Syntheses of L-threose and D-erythrose analogues modified at position 2

Article abstract of DOI:10.1016/S0957-4166(98)00126-8

2-O-Methyl-D-erythrose, 2-O-methyl-L-threose, 2-deoxy-D- and L- erythrose, and the corresponding acetonides have been prepared from the commercially available D-isoascorbic and L-ascorbic acids. The proportion of cyclic (α and β furanoses) and acyclic (aldehyde and hydrate) forms was determined in aqueous (D₂O) solution by ¹H and ¹³C NMR spectroscopy.

Full text of DOI:10.1016/S0957-4166(98)00126-8

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 9 (1998) 1359–1367
Syntheses of L-threose and D-erythrose analogues modified at
position 2
Corinne André, Jean Bolte and Colette Demuynck ∗
Université Blaise-Pascal, Département de Chimie (UMR 6504 — SEESIB), 63177 Aubière Cédex, France
Received 22 January 1998; accepted 25 March 1998
Abstract
2-O-Methyl-D-erythrose, 2-O-methyl-L-threose, 2-deoxy-D- and L-erythrose, and the corresponding acetonides
have been prepared from the commercially available D-isoascorbic and L-ascorbic acids. The proportion of cyclic
(α and β furanoses) and acyclic (aldehyde and hydrate) forms was determined in aqueous (D2O) solution by 1H
and 13C NMR spectroscopy. © 1998 Elsevier Science Ltd. All rights reserved.
1. Introduction
Monosaccharides are the chemical units from which all members of the major family of natural
products, the carbohydrates, are built. Among monosaccharides, tetroses constitute probably the most
poorly characterized group. All of the oldest synthetic procedures involve degradation of an appropriate
sugar1a or sugar derivative.1b,c Among the modern methods2a from a non-carbohydrate source, we can
note the preparation of L- and D-erythrose acetonides using: (1) microbial metabolites as homochiral
starting materials;2b (2) D-glyceraldehyde acetonide and an iterative process with the highly stereoselec-
tive thiazole addition;3a,b (3) the Sharpless asymmetric epoxidation3c of allylic alcohols, a now common
method used in the construction of sugars.
We focused on the syntheses of substituted butanals, potential substrates of two enzymes, transketolase
and fructose-1,6-bisphosphate aldolase (FB-aldolase). These enzymes are interesting and complementary
tools for the enzymatic syntheses of monosaccharide analogues by C–C bond forming reactions.4 Our
aim was to synthesize L-threose and D-erythrose analogues, because these compounds are able to lead
to close analogues of D-fructose and L-sorbose by transketolase catalysis or to new heptuloses of the D
or L series using FB-aldolase. The results concerning this enzymatic study have already been published5
and, in this paper, we will describe the syntheses of 2-deoxy-D- and L-erythrose 2a and 2b, 2-O-methyl-
D-erythrose 1a and 2-O-methyl-L-threose 1b derivatives and the corresponding acetonides. Compounds
∗
Corresponding author. E-mail: demuynck@chisgl.univ-bpclermont.fr
0957-4166/98/$19.00 © 1998 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(98)00126-8

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1a and 1b have not been described before; 2a and 2b have been synthesized before from 3-deoxy-D-
erythropentose6 and from L-malic acid7 respectively.
We present here the synthesis of 1a and 1b starting with inexpensive D-isoascorbic and L-ascorbic
acids. These two acids have been used before, especially by Abushanab8 and Depezay9 to obtain two
butanetriol enantiomers. For the deoxy compound 2a and 2b, we first tried the method from L-malic acid7
but the material obtained in this manner is contaminated by (2S)-2,4-dihydroxybutanal and is difficult
to purify. We then developed another method starting with the chiral (S)-2,2-dimethyl-1,3-dioxolane-
4-methanol ((S)-solketal) for the obtention of the D isomer 2a. Finally, as the synthesis of 1a and 1b
from L-ascorbic and D-isoascorbic acids offers a possible access to both enantiomers of 2, we decided
to explore this path also. In the last part of this study, the proportion of cyclic (α and β furanoses) and
acyclic (aldehyde and hydrate) forms of 1a, 1b, 2a and 2b were determined in aqueous (D2O) solution
by 1H and 13C NMR spectroscopy.
2. Results and discussion
The commercially available D-isoascorbic and L-ascorbic acids were converted, in two steps ac-
cording to the strategy of Abushanab et al.,8 into two intermediary synthons containing two stere-
ogenic centers, ethyl (2R,3R)-3,4-O-isopropylidene-2,3,4-trihydroxybutanoate 3a and ethyl (2R,3S)-
3,4-O-isopropylidene-2,3,4-trihydroxybutanoate 3b in excellent yields (Scheme 1). In the first step, the
starting acid was converted into the acetonide. Cleavage of the double bond with aqueous hydrogen
peroxide followed by esterification with ethyl iodide gave the two intermediary esters 3a and 3b.
Compound 3a will lead to (S)-3,4-dihydroxybutanal 2a and (2R,3R)-2-O-methyl-3,4-dihydroxybutanal
1a (2-deoxy-D-erythrose and 2-O-methyl-D-erythrose) and, by the same reactions, 3b will lead to (R)-
3,4-dihydroxybutanal 2b and (2R,3S)-2-O-methyl-3,4-dihydroxybutanal 1b (2-deoxy-L-erythrose and 2-
O-methyl-L-threose) and the corresponding acetonides.
2.1. Syntheses of 2-O-methyl-D-erythrose 1a and 2-O-methyl-L-threose 1b and the corresponding
acetonides 5a and 5b
Among the numerous procedures of alkylation of hydroxyl groups described in the literature, it appears
that the methylation using methyl iodide and silver oxide10 is the most efficient for substrates possessing
a lactone or an ester group. In the process described here, the hydroxyester and the alkyl iodide were
simply dissolved in dry acetonitrile. Powdered silver oxide was added to this mixture and stirred at
reflux overnight. Silver salts were eliminated by filtration and the methoxyester acetonide was isolated
in a pure form by evaporation of the solvent. No racemization on carbon 2 was observed during this
step. Ethyl (2R,3R)-2-O-methyl-3,4-O-isopropylidene-3,4-dihydroxybutanoate 4a and ethyl (2R,3S)-2-
O-methyl-3,4-O-isopropylidene-3,4-dihydroxybutanoate 4b were obtained in 95% and 97% yield.
To obtain the desired aldehydes, the general procedure adopted was to add the organic compound to
1:5 equiv. of DIBAH, both in toluene at −78°C. We chose a commercial toluene solution which is more
stable than the usual THF or hexane solution.11 The reduction of each of the two ester diastereomers by
DIBAH under these experimental conditions provided the corresponding aldehydes in high yields, 95%
for the 2-O-methyl-D-erythrose acetonide 5a and 97% for the 2-O-methyl-L-threose acetonide 5b.
Deprotection of the acetonide group with an acid resin in aqueous solution permitted 2-O-methyl-
D-erythrose 1a and 2-O-methyl-L-threose 1b to be obtained. Free aldehydes were not isolated and the
solution was used directly for enzymatic assays and for NMR studies. So, the development of this simple

C. André et al. / Tetrahedron: Asymmetry 9 (1998) 1359–1367
1361
Scheme 1. (a) (i) CuSO4, dry acetone. (ii) H2O2, K2CO3, H2O, 20°C then EtI, refluxing CH3CN. (b) MeI, HgO2, CH3CN. (c)
DIBAL-H, toluene. (d) Resin H+, H2O. (e) TsCl, Et3N, DMAP, CH2Cl2. (f) LiCl, DMF. (g) Pd/C (10%), Et3N, MeOH
asymmetric synthetic route using D-isoascorbic and L-ascorbic acids as starting materials has allowed us
to isolate two enantiomerically pure aldehydes of the desired configuration.
2.2. Syntheses of 2-deoxy-D-and L-erythrose 2a and 2b and the corresponding acetonides 7a and 7b
2.2.1. From D-isoascorbic and L-ascorbic acids
In this procedure,12 the hydroxyesters 3a and 3b were respectively converted into the crystalline
tosylates by treatment with p-toluenesulfonyl chloride in pyridine. The tosylate, when heated at 85°C
with lithium chloride in dimethylformamide, gave a mixture of erythro and threo chloroesters. The
diastereomeric mixture was subjected, without separation, to hydrogenolysis with 10% palladium on
carbon in the presence of triethylamine. The ester, thus obtained in excellent yield, was reduced with
DIBAH in toluene as described before for the methoxy esters to afford the aldehyde alone.
Following this sequence of reactions, D-isoascorbic acid was converted into the 2-deoxy-D-erythrose
acetonide 7a in an overall yield of 31% and L-ascorbic acid was converted into the 2-deoxy-L-erythrose
acetonide 7b in an overall yield of 62%.
The two free aldehyde enantiomers, 2-deoxy-D- and L-erythrose, 2a and 2b, have been obtained in
aqueous solution by hydrolysis in the presence of acid resin (DOWEX WX8).
2.2.2. From C3 synthon (S)-solketal
This method consists of the synthesis of a chiral dithiane, 2-[(2S)-2,3-O-isopropylidene-2,3-
dihydroxypropyl]-1,3-dithiane 9. This compound was already synthesized from L-malic acid by Mori et
al.13 and used as a chiral synthon in various polyol syntheses. We thought that it could be more easily
prepared from the commercially available (S)-solketal. The aldehyde group can be introduced by use of
the cyclic 2-lithio-1,3-dithiane which acts as a formyl anion equivalent (Scheme 2).

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C. André et al. / Tetrahedron: Asymmetry 9 (1998) 1359–1367
Scheme 2. (a) TsCl, Et3N, CHCl3, 85%. (b) NaI, methylethylketone, 75%. (c) 2-TMS-1,3-dithiane, n-BuLi, THF, 84%. (d)
TBAF, THF, 67%. (e) CH3I, acetone, 71%. (f) Resin H+, H2O
The (S)-solketal was first converted into the known (S)-tosylate14 with tosyl chloride in triethylamine
in 85% yield. The corresponding iodide was then obtained from tosylate by treatment with sodium
iodide in acetone15 in 75% yield. The iodide was transformed into the 1,3-dithiane via a trimethylsilyl
compound:16 the coupling of a trimethylsilyl-1,3-lithiodithiane at −25°C for 2 h with iodide gave the
adduct 8 in 84% yield. The trimethylsilyl group was then eliminated by action of tetrabutylammonium
fluoride in THF. The thioacetal was converted into the parent aldehyde by reaction with methyl iodide in
moist acetone under reflux with a 71% yield. Thus, 2-deoxy-D-erythrose acetonide 7a has been prepared
from (S)-solketal by a five step procedure in 25% overall yield. The hydrolysis of the 2-deoxy-D-erythrose
acetonide 7a in the presence of an acid resin in aqueous solution gave the corresponding free aldehyde,
the 2-deoxy-D-erythrose 2a.
3. Conformational study
L-Threose and D-erythrose analogues and their corresponding acetonides prepared following the
previous procedures were assayed as substrates for transketolase5 and FB-aldolase. Even though the
activities of FB-aldolase towards the substrates were high enough to allow the synthesis of rare heptulose-
1-phosphates of D and L series, all substrates present high Km values and suffer from low reactivity and
we did not succeed in carrying out TK catalyzed syntheses. The hindrance of the dioxolane ring could
explain the low reactivity of the acetonides. The case of unprotected substrates 1 and 2 is different. These
compounds are capable of existing in aqueous solution in several forms in equilibrium: free aldehyde,
hydrated aldehyde, and two hemiacetal anomers. Since TK reaction needs an aldehyde to be realized,
it has seemed necessary to us to measure the percentage of cyclic and acyclic forms present in aqueous
solution in the cases of 2-deoxy-D- and L-erythrose and for 2-O-methyl-D-erythrose and 2-O-methyl-L-
threose. Such a study has already been done by Seriani et al. for 2-deoxy-D-erythrose.6
The proportion of cyclic (α and β furanoses) and acyclic (aldehyde and hydrate) forms were deter-
1
mined by H and 13C NMR spectroscopy. The chemical shifts of the deoxy and methoxy substituted
furanoses in D2O at 25°C are given in Table 1.
For the 2-deoxy-D- and L-erythrose, in the cyclic form, the β-configuration was attributed to the
major tautomer on the basis of the results of Seriani. Our results are in agreement with his study. For
the methoxy compounds, the α/β configuration was attributed by noting that, in all aldofuranose rings
studied to date,6 the C-1 signal of the anomer having O-1 and O-2 trans (β form) resonates downfield of
the C-1 signal of its anomeric partner having O-1 and O-2 cis (α form).
1
One notices that according to H and 13C NMR spectra the free aldehyde form is undetectable. The
percentages of each form present in aqueous solution have been calculated by quantitative 13C NMR
spectroscopy in D2O at 25°C and are given in Table 2, together with literature data for D-erythrose and
threose.

C. André et al. / Tetrahedron: Asymmetry 9 (1998) 1359–1367
1363
Table 1
1 H and 13C NMR shifts of 2-deoxy-D- and L-erythrose 2a and 2b, 2-O-methyl-D-erythrose 1a and
2-O-methyl-L-threose 1b in D2O at 25°C
Table 2
Behavior of 2-deoxy-D- and L-erythrose 2a and 2b, 2-O-methyl-D-erythrose 1a and 2-O-methyl-L-
threose 1b in aqueous (D2O) solution
For erythrose derivatives, the β form predominates and the presence of a substituent in position 2
decreases the proportion of the acyclic form which becomes undetectable for 2-methoxy compounds.
This phenomenon of cyclisation, in aqueous solution, of the tetroses synthesized, could explain their
poor activities towards transketolase since the concentrations of the actual substrates (free aldehydic
form) is small, very inferior to the Km values, so that the reactions rates are low. The case of natural
substrates like ribose-5-phosphate, which also exists mainly in a hemiacetal form, is probably different
as the open form could be specifically stabilized in the active site of the enzyme.
In summary, the enantiomerically pure 2-O-methyl-L-threose and 2-O-methyl-D-erythrose and the

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C. André et al. / Tetrahedron: Asymmetry 9 (1998) 1359–1367
corresponding acetonides were, for the first time, efficiently synthesized from commercially available
D-isoascorbic and its C5 epimer, L-ascorbic acid. Both enantiomers of 3,4-dihydroxybutanal were
also obtained from the same acids as well as the 3S enantiomer from enantiomerically pure solketal.
These four enantiomerically pure tetrose analogues are interesting synthons for enzymatic or chemical
syntheses. In addition, the NMR study has shown that, in the aldofuranose system, 2-O-methylation
greatly enhances the proportion of the cyclic hemiacetal forms in aqueous solution.
4. Experimental
4.1. General
1H and 13C NMR spectra were generally obtained in CDCl3 at 100 and 400 MHz, respectively, on an
AC400 Brucker spectrometer. Chemical shifts are expressed in ppm from tetramethylsilane (using as a
reference residual CHCl3). Optical rotations were measured on a Perkin–Elmer 141 spectropolarimeter.
Mass spectra were performed on a VGMM 305 spectrometer. We did not observe, for all compounds
synthesized owning an acetonide group, the molecular ion (M+). The values obtained for these componds
corresponded to the immediate fragmentation of a methyl group and so we will give (M−CH3) values.
For flash chromatography, silica gel GEDURAN SI 60 (0.040–0.063 mm, Merck) was employed while
TLC analyses were performed on silica gel plates (Kieselgel 60 PF).
4.2. Ethyl (2R,3R)-3,4-O-isopropylidene-2,3,4-trihydroxybutanoate 3a
A mechanically stirred suspension of 50 g (284 mmol) of D-isoascorbic acid in acetone (250 ml)
was treated with 90 g of anhydrous CuSO4. After the reaction was stirred at room temperature for
24 h, a second 90 g portion of CuSO4 was added, and stirring was continued for an additional 24
h. The reaction mixture was then filtered and concentrated, giving a near-quantitative yield of 3,4-O-
isopropylidene-D-isoascorbic acid. The isopropylidene derivative was then dissolved in water (300 ml)
containing 100 g of K2CO3. This solution was chilled in an ice bath and stirred while 30% H2O2 (87 ml)
was slowly added. During the addition, the temperature was maintained below 20°C. The solution was
stirred overnight and then concentrated in vacuo. The moist solid was extracted with boiling absolute
EtOH. After filtration and evaporation, the salt was dried under vacuum to provide 62 g of material.
Treatment of a mechanically stirred suspension of the salt with EtI (30 ml) in CH3CN (400 ml) at reflux
for 24 h gave, after concentration and removal of the inorganic salt, the crude ester 3a: 28.69 g (50% from
D-isoascorbic); [α]D25=−23.6 (c 3.9, CHCl3); (lit.8 [α]D=−29.14 (c 156, MeOH)); MS, 189 (M−CH3).
1H NMR (CDCl3) δ 1.20 (t, 3H, Jvic=7.1 Hz); 1.23 (s, 3H); 1.31 (s, 3H); 3.47 (d, 1H, OH, J=5.7 Hz);
3.92 (dd, 1H, Jgem=7.2 Hz, Jvic=6.3 Hz); 4.01 (dd, 1H, Jgem=7.3 Hz, Jvic=6.5 Hz); 4.03 (dd, 1H, Jgem=7.2
Hz, JOH=5.7 Hz); 4.14 (q, 2H, Jvic=7.2 Hz); 4.20 (m, 1H). 13C NMR (CDCl3) δ 14.13 (C7); 25.10 and
26.34 (Ca and Cb); 61.89 (C6); 65.04 (C2); 71.09 (C4); 76.78 (C3); 109.95 (C5); 172.07 (C1).
4.3. Ethyl (2R,3S)-3,4-O-isopropylidene-2,3,4-trihydroxybutanoate 3b
From L-ascorbic acid using the above procedure: 46.35 g (80% from L-isoascorbic); [α]D25=+16.6 (c
1
2.9, CHCl3); MS, 189 (M−CH3). H NMR (CDCl3) δ 1.19 (t, 3H, Jvic=7.1 Hz); 1.23 (s, 3H); 1.30 (s,
3H); 3.18 (d, 1H, OH, J=7.9 Hz); 3.94 (dd, 1H, Jgem=8.1 Hz, Jvic=7.0 Hz); 4.01 (dd, 1H, Jgem=8.1 Hz,
Jvic=7.0 Hz); 4.04 (dd, 1H, Jgem=3.2 Hz, JOH=8.0 Hz); 4.18 (q, 2H, Jvic=7.0 Hz); 4.30 (m, 1H). 13C NMR

C. André et al. / Tetrahedron: Asymmetry 9 (1998) 1359–1367
1365
(CDCl3) δ 14.13 (C7); 25.34 and 26.08 (Ca and Cb); 61.94 (C6); 65.62 (C2); 70.32 (C4); 76.37 (C3);
109.92 (C5); 172.10 (C1).
4.4. Ethyl (2R,3R)-2-O-methyl-3,4-O-isopropylidene-3,4-dihydroxybutanoate 4a
Compound 3a (2 g, 9.8 mmol) was dissolved in CH3CN (60 ml) and CH3I (20 ml). The mixture
was stirred at reflux overnight with Ag2O (3.6 g). Methylation was complete based on TLC (silica gel,
CHCl3). The solids were removed by filtration and the filtrate concentrated to dryness to give the methyl
ester 4a: 2.0 g (95%); [α]D25=−1.6 (c 3.6, CHCl3); MS, 203 (M−CH3). H NMR (CDCl3) δ 1.23 (t,
1
3H, Jvic=7.1 Hz); 1.27 (s, 3H); 1.31 (s, 3H); 3.40 (s, 3H); 3.75 (dd, 1H, Jgem=8.3 Hz, Jvic=5.9 Hz); 3.81
(d, 1H, Jvic=6.3 Hz); 3.98 (dd, 1H, Jgem=8.1 Hz, Jvic=6.3 Hz); 3.90 (q, 2H, Jvic=7.2 Hz); 4.31 (m, 1H).
13C NMR (CDCl3) δ 14.01 (C7); 25.37 and 26.13 (Ca and Cb); 58.51 (C8); 60.76 (C6); 65.96 (C2); 77.10
(C4); 81.28 (C3); 109.75 (C5); 170.89 (C1).
4.5. Ethyl (2R,3S)-2-O-methyl-3,4-O-isopropylidene-3,4-dihydroxybutanoate 4b
From 3b using the above procedure was afforded 4b: 2.1 g (97%); [α]D25=+0.4 (c 1.54, CHCl3); MS,
1
203 (M−CH3). H NMR (CDCl3) δ 1.19 (t, 3H, Jvic=7.1 Hz); 1.25 (s, 3H); 1.32 (s, 3H); 3.40 (s, 3H);
3.98 (dd, 1H, Jgem=8.1 Hz, Jvic=6.3 Hz); 4.01 (d, 1H, Jvic=6.1 Hz); 4.05 (dd, 1H, Jgem=8.0 Hz, Jvic=6.7
Hz); 4.11 (q, 2H, Jvic=7.1 Hz); 4.47 (m, 1H). 13C NMR (CDCl3) δ 14.13 (C7); 25.20 and 26.26 (Ca and
Cb); 58.72 (C8); 61.16 (C6); 65.42 (C2); 75.67 (C4); 81.58 (C3); 109.81 (C5); 169.79 (C1).
4.6. (2R,3R)-2-O-Methyl-3,4-O-isopropylidene-3,4-dihydroxybutanal 5a
Compound 4a (1.6 g, 8.5 mmol) was dissolved in dry toluene (53 ml). The solution was maintained
under nitrogen and cooled to −78°C. A quantity (8.6 ml, 1.5 equiv.) of 1.5 M DIBAL-H solution in
toluene was introduced into the flask. After 15 min, 25 ml of methanol was added and the solution was
slowly warmed to room temperature. A sodium potassium tartrate saturated solution (2 ml), 4 ml of brine
and 70 ml of AcOEt were added with MgSO4. After 1 h, the solids were removed by filtration and the
filtrate concentrated to dryness to give the aldehyde 5a: 1.2 g (97%); [α]D25=+2.1 (c 5.3, CHCl3); MS,
159 (M−CH3). 1H NMR (CDCl3) δ 1.28 (s, 3H); 1.40 (s, 3H); 3.43 (s, 3H); 3.55 (dd, 1H, Jvic=2.0 Hz,
Jvic=6.1 Hz); 3.90 (dd, 1H, Jgem=8.7 Hz, Jvic=5.3 Hz); 4.03 (dd, 1H, Jgem=8.6 Hz, Jvic=6.3 Hz); 4.23 (m,
1H); 9.68 (d, 1H, Jvic=2.0 Hz). 13C NMR (CDCl3) δ 24.97 and 26.33 (Ca and Cb); 58.75 (C8); 65.72
(C2); 74.71 (C4); 85.26 (C3); 109.49 (C5); 201.14 (C1).
4.7. (2R,3S)-2-O-Methyl-3,4-O-isopropylidene-3,4-dihydroxybutanal 5b
From 4b using the above procedure was afforded 5b: 1.2 g (97%); [α]D25=−4.1 (c 4.1, CHCl3); MS,
159 (M−CH3). 1H NMR (CDCl3) δ 1.25 (s, 3H); 1.35 (s, 3H); 3.45 (s, 3H); 3.58 (dd, 1H, Jvic=2.1 Hz,
Jvic=6.3 Hz); 3.90 (dd, 1H, Jgem=8.7 Hz, Jvic=5.5 Hz); 4.06 (dd, 1H, Jgem=8.5 Hz, Jvic=5.9 Hz); 4.28 (m,
1H); 9.60 (d, 1H, Jvic=2.0 Hz). 13C NMR (CDCl3) δ 24.56 and 26.23 (Ca and Cb); 58.35 (C8); 65.67
(C2); 75.03 (C4); 84.95 (C3); 110.10 (C5); 201.65 (C1).

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C. André et al. / Tetrahedron: Asymmetry 9 (1998) 1359–1367
4.8. (S)-3,4-O-Isopropylidene-3,4-dihydroxybutanal 7a
From the 2-deoxyester 6a using the above procedure was afforded 7a: 1.2 g (97%); [α]D25=+8.3 (c
1
1.3, CHCl3); (lit.17 [α]D24=+16.5 (c 5.32, CHCl3)); MS, 129 (M−CH3). H NMR (CDCl3) δ 1.30 (s,
3H); 1.37 (s, 3H); 2.65 (ddd, 1H, Jgem=15.3 Hz, Jvic=7.1 Hz, Jvic=2.0 Hz); 2.85 (ddd, 1H, Jgem=15.7 Hz,
Jvic=6.7 Hz, Jvic=2.1 Hz); 3.60 (dd, 1H, Jgem=8.3 Hz, Jvic=7.1 Hz); 4.15 (dd, 1H, Jgem=8.1 Hz, Jvic=6.3
Hz); 4.41 (m, 1H); 9.80 (d, 1H, Jvic=2.0 Hz). 13C NMR (CDCl3) δ 25.15 and 25.78 (Ca and Cb); 47.56
(C2); 68.80 (C4); 71.53 (C3); 109.28 (C5); 198.98 (C1).
4.9. (R)-3,4-O-Isopropylidene-3,4-dihydroxybutanal 7b
From the 2-deoxyester 6b using the above procedure was afforded 7b: 1.2 g (97%); [α]D25=−7.9
1
(c 2.9, CHCl3); MS, 129 (M−CH3). H NMR (CDCl3) δ 1.29 (s, 3H); 1.37 (s, 3H); 2.62 (ddd, 1H,
Jgem=15.1 Hz, Jvic=6.7 Hz, Jvic=2.0 Hz); 2.83 (ddd, 1H, Jgem=15.0 Hz, Jvic=5.9 Hz, Jvic=2.1 Hz); 3.56
(dd, 1H, Jgem=8.1 Hz, Jvic=7.0 Hz); 4.08 (dd, 1H, Jgem=8.0 Hz, Jvic=6.5 Hz); 4.47 (m, 1H); 9.80 (d, 1H,
Jvic=2.1 Hz). 13C NMR (CDCl3) δ 25.40 and 26.75 (Ca and Cb); 47.79 (C2); 69.10 (C4); 70.61 (C3);
109.20 (C5); 200.01 (C1).
4.10. 2-[(2S)-2,3-O-Isopropylidene-2,3-dihydroxypropyl]-2-trimethylsilyl-1,3-dithiane 8
2-Trimethylsilyl-1,3-dithiane (4.6 g, 24 mmol) was dissolved in dry THF. The solution was maintained
under nitrogen and cooled to −40°C. A quantity (1.5 g, 24 mmol) of 1.5 M n-butyllithium solution in
hexane was introduced into the flask and the mixture was stirred for 2 h at −25°C. Then the solution
was cooled to −78°C and (R)-2,2-dimethyl-4-(iodomethyl)-1,3-dioxan (5.8 g, 24 mmol) was added. The
solution was stirred for 3 h at −78°C and slowly warmed to room temperature. After 24 h, 370 ml of
H2O were added and the aqueous layer was treated with CHCl3. The organic layer was separated, dried
over MgSO4, filtered and concentrated to give 8: 6.2 g (84%); [α]D25=−2.1 (c 2.2, CHCl3); MS, 291
1
(M−CH3). H NMR (CDCl3) δ 0.15 (s, 9H); 1.25 (s, 3H); 1.39 (s, 3H); 2.01 (dd, 2H, Jgem=8.1 Hz,
Jvic=4.4 Hz); 2.68 (pseudo t, 2H, Jvic=4.0 Hz); 2.83 (pseudo t, 2H, Jvic=4.3 Hz); 2.96 (m, 2H); 3.25 (dd,
1H, Jgem=8.1 Hz, Jvic=5.9 Hz); 3.56 (dd, 1H, Jgem=8.3 Hz, Jvic=6.7 Hz); 4.25 (m, 1H). 13C NMR (CDCl3)
δ 25.14 and 25.63 (Ca and Cb); 26.83 (C5); 29.88 (3CH3); 30.01 and 30.51 (C4 and C6 ); 34.03 (C2);
0
0
0
0
38.70 (C6 ); 70.20 (C5 ); 75.60 (C4 ); 110.37 (C2 ).
4.11. 2-[(2S)-2,3-O-Isopropylidene-2,3-dihydroxypropyl]-1,3-dithiane 9
To a solution of 8 (5 g, 16.3 mmol) in 300 ml of dry THF was added 2 ml of tetrabutylammonium
fluoride. The solution was stirred for 6 h at room temperature and then extracted with AcOEt. The organic
layer was washed with H2O and brine and then dried over MgSO4. The solvent was removed and the
residue submitted to flash chromatography (pentane:ether=80:20) to give 9: 3.0 g (67%); [α]D25=−9.3 (c
5.1, CHCl3); (lit.18 [α]D23=−9.05, CHCl3); MS, 259 (M−CH3). 1H NMR (CDCl3) δ 1.30 (s, 3H); 1.37
(s, 3H); 1.99 (dd, 2H, Jgem=8.3 Hz, Jvic=4.3 Hz); 2.76 (pseudo t, 2H, Jvic=4.1 Hz); 2.80 (pseudo t, 2H,
Jvic=4.3 Hz); 2.88 (m, 2H); 3.53 (dd, 1H, Jgem=8.2 Hz, Jvic=6.4 Hz); 4.05 (dd, 1H, Jgem=8.1 Hz, Jvic=6.3
Hz); 4.15 (dd, 1H, Jgem=9.4 Hz, Jvic=4.2 Hz); 4.34 (m, 1H). 13C NMR (CDCl3) δ 25.64 and 25.78 (Ca
0
0
0
and Cb); 27.04 (C5); 29.40 and 30.16 (C4 and C6 ); 30.39 (C2); 39.96 (C6 ); 69.24 (C5 ); 72.59 (C4 );
0
109.09 (C2 ).

C. André et al. / Tetrahedron: Asymmetry 9 (1998) 1359–1367
1367
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