–C1), 4.38 (dd, 1H, J4,5 6.6,
Jgem 11.8, H0–C5); 13C NMR δ 14.4 and 14.7 ((CH3CH2)2S-), 25.6 ((CH3CH2S)2-), 26.4 (C(CH3)2),
54.5 (C-1), 65.30 (C-5), 71.1, 74.5 and 76.3 (C-2, C-3, C-4), 109.1 (C(CH3)2); IR (KBr, liquid film):
3475, 3000, 1455, 1385, 1375, 1215, 1160, 1065, 860, 790 cm−1; MS (m/e) (relative intensity): 296
(2%, M+), 235 (2, M+−C2H5S), 217 (1, C10H17O3S+), 177 (15, C7H13OS2 ), 161 (4, C7H13O4 ), 135
+
+

Y. Arroyo-Gómez et al. / Tetrahedron: Asymmetry 10 (1999) 973–990
985
(100, C5H11S2 ), 75 (45, C3H5S+), 59 (50, C3H7O+), 43 (49, C2H3O+). Anal. calcd for C12H24O4S2: C,
48.62; H, 8.16. Found: C, 48.68; H, 8.14.
+
3.6.1.2. 4,5-O-Isopropylidene-D-arabinose diethyldithioacetal 21. 1H NMR δ 1.29 (t, 6H, Jvic 7.4,
(CH3CH2S)2-), 1.36 and 1.43 (2s, each 3H, C(CH3)2), 2.60–2.79 (m, 4H, (CH3CH2S)2-), 3.39 (d, 1H,
Jvic 2.3, HO), 3.74–3.76 (m, 1H, HO), 3.94–4.22 (6H, m, H–C1, H–C2, H–C3, H–C4, H–C5, H0–C5);
13C NMR δ 14.4 and 14.5 ((CH3CH2S)2-), 23.5 and 25.2 ((CH3CH2S)2-), 25.4 and 26.9 (C(CH3)2), 55.6
(C-1), 67.1 (C-5), 70.2, 71.1 and 76.2 (C-2, C-3, C-4), 109.1 (C(CH3)2).
3.6.2. To aldehyde 16
Following the above-described procedure for the addition of EETMS to compound 17, starting from
compound 16 (534 mg, 1.95 mmol) in THF (1 ml), EETMS (296 mg, 1.95 mmol) and n-BuLi (1.52
1
ml, 2.44 mmol), 900 mg (quantitative yield by H NMR spectrum) of crude reaction were obtained,
and without further purification, dissolved in THF (5 ml) and treated at 45°C with LiAlH4 (225 mg, 5.9
mmol). The work-up described above led to a crude product containing compounds 24, 25 and 26 in a
9:64:27 ratio (estimated by integration of the signals corresponding to H–C5 in the 1H NMR spectrum of
the crude reaction). Column chromatography using hexane:Et2O (10:1) as the eluent afforded pure 24 (27
mg, 5% yield) as a colorless oil and a fraction (387 mg, 67% yield) containing a mixture of compounds
25 and 26. After subsequent flash chromatography (hexane:Et2O, 15:1) pure 25 and 26 were obtained as
colorless oils.
3.6.2.1. 2-Deoxy-4,5-O-isopropylidene-D-threo pentose diethyldithioacetal 24. Rf=0.40 (hexane:Et2O,
1:1), [α]D20=27.5 (c 1.5, CHCl3); 1H NMR δ 1.27 (t, 6H, Jvic 7.5, (CH3CH2S)2-), 1.37 and 1.45 (2s, each
0
0
3H, C(CH3)2), 1.74 (ddd, 1H, J2,1 10.3, Jgem 14.3, J2,3 2.6, H–C2), 2.04 (ddd, 1H, J2 ,1 4.3, Jgem 14.3, J2 ,3
9.9, H–C2), 2.35 (d, 1H, JOH,3 6.0, HO–C3, exchangeable with D2O), 2.56–2.77 (m, 4H, (CH3CH2S)2-),
3.75–3.82 (m, 1H, H–C4), 3.82–3.95 (m, 1H, H–C3), 3.99–4.06 (m, 2H, H–C5), 4.10 (dd, 1H, J1,2
10.3, J1,2 4.3, H–C1); 13C NMR δ 14.5 ((CH3CH2S)2-), 24.1 and 24.4 ((CH3CH2S)2-) 25.2 and 26.5
0
(C(CH3)2), 40.4 (C-2), 47.7 (C-1), 65.9 (C-5), 69.6 and 78.6 (C-3, C-4), 109.6 (C(CH3)2); MS (m/e)
(relative intensity): 280 (3%, M+), 219 (2, M+−C2H5S), 201 (5, C10H17O2S+), 161 (15, C7H13O2S+),
131 (93, C6H10OS+), 101 (11, C5H9O2 ), 85 (26, C4H5O2 ), 59 (100, C3H7O+), 43 (32, C2H3O+). Anal.
calcd for C12H24O3S2: C, 51.39; H, 8.63. Found: C, 51.29; H, 8.64.
+
+
3.6.2.2. 4,5-O-Isopropylidene-D-lyxose diethyldithioacetal 25. Rf=0.34 (hexane:Et2O, 1:1).
1
[α]D20=+22 (c 1.2, CHCl3); H NMR δ 1.29 and 1.30 (2t, each 3H, Jvic 7.4, (CH3CH2S)2-), 1.39
and 1.45 (2s, each 3H, C(CH3)2), 2.47 (d, 1H, JOH,2 6.5, HO–C2, exchangeable with D2O), 2.66 and
2.74 (2c, each 2H, Jvic 7.4, (CH3CH2S)2), 2.77 (d, 1H, JOH,3 3.6, HO–C3, exchangeable with D2O),
3.72–3.76 (m, 1H, H–C3, the signal turned into dd on addition of D2O, J3,2 8.5, J3,4 3.2), 3.77–3.82 (m,
1H, H–C2, the signal turned into dd on addition of D2O, J2,1 2.3, J2,3 8.5), 3.94 (dd, 1H, J5,4 7.0, Jgem 8.4,
H–C5), 4.11 (dd, 1H, J5 ,4 6.7, Jgem 8.4, H0–C5), 4.28 (d, 1H, J1,2 2.3, H–C1), 4.42 (ddd, 1H, J4,3 3.2,
0
J4,5 6.7, J4,5 7.0, H–C4); 13C NMR δ 14.5 and 14.6 ((CH3CH2S)2-), 25.2 and 26.4 (C(CH3)2), 25.7 and
0
25.9 ((CH3CH2S)2-), 54.7 (C-1), 66.4 (C-5), 71.1, 73.9 and 75.7 (C-2, C-3, C-4), 109.2 (C(CH3)2); IR
(KBr, liquid film): 3495, 2995, 1460, 1385, 1375, 1215, 1160, 1065, 860, 795 cm−1; MS (m/e) (relative
intensity): 296 (3%, M+), 235 (2, M+−C2H5S), 217 (1, C10H17O3S+), 177 (19, C7H13OS2 ), 161 (7,
+
C7H13O4 ), 135 (100, C5H11S2 ), 75 (30, C3H5S+), 59 (43, C3H7O+), 43 (30, C2H3O+). Anal. calcd for
C12H24O4S2: C, 48.62; H, 8.16. Found: C, 48.65; H, 8.17.
+
+

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Y. Arroyo-Gómez et al. / Tetrahedron: Asymmetry 10 (1999) 973–990
3.6.2.3. 4,5-O-Isopropylidene-D-xylose diethyldithioacetal 26. Rf=0.20 (hexane:Et2O, 1:1);
[α]D20=+56.3 (c 0.25, CHCl3); H NMR δ 1.29 and 1.30 (2t, each 3H, Jvic 7.4, (CH3CH2S)2-),
1
1.39 and 1.46 (2s, each 3H, C(CH3)2), 2.65 (d, 1H, JOH,3 7.8, HO–C3, exchangeable with D2O),
2.64–2.81 (m, 4H, (CH3CH2S)2-), 3.36 (d, 1H, JOH,2 2.8, HO–C2, exchangeable with D2O), 3.51 (ddd,
1H, J2,1 8.8, J2,OH 2.8, J2,3 1.5, H–C2, the signal turned into dd on addition of D2O, J2,1 8.8, J2,3 1.5),
3.86 (dd, 1H, J5,4 7.0, Jgem 8.1, H–C5), 4.01 (ddd, 1H, J3,OH 7.8, J3,2 1.5, J3,4 5.1, H–C3, the signal turned
into dd upon addition of D2O), 4.06 (d, 1H, J1,2 8.8, H–C1), 4.08 (dd, 1H, J5 ,4 6.5, Jgem 8.1, H–C50),
0
4.28 (ddd, 1H, J4,3 5.1, J4,5 7.0, J4,5 6.5, H–C4); 13C NMR δ 14.4 and 14.5 ((CH3CH2S)2-), 24.0 and
0
25.7 ((CH3CH2S)2-), 25.5 and 26.5 (C(CH3)2), 55.3 (C-1), 66.1 (C-5), 70.3, 72.9 and 76.6 (C-2, C-3,
C-4), 109.8 (C(CH3)2); IR (KBr, liquid film): 3425, 3000, 1450, 1385, 1210, 1165, 1080, 895, 810, 760
cm−1; MS (m/e) (relative intensity): 296 (2%, M+), 217 (2, C10H17O3S+), 177 (10, C7H13OS2 ), 161
+
(12, C7H13O4 ), 135 (100, C5H11S2 ), 101 (25, C5H9O2 ), 75 (27, C3H5S+), 43 (42, C2H3O+). Anal.
calcd for C12H24O4S2: C, 48.62; H, 8.16. Found: C, 48.62; H, 8.15.
+
+
+
3.6.3. To aldehyde 19
Following the above-described procedure for the addition of EETMS to compound 17, starting from
compound 19 (443 mg, 3.1 mmol) in THF (1 ml), EETMS (471 mg, 3.1 mmol) and n-BuLi (2.43 ml,
1
3.89 mmol), 960 mg (quantitative yield by H NMR spectrum) of crude reaction were obtained. The
crude reaction, without further purification, was treated with LiAlH4 under two different experimental
conditions:
3.6.4. Experiment A
The crude reaction (300 mg) was dissolved in THF (7 ml) and treated with LiAlH4 (100 mg, 2.6 mmol)
at 45°C, and stirred for 1 h. The above-described work-up led to a crude mixture containing compounds
29, 30 and 31 in a 59:23:18 ratio (determined by integration of signals of H–C5 in the 1H NMR spectrum
of the crude reaction). Column chromatography using hexane:Et2O (10:1) as the eluent afforded pure 29
(120 mg, 0.45 mmol, 46% yield) and a fraction (87 mg, 0.31 mmol, 32% yield) containing a mixture of
compounds 30 and 31. After subsequent flash chromatography (hexane:Et2O, 15:1), pure 30 and 31 were
obtained as colorless oils.
3.6.4.1. 2,3-Dideoxy-4,5-O-isopropylidene-D-glycero pentose diethyldithioacetal 29. Rf=0.25
(hexane:Et2O, 1:1). [α]D20=+12 (c 0.6, CHCl3); H NMR δ 1.26 (t, 6H, Jvic 7.4, (CH3CH2S)2-), 1.35
1
and 1.41 (2s, each 3H, C(CH3)2), 1.73–2.03 (m, 4H, H–C2, H–C3), 2.53–2.72 (m, 4H, (CH3CH2S)2-),
0
0
3.53 (dd, 1H, J5,4 6.7, Jgem 7.5, H–C5), 3.81 (dd, 1H, J1,2=J1,2 6.4, H–C1), 4.04 (dd, 1H, J5 ,4 6.0, Jgem
7.5, H0–C5) 4.02–4.13 (m, 1H, H–C4); 13C NMR δ 14.5 ((CH3CH2S)2), 24.0 and 24.2 ((CH3CH2S)2-),
25.7 and 26.9 (C(CH3)2), 31.4 and 32.2 (C-2, C-3), 51.1 (C-1), 69.3 (C-5), 75.5 (C-4), 108.9 (C(CH3)2);
IR (KBr, liquid film): 3010, 1455, 1385, 1375, 1220, 1155, 1065, 860, 790 cm−1; MS (m/e) (relative
intensity): 264 (19%, M+), 249 (12, M+−CH3), 203 (19, M+−C2H5S), 189 (17, C19H1702S+), 145 (100,
C7H13OS+), 117 (34, C6H13O2 ), 101 (64, C5H9O2 ), 83 (43, C5H7O+), 61 (11, C2H5S+), 43 (35,
C2H3O+). Anal. calcd for C12H24O2S2: C, 54.50; H, 9.15. Found: C, 54.68; H, 9.12.
+
+
3.6.4.2. (2R)-3-Deoxy-4,5-O-isopropylidene-D-glycero pentose diethyldithioacetal 30. Rf=0.60
1
(hexane:Et2O, 1:1); [α]D20=+52.4 (c 0.6, CHCl3); H NMR δ 1.21 and 1.22 (2t, each 3H, Jvic 7.4,
(CH3CH2S)2-), 1.30 and 1.36 (2s, each 3H, C(CH3)2), 1.85 (ddd, 1H, J3,2 8.2, Jgem 14.2, J3,4 8.2,
H–C3), 1.99 (ddd, 1H, J3 ,2 3.0, Jgem 14.2, J3 ,4 4.6, H0–C3), 2.57–2.74 (m, 4H, (CH3CH2S)2-), 3.34
0
0

Y. Arroyo-Gómez et al. / Tetrahedron: Asymmetry 10 (1999) 973–990
987
(1H, d, JOH,2 2.4, HO–C2, exchangeable with D2O), 3.55 (dd, 1H, J5,4 7.3, Jgem 8.1, H–C5), 3.80 (d,
1H, J1,2 5.6, H–C1), 3.82–4.07 (m, 1H, H–C2), 4.04 (dd, 1H, J5 ,4, 6.0, Jgem 8.1, H0–C5), 4.25 (dddd,
0
1H, J4,3 8.2, J4,3 4.6, J4,5 7.3, J4,5 6.0, H–C4); 13C NMR δ 14.5 and 14.6 ((CH3CH2S)2-), 25.1 and
25.8 ((CH3CH2S)2-), 25.8 and 26.9 (C(CH3)2), 36.9 (C-3), 57.7 (C-1), 69.5 (C-5), 72.1 and 74.7 (C-2,
C-4), 109.2 (C(CH3)2); IR (KBr, liquid film): 3500, 3000, 1460, 1385, 1375, 1220, 1160, 1070, 870,
790 cm−1; MS (m/e) (relative intensity): 280 (5%, M+), 265 (5, M+−CH3), 262 (3, M+−H2O), 145 (40,
0
0
C7H13O3 ), 135 (100, C5H11S2 ), 115 (15, C6H11O2 ), 107 (28, C3H7S2 ), 75 (56, C3H7S+), 43 (36,
C2H3O+). Anal. calcd for C12H24O3S2: C, 51.39; H, 8.63. Found: C, 51.29; H, 8.64.
+
+
+
+
3.6.4.3. (2S)-3-Deoxy-4,5-O-isopropylidene-D-glycero pentose diethyldithioacetal 31. Rf=0.67
(hexane:Et2O, 1:1); [α]D20=−42.6 (c 0.65, CHCl3); 1H NMR δ 1.28 (t, 6H, Jvic 7.4, (CH3CH2S)2-), 1.37
and 1.42 (2s, each 3H, C(CH3)2), 1.73 (ddd, 1H, J3 ,2 9.9, Jgem 14.0, J3 ,4 4.5, H0–C3), 2.12 (ddd, 1H,
J3,2 2.3, Jgem 14.0, J3,4 8.0, H–C3), 2.63–2.76 (m, 4H, (CH3CH2S)2-), 2.95 (d, 1H, JOH,2 3.3, HO–C2,
exchangeable with D2O), 3.61 (dd, 1H, J5,4 7.1, Jgem 8.1, H–C5), 3.79 (d, 1H, J1,2 6.2, H–C1), 3.91 (m,
0
0
0
0
1H, H–C2, the signal turned into ddd on addition of D2O, J2,1 6.2, J2,3 9.9, J2,3 2.3), 4.12 (dd, 1H, J5 ,4
6.0, Jgem 8.1, H0–C5), 4.35 (dddd, 1H, J4,3 4.5, J4,3 8.0, J4,5 7.1, J4,5 6.0, H–C4); 13C NMR δ 14.4 and
14.5 ((CH3CH2S)2-), 24.6 and 25.5 ((CH3CH2S)2-), 25.6 and 26.9 (C(CH3)2), 38.0 (C-3), 58.6 (C-1),
69.7 and 73.5 (C-2, C-4, C-5), 108.6 (C(CH3)2); IR (KBr, liquid film): 3500, 3000, 1460, 1385, 1375,
1220, 1160, 1070, 835, 790 cm−1; MS (m/e) (relative intensity): 280 (3%, M+), 265 (6, M+−CH3), 145
0
0
+
+
+
+
(38, C7H13O3 ), 135 (99, C5H11S2 ), 115 (20, C6H11O2 ), 107 (37, C3H7S2 ), 75 (100, C3H7S+), 61
(23, C2H5S+), 43 (26, C2H3O+). Anal. calcd for C12H24O3S2: C, 51.39; H, 8.63. Found: C, 51.32; H,
8.68.
3.6.5. Experiment B
The crude reaction (650 mg) was dissolved in THF (14 ml), treated with LiAlH4 (238 mg, 6.3
mmol) and refluxed for 1 h. The above-described work-up led to a residue which was purified by flash
chromatography (hexane:Et2O, 10:1) to yield pure 29 (392 mg, 1.5 mmol, 71%) as the only product.
3.7. Acetonation. General procedure15c
3.7.1. Of diol 20
To a solution of diol 20 (89 mg, 0.3 mmol) in C6H6 (2 ml), 2,2-dimethoxypropane (DMP, 0.074 ml,
0.6 mmol), and PTSA (0.85 mg, 4.30×10−3 mmol) were added. The mixture was refluxed for 30 min,
and then the solvent was removed under reduced pressure. DMP (21×10−3 mg, 0.17 mmol) in C6H6 (1
ml) was subsequently added, the solvent was evaporated under reduced presssure, and the residue was
treated with a saturated aqueous solution of NaHCO3 (1 ml) and pentane (4 ml). The organic layer was
washed with a saturated aqueous solution of NaCl, dried over Na2SO4, and the solvent removed under
reduced pressure. The resulting crude reaction was purified by flash chromatography (hexane:Et2O, 10:1)
to afford pure 22 (97 mg, 97%) as a colorless oil.
3.7.1.1. 2,3:4,5-Di-O-isopropylidene-D-ribose diethyldithioacetal 22. Rf=0.47 (hexane:Et2O, 4:1);
[α]D20=−121.6 (c 0.74, CHCl3); 1H NMR δ 1.28 and 1.29 (2t, each 3H, Jvic 7.4, (CH3CH2S)2-), 1.34 (s,
6H, C(CH3)2), 1.42 and 1.49 (2s, each 3H, C(CH3)2), 2.63–2.84 (m, 4H, (CH3CH2S)2-), 3.92 (dd, 1H,
0
J
5,4 5.6, Jgem 8.6, H–C5), 4.11 (dd, 1H, J3,2 6.5, J3,4 9.3, H–C3), 4.15 (dd, 1H, J5 ,4 6.2, Jgem 8.6, H0–C5),
0
4.28 (d, 1H, J1,2 4, H–C1), 4.56 (dd, 1H, J2,1 4, J2,3 6.5, H–C2), 4.64 (ddd, 1H, J4,3 9.3, J4,5 5.6, J4,5 6.2,

988
Y. Arroyo-Gómez et al. / Tetrahedron: Asymmetry 10 (1999) 973–990
H–C4); 13C NMR δ 14.5 and 14.4 ((CH3CH2S)2-), 24.7 (C(CH3)2 and CH3CH2S), 25.5 (CH3CH2S),
25.4, 26.5 and 26.8 (C(CH3)2), 50.2 (C-1), 68.31 (C-5), 73.2, 76.7 and 81.3 (C-2, C-3, C-4), 109.2 and
109.7 (C(CH3)2); IR (KBr, liquid film): 3000, 1455, 1385, 1255, 1215, 1160, 1070, 855 cm−1; MS (m/e)
+
+
(relative intensity): 336 (8%, M+), 263 (3, C11H19O3S2 ), 217 (22, C10H17O3S+), 177 (6, C6H9O2S2 ),
+
+
+
+
135 (100, C5H11S2 ), 101 (34, C5H9O2 ), 87 (53, C4H7O2 ), 85 (32, C4H5O2 ), 43 (100, C2H3O+).
Anal. calcd for C15H28O4S2: C, 53.53; H, 8.39. Found: C, 53.49; H, 8.41.
3.7.2. Of crude reaction of diols 20 and 21
To a solution of crude reaction containing diols 20 and 21 (178 mg, 0.6 mmol) in C6H6 (4 ml), DMP
(0.15 ml, 1.2 mmol) and PTSA (1.7 mg, 8.6 mmol) were added following the above-described procedure
for the acetonation of compound 20. Work-up led to a crude mixture (200 mg) containing 22:23 in a
88:12 ratio determined by 1H NMR (H–C5). Column chromatography using hexane:Et2O (25:1) as the
eluent, afforded pure 22 and 23 as colorless oils.
3.7.2.1. 2,3:4,5-Di-O-isopropylidene-D-arabinose diethyldithioacetal, 23. Rf=0.42 (hexane:Et2O,
4:1); [α]D20=+102 (c 0.57, CHCl3); 1H NMR δ 1.26 and 1.28 (2t, each 3H, Jvic 7.4, (CH3CH2S)2-), 1.34,
1.38, 1.42 and 1.45 (4s, each 3H, C(CH3)2), 2.67–2.80 (m, 4H, (CH3CH2S)2-), 3.96 (dd, 1H, J5,4 4.2,
Jgem 8.3, H–C5), 4.03 (d, 1H, J1,2 2.6, H–C1), 4.05–4.16 (m, 3H, H–C3, H–C4 and H0–C5), 4.29 (dd,
1H, J2,1 2.6, J2,3 6.9, H–C2); 13C NMR δ 14.3 and 14.4 ((CH3CH2S)2-), 24.9 and 25.2 ((CH3CH2S)2-),
26.6, 27.1, 27.3 and 28.3 (C(CH3)2), 52.3 (C-1), 67.7 (C-5), 77.1, 79.1 and 84.4 (C-2, C-3, C-4), 109.7
and 110.2 (C(CH3)2); IR (KBr, liquid film): 3000, 1460, 1385, 1375, 1220, 1160, 1070, 890, 855 cm−1;
+
MS (m/e) (relative intensity): 336 (10%, M+), 263 (4, C11H19O3S2 ), 217 (27, C10H17O3S+), 177 (4,
+
+
+
+
+
C6H9O2S2 ), 135 (73, C5H11S2 ), 101 (30, C5H9O2 ), 87 (32, C4H7O2 ), 85 (27, C4H5O2 ), 43 (100,
C2H3O+). Anal. calcd for C15H28O4S2: C, 53,53; H, 8.39. Found: C, 53.51; H, 8.43.
3.7.3. Of diol 25
Following the above-described procedure for the acetonation of compound 20, starting from compound
25 (32.2 mg, 0.11 mmol) in C6H6 (1 ml), DMP (0.027 ml, 0.22 mmol), and PTSA (0.31 mg, 1.61×10−3
mmol), compound 27 (19 mg, 0.055 mmol, 50% yield) was obtained as a colorless oil after flash
chromatography using hexane:Et2O (15:1) as the eluent.
3.7.3.1. 2,3:4,5-Di-O-isopropylidene-D-lyxose diethyldithioacetal 27. Rf=0.35 (hexane:Et2O, 4:1);
[α]D20=−35 (c 0.33, CHCl3); 1H NMR δ 1.28 (t, 6H, Jvic 7.4, (CH3CH2S)2-), 1.36, 1.38, 1.44 and 1.54
(4s, each 3H, C(CH3)2), 2.61–2.92 (m, 4H, (CH3CH2S)2-), 3.85 (dd, 1H, J5,4 8.1, Jgem 7.8, H–C5), 4.05
(dd, 1H, J5 ,4 6.3, Jgem 7.8, H0–C5), 4.14 (dd, 1H, J3,2 5.7, J3,4 3.0, H–C3), 4.21 (d, 1H, J1,2 10.0, H–C1),
0
4.26 (dd, 1H, J2,1 10.0, J2,3 5.7, H–C2), 4.56 (ddd, 1H, J4,3 3.0, J4,5 8.1, J4,5 6.3, H–C4); 13C NMR δ 14.2
0
and 14.4 ((CH3CH2S)2-), 24.0 and 24.8 ((CH3CH2S)2), 25.3, 25.8, 26.5 and 26.7 (C(CH3)2), 49.6 (C-1),
66.4 (C-5), 73.7, 76.4 and 79.0 (C-2, C-3, C-4), 109.0 and 109.6 (C(CH3)2); IR (KBr, liquid film): 3000,
1460, 1385, 1260, 1220, 1160, 1070, 885 cm−1; MS (m/e) (relative intensity): 336 (3%, M+), 321 (4,
M+−CH3), 278 (4, C12H22O3S2 ), 217 (27, C10H17O3S+), 177 (31, C6H9O2S2 ), 135 (100, C5H11S2 ),
+
+
+
101 (59, C5H9O2 ), 87 (55, C4H7O2 ), 85 (49, C4H5O2 ), 59 (58, C3H7O+), 43 (98, C2H3O+). Anal.
calcd for C15H28O4S2: C, 53.53; H, 8.39. Found: C, 53.62, H; 8.36.
+
+
+

Y. Arroyo-Gómez et al. / Tetrahedron: Asymmetry 10 (1999) 973–990
989
3.7.4. Of diol 26
Following the above-described procedure for the acetonation of compound 20, starting from com-
pound 26 (32.5 mg, 0.11 mmol) in C6H6 (1 ml), DMP (0.027 ml, 0.22 mmol), and PTSA (0.31 mg,
1.61×10−3 mmol), compound 28 (17 mg, 0.051, 46% yield) was obtained as a colorless oil after flash
chromatography using hexane:Et2O (15:1) as the eluent.
3.7.4.1. 2,3:4,5-Di-O-isopropylidene-D-xylose diethyldithioacetal 28. Rf=0.36 (hexane:Et2O, 4:1);
[α]D20=−55.1 (c 0.33, CHCl3); 1H NMR δ 1.27 and 1.28 (2t, each 3H, Jvic 7.4, (CH3CH2S)2-), 1.38 (s,
3H, C(CH3)2), 1.44 (s, 6H, C(CH3)2) and 1.47 (s, 3H, C(CH3)2), 2.66–2.85 (m, 4H, (CH3CH2S)2-), 3.91
(d, 1H, J1,2 5.2, H–C1), 3.92 (dd, 1H, J5,4 7.5, Jgem 8.0, H–C5), 4.06 (dd, 1H, J5 ,4 6.7, Jgem 8.0, H0–C5),
0
4.15 (dd, 1H, J3,2 7.4, J3,4 3.2, H–C3), 4.34 (dd, 1H, J2,1 5.2, J2,3 7.4, H–C2), 4.34 (ddd, 1H, J4,3 3.2, J4,5
7.5, J4,5 6.7, H–C4); 13C NMR δ 14.3 and 14.4 ((CH3CH2S)2-), 24.9 and 25.3 ((CH3CH2S)2-), 25.6,
0
26.1, 27.2 and 27.4 (C(CH3)2), 53.0 (C-1), 65.9 (C-5), 75.3, 78.7 and 80.0 (C-2, C-3, C-4), 109.8 and
110.1 (C(CH3)2); IR (KBr, liquid film): 3000, 1455, 1380, 1370, 1225, 1160, 1075, 995, 885 cm−1; MS
+
+
(m/e) (relative intensity): 336 (6%, M+), 217 (5, C10H17O3S+), 177 (4, C6H9O2S2 ), 135 (81, C5H11S2 ),
101 (56, C5H9O2 ), 87 (32, C4H7O2 ), 85 (33, C4H5O2 ), 59 (43, C3H7O+), 43 (100, C2H3O+). Anal.
calcd for C15H28O4S2: C, 53,53; H, 8.39. Found: C, 53.58; H, 8.38.
+
+
+
Acknowledgements
We thank Junta de Castilla y León for financial support and to Ana Ma Martín Castro for the English
translation.
References
1. Aitken, R. A.; Kilényi, S. N. Asymmetric Synthesis; Blackie Academic and Professional, Chapman & Hall, 1992.
2. (a) McGarvey, G. J.; Kimura, M.; Oh, T.; Williams, J. M. J. Carbohyd. Chem. 1984, 3, 125. (b) Jurczak, J.; Pikul, S.; Baner,
T. Tetrahedron 1986, 42, 447. (c) Mulzer, J.; Altenbach, H.-J.; Braun, M.; Krohn, K.; Reissig, H.-U. Organic Synthesis
Highlights. VCH: Weinheim, 1991; p. 25.
3. Tetrose derivatives: (a) Rosen, T.; Taschner, M. J.; Heathcook, C. H. J. Org. Chem. 1984, 49, 3994. (b) Mukaiyama, T.;
Suzuki, K.; Yamada, T.; Tabusa, F. Tetrahedron 1990, 46, 265. (c) Carreaux, F.; Dureault, A.; Depezay, J. C. Synlett 1992,
527. (d) Inanaga, J.; Sugimoto, Y.; Yokoyama, Y.; Hanamoto, T. Tetrahedron Lett. 1992, 33, 8109. (e) Muri, Y.; Asai,
A.; Okumara, A.; Furukawa, H. Tetrahedron 1995, 51, 5299–5315. (f) André, C.; Bolte, J.; Demuynck, C. Tetrahedron:
Asymmetry 1998, 9, 1359.
4. Pentose derivatives: (a) Kovács, I.; Tóth, Z.; Herczegh, P.; Sztaricskai, F. Tetrahedron: Asymmetry 1993, 4, 2261. (b) Al-
Tel, T. H.; Al-Qawasmeh, R. A.; Schröder, C.; Voelter, Tetrahedron 1995, 51, 3141. (c) Wucherpfennig U.; Logothetis, T.
A.; Eilitz, U.; Burger, K. Tetrahedron 1996, 52, 143.
5. Glyceraldehyde derivatives: (a) Jackson, D. Y. Synth. Commun. 1988, 18, 337. (b) Schmid, C. R.; Bryant, J. D.;
Dowlatzedah, M.; Phillips, J. L.; Prather, D. E.; Schantz, R. D.; Sear, N. L.; Vianco, C. S. J. Org. Chem. 1991, 56, 4056.
(c) Hertel, L. W.; Grossman, C. S.; Kroin, J. S. Synth. Commun. 1991, 21, 151. (e) Niu, C.; Petterson, T.; Miller, M. J. J.
Org. Chem. 1996, 61, 1014.
6. Tetrose derivatives: (a) Roush, W. R.; Brown, R. J. J. Org. Chem. 1982, 47, 1373. (b) Achmatowicz, B.; Raubo, P.; Wicha,
J. J. Org. Chem. 1992, 57, 6593.
7. Pentose derivatives: (a) Ma, P.; Martin, V. S.; Masamune, S.; Sharpless, K. B.; Viti, S. M. J. Org. Chem. 1982, 47, 1380.
(b) Minami, N.; Ko, S. S.; Kishi, Y. J. Am. Chem. Soc. 1982, 104, 1109. (c) Lee, A. W. M.; Martin, V. S.; Masamune, S.;
Sharpless, K. B.; Walker, F. J. J. Am. Chem. Soc. 1982, 104, 3515. (d) Raifeld, Y. E.; Nikitenko, A. A.; Arshava, B. M.;
Mikerin, I. E.; Zilberg, L. L. Tetrahedron 1994, 50, 8603. (e) Giner, J. L. Tetrahedron Lett. 1998, 39, 2479.

990
Y. Arroyo-Gómez et al. / Tetrahedron: Asymmetry 10 (1999) 973–990
8. Hexose derivatives: Ko, S. Y.; Lee, A. W. M.; Masamune, S.; Reed III, L. A.; Sharpless, K. B.; Walker, F. J. Tetrahedron
1990, 47, 1378.
9. L-Glyceraldehyde derivatives: Raubo, P.; Wicha, J. Tetrahedron: Asymmetry 1995, 6, 577.
10. Ko, S. Y.; Malik, M. Tetrahedron Lett. 1993, 34, 4675.
11. (a) Pottie, M.; Lathauwer, G.; Vandewalle, M. Bull. Soc. Chim. Belg. 1994, 103, 285. (b) Bestmann, H. J.; Bauriegel, L.
Tetrahedron Lett. 1995, 36, 853.
12. (a) Solladié G. Pure Appl. Chem. 1988, 60, 1699. (b) Solladié G.; Almario, A. Tetrahedron: Asymmetry 1994, 5, 1717.
13. Scolastico, S.; Maffioli, S. I.; Poli, G.; Pagni, P.; Zanda, M. Gazz. Chim. Ital. 1995, 125, 505.
14. (a) Murakami, M.; Mukaiyama, T. Chem. Lett. 1982, 241. (b) Báñez Sanz, J. M.; Galisteo Gozález, D.; López Sastre, J.
A.; Rodríguez Amo, J. F.; Romero-Avila, M. C.; Sanz Tejedor, M. A. An. Quim. 1993, 89, 365. (c) Mukaiyama, T.; Suzuki,
K.; Yamada, T.; Tabusa, F. Tetrahedron 1990, 46, 265. (d) Marshall, J. A.; Seletsky, B. M.; Luke, G. P. J. Org. Chem. 1994,
59, 3413. (e) Marshall, J. A.; Hinkle, K. W. J. Org. Chem. 1996, 61, 105. (f) Gypser, A.; Petereck, M.; Scharf, H. D. J.
Chem. Soc., Perkin Trans. 1 1997, 1013.
15. (a) Mukaiyama, T.; Yamaguchi, M.; Kato, J. Chem. Lett. 1981, 1505. (b) Suzuki, K.; Yuki, Y.; Mukaiyama, T. Chem.
Lett. 1981, 1529. (c) Dondoni, A.; Merino, P. Synthesis 1992, 196. (d) Dondoni, A.; Merino, P.; Franco, S.; Junquera, F.
Merchán, F. L.; Tejero, T.; Vertolasi, V. Chem. Eur. J. 1995, 1, 505.
16. (a) Musakabe, M.; Sato, F. J. Chem. Soc., Chem. Commun. 1986, 989. (b) Mikami, K.; Terada, M.; Nakai, T. Tetrahedron:
Asymmetry 1991, 2, 993. (c) Honda, T.; Hayakawa, T.; Kondo, H.; Okuyama, A.; Subuki, M. T. Chem. Lett. 1991, 1861.
(d) Saba, A. Tetrahedron: Asymmetry 1992, 3, 371. (e) Metz, P.; Schoop, A. Tetrahedron 1993, 49, 10597. (f) Metz, P.;
Schoop, A. Tetrahedron 1995, 51, 9023. (g) Pakulski, Z.; Zamajski, A. Tetrahedron 1995, 51, 871.
17. (a) Casiraghi, G.; Rasu, G. Synthesis 1995, 607. (b) Spanu, P.; Rassu, G.; Ulgheri, F.; Zanardi, F.; Battistini, L.; Casiraghi,
G. Tetrahedron 1996, 52, 4829. (c) Báñez Sanz, J. M.; Maestro Fernández, A.; López Sastre, J. A.; Romero-Avila, M. C.
Synthesis 1998, 1023.
18. (a) Báñez Sanz, J. M.; Galisteo González, D.; López Sastre, J. A.; Molina, J.; Rodríguez Amo, J. F.; Romero-Avila, M. C.;
Sanz Tejedor, M. A. J. Carbohyd. Chem. 1993, 12, 291. (b) Galisteo González, D.; López Sastre, J. A.; Martínez, M. H.;
Rodríguez Amo, J. F.; Sanz Tejedor, M. A. An. Chem. 1994, 90, 221.
19. Arroyo Gómez, Y.; López Sastre, J. L.; Rodríguez Amo, J. F.; Sanz Tejedor, M. A. J. Chem. Soc., Perkin Trans. 1. 1996,
2933.
20. (a) Zinner, H.; Brandhoff, H.; Sohmadke, H.; Kristen, H.; Hann, R. Chem. Ber. 1959, 92, 3151. (b) Gómez, A.; López, M.
Ann. Quím. 1968, 643, 1077.
21. Wong, M. I. H.; Gray, G. R. J. Am. Chem. Soc. 1978, 100, 3548.
22. Raifeld, Y. E.; Nikikenko, A. A.; Arshava, B. M.; Mikerin, J. E.; Zilberg, L. L.; Vid, G. Y.; Lang, S. A.; Lee, V. J.
Tetrahedron 1994, 50, 8603.
23. (a) Mitsuya, H.; Broder, S. Proc. Natl. Acad. Sci. USA. 1986, 83, 1911. (b) Herdewijn, P.; Balzarini, J.; De Clerq, E.;
Pauwels, R.; Baba, M.; Broder, S.; Vanderhaeghe, H. J. Med. Chem. 1987, 30, 1270.
24. (a) Durette, Ph. L.; Horton, D. Advances in Carbohydrate Chemistry and Biochemistry; Tipson, R. S., Ed. Academic Press,
1971; pp. 68–73. (b) Schnarr, G. W.; Vyas, D. M.; Szarek, W. A. J. Chem. Soc., Perkin Trans. 1 1979, 496. (c) Horton,
D.; Wander, J. D. J. Org. Chem. 1974, 39, 1859. (d) Velasco, D.; Castells, J.; López-Calahorra, F.; Jaime, C. J. Org. Chem.
1990, 55, 3526. (e) Rao, S. P.; Grindley, T. B. Carbohyd. Res. 1991, 218, 83.
25. Bernady, K. F.; Floyd, M. B.; Poletto, J. F.; Weiss, M. J. J. Org. Chem. 1979, 44, 1438.
26. The diastereoisomeric alcohols 2 and 3 have the same configuration at sulfur and different at C-1.18a