A highly stereoselective synthesis of D-erythrose derivatives by one-carbon homologation of 2,3-O-isopropylidene-D-glyceraldehyde with (R)-methyl p-tolyl sulfoxide

Article abstract of DOI:10.1016/S0957-4166(00)00005-7

A highly diastereoselective three-step synthesis of 2-O-benzyl-3,4-O-isopropylidene-D-erythrose 9 is described (de >98%; 50% overall yield) starting from D-glyceraldehyde acetonide and (R)-methyl p-tolyl sulfoxide. Treatment of 9 with trifluoroacetic acid

Full text of DOI:10.1016/S0957-4166(00)00005-7

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 11 (2000) 789–796
A highly stereoselective synthesis of D-erythrose derivatives
by one-carbon homologation of 2,3-O-isopropylidene-
D-glyceraldehyde with (R)-methyl p-tolyl sulfoxide
Y. Arroyo-Gómez, J. F. Rodríguez-Amo, M. Santos-García and M. A. Sanz-Tejedor ∗
Departamento de Química Orgánica (E.T.S.I.I.), Universidad de Valladolid, Paseo del Cauce s/n, 47011, Valladolid, Spain
Received 11 November 1999; accepted 31 December 1999
Abstract
A highly diastereoselective three-step synthesis of 2-O-benzyl-3,4-O-isopropylidene-D-erythrose 9 is described
(de >98%; 50% overall yield) starting from D-glyceraldehyde acetonide and (R)-methyl p-tolyl sulfoxide. Treat-
ment of 9 with trifluoroacetic acid gives 2-O-benzyl-D-erythrofuranose. © 2000 Elsevier Science Ltd. All rights
reserved.
1. Introduction
The inherent chirality in monosaccharides and polyhydroxyl compounds makes them valuable starting
materials for the asymmetric synthesis of other more elaborate molecules.1 Amongst these compounds,
optically active tethroses and their derivatives are especially interesting, since they are very useful C-4
building blocks for the synthesis of a large variety of biologically interesting compounds, such as acyclic
fatty acids, metabolites,2 nucleosides,3 and other monosaccharides,3b,4 not to mention many other mole-
cules of biological interest.5 This accounts for the importance of finding new methodologies enabling the
synthesis of erythrose, threose and their derivatives, in high chemical yields and enantiomeric excess, so
that they can be used in total synthesis.
D-Erythrose derivatives have been prepared by transforming naturally occurring chiral compounds,2f,6
enzymatic resolution,7 or asymmetric synthesis.8–12 Outstanding examples of the latter methodology
are: (1) the Sharpless asymmetric epoxidation of C-4 allylic alcohols8 and/or related methods,9 and (2)
the iterative chain elongation of 2,3-O-isopropylidene-D-glyceraldehyde 1 by using Dondoni’s method11
(via thiazole intermediates), or our recently described method using ethyl ethylthiomethyl sulfoxide as
a formyl anion equivalent.12 These methods afford high diastereoselectivities, but all of them require
chromatographic stereoisomer separations in order to obtain enantiomerically pure products.
∗
Corresponding author. E-mail: atejedor@dali.eis.uva.es
0957-4166/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(00)00005-7
tetasy 3228

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2. Results and discussion
In this paper we report an efficient and highly stereoselective synthesis of D-erythrose derivatives by
means of the one-carbon chain elongation of 2,3-O-isopropylidene-D-glyceraldehyde 1 by using readily
available (+)-(R)-methyl p-tolyl sulfoxide 2 as the nucleophilic reagent. The addition of the lithium salt
of sulfoxide 2 to aldehyde 1 gave rise to the corresponding β-hydroxysulfoxide 3, in 70% yield, as the
1
single diastereoisomer (only one diastereoisomer could be detected in the H and 13C NMR spectra of
the crude reaction). The high diastereoselectivity of the process is attributed to the matched asymmetric
induction of both the chiral aldehyde and the nucleophile (Table 1).
Table 1
Addition of sulfoxide 2 to aldehyde 1 and protection of the hydroxyl group of compound 3
The protection of alcohol 3 as the corresponding TBS-ether was not successful. The reaction of 3
with t-butyldimethylsilyl chloride in DMF–imidazole gave rise, after three days at 70°C, to the desired
product 4 in only 15% yield. Alternatively, the employment of a more reactive silylation reagent, such
as trimethylsilyl trifluoromethanesulfonate in Et3N, gave rise to the TMS-ether 5 in 80% yield (Table
1). Pummerer rearrangement of compound 5 using acetic anhydride and sodium acetate yielded the
corresponding S-ketals 6 and 7, epimers at C-1 (Scheme 1). Under these conditions hydrolysis of the TMS
group and further transformation of the intermediate carbinol into its corresponding O-acetyl derivative
took place. Both epimers 6 and 7 are stable compounds which, after desulfurisation with Ra–Ni according
to the method described by Solladié,13 can be transformed into erythritol, bearing differentially protected
hydroxyl groups.
β-Hydroxysulfoxide 3 has also been transformed into its O-benzyl derivative by treatment with
BnBr/NaH/tBu4NI, yielding the benzylic ether 8 in a good yield. Compound 8 was submitted to a
Pummerer rearrangement with Ac2O/NaOAc, and the resulting product was treated with DIBAH in
dichloromethane, at −78°C, to give 2-O-benzyl-3,4-O-isopropylidene-D-erythrose 9 in a 60% yield
(Scheme 2). Alternatively the O-benzyl derivative 8 was submitted to a Pummerer rearrangement with

Y. Arroyo-Gómez et al. / Tetrahedron: Asymmetry 11 (2000) 789–796
791
Scheme 1.
trifluoroacetic anhydride/lutidine combination at 0°C. Subsequent treatment of the Pummerer product
with saturated aqueous sodium hydrogen carbonate14 is enough to afford aldehyde 9 in quantitative
yield (Scheme 2). It should be noted that the Pummerer rearrangement of sulfoxide 6 and subsequent
hydrolysis, following the last procedure, occurs under exceptionally mild conditions. This is an especially
interesting result since it allows the synthesis of D-erythrose derivative 9, with the hydroxyl groups
differently protected, in only three steps from aldehyde 1. The overall yield of 9 starting from 1 is
50%. The configuration of compound 9 could be assigned unequivocally since specific rotation and
spectroscopic data coincide with those described in the literature.11b Hence, this confirmed the R absolute
configuration at C-2 assigned to β-hydroxysulfoxide 3, obtained by reaction of aldehyde 1 with the anion
of 2 (Table 1).
Scheme 2.
Aldehyde 9 was treated with trifluoroacetic acid,15 to give the corresponding 2-O-benzyl-D-
erythrofuranose 10, as a mixture of α and β anomers. Configurations of both anomers have been
established from Demuynck’s results5b,16 for analogous derivatives; the C-1 signal of the β anomer
resonates downfield of the C-1 signal of its anomeric partner α anomer (Scheme 2). Compound 10 is a
versatile four-carbon unit which has been used for the synthesis of both enantiomers of epi-muricatacin.17
In summary, 2-O-benzyl-3,4-O-isopropylidene-D-erythrose 9 has been prepared from 2,3-O-
isopropylidene-D-glyceraldehyde and (R)-methyl p-tolyl sulfoxide by a three-step procedure with a high
diastereoselectivity (>98%) and in 50% overall yield. The aldehyde group was obtained directly from

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Y. Arroyo-Gómez et al. / Tetrahedron: Asymmetry 11 (2000) 789–796
the Pummerer reaction after work-up with saturated aqueous solution of NaHCO3. Acetonide hydrolysis
of 9 with TFA gave 2-O-benzyl-D-erythrofuranose 10. Following a parallel chemistry, L-erythrose
derivatives could be obtained from L-glyceraldehyde and (S)-methyl p-tolyl sulfoxide.
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; CF3SO3SiMe3 was distilled at reduced
pressure. NaH (60% mineral oil) was activated by repeated treatments with hexane, and further removal
of the residual solvent at reduced pressure. All reaction vessels were flame-dried and flushed with
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.
Silica gel Merck 60 (230–400 mesh) was used 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 (300 MHz, CDCl3) and 13C NMR (80 MHz, CDCl3) spectra were performed with a Bruker
AC-300 spectrometer. Chemical shifts are given 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
1
in hertz. Diastereoisomeric ratios were determined by integration of well-separated signals of the H
NMR spectra. IR spectra were measured by using a Nicolet FTIR-20-SX spectrometer. Mass spectra were
recorded by the direct insertion technique by electronic impact (EI), by 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 synthesised from 1,2:5,6-di-O-isopropylidene-D-
mannitol by oxidation with sodium periodate.18 (S)-Menthyl p-toluenesulfinate and (R)-methyl p-tolyl
sulfoxide 2 were prepared as described previously.19,20
3.2. Addition of (R)-(+)-methyl p-tolyl sulfoxide 2 to 2,3-O-isopropylidene-D-glyceraldehyde 1
A solution of sulfoxide 2 (1 g, 6.5 mmol) in THF (25 ml) was slowly added to a solution of LDA21 (6.5
mmol) in THF (19 ml) at −78°C and the resulting mixture was stirred for 1 h. Then, a solution of aldehyde
1 (840 mg, 6.5 mmol) in THF (25 ml) was slowly added at the same temperature, the reaction mixture
was stirred for an additional hour and was allowed to reach room temperature (about 2 h). The reaction
mixture was quenched with saturated NH4Cl aqueous solution and extracted with dichloromethane (3×20
ml). The combined organic layers were dried (Na2SO4), the solvent was removed under reduced pressure,
and the residue was purified by flash chromatography (hexane:ethyl acetate, 3:2) to give compound 3
(1.27 g, 4.55 mmol, 70%) as a white solid.

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793
3.2.1. S(R)-1-Deoxy-1-(p-tolylsulfinyl)-3,4-O-isopropylidene-D-erythritol 3
Mp 66–68°C (hexane:Et2O); Rf=0.47 (hexane:AcOEt, 9:1); [α]D20=+162.0 (c 0.5, CHCl3); 1H NMR
δ 1.31 and 1.41 (2 s, each 3H, C(CH3)2), 2.43 (s, 3H, CH3-Ar), 2.90 (dd, 1H, J1,2 9.9, Jgem 13.2, H-C1),
3.10 (dd, 1H, J1 ,2 1.4, Jgem 13.2, H0-C1), 3.90 (ddd, 1H, J3,2 7.6, J3,4 5.0, J3,4 6.5, H-C3), 4.02 (dd,
0
0
1H, J4,3 5.0, Jgem 8.7, H-C4), 4.12 (dd, 1H, J4 ,3 6.5, Jgem 8.7, H0-C4), 4.15 (d, 1H, JOH,2 2.9, OH-C2),
0
4.23 (dddd, 1H, J2,1 9.9, J2,1 1.4, J2,OH 2.9, J2,3 7.6, H-C2), 7.35 and 7.56 (AA0BB0 system, 4H, C6H4);
0
13C NMR δ 21.4 (CH3-Ar), 25.1 and 26.7 (C(CH3)2), 59.0 (C-1), 66.8 (C-4), 71.0 and 77.7 (C-2, C-3),
109.7 (C(CH3)2), 123.9 and 130.2 (CH-arom.), 140.4 and 142.2 (C-arom.); IR (KBr, liquid film): 3500,
3000, 1600, 1500, 1465, 1420, 1390, 1375, 1250, 1215, 1155, 1070, 845, 815, 730 cm−1; MS (m/e)
+
(relative intensity): 284 (0.1, M+), 269 (5, M+−CH3), 139 (72, C7H7OS+), 127 (50, C7H11O2 ), 101 (46,
+
+
+
C5H9O2 ), 91 (29, C7H7 ), 73 (26, C3H5O2 ), 43 (100, C2H3O+). Anal. calcd for C14H20O4S: C, 59.13;
H, 7.09. Found: C, 59.26; H, 7.06.
3.3. S(R)-1-Deoxy-1-(p-tolylsulfinyl)-2-O-(t-butyldimethylsilyl)-3,4-O-isopropylidene-D-erythritol 4
To a solution of alcohol 3 (100 mg, 0.35 mmol) in DMF (0.2 ml), imidazole (47 mg, 0.70 mmol) and
t-BuMe2SiCl11b (106 mg, 0.70 mmol) were added. The solution was stirred for 36 h at 70°C, cooled to rt,
poured into water (15 ml), and extracted with ether (2×5 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, 3:1) to give compound 4 (20 mg, 0.052 mmol, 15%) as a colourless oil.
1
Rf=0.11 (hexane:Et2O, 3:1); [α]D20=+111.3 (c 0.2, CHCl3); H NMR δ 0.11 and 0.12 (2 s, each 3H,
(CH3)2Si-), 0.90 (s, 9H, (CH3)3CSi-), 1.34 and 1.36 (2 s, each 3H, C(CH3)2), 2.41 (s, 3H, CH3-Ar), 2.90
(dd, 1H, J1,2 6.6, Jgem 13.5, H-C1), 3.13 (dd, 1H, J1 ,2 3.5, Jgem 13.5, H0-C1), 3.87 (dd, 1H, J4,3 5.4, Jgem
0
8.4, H-C4), 4.00 (ddd, 1H, J2,1 6.6, J2,1 3.5, J2,3 6.7, H-C2), 4.05 (0dd, 1H, J4 ,3 6.4, Jgem 8.4, H0-C4), 4.31
0
0
(ddd, 1H, J3,2 6.7, J3,4 5.4, J3,4 6.4, H-C3), 7.32 and 7.54 (AA BB system, 4H, C6H4); 13C NMR δ −4.0
and −4.6 ((CH3)2Si-), 18.0 ((CH3)3CSi-), 21.4 (CH3-Ar), 25.2 and 26.6 (C(CH3)2), 25.7 ((CH3)3CSi-),
63.5 and 66.4 (C-1, C-4), 69.1 and 78.0 (C-2, C-3), 109.5 (C(CH3)2), 124.2 and 130.0 (CH-arom.), 141.5
and 141.6 (C-arom.).
0
0
3.4. S(R)-1-Deoxy-1-(p-tolylsulfinyl)-2-O-(trimethylsilyl)-3,4-O-isopropylidene-D-erythritol 5
To a solution of alcohol 3 (100 mg, 0.35 mmol) in CH2Cl2 (2 ml), triethylamine (0.085 ml, 0.61
mmol) and trimethylsilyl trifluoromethanesulfonate22 (0.1 ml, 0.54 mmol) were added. The solution was
stirred at 0°C for 30 min, poured into ice, and extracted with ether (2×5 ml). The combined ethereal
layers were dried over Na2SO4, the solvent was removed under reduced pressure, and the residue was
purified by column chromatography (CH2Cl2:acetone, 10:1) to give compound 5 (100 mg, 0.28 mmol,
80%) as a white solid. Mp 77–79°C (hexane:Et2O); Rf=0.80 (CH2Cl2:acetone, 10:1); [α]D20=+109.9 (c
1
1.0, CHCl3); H NMR δ 0.14 (s, 9H, (CH3)3Si-), 1.32 and 1.36 (2 s, each 3H, C(CH3)2), 2.41 (s, 3H,
CH3-Ar), 2.97 (dd, 1H, J1,2 5.8, Jgem 13.6, H-C1), 3.12 (dd, 1H, J1 ,2 4.5, Jgem 13.6, H0-C1), 3.83 (dd,
0
0
0
1H, J4,3 5.2, Jgem 8.5, H-C4), 3.95 (ddd, 1H, J2,1 5.8, J2,1 4.5, J2,3 11.3, H-C2), 4.03 (dd, 1H, J4 ,3 6.3,
Jgem 8.5, H0-C4), 4.21 (ddd, 1H, J3,2 11.3, J3,4 5.2, J3,4 6.3, H-C3), 7.30 and 7.54 (AA0BB0 system, 4H,
0
C6H4); 13C NMR δ 0.0 ((CH3)3Si-), 21.0 (CH3-Ar), 25.8 and 26.2 (C(CH3)2), 62.6 and 65.9 (C-1, C-4),
68.5 and 77.7 (C-2, C-3), 109.3 (C(CH3)2), 123.9 and 129.6 (CH-arom.), 141.1 and 141.2 (C-arom.); IR
(KBr, liquid film): 2953, 1600, 1500, 1465, 1420, 1357, 1211, 1150, 1075, 1025, 958, 891, 845, 805, 710
cm−1; MS (m/e) (relative intensity): 341 (7, M+−[O]), 139 (46, C7H7OS+), 127 (100, C7H11O2 ), 101
+
(94, C5H9O2 ), 91 (29, C7H7 ), 73 (71, C3H9Si+), 43 (71, C2H3O+).
+
+

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3.5. S(R)-1-Deoxy-1-(p-tolylsulfinyl)-2-O-(benzyl)-3,4-O-isopropylidene-D-erythritol 8
To a solution of compound 3 (500 mg, 1.76 mmol) in THF (40 ml), a suspension of NaH (46 mg,
1.94 mmol) in THF was added at rt. The mixture was stirred at reflux for 30 min, cooled at rt, and then
tBu4NI (65 mg, 0.01 mmol) and benzyl bromide11b (0.21 ml, 1.76 mmol) were successively added. The
solution was stirred for 20 h at rt, the solvent was removed under reduced pressure, and the residue was
treated with saturated aqueous NaHCO3 (20 ml) and extracted with CH2Cl2 (2×10 ml). The combined
organic extracts were dried (Na2SO4), the solvent was removed under reduced pressure, and the residue
was purified by flash chromatography (hexane:Ac2OEt, 2:1) to yield 8 (461 mg, 1.23 mmol, 70%) as a
colourless oil. Rf=0.67 (hexane:Ac2OEt, 9:1); [α]D20=+89.8 (c 1.0, CHCl3); 1H NMR δ 1.33 and 1.38 (2
0
s, each 3H, C(CH3)2), 2.40 (s, 3H, CH3-Ar), 3.10 (dd, 1H, J1,2 4.8, Jgem 13.8, H-C1), 3.19 (dd, 1H, J1 ,2
5.5, Jgem 13.8, H0-C1), 3.73 (ddd, 1H, J2,1 4.8, J2,1 5.5, J2,3 6.2, H-C2), 3.82 (dd, 1H, J4,3 5.3, Jgem 8.6,
0
H-C4), 4.05 (dd, 1H, J4 ,3 6.6, Jgem 8.6, H0-C4), 4.24 (ddd, 1H, J3,2 6.2, J3,4 5.3, J3,4 6.6, H-C3), 4.53 and
4.56 (AB system, 2H, J 11.5, PhCH2), 7.24–7.34 (m, 5H, C6H5), 7.33 and 7.49 (AA0BB0 system, 4H,
C6H4); 13C NMR δ 21.42 (CH3-Ar), 25.0 and 26.5 (C(CH3)2), 59.8 (C-1), 66.3 (C-4), 74.2 (PhCH2),
75.6 and 77.0 (C-2, C-3), 109.8 (C(CH3)2), 124.3 and 130.0 (CH-arom.), 127.7, 127.9 and 128.4 (C6H5),
137.4 (CPh-CH2), 140.7 and 140.8 (C-arom.); IR (KBr, liquid film): 2925, 1618, 1460, 1385, 1250,
1050, 845, 750 cm−1; MS (m/e) (relative intensity): 359 (4%, M+−Me), 139 (13, C7H7OS+), 127 (32,
0
0
+
+
+
C7H11O2 ), 101 (21, C5H9O2 ), 91 (100, C7H7 ), 43 (30, C2H3O+). Anal. calcd for C21H26O4S: C,
67.35; H, 7.00. Found: C, 67.41; H, 6.96.
3.6. Pummerer-type rearrangement of compound 5, with NaAcO/Ac2O13a,b
To a solution of compound 5 (107 mg, 0.30 mmol) in Ac2O (3 ml), NaOAc (28 mg, 0.35 mmol) was
added. The solution was refluxed for 2.5 h, cooled at rt, diluted with benzene (7 ml), and filtered through
a Celite pad. The solvent was removed under reduced pressure and the residue was purified by flash
chromatography (hexane:AcOEt, 6:1) affording pure 6 (24 mg, 0.07 mmol, 19%) and 7 (33 mg, 0.09
mmol, 26%) as colourless oils.
3.6.1. 1,2-Di-O-acetyl-1-(p-tolylthio)-3,4-O-isopropylidene-D-erythritol
1
Minor epimer 6. Rf=0.85 (hexane:AcOEt, 6:1); [α]D20=+29.8 (c 0.3, CHCl3); H NMR δ 1.37 and
1.43 (2 s, each 3H, C(CH3)2), 2.04 and 2.08 (2 s, each 3H, OCOCH3), 2.33 (s, 3H, CH3-Ar), 3.87 (dd,
1H, J4,3 5.5, Jgem 8.6, H-C4), 4.07 (dd, 1H, J4 ,3 6.4, Jgem 8.6, H0-C4), 4.44 (ddd, 1H, J3,2 7.6,=J3,4 6.4, J3,4
5.5, H-C3), 5.32 (dd, 1H, J2,1 3.1, J2,3 6.4, H-C2), 6.31 (d, 1H, J1,2 3.1, H-C1), 7.12 and 7.37 (AA0BB0
system, 4H, C6H4); 13C NMR δ 20.8 and 20.9 (OCOCH3), 21.2 (CH3-Ar), 25.3 and 26.5 (C(CH3)2),
66.8 (C-4), 73.4, 74.1 and 81.5 (C-1, C-2, C-3), 109.8 (C(CH3)2), 129.9 and 133.4 (CH-arom.), 138.7
and 139.4 (C-arom.); IR (KBr, liquid film): 3000, 2950, 1750, 1600, 1500, 1495, 1365, 1210, 950, 805
cm−1; MS (m/e) (relative intensity): 368 (2, M+), 245 (4), 187 (7), 124 (40), 85 (15), 43 (100, C2H3O+).
Major epimer 7. Rf=0.68 (hexane:AcOEt, 6:1); [α]D20=−15.4 (c 0.3, CHCl3); 1H NMR δ 1.30 and 1.31
(2 s, each 3H, C(CH3)2), 2.09 and 2.10 (2 s, each 3H, OCOCH3), 2.34 (s, 3H, CH3-Ar), 3.89 (dd, 1H,
0
0
J4,3 6.1, Jgem 8.4, H-C4), 4.06 (dd, 1H, J4 ,3 6.3, Jgem 8.4, H0-C4), 4.27 (ddd, 1H, J3,2 5.6, J3,4 6.1, J3,4
0
0
6.3, H-C3), 5.39 (dd, 1H, J2,1 4.4, J2,3 5.6, H-C2), 6.11 (d, 1H, J1,2 4.4, H-C1), 7.14 and 7.42 (AA0BB0
system, 4H, C6H4); 13C NMR δ 20.7 and 20.9 (OCOCH3), 21.2 (CH3-Ar), 25.3 and 26.4 (C(CH3)2),
65.3 (C-4), 72.8, 74.2 and 79.3 (C-1, C-2, C-3), 109.5 (C(CH3)2), 127.1 and 130.0 (CH-arom.), 134.4
and 139.1 (C-arom.); IR (KBr, liquid film): 3000, 2950, 1750, 1600, 1500, 1495, 1365, 1210, 950, 805

Y. Arroyo-Gómez et al. / Tetrahedron: Asymmetry 11 (2000) 789–796
795
+
cm−1; MS (m/e) (relative intensity): 368 (1, M+), 245 (3, C11H17O6 ), 187 (4), 124 (24), 85 (15), 43
(100, C2H3O+). HRMS calcd for C18H24O6S: 368.1294; found: 368.1295.
3.7. 2-O-Benzyl-3,4-O-isopropylidene-D-erythrose 9
3.7.1. Method A13a,b
To a solution of compound 8 (47 mg, 0.13 mmol) in Ac2O (1.5 ml), NaOAc (12 mg, 0.15 mmol)
was added. The solution was refluxed for 2.5 h, cooled at rt, diluted with benzene (4 ml), and filtered
through a Celite pad. The solvent was removed under reduced pressure. The residue was diluted with
dry CH2Cl2 (10 ml) and treated with DIBAH (0.28 ml, 0.28 mmol, 1 M in dichloromethane) at −78°C.
The mixture was stirred for 30 min, then saturated aqueous sodium tartrate (0.5 ml) was added, and
the reaction mixture was allowed to reach room temperature. The organic layer was dried (MgSO4), the
solvent was removed under reduced pressure, and the residue was purified by TLC (hexane:Et2O, 1:2)
affording pure 9 (20 mg, 0.08 mmol, 60%), as a colourless oil. Rf=0.40 (hexane:Et2O, 1:2); [α]D20=+28.7
(c 1.2, CHCl3). Spectroscopic data of 9 coincide with those reported previously:11b 1H NMR δ 1.34 and
1.43 (2 s, 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, J3,2 6.1, J3,4 5.5, J3,4’ 6.3, H-C3), 4.71 and
0
4.59 (AB system, 2H, Jgem 11.6, PhCH2), 7.35 (m, 5H, C6H5), 9.70 (d, 1H, J1,2 2.0, H-C1).
3.7.2. Method B14
To a solution of compound 8 (73 mg, 0.19 mmol), at 0°C, in CH3CN (0.5 ml), 2,6-lutidine (0.05 ml,
0.42 mmol) and trifluoroacetic anhydride (0.055 ml, 0.39 mmol) in CH3CN (0.35 ml) were added. The
mixture was stirred at rt for 3 h, treated with saturated aqueous NaHCO3 (1 ml), and extracted with
AcOEt (3×0.5 ml). The organic layer was dried (Na2SO4) and the solvent was removed under reduced
pressure, to give aldehyde 9 (47 mg, 0.19 mmol, quantitative yield) as a colourless oil.
3.8. 2-O-Benzyl-D-erythrofuranose10
To a solution of compound 9 (100 mg, 0.31 mmol) in CH3CN (1 ml), trifluoroacetic acid (0.02 ml,
0.31 mmol) was added at rt. The mixture was stirred for 90 min, treated with saturated aqueous NaHCO3
(2 ml), and extracted with AcOEt (3×1 ml). The organic layer was dried (Na2SO4) and the solvent was
removed under reduced pressure, to give compound 10 (58 mg, 0.28 mmol, 89%) as a 63:37 mixture
1
of α,β anomers. β Anomer: Rf=0.24 (hexane:Et2O, 1:2); H NMR δ 3.85 (dd, 1H, J4,3 3.2, Jgem 9.8,
H-C4), 3.88 (dd, 1H, J2,1 2.1, J2,3 5.2, H-C2), 4.14 (dd, 1H, J4 ,3 4.6, Jgem 9.8, H0-C4), 4.38 (ddd, 1H,
0
0
J3,2 5.2, J3,4 3.2, J3,4 4.6, H-C3), 4.66 and 4.76 (AB system, 2H, Jgem 11.6, PhCH2), 5.42 (d, 1H, J1,2
2.1, H-C1), 7.20–7.50 (m, 5H, C6H5); 13C NMR δ 70.3 (C-3), 72.9 (PhCH2 and C-4), 83.6 (C-2), 100.4
(C-1), 128.0, 128.4 and 128.6 (CH-arom.), 136.8 (C-arom.). α Anomer: Rf=0.24 (hexane:Et2O, 1:2); 1H
0
NMR δ 3.81 (dd, 1H, J1,2 4.3, J2,3 4.5, H-C2), 3.95 (dd, 1H, J4,3 4.6, Jgem 10.0, H-C4), 4.05 (dd, 1H, J4 ,3
1.5, Jgem 10.0, H0-C4), 4.26 (ddd, 1H, J3,2 4.5, J3,4 1.5, J3,4 4.6, H-C3), 4.63 and 4.66 (AB system, 2H,
0
Jgem 11.5, PhCH2), 5.28 (d, 1H, J1,2 4.3, H-C1), 7.20–7.50 (m, 5H, C6H5); 13C NMR δ 69.6 (C-3), 72.1
and 72.6 (PhCH2 and C-4), 78.2 (C-2), 95.2 (C-1), 128.0, 128.2, and 128.7 (CH-arom.), 136.8 (C-arom.).
MS (m/e, CI) (relative intensity): 211 (100, M++1), 193 (57, M++1−H2O), 137 (91, C9H12O+), 119 (7,
+
M+−Bn), 103 (28, M+−OBn), 91 (2, C7H7 ).

796
Y. Arroyo-Gómez et al. / Tetrahedron: Asymmetry 11 (2000) 789–796
Acknowledgements
We thank Junta de Castilla y León for financial support and Ana Ma Martín Castro for the English
translation.
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