A practical route to multifunctional 2-azido-2-deoxy-D-glucopyranosyl donors

Full text of DOI:10.1021/jo990811p

J . Org. Chem. 1999, 64, 7277-7280
7277
O-2 triflate derivatives of â-mannosides15,16 and 1,6-
anhydro-â-mannopyranoses,17-19 azide-displacement in
2-deoxy-2-iodo-1,6-anhydroglucopyranose,20 and conver-
sion of glucosamine derivatives in one step by diazo-
transfer21-24 using TfN3, or through 2-deoxy-2-hydra-
zinoglucopyranose.25 Despite many attempts, a high-
yielding protocol that can be used safely to afford differ-
entially protected azidoglucose derivatives on the mul-
tigram scale is still missing.
A P r a ctica l Rou te to Mu ltifu n ction a l
2-Azid o-2-d eoxy-D-glu cop yr a n osyl Don or s
Vince Pozsgay†
National Institute of Child Health and Human
Development, National Institutes of Health, 6 Center Drive,
MSC 2720, Bethesda, Maryland 20892-2720
Received May 18, 1999
Our program26,27 aimed at synthetic oligosaccharide-
based glycoconjugate vaccines28 against the Gram-nega-
tive pathogen Shigella dysenteriae type 1 requires rela-
tively large amounts of 2-azido-2-deoxy-D-glucopyranosyl
blocks as glycosyl donors for fashioning an R-linked
N-acetyl-D-glucosamine residue that is part of the O-
specific polysaccharide of this bacterium. Ideally, such
donors are equipped with protecting group(s) that permit
regioselective deprotection in a single step for extension
of the existing oligosaccharide chain. Here we describe a
practical route to 2-azido-2-deoxyglucopyranosyl building
blocks that feature diverse protecting group patterns
from an easily available starting material.
N-Acyl derivatives of 2-amino-2-deoxy-D-glucopyranose
(1) are frequent components of naturally occurring gly-
coconjugates1 including N- and O-linked glycoproteins,
glycosaminoglycans (e.g., hyaluronic acid, heparin, kera-
tan sulfate), proteoglycans, glycolipids, bacterial capsular
polysaccharides,2,3 lipopolysaccharides,4 teichuronic ac-
ids,5 antibiotics,6,7 and other materials. As a consequence
of this biological rationale, development of synthetic
schemes for elaborating glycosides of 1 has been targeted
Our approach capitalizes on the observation of van
Boom, who found that azide substitution of a triflyloxy
group at C-2 of â-linked mannopyranose derivatives
affords 2-azido-gluco compounds, whereas the corre-
sponding R-diastereomers are unreactive.15 Previous
examples for employing this principle for the preparation
of 2-azidoglucose derivatives15,16,29 used either â-linked
O-mannosides that are difficult to synthesize and to
convert into glycosyl donors or 1,3,4,6-tetra-O-acetyl-â-
D-mannopyranose, for which no efficient synthetic ap-
proach is available. In our logic the synthetic target is
approached from a manno precursor that already con-
tains a good leaving group at the anomeric position that
(1) by its proper configuration does not interfere with the
nucleophilic introduction of the azido group and (2) can
be exploited for anomeric activation. In putting this
concept into practice we capitalized on the easy avail-
ability of phenyl 1-thio-â-D-mannopyranoside (2) in large
quantities.30 Next we describe how this concept was
realized.
by many investigators. In these endeavors the presence
of an (acyl)amino functionality at the C-2 carbon atom
next to the anomeric center introduces a major challenge.
Numerous “participating” N-protecting groups have been
proposed for the synthesis of 1,2-trans (â) glycosides of
1.8 In contrast, syntheses of 1,2-cis-linked (R) 2-amino-
2-deoxy-D-glucopyranosides almost always rely on 2-azido-
2-deoxyglucopyranose-derived donors.8 The crucial step
in the synthesis of such derivatives is the introduction
of the azido functionality at C-2 in a diastereoselective
process. Available methods include azidonitration,9 azi-
dochlorination,10 and azidoselenation11,12 of glycals, azide-
opening of 2,3-mannoepoxides,13,14 azide-displacement of
† Tel: 301-402-0036. Email: vipo@helix.nih.gov.
(1) Glycosciences: composition, structure, and function; Allen, H. J .,
Kisailus, E. C. Eds.; Marcel Dekker: New York, 1992.
(2) Kenne, L.; Lindberg, B. In The Polysaccharides; Aspinall, G. O.,
Ed.; Academic Press: New York, 1983; Vol. 2, pp 287-363.
(3) Lindberg, B. Adv. Carbohydr. Chem. Biochem. 1990, 48, 279-
318.
(4) Mamat, U.; Seydel, U.; Grimmecke, D.; Holst, O.; Rietschel, E.
T. In Comprehensive Natural Product Chemistry, Vol. 3; Pinto, B. M.,
Ed.; Elsevier: Amsterdam, 1999, in press.
(5) J ennings, H. J .; Pon, R. A. In Polysaccharides in medicinal
applications; Dumitriu, S., Ed.; Marcel Dekker: New York, 1996; pp
443-479.
(6) Griesebach, H. Adv. Carbohydr. Chem. Biochem. 1978, 35, 81-
126.
(7) Umezawa, S. Adv. Carbohydr. Chem. Biochem. 1974, 30, 111-
182.
(8) Banoub, J .; Boullanger, P.; Lafont, D. Chem. Rev. 1992, 92,
1167-1195.
(9) Lemieux, R. U.; Ratcliffe, R. M. Can. J . Chem. 1979, 57, 1244-
1251.
(15) Vos, J . N.; van Boom, J . H.; van Boeckel, C. A. A.; Beetz, T. J .
Carbohydr. Chem. 1984, 3, 117-124.
(16) Pozsgay, V.; Glaudemans, C. P. J .; Robbins, J . B.; Schneerson,
R. Tetrahedron 1992, 48, 10249-10264.
(17) Hori, H.; Nihsida, Y.; Ohrui, H.; Meguro, H. J . Org. Chem. 1989,
54, 1346-1353.
(18) Kloosterman, M.; de Nijs, M. P.; van Boom, J . H. J . Carbohydr.
Chem. 1986, 5, 215-233.
(19) Dasgupta, F.; Garegg, P. J . Synthesis 1988, 626-628.
(20) Tailler, D.; J acquinet, J . C.; Noirot, A.-M.; Beau, J .-M. J . Chem.
Soc., Perkin Trans 1 1992, 3163-3164.
(21) Vasella, A.; Witzig, C.; Chiara, J .-L.; Martin-Lomas, M. Helv.
Chim. Acta 1991, 74, 2073-2077.
(22) Buskas, T.; Garegg, P. J .; Konradsson, P.; Maloisel, J .-L.
Tetrahedron Asymmetry 1994, 5, 2187-2194.
(23) Alper, P. B.; Hung, S.-C.; Wong, C.-H. Tetrahedron Lett. 1996,
37, 6029-6032.
(10) Bovin, N. V.; Zurabyan, S. E.; Khorlin, A. Y. Carbohydr. Res.
1981, 98, 25-35.
(24) Olsson, L.; J ia, Z. J .; Fraser-Reid, B. J . Org. Chem. 1998, 63,
3790-3792.
(11) Czernecki, S.; Ayadi, E.; Randriamandimby, D. J . Chem. Soc.,
Chem. Commun 1994, 35-36.
(25) Dasgupta, F.; Garegg, P. J . J . Chem. Soc., Chem. Commun
1989, 1640-1641.
(12) Chelain, E.; Czernecki, S.; Chmielewski, M.; Kaluza, Z. J .
Carbohydr. Chem. 1996, 15, 571-579.
(26) Pozsgay, V. J . Am. Chem. Soc. 1995, 117, 6673-6681.
(27) Pozsgay, V. J . Org. Chem. 1998, 63, 5983-5999.
(28) Pozsgay, V.; Chu, C.; Pannell, L.; Wolfe, J .; Robbins, J . B.;
Schneerson, R. Proc. Natl. Acad. Sci. 1999, 96, 5194-5197.
(29) Pavliak, V.; Kovac, P. Carbohydr. Res. 1991, 210, 333-337.
(13) Paulsen, H.; Koebernick, H.; Stenzel, W.; Ko¨ll, P. Tetrahedron
Lett. 1975, 1493-1496.
(14) Paulsen, H.; Stenzel, W. Ber. Dtsch. Chem. Ges. 1978, 111,
2334-2347.
10.1021/jo990811p This article not subject to U.S. Copyright. Published 1999 by the American Chemical Society
Published on Web 08/31/1999

7278 J . Org. Chem., Vol. 64, No. 19, 1999
Notes
Sch em e 1a
a
Reagents and conditions: (a) 2 equiv of TBDPSiCl, C5H5N, 25 °C, 24 h, 86%; (b) DMP, CSA, 25 °C, 10 min, 96%; (c) Bu4NF, THF, 25
°C, 24; (d) Ac2O, C5H5N, 25 °C, 2 h; (e) TFA/MeOH, 25 °C, 2 h, 74% for three steps; (f) 1.2 equiv of Bu2SnO, C6H6, reflux, 2 h, then MBnBr,
Bu4NI, 65-70 °C, 90 min, 66%; (g) Tf2O, C5H5N, -15 °C, 20 min, (h) NaN3, DMF, 25 °C, 84% for two steps; (i) 2.6 equiv of Ce(NH4)2(NO3)6,
MeCN, H2O, 25 °C, 2 h; (j) 1.4 equiv of (CA)2O, C5H5N, 25 °C, 1 h, 94% for two steps. Abbreviations: CA, monochloroacetyl; MBn,
4-methoxybenzyl; Tf, trifluoromethanesulfonyl.
Our method is depicted in Scheme 1. The goal in the
initial phase was to introduce protecting groups at O-3,4,
and 6, leaving the hydroxyl group at C-2 unprotected.
Thus, compound30 2 was treated with tert-butyldiphen-
ylsilyl chloride to afford the silylated intermediate 3,
which was converted into the acetal 4 by treatment with
dimethoxypropane in the presence of CSA. Next, the silyl
group was removed by exposure of crude 4 to Bu4NF to
afford the diol 5, which was acetylated in situ with acetic
anhydride and pyridine. The diacetate 6 so obtained could
be isolated in sufficient purity by crystallization without
the need of chromatography. Subsequently, the acetal
protection was removed by acid hydrolysis to provide the
diol 7 in an analytically pure form after crystallization
(71% for five steps without isolating the intermediates).
Next, compound 7 was treated with dibutyltin oxide,
followed by treatment of the intermediate stannylidene
acetal with 4-methoxybenzyl bromide31 under standard
conditions32 to yield the benzyl ether 8. With the prepa-
ration of the partially protected derivative 8 that contains
only HO-2 free, the stage was set for introduction of the
azide group at C-2 using van Boom’s protocol.15 Thus,
reaction of 8 with triflic anhydride/pyridine afforded the
sulfonate 9. This was treated in situ with NaN3 to provide
the targeted 2-azido-2-deoxy-thioglucoside derivative 10
in pure form in 84% yield after column chromatographic
purification. To demonstrate the flexibility of our ap-
proach, 10 was converted to the fully acylated glu-
cosamine donor 12 in a two-step sequence involving
oxidative removal of the methoxybenzyl group to afford
the alcohol 11, which upon treatment with monochloro-
acetic anhydride provided the fully acylated glucosamine
donor 12.
anomeric activation by thiophilic reagents33,34 or can be
replaced by other leaving groups if so required, e.g., by
halogens in one step35 or by the powerful trichloroace-
timidoyl group36 after hydrolytic removal of the phe-
nylthio moiety. The protecting groups in 10 and 12 are
stable under a variety of glycosylation conditions and
allow orthogonal deprotection at either O-3 or O-4 and
O-6 for glycosylation or to introduce other protecting
groups. The starting material is easily available, and the
protocol can be performed at the multigram scale.
Therefore, our method is likely to complement the
already established protocols for the synthesis of azido-
glucopyranose donors.
Exp er im en ta l Section
Gen er a l Meth od s. Optical rotations were measured at room
temperature with an automatic polarimeter in CHCl3. Melting
points are uncorrected. TLC was performed on Kieselgel 60 F254
(Merck) with detection by charring with sulfuric acid. Column
chromatography was performed on silica gel 60 (Merck 0.063-
0.200 mm). The 1H and 13C NMR spectra were recorded at 300
and 75 MHz nominal frequencies, respectively, in CDCl3 solu-
tions. Internal references were TMS (0.000 ppm for 1H) and
CDCl3 (77.00 ppm for 13C). The mass spectra were recorded in
the chemical ionization mode using NH3 as the ionizing gas.
Elemental analyses were performed by Atlantic Microlab, Inc.,
Norcross, GA.
P h en yl 6-O-ter t-Bu tyld ip h en ylsilyl-1-th io-â-D-m a n n op y-
r a n osid e (3). To a solution of 2 (52 g, 191 mmol) in C5H5N (200
mL) was added tert-butyldiphenylsilyl chloride (100 mL, 385
mmol) at 25 °C. After 24 h the solution was concentrated.
Toluene was added to and evaporated from the residue several
times followed by extractive workup (CHCl3/H2O). Column
chromatographic purification of the residue using 19:1 EtOAc-
MeOH as the eluant afforded crystalline 3 (83.5 g, 86%): mp
129-131 °C, [R]D -84° (c 1.0); NMR 1H δ 7.69-7.22 (m, 15 H),
4.86 (br s, 1 H), 4.16 (br s, 1 H), 4.02-3.9 (m, 2 H), 3.83 (dt, 1
H), 3.58 (m, 1 H), 2.41 (m, 1 H), 2.65 (br s, 3 H), 1.05 (s, 9 H);
In summary, we developed a practical approach to the
azidoglucose donors 10 and 12 that are versatile building
blocks for fashioning R-linked 2-amino-2-deoxyglucopy-
ranose residues in complex molecules. The phenylthio
group at their anomeric position may be used for direct
(33) Norberg, T. In Modern methods in carbohydrate synthesis;
Khan, S. H., O’Neill, R. A., Eds.; Harwood Academic Publishers:
Amsterdam, 1996; pp 82-106.
(30) Pedretti, V.; Veyrie`res, A.; Sinay¨, P. Tetrahedron 1990, 46, 77-
88.
(34) Garegg, P. J . Adv. Carbohydr. Chem. Biochem. 1997, 52, 179-
205.
(31) Kornblum, N.; Smiley, R. A.; Blackwood, R. K.; Iffland, D. C.
J . Am. Chem. Soc. 1955, 77, 6269-6280.
(32) David, S. In Preparative carbohydrate chemistry; Hanessian,
S., Ed.; Marcel Dekker: New York, 1997; pp 69-83.
(35) Weygand, F.; Ziemann, H. J ustus Liebigs Ann. Chem. 1962,
657, 179-198.
(36) Schmidt, R. R.; Kinzy, W. Adv. Carbohydr. Chem. Biochem.
1994, 50, 21-123.

Notes
J . Org. Chem., Vol. 64, No. 19, 1999 7279
13C δ 135.6, 130.9, 129.9, 129.0, 127.8, 127.4, 87.0, 78.9, 75.0,
72.1, 70.0, 64.9, 26.8; CI-MS m/z 528 (M + NH4+). Anal. Calcd
for C28H34O5SSi: C, 65.85, H, 6.71. Found: C, 65.06; H, 6.71.
that had physical properties identical to those of the preparation
obtained in (a).
P h en yl 4,6-Di-O-a cetyl-3-O-(4-m eth oxyben zyl)-1-th io-â-
D-m a n n op yr a n osid e (8). A mixture of 7 (10.0 g, 28.1 mmol),
Bu2SnO (8.4 g, 33.7 mmol), and benzene (200 mL) was stirred
under reflux for 2 h using a Dean-Stark adapter to remove
water. Approximately 50 mL of benzene was removed by
distillation. The solution was cooled to 65-70 °C and was treated
with 4-methoxybenzyl bromide (20 mL of an approximately 30%
solution in benzene) followed by Bu4NI (2.5 g). After 90 min,
TLC (3:1 hexane-EtOAc) indicated the disappearance of 7. The
solution was cooled to 0 °C and then was treated with aqueous
solutions of NaHCO3 and NaHSO3. Most of the benzene was
removed by distillation. The residue was equilibrated between
CHCl3 and H2O. The organic layer was concentrated, and the
residue was partially dissolved in EtOAc and hexane. The slurry
so obtained was applied to a column of silica gel (4 cm high)
made in a fritted-glass funnel (14 cm in diameter) in 4:1 hexane-
EtOAc. Elution by a gradient of hexane-EtOAc (4:1 to 1:1)
afforded crystalline 8 (8.9 g, 66%): mp 124-126 °C, [R]D -83°
P h en yl 6-O-ter t-Bu tyldiph en ylsilyl-2,3-O-isopr opyliden e-
1-th io-â-D-m a n n op yr a n osid e (4). To a solution of 3 (50 g) in
acetone (100 mL) were added 2,2-dimethoxypropane (200 mL)
and CSA (approximately 2 g). After 10 min at 25 °C TLC (3:1
hexane-EtOAc) indicated the disappearance of 3. The solution
was treated with TEA, and then the volatiles were removed by
distillation. The residue was equilibrated between CHCl3 and
H2O. The organic layer was dried (Na2SO4) and concentrated to
afford 4 (51.5 g, 96%) as a thick syrup: [R]D -126° (c 1.2); NMR
1H δ 7.75-7.20 (m, 15 H), 5.07 (d, 1 H, J ) 1.8 Hz), 4.42 (dd, 1
H, J ) 1.8 Hz, J ) 5.4 Hz), 4.09 (t, 1 H, J ) 6.3 Hz), 3.95 (m, 2
H), 3.88 (m, 1 H), 3.38 (m, 1 H), 2.77 (br s, 1 H), 1.58 and 1.42
(2 s, 2 × 3 H), 1.06 (s, 9 H); 13C δ 135.6, 135.5, 130.4, 129.8,
128.9, 127.8, 127.1, 111.3, 84.1, 80.0, 78.0, 75.9, 71.2, 64.9, 28.1,
26.8, 26.4; CI-MS m/z 568 (M + NH4+). Anal. Calcd for
C31H38O5SSi: C, 67.48, H, 7.12. Found: C, 67.16; H, 6.89.
P h en yl 4,6-Di-O-a cetyl-1-th io-â-D-m a n n op yr a n osid e (7).
(a) To a solution of 4 (48.5 g, 88 mmol) in THF (100 mL) was
added Bu4NF (30 mL of a 1 M solution in THF) at 25 °C. After
24 h, the solution containing 5 was treated with C5H5N (20 mL)
and Ac2O (20 mL). After 2 h, the volatiles were removed by
distillation. Toluene was added to and removed by distillation
from the residue several times. The crystalline residue was
triturated with ether and hexane. Filtration afforded a solid (6)
that was dissolved in CH2Cl2 (150 mL). To this solution were
added TFA (50 mL) and MeOH (30 mL) at 25 °C. After 2 h, the
solution was concentrated, and the residue was triturated with
ether and diisopropyl ether to afford 7 (23.2 g, 74% for three
steps): mp 149-150 °C, [R]D -122° (c 0.8) NMR 1H δ 7.9-7.3
(m, 5 H), 5.05 (t, 1 H, J ) 9.8 Hz), 4.85 (s, 1 H), 4.28 (dd, 1 H,
J ) 6.1 Hz, J ) 12.1 Hz), 4.19 (dd, 1 H, J ) 2.2 Hz, 12.1 Hz),
3.69 (dd, 1 H, J ) 4.8 Hz), 3.62 (1 H, ddd), 3.02 (br d, 1 H), 2.72
(br d, 1 H), 2.13, 2.08 (2 s, 2 × 3 H); 13C δ 131.0, 129.0, 127.8,
87.2, 76.0, 73.5, 72.1, 69.7, 62.8, 21.0, 20.8; CI-MS m/z 374 (M
+ NH4+). Anal. Calcd for C16H20O7S: C, 53.95, H, 5.66. Found:
C, 53.66; H, 5.64.
1
(c 1.2); NMR H δ 5.25 (t, 1 H, J ) 9.7 Hz), 4.77 (br s, 1 H), 4.62
and 4.48 (2 d, 2 H, J ≈ 12 Hz), 4.27 (m, 1 H), 4.22 (dd, 1 H, J )
6.3 Hz, J ) 12.1 Hz), 4.12 (dd, 1 H, J ) 2.6 Hz, J ) 12.1 Hz),
3.80 (s, 3 H), 3.56 (ddd, 1 H), 3.53 (dd, 1 H, J ) 3.5 Hz, J ) 9.4
Hz), 2.87 (br s, 1 H), 2.05 and 2.03 (2 s, 2 × 3 H); 13C δ 170.6,
169.6, 159.5, 134.6, 131.0, 129.4, 128.8, 113.9, 86.7, 78.6, 76.1,
71.2, 69.5, 67.3, 62.9, 55.2, 20.8, 20.7; CI-MS m/z 494 (M +
NH4+). Anal. Calcd for C24H28O8S: C, 60.49, H, 5.92. Found: C,
60.23; H, 5.90.
P h en yl 4,6-Di-O-a cetyl-2-a zid o-2-d eoxy-3-O-(4-m eth oxy-
ben zyl)-1-th io-â-D-glu cop yr a n osid e (10). To a stirred mixture
of 8 (11.0 g, 23 mmol), dry CH2Cl2 (100 mL), and C5H5N (11
mL) at -15 °C was added trifluoromethanesulfonic anhydride
(5.5 mL, 32.7 mmol). After 20 min, the reaction mixture was
treated with ice-cold aqueous NaHCO3 solution. The mixture
was concentrated under vacuum. Toluene was added to and
evaporated from the residue several times to afford 9 as a
syrup: NMR 1H δ 7.56 (m, 2 H), 7.33 (m, 3 H), 7.20 (d, 2 H),
6.97 (d, 2 H), 5.39 (d, 1 H, J ) 2.8 Hz), 5.14 (t, 1 H, J ) 10.8
Hz), 4.85 (br s, 1 H), 4.74 and 4.41 (2 d, 2 × 1 H, J ≈ 12 Hz),
4.16 (d, 2 H, J ) 4.6 Hz); 3.80 (s, 3 H), 3.65 (dd, 1 H, J ) 3.1 Hz,
(b) A solution of 2 (48.5 g, 178 mmol), tert-butyldiphenylsilyl
chloride (53 mL, 203 mmol), and imidazole (13.5 g) in C5H5N
(250 mL) was kept at 25 °C for 24 h. TLC (9:1 EtOAc-MeOH)
indicated completed disappearance of 2. The volatiles were
removed by distillation. Toluene was added to and evaporated
from the residue several times to afford a syrupy material (3)
that was dissolved in acetone (75 mL). To this solution were
added 2,2-dimethoxypropane (300 mL) and CSA (approximately
2 g). After 10 min at 25 °C TLC (1:1 hexane-EtOAc) indicated
the disappearance of 3. The solution was treated with aqueous
NaHCO3, and then the volatiles were removed by distillation.
The residue was equilibrated between CHCl3 and H2O. The
organic layer was dried (Na2SO4) and concentrated to a thick
syrup (4). A solution of crude 4 in anhydrous THF (300 mL) was
treated with Bu4NF in THF (100 mL of a 1 M solution in THF).
After 24 h at 25 °C TLC (1:1 hexane-EtOAc) showed complete
disappearance of 4 and the formation of a product (5). Ap-
proximately half of the volatiles were removed by distillation.
The solution was treated with pyridine (125 mL), Ac2O (125 mL),
and 4-(dimethylamino)pyridine (0.5 g). After 2 h the volatiles
were removed by distillation. Toluene was added to and removed
by distillation from the residue several times. The crystalline
residue was triturated with ether and hexane. Filtration afforded
impure 6. [An analytical sample was obtained by column
chromatographic purification of a previous batch using 2:1
hexane-EtOAc as the eluant. Pure 6: mp 128-130 °C, [R]D
9.8 Hz), 3.59 (ddd, 1 H, J ) 3.1 Hz), 2.06, 1.97 (2 s, 2 × 3 H); 13
C
δ 170.6, 169.2, 132.0, 130.0, 129.2, 128.4, 113.9, 84.5, 83.8, 76.8,
76.0, 72.1, 66.8, 62.8, 55.2, 20.7. To a stirred solution of this
residue in DMF (80 mL) was added NaN3 (4.0 g, 59.7 mmol).
After the disappearance of 9 as checked by TLC (2:1 hexane-
EtOAc) the reaction mixture was concentrated under vacuum.
Extractive workup (CHCl3/H2O) followed by chromatographic
purification using 2:1 hexane-EtOAc as the eluant afforded 10
(9.7 g, 84% for two steps) as a syrup that crystallized upon
standing: [R]D -74° (c 0.8); NMR 1H δ 4.86 (t, 1 H, J ) 10.0
Hz), 4.49 (d, 1 H, J ) 9.9 Hz), 4.22 (dd, 1 H, J ) 12 Hz), 4.17
(dd, 1 H), 3.84 (s, 3 H), 3.72-3.50 (m, 2 H), 3.30 (t, 1 H, J ≈ 10
Hz), 2.11, 2.00 (2 s, 2 × 3 H); 13C δ 171.0, 169.5, 134.0-128.5,
113.5, 86.2, 78.3, 76.2, 71.8, 69.1, 67.2, 62.8, 55.1, 20.8, 20.6;
CI-MS m/z 519 (M + NH4+). Anal. Calcd for C24H27N3O7S: C,
57.47, H, 5.43. Found: C, 57.45; H, 5.43.
P h en yl 4,6-Di-O-acetyl-2-azido-3-O-ch lor oacetyl-2-deoxy-
1-th io-â-D-glu cop yr a n osid e (12). To a stirred solution of 10
(16.9 mmol) in a 10:1 mixture of MeCN and H2O was added Ce-
(NH4)2(NO3)6 (24.0 g, 43.8 mmol) at 25 °C. After 2 h TLC
indicated disappearance of 10 and the formation of a single
1
product [11: NMR H δ 4.83 (dd, 1 H, J ) 10.1 Hz, J ) 9.6 Hz);
4.44 (s, 1 H, J ) 10.1 Hz), 4.26 (dd, 1 H, J ) 12.0 Hz, J ) 5.0
Hz), 4.19 (dd, 1 Hz), 3.90 (s, 3 H), 3.623 (dd, 1 H), 3.618 (ddd, 1
H), 3.33 (t, 1 H, J ) 9.8 Hz), 2.72 (d, 1 H, J ) 4.5 Hz), 2.12, 2.09
(2 s, 2 × 3 H)]. The reaction mixture was treated with aqueous
solutions of NaHSO3 and NaHCO3, followed by removal of MeCN
under vacuum. The residue was equilibrated between CHCl3 and
H2O. The organic layer was dried (Na2SO4) and concentrated to
a volume of approximately 50 mL. To this solution were added
C5H5N (3 mL) and monochloroacetic anhydride (4 g, 23.0 mmol)
at 25 °C. After 1 h the reaction mixture was treated with
aqueous NaHCO3 solution. Extractive workup (CHCl3/H2O)
followed by column chromatographic purification using 2:1
hexane-EtOAc as the eluant afforded 12 (6.6 g, 94% for two
1
-120° (c 1.0); NMR H δ 7.56-7.22 (m, 5 H), 5.08 (t, 1 H, J ≈ 8
Hz), 5.00 (br s, 1 H), 4.45 (br d, 1 H), 4.28-4.12 (m, 3 H), 3.61
(m, 1 H), 2.07, 2.05, 1.60, 1.38 (4 s, 4 × 3 H); 13C δ 130.9, 128.9,
127.5, 84.4, 76.8, 75.7, 75.6, 69.0, 63.3, 27.4, 26.2, 20.9, 20.8;
CI-MS m/z 414 (M + NH4+). Anal. Calcd for C19H24O7S: C,
57.56, H, 6.10. Found: C, 57.38; H, 6.09.] A solution of the
intermediate 6 in CH2Cl2 (300 mL) was treated with MeOH (50
mL) and TFA (150 mL) at 25 °C. After 15 min, the solution was
concentrated. Toluene was added to and removed by distillation
from the residue several times. The residue was triturated in
ether and diisopropyl ether to afford 7 (45.5 g, 71% for five steps)

7280 J . Org. Chem., Vol. 64, No. 19, 1999
Additions and Corrections
steps) as a syrup: [R]D -62° (c 1.1); NMR 1H δ 7.6-7.3 (m, 5
H), 5.10 (t, 1 H, J ) 9.6 Hz); 4.95 (t, 1 H, J ) 9.8 Hz), 4.52 (d,
1 H, J ) 10.0 Hz), 4.23 (dd, 1 H, J ) 4.7 Hz, J ) 12.1 Hz), 4.17
(dd, 1 H, J ) 2.5 Hz, J ) 12.1 Hz), 4.03 (dd, 2 H, J ) 14.6 Hz),
3.71 (ddd, 1 H), 3.43 (t, 1 H, J ) 10.0 Hz), 2.08, 2.01 (2 s, 2 × 3
H); 13C δ 170.5, 169.7, 166.5, 134.1, 130.0, 129.1, 129.0, 85.9,
75.7, 67.8, 67.1, 62.4, 61.9, 40.3, 20.7, 20.5; CI-MS m/z 475 (M
+ NH4+). Anal. Calcd for C18H20ClN3O7S: C, 47.22, H, 4.40.
Found: C, 47.48; H, 4.52.
Ack n ow led gm en t. The author thanks Dr. Go¨ran
Ekborg and Ms. J ennifer Wolfe for technical help and
Mr. Wesley White for the mass spectra.
J O990811P
Additions and Corrections
Vol. 63, 1998
An a M. Gom ez,* Ger a r d o O. Da n elo´n , Ser a fı´n Va lver d e,
a n d J . Cr isto´ba l Lo´p ez. Regio- and Stereocontrolled 6-Endo-
Trig Radical Cyclization of Vinyl Radicals: A Novel Entry to
Carbasugars from Carbohydrates.
Page 9626, reference 6. We inadvertantly overlooked
the following reports of 6-exo-trig cyclizations to form
carbasugars: (a) Schmid, W.; Whitesides, G. M. J . Am.
Chem. Soc. 1990, 112, 9670. (b) Andersson, F. O.;
Classon, B.; Samuelsson, B. J . Org. Chem. 1990, 55, 4999.
(c) Marco-Contelles, J .; Pozuelo, C.; J imeno, M. L.;
Mart´ınez, L.; Mart´ınez-Gran, A. J . Org. Chem. 1992, 57,
2625 and references cited to previous work. We thank
Dr. Marco-Contelles for calling our attention to ref c
above.
J O994005U
10.1021/jo994005u
Published on Web 08/31/1999