Synthesis of differentially protected ribitol derivatives from 3,4-O-benzylidene-D-ribono-1,5-lactone

Article abstract of DOI:10.1016/j.tetasy.2004.12.008

Several differentially protected ribitol derivatives were synthesised using 3,4-O-benzylidene-d-ribono-1,5-lactone as versatile starting compounds for oligosaccharide synthesis. The obtained ribitol derivatives allow the regiospecific coupling of glycosyl

Full text of DOI:10.1016/j.tetasy.2004.12.008

Tetrahedron:
Asymmetry
Tetrahedron: Asymmetry 16 (2005) 507–511
Synthesis of differentially protected ribitol derivatives from
3,4-O-benzylidene-D-ribono-1,5-lactone
Dirk J. Lefeber, Peter Steunenberg,
Johannes F. G. Vliegenthart and Johannis P. Kamerling*
Bijvoet Center, Department of Bio-Organic Chemistry, Utrecht University, Padualaan 8, NL-3584 CH Utrecht, The Netherlands
Received 12 November 2004; accepted 10 December 2004
Abstract—Several differentially protected ribitol derivatives were synthesised using 3,4-O-benzylidene-D-ribono-1,5-lactone as ver-
satile starting compounds for oligosaccharide synthesis. The obtained ribitol derivatives allow the regiospecific coupling of glycosyl
donors to either of the hydroxyl groups of ribitol and can be applied for the preparation of polyhydroxylated compounds.
Ó 2004 Elsevier Ltd. All rights reserved.
1. Introduction
benzaldehyde was postulated to be 3,5-O-benzylidene-
D-ribono-1,4-lactone 2,4 and as such it was used by oth-
ers.5,6 However, in 1985 crystallographic studies of the
acetylated compound showed the reaction product to
be 3,4-O-benzylidene-D-ribono-1,5-lactone 3 instead of
the 3,5-O-acetal.7 The use of the 1,5-lactone has been de-
scribed in the preparation of (2R,3S,4R)-dihydroxypro-
line8 and pyrrolidine derivatives.9
Ribitol is a common monosaccharide constituent of
many bacterial capsular polysaccharides, such as those
from Streptococcus pneumoniae types 6, 10A and 13,1
and from Haemophilus influenzae type b.2 Since in poly-
saccharides different hydroxyl groups of ribitol may be
involved in the glycosidic linkage, regiospecific protec-
tion strategies are required for the synthesis of ribitol-
containing oligosaccharides. Furthermore, differently
protected alditols are attractive synthetic intermediates
for the preparation of various classes of polyhydroxyl-
ated compounds.3
In the context of our synthetic studies on ribitol-con-
taining oligosaccharide fragments of bacterial polysac-
charides, herein we report easily accessible protocols
for the preparation of three differentially protected
ribitol derivatives starting from 3,4-O-benzylidene-D-
ribono-1,5-lactone 3: 3,4-O-benzylidene-D-ribitol 4,
3,4-O-benzylidene-1-O-tert-butyldimethylsilyl-D-ribitol
In 1968 the product of the reaction of D-ribonolactone 1
(Scheme 1) with concentrated hydrochloric acid and
O
O
O
2
Ph
O
OH
O
HO
HO
OH
a
b
O
O
O
OH
O
O
OH OH
O
O
Ph
OH
Ph
4
1
3
Scheme 1. Reagents and conditions: (a) PhCHO, HCl, 87%; (b) NaBH4, MeOH, THF, 55 °C, 85%.
*
Corresponding author. Tel.: +31 30 253 34 79; fax: +31 30 254 09 80; e-mail: j.p.kamerling@chem.uu.nl
Present address: Laboratory of Pediatrics and Neurology, Reinier Postlaan 4, 6525 GC Nijmegen, The Netherlands.
0957-4166/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2004.12.008

508
D. J. Lefeber et al. / Tetrahedron: Asymmetry 16 (2005) 507–511
6, and 3-O-allyl-2-O-tert-butyldimethylsilyl-5-O-tert-
butyldiphenylsilyl-D-ribitol 10.
product. First of all, two acetyl groups, a benzylidene
group and a tert-butyldimethylsilyl group are present.
A downfield shifted H-2 was shown (d 5.01 ppm, ddd),
which corresponds to an acetylated O-2, thereby indicat-
ing the migration of the silyl group from O-2 to O-1.
Furthermore, a comparison of the H-1 chemical shifts
in acetylated 6 with acetylated 4 (Scheme 1) showed an
upfield shift from >4.10 to 3.93 and 3.84 ppm, support-
ing that O-1 is not acetylated in 6. The position of the
acetal proton at d 5.84 ppm indicated that the 1,3-dioxo-
lane ring system was intact. A similar silyl migration
under reducing conditions with sodium borohydride
has been observed before.11 Thus, due to a facile silyl
migration, ribitol derivative 6 is obtained, which can
be used for reactions at O-2 with the option of selective
protection of the primary hydroxyl functions.
2. Results and discussion
Key compound 3,4-O-benzylidene-D-ribono-1,5-lactone
3 (Scheme 1) was prepared by reaction of D-ribono-
1,4-lactone 1 with benzaldehyde and concentrated HCl
1
in 87% yield. H NMR analysis of acetylated 3 showed
a downfield shifted H-2 (d 5.53 ppm, d, J2,3 3.2 Hz), a
benzylidene proton at d 5.81 ppm, characteristic for an
acetal proton in a 1,3-dioxolane ring system, and a
ROESY contact between H-3 and H-4, in agreement
with the orientation of H-3 and H-4 in compound 3
(cis), but not in compound 2. Opening and reduction
of lactone 3 by using sodium borohydride and methanol
in tetrahydrofuran afforded 4 in a yield of 85%. 1H
NMR analysis of the acetylated product showed a
downfield shifted H-2 (d 5.16 ppm, ddd), and an acetal
proton at d 5.84 ppm, which is evidence for a benzylid-
ene group in a 5-membered ring. Ribitol derivative 4 can
be used for coupling at O-2 after protection of the pri-
mary hydroxyl groups, if no selectivity of the primary
hydroxyl groups is required.
The synthesis of a ribitol derivative in which O-3 and O-4
are selectively accessible, was started from D-ribonolac-
tone derivative 5 (Scheme 3). Debenzylidenation of 5
without affecting the silyl group was accomplished by
catalytic hydrogenation using a palladium catalyst in
ethyl acetate, affording 7 in 97% yield. It should be noted
that hydrogenation of 5 in ethanol led to cleavage of the
silyl group. The cleavage of a tert-butyldimethylsilyl
group has been described before during a transfer hydro-
genation in methanol.12 The identity of 7 was confirmed
by NMR analysis. The position of C-4 in the 13C NMR
spectrum of 7 (d 84.6 ppm) is characteristic for a 1,4-lac-
For the preparation of ribitol derivative 6 (Scheme 2),
compound 3 was silylated with tert-butyldimethylsilyl
(TBDMS) chloride10 to afford 5 in 95% yield. The posi-
1
1
tion of the acetal proton in the H NMR spectrum (d
tone; the H NMR spectrum of acetylated 7 showed a
5.71 ppm) indicated a benzylidene group in a 1,3-dioxo-
lane ring system, and the chemical shifts of C-3 and C-4
in the 13C NMR spectrum (range d 73-77 ppm8)
indicated a 1,5-lactone. Reduction of 5 using sodium
borohydride and methanol in tetrahydrofuran afforded
6 as the only product in 86% yield. The identity of 6
was derived from the 1H NMR analysis of the acetylated
downfield shifted H-3 (d 5.31 ppm, dd) and a non-O-
acetylated O-4 (d 4.65 ppm, m). A similar rearrangement
of a ribono-1,5-lactone to a ribono-1,4-lactone after
debenzylidenation with trifluoroacetic acid had been
found previously.8 For the selective protection of O-5
in 7, the tert-butyldiphenylsilyl (TBDPS) group was
chosen,13 and reaction of 7 with tert-butyldiphenylsilyl
HO
OH
O
O
a
b
O
O
OTBDMS
O
O
O
O
Ph
OH
O
Ph
OTBDMS
O
Ph
6
5
3
Scheme 2. Reagents and conditions: (a) TBDMSCl, C5H5N, DMAP, 95%; (b) NaBH4, MeOH, THF, 55 °C, 86%.
O
HO
a
TBDPSO
O
O
b
O
O
O
O
Ph
OTBDMS
O
OH OTBDMS
OH OTBDMS
8
5
7
TBDPSO
OH OTBDMS
OH
c
O
d
O
TBDPSO
AllO OTBDMS
OAll
10
9
Scheme 3. Reagents and conditions: (a) H2, 10% Pd/C, EtOAc, 97%; (b) TBDPSCl, CH2Cl2, C5H5N, DMAP, 80%; (c) (i) AocCl, CH2Cl2, C5H5N,
0 °C, 84%, (ii) (PPh3)4Pd(0), CH3CN, He, 55 °C, 75%; (d) NaBH4, MeOH, THF, 55 °C, 86%.

D. J. Lefeber et al. / Tetrahedron: Asymmetry 16 (2005) 507–511
509
chloride14 gave 8 in 80% yield. The remaining hydroxyl
function at C-3 was chosen to be allylated. Sodium
hydride-mediated allylation of 8 turned out to be impos-
sible due to opening of the base-labile lactone. Therefore,
a two-step allylation procedure was used.15 Allyloxy-
carbonylation and subsequent decarboxylation using tet-
rakis-triphenylphosphine-palladium(0) gave 9 in 63%
yield. Reductive opening of the lactone using sodium
borohydride and methanol in tetrahydrofuran afforded
the ribitol derivative 10 in a yield of 86%. The 1H
NMR spectrum of acetylated 10 showed a downfield
shifted H-4 (d 5.23, dt), and the presence of two acetyl
groups, a TBDMS group, a TBDPS group and an allyl
group. The resulting ribitol derivative 10 allows the gly-
cosidic coupling to either of the skeleton oxygen atoms.
and the precipitate collected by filtration. The residue
was washed with aq 10% NaHCO3 and water, and
recrystallised from refluxing acetone, yielding 3 (7.75 g,
87%). 1H NMR (DMSO-d6): d 7.46–7.32 (m, 5H,
PhCH), 5.74 (s, 1H, PhCH), 4.69 (dd, 1H, J3,4 8.0, J2,3
3.2 Hz, H-3), 4.64 (br d, 1H, J4,5b 1.6 Hz, H-4), 4.62
(d, 1H, H-2), 4.42 (dd, 1H, J5a,5b 13.1 Hz, H-5b), 4.32
1
(d, 1H, H-5a); H NMR (CDCl3 + MeOH-d3): d 7.47–
7.39 (m, 5H, PhCH), 5.81 (s, 1H, PhCH), 4.84 (dd,
1H, J3,4 8.1, J2,3 3.3 Hz, H-3), 4.69 (m, 1H, H-4), 4.56
(d, 1H, H-2), 4.39 (dd, 1H, J5a,5b 13.2 Hz, H-5). For fur-
ther analysis, a small amount of 3 was acetylated with
1
Ac2O in pyridine. H NMR (CDCl3): d 7.47–7.39 (m,
5H, PhCH), 5.81 (s, 1H, PhCH), 5.53 (d, 1H, J2,3
3.2 Hz, H-2), 4.84 (dd, 1H, J3.4 8.0 Hz, H-3), 4.69 (br
d, 1H, H-4), 4.59 (d, 1H, J5a,5b 13.4 Hz, H-5a), 4.38
(dd, 1H, J4,5b 1.7 Hz, H-5b), 2.25 (s, 3H, CH3CO).
3. Conclusion
To a solution of 3 (200 mg, 0.85 mmol) in THF (2.5 mL)
was added NaBH4 (80 mg). The mixture was heated to
55 °C, and MeOH (0.8 mL) was added dropwise over
30 min. After 1 h, TLC (95:5 CH2Cl2–MeOH) showed
complete conversion of 3 into 4 (Rf 0.45). Then, the mix-
ture was quenched by addition of HOAc, and coconcen-
trated with MeOH. The crude product was purified by
column chromatography (98:2 CH2Cl2–MeOH) to yield
4 (170 mg, 85%). For analysis, a small aliquot was acet-
ylated with Ac2O in pyridine. 1H NMR (CDCl3): d 7.49–
7.37 (m, 5H, PhCH), 5.84 (s, 1H, PhCH), 5.16 (ddd, 1H,
H-2), 2.08, 2.07 and 2.06 (3 s, each 3H, CH3CO).
3,4-O-Benzylidene-D-ribono-1,5-lactone has been shown
to be a versatile compound for the preparation of sev-
eral differentially protected ribitol derivatives. These
products can be used for the regiospecific coupling of
protected sugar donors to one of the hydroxyl groups
of ribitol or for the preparation of polyhydroxylated
compounds.
4. Experimental
4.1. General methods
4.3. 3,4-O-Benzylidene-2-O-tert-butyldimethylsilyl-D-
ribono-1,5-lactone, 5
All reagents were used as obtained commercially, with-
out any further purification. Reactions were monitored
by TLC on Kieselgel 60 F254 (Merck); compounds were
visualised, after examination under UV light, by char-
ring with phenol–sulfuric acid or KMnO4 and Na2CO3
in water. In the work-up procedures of reaction mix-
tures, organic solutions were washed with appropriate
amounts of the indicated aqueous solutions, then dried
over MgSO4 and concentrated under reduced pressure
at 20–40 °C on a water bath. Column chromatography
was performed on Kieselgel 60 F254 (Merck, 70–230
mesh). Optical rotations were measured in CHCl3 with
a Perkin–Elmer 241 polarimeter, using a 10-cm l-mL
To a solution of 3 (7.75 g, 33 mmol) in pyridine (60 mL)
at 0 °C were added TBDMSCl (7.7 g, 50 mmol) and a
catalytic amount of DMAP. The mixture was allowed
to reach room temperature, and after 20 h, a second
portion of TBDMSCl (2.0 g, 13 mmol) was added. After
25 h, TLC (95:5 CH2Cl2–MeOH) showed complete con-
version of 3 into 5. The mixture was diluted with EtOAc,
washed with aq 10% NaHCO3 and aq 10% NaCl, and
the organic layer dried, filtered and concentrated. Col-
umn chromatography (7:3 toluene–EtOAc) of the resi-
due afforded
5 as a white solid (11.0 g, 95%).
1
cell. H NMR spectra were recorded at 27 °C with a
[a]D = À134 (c 0.9, CHCl3); Rf 0.89 (95:5 CH2Cl2–
MeOH); 1H NMR (CDCl3): d 7.47–7.33 (m, 5H,
PhCH), 5.71 (s, 1H, PhCH), 4.64 (dd, 1H, J2,3 3.2, J3,4
8.0 Hz, H-3), 4.51 (dd, 1H, J4,5b 1.4 Hz, H-4), 4.45 (d,
1H, H-2), 4.36 (d, 1H, J5a,5b 13.4 Hz, H-5a), 4.15 (dd,
1H, H-5b), 0.94 (s, 9H, SiC(CH3)3), 0.20 and 0.13 (2 s,
each 3H, Si(CH3)2); 13C NMR (CDCl3): d 169.4 (C-1),
135.1, 129.8, 128.2 and 127.2 (PhCH), 104.1 (PhCH),
77.3, 73.1 and 69.6 (C-2, C-3, C-4), 67.0 (C-5), 25.6
(SiC(CH3)3), 18.2 (SiC(CH3)3). Anal. Calcd for
C18H26O5Si (350.5): C, 61.69; H, 7.48. Found: C,
61.80; H, 7.47.
Bruker AC 300 spectrometer; the values of dH are given
in ppm relative to the signal for internal Me4Si (d 0) for
solutions in CDCl3. 13C (APT, 75 MHz) NMR spectra
were recorded at 27 °C with a Bruker AC 300 spectro-
meter; indicated ppm values for dC are relative to the
signal of CDCl3 (d 76.9) for solutions in CDCl3. Two-
dimensional 1H–1H correlation spectra (TOCSY and
ROESY) were recorded using a Bruker AMX 500 appa-
ratus (500 MHz) at 27 °C. Elemental analyses were car-
ried out by H. Kolbe Mikroanalytisches Laboratorium
(Mulheim an der Ruhr, Germany).
¨
4.2. 3,4-O-Benzylidene-D-ribitol, 4
4.4. 3,4-O-Benzylidene-1-O-tert-butyldimethylsilyl-D-
ribitol, 6
To
a solution of D-ribono-1,4-lactone 1 (5.56 g,
38 mmol) in benzaldehyde (50 mL) was added concen-
trated HCl (5 mL). After 7 h, Et2O (60 mL) was added,
To a solution of 5 (491 mg, 1.4 mmol) in dry THF
(5 mL) was added NaBH4 (130 mg). The mixture was

510
D. J. Lefeber et al. / Tetrahedron: Asymmetry 16 (2005) 507–511
heated to 55 °C, and MeOH added dropwise over
30 min. After 1 h, TLC (95:5 CH2Cl2–MeOH) showed
complete conversion of 5 into 6 (Rf 0.76). Then, the mix-
ture was quenched with HOAc and coconcentrated with
MeOH and toluene. The residue was purified by column
135.4–127.5 ((Ph)2SiC(CH3)3), 84.2, 70.3 and 69.9
(C-2, C-3, C-4), 63.4 (C-5), 26.5 ((Ph)2SiC(CH3)3),
25.2 ((CH3)2SiC(CH3)3), 18.8 ((Ph)2SiC(CH3)3), 18.1
((CH3)2SiC(CH3)3). Anal. Calcd for C27H40O5Si2
(500.8): C, 64.76; H, 8.05. Found: C, 65.01; H, 7.98.
chromatography (7:3 toluene–EtOAc) to yield
(400 mg, 86%). For analysis, a small amount of 6 was
acetylated with Ac2O in pyridine. H NMR (CDCl3): d
6
4.7. 3-O-Allyl-2-O-tert-butyldimethylsilyl-5-O-tert-butyl-
diphenylsilyl-D-ribono-1,4-lactone, 9
1
7.48–7.37 (m, 5H, PhCH), 5.84 (s, 1H, PhCH), 5.01
(ddd, 1H, J2,3 8.3, J1a,2 2.7, J1b,2 3.8 Hz, H-2), 4.52
(dd, 1H, J3,4 6.1 Hz, H-3), 4.49–4.42 (m, 2H, H-4 and
H-5), 4.08 (dd, 1H, J5a,5b 12.8 Hz, H-5), 3.93 (dd, 1H,
J1a,1b 11.5 Hz, H-1a), 3.84 (dd, 1H, H-1b), 2.09 and
2.05 (2 s, each 3H, CH3CO), 0.88 (s, 9H, SiC(CH3)3),
0.03 (s, 6H, Si(CH3)2).
A stirred solution of 8 (3.5 g, 7.0 mmol) in dry acetoni-
trile (3.3 mL) and dry pyridine (1.1 mL) was cooled to
0 °C. Allyl chloroformate (1.46 mL, 14 mmol) in dry
acetonitrile (3.3 mL) was added dropwise over 45 min,
and stirring at 0 °C continued for 1 h. Then, TLC (9:1
toluene–EtOAc) showed complete conversion of 8 into
9 (Rf 0.83). After hydrolysing the remaining allyl chloro-
formate by addition of ice, the mixture was diluted with
EtOAc, washed with water, dried, filtered and concen-
trated. The residue was purified by column chromato-
graphy (toluene) (3.4 g, 84%). [a]D = +27 (c 1, CHCl3);
1H NMR (CDCl3): d 7.66–7.61, 7.44–7.38 (2 m, 10H,
Ph2Si), 5.97–5.84 (m, 1H, CH2–CH@CH2), 5.39 (br d,
1H, J2,3 6.0, J3,4 < 1.0 Hz, H-3), 5.38–5.31, 5.27–5.22
(2 m, each 1H, CH2–CH@CH2), 4.88 (d, 1H, H-2),
4.69–4.56 (m, 2H, CH2–CH@CH2), 4.47 (m, 1H, J4,5a
1.8, J4,5b 2.5 Hz, H-4), 3.91 (dd, 1H, J5a,5b 11.8 Hz, H-
5b), 3.80 (dd, 1H, H-5a), 1.06 (s, 9H, (Ph)2SiC(CH3)3),
0.93 (s, 9H, (CH3)2SiC(CH3)3), 0.21 and 0.14 (2 s, each
3H, Si(CH3)2); 13C NMR (CDCl3): d 173.5 (C-1), 153.8
(CO–CH2–CH@CH2), 135.3–127.8 ((Ph)2SiC(CH3)3),
119.1 (CH2–CH@CH2), 81.4, 74.8, 68.8 (C-2, C-3,
C-4), 68.6 (CH2–CH@CH2), 63.3 (C-5), 26.6
((Ph)2SiC(CH3)3), 25.3 ((CH3)2SiC(CH3)3), 18.9
((Ph)2SiC(CH3)3), 18.0 ((CH3)2SiC(CH3)3). Anal. Calcd
for C31H44O7Si2 (584.86): C, 63.66; H, 7.58. Found: C,
63.69; H, 7.70.
4.5. 2-O-tert-Butyldimethylsilyl-D-ribono-1,4-lactone, 7
A solution of 5 (10.8 g, 31 mmol) in EtOAc (150 mL),
containing 10% Pd/C (2.5 g), was hydrogenated for
6 h, then the mixture filtered over Celite and concen-
trated. The residue was dissolved in EtOAc (150 mL),
10% Pd/C (1.5 g) was added and the suspension sub-
jected to a second hydrogenation. After 2 h, the mixture
was filtered over Celite and concentrated. The crude
product was purified by column chromatography (95:5
CH2Cl2–MeOH) to obtain 7 as a white solid (8.0 g,
97%). [a]D = +24 (c 1.4, MeOH); Rf 0.64 (95:5
CH2Cl2–MeOH); 1H NMR (CDCl3): d 4.68 (d, 1H,
J2,3 5.5 Hz, H-2), 4.47 (m, 1H, J3,4 0.9, J4,5a 2.4, J4,5b
2.6 Hz, H-4), 4.31 (ddd, 1H, J3,OH 1.8 Hz, H-3), 3.97
(ddd, 1H, J5a,5b 12.6, H-5b), 3.79 (ddd, 1H, H-5a),
0.94 (s, 9H, SiC(CH3)3), 0.23 and 0.20 (2 s, each 3H,
Si(CH3)2); 13C NMR (CDCl3): d 170.5 (C-1), 84.6,
70.4 and 69.9 (C-2, C-3, C-4), 61.6 (C-5), 25.5
(SiC(CH3)3), 18.1 (SiC(CH3)3). Anal. Calcd for
C11H22O5Si (262.4): C, 50.36; H, 8.45. Found: C,
51.43; H, 8.53. For further analysis, a small amount of
7 was acetylated with Ac2O in pyridine. 1H NMR
(CDCl3): d 5.31 (dd, 1H, J2,3 5.9, J3,4 2.0 Hz, H-3),
4.64 (m, 1H, J4,5a 3.4, J4,5b 3.9 Hz, H-4), 4.59 (d, 1H,
H-2), 4.38 (dd, 1H, J5a,5b 12.6 Hz, H-5a), 4.24 (dd, 1H,
H-5b), 2.12 and 2.10 (2 s, each 3H, CH3CO), 0.91 (s,
9H, SiC(CH3)3), 0.20 and 0.13 (2 s, each 3H, Si(CH3)2).
The allyloxycarbonylated product (2.4 g, 4.1 mmol) was
concentrated twice with dry THF, then dissolved in dry
THF (10 mL) and purged with helium. After the addition
of a catalytic amount of yellow tetrakis-triphenylphos-
phine-palladium(0), the mixture was heated to 55 °C on
an oil bath. After 20 min, when TLC (8:2 toluene–
EtOAc) showed complete conversion into 9 (Rf 0.67),
the mixture was coconcentrated with toluene. The residue
was purified by column chromatography (4:6 hexane–tolu-
ene, then toluene) to yield 9 as a sirup (1.2 g, 75%).
4.6. 2-O-tert-Butyldimethylsilyl-5-O-tert-butyldiphenyl-
silyl-D-ribono-1,4-lactone, 8
1
[a]D = +35 (c 1.3, CHCl3); H NMR (CDCl3): d 7.65–
To a solution of 7 (3.5 g, 14 mmol) in CH2Cl2 (66 mL)
and pyridine (4.4 mL) were added TBDPSCl (4.1 mL,
15 mmol) and Et3N (1.0 mL). After 16 h, the mixture
was quenched with ice, diluted with CH2Cl2, washed
with 10% aq NaHCO3, dried, filtered and concentrated.
The residue was purified by column chromatography
7.61, 7.46–7.38 (2 m, 10H, Ph2Si), 5.96–5.87 (m, 1H,
CH2–CH@CH2), 5.34–5.28, 5.22–5.18 (2 m, each 1H,
CH2–CH@CH2), 4.20 (dd, 1H, J2,3 5.4, J3,4 1.4 Hz, H-
3), 4.36 (d, 1H, H-2), 4.39–4.31, 4.25–4.18 (2 m, each
1H, CH2–CH@CH2), 3.87 (dd, 1H, J4,5a 2.5, J5a,5b
11.8 Hz, H-5a), 3.76 (dd, 1H, J4,5b 3.4 Hz, H-5b), 1.05
(s, 9H, (Ph)2SiC(CH3)3), 0.87 (s, 9H, (CH3)2SiC(CH3)3),
0.09 and 0.06 (2 s, each 3H, Si(CH3)2); 13C NMR
(CDCl3): d 173.5 (C-1), 133.7 (CH2–CH@CH2), 135.3–
127.8 ((Ph)2SiC(CH3)3), 118.1 (CH2–CH@CH2), 85.6,
74.4 and 70.5 (C-2, C-3, C-4), 71.6 (CH2–CH@CH2),
(9:1 toluene–EtOAc) to afford
8
(5.4 g, 80%).
[a]D = +17 (c 1, CHCl3); Rf 0.54 (9:1 toluene–EtOAc);
1H NMR (CDCl3): d 7.71–7.67, 7.39–7.31 (2 m, 10H,
Ph2Si), 4.82 (d, 1H, J2,3 5.6 Hz, H-2), 4.34 (m, 1H J3,4
1.2, J4,5a 1.7, J4,5b 2.4 Hz, H-4), 4.28 (dd, 1H, H-3),
3.82 (dd, 1H, J5a,5b 11.8 Hz, H-5a), 3.64 (dd, 1H,
H-5b), 1.04 (s, 9H, (Ph)2SiC(CH3)3), 0.93 (s,
9H, (CH3)2SiC(CH3)3), 0.23 and 0.17 (2 s, each
3H, Si(CH3)2); 13C NMR (CDCl3): d 174.4 (C-1),
62.7
(C-5),
26.7
((Ph)2SiC(CH3)3),
25.5
((CH3)2SiC(CH3)3), 18.8 ((Ph)2SiC(CH3)3), 18.0
((CH3)2SiC(CH3)3). Anal. Calcd for C30H44O5Si2
(540.8): C, 66.62; H, 8.20. Found: C, 66.65; H, 8.15.

D. J. Lefeber et al. / Tetrahedron: Asymmetry 16 (2005) 507–511
511
4.8. 3-O-Allyl-2-O-tert-butyldimethylsilyl-5-O-tert-butyl-
diphenylsilyl-D-ribitol, 10
Acknowledgements
This work was supported by the European Union pro-
gram VACNET (grant ERB BIO 4CT960158).
To a solution of 9 (700 mg, 1.28 mmol) in THF (7 mL)
was added NaBH4 (100 mg), and the mixture heated
to 55 °C. A few drops of MeOH were added, and after
1 h, TLC (9:1 toluene–EtOAc) showed complete conver-
sion of 9 into 10 (Rf 0.21). The mixture was diluted with
MeOH, quenched with HOAc and coconcentrated with
toluene. The residue was purified by column chromato-
graphy (95:5 toluene–EtOAc) to yield 10 (600 mg, 86%).
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