A novel synthesis of 2-deoxy-L-ribose

Article abstract of DOI:10.1016/S0957-4166(00)00146-4

We report a new synthesis of 2-deoxy-L-ribose starting from the commercially available (R)-(+)-5-hydroxymethyl-5H-furan-2-one. The key step is a 1,4-addition of (PhMe₂Si)₂Cu(CN)Li₂ which proceeds with complete diastereoselection. Copyright (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0957-4166(00)00146-4

Tetrahedron: Asymmetry 11 (2000) 1869±1876
A novel synthesis of 2-deoxy-l-ribosey
Fabio Fazio and Manfred P. Schneider*
FB 9-Bergische Universitat-GH-Wuppertal, D-42097 Wuppertal, Germany
È
Received 22 December 1999; revised 10 April 2000; accepted 11 April 2000
Abstract
We report a new synthesis of 2-deoxy-l-ribose starting from the commercially available (R)-(+)-5-
hydroxymethyl-5H-furan-2-one. The key step is a 1,4-addition of (PhMe2Si)2Cu(CN)Li2 which proceeds
with complete diastereoselection. # 2000 Elsevier Science Ltd. All rights reserved.
1. Introduction
The title compound constitutes the central building block for l-enantiomers of both natural
and synthetically modi®ed nucleosides, several of which are highly valuable antiviral agents.1 Thus,
l-thymidine (l-T), l-30-thiacytidine (l-3-TC, `Lamivudine'), l-5-¯uoro-30-thiacytidine (l-FTC),
l-20,30-dideoxycytidine (l-ddC) and l-5-¯uoro-20,30-dideoxycytidine (l-5-FddC) have shown
excellent antiviral activities with greatly reduced toxicities in mammalian systems as compared to
the corresponding d-nucleosides. Furthermore, l-nucleosides and derivatives thereof, both with
the l-ribose or 2-deoxy-l-ribose backbone, are attractive building blocks for the corresponding
oligonucleotides useful in `antisense' therapy for the binding of fragmental d-mRNA.2
As a great advantage for therapeutic applications and in contrast to the corresponding d-oligo-
deoxynucleotides (d-DNA) such enantiomeric l-DNA oligomers display considerably enhanced
resistance towards the action of nucleases.3
In order to develop versatile synthetic strategies towards such molecules and, obvious from the
retrosynthetic analysis outlined in Scheme 1, ¯exible and facile routes to both: (a) structurally
variable bases; and (b) l-riboses and derivatives thereof are required.
2. Results and discussion
Several synthetic approaches to 2-deoxy-l-ribose have been published in recent years, practically
all of them starting with molecules from the `chiral pool' such as l-arabinose or l-ascorbic acid.4
* Corresponding author. E-mail: schneid@uni-wuppertal.de
y
Added in proof: German patent application DE 100 20 275.6 of 25 April 2000.
0957-4166/00/$ - see front matter # 2000 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(00)00146-4

1870
F. Fazio, M. P. Schneider / Tetrahedron: Asymmetry 11 (2000) 1869±1876
Scheme 1.
Alternatively, the required absolute con®guration was introduced by asymmetrisation of an
achiral starting material, e.g. by employing the Sharpless epoxidation.5
In order to develop a more ¯exible strategy aimed at the synthesis of l-ribose, 2-deoxy-l-
ribose, 2,3-dideoxy-l-ribose and also unnatural derivatives functionalized at the crucial 30-position
in nucleosides, we decided to explore a novel route to such molecules starting from the a,b-
unsaturated lactone 1 (Scheme 2).
Scheme 2. Reagents and conditions: (a) H2SO4 (30% sol. in water), MeOH, rt, 2 h
Compound 1 is commercially available but can also be synthesized conveniently from inexpensive
l-ascorbic acid via a published procedure6 (Scheme 2).
Reaction of the key intermediate 86 with catalytic amounts (2%) of H2SO4 in MeOH produced
1 in 66% yield (35% overall yield from l-ascorbic acid). For the determination of the enantio-
meric purity of 1 via HPLC we decided to convert this material into the corresponding tert-
butyldiphenylsilyl derivative 9 (Scheme 3).
First attempts along these lines using more standard conditions (Et3N, DMAP, t-BuPh2SiCl)8
failed. Depending on the employed reaction times various degrees of racemization were observed
which we attribute to the transient deprotonation of the allylic proton at C-5 (compare Scheme 3).
In contrast, using t-BuPh2SiCl and NH4NO37 the desired derivative 9 was obtained with excellent
yield and free of racemization.
Using ent-9, prepared from commercially available ent-1 as a reference, the HPLC analysis
(column LiChoCART 250-4 (S,S)-Whelk-5 mm, eluent hexane:isopropanol (97:3), ¯ow rate 1 ml/
min, detector UV 254 nm) revealed an enantiomeric purity of >98% (Fig. 1).

F. Fazio, M. P. Schneider / Tetrahedron: Asymmetry 11 (2000) 1869±1876
1871
Scheme 3. Reagents and conditions: (a) tert-butyldiphenylsilyl chloride, NH4NO3, DMF, rt, 24 h; (b) tert-butyl-
diphenylsilyl chloride, Et3N, DMAP, dichloromethane, argon, 0ꢀC±rt, 4 h
Figure 1. HPLC analysis. Column: LiChroCART 250±4 1.50614. (S,S)-Whelk 01 (5 mm), eluent: n-hexane:isopropanol
(97:3); ¯ow rate: 1.0 ml/min
Constituting a `Michael' system, we felt that nucleophilic 1,4-addition would allow the con-
venient introduction of various substituents into the 30-position of nucleosides and this with high
diastereoselectivity being directed by the suitably protected 5-hydroxymethyl group in 1.
While `soft' nucleophiles (based on sulfur, nitrogen, phosphorus) can successfully be employed
for such 1,4-additions, all our initial e€orts to introduce derivatives of the `hard' nucleophile
oxygen failed.
Based on previous experiments described by Fleming et al.9 related to the diastereoselective
addition of silyl cuprate reagents to Michael systems, and due to the fact that the silyl functions in
the resulting derivatives can be transformed into the corresponding hydroxyl groups10 with
retention of con®guration, we report here the successful synthesis of 2-deoxy-l-ribose and related
building blocks in enantiomerically pure form (Scheme 4).
(R)-(+)-5-Hydroxymethyl-5H-furan-2-one 1 was ®rst converted into the corresponding benzyl
ether 2, thus carrying a protective group which would: (a) be stable under the reaction conditions;
(b) direct the entering substituent diastereoselectively to the opposite face; and (c) be easily
removable by catalytic hydrogenation. While more classical methods for the introduction of the

1872
F. Fazio, M. P. Schneider / Tetrahedron: Asymmetry 11 (2000) 1869±1876
Scheme 4. Reagents and conditions: (a) BnOC(ˆNH)CCl3, CF3SO3H, dichloromethane:cyclohexane (2:1), rt, 2 h; (b)
(PhMe2Si)2Cu(CN)Li2, THF, ^45ꢀC, 1 h; (c) Br2, AcOOH, AcOH, rt, 5 h; (d) disiamylborane, THF, rt, 24 h; (e)
HCOOH, Pd/C, 10%, MeOH, rt, 1 h
benzyl group (NaH/BnBr, Ag2O/BnBr)11 failed, 2 was obtained in 84% yield using benzyl tri-
12
chloroacetamidate in the presence of CF3SO3H. Cuprate addition of (PhMe2Si)2Cu(CN)Li2 to
2 a€orded the corresponding silyl derivative 3 in 90% yield. As to judge from the 13C NMR of 3,
only one diastereoisomer was produced.
Conversion of the silyl derivative 3 into the corresponding hydroxyl derivative 4 was achieved
with complete retention of con®guration using Br2 (1 M in AcOH) and AcOOH at rt for 5 h.
Compound 4 was obtained in 65% yield. Reduction of the lactone 4 was accomplished with di-
siamylborane13 leading to 5 as anomeric mixture (a:b=70:30 in CDCl3) in 60% yield. Deprotec-
tion of 5 using transfer hydrogenation14 (HCOOH, Pd/C 10%) resulted in the production of 2-
deoxy-l-ribose 6 and 7 in 80% yield as anomeric mixture of the furanoside and pyranoside forms.
The spectroscopic data for the isomeric mixture of 2-deoxy-l-ribose (four diastereoisomers) were
consistent with those of 2-deoxy-d-ribose.
Using the above outlined strategy towards l-enantiomers of nucleosides we are presently
employing enantiomerically pure 5 as well as 6 and 7 as central building blocks.
3. Experimental
3.1. General
Reagents were obtained from commercial suppliers and used without further puri®cation. All
glassware and syringes were dried in an oven overnight, allowed to cool and stored under a
positive pressure of argon before use. The solvents were dried before use as follows: cyclohexane and
dichloromethane over P2O5, THF distilled from potassium/benzophenone ketyl, DMF over CaO.
CuCN was dried under vacuum (10^3 mbar) at 120ꢀC overnight (CAUTION: CuCN is very toxic,

F. Fazio, M. P. Schneider / Tetrahedron: Asymmetry 11 (2000) 1869±1876
1873
handle this substance with protective gloves, do NOT dry it over P2O5). NH4NO3 was dried
overnight in a desiccator containing P2O5 (CAUTION: NH4NO3 is a potential explosive, handle
with care, do NOT heat). Merck silica gel 60 (70±230 mesh) was used for column chromatography.
Tlc were run on SiO2 60F254 (Merck), detection with UV and vaniline/H2SO4 reagent. 1H and 13
C
NMR spectra were measured at 400 MHz (Bruker). Chemical shifts are reported relative to CDCl3
at 7.27 ppm. IR spectra were measured with a Perkin±Elmer Infrared spectrophotometer 1420; the
optically rotations with a Perkin±Elmer 241 instrument (thermostated at +20ꢀC, chloroform stabilized
with 1% ethanol). Mass spectra were measured with a Variant MAT 311 A (EI, 70 eV) spectrometer.
Elemental analyses were carried out with an Elementar Vario EL. The melting points are uncorrected.
3.2. (R)-(+)-5-Hydroxymethyl-5H-furan-2-one 1
To a stirred solution of 3-(2,2-dimethyl[1,3]dioxolan-4-yl)acrylic acid ethyl ester 8 (M.W.
200.23, 12.2 g, 60.81 mmol) in 30 ml of MeOH, 200 ml of a 30% aqueous solution of H2SO4 were
added. After 2 h the weakly basic ion exchange resin Amberlite IRA-93 was added portionwise
until the pH was adjusted to 6±6.5. The mixture was ®ltered and the solvent was removed under
reduced pressure. The crude product was puri®ed by chromatography on silica gel using AcOEt
as eluent. Yield 4.6 g (66%), white crystals, m.p. 43±44ꢀC (from CHCl3/Et2O). Rf: 0.45 AcOEt.
20
1
‰ꢀŠD =+124 (c 1.08, CHCl3, lit.15 +136.09 (c 1.69, H2O)). H NMR (CDCl3) ꢁ 7.49 (dd, J=5.83
Hz, J=1.57 Hz, 1H), 6.19 (dd, J=5.76 Hz, J=2.03 Hz, 1H), 5.15 (m, 1H), 3,98 (dd, J=12.19 Hz,
J=3.37 Hz, 1H), 3.79 (dd, J=12.19 Hz, J=4.88 Hz, 1H), 2.58 (br, 1OH); 13C NMR (CDCl3) ꢁ
173.02, 153.45, 122.97, 83.98, 62.39; IR (KBr, cm^1) 3350, 3085, 2920, 2860, 1735, 1595, 1395, 1325;
MS m/z 85 (100%), 57, 42. Anal. calcd for C5H6O3: C, 52.58; H, 5.25. Found: C, 52.30; H, 5.21.
3.3. (R)(+)-5-Benzyloxymethyl-5H-furan-2-one 2
(R)-(+)-5-Hydroxymethyl-5H-furan-2-one 1 (M.W. 114.10, 4.0 g, 35.05 mmol) was stirred
under argon in a 300 ml mixture of dry dichloromethane:cyclohexane (2:1). The reaction mixture
was cooled to 0ꢀC and trichloroacetamidic acid benzyl ester (M.W. 252.53, 7.2 ml, 38.55 mmol,
1.1 equiv.) and tri¯uoromethanesulfonic acid (M.W. 150.08, 305.6 mL, 3.50 mmol, 0.1 equiv.)
were added. After 10 min at 0ꢀC the temperature was increased to rt and the mixture was stirred
for an additional 2 h. The mixture was washed with HCl 1N (2Â20 ml), water, brine and the
organic layer was dried over anhydrous Na2SO4. The crude product was puri®ed by chromatography
on silica gel using as eluent Et2O:hexane (2:1). Yield: 6.0 g (84%), oil, Rf: 0.28 Et2O:hexane (2:1).
20
1
‰ꢀŠD =+137 (c 1.31, CHCl3). H NMR (CDCl3) ꢁ 7.50 (dd, J=5.67 Hz, J= 1.39 Hz, 1H), 7.38±
7.27 (m, 5H), 6.17 (dd, J=5.67 Hz, J=1.96 Hz, 1H), 5.17 (m, 1H), 4.58 (s, 2H), 3.74 (dd,
J=10.35 Hz, J=5.19 Hz, 1H), 3.69 (dd, J=10.50 Hz, J=5.05 Hz, 1H); 13C NMR (CDCl3) ꢁ
172.63, 153.80, 137.27, 128.46, 127.93, 127.67, 122.55, 82.13, 13.74, 69.47; IR (®lm, cm^1) 3070, 3045,
3015, 2890, 2845, 1750, 1590, 1485, 1440, 1355, 1320; MS m/z 204, 161, 151, 126, 108, 98, 91, 82,
77, 62, 49, 44 (100%), 36. Anal. calcd for C12H12O3: C, 70.51; H, 5.87. Found: C, 69.95; H, 5.76.
3.4. Dimethylphenylsilyl lithium
A solution of phenyldimethylchlorosilane (M.W. 170.72, 7.1 ml, 43.09 mmol) in ca. 40 ml of
dry THF was added under argon at 0ꢀC to lithium powder (Aldrich 37 239-0, A.W. 6.94, 897 mg,
129.27 mmol, 3 equiv.). The ¯ask was put into a sonicator for 15 min and the purple solution was

1874
F. Fazio, M. P. Schneider / Tetrahedron: Asymmetry 11 (2000) 1869±1876
stirred overnight at ^5ꢀC. To establish the total amount of base, the solution was titrated with HCl
0.1N (standard solution), using phenolphthalein as indicator (the transformation could be considered
quantitative). To our experience, for best results, this reagent must be transferred via cannula.
3.5. (4R,5S)-(^)-5-Benzyloxymethyl-4-(dimethylphenylsilanyl)dihydrofuran-2-one 3
A suspension of CuCN (M.W. 89.56, 1.9 g, 21.54 mmol, 1.1 equiv.) in 100 ml of dry THF was
stirred under argon at ^45ꢀC. Ph(Me)2SiLi from Section 3.4 (see above, 43.09 mmol, 2.2 equiv.)
was added via cannula and the mixture was vigorously stirred for 30 min. At ^45ꢀC, (R)-(+)-5-
benzyloxymethyl-5H-furan-2-one 2 (M.W. 204.22, 4.0 g, 19.58 mmol) in 15 ml of dry THF was
then slowly added via a syringe. The reaction mixture was stirred for 1 h, then quenched at ^45ꢀC
with a saturated aqueous solution of NH4Cl. The mixture was ®ltered, AcOEt (20 ml) was added,
and the separated organic phase was washed with water, brine, and then dried over anhydrous
Na2SO4. Chromatographic separation was carried out on silica gel using as eluent hexane:AcOEt
20
1
(3:1). Yield 6.0 g (90%), oil, Rf: 0.44 hexane:AcOEt (3:1). ‰ꢀŠD =^22 (c 1.08, CHCl3). H NMR
(CDCl3) ꢁ 7.48±7.27 (m, 10H), 4.51 (m, 1H), 4.49 (s, 2H), 3.57 (dd, J=11.18 Hz, J=2.49 Hz, 1H),
3.36 (dd, J=11.19 Hz, J=4.68 Hz, 1H), 2.64 (dd, J=17.70 Hz, J=9.96 Hz, 1H), 2.38 (dd,
J=17.74 Hz, J=11.06 Hz, 1H), 1.96 (q, J=9.66 Hz, 1H), 0.37 (s, 3H), 0.35 (s, 3H); 13C NMR
(CDCl3) ꢁ 176.87, 137.68, 135.26, 133.70, 129.88, 128.21, 127.75, 127.67, 82.05, 73.45, 71.38,
31.33, 24.07, ^4.53, ^5.15; IR (®lm, cm^1) 3045, 3010, 2930, 2890, 2840, 1950, 1875, 1760, 1580, 1485,
1440, 1415, 1350; MS m/z 340, 325, 280, 271, 262, 241, 219, 191, 165, 156, 136, 117, 105, 91 (100%),
84, 75, 65, 57, 43. Anal. calcd for C20H24O3Si: C, 70.48; H, 7.04. Found: C, 69.78; H, 6.97.
3.6. (4R,5S)-(^)-5-Benzyloxymethyl-4-hydroxydihydrofuran-2-one 4
To a stirred solution of (4R,5S)-(^)-5-benzyloxymethyl-4-phenyldimethylsilyldihydrofuran-2-
one 3 (M.W. 340.49, 5.0 g, 14.68 mmol) in 100 ml of AcOOH (39% in AcOH), at 0ꢀC, under
argon, Br2 (1 M in AcOH, 7.3 ml, 0.5 equiv.) was added dropwise and the mixture was stirred for
5 h at rt. The solution was diluted with Et2O (100 ml) and under stirring at 0ꢀC 20 ml of an
aqueous solution of Na2S2O3 were carefully added. The organic layer was separated, and treated
under stirring with 20 ml of a saturated aqueous solution of NaHCO3 followed by an addition of
NaHCO3 powder until no further gas evolution was observed. The organic phase was washed
again with 20 ml of a saturated aqueous solution of NaHCO3, brine and then dried over
anhydrous Na2SO4. Chromatographic puri®cation was achieved on silica gel using as eluent
hexane:AcOEt (1:1). Yield 2.1 g (65%), oil, Rf: 0.26 hexane:AcOEt (1:1). ‰ꢀŠ2D0=^5 (c 1.38,
CHCl3). 1H NMR (CDCl3) ꢁ 7.38±7.27 (m, 5H), 4.60±4.47 (complex, 4H), 3.70 (dd, J=10.70 Hz,
J=3.21 Hz, 1H), 3.66 (dd, J=10.73 Hz, J=3.59 Hz, 1H), 2.93 (dd, J=18.05 Hz, J=6.8 Hz, 1H),
2.45 (dd, J=17.96 Hz, J=2.65 Hz, 1H), 2.09 (br, 1 OH); 13C NMR (CDCl3) ꢁ 175.89, 137.28,
128.53, 127.98, 127.65, 86.26, 73.75, 69.71, 69.41, 38.37; IR (®lm, cm^1) 3440, 3060, 3030, 2920,
2860, 1770, 1490, 1475, 1450, 1430, 1360; MS m/z 222, 176, 159, 133, 116, 105, 98, 91 (100%), 83,
77, 70, 65, 57, 51, 43. Anal. calcd for C12H14O4: C, 64.79; H, 6.30. Found: C, 64.21; H, 6.12.
3.7. ꢀ,ꢂ-(4R,5S)-(^)-5-Benzyloxymethyltetrahydrofuran-2,4-diol 5
To a stirred solution of 2-methyl-2-butene (M.W. 70.14, 19 ml, 182.23 mmol, 22.5 equiv.) in 20
ml of dry THF, at 0ꢀC, under argon, a 1 M solution of BH3±THF (45.3 ml, 5.6 equiv.) was added

F. Fazio, M. P. Schneider / Tetrahedron: Asymmetry 11 (2000) 1869±1876
1875
and the mixture was stirred for 20 min. Then (4R,5S)-(^)-5-benzyloxymethyl-4-hydroxy-
dihydrofuran-2-one 4 (M.W. 222.24, mmol 8.09, 1.8 g) in 10 ml of dry THF was added dropwise.
After stirring for 24 h, water (20 ml) was added and the reaction mixture was re¯uxed for 30 min.
Then at 0ꢀC 20 ml of a 30% aqueous solution of H2O2 was added dropwise and the pH was
adjusted to 8 with NaOH 2N. The mixture was stirred for an additional 10 min. AcOEt (30 ml)
was added and the organic layer was separated. The aqueous phase was extracted twice with
AcOEt and the collected organic layers were washed with brine and dried over anhydrous
Na2SO4. The solvents were removed under vacuum (bath temperature max 30ꢀC). Chromatographic
puri®cation was carried out on silica gel using as eluent AcOEt:hexane (3:1). Yield 1.1 g (60%),
20
1
oil, Rf: 0.26 AcOEt:hexane (3:1). ‰ꢀŠD =^32 (c 1.22, CHCl3, 2 h). a:b=70:30. a-Anomer: H
NMR (CDCl3) ꢁ 7.37±7.27 (m, 5H), 5.54 (d, J=4.78 Hz, 1H), 4.52 (s, 2H), 4.35 (dt, J=4.48 Hz,
J=1.50 Hz, 1H), 4.23 (d, J=5.98 Hz, 1H), 3.50 (dd, J=10.18 Hz, J=4.73 Hz, 1H), 3.45 (br, 2
OH), 3.41 (dd, J=10.17 Hz, J=5.09 Hz, 1H), 2.13 (d, J=13.40 Hz, 1H), 1.98 (d, J=13.73 Hz, 1H);
13C NMR (CDCl3) ꢁ 137.78, 128.37, 127.71, 127.61, 99.24, 85.86, 73.44, 73.33, 70.49, 41.30. b-
1
Anomer: H NMR (CDCl3) ꢁ 7.37±7.27 (m, 5H), 5.54 (d, J=4.78 Hz, 1H), 4.57 (d, J=6.10 Hz,
2H), 4.44 (m, 1H), 4.05 (q, J=4.06 Hz, 1H), 3.61 (d, J=4.22 Hz, 2H), 3.45 (br, 2 OH), 2.13 (d,
J=3.05 Hz, 1H), 2.11 (d, J=5.08 Hz, 1H); 13C NMR (CDCl3) ꢁ 137.21, 128.51, 127.98, 127.85,
99.03, 84.95, 73.66, 73.10, 71.26, 43.61; IR (®lm, cm^1) 3350, 3000, 2900, 2840, 1715, 1480, 1440;
MS m/z 206, 115, 107, 91, 71, 59, 45 (100%). Anal. calcd for C12H16O4: C, 64.21; H, 7.13. Found:
C, 64.05; H, 7.08.
3.8. 2-Deoxy-l-ribose 6 and 7
A solution of methanol containing 10% formic acid was degassed under vacuum for 5 min,
then 20 ml of this solution were added carefully under argon to 1 g of Pd/C 10%. To this
suspension, a,b-(4R,5S)-(^)-5-benzyloxymethyltetrahydrofuran-2,4-diol 5 (M.W. 224.25, 0.89
mmol, 200 mg), dissolved in 10 ml of the same solution, was added dropwise with stirring. After 1
h the catalyst was ®ltered o€ and washed with 5 ml of distilled water. The solvents were removed
under vacuum (bath temperature max 30ꢀC). The crude product was puri®ed by column chro-
matography using as eluent AcOEt:MeOH (9:1). The title compound was isolated as a syrup
which was crystallized from AcOEt:MeOH (4:1). Yield 95 mg (80%), white crystals, m.p. 89±
90ꢀC (from AcOEt:MeOH, 4:1). Rf: 0.25 AcOEt:MeOH (9:1). ‰ꢀŠD20=+52 (c 1.0, H2O, 24 h); lit.16a
+52 (c 0.5, H2O); lit.16b for 2-deoxy-d-ribose, ^51 (c 1.3, H2O); lit.16c ^52 (c 1.05, H2O). The
spectroscopic data were consistent with those of commercially available 2-deoxy-d-ribose.
3.9. (R)-(+)-5-(tert-Butyldiphenylsilanyloxymethyl)-5H-furan-2-one 9
To a stirred solution of (R)-(+)-5-hydroxymethyl-5H-furan-2-one 1 (M.W. 114.10, 50 mg, 0.44
mmol) in 2 ml of dry DMF, under argon, at rt were added NH4NO3 (M.W. 80.04, 105.2 mg, 1.31
mmol, 3 equiv.) and tert-butyldiphenylsilyl chloride (M.W. 274.87, 145.7 ml, 0.57 mmol, 1.3
equiv.). After 24 h water (10 ml) was added and the mixture was extracted with Et2O (3Â10 ml),
the organic layer was dried over anhydrous Na2SO4 and the solvent evaporated under reduced
pressure. The crude product was puri®ed by chromatography on silica gel using as eluent
hexane:AcOEt (4:1). Yield 140 mg (91%), white crystals, m.p. 79±80ꢀC (from pentane/Et2O). Rf:
20
1
0.37 hexane:AcOEt (4:1). ‰ꢀŠD =+76 (c 1.15, CHCl3). H NMR (CDCl3) ꢁ 7.62±7.36 (complex,
11H), 6.15 (dd, J=5.77 Hz, J=1.76 Hz, 1H), 5.04 (m, 1H), 3.93 (dd, J=10.68 Hz, J=4.57 Hz,

1876
F. Fazio, M. P. Schneider / Tetrahedron: Asymmetry 11 (2000) 1869±1876
1H), 3.88 (dd, J=11.18 Hz, J=5.08 Hz, 1H), 1.02 (s, 9H); 13C NMR (CDCl3) ꢁ 172.82, 153.94,
135.58, 132.79, 130.00, 127.86, 122.71, 83.19, 63.43, 26.70, 19.21; IR (KBr, cm^1) 3090, 3050,
2880, 1960, 1890, 1740, 1595, 1450, 1420, 1380; MS m/z 295, 199 (100%), 181, 135, 77, 55. Anal.
calcd for C21H24O3Si: C, 71.48; H, 6.80. Found: C, 70.89; H, 6.45.
References
1. (a) Okabe, M.; Sun, R. C.; Tam, S. Y. K.; Todaro, L. J.; Co€en, D. L. J. Org. Chem. 1988, 53, 4780. (b) Spadari,
S.; Maga, G.; Focher, F.; Ciarrocchi, G.; Manservigi, R.; Ariamone, F.; Capobianco, M.; Carcuro, A.; Colonna,
F.; Iotti, S.; Garbesi, A. J. Med. Chem. 1992, 35, 4214. (c) Chang, C. N.; Doong, S. L.; Zhou, J. H.; Beach, J. W.;
Jeong, L. S.; Chu, C. K.; Tsai, C. H.; Cheng, Y. C. J. Biol. Chem. 1992, 267, 13938. (d) Chang, C. N.; Skalski, V.;
Zhou, J. H.; Cheng, Y. C. J. Biol. Chem. 1992, 267, 22414. (e) Beach, J. W.; Jeong, L. S.; Alves, A. J.; Pohl, D.;
Kim, H. O.; Chang, C. N.; Coong, S. L.; Schinazi, R. F.; Cheng, Y. C.; Chu, C. K. J. Org. Chem. 1992, 57, 2217.
(f) Hoong, L. K.; Strange, L. E.; Liotta, D. C.; Koszalka, G. W.; Burns, C. L.; Schinazi, R. F. J. Org. Chem. 1992,
57, 5563. (g) Lin, T. S.; Luo, M. Z.; Liu, M. C.; Pai, B.; Dutschman, G. E.; Cheng, Y. C. J. Med. Chem. 1994, 37,
798.
2. (a) Damha, M. J.; Giannaris, P. A.; Marfey, P. Biochemistry 1994, 33, 7877. (b) Hashimoto, Y.; Iwanami, N.;
Fujimori, S.; Shudo, K. J. Am. Chem. Soc. 1993, 115, 9883. (c) Fujimori, S.; Shudo, K.; Hashimoto, Y. J. Am.
Chem. Soc. 1992, 114, 9731.
3. (a) Anderson, D. J.; Reisher, R. J.; Taylor, A. J.; Wechter, W. J. Nucleosides Nucleotides 1984, 3, 499. (b)
Fujimori, S.; Shudo, K.; Hashimoto, Y. J. Am. Chem. Soc. 1990, 112, 7436. (c) Morvan, F.; Genu, C.; Rayner, B.;
Gosselin, G.; Imbach, J. L. Biochem. Biophys., Res. Commun. 1990, 172, 537.
4. (a) Kita, Y.; Tamura, O.; Itoh, F.; Yasuda, H.; Kishino, H.; Ke, Y. Y.; Tamura, Y. J. Org. Chem. 1988, 53, 554.
(b) Vargeese, C.; Abushanab, E. J. Org. Chem. 1990, 55, 4400. (c) Kozikowski, A. P.; Ghosh, A. K. J. Org. Chem.
1984, 49, 2762. (d) Jung, M. E.; Xu, Y. Tetrahedron Lett. 1997, 38, 4199.
5. Jung, M. E.; Nichols, C. J. Tetrahedron Lett. 1998, 39, 4615.
6. (a) Hubschwerlen, C. Synthesis 1986, 962. (b) Hafele, B.; Jager, V. Liebigs Ann. Chem. 1987, 85.
7. Hardinger, S.; Wijaya, N. Tetrahedron Lett. 1993, 34, 3821.
8. Ortuno, R. M.; Ballesteros, M.; Corbera, J.; Sanchez-Ferrando, F.; Font, J. Tetrahedron 1988, 44, 1711.
9. (a) Fleming, I.; Reddy, N. L.; Takaky, K.; Ware, A. C. J. Chem. Soc., Chem. Commun. 1987, 1472. (b) Crump,
R. A. N. C.; Fleming, I.; Urch, C. J. J. Chem. Soc., Perkin Trans. 1 1994, 701. (c) Fleming, I.; Newton, T. W.
J. Chem. Soc., Perkin Trans. 1 1984, 1805. (d) Fleming, I.; Newton, T. W.; Roessier, F. J. Chem. Soc., Perkin
Trans. 1 1981, 2527. (e) Fleming, I.; Parker, D. C.; Plaut, H. E.; Sanderson, P. E. J. J. Chem. Soc., Perkin Trans. 1
1995, 317.
10. (a) Fleming, I.; Henning, R.; Plaut, H. J. Chem. Soc., Chem. Commun. 1984, 29. (b) Fleming, I.; Sanderson, E. J.
Tetrahedron Lett. 1987, 28, 4229. (c) Kolb, H. C.; Ley, S. V.; Slawin, A. M. Z.; Williams, D. J. J. Chem. Soc.,
Perkin Trans. 1 1992, 2735.
11. Camps, P.; Cardellach, J.; Font, J.; Ortuno, R. M.; Ponsati, O. Tetrahedron 1982, 38, 2395.
12. (a) Ager, D. J.; Fleming, I.; Patel, S. K. J. Chem. Soc., Perkin Trans. 1 1981, 2520. (b) Gilman, H.; Lichtenwalter,
G. D. J. Am. Chem. Soc. 1958, 80, 608. (c) Sharma, S.; Oehlschlager, A. C. Tetrahedron 1989, 45, 557.
13. (a) Giudici, T. A.; Fluharty, A. L. J. Org. Chem. 1967, 32, 2043. (b) Kohn, P.; Samaritano, R. H.; Lerner, L. M.
J. Am. Chem. Soc. 1965, 87, 5475. (c) Brown, H. C.; Bigley, D. B.; Arora, S. K.; Yoon, N. M. J. Am. Chem. Soc.
1970, 92, 7161.
14. Rao, V. S.; Perlin, A. S. Carbohydr. Res. 1980, 83, 175.
15. Ortuno, R. M.; Bigorra, J.; Font, J. Tetrahedron 1987, 43, 2199.
16. (a) Gakhokidze, R. A.; Sidamonidze, N. N. J. Org. Chem. USSR 1987, 1017. (b) Harada T.; Mukaiyama, T.
Chem. Lett. 1981, 1109. (c) Gasparini, F.; Vogel, P. J. Org. Chem. 1990, 55, 2451.