2,4-Diazido-2,4,6-trideoxy-L-hexopyranoses as valuable building units in the synthesis of natural products

Article abstract of DOI:10.1016/j.tetasy.2003.11.018

Synthesis of five L-enantiomers of 2,4-diazido-2,4,6-trideoxy-pyranoses has been accomplished. These sugars were prepared via the regioselective protection of hydroxyl groups in L-rhamnoside and L-fucoside, followed by triflation and subsequent S_N

Full text of DOI:10.1016/j.tetasy.2003.11.018

Tetrahedron:
Asymmetry
Tetrahedron: Asymmetry 15 (2004) 299–306
2,4-Diazido-2,4,6-trideoxy-L-hexopyranoses as valuable building
units in the synthesis of natural products
Anna Banaszek* and Vladimir Zaitsev
Institute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-049 Warsaw, Poland
Received 3 October 2003; accepted 14 November 2003
Abstract—Synthesis of five L-enantiomers of 2,4-diazido-2,4,6-trideoxy-pyranoses has been accomplished. These sugars were pre-
L-rhamnoside and L-fucoside, followed by triflation and subsequent
pared via the regioselective protection of hydroxyl groups in
SN2 substitution with azido nucleophiles.
ꢀ 2003 Elsevier Ltd. All rights reserved.
1. Introduction
charides12 and glycopeptides,13 which contain an amino-
sugar unit, due to the unique properties of the azido
moiety to serve as a protective, nonactive group, easily
convertible into amino function.
In recent years interest in the 2,4-diamino-2,4,6-tride-
oxy-hexoses has markedly increased. This has been
caused by their direct involvement in biological and
immunochemical phenomena. These sugars have been
recognized in Gram-negative pathogens as components
of O-specific polysaccharides of the different types of
Shigella1 as well as of the capsular polysaccharides of
Bacteroides fragilis2 and Streptococus pneumoniae.3 In
addition, the fragments of 2,4-diamino-2,4,6-trideoxy-
hexoses can be found in the structures of bacterial
polysaccharides of 5,7-diamino-3,5,7,9-tetradeoxy-non-
ulosonic acids4 and have been used for their synthesis.5
On the other hand, these aminosugars have also been
isolated from kasugamycin6 and other aminoglycosidic
antibiotics.7
2. Results and discussion
Previous routes to 2,4-diazido-2,4,6-trideoxyhexopyr-
anosides used commercially available monosaccharides
(glucose, mannose, rhamnose, and fucose) as starting
materials. Their transformation into the desired 2,4-
diazido compounds was performed via epoxide forma-
tion/ring opening, or by nucleophilic substitution of
sulfonate groups. Our own synthetic sequence, depicted
in Schemes 1–3 also utilizes similar reactions for con-
version of L-rhamnose and L-fucose derivatives. How-
Most of the syntheses of 2,4-diamino-2,4,6-trideoxy-
ever, improved processes of displacement of the
sulfonate function by azide ion without oxirane ring
cleavage or opening of the oxirane ring by azide without
displacing the mesyl function, now allow the prepara-
tion of 2,4-diazido sugars of the required configuration
and in a satisfactory yield.
hexopyranoses concerns the
also utilized for the synthesis of polysaccharides.9 Syn-
theses of
-enantiomers are rather rare,5;10;11 therefore
D
-enantiomers,8 which were
L
there is a constant need to develop efficient methodol-
ogies for their preparation.
As a part of our progress in the synthesis of isomeric 2,4-
diamino-2,4,6-trideoxy-hexopyranoses of the defined
structure, we present here convenient routes to their
precursors that is, L-diazido sugars. The azido sugars
are valuable synthons in the synthesis both of disac-
Approaching the synthesis of methyl 2,4-diazido-2,4,6-
trideoxy-a-
pyranoside 1 was regioselectively protected at C-3 by a
p-methoxybenzyl (PMB) residue in a Bu3SnO mediated
reaction,14 to give 2a (Scheme 1). Further manipulation
with the blocking groups, as shown in Scheme 1, led to
L
-ido-pyranoside
6
methyl-a-L-rhamno-
methyl 2,4-di-O-acetyl-a-L-rhamno-pyranoside 2c in
high yield. This was converted to the 3-O-triflate deriv-
ative 2d furnishing, after treatment with MeONa
* Corresponding author. Tel.: +48-22-632-3221; fax: +48-22-632-6681;
e-mail: mlynar@icho.edu.pl
0957-4166/$ - see front matter ꢀ 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2003.11.018

300
A. Banaszek, V. Zaitsev / Tetrahedron: Asymmetry 15 (2004) 299–306
solution, the epoxide 3a. The 2-OH group in 3a was sulf-
OMe
OMe
OMe
onylated (MsCl, TsCl, Tf2O) to give the corresponding
derivatives 3b,c. The oxirane ring in 2-O-methyl deriv-
ative 3b was regioselectively cleavaged using TMSN3 in
the presence of BF3 etherate11b;15 to afford 4-azido sug-
ars 4. As indicated by the coupling constants (J1;2 3.9,
J2;3 5.7, J3;4 5.5, J4;5 3.7 Hz) the conformation of 4 is
a
e
g
O
O
O
HO
RO
O
OR'
HO
OR
OH
1
OR
3a: R = H
3b: R = Ms
3c: R = Tf
2a: R = H, R' = PMB
2b: R = Ac, R' = PMB
2c: R = Ac, R' = H
2d: R = Ac, R' = Tf
f
b
c
d
d
1
slightly distorted to C4 form due to 1,3-diaxial inter-
4
action in C1.
OMe
OMe
OMe
OR
OH
e
Assuming that a direct substitution of the mesyl group
in 4 by an azide ion could not be efficient enough due to
the axial–axial arrangement of 1-OMe-2-OMs,16 com-
pound 4 was converted first into the oxirane derivative
5. Compound 5 was treated with TMSN3/BF3ÆOEt2
O
O
g
i
O
O
N3
N3
OMs
N3
N3
5
4
6a: R = H
6b: R = Ac
6c
: R = Tf
b
d
species to afford 2,4-diazido sugar of a-L-ido configu-
OMe
ration 6. The NMR data (J1;2 6.2, J2;3 9.0, J3;4 8.1, J4;5
5.0 Hz) confirmed high predominance of 4C1 confor-
mation due to 1,3-diaxial interaction of 2,4-azido
groups, reinforced further by an 1,3-interaction of neg-
ative 4N3 group with the ring oxygen and are in full
agreement with the conclusion of Paulsen and Koeber-
OAc
OAc
OAc
O
O
h
h
O
6b
OR
OAc
N3
N3
N3
N3
N3
N3
9
8a: R = H
8b: R = Ac
7
nick regarding 2,4-diazido-a-D
-ido enantiomer.8b
Scheme 1. Reagents and conditions: (a) (1) Bu2SnO, (2) PMBI; (b)
Ac2O, Py; (c) CAN; (d) Tf2O, Py; (e) MeONa, MeOH; (f) MsCl, Py;
(g) TMSN3/BF3ÆOEt2; (h) Ac2O, AcOH, H2SO4; (i) NaNO2, DMF.
Because 1,2-substituents in 3c are rather pseudo-axial and
3-OTf is a very effective leaving group, it was interesting to
check whether it would be possible to displace the 2-OTf
group in the epoxide 2c by an azide ion. For this purpose
compound 3c was treated with NaN3 (or Bu4NN3) in
DMF. The reaction mixture was stirred at room temper-
ature, then at 60ꢁC. Unfortunately, the substrate failed to
react and after a long time decomposed.
OMe
O
OMe
RO
O
OMe
b
O
O
a
O
N3
R'O
OR
OR
11a: R = H
11b: R = Tf
10a: R = R' = H
12
10b: R = H, R' = PMB
10c: R = Ac, R' = PMB
10d: R = Ac, R' = H
10e: R = Ac, R' = Tf
Compound 6a was utilized for the preparation of L-talo
isomer 8 in a simple triflation of the 3-OH group, fol-
lowed by reaction with NaNO2.
OR
OAc
N3
OAc
OMe
N3
O
d
O
N3
N3
A very similar reaction sequence was performed with
methyl b-L-rhamnoside 10 providing, in the final step,
13a: R = H
13b: R = Ac
c
14
methyl 2,4-diazido-2,4,6-trideoxy-b-
14 (Scheme 2).
L-gulopyranoside
Scheme 2. Reagents and conditions: (a) NaN3, 18-crown-6, DMF; (b)
(g) TMSN3/BF3ÆOEt2; (c) Ac2O, Py; (d) Ac2O, AcOH, H2SO4.
For the preparation of starting sugar 10a the glycosyl-
ꢀ
ation procedure of Hodosi and Kovac via ꢀlocked ano-
meric configurationꢁ was applied.17 Accordingly,
reaction of L-rhamnose with Bu2SnO gave the 1,2-O-cis-
OAll
OR
OAll
OTf
OAll
OH
a
O
O
stannylene acetal, which upon treatment with MeI
underwent substitution at C-1 by a methyl group.
b-Glycoside 10a thus obtained in 70% yield was
accompanied by the 3-OMe derivative, which resulted
from the isomerization of the acetal (1,2 fi 1,3). Further
synthetic steps, depicted in Scheme 2, were fully analo-
gous to the transformation of the a-anomer. The sta-
bility of the epoxide ring in 11a during introduction of
the 2-O-triflate group and its displacement by azide
allowed 12 containing the 2-N3 moiety to be produced.5
Oxirane ring cleavage with TMSN3/BF3ÆOEt2 provided
b
O
c
OR'
OBz
OH
OH
OTf
OH
15
17
16a: R = H, R' = Bz
16b: R = Bz, R' = H
OAc
OAll
OTf
OAll
c
O
e
O
O
N3
BzO
N3
BzO
N3
OR
N3
N3
18
20
OAc
OAll
19a: R = Bz
19b: R = H
19c: R = Tf
d
f,g
O
b
N3
required L-gulo isomer 13a in high yield.
N3
21
Removal of 1-O-methyl group in all the 2,4-diazido
sugars was readily performed by acetolysis (Ac2O–
AcOH–H2SO4) to give the corresponding a,b-1-O-acetyl
derivatives.
Scheme 3. Reagents and conditions: (a) (1) Bu2SnO, benzene, reflux, (2)
BzCl; (b) Tf2O, Py; (c) NaN3, 18-crown-6, DMF; (d) MeONa, MeOH;
(e) PdCl2, AcOH, H2O, AcONa; (f) NaNO2, DMF; (g) Ac2O, Py.

A. Banaszek, V. Zaitsev / Tetrahedron: Asymmetry 15 (2004) 299–306
301
Utilizing
diazido-2,4,6-trideoxy-
accomplished. The synthesis begins from allyl a-
fucoside 15, which was converted into 3-O-benzoyl
derivative 16a via a Bu2SnO/BzCl reaction. The esteri-
fication process was accompanied by the known
migration of the benzoyl residue to furnish 2-O-benzoyl
derivative 16b. Compound 16a was readily transformed
into the 2,4-di-O-triflate derivative 17 in high yield
(Scheme 3).
L
-fucose as the precursor of a synthesis of 2,4-
and toluene (10 mL) were added and the solvents were
evaporated. The residue was dried in vacuo for 30 min
leaving a white powder. To this, dry DMF (20 mL) was
added and the mixture was vigorously stirred. A solu-
tion of PMBI (3.72 g, 15 mmol) in DMF (2.5 mL) was
added in two portions in 2 h intervals between the
additions. After 3 h the mixture was diluted with ether,
filtered, and washed with brine. The solvent was evap-
orated to dryness and the residue was chromatographed
on a silica gel column (ether). Eluted first was methyl 2a
L
-mannose and -altrose was
L
L
-
(1.26 g, 42%). Colorless oil, Rf 0.5 (ether); ½aꢁ ¼ ꢂ22:9
D
Displacement of O-triflate residues by azide was con-
ducted with NaN3/18-crown-6 or with Bu4NN3 in
DMF. It was noticed that the displacement of the 4-OTf
group proceeds much faster than that of the 2-OTf at
temperatures below 40 ꢁC, leading to 18. To substitute
the 2-OTf residue the temperature had to be raised to
60 ꢁC, affording after 2 h diazido derivative 19a. 1-O-
Deallylation of 19a was performed by the use of PdCl2
in MeOH,18 or PdCl2/AcOH, AcONa,19 to give after
acetylation 1,3-di-O-acetyl-2,4-diazido-3-O-benzoyl-a,b-
(c 0.95, CHCl3); 1H NMR (400 MHz, CDCl3) d: 7.3, 6.9
(2d, 4H, Ph), 4.71 (d, 1H, J 1.5 Hz, H-1), 4.63, 4.48 (2d,
2H, J 11.3 Hz, CH2Ph), 4.00 (m, 1H, H-2), 3.81 (s, 3H,
MeOPh), 3.64 (pq, 1H, J 6.6, 9.2 Hz, H-5), 3.60 (dd, 1H,
J 3.2, 9.2 Hz), 3.52 (t, 1H, J 9.2 Hz, H-4), 3.36 (s, 3H,
OMe), 2.36 (br s, 1H, OH), 2.12 (br s, 1H, OH), 1.31 (d,
3H, J 6.2 Hz, Me); 13C NMR (50 MHz, CDCl3) d: 129.6,
114.1, 100.4, 71.3, 79.5, 71.5, 67.7, 67.5, 55.3, 54.8, 17.6
(C-6); IR (film, cmꢂ1) m: 3440 (br), 1613, 1587, 1515,
1250. HRMS (ESI): exact mass calcd for C15H22O6Na
[M+Na]þ 321.1309, found 321.1326. Eluted with ethyl
acetate was 1 (0.78 g, 44%).
L
-manno-pyranoside 20.
Inversion of the configuration at C-3 of 19 was accom-
plished via a reaction sequence involving deblocking of
the 3-O-Bz, introduction of the 3-OTf and its displace-
ment using NaNO2, thus leading to 2,4-diazido-2,4,6-
3.3. Methyl 2,4-di-O-acetyl-3-O-(p-methoxy)benzyl-a-L-
rhamnopyranoside 2b
trideoxy-a-L-altro-pyranoside 21.
A solution of 2a (1.26 g, 4.2 mmol) in the mixture of
Ac2O and pyridine (1:1, 10 mL) was left overnight, then
evaporated with toluene (three times) and dried in vacuo
to give 2b (1.62 g, nearly quantitative yield). Colorless
The azido sugars presented herein are valuable building
blocks in the synthesis of the disaccharide part of gly-
coproteins and glycolipids. In addition, they can be used
as the starting material for different carbohydrate-based
mimetics.
oil, Rf 0.8 (ethyl acetate–hexanes, 1:1); ½aꢁ ¼ ꢂ6:2 (c
D
2.02, CHCl3); 1H NMR (200 MHz, CDCl3) d: 7.18, 6.85
(2d, 4H, Ar), 5.32 (dd, 1H, J 3.4, 1.7 Hz, H-2), 5.00 (m,
1H, H-4), 4.63 (d, 1H, J 1.7 Hz, H-1), 4.3, 4.6 (2d, 2H, J
11.7 Hz, CH2Ph), 4.00 (m, 1H, H-2), 3.80 (s, 3H, Me-
OPh), 3.8–3.6 (m, 2H, H-3, H-5), 3.35 (s, 3H, MeO),
2.14, 2.01 (2s, 6H, 2 Ac), 1.20 (d, 3H, J 6.4 Hz, Me); IR
(film, cmꢂ1) m: 1748, 1613, 1515, 1231. HRMS (ESI):
exact mass calcd for C19H26O8Na [M+Na]þ 405.1520,
found 405.1542.
3. Experimental
3.1. General
Optical rotations were measured with a JASCO Dip-360
Digital Polarimeter at room temperature. 1H NMR
spectra were recorded on Varian-400 (400 MHz) spec-
trometers with Me4Si as internal standard. High-reso-
lution mass spectra were taken on a Mariner PerSeptive
Biosystems mass spectrometer with time-of-flight (TOF)
detector. IR spectra were taken with a Perkin Elmer FT-
IR-1600 spectrophotometer. Reactions were controlled
using TLC on silica [Merck alu-plates (0.2 mm)]. All
reagents and solvents were purified and dried according
to common methods. All organic solutions were dried
over MgSO4. Reaction products were purified by flash
chromatography using Merckꢁs Kieselgel 60 (240–400
mesh or 70–230 mesh).
3.4. Methyl 2,4-di-O-acetyl-a-L-rhamnopyranoside 2c
A solution of 2b (1.62 g, 4.2 mmol) and CAN (4.85 g,
8.9 mmol) in the mixture MeCN–H2O (9:1, 50 mL) was
stirred until disappearance of the substrate (ꢀ2 h). A
two-phase system was carefully poured out into 50 mL
of satd aq NaHCO3. The mixture was extracted with
CH2Cl2. The combined organic extracts were washed
with brine and evaporated. The residue was chroma-
tographed on a silica gel (ether) to give 2c (0.79 g,
71%). Colorless needles, mp 105 ꢁC (hexane); Rf 0.5
3.2. Methyl 3-O-(p-methoxy)benzyl-a-
side 2a
L
-hamnopyrano-
(ethyl acetate–hexanes, 1:1); ½aꢁ ¼ ꢂ38:3 (c 0.95,
D
1
CHCl3); H NMR (200 MHz, CDCl3) d: 5.04 (dd, 1H,
J 1.6 Hz, H-2), 4.84 (t, 1H, J 9.9, 9.7 Hz, H-4), 4.64 (d,
1H, J 1.6 Hz, H-1), 4.0 (ddd, 1H, J 9.7, 7.3, 1.6 Hz, H-
3), 3.80 (dq, 1H, J 9.7, 6.2 Hz, H-5), 3.37 (s, 3H, OMe),
2.16, 2.14 (2 s, 6H, 2Ac), 2.05 (d, 1H, J 7.3 Hz, OH),
1.22 (d, 3H, J 6.2 Hz, Me); 13C NMR (50 MHz,
A suspension of Bu2SnO (2.49 g, 10 mmol) in dry MeOH
(50 mL) containing methyl a- -rhamnopyranoside
(1.78 g, 10 mmol) was heated under reflux until a clear
solution was formed (ꢀ1 h). Then CsF (2.28 g, 15 mmol)
L

302
A. Banaszek, V. Zaitsev / Tetrahedron: Asymmetry 15 (2004) 299–306
CDCl3) d: 98.1, 74.7, 72.7, 68.6, 65.7, 55.1, 21.0, 17.4;
IR (KBr, cmꢂ1) m: 3537 (sharp), 1737 (Ac), 1250, 1239.
Anal. Calcd for C11H18O7: C, 50.38; H, 6.92. Found:
C, 50.37; H, 7.07.
3.8. Methyl 3,4-anhydro-6-deoxy-2-O-trifluoromethane-
sulfonyl-a- -altropyranoside 3c
L
Prepared according to the procedure described for 2d.
White solid; ½aꢁ ¼ ꢂ47:6 (c 0.70, CHCl3).
D
3.5. Methyl 2,4-di-O-acetyl-3-O-trifluoromethanesulfon-
yl-a-L-rhamnopyranoside 2d
3.9. Methyl 4-azido-4,6-dideoxy-2-O-methanesulfonyl-
a-L-idopyranoside 4
To a solution of 2c (0.79 g, 3.02 mmol) in dry CH2Cl2
(15 mL) a mixture of Tf2O (0.8 mL, 4.5 mmol) and
pyridine (0.8 mL) in CH2Cl2 (20 mL) was added at
0 ꢁC and the reaction mixture was stirred for 10 min.
Then the solvent was evaporated. Co-evaporation of
the residue with toluene left a syrup, which was
extracted with hot hexane (3 · 25 mL), to give 2d
(1.14 g, 96%). Colorless crystals; mp 123–124 ꢁC (with
To a suspension of 3b (0.20 g, 0.85 mmol) in TMSN3
(1.0 mL), BF3ÆEt3O (0.1 mL) was added and the reaction
mixture was stirred at rt until no more starting material
was detected by TLC. Then the solution was poured
onto ice and extracted with CH2Cl2. The extracts were
washed with aqueous solution Na2CO3, dried, and
evaporated. Chromatography on silica gel (ether–hex-
anes, 1:1) gave 4 (0.15 g, 63%) as a pale yellow oil. Rf 0.8
decomp.); Rf 0.5 (ethyl acetate–hexanes, 1:3); ½aꢁ ¼
1
D
(ether–hexanes, 2:1); ½aꢁ ¼ ꢂ50:5 (c 2.00, CHCl3); H
D
ꢂ39:8 (c 0.85, CHCl3); HRMS (ESI): exact mass calcd
for C12H17O9SF3Na [M+Na]þ 417.0438, found
417.0448.
NMR (200 MHz, CDCl3) d: 4.77 (d, 1H, J 3.9 Hz, H-1),
4.50 (d, 1H, J 3.9 Hz, H-2), 4.28 (dq, 1H, J 6.7, 3.7 Hz,
H-5), 4.10 (ddd, 1H, J 7.2, 5.7, 5.5 Hz, H-3), 3.51 (dd,
1H, J 5.5, 3.7 Hz, H-4), 3.46 (s, 3H, MeO), 3.23 (d, 1H, J
7.2 Hz, OH), 3.15 (s, 3H, Me-SO3), 1.32 (d, 3H, J 6.7
Hz, Me); 13C NMR (50 MHz, CDCl3) d: 98.3, 75.6, 68.9,
64.2. 62.4, 56.0, 38.6, 15.5. Anal. Calcd for
C8H15O6SN3: C, 34.16; H, 5.33; N, 14.95. Found: C,
34.57; H, 5.38; N, 14.34.
3.6. Methyl 3,4-anhydro-6-deoxy-a-L-altropyranoside 3a
To a solution of 2d (1.14 g, 2.89 mmol) in MeOH,
(10 mL) 2 M NaOH (3 mL) was added dropwise at rt
and the mixture was stirred for 0.5 h. Then it was neu-
tralized with AcOH, evaporated and the residue was
extracted with CH2Cl2. Removal of the solvent and
column chromatography of the residue (hexane–ether,
1:1) gave 3a as a white solid (0.34 g, 74%), mp 65–66 ꢁC;
3.10. Methyl 2,3-anhydro-4-azido-4,6-dideoxy-a-L-gulo-
pyranoside 5
½aꢁ ¼ ꢂ79:5 (c 1.70, CHCl3); 1H NMR (200 MHz,
To a solution of 4 (90 mg, 0.33 mmol) in dry MeOH
(2 mL) 1 M MeONa (0.3 mL) was added. After 1 h the
reaction mixture was worked up as described for 3a to
give 5 (60 mg, quantitative yield). Colorless oil; Rf 0.6
D
CDCl3) d: 4.40 (d, 1H, J 4.4 Hz, H-1), 4.29 (q, 1H, J 7.1,
H-5), 3.80 (dd, 1H, J 6.6, 4.4 Hz, H-2), 3.27, 3.03 (2d,
2H, J 4.0 Hz, H-3, H-4), 2.07 (d, 1H, J 6.6 Hz, OH), 1.42
(d, 3H, J 7.1 Hz, Me); 13C NMR (50 MHz, CDCl3) d:
99.6, 66.0, 65.8, 53.7, 52.9, 56.2, 17.5.
1
(ether–hexanes, 1:1); ½aꢁ ¼ ꢂ64:5 (c 0.67, CHCl3); H
D
NMR (400 MHz, CDCl3) d: 4.93 (d, 1H, J 3.0 Hz, H-1),
4.10 (dq, 1H, J 6.6, 1.8 Hz, H-5), 3.54 (dd, 1H, J 3.7,
2.2 Hz, H-3), 3.46 (s, 3H, MeO), 3.45–3.35 (m, 1H, H-2),
3.36 (t, 1H, J 1.8 Hz, H-4), 1.27 (d, 3H, J 6.6 Hz, Me);
1H NMR (400 MHz, C6D6) d: 4.46 (d, 1H, J 3.1 Hz, H-
1), 3.96 (dq, 1H, J 6.6, 1.8 Hz, H-5), 3.12 (s, 3H, MeO),
2.86 (dd, 1H, J 3.7, 2.2 Hz, H-3), 2.81 (ddd, 1H, J 3.7,
3.11, 0.5 Hz, H-2), 1.37 (m, 1H, H-4), 1.00 (d, 3H, J
6.6 Hz, Me); 13C NMR (50 MHz, C6D6) d: 95.2, 63.5,
57.8, 55.1, 50.7, 50.5, 16.8.
3.7. Methyl 3,4-anhydro-6-deoxy-2-O-methanesulfonyl-
a-L-altropyranoside 3b
To a solution of 3a (0.14 g, 0.88 mmol) in dry CH2Cl2
(10 mL) pyridine (0.3 mL) and MsCl (0.15 mL, 2.0 mmol)
were added. After 12 h a satd aq solution of NaHCO3
(0.5 mL) was added and the mixture was stirred for 0.5 h.
The organic layer was separated and the water phase was
extracted with dichloromethane. The combined organic
solution was washed with brine, filtered through a layer
of MgSO4, and concentrated to give a crystalline 3b
(0.21 g, quantitative yield). Mp 106–107 ꢁC (chloroform–
3.11. Methyl 2,4-diazido-2,4,6-trideoxy-a-L-idopyrano-
side 6a
A suspension of 5 (0.63 g, 3.41 mmol) in TMSN3
(3.0 mL) was treated with BF3ÆOEt2 (0.5 mL). Further
proceeding––analogous to that described for 4, to give
0.69 g of 6a. Yield 89%; colorless oil; Rf 0.65 (ether–
hexane); Rf 0.7 (ether–hexanes, 2:1); ½aꢁ ¼ ꢂ56:5 (c
D
1
1.00, CHCl3); H NMR (400 MHz, CDCl3) d: 4.62 (d,
1H, J 4.3 Hz, H-1), 4.55 (dd, 1H, J 4.3, 0.5 Hz, H-2), 4.31
(q, 1H, J 7.0 Hz, H-5), 3.42 (pq, 1H, J 0.7, 1.4, 3.7 Hz, H-
3 or H-4), 3.41 (s, 3H, OMe), 3.11 (s, 3H, MeSO3), 3.08
(dt, 1H, J 0.7, 3.7 Hz), 1.44 (d, 3H, J 7.0 Hz, H-6); 13C
NMR (50 MHz, CDCl3) d: 96.2, 72.3, 65.9, 53.3, 51.2,
56.2, 38.3, 17.1. Anal. Calcd for C8H14O6S: C, 40.34; H,
5.88; S, 13.45. Found: C, 40.46; H, 6.03; S, 13.24.
1
hexanes, 1:1); ½aꢁ ¼ ꢂ41:1 (c 0.19, CHCl3); H NMR
D
(200 MHz, CDCl3) d: 4.57 (d, 1H, J 5.0 Hz, H-1), 4.26
(dq, 1H, J 6.8, 4.4 Hz, H-5), 3.82 (dt, 1H, J 6.7 Hz, H-3),
3.55 (dd, 1H, J 6.7, 4.4 Hz, H-4), 3.47 (s, 3H, OMe), 3.45
(dd, 1H, J 6.7, 5.0 Hz, H-2), 2.98 (d, 1H, J 6.0 Hz, OH),
1.29 (d, 3H, J 6.8 Hz, Me); 13C NMR (50 MHz, CDCl3)

A. Banaszek, V. Zaitsev / Tetrahedron: Asymmetry 15 (2004) 299–306
303
d: 99.2, 69.9, 65.6, 63.5, 62.9, 56.2, 15.1; IR (film, cmꢂ1
m: 3446 (OH), 2111 (N3), 1260.
)
Yield 78%; mp 166–167 ꢁC; ½aꢁ ¼ ꢂ53:2 (c 0.74,
D
CHCl3). Anal. Calcd for C7H12O3N6: C, 36.83; H, 5.26;
N, 36.85. Found: C, 36.97; H, 5.41; N, 37.01.
3.12. Methyl 3-O-acetyl-2,4-diazido-2,4,6-trideoxy-a-
idopyranoside 6b
L
-
Usual acetylation of 8a afforded 8b. ½aꢁ ¼ ꢂ94:8 (c 0.77,
D
1
CHCl3); H NMR (400 MHz, CDCl3) d: 5.37 (t, 1H, J
4.1 Hz, H-3), 4.69 (d, 1H, J 1.1 Hz, H-1), 4.00 (pq, 1H, J
1.9, 6.5 Hz H-5), 3.88 (td, 1H, J 1.1, 4.1 Hz, H-2), 3.80
(ddd, 1H, J 1.0, 1.9, 2.9 Hz, H-4), 2.21 (s, 3H, OAc), 1.32
(d, 3H, J 6.5 Hz, Me); HRMS (ESI): exact mass calcd for
C9H14O4N6Na [M+Na]þ 293.0969, found 293.0969.
Usual acetylation of 6a gave 6b as a syrup. ½aꢁ ¼ ꢂ61:1
D
(c 0.90, CHCl3); 1H NMR (400 MHz, CDCl3) d: 5.10 (t,
1H, J 8.1 Hz, H-3), 4.53 (d, 1H, J 6.2 Hz, H-1), 4.30 (pq,
1H, J 5.0, 6.9 Hz H-5), 3.64 (dd, 1H, J 5.0, 8.1 Hz, H-4),
3.49 (s, 3H, OMe), 3.45 (dd, 1H, J 6.2, 8.9 Hz, H-2), 2.16
(s, 3H, OAc), 1.29 (d, 3H, J 6.9 Hz, Me); 13C NMR
(100 MHz, CDCl3) d: 98.9, 70.3, 67.4, 62.6, 62.1, 56.4,
20.8, 14.4; HRMS (ESI): exact mass calcd for C9
H14O4N6Na [M+Na]þ 293.0969, found 293.0986.
3.15. 1,3-Di-O-acetyl-2,4-diazido-2,4,6-trideoxy-a-L-
talopyranose 9
Acetolysis of 8b was performed according to the pro-
cedure described for 7, to give 9 as a=b mixture in 72%
yield. Chromatography on silica gel (hexane–ether, 7:3)
gave the a anomer in the first fraction: ½aꢁ ¼ ꢂ73:5 (c
0.46, CHCl3); 1H NMR (400 MHz, C6D6) dD: 6.11 (d, 1H,
J 1.6 Hz), 5.08 (t, 1H, J 4.1 Hz, H-3), 3.52 (pq, 1H, J 2.1,
6.3 Hz H-5), 3.29 (dq, 1H, J 1.6, 4.1 Hz, H-2), 3.14 (m,
1H, H-4), 1.74, 1.55 (2s, 2 · 3H, 2 · Ac), 0.99 (d, 3H, J
6.3 Hz, Me); HRMS (ESI): exact mass calcd for
C10H14O5N6Na [M+Na]þ 321.0918, found 321.0934.
3.13. 1,3 Di-O-acetyl-2,4-diazido-2,4,6-trideoxy-a-L-ido-
pyranose 7
Compound 6b (0.135 g, 0.5 mmol) was dissolved in Ac2O
(4 mL), AcOH (2 mL), and the solution was cooled to
)20 ꢁC. 1 M H2SO4 in Ac2O (0.4 mL) was added. The
reaction was monitored by TLC (CH2Cl2–acetone, 9:1),
raising the temperature to 25 ꢁC. After finishing of the
reaction AcONa (0.2 g) was added and the mixture was
concentrated, then subjected to column chromatogra-
phy. Eluted first (CH2Cl2–acetone, 7:3) was the a ano-
b-Anomer: ½aꢁ ¼ þ84:2 (c 0.33, CHCl3); 1H NMR
D
(400 MHz, C6D6) d: 5.32 (d, 1H, J 1.6 Hz, H-1), 4.52
(t, 1H, J 4.1 Hz, H-3), 3.36 (ddd, 1H, J 0.8, 1.8, 4.1 Hz
H-2), 2.83 (ddd, 1H, J 0.8, 1.8, 4.1 Hz, H-4), 2.78 (pq,
1H, J 1.8, 6.4 Hz, H-5), 1.74, 1.57 (2s, 2 · 3H, 2 · Ac),
1.00 (d, 3H, J 6.4 Hz, Me); HRMS (ESI): exact mass
calcd for C10H14O5N6Na [M+Na]þ 321.0918, found
321.0934.
1
mer (59 mg, 39%) 7: ½aꢁ ¼ ꢂ18:6 (c 0.83, CHCl3); H
D
NMR (400 MHz, CDCl3) d: 5.84 (d, 1H, J 6.7 Hz, H-1),
5.19 (t, 1H, J 8.3, 8.5 Hz, H-3), 4.34 (pq, 1H, J 5.0,
6.9 Hz, H-5), 3.70 (dd, 1H, J 5.0, 8.3 Hz, H-4), 3.60 (dd,
1H, J 6.7, 8.5 Hz, H-2), 2.19, 2.16 (2s, 2 · 3H, 2 · Ac),
1.34 (d, 3H, J 6.9 Hz, Me); IR (KBr, cmꢂ1) m: 2109,
1760; HRMS (ESI): exact mass calcd for
C10H14O5N6Na [M+Na]þ 321.0918, found 321.0934.
Eluted second was the b anomer (42 mg, 28%):
3.16. Methyl b-
L
-rhamnopyranoside 10a and methyl 3-O-
½aꢁ ¼ þ116:3 (c 0.59, CHCl3); 1H NMR (400 MHz,
methyl-b- -rhamnopyranoside
L
D
CDCl3) d: 6.10 (d, 1H, J 3.0 Hz, H-1), 5.40 (t, 1H, J
6.2 Hz, H-3), 4.22 (pq, 1H, J 4.1, 6.7 Hz, H-5), 3.58 (dd,
1H, J 4.1, 6.2 Hz, H-4), 3.56 (dd, 1H, J 3.0, 6.2 Hz, H-2),
2.18, 2.17 (2s, 2 · 3H, 2 · Ac), 1.40 (d, 3H, J 6.7 Hz, Me);
HRMS (ESI): exact mass calcd for C10H14O5N6Na
[M+Na]þ 321.0918, found 321.0933.
A suspension of Bu2SnO (2.05 g, 8.2 mmol) in dry
MeOH (30 mL) containing -rhamnose hydrate (1,82 g,
L
10 mmol) was heated to reflux until a clear solution was
formed (30 min). Then CsF (1.90 g, 12 mmol) and tolu-
ene (10 mL) were added and the solvents were evapo-
rated in vacuo. The residue was dried in vacuo for
10 min leaving a white powder. To this, dry DMF
(35 mL) was added and the mixture was vigorously
stirred. After 10 min a solution of MeI (0.77 mL,
1.2 mmol) in DMF (2.5 mL) was slowly added 10 min
and the mixture was stirred for 3 h. Then the solvent was
evaporated and the residue was chromatographed on a
silica gel column (CH2Cl2–MeOH, 9:1 > 1:1). Eluted first
3.14. Methyl 2,4-diazido-2,4,6-trideoxy-a-L-talopyrano-
side 8a
To a solution of 6a (0.65 g, 2.85 mmol) in dry CH2Cl2
(15 mL) a mixture of Tf2O (0.70 mL, 4.28 mmol) and
pyridine (0.8 mL) in CH2Cl2 (70 mL) was added at
)10 ꢁC and the reaction mixture was allowed to stay for
10 min. Then it was diluted with CH2Cl2, washed with
brine, filtered through a layer of MgSO4, and concen-
trated. The residue was dried by three times evaporation
with toluene, then the crude tiflate (1.0 g) was dissolved
in DMF (30 mL). To this solution, sodium nitrite (0.3 g,
4.4 mmol) was added and the mixture was stirred over-
night at rt. The solvent was evaporated in vacuo and the
residue was taken into CH2Cl2, washed with water and
brine, dried over MgSO4 and concentrated. Crystalli-
zation from chloroform–hexane afforded 8a (0.51 g).
was methyl 3-methyl-b-L-rhamnopyranoside (0.44 g,
28%). White solid; mp 114–115 ꢁC (CH2Cl2–hexane)
characterized as its 2,4-di-O-acetyl derivative: mp 122–
123 ꢁC; ½aꢁ ¼ þ84:0 (c 0.25, CHCl3); 1H NMR
D
(400 MHz, CDCl3) d: 5.58 (dd, 1H, J 1.1, 3.3 Hz, H-
2), 4.93 (t, 1H, J 9.6, 9.8 Hz, H-4), 4.43 (d, 1H, J 1.1 Hz,
H-1), 3.53 (s, 3H, CH3Ph), 3.46 (pq, 1H, J 6.3, 9.6 Hz,
H-5), 3.35 (s, 3H, Me), 3.31 (dd, 1H, J 3.3, 9.8 Hz, H-3),
2.10, 2.18 (2s, 2 · 3H, 2 · Ac), 1.28 (d, 3H, J 6.3 Hz, Me).
Anal. Calcd for C12H20O7: C, 52.17; H, 7.25. Found: C,

304
A. Banaszek, V. Zaitsev / Tetrahedron: Asymmetry 15 (2004) 299–306
52.16; H, 7.35. Eluted second was 10a (1.03 g, 70%).
(200 MHz, CDCl3) d: 5.67 (dd, 1H, J 1.0, 3.5 Hz, H-2),
5.18 (t, 1H, J 9.7 Hz, H-4), 4.90 (dd, 1H, J 3.5, 9.9 Hz,
H-3), 4.50 (d, 1H, J 1.0 Hz, H-1), 3.52 (s, 3H, OMe),
3.58 (dq, 1H, J 6.2, 9.7 Hz, H-5), 2.20, 2.13 (2s, 2 · 3H,
2 · Ac), 1.33 (d, 3H, J 6.2 Hz, Me); IR (KBr, cmꢂ1) m:
1756. Anal. Calcd for C12H17O9SF3: C, 36.55; H, 4.35.
Found: 36.72; H, 4.64.
Colorless oil; mp 155–156 ꢁC; ½aꢁ ¼ þ84:4 (c 0.74,
D
CHCl3); 1H NMR (400 MHz, CDCl3) d: 5.47 (dd, 1H, J
3.2, 1.1 Hz, H-2), 5.07 (t, 1H, J 10.1 Hz, H-4), 5.02 (dd,
1H, J 3.2, 10.0 Hz, H-3), 4.50 (d, 1H, H-1), 3.54 (pq, 1H,
J 6.3, 10.0 Hz, H-5), 3.52 (s, 3H, Me), 2.16, 2.03, 1.97
(3s, 3 · 3H, 3 · Ac), 1.28 (d, 3H, J 6.3 Hz, Me). Anal.
Calcd for C13H20O8: C, 51.32; H, 6.58. Found: C, 50.99;
H, 6.85. Eluted third was substrate (0.37 g).
3.21. Methyl 3,4-anhydro-6-deoxy-b-
L
-altropyranoside
11a
3.17. Methyl 3-O-(p-methoxy)benzyl-b-L-rhamnopyrano-
side 10b
1
Pale yellow oil; ½aꢁ ¼ þ61:0 (c 1.60, CHCl3); H NMR
D
(200 MHz, CDCl3) d: 4.40 (d, 1H, J 1.8 Hz, H-1), 4.08
(q, 1H, J 6.9 Hz, H-5), 4.02 (t, 1H, J 1.8, 2.0 Hz, H-
2), 3.50 (s, 3H, OMe), 3.43 (ddd, 1H, J 1.0, 2.0, 3.9 Hz,
H-3), 3.05 (d, 1H, J 3.9 Hz, H-4), 2.35 (d, 1H, OH), 1.44
(d, 3H, J 6.9 Hz, Me); 13C NMR (50 MHz, CDCl3) d:
97.9, 70.2, 64.8, 55.1, 54.9, 56.8, 19.1.
Prepared from 10a. Yield 84%; colorless crystals; mp
130 ꢁC; ½aꢁ ¼ þ95:2 (c 0.42, CHCl3); 1H NMR
D
(400 MHz, CDCl3) d: 6.88–7.29 (m, 4H, Ph), 4.71–4.45
(2d, 2H, J 11.6 Hz, CH2Ph), 4.31 (d, 1H, J 1.1 Hz, H-1),
4.10 (t, 1H, J 1.1 Hz, H-2), 3.60 (t, 1H, J 9.1 Hz, H-4),
3.55 (s, 3H, CH3), 3.28 (m, 2H, H-3, H-5), 2.28, 2.22
(2bs, 2 · OH), 1.36 (d, 3H, J 6.1 Hz, Me); 13C NMR
(100 MHz, CDCl3) d: 129.5, 114.0, 100.7, 80.7, 71.7,
71.3, 70.6, 67.6, 56.9, 17.7. Anal. Calcd for C15H22O6: C,
60.39; H, 7.43. Found: C, 60.24; H, 7.51. Eluted second
was the substrate (0.41 g).
3.22. Methyl 3,4-anhydro-6-deoxy-2-O-trifluoromethane-
sulfonyl-b-L-altropyranoside 11b
Prepared from 11a in 89% yield; colorless oil;
½aꢁ ¼ þ39:0 (c 0.60, CHCl3). Anal. Calcd for
D
C8H11O6SF3: C, 32.88; H, 3.79. Found: 32.77; H, 4.07.
3.18. Methyl 2,4-di-O-acetyl-3-O-(p-methoxy)benzyl-b-L-
rhamnopyranoside 10c
3.23. Methyl 3,4-anhydro-2-azido-2,6-dideoxy-b-L-allo-
pyranoside 12
Prepared from 10b in theoretical yield; mp 140 ꢁC
1
(ether–hexane); ½aꢁ ¼ þ87:0 (c 0.95, CHCl3); H NMR
D
(200 MHz, CDCl3) d: 7.22, 6.80 (2d, 4H, Ph), 5.57 (dd,
1H, J 1.1, 3.3 Hz, H-2), 4.95 (t, 1H, J 9.7 Hz, H-4), 4.38
(d, 1H, J 1.1 Hz, H-1), 4.60, 4.35 (2d, 2H, J 11.9 Hz,
CH2Ph), 3.80 (s, 3H, MeOPh), 3.50 (s, 3H, OMe), 3.45
(dd, 1H, J 3.3, 9.7 Hz, H-3), 3.40–3.30 (dq, 1H, J 6.2,
9.7 Hz, H-5), 2.20, 2.00 (2s, 2 · 3H, 2 · Ac), 1.25 (d, 3H,
Me); 13C NMR (50 MHz, CDCl3) d: 129.4, 113.7, 99.9,
75.9, 72.3, 70.5, 70.4, 67.5, 57.2, 55.2, 21.0, 20.9, 17.4.
Anal. Calcd for C19H26O6: C, 59.68; H, 6.85. Found: C,
60.04; H, 7.23.
A suspension of NaN3 (0.29 g, 4.5 mmol), 11b (0.46 g,
1.60 mmol) and 18-crown-6 (1.15 g, 4.4 mmol) in toluene
(10 mL) was stirred at rt overnight, then it was diluted
with toluene, filtered, washed with water and brine to
give, after drying over MgSO4 and evaporation of the
solvent 12 (0.23 g, 78%). White solid, mp 65 ꢁC (hex-
anes); ½aꢁ ¼ þ108:0 (c 1.00, CHCl3); 1H NMR
D
(400 MHz, CDCl3) d: 4.40 (d, 1H, J 7.6 Hz, H-1),
4.10 (q, 1H, J 6.8 Hz, H-5), 3.58 (dd, 1H, J 2.0, 7.6 Hz,
H-2), 3.50 (s, 3H, OMe), 3.44 (ddd, 1H, J 2.0, 4.2,
1.0 Hz, H-3), 3.15 (d, 1H, J 4.2 Hz, H-4), 1.41 (d, 3H, J
6.2 Hz, Me); 13C NMR (50 MHz, CDCl3) d: 100.1, 57.1,
70.4, 60.3, 58.1, 54.5, 18.9; IR (KBr, cmꢂ1) m: 2130, 2108.
Anal. Calcd for C7H11O3N3: C, 45.40; H, 5.99; N, 22.69.
Found: 45.32; H, 6.28; N, 22.15.
3.19. Methyl 2,4-di-O-acetyl-b-L-rhamnopyranoside 10d
Prepared from 10c in 72% yield; colorless crystals; mp
165 ꢁC (ether–hexane); ½aꢁ ¼ þ20:0 (c 0.13, CHCl3); 1H
D
NMR (200 MHz, CDCl3) d: 5.40 (dd, 1H, J 1.0, 3.6 Hz,
H-2), 4.82 (t, 1H, J 9.5, 9.7 Hz, H-4), 4.45 (d, 1H, J
1.0 Hz, H-1), 4.78 (ddd, 1H, J 3.6, 7.3, 9.7 Hz, H-3), 3.51
(s, 3H, OMe), 3.55–3.40 (dq, 1H, J 6.2, 9.5 Hz, H-5),
2.38 (d, 1H, J 7.3 Hz, OH), 2.19, 2.13 (2s, 2 · 3H,
2 · Ac), 1.30 (d, 3H, J 6.2 Hz, Me); 13C NMR (50 MHz,
CDCl3) d: 99.8, 74.6, 71.4, 71.2, 70.2, 57.2, 21.0, 17.5; IR
(KBr, cmꢂ1) m: 3424, 1738, 1723. Anal. Calcd for
C11H18O7: C, 50.38; H, 6.92. Found: C, 50.04; H, 7.20.
3.24. Methyl 2,4-diazido-2,4,6-trideoxy-b-
side 13a
L
-gulopyrano-
1
Prepared from 12 in 88% yield; colorless oil; H NMR
(400 MHz, C6D6) d: 4.38 (d, 1H, J 8.1 Hz, H-1), 3.78
(dq, 1H, J 1.7, 6.5 Hz, H-5), 3.55 (t, 1H, J 3.7 Hz, H-3),
3.41 (dd, 1H, J 3.0, 8.1 Hz, H-2), 2.88 (dd, 1H, J 1.7,
3.4 Hz, H-4), 1.66 (br s, 1H, OH), 1.02 (d, 3H, J 6.5 Hz,
Me); 13C NMR (50 MHz, CDCl3) d: 100.9, 69.6, 68.0,
63.8, 61.0, 56.7, 16.8.
3.20. Methyl 2,4-di-O-acetyl-3-O-trifluoromethane-
sulfonyl-b-L-rhamnopyranoside 10e
13a was converted further into 3-O-acetyl derivative
13b: ½aꢁ ¼ þ25:5 (c 0.80, CHCl3); 1H NMR (400 MHz,
Prepared from 10d in 96% yield; colorless crystals, mp
100–101 ꢁC; ½aꢁ ¼ þ45:0 (c 0.95, CHCl3); 1H NMR
D
D

A. Banaszek, V. Zaitsev / Tetrahedron: Asymmetry 15 (2004) 299–306
305
CDCl3) d: 5.28 (t, 1H, J 3.6 Hz, H-3), 4.58 (d, 1H, J
8.1 Hz, H-1), 4.02 (pq, 1H, J 1.7, 6.5 Hz, H-5), 3.59 (dd,
1H, J 8.1, 3.4 Hz, H-2), 3.47 (dd, 1H, J 1.7, 3.6 Hz, H-4),
3.45 (s, 3H, OMe), 3.47 (dd, 1H, J 1.7, 3.6 Hz, H-4), 2.14
(s, 3H, OAc), 1.35 (d, 3H, J 6.5 Hz, Me). HRMS (ESI):
exact mass calcd for C9H14O4N6Na [M+Na]þ 293.0969,
found 293.0985.
3H, J 6.6 Hz, Me); 13C NMR (100 MHz, CDCl3) d: 15.9,
65.9, 67.0, 68.7, 70.8, 74.5, 97.9, 117.9, 128.4, 129.7,
129.8, 138.3, 133.2, 133.5, 166.4. HRMS (ESI): exact
mass calcd for C16H20O6Na [M+Na]þ 331.1149, found
331.1157.
3.28. Allyl 3-O-benzoyl-2,4-di-O-trifluoromethane-
sulfonyl-a-L-fucopyranoside 17
3.25. 1,3-Di-O-acetyl-2,4-diazido-2,4,6-trideoxy-a=b-L-
gulopyranose 14
A solution of 16a (0.7 g, 2.27 mmol) in CH2Cl2 (15 mL)
pyridine (2.5 mL) then Tf2O (1.12 mL, 6.81 mmol) was
added dropwise at )15 ꢁC. The temperature was allowed
to attain 0 ꢁC. THL (hexane–ether, 1:1) showed com-
plete conversion of 16a into the corresponding di-O-
triflyl derivative. Solid NaHCO3 was added and the
mixture was evaporated to dryness. Flash chromato-
graphy gave 17 (1.2 g, 92%) as white solid.
Acetolysis of 13b was performed according to the pro-
cedure described for 6b, to give 14 in 68% yield. Chro-
matography (hexane–ether, 7:3) gave b-anomer as a sole
product: ½aꢁ ¼ ꢂ12:7 (c 0.91, CHCl3); 1H NMR
D
(400 MHz, CDCl3) d: 5.88 (d, 1H, J 8.7 Hz, H-1), 5.88 (t,
1H, J 3.3 Hz, H-3), 4.17 (pq, 1H, J 1.7, 6.5 Hz, H-5),
3.77 (dd, 1H, J 3.3, 8.7 Hz, H-2), 3.52 (dd, 1H, J 1.7,
3.7 Hz, H-4), 2.16, 2.18 (2s, 2 · 3H, 2 · Ac), 1.34 (d, 3H,
J 6.5 Hz, Me); 13C NMR (50 MHz, CDCl3) d: 16.6, 20.7,
20.9, 57.1, 61.7, 69.7, 69.9, 91.4, 169.0, 169.3, 169.2.
HRMS (ESI): exact mass calcd for C10H14O5N6Na
[M+Na]þ 321.0918, found 321.0931.
½aꢁ ¼ ꢂ148:5 (c 0.68, CHCl3. HRMS (ESI): exact mass
D
calcd for C18H18O10F6S2Na [M+Na]þ 595.0138, found
595.0162.
3.29. Allyl 4-azido-3-O-benzoyl-2,6-dideoxy-2-O-tri-
fluoromethanesulfonyl-a-L-glucopyranoside 18
a-Anomer was not isolated.
To a solution of 17 (1.0 g, 1.75 mmol) in DMF (15 mL)
NaN3 (0.34 g, 5.25 mmol) or Bu4NN3 (3 g, 4.75 mmol)
was added and the mixture was stirred below 40 ꢁC.
TLC (hexane–ether, 7:3) revealed a single spot. The
suspension was poured into ice-cold water and extracted
with ether. Evaporation of the solvent followed by flash
chromatography afforded 18 (0.62 g, 77%). White solid;
3.26. Allyl a-L-fucopyranoside 15
Prepared according to the procedure described in Ref.
20: mp 156–157 ꢁC; ½aꢁ ¼ ꢂ191:6 (c 0.76, MeOH).
Lit.21: mp 154–158 ꢁC; ½aDꢁ ¼ ꢂ190 (MeOH).
D
1
mp 43–43 ꢁC; ½aꢁ ¼ ꢂ149:2 (c 1.10, CHCl3); H NMR
D
(400 MHz, CDCl3) d: 8.10–7.50 (m, 5H, Ph), 5.90 (m,
1H, All), 5.84 (t, 1H, J 9.9 Hz, H-3), 5.28–5.38 (m, 1H,
All), 5.13 (d, 1H, J 3.7 Hz, H-1), 4.87 (dd, 1H, J 3.7,
9.9 Hz, H-2), 3.88 (dq, 1H, J 6.2, 9.9 Hz, H-5), 3.37 (t,
1H, J 9.9 Hz, H-4), 1.39 (d, 3H, J 6.2 Hz, Me); IR (KBr,
cmꢂ1) m: 2113, 1732, 1648, 1602.
3.27. Allyl 3-O-benzoyl-a-
L-fucopyranoside 16a and
allyl 2-O-benzoyl-a- -fucopyranoside 16b
L
A suspension of 15a (2.04 g, 10 mmol) and Bu2SnO
(2.74 g, 11 mmol) in benzene (50 mL) was heated under
reflux with azeotropic removal of water for 3 h. After
cooling to 0 ꢁC BzCl (1.28 mL, 11 mmol) was added
dropwise and the mixture was stirred for 15 min at
ambient temperature. Then it was diluted with benzene
and poured into ice-cold aq NaHCO3 solution. The
organic layer was separated and the aqueous layer was
extracted with CH2Cl2. Concentration of extracts and
chromatography (hexane–AcOEt, 7:3) gave in the first
fraction 16b (0.83 g, 27%). Mp 115–116 ꢁC;
3.30. Allyl 2,4-diazido-3-O-benzoyl-2,4,6-trideoxy-a-L-
mannopyranoside 19a
A suspension of 19a (1.3 g, 2.27 mmol) in DMF was
added NaN3 (0.44 g, 6.80 mmol) and 18-crown-6 (1 g)
and the mixture was heated at 60 ꢁC. TLC (hexane–
ether, 7:3) indicated complete reaction (2 h). The mix-
ture was poured into ice-cold water and extracted with
ether. Evaporation of the solvent followed by the fil-
tration through a short column of silica gel yielded 19a
½aꢁ ¼ ꢂ191:7 (c 0.99, CHCl3); 1H NMR (400 MHz,
D
CDCl3) d: 8.10–7.50 (m, 5H, Ph), 5.97–5.88 (m, 1H, All),
5.47 (dd, 1H, J 3.0, 10.4 Hz, H-2), 5.38–5.26 (m, 1H,
All), 5.20 (d, 1H, J 3.0 Hz, H-1), 5.07 (dd, 1H, J 7.7,
10.4 Hz, H-3), 4.75 (d, 1H, J 7.7, H-4), 4.03 (q, 1H, J
6.5 Hz, H-5), 1.43 (d, 3H, J 6.5 Hz, Me). HRMS (ESI):
exact mass calcd for C16H20O6Na [M+Na]þ 331.1149,
found 331.1149. Eluted second was 16a (1.45 g, 47%).
(0.63 g, 77%). Colorless oil; ½aꢁ ¼ ꢂ156:0 (c 1.41,
D
1
CHCl3); H NMR (400 MHz, CDCl3) d: 7.49–8.13 (m,
5H, Ph), 5.90 (m, 1H, All), 5.54 (dd, 1H, J 3.7, 9.9 Hz,
H-3), 5.24–5.34 (m, 1H, All), 4.85 (d, 1H, J 1.0 Hz, H-1),
4.17 (dd, 2H, J 1.0, 3.7 Hz, H-2), 3.98–4.04 (m, 1H, All),
3.72 (pq, 1H, J 6.0, 9.9 Hz, H-4), 1.40 (d, 3H, J 6.0 Hz,
Me); 13C NMR (100 MHz, CDCl3) d: 18.3, 61.4, 63.2,
67.2, 68.4, 72.6, 96.9, 118.2, 128.6, 128.7, 130.0, 133.0,
133.7, 165.5; IR (KBr, cmꢂ1) m: 2113, 1755. HRMS
(ESI): exact mass calcd for C16H19O4N6 [M]þ 359.1468,
found 359.1473.
Mp 123–124 ꢁC; ½aꢁ ¼ ꢂ218:8 (c 0.82, CHCl3); 1H
D
NMR (400 MHz, CDCl3) d: 8.10–7.42 (m, 5H, Ph), 5.94
(m, 1H, All), 5.35 (m, 1H, All), 5.31 (dd, 1H, J 3.2,
10.2 Hz, H-3), 5.23 (m, 1H, All), 4.99 (d, 1H, J 4.0 Hz,
H-1), 4.26 (m, 1H, All), 4.16–4.10 (m, 2H, H-2, H-5),
3.99 (d, 1H, J 2.5 Hz, H-4), 2.10 (m, 2H, 2OH), 1.29 (d,

306
A. Banaszek, V. Zaitsev / Tetrahedron: Asymmetry 15 (2004) 299–306
3.31. 1-O-Acetyl-2,4-diazido-3-O-benzoyl-2,4,6-tride-
oxy-a- -mannopyranose 20a and 20b
(ESI): exact mass calcd for C11H16O4N6Na [M+Na]þ
319.1125, found 319.1144.
L
A suspension of 19a (0.179 g, 0.5 mmol) and PdCl2
(0.18 g, 0.5 mmol) in Ac2O–H2O (20:1, 10 mL) contain-
ing AcONa (0.18 g) was stirred overnight at rt. Removal
of the solvents, then filtration through a short column of
silica gel (hexane–ether, 7:3) gave a mixture of two
products. Usual acetylation followed by chromatogra-
phy (hexane–ether, 3:1) yielded b-anomer 20b in the first
References and notes
1. (a) Cohen, D.; Block, C.; Green, M. S.; Lowell, G.; Ofek,
I. J. Clin. Microbiol. 1989, 27, 162–167; (b) Cohen, D.;
Green, M. S.; Block, C.; Roauch, T.; Ofek, I. J. Infect.
Dis. 1988, 157, 1068–1071; (c) Taylor, D. N.; Trofa, A. C.;
Sadoff, J.; Chu, C.; Bryla, D.; Shiloach, J.; Cohen, D.;
Ashkenazi, S.; Lerman, Y.; Egan, W.; Schneerson, R.;
Robbins, J. B. Infect. Immun. 1993, 61, 3678–3687.
2. (a) Kontrohr, T. Carbohydr. Res. 1977, 58, 498–500; (b)
Baumann, H.; Tziabanos, A. O.; Brisson, J.-R.; Kasper,
D. L.; Jennings, H. J. Biochemistry 1992, 31, 4081–4089.
3. Jennings, H. J.; Lugowski, C.; Young, N. M. Biochemistry
1980, 19, 4712–4719.
1
fraction (51 mg, 28%). ½aꢁ ¼ ꢂ2:7 (c 0.47, CHCl3); H
D
NMR (400 MHz, CDCl3) d: 7.48–8.12 (m, 5H, Ph),
5.85 (d, 1H, J 1.3 Hz, H-1), 5.14 (dd, 1H, J 3.5, 10.1 Hz,
H-3), 4.33 (dd, 1H, J 1.1, 3.5 Hz, H-2), 3.66 (t, 1H, J
9.9 Hz, H-4), 3.47 (pq, 1H, J 6.1, 9.9 Hz, H-5), 2.18 (s,
3H, Ac), 1.45 (d, 3H, J 6.1 Hz, Me); 13C NMR
(100 MHz, CDCl3) d: 18.4, 20.9, 60.3, 62.5, 69.7, 72.2,
91.4, 128.4, 130.0, 133.9, 165.5, 168.6. HRMS (ESI):
exact mass calcd for C15H16O5N6Na [M+Na]þ 383.1074,
found 383.1087. Eluted second was 20a (77 mg, 42%).
4. (a) Knirel, Y. A.; Kochetkov, N. K. Biochemistry (Mos-
cow) 1994, 59, 1325–1383; (b) Castric, P.; Cassels, F. J.;
Carlson, R. W. J. Biol. Chem. 2001, 276, 26479–26485.
1
Mp 63–64 ꢁC; ½aꢁ ¼ ꢂ136:4 (c 0.45, CHCl3); H NMR
D
(400 MHz, CDCl3) d: 7.45–8.13 (m, 5H, Ph), 6.10 (d,
1H, J 1.9 Hz, H-1), 5.49 (dd, 1H, J 3.7, 9.9 Hz, H-3),
4.19 (dd, 1H, J 1.9, 3.7 Hz, H-2), 3.72–3.80 (m, 2H, H-4,
H-5), 2.18 (s, 3H, Ac), 1.41 (d, 3H, J 6.6 Hz, Me);
HRMS (ESI): exact mass calcd for C15H16O5N6Na
[M+Na]þ 383.1074, found 383.1092.
€
5. Tsvetkov, Y. E.; Shashkov, A. S.; Knirel, Y. A.; Zahrin-
ger, U. Carbohydr. Res. 2001, 335, 221–243.
6. Suhara, T.; Maeda, K.; Umezawa, H. Tetrahedron Lett.
1966, 7, 1239–1244.
7. Umezawa, S. Adv. Carbohydr. Chem. Biochem. 1974, 30,
111–182.
^
^
ꢀ
ꢀ
8. (a) Capek, K.; Capkova, J.; Jary, J.; Knirel, Y. A.;
Shashkov, A. S. Collection Czechoslovak Chem. Commun.
1987, 52, 2248–2259; (b) Paulsen, H.; Koebernick, H.
Chem. Ber. 1976, 109, 90–103; (c) Smid, P.; Jorning, W. P.
A.; van Duuren, A. M. G.; Boons, G. J. P. H.; van der
Marel, G. A.; van Boom, J. H. J. Carbohydr. Chem. 1992,
11, 849–865, and references cited therein.
3.32. Allyl 2,4-diazido-2,4,6-trideoxy-a-L-mannopyranose
19b
Prepared by usual deprotection of 3-O-Bz in 19a using
2 M MeONa in MeOH. ½aꢁ ¼ ꢂ136:7 (c 0.78, CHCl3).
€
9. (a) Paulsen, H.; Lockhoff, O.; Schroder, B.; Stenzel, W.
D
Carbohydr. Res. 1979, 68, 239–255; (b) Medgyes, A.;
Farkas, E.; Liptak, A.; Pozsgay, V. Tetrahedron 1997, 53,
4159–4178.
HRMS (ESI): exact mass calcd for C9H14O3N6Na
[M+Na]þ 277.1020, found 277.1038.
10. (a) Zehavi, U.; Sharon, N. J. Org. Chem. 1972, 37, 2141–
2145; (b) Jeanloz, R. W.; Rapin, A. M. C. J. Org. Chem.
1963, 28, 2978–2983.
11. (a) Banaszek, A.; Pakulski, Z.; Zamojski, A. Carbohydr.
Res. 1995, 279, 173–182; (b) Banaszek, A.; Janisz, B.
Tetrahedron: Asymmetry 2000, 11, 4693–4700.
12. Paulsen, H. Angew. Chem., Int. Ed. Engl. 1982, 21, 155–
173.
3.33. Allyl 2,4-diazido-2,4,6-trideoxy-3-O-trifluoro-
methanesulfonyl-a-L-mannopyranoside 19c
Prepared according to the procedure described for 17
was used in a crude state for epimerization reaction.
13. (a) Jiaang, W.-T.; Chang, M.-X.; Tseng, P.-H.; Chen,
S.-T. Tetrahedron Lett. 2000, 41, 3127–3130; (b) Wong,
C.-H.; Hendrix, M.; Manning, D. D.; Rosenbohm,
C.; Greenberg, W. A. J. Am. Chem. Soc. 1998, 120,
8319–8327.
14. Izumi, M.; Suhara, Y.; Ichikawa, Y. J. Org. Chem. 1998,
63, 4811–4816.
15. Janairo, G.; Kowolik, W.; Voelter, W. Liebigs Ann. Chem.
1987, 165–167.
3.34. Allyl 3-O-acetyl-2,4-diazido-2,4,6-trideoxy-a-L-
altropyranoside 21
Triflate 19c (0.4 g, 1.0 mmol) was stirred with NaNO2
(0.2 g, 3 mmol) and 18-crown-6 (0.3 g) at 40 ꢁC until the
reaction was completed TLC (hexane–ether, 7:3). Then
the mixture was poured into ice-cold water and
extracted with ether. Evaporation of the solvent and
subsequent acetylation of the residue afforded 21, which
was purified by flash chromatography to yield white
16. Karpiesiuk, W.; Banaszek, A.; Zamojski, A. Carbohydr.
Res. 1989, 186, 156–162, and references cited therein.
ꢀꢁ
17. (a) Hodosi, G.; Kovac, P. J. Am. Chem. Soc. 1997, 119,
1
2335–2336; (b) Srivastava, V. K.; Schuerch, C. Tetrahe-
dron Lett. 1979, 3269–3273.
solid (0.21 g, 71%). ½aꢁ ¼ ꢂ91:9 (c 0.42, CHCl3); H
D
NMR (400 MHz, CDCl3) d: 5.85–5.95 (m, 1H, All),
5.21–5.34 (m, 1H, All), 5.07 (dd, 1H, J 3.7, 6.2 Hz, H-3),
4.71 (d, 1H, J 3.3 Hz, H-1), 4.14 (q, 1H, J 6.6 Hz, H-5),
3.87 (dd, 1H, J 3.3, 6.2 Hz, H-2), 3.49 (dd, 1H, J 3.7,
7.8 Hz, H-4), 2.17 (s, 3H, Ac), 1.36 (d, 3H, J 6.6 Hz,
Me); 13C NMR (100 MHz, CDCl3) d: 18.0, 20.7, 59.7,
60.4, 65.4, 68.8, 70.0, 97.1, 117.4, 133.4, 170.1. HRMS
18. Yu, B.; Yu, H.; Han, X. Synlett 1999, 753–755.
19. Iuima, H.; Ogawa, T. Carbohydr. Res. 1988, 172, 183–193.
20. Vermeer, J. H.; van Dijk, C. M.; Kamerling, J. P.;
Vliegenthart, J. F. G. Eur. J. Org. Chem. 2001, 193–
209.
21. Garegg, P. J.; Norberg, T. Carbohydr. Res. 1976, 52, 235–
240.