DAST-mediated regioselective anomeric group migration in saccharides

Article abstract of DOI:10.1021/jo900516r

(Chemical Equation Presented) When saccharides bearing a sulfur, selenium, or oxygen substituent at the anomeric center and an unprotected hydroxyl group either at C-4 or C-6 were subjected to fluorination with DAST in dichloromethane, a regioselective mi

Full text of DOI:10.1021/jo900516r

DAST-Mediated Regioselective Anomeric Group Migration in
Saccharides
Po-Chiao Lin,† Avijit Kumar Adak,† Shau-Hua Ueng, Li-De Huang, Kuo-Ting Huang,
Ja-an Annie Ho, and Chun-Cheng Lin*
Department of Chemistry, National Tsing Hua UniVersity, Hsichu-300, Taiwan, and Institute of Chemistry
and Genomic Research Center, Academia Sinica, Taipei, Taiwan
cclin66@mx.nthu.edu.tw
ReceiVed March 8, 2009
When saccharides bearing a sulfur, selenium, or oxygen substituent at the anomeric center and an
unprotected hydroxyl group either at C-4 or C-6 were subjected to fluorination with DAST in
dichloromethane, a regioselective migration of the anomeric substituent to the C-4 or C-6 position was
observed. Certain saccharides gave a mixture of migration and normal fluorination products whereas
others yielded mainly or exclusively migration products (ꢀ-glycosyl fluorides). The high thermal and
chemical stability of migrated glycosyl fluorides were demonstrated to be an important precursor for
many significant carbohydrate analogies. It is therefore suggested that these migrations may have useful
applications in organic synthesis.
Introduction
oligosaccharides due to its increased stability during storage and
increased reactivity upon activation with a variety of reagents.4
Elemental F2, however, is extremely reactive (even with glass)
and hazardous and thus has become obsolete; it has been
replaced with safe and selective agents for fluorination of organic
molecules, and these agents are compatible with ordinary
laboratory equipment.5 Nucleophilic reagents, including 2,2-
difluoro-1,3-dimethylimidazolidine6 and bis(2-methoxyethyl)-
aminosulfur trifluoride,7 and a wide range of electrophilic
reagents bearing R2N-F or R3N+-F units such as 1-chlorom-
ethyl-4-fluorodiazoniabicyclo[2.2.2]octane bis(tetrafluoroborate)8
have been developed and utilized as safer alternatives to F2.
Diethylaminosulfur trifluoride (DAST, Et2NSF3)9 has long
been used as a nucleophilic fluorinating agent that transforms
alcohols into monofluorides. In carbohydrate chemistry, DAST
Introduction of a fluorine atom or fluorinated group into
organic molecules changes the physical, chemical, and physi-
ological properties of the derived molecules due to the greater
stability of the C-F bond and lipophilicity of the fluorinated
moiety.1 The presence of a fluorine atom in the vicinity of the
anomeric position in saccharides reinforces the glycosidic bond,
which enhances the therapeutic value of sugar- or nucleoside-
based pharmaceuticals.2 Furthermore, the unique specificities
of the fluorine atom combined with its ability to form hydrogen
bonds make fluorine an ideal substituent for hydrogen or
hydroxyl groups in substrates because fluorine can enhance
binding efficacy and selectivity in pharmaceuticals.3 Apart from
these desirable characteristics, a fluorine atom at the anomeric
position of saccharides constitutes a very important class of
glycosyl donor having potential application in the synthesis of
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Toshima, K. Carbohydr. Res. 2000, 327, 15–26. (c) Huang, K.-T.; Winssinger,
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* To whom correspondence should be addressed. Fax: +886-3-5753147.
† P.-C.L. and A.K.A. contributed equally to this work.
(1) (a) O’Hagan, D.; Rzepa, H. S. Chem. Commun. 1997, 7, 645–652. (b)
Dolbier, W. R., Jr. J. Fluorine Chem. 2005, 126, 157–163.
(2) (a) Borrachero, P.; Cabrera-Escribano, F.; Carmona, A. T.; Gomez-
Guillen, M. Tetrahedron: Asymmmetry 2000, 11, 2927–2946. (b) Namchuk,
M. N.; McCarter, J. D.; Becalski, A.; Andrews, T.; Withers, S. G. J. Am. Chem.
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10.1021/jo900516r CCC: $40.75
Published on Web 05/14/2009
2009 American Chemical Society
J. Org. Chem. 2009, 74, 4041–4048 4041

Lin et al.
TABLE 1. DAST-Mediated Regioselective C1fC6 Migrations in
Saccharides
SCHEME 1. DAST-Mediated 1,6-Anomeric Thiol Group
Migration
has been mainly used to prepare glycosyl fluoride donors10a and
to replace nonanomeric hydroxyl groups by fluorines.10b In
addition, DAST-mediated 1,2-migration of the anomeric sub-
stituent has been applied in the synthesis of oligosaccharides
as demonstrated by the seminal work of Nicolaou et al.11
Although DAST-mediated C1fC2 migrations are common in
saccharides, the corresponding C1fC4 and C1fC6 migrations
have been less well characterizedsonly a few reports described
the migration of the anomeric methoxy group to the C-6 position
in galactobioside12 and lactoside.13 To date, there have been
no systematic studies on the scope of this reaction. Herein, we
report a serendipitous observation of a C1fC6 migration in a
monosaccharide, which prompted us to focus on DAST-
mediated migration.
Results and Discussion
a DAST (10 equiv), rt, CH2Cl2, 1 h.
Initially, compound 1 was designed as a precursor to
synthesize compound 2 by fluorination with DAST. However,
thioglycoside 1 exposured to DAST (1.5 equiv) at 0 °C in
dichloromethane followed by gradual warming of the reaction
to room temperature over 30 min, resulting in a single compound
in 90% yield that was identified as migration product 3 instead
of the expected substitution product 2 (Scheme 1). The
stereochemistry at C1 in 3 was expected based on mechanistic
DAST (Table 1). When these 6-hydroxy saccharides were
subjected to the DAST reaction conditions, the corresponding
C1fC6 migration glycosyl fluorides 5a-e and 5g-k were
isolated in high yields as mainly or exclusively the ꢀ-anomer
except when using 4f. Moreover, the DAST-mediated C1fC6
migration tolerated a variety of C2 substituents (e.g., OBz, OBn,
NHTroc, and NPhth). However, O-methyl- or O-allylglycosides
(4d,e) gave mixtures of both migration and substitution products
with poor selectivities (5d/6d ) 5:3 and 5e/6e ) 1:1). The poor
selectivity most likely resulted from the lower nucleophilicity
of oxygen atom compared to sulfur atom, which benefits the
reaction efficiency. Changes to the reaction conditions did not
lead to the predominant formation of migration product over
substitution product. For example, performing the reaction at
-30 °C or in different solvents (THF and CH3CN) yielded a
mixture of both migration and substitution products. In a
saccharide having an azido moiety at the anomeric center (4f),
the azido group did not migrate even in the presence of a large
excess of DAST (10 equiv), which yielded only substitution
product 6f (Table 1, entry 6). Notably, the C2 benzyl ether-
protected thioglycoside 4g gave mixtures of anomers 5g (R/ꢀ
) 2:3) in reasonable yields (Table 1, entry 7). Furthermore,
this powerful migration reaction proved to be feasible for
2-deoxy-2-amino-protected sugars (Table 1, entries 8-12).
Although the 2-deoxy-2-azido derivative (4k) delivered both
migration and substitution products in 76% yield (Table 1, entry
11), 2-N-acetylamino-ꢀ thioglucoside 4l produced oxazoline
derivative 7 as the only isolated product in 69% yield (Table 1,
entry 12) under identical reaction conditions. Thus, the results
in Table 1 indicate that a sulfur, selenium, or oxygen substituent
at the anomeric center can reliably affect a smooth C1fC6
migration of the anomeric group in saccharides.
1
grounds, and this compound gave the anticipated H and 13C
NMR and high-resolution mass spectra. The data unambiguously
identified 3 as the ꢀ-glycosyl fluoride. Briefly, the anomeric
proton of compound 3 exhibited a large downfield shift and
split into a double-doublet with a large coupling constant (δH
5.65, dd, JH-F ) 51.2, 6 Hz), and the 13C chemical shift of C1
was observed in the expected region as a doublet (δC 106.60,
d, JC-F ) 219 Hz), which is typical for a ꢀ-fluoride.14 Extensive
evaluation of a variety of reaction conditions, for example
increasing the DAST molar ratio to 10 equiv, lowering the
reaction temperature to -30 °C, or performing the reaction at
ambient temperature, suggested that compound 3 was the sole
reaction product. Thus, the standard reaction conditions for
C1fC6 migrations in glycosides entailed using DAST (1.5
equiv) at room temperature in dichloromethane for 0.5 h.
Accordingly, a variety of glucosides 4a-l (X ) STol, SBn,
SePh, OMe, O-allyl, or N3) were prepared by standard
protection-deprotection methods15 to achieve fluorination with
(9) Middleton, W. J. J. Org. Chem. 1975, 40, 574–578.
(10) (a) Yokoyama, M. Carbohydr. Res. 2000, 327, 5–14. (b) Dax, K.; Albert,
M.; Ortner, J.; Paul, J. B. J. Carbohydr. Res. 2000, 327, 47–86.
(11) (a) Nicolaou, K. C.; Ladduwahetty, T.; Randall, J. L.; Chucholowski,
A. J. Am. Chem. Soc. 1986, 108, 2466–2467. (b) Nicolaou, K. C.; Rodriguez,
R. M.; Mitchell, H. J.; Suzuki, H.; Fylaktakidou, K. C.; Baudoin, O.; van Delft,
F. L. Chem.sEur. J. 2000, 6, 3095–3115.
(12) (a) Kihlberg, J.; Frejd, T.; Jansson, K.; Magnusson, G. Carbohydr. Res.
1988, 176, 287–294. (b) Dax, K.; Albert, M.; Ortner, J.; Paul, B. J. Carbohydr.
Res. 2000, 327, 47–86.
Next, ꢀ-thiogalactosides 8 and 9 with a free hydroxyl at C-6
were subjected to DAST-mediated C1fC6 migration (Scheme
2). Again, smooth migration of the arylthiol from C1 to C6
was observed using a C2 benzoylated ꢀ-thiogalactoside 8 to
(13) Cai, S.; Hakomori, S.; Toyokuni, T. J. Org. Chem. 1992, 57, 3431–
3437.
(14) Michalik, M.; Hein, M.; Frank, M. Carbohydr. Res. 2000, 327, 185–
218.
(15) Birberg, W.; Lonn, H. Tetrahedron Lett. 1991, 32, 7453–7456.
4042 J. Org. Chem. Vol. 74, No. 11, 2009

RegioselectiVe Anomeric Group Migration in Saccharides
TABLE 2. Effect of the Nature of Anomeric Groups on
DAST-Mediated Regioselective C1fC6 Migration
SCHEME 2. Outcomes of DAST-Mediated Reactions onto
Galactosyl, Glucosyl, and Furanosyl Thioglycosides
a Reaction performed at -30 to -20 °C; 78% yield of 24a. b Yields
of 25a in THF and acetonitrile are 60% and 44%, respectively.
produce ꢀ-galactosyl fluoride 10 in high yield (87%). However,
C2 benzyl ether-protected galactoside 9 produced a ꢀ-galactosyl
fluoride, 11, in a moderate yield (50%) in conjunction with a
mixture of unidentified products, one of which presumably
contained the R-anomer. Furthermore, to extend the reaction
and its scope, a regioselective C1fC5 migration was performed
onto furanoside 12 to produce the migration product 13 in 83%
yield under similar reaction conditions. However, R-thiogluco-
side 14 gave only substitution product 15 in a good yield of
86%. These findings suggested a mechanism for DAST mediated
C1fC6 migration because under similar reaction conditions the
corresponding ꢀ-anomer 1 gave only migration product 3
(Scheme 1).
Mechanistically, we surmised that the free hydroxyl group
in saccharide 4 reacted with DAST to produce an alkoxy-
N,N-dialkylaminodifluorosulfane intermediate 16 (Scheme
3).16 Intermediate 16 adopts the 1C4 chair conformation (17)
to facilitate the formation of thiol-bridged ring intermediate
18. As shown in Scheme 3, through route a, subsequent
neighboring group participation of the C2-O-acyl protecting
group (OR ) OBz) led to formation of a more stable cyclic
benzoxonium ion 19 in which the anomeric oxygen is oriented
axially.11a Attack by fluoride ion at the anomeric carbon on
19 led to the exclusive formation of ꢀ-glycosyl fluoride, such
as 5a. The formation of oxazoline product 7 (Table 1, entry
12) further supports the proposed neighboring group partici-
pation mechanism (route c). However, in chair conformation
22, derived from R-thioglycoside 14, the leaving group and
thiol nucleophile are antiperilanar, which only produced
substitution product 15. Thus, formation of ꢀ-glycosyl
fluorides is stereoselective, and this mechanism accounts well
for the selectivities observed during C-F bond formation.
Furthermore, the nature of the C2 protecting group overrides
the controlling effect of stereoselective glycosyl fluoride
formation. In route b of Scheme 3, the resonance of the ring
oxygen lone-pair electrons allowed the formation of a cyclic
alkoxycarbenium 20, in which fluoride ion can attack at either
faces of the anomeric center to give an anomeric mixture of
products. For example, 4g, without a participating group (Z
) Bn) at C2, yielded fluorides 5g with R/ꢀ ) 2/3 (Table 1,
entry 7). However, through participation of the C2 N-
acetylamido group, the DAST-induced anomeric group
migration provided a stable oxazoline derivative 7, which
was found not susceptible to be attacked by the fluoride ion
(Table 1, entry 12). Notably, electron-withdrawing substit-
uents (NPhth vs NHTroc) at C2 weakened the nucleophilicity
of the anomeric S atom and inhibited the C1fC6 migration
(Table 1, entries 8 vs 9). However, this effect can be
overcome by changing the hydroxyl-protecting group as
electron-donating group (Table 1, entries 8 vs 10).
To gain insight into the electronic effect of the anomeric
S-substituent, we synthesized saccharides 23a-d with different
electronic properties of anomeric S-substituents (Table 2).
DAST-mediated reactions indicated that electron-withdrawing
4-chlorophenyl thiol 23a produced only migration product 24a
in 85% yield (Table 2, entry 1), whereas the relatively stronger
nucleophile, electron-donating 4-methoxyphenyl thiol (23b,
Table 2, entry 2), enhanced the yield of the migration product
to 95%. Additionally, the nature of the C-2 protecting group
also determined the stereochemical outcome of the reaction, only
producing ꢀ-anomer. Interestingly, thioglycoside 23c bearing
an electron-donating benzyl ether protecting group at C2
produced 1,6-dideoxy-1,6-epithio glycoside 26 (Table 2, entry
3), indicating the formation of proposed intermediate 18.17
However, the less nucleophilic S-acetyl protecting group in 23d
did not migrate at all, giving substitution product 25d in a
moderate 51% yield (Table 2, entry 4).
To study the solvent effect on DAST-mediated migration,
saccharide 23a (Table 2, entry 1) was subjected to standard
reaction conditions except that the reaction temperature was
maintained between -30 and -20 °C. As expected, migration
product 24a was only obtained in a 78% yield. However, a
change of solvent from less polar (dichloromethane) to more
polar (THF and acetonitrile) led to predominant formation of
substitution product 25a (see footnote b in Table 2). This may
due to the better solvation nature of polar solvents, which
suppresses migration by enhancing the nucleophilicity of the
fluoride ion.
To explore the potential of DAST-mediated anomeric group
migration at other positions in saccharides,18 thioglycosides
27-29 were prepared and their migration efficiencies were
examined (Scheme 4). Notably, the orientation of the free
(17) (a) Plet, J. R. H.; Porter, M. J. Chem. Commun. 2006, 11, 1197–1199.
(b) Lundt, I.; Skelbaek-Pedersen, B. Acta Chem. Scand. Ser. B 1981, 35, 637–
(16) Sutherland, A.; Vederas, J. C. Chem. Commun. 1999, 17, 1739–1740.
642.
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Lin et al.
SCHEME 3. Plausible Mechanism for the C1fC6 Migrations of Anomeric Groups Mediated by DAST
SCHEME 4. Stereoselective C1fC4 Migration of Anomeric Groups Mediated by DAST
hydroxyl in relation to the anomeric thiol group was crucial
for migration. The syn relationship between C4-hydroxyl and
C1-tolylthiol in ꢀ-thiogalactoside 27 resulted in formation of
intermediate 30. We propose that reactive conformation should
C2-benzononium ion 35, resulting in exclusive formation of
ꢀ-anomer. However, the R-glycosidic bond in thiogalactoside
29 did not migrate and produced only substitution product 38
in 85% yield. The more stable R-thioglycosidic bond in
intermediate 37 might be the factor to inhibit the migration of
the anomeric S atom.
One of the notable advantages of glycosyl fluorides as
glycosyl donors is their high thermal and chemical stability
relative to other glycosyl halides. Therefore, several possible
applications of the migration products can be envisaged on the
basis of the literature (Figure 1). For example, 6-deoxy-6-
thioglycosyl fluoride 5a could be used to synthesize the
corresponding oligosaccharide following desulfurization to
1
adopt C4 conformation to draw thiol nucleophile closing to
leaving group. However, the periplanar relationship between
nucleophile and leaving group makes the displacement impos-
sible. Thus, only substitution product 32 (85%) was obtained.
In contrast, ꢀ-thioglucoside 28 had a C4-hydroxyl anti to the
anomeric thiol group, which could potentially form the bicyclic
intermediate 34; producing only migration product 36 (75%)
stereoselectively. The stereochemistry of the newly formed
anomeric fluoride was governed by the assistance of the similar
4044 J. Org. Chem. Vol. 74, No. 11, 2009

RegioselectiVe Anomeric Group Migration in Saccharides
SCHEME 5. Synthesis of Polyhydroxylated Cyclohexanone
41a
We demonstrated the application of these facile migrations
as shown in Scheme 5 for the synthesis of polyhydroxylated
cyclohexanone 41, which provides a practical route to a large
variety of bioactive hexitols, such as aminocyclitols, and
pseudosugars.26 Thus, oxidation of the phenylselenide in 5c with
m-chloroperoxybenzoic acid in dichloromethane at -15 °C
followed by thermal elimination of the resulting selenoxide with
dimethyl sulfide in the presence of triethylamine at reflux
temperature afforded 6-deoxyhex-5-enopyranoside 40. Mercu-
ry(II)-mediated Ferrier rearrangement27 of 40 in a mixture of
H2O/acetone at reflux temperature produced partially protected
cyclohexanone derivative 41 with a newly formed hydroxyl
group at the axial position.
a Key: (a) 70% m-chloroperoxybenzoic acid, dry CH2Cl2, -15 °C, 1 h;
(b) dimethyl sulfide, triethylamine (2 equiv), reflux for 5 h (88% yield for
two steps); (c) mercury(II) bromide, H2O/acetone, reflux for 4.5 h, 50%
yield.
Conclusion
In conclusion, we have systematically investigated the scope
of the regioselective DAST-mediated C1fC6 and C1fC4
migrations of anomeric groups in saccharides. Our results
demonstrate that an aryl or alkyl sulfide at the anomeric position
in the presence of a suitable electron donor group on C2 reliably
facilitates these migrations with stereoselective formation of a
C-F bond. In addition, the anomeric migratory group and the
free hydroxyl group should have an anti relationship to facilitate
SN2 attack by the migratory group. Our results suggest that these
migrations would be very useful in the synthesis of various types
of oligosaccharides.
FIGURE 1. Potential application of DAST-mediated C1fC6 migration
product.
generate 6-deoxysugars (Figure 1, route a).11,19 Similarly,
glycosylation followed by conversion of the arylthiol to car-
boxylic acid20 would provide easy access to glucuronic oli-
gosaccharides (Figure 1, route b). Due to the presence of the
electron-withdrawing carboxylic acid function, glucuronic acid
donors are less reactive and often result in a poor yield of
glycosylation products.21 DAST-mediated synthesis offers an
alternative to glucuronic donors. Furthermore, aryl sulfides can
be converted to sulfoxides or sulfones (Figure 1, route c), which
have rich chemistry for further transformation to C-glycosides.
Sulfoxides can be converted to alcohols or aldehydes, which
can be further functionalized to useful saccharide intermedi-
ates.22 Carbocyclic polyols are important components of many
biologically active molecules, the effects of which range from
cellular regulation to the selective inhibition of enzymes;23 as
such, various methods have been developed to obtain these
bioactive molecules.24 The synthesis of a common precursor,
6-deoxyhex-5-enopyranose derivatives, 39, can be obtained
either via elimination of the arylsulfide or arylselenide (Figure
1, route d) followed by metal catalysis to produce carbapyra-
noses.25 Finally, the interesting product 26 could be used as a
glycoside donor (Figure 1, route e) for the synthesis of 6-deoxy
saccharides.19
Experimental Section
General Procedure for DAST-Mediated Anomeric Group
Migration in Saccharides. DAST (1.5 equiv) was added to a
solution of starting material (1.0 equiv) in CH2Cl2 (4 mL) at 0 °C,
and the resulting mixture was stirred for 0.5 h. After being stirred
for another 0.5 h at room temperature, the reaction mixture was
quenched by aqueous NaHCO3 (satd) (4 mL) and diluted with
CH2Cl2 (10 mL). The layers were separated, the aqueous layer was
extracted with CH2Cl2 (10 mL), the combined organic layer was
dried over anhydrous MgSO4 and filtered, and the solvents were
evaporated at reduced pressure to give the crude product. The
residue was purified by flash silica gel column chromatography
eluting with a mixture n-hexanes and ethyl acetate to afford the
pure products.
2,3,4-Tri-O-benzoyl-6-deoxy-6-S-ethyl-6-thio-ꢀ-D-glucopyra-
nosyl fluoride (3): 1H NMR (400 MHz, CDCl3) δ 7.97 (d, J ) 7.2
Hz, 2H), 7.94 (d, J ) 7.2 Hz, 2H), 7.87 (d, J ) 7.2 Hz, 2H),
7.56-7.30 (m, 9H), 5.83 (t, J ) 8.4 Hz, 1H), 5.65 (d, J ) 51.2, 6
Hz, 1H), 5.66 (t, J ) 8.4 Hz, 1H), 5.58 (t, J ) 8.4 Hz, 1H), 2.91
(19) Stick, R. V.; Tilbrook, D. M. G.; William, S. J. Tetrahedron Lett. 1997,
38, 2741–2744.
(20) Yu, B.; Zhu, X.; Hui, Y. Org. Lett. 2000, 2, 2539–2541.
(21) van den Bos, L. J.; Codee, J. D. C.; van der Toorn, J. C.; Boltje, T. J.;
van Boom, J. H.; Overkleeft, H. S.; van der Marel, G. A. Org. Lett. 2004, 6,
2165–2168.
(22) (a) Colobert, F.; Mazery, R. D.; Solladie, G.; Carreno, M. C. Org. Lett.
2002, 4, 1723–1725. (b) Carreno, M. C.; Mazery, R. D.; Urbano, A.; Colobert,
F.; Solladie, G. J. Org. Chem. 2003, 68, 7779–7787.
(23) Hinterding, K.; Alonso-Diaz, D.; Waldmann, H. Angew. Chem., Int. Ed.
1998, 37, 688–749.
(24) Ferrier, R. J.; Middleton, S. Chem. ReV. 1993, 93, 2779–2831.
(25) (a) Ko, K. S.; Zea, C. J.; Pohl, N. L. J. Am. Chem. Soc. 2004, 126,
13188–13189. (b) Dalko, P. I.; Sinay, P. Angew. Chem., Int. Ed. 1999, 38, 773–
777. (c) Myers, A. G.; Gin, D. Y.; Rogers, D. H. J. Am. Chem. Soc. 1993, 115,
2036–2038.
(18) Attempts to introduce fluoride by regioselective anomeric group
migration at the C3 position in mannopyranosides 42 were disappointing. While
R-mannopyranoside 42a (R ) Bz) showed migration of a benzoyl ester to C3
(43a) under standard reaction conditions, product from 42b (R ) Bn) decom-
posedduring column chromatography.
(26) (a) Barton, D. H. R.; Camara, J.; Dalko, P.; Gero, S. D.; Quiclet-Sire,
B.; Stu¨tz, P. J. Org. Chem. 1989, 54, 3764–3766. (b) Barton, D. H. R.; Augy-
Dorey, S.; Camara, J.; Dalko, P.; Delaumeny, J. M.; Gero, S. D.; Quiclet-Sire,
B.; Eustache, J.; Stu¨tz, P. Tetrahedron 1990, 46, 215–230.
(27) Ferrier, R. J. J. Chem. Soc., Perkin Trans. 1 1979, 1455–1458.
J. Org. Chem. Vol. 74, No. 11, 2009 4045

Lin et al.
(s, 1H), 2.90 (d, J ) 6 Hz, 1H), 2.67 (m, 2H), 1.24 (t, J ) 7.2 Hz,
3H); 13C NMR (100 MHz, CDCl3) δ 165.47, 165.14, 164.89,
133.56, 133.51, 133.38, 129.87, 129.81, 129.76, 129.67, 128.58,
128.45, 128.41, 128.34, 128.26, 106.60 (d, J ) 219 Hz), 75.53,
75.50, 71.51, 71.42, 71.33, 71.23, 70.54, 33.20, 27.29, 14.58; HRMS
(FAB) calcd for C29H28FO7S 539.1540 [M + H]+, found 539.1530.
2,3,4-Tri-O-benzoyl-6-deoxy-6-S-(4-methylphenyl)-6-thio-ꢀ-
2H), 4.21 (dd, J ) 14.0, 6.0 Hz, 1H), 3.75 (d, J ) 4.8 Hz, 1H);
13C NMR (100 MHz, CDCl3) δ 165.76, 165.50, 165.23, 165.12,
165.01, 164.91, 133.99, 133.56, 133.51, 133.48, 133.38, 133.23,
133.21, 133.19, 129.89, 129.80, 129.75, 129.25, 128.85, 128.74,
128.67, 128.62, 128.46, 128.42, 128.32, 128.27, 117.89, 117.73,
106. 0 (d, J ) 219 Hz), 99.67, 81.21 (d, J ) 175 Hz), 74.12, 73.31,
73.11, 72.80, 72.66, 71.70, 71.57, 71.24, 70.03, 68.91, 68.82, 68.62;
HRMS (FAB) for C30H28O8F 535.1755 [M + H]+, found 535.1768.
2,3,4-Tri-O-benzoyl-6-deoxy-6-fluoro-ꢀ-D-glucopyranosyl azide
(6f): 1H NMR (400 MHz, CDCl3) δ 7.92-7.97 (m, 4H), 7.80-7.83
(m, 2H), 7.50-7.54 (m, 2H), 7.36-7.44 (m, 5H), 7.25-7.29 (m,
2H), 5.93 (t, J ) 9.7 Hz, 1H), 5.57 (t, J ) 9.7 Hz, 1H), 5.48 (dd,
J ) 9.7, 8.8 Hz, 1H), 4.96 (d, J ) 8.8 Hz, 1H), 4.54-4.71 (m,
2H), 4.09-4.18 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 165.6,
165.1, 164.9, 133.7, 133.5, 133.4, 129.9, 129.8, 129.7, 128.6, 128.5,
128.5, 128.4, 128.4, 128.3, 88.2, 81.1 (d, 1J ) 175.5 Hz), 75.3 (d,
1
D-glucopyranosyl fluoride (5a): H NMR (400 MHz, CDCl3) δ
7.86-7.96 (m, 6H), 7.22-7.49 (m, 11H), 7.00 (d, J ) 8.0 Hz,
2H), 5.85 (t, J ) 8.2 Hz, 1H), 5.75-5.60 (m, 2H), 5.70 (t, J ) 8.2
Hz, 1H), 4.15-4.19 (m, 1H), 3.25 (dd, J ) 14.2, 3.7 Hz, 1H),
3.25 (dd, J ) 14.2, 7.6 Hz, 1H), 2.25 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 165.5, 165.3, 165.0, 137.1, 133.7, 133.7, 133.6, 131.5,
131.1, 130.0, 129.9, 128.8, 128.7, 128.6, 128.5, 106.7 (d, 1J ) 219
Hz), 73.9, 71.3 (d, 2J ) 29.4 Hz), 71.2 (d, 3J ) 7.6 Hz), 70.5,
37.2, 21.1; HRMS (FAB) calcd for C34H29O7FS 600.1619 [M+],
found 600.1618.
3
2J ) 19.5 Hz), 72.6, 71.1, 68.2 (d, J ) 6.7 Hz); HRMS (FAB)
calcd for C27H23O7N3F 520.1517 [M + H]+, found 520.1520.
2,3,4-Tri-O-benzoyl-6-deoxy-6-S-(4-methylphenyl)-6-thio-r-
D-glucopyranosyl fluorides (5g(r)): 1H NMR (400 MHz, CDCl3)
δ 7.28-7.35 (m, 13H), 7.23-7.25 (m, 2H), 7.18-7.21 (m, 2H),
7.04-7.07 (m, 2H), 5.51 (dd, J ) 53.0, 2.6 Hz, 1H), 4.95 (d, J )
10.9 Hz, 1H), 4.90 (d, J ) 11.0 Hz, 1H), 4.82 (d, J ) 10.9 Hz,
1H), 4.78 (d, J ) 11.8 Hz, 1H), 4.70 (d, J ) 11.8 Hz, 1H), 4.55
(d, J ) 11.0 Hz, 1H), 4.05 (ddd, J ) 9.3, 6.6, 2.8 Hz, 1H), 3.97 (t,
J ) 9.3 Hz, 1H), 3.50-3.59 (m, 2H), 3.31 (dd, J ) 14.8, 2.8 Hz,
1H), 3.01 (dd, J ) 14.8, 6.6 Hz, 1H), 2.29 (s, 3H); 13C NMR (125
MHz, CDCl3) δ 138.8, 138.3, 137.9, 137.6, 136.4, 132.6, 130.3,
129.7, 128.5, 128.4, 128.0, 127.9, 127.8, 127.7, 105.0 (d, 1J ) 226.5
Hz), 81.3, 79.6 (d, 2J ) 24.6 Hz), 79.2, 75.7, 75.0, 73.5, 72.0, 36.5,
20.9; HRMS (FAB) calcd for C34H36O4FS 559.2313 [M + H]+,
found 559.2318.
2,6-Dideoxy-3,4-di-O-benzoyl-2-N-phthalimido-6-S-(4-meth-
ylphenyl)-6-thio-ꢀ-D-glucopyranosyl fluoride (5h): 1H NMR
(CDCl3, 400 MHz) δ 7.67-7.87 (m, 8H), 7.20-7.43 (m, 8H), 7.03
(d, J ) 7.9 Hz, 2H), 6.18 (dd, J ) 52.3, 7.8 Hz, 1H), 6.17 (t, J )
9.6 Hz, 1H), 5.55 (t, J ) 9.6 Hz, 1H), 4.60-4.68 (m, 1H),
4.06-4.11 (m, 1H), 3.22-3.25 (m, 1H), 3.13 (dd, J ) 14.3, 7.9
Hz, 1H), 2.29 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 167.5, 165.5,
165.2, 137.0, 134.4, 133.9, 133.6, 133.4, 131.4, 130.9, 129.7, 128.5,
128.4, 128.3, 123.7, 104.3 (d, J ) 216 Hz), 73.4, 70.1 (d, J )
10.3), 54.9 (d, J ) 24 Hz), 36.6, 21.0; HRMS (FAB) calcd for
C35H28O7NFS 625.1561 [M+], found 625.1571.
2,3,4-Tri-O-benzoyl-6-deoxy-6-S-benzyl-6-thio-ꢀ-D-glucopy-
ranosyl fluoride (5b): 1H NMR (400 MHz, CDCl3) δ 8.05 (d, J )
7.6 Hz, 2H), 7.91 (d, J ) 7.6 Hz, 2H), 7.86 (d, J ) 7.6 Hz, 2H),
7.60-7.15 (m, 14H), 5.82 (t, J ) 8.4 Hz, 1H), 5.69, 5.57 (dd, J )
48.4, 6.4 Hz), 5.63 (t, J ) 8.4 Hz, 1H), 5.60 (dd, J ) 6.4, 8.4 Hz,
1H), 4.07 (td, J ) 9.2, 5.2 Hz, 1H), 3.83 (dd, J ) 18, 13.6 Hz,
2H); 13C NMR (400 MHz, CDCl3) δ 165.49, 165.08, 164.91,
137.76, 133.57, 133.54, 133.40, 129.88, 129.83, 129.76, 129.05,
128.72, 128.65, 128.57, 128.44, 128.35, 127.06, 107.75, 105.56,
75.36, 71.60, 71.50, 71.42, 71.32, 70.60, 36.96, 32.07; HRMS
(FAB) calcd for C34H30FO7S 601.1696 [M + H]+ found 601.1705.
2,3,4-Tri-O-benzoyl-6-deoxy-6-Se-phenyl-6-seleno-ꢀ-D-glu-
1
copyranosyl fluoride (5c): H NMR (400 MHz, CDCl3) δ 7.96
(d, J ) 7.8 Hz, 2H), 7.90 (d, J ) 7.8 Hz, 2H), 7.85 (d, J ) 7.8 Hz,
2H), 7.56-7.18 (m, 14H), 5.80 (t, d, J ) 8.4 Hz, 1H), 5.71, 5,58
(dd, J ) 48.4, 5.6 Hz, 1H), 5.65 (t, J ) 8.8 Hz, 1H), 5.55 (m, 1H),
4.17 (ddd, J ) 8, 8, 4 Hz, 1H), 3.28 (dd, J ) 13.2, 3.6 Hz, 1H),
3.22 (dd, J ) 13.2, 8 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ
165.42, 165.13, 164.87, 133.58, 133.52, 133.40, 133.15, 129.87,
129.83, 129.77, 129.47, 129.13, 128.69, 128.62, 128.56, 128.43,
128.41, 128.35, 127.38, 107.64, 105.45, 74.37, 74.33, 71.49, 71.29,
71.20, 71.11, 29.22; HRMS (FAB) calcd for C23H27FO7Se 634.0906
[M+], found 634.0904.
2,3,4-Tri-O-benzoyl-6-methyl-ꢀ-D-glucopyranosyl fluoride (5d)
and methyl 2,3,4-tri-O-benzoyl-6-deoxy-6-fluoro-ꢀ-D-glucopy-
1
ranoside (6d): H NMR (400 MHz, CDCl3) migration product δ
4-Methylphenyl 3,4-di-O-benzoyl-2,6-dideoxy-2-N-phthalimido-
6-fluoro-1-thio-ꢀ-D-glucopyranoside (6h): 1H NMR (CDCl3, 400
MHz) δ 7.89 (d, J ) 8.0 Hz, 2H), 7.73-7.68 (m, 6H), 7.48-7.31
(m, 6H), 7.24-7.20 (m, 2H), 7.09 (d, J ) 8.0 Hz, 2H), 6.24 (t, J
) 9.8 Hz, 1H), 5.81 (dd, J ) 50.4, 10.4 Hz, 1H), 5.50 (t, J ) 9.6
Hz, 1H), 4.65-4.63 (m, 1H), 4.56-4.50 (m, 2H), 4.16-4.12 (m,
1H), 2.32 (s, 3H); 13C NMR (CDCl3, 100 MHz) δ 168.28, 165.89,
165.39, 139.06, 134.68, 134.52, 134.16, 133.75, 133.50, 131.48,
130.06, 130.00, 128.67, 128.51, 127.20, 123.90, 83.71, 81.75 (J )
175 Hz), 72.20, 69.24, 54.01, 21.43; HRMS (ESI) calcd for
C35H28O7NFNaS 648.1468 [M + Na+], found 648.1475.
8.00-7.94 (m, 4H), 7.90 (d, J ) 8 Hz, 2H), 7.54-7.26 (m, 9H),
5.87 (t, J ) 10 Hz, 1H), 5.74, 5.61 (dd, J ) 51.6(H-F), 6 Hz,
1H), 5.67 (t, J ) 10 Hz, 1H), 5.61 (t, J ) 10 Hz, 1H), 4.19 (quint,
J ) 5.2 Hz, 1H), 3.70 (d, J ) 4.4 Hz, 2H), 3.40 (s, 3H); substitution
product δ 8.00-7.94 (m, 4H), 7.83 (d, J ) 4.4 Hz, 2H), 7.54-7.26
(m, 9H), 5.93 (t, J ) 10 Hz, 1H), 5.53 (t, J ) 10 Hz, 1H), 5.52
(dd, J ) 10, 7.6 Hz, 1H), 4.63 (d, J ) 8 Hz, 1H), 4.69 (d, J ) 3.6
Hz, 1H), 4.57 (d, J ) 4 Hz, 1H), 4.07 (ddt, J ) 20, 10, 4 Hz, 1H),
3.59 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 165.75, 165.49,
165.21, 165.13, 165.06, 164.89, 133.54, 133.50, 133.37, 133,22,
133.19, 129.88, 129.80, 129.75, 129.70, 129.24, 128.73, 128.64,
128.45, 128.41, 128.33, 128.30, 128.26, 101.68, 105.49, 101.91,
82.41, 80.66, 73.99, 73.31, 73.11, 72.80, 71.68, 71.57, 71.47, 71.28,
68.88, 68.81, 68.60, 59.53, 57.10; HRMS (FAB) calcd for
C28H26FO8 509.1612 [M + H]+, found 509.1622.
2,3,4-Tri-O-benzoyl-6-(2-propen-1-yl)-ꢀ-D-glucopyranosyl fluo-
ride (5e) and 2-propen-1-yl 2,3,4-tri-O-benzoyl-6-deoxy-6-fluoro-
ꢀ-D-glucopyranoside (6e): 1H NMR (400 MHz, CDCl3) substitu-
tion product δ 7.97-7.81 (m, 6H), 7.54-7.26 (m, 9H), 5.91 (t, J
) 9.5 Hz, 1H), 5.86-5.76 (m, 1H), 5.56-5.48 (m, 2H), 5.29-5.17
(m, 2H), 4.91 (d, J ) 7.6 Hz, 1H), 4.55 (d, J ) 4.8 Hz, 2H), 4.42
(dd, J ) 13.0, 4.4 Hz, 1H), 4.19 (dd, J ) 13.0, 6.2 Hz, 1H), 4.02
(d, J ) 6 Hz, 1H); migration product δ 8.00-7.82 (m, 6H),
7.55-7.26 (m, 9H), 5.87-5.83 (m, 1H), 5.60-5.70 (m, 1H), 5.58
(dd, J ) 44.0, 9.6 Hz, 1H), 5.61-5.58 (m, 2H), 5.52 (t, J ) 9.6
Hz, 1H), 5.21 (dd, J ) 10.2, 4.2 Hz, 2H), 4.67 (d, J ) 4.8 Hz,
2,6-Dideoxy-3,4-di-O-benzoyl-2-N-[(2,2,2-trichloroethoxycar-
bonyl)amino]-6-S-(4-methylphenyl)-6-thio-ꢀ-D-glucopyranosyl
1
fluoride (5i): H NMR (CDCl3, 400 MHz) δ 7.92-7.88 (m, 4H),
7.54-7.50 (m, 2H), 7.40-7.34 (m, 4H), 7.25 (d, J ) 8.4 Hz, 2H),
7.02 (d, J ) 8.0 Hz, 2H), 5.63-5.55 (m, 3H), 5.50 (dd, J ) 35.2,
5.5 Hz, 1H), 4.70 (d, J ) 12 Hz, 1H), 4.59 (d, J ) 12 Hz, 1H),
4.14-4.07 (m, 1H), 4.04-3.99 (m, 1H), 3.26 (qd, J ) 4.4, 7.4 Hz,
2H), 2.28 (s, 3H); 13C NMR (CDCl3, 100 MHz) δ 166.78, 165.62,
154.46, 136.85, 133.64, 133.56, 132.27, 130.61, 130.12, 130.02,
129.98, 129.58, 129.07, 128.60, 128.53, 93.77 (d, J ) 222 Hz),
74.80, 72.37, 71.40, 69.50, 54.79, 36.90, 21.19; HRMS (ESI) calcd
for C30H27O7NFSCl3Na 692.0456 [M + Na+], found 692.0466.
2,6-Dideoxy-3,4-di-O-benzyl-2-N-phthalimido-6-S-(4-meth-
ylphenyl)-6-thio-ꢀ-D-glucopyranosyl fluoride (5j): 1H NMR
(CDCl3, 400 MHz) δ 7.68-7.66 (m, 4H), 7.34-7.27 (m, 6H), 7.08
4046 J. Org. Chem. Vol. 74, No. 11, 2009

RegioselectiVe Anomeric Group Migration in Saccharides
(d, J ) 6.4 Hz, 2H), 6.98 (d, J ) 8.0 Hz, 2H), 6.89-6.83 (m, 4H),
5.84 (dd, J ) 53.0, 7.6 Hz, 1H), 4.91 (d, J ) 11.2 Hz, 1H), 4.78
(d, J ) 12.0 Hz, 1H), 4.66 (d, J ) 12.0 Hz, 1H), 4.40 (d, J ) 12.0
Hz, 1H), 4.35 (d, J ) 8.4 Hz, 1H), 4.31-4.26 (m, 1H), 3.77-3.66
(m, 2H), 3.38 (dd, J ) 14.0, 2.0 Hz, 1H), 3.04 (dd, J ) 13.0, 6.1
Hz, 1H), 2.31 (s, 3H); 13C NMR (CDCl3, 100 MHz) δ 168.05,
137.70, 136.07, 134.16, 133.71, 132.74, 131.50, 130.02, 129.80,
129.51, 128.45, 128.01, 127.89, 127.32, 123.56, 105.35 (d, J )
210 Hz), 83.64, 82.07, 79.15, 75.06, 74.79, 74.26, 57.43, 36.24,
20.92; HRMS (FAB) calcd for C35H32O5NFS 597.1985 [M +], found
597.1978.
21.3; HRMS (FAB) calcd for C34H36O4FS 559.2327 [M + H]+,
found 559.2318.
2,3-Di-O-benzoyl-6-deoxy-6-S-(4-methylphenyl)-6-thio-ꢀ-D-ri-
bofuranosyl fluoride (13): 1H NMR (CDCl3, 400 MHz) δ
8.05-7.95 (m, 4H), 7.57-7.51 (m, 2H), 7.46-7.36 (m, 6H), 7.12
(d, J ) 7.9 Hz, 2H), 5.77-5.75 (m, 2H), 5.45 (t, J ) 2.7 Hz, 1H),
5.08 (dd, J ) 44.8, 7.6 Hz, 1H), 4.39-4.34 (m, 1H), 4.15-4.09
(m, 1H), 2.32 (s, 3H); 13C NMR (CDCl3, 100 MHz) δ 165.87,
165.14, 138.46, 133.48, 133.40, 132.91, 129.94, 129.76, 128.49,
128.40, 118.97, 107.61 (d, J ) 221 Hz), 71.26, 69.91, 68.60, 39.13,
21.11; HRMS (ESI) calcd for C26H24O5SF 467.1328 [M + H]+,
found 467.1323.
Ethyl 2,3,4-tri-O-benzoyl-6-fluoro-1-thio-r-D-glucopyrano-
side (15): 1H NMR (400 MHz, CDCl3) δ 7.97-7.96 (m, 4H), 7.86
(d, J ) 7.2 Hz), 7.55-7.27 (m, 9H), 6.06 (t, J ) 10 Hz, 1H), 5.95
(d, J ) 6 Hz, 1H), 5.55 (t, J ) 10 Hz, 1H), 5.49 (dd, J ) 10, 5.6
Hz, 1H), 4.47 (dddd, J ) 22, 10.4, 2.8, 4.4 Hz), 4.65, 4.54 (dm, J
) 43.6 Hz (H-F), 2H), 2.65 (nintet, J ) 6 Hz, 2H), 1.30 (t, J )
7.6 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 165.63, 165.39, 165.30,
133.50, 133.41. 133.14, 129.99, 129.89, 129.69, 129.17, 129.02,
128.85, 128.46, 128.29, 82.39, 80.63, 82.23, 71.63, 70.90, 69.15,
68.96, 68.80, 68.51, 24.40, 14.63; HRMS (FAB) calcd for
C29H28FO7S 539.1540 [M + H]+, found 539.1530.
2,3,4-Tri-O-benzoyl-6-S-(4-chlorophenyl)-6-deoxy-6-thio-ꢀ-D-
glucopyranosyl fluoride (24a): 1H NMR (CDCl3, 400 MHz) δ 7.95
(d, J ) 7.4 Hz, 2H), 7.90 (d, J ) 7.4 Hz, 2H), 7.85 (d, J ) 7.4 Hz,
2H), 7.55-50 (m, 2H), 7.45 (t, J ) 7.4 Hz, 1H), 7.38-7.34 (m,
4H), 7.32-7.26 (m, 4H), 7.16 (d, J ) 8.4 Hz, 2H), 5.78 (t, J ) 8.0
Hz, 1H), 5.65 (t, J ) 8.2 Hz, 1H), 5.64 (dd, J ) 51.3, 5.3 Hz, 1H),
5.56-5.52 (m, 1), 4.15-4.10 (m, 1H), 3.32 (dd, J ) 14.3, 4.0 Hz,
1H), 3.24 (dd, J ) 14.3, 7.3 Hz, 1H); 13C NMR (CDCl3, 100 MHz)
δ 165.34, 165.12, 164.85, 133.69, 133.57, 133.46, 132.87, 131.63,
129.87, 129.82, 129.76, 129.14, 128.61, 128.50, 128.48, 128.42,
128.37, 106.44 (d, J ) 219 Hz), 73.79 (d, J ) 3 Hz), 71.17, 71.00,
70.89 (d, J ) 5 Hz), 70.21, 36.72; HRMS (FAB) calcd for
C33H26O7ClFS 620.1072 [M+], found 620.1062.
2,3,4-Tri-O-benzoyl-6-deoxy-6-S-(4-methoxyphenyl)-6-thio-ꢀ-
D-glucopyranosyl fluoride (24b): 1H NMR (CDCl3, 400 MHz) δ
7.95 (d, J ) 7.4 Hz, 2H), 7.89-7.84 (m, 4H), 7.51 (t, J ) 7.4 Hz,
2H), 7.45 (t, J ) 7.4 Hz, 1H), 7.37-7.31 (m, 6H), 7.29 (d, J ) 7.6
Hz, 2H), 5.76 (t, J ) 8.0 Hz, 1H), 5.63 (t, J ) 8.3 Hz, 1H), 5.62
(dd, J ) 51.1, 5.5 Hz, 1H), 5.54-5.51 (m, 1H), 4.09-4.04 (m,
1H), 3.75 (s, 3H), 3.23 (dd, J ) 14.2, 4.0 Hz, 1H), 3.16 (dd, J )
14.2, 7.4 Hz, 1H); 13C NMR (CDCl3, 100 MHz): δ 165.37, 165.12,
164.86, 159.36, 134.08, 133.54, 133.53, 133.41, 129.86, 129.82,
129.76, 128.66, 128.56, 128.40, 128.35, 125.14, 114.67, 106.46 (d,
J ) 219 Hz), 73.73 (d, J ) 3 Hz), 71.19, 70.24, 55.24, 38.28;
HRMS (FAB) calcd for C34H29O8FS 616.1567 [M+], found
616.1567.
2-Azido-2,6-dideoxy-3,4-di-O-benzoyl-6-S-(4-methylphenyl)-
6-thio-ꢀ-D-glucopyranosyl fluoride (5k) and 4-methylphenyl
2-azido-2,6-dideoxy-3,4-di-O-benzoyl-6-fluoro-1-thio-ꢀ-D-glu-
copyranoside (6k): 1H NMR (400 MHz, CDCl3) migration product
δ 7.93-7.83 (m, 4H), 7.53-7.45 (m, 2H), 7.37-7.32 (m, 4H),
7.25-7.19 (m, 2H), 7.02 (d, J ) 8.0 Hz, 2H), 5.87 (d, J ) 9.2 Hz,
1H), 5.44 (dd, J ) 52, 9.2 Hz, 1H), 4.15 (dt, J ) 9.4, 2.2 Hz, 1H),
3.63 (ddd, J ) 2.4, 2.4, 2.4 Hz, 1H), 3.47 (dd, 10.6, 3.4 Hz, 1H),
3.19 (dd, J ) 12.8, 30.0 Hz, 1H), 3.02 (dd, J ) 14.4, 8.8 Hz, 1H),
2.28 (s, 3H); substitution product δ 7.93-7.83 (m, 4H), 7.53-7.45
(m, 2H), 7.37-7.32 (m, 4H), 7.25-7.19 (m, 2H), 7.02 (d, J ) 8.0
Hz, 2H), 5.85 (d, J ) 9.2 Hz, 1H), 5.43 (d, J ) 9.2 Hz, 1H), 5.36
(t, J ) 9.4 Hz, 1H), 4.96 (d, J ) 3.2 Hz, 1H), 4.32 (dt, J ) 28, 2.8
Hz, 1H), 3.88-3.84 (m, 1H), 3.12 (dd, J ) 16.8, 7.6 Hz, 1H),
2.28 (s, 3H); 13C NMR (CDCl3, 100 MHz) δ 165.72, 165.65,
165.54, 165.44, 137.25, 134.74, 133.81, 133.66, 133.43, 131.66,
131.36, 130.40, 130.20, 130.00, 129.25, 128.95, 128.88, 128.61,
128.59, 128.50, 106.08 (d, J ) 228 Hz), 99.05, 86.48, 81.42 (d, J
) 175 Hz), 72.57, 71.62, 71.59, 71.12, 70.81, 70.17, 69.19, 61.91,
61.68, 55.66, 36.75, 21.18; HRMS (ESI) calcd for C27H24N3O5FNaS
544.1318 [M + Na]+, found 544.1323.
2-Methyl-4,5-(3,4-di-O-benzoyl-6-S-(4-methylphenyl)-6-thio-
1
1,2-dideoxy-r-D-glucopyrano)[2,1-d]-2-oxazoline (7): H NMR
(CDCl3, 400 MHz) δ 8.04 (d, J ) 8.4 Hz, 2H), 7.94 (d, J ) 8.4
Hz, 2H), 7.58-7.54 (m, 2H), 7.44-7.39 (m, 4H), 7.24-7.22 (m,
2H), 6.99 (d, J ) 8.0 Hz, 2H), 6.06 (d, J ) 7.2 Hz, 1H), 5.60 (t,
J ) 2.0 Hz, 1H), 5.30 (d, J ) 8.5 Hz, 1H), 4.29 (d, J ) 6.8 Hz,
1H), 3.36 (td, J ) 8.2, 3.2 Hz, 1H), 3.26 (dd, J ) 14.0, 3.2 Hz,
1H), 3.05 (dd, J ) 14.0, 8.0 Hz, 1H), 2.25 (s, 3H), 1.98 (s, 3H);
13C NMR (CDCl3, 150 MHz) δ 166.67, 165.09, 164.76, 136.74,
133.47, 133.44, 131.41, 131.08, 130.92, 129.94, 129.75, 129.66,
129.28, 129.08, 128.44, 128.37, 99.59, 71.75, 70.42, 68.40, 64.73,
38.13, 20.98, 13.75; HRMS (ESI) calcd for C29H28NO6S 518.1637
[M + H]+, found 518.1641.
2,3,4-Tri-O-benzoyl-6-deoxy-6-S-(4-methylphenyl)-6-thio-ꢀ-
D-galactopyranosyl fluoride (10): 1H NMR (400 MHz, CDCl3) δ
7.78-8.08 (m, 6H), 7.32-7.63 (m, 9H), 7.25 (d, J ) 7.9 Hz, 2H),
6.04 (br, 1H), 7.10 (d, J ) 7.9 Hz, 2H), 5.85 (ddd, J ) 12.0, 10.5,
7.0 Hz, 1H), 5.57 (dd, J ) 10.5, 3.3 Hz, 1H), 5.53 (dd, J ) 52.1,
7.0 Hz, 1H), 4.07 (t, J ) 6.7 Hz, 1H), 3.30 (dd, J ) 14.2, 6.7 Hz,
1H), 3.13 (dd, J ) 14.2, 6.7 Hz, 1H), 2.31 (s, 3H); 13C NMR (100
MHz, CDCl3) δ 165.7, 165.5, 165.3, 137.7, 133.9, 133.7, 133.6,
131.5, 130.7, 130.3, 130.2, 130.0, 129.0, 128.8, 128.6, 128.5, 107.5
(d, 1J ) 217.5 Hz), 73.2, 71.2 (d, 3J ) 10.4 Hz), 70.1 (d, 2J )
25.1 Hz), 68.3, 35.0, 21.2; HRMS (FAB) calcd for C34H29O7FS
600.1619 [M+], found 600.1618.
Acetyl 2,3,4-tri-O-acetyl-6-deoxy-6-fluoro-1-thio-ꢀ-D-glucopy-
1
ranoside (25d): H NMR (400 MHz, CDCl3) δ 5.30 (t, J ) 9.6
Hz, 1H, HC(3)), 5.28 (d, J ) 10 Hz, 1H), 5.10 (dd, J ) 10, 9.6
Hz, 1H), 5.09 (t, J ) 9.6 Hz, 1H), 4.47 (ddd, J ) 47.2, 10.8, 2.4
Hz, 1H), 4.40 (ddd, J ) 47.2, 10.8, 2.4 Hz, 1H), 3.83 (dddd, J )
21.6, 10.8, 4, 2.4 Hz, 1H), 2.39 (s, 3H), 2.06, 2.03, 2.02 (s, 3H ×
3); 13C NMR (100 MHz, CDCl3) δ 191.90, 170.01, 169.25, 169.19,
81.85, 80.09, 80.16, 76.84, 74.99, 69.09, 67.95, 67.88, 30.76, 20.50;
HRMS (FAB) calcd for C14H20FO8S 367.0863 [M + H]+, found
367.0861.
2,3,4-Tri-O-benzyl-6-deoxy-6-S-(4-methylphenyl)-6-thio-ꢀ-D-
1
galactopyranosyl fluoride (11): H NMR (400 MHz, CDCl3) δ
7.27-7.40 (m, 15H), 7.19-7.22 (m, 2H), 7.07-7.09 (m, 2H), 5.56
(dd, J ) 53.7, 2.7 Hz, 1H), 5.01 (d, J ) 11.1 Hz, 1H), 4.84 (d, J
) 11.8 Hz, 1H), 4.83 (d, J ) 11.8 Hz, 1H), 4.77 (d, J ) 11.8 Hz,
1H), 4.71 (d, J ) 11.8 Hz, 1H), 4.52 (d, J ) 11.1 Hz, 1H),
4.13-4.14 (m, 1H), 4.03 (ddd, J ) 25.2, 10.1, 2.7 Hz, 1H),
3.89-3.95 (m, 2H), 3.08 (dd, J ) 13.5, 5.6 Hz, 1H), 2.99 (dd, J )
13.5, 8.5 Hz, 1H), 2.31 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
138.6, 138.5, 138.3, 137.1, 131.7, 130.6, 130.2, 128.7, 128.7, 128.6,
128.5, 128.2, 128.1, 128.1, 128.0, 127.8, 103.5 (d, 1J ) 224.8 Hz),
79.0, 75.9 (d, 2J ) 23.5 Hz), 75.3, 74.8, 74.0, 73.5, 72.3, 34.4,
1,6-Anhydro-6-deoxy-6-thio-2,3,4-tri-O-benzyl-ꢀ-D-glucopy-
ranose (26): 1H NMR (CDCl3, 400 MHz) δ 7.32-7.26 (m, 15H),
5.45 (s, 1H), 4.78 (d, J ) 5.9 Hz, 1H), 4.68-4.54 (m, 6H), 3.65 (t,
J ) 4.7 Hz, 1H), 3.52 (d, J ) 4.0 Hz, 1H), 3.34 (d, J ) 5.6 Hz,
1H), 2.92 (q, J ) 6.4, 6.2 Hz, 1H), 2.76 (d, J ) 9.6 Hz, 1H); 13C
NMR (CDCl3, 100 MHz): δ 138.26, 138.04, 137.76, 128.45, 128.33,
127.90, 127.88, 127.83, 127.70, 127.62, 82.91, 82.43, 80.85, 79.27,
78.01, 73.24, 72.16, 71.77, 35.77; HRMS (FAB) calcd for
C27H29O4S 449.1787 [M+], found 449.1785.
J. Org. Chem. Vol. 74, No. 11, 2009 4047

Lin et al.
4-Methylphenyl 2,3,6-tri-O-benzoyl-4-deoxy-4-fluoro-1-thio-
ꢀ-D-glucopyranoside (32): H NMR (400 MHz, CDCl3) δ 8.09
5.99, 5,87 (ds, J ) 50.4(F-H) Hz, 1H), 5.70 (dd, J ) 6, 2.8 Hz,
1H), 5.50 (quint, J ) 2.4 Hz, 1H), 5.08 (s, 1H), 4.88 (s, 1H); 13C
NMR (100 MHz, CDCl3) δ 164.91, 164.84, 148.77, 133.78, 133.62,
133.51, 130.07, 129.98, 129.94, 129.01, 128.76, 128.50, 128.49,
128.44, 106.16, 103.89, 99.80, 69.85, 69.26, 68.89, 67.45; HRMS
(FAB) calcd for C22H22FO7 477.1350 [M + H]+, found 477.1337.
[2S-(2r,3ꢀ,4r,5r)]-2,3,4-Tri-O-benzoyl-5-hydroxycyclohex-
1
(d, J ) 6.4 Hz, 2H), 7.98 (d, J ) 8 Hz, 2H), 7.95 (d, J ) 8 Hz,
2H), 7.66-7.33 (m, 11H), 6.95 (d, J ) 8 Hz, 2H), 5.84 (dt, J )
13.6, 9.6 Hz, 1H), 5.38 (d, J ) 9.6 Hz, 1H), 4.92 (d, J ) 10 Hz,
1H), 4.82 (d, J ) 12 Hz, 1H), 4.78, 4.66 (dt, J ) 50.8(H-F), 9.6
Hz, 1H), 4.59 (dd, J ) 12, 9.6 Hz, 1H), 4.08 (ddd, J ) 12, 5.6, 2.4
Hz, 1H), 2.29 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 166.99,
165.56, 165.06, 138.71, 133.98, 133.38, 133.28, 129.85, 129.63,
129.09, 128.94, 128.42, 128.36, 127.40, 87.97, 86.09, 86.17, 75.72,
75.50, 74.30, 74.10, 62.66, 21.15; HRMS (FAB) calcd for
C34H30FO7S 601.1696 [M + H]+, found 601.1692.
2,3,6-Tri-O-benzoyl-4-deoxy-4-S-(4-methoxyphenyl)-4-thio-ꢀ-
D-galactopyranosyl fluoride (36): 1H NMR (400 MHz, CDCl3) δ
8.00 (d, J ) 6.8 Hz, 2H), 7.99 (d, J ) 6.8 Hz, 2H), 7.82 (d, J )
7.2 Hz, 2H), 7.60-7.23 (m, 13H), 5.91 (ddd, J ) 11.6, 9.6, 6.4
Hz, 1H), 5.58, 5.45 (dd, J ) 51.6, 6.4 Hz, 1H), 5.44 (d, J ) 9.6
Hz, 1H), 4.89 (d, J ) 5.6 Hz, 2H), 4.46 (td, J ) 5.6, 2 Hz, 1H),
4.12 (t, J ) 2 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 166.12,
165.72, 164.98, 137.30, 133.50, 133.37, 133.28, 132.82, 130.17,
129.85, 129.81, 129.76, 129.44, 128.97, 128.59, 128.46, 128.39,
128.21, 108.27, 106.09, 72.89, 72.82, 69.84, 69.58, 64.25, 51.66,
29.68, 20.84; HRMS (FAB) calcd for C34H29FO7S 600.1618 [M+],
found 600.1609.
4-Methylphenyl 2,3,6-tri-O-benzyl-4-deoxy-4-fluoro-1-thio-
r-D-glucopyranoside (38): 1H NMR (400 MHz, CDCl3) δ 7.25-7.39
(17H, m), 7.04 (2H, d, J ) 8.0 Hz), 5.51 (1H, dd, J ) 2.9, 5.4
Hz), 4.88 (1H, d, J ) 11.2 Hz), 4.83 (1H, d, J ) 11.2 Hz), 4.75
(1H, d, J ) 11.7 Hz), 4.70 (1H, d, J ) 11.7 Hz), 4.56 (1H, d, J )
12.1 Hz), 4.55 (1H, dd, J ) 51.9, 10.0 Hz), 4.51-4.49 (m, 1H),
4.48 (1H, d, J ) 11.8 Hz), 3.87-3.96 (1H, m), 3.82 (1H, dd, J )
5.5, 9.7 Hz), 3.69-3.71 (2H, m), 2.30 (3H, s); 13C NMR (100 MHz,
CDCl3) δ 138.38, 137.89, 137.55, 132.35, 129.91, 129.74, 128.42,
128.30, 128.07, 127.92, 127.65, 127.55, 89.55 (d, J ) 182 Hz),
87.21, 80.13, 79.96, 78.56, 78.47, 75.22, 73.49, 72.76, 69.44, 69.19,
68.24, 29.67, 21.07; HRMS (FAB) calcd for C34H35FO4SNa [M +
Na]+ 581.2138, found 581.2141.
1
anone (41): H NMR (CDCl3, 400 MHz) δ 8.01 (d, J ) 7.4 Hz,
2H), 7.97 (d, J ) 7.4 Hz, 2H), 7.89 (d, J ) 7.4 Hz, 2H), 7.53-7.36
(m, 7H), 7.29 (t, J ) 7.8 Hz, 2H), 6.38 (t, J )10.2 Hz, 1H), 5.80
(d, J ) 10.4 Hz, 1H), 5.75 (dd, J ) 10.1, 2.3 Hz, 1H), 4.65 (dd, J
) 5.7, 3.0 Hz, 1H), 2.93(d, J ) 3.2 Hz, 2H); 13C NMR (CDCl3,
100 MHz) δ 196.70, 167.38, 165.64, 165.47, 133.97, 133.91,
133.84, 133.75, 133.48, 133.35, 130.34, 130.07, 129.92, 129.87,
129.69, 128.69, 128.66, 128.63, 128.59, 128.46, 128.41, 128.38,
77.08, 74.55, 70.16, 66.91, 43.24; HRMS (ESI) calcd for C27H23O8
475.1393 [M + H]+, found 475.1401.
4-Methylphenyl 2,3,6-tri-O-benzoyl-1-thio-r-D-mannopyra-
noside (43a): 1H NMR (400 MHz, CDCl3) δ 8.30, (2H, d, J ) 8.4
Hz, ArH), 8.08 (2H, d, J ) 8.3 Hz, ArH), 7.97 (2H, d, J ) 8.5 Hz,
ArH), 7.36-7.63, (11H, m, ArH), 6.98 (2H, d, J ) 8.1 Hz, ArH),
5.68 (1H, dd, J ) 3.4, 3.4 Hz, H-3), 5.62 (1H, d, J ) 3.4 Hz, H-2),
5.51 (1H, s, H-1), 4.91 (1H, ddd, J ) 2.1, 5.3, 10.0 Hz, H-5), 4.82
(1H, dd, J ) 5.3, 12.0, Hz, H-6b), 4.70 (1H, dd, J ) 2.1, 12.0 Hz,
H-6a), 4.30 (1H, dd, J ) 3.4, 10.0, Hz, H-4), 2.02 (3H, s, CH3);
13C NMR (100 MHz, CDCl3) δ 166.86, 166.12, 164.64, 138.02,
133.71, 133.57, 133.15, 132.61, 131.30, 130.39, 129.82, 129.77,
129.05, 128.90, 128.58, 128.47, 128.37, 85.99, 71.87, 69.61, 68.02,
64.77, 64.09, 21.06; HRMS (FAB) calcd for C34H30O8SNa [M +
Na]+ 621.1559, found 621.1559.
Acknowledgment. This work was financially supported by
the National Tsing Hua University, Academia Sinica, and the
National Science Council, Taiwan.
Supporting Information Available: 1H and 13C NMR
spectra for all new compounds. This material is available free
of charge via the Internet at http://pubs.acs.org.
6-Deoxy-2,3,4-tri-O-benzoyl-ꢀ-D-xylo-hex-5-enopyranosyl fluo-
1
ride (40): H NMR (400 MHz, CDCl3) δ 8.08-8.05 (m, 6H),
7.63-7.56 (m, 3H), 7.46-7.37 (m, 6H), 6.09 (d, J ) 6 Hz, 1H),
JO900516R
4048 J. Org. Chem. Vol. 74, No. 11, 2009