Stereocontrolled Synthesis of α-C-Galactosamine Derivatives via Chelation-Controlled C-Glycosylation

Article abstract of DOI:10.1021/jo971727h

The samarium diiodide-promoted reduction of 2-deoxy-2-acetamidogalactosyl pyridyl sulfone α-5 with ketones or aldehydes under Barbier conditions led unexpectedly to the stereoselective synthesis of α-C-galactosamine derivatives in good yields. With carbon

Full text of DOI:10.1021/jo971727h

J . Org. Chem. 1998, 63, 2507-2516
2507
Ster eocon tr olled Syn th esis of r-C-Ga la ctosa m in e Der iva tives via
Ch ela tion -Con tr olled C-Glycosyla tion
Dominique Urban, Troels Skrydstrup,*,† and J ean-Marie Beau*
Universite´ Paris-Sud, Laboratoire de Synthe`se de Biomole´cules, URA CNRS 462,
Institut de Chimie Mole´culaire, F91405 Orsay Ce´dex, France
Received September 16, 1997
The samarium diiodide-promoted reduction of 2-deoxy-2-acetamidogalactosyl pyridyl sulfone R-5
with ketones or aldehydes under Barbier conditions led unexpectedly to the stereoselective synthesis
of R-C-galactosamine derivatives in good yields. With carbonyl substrates, R:â selectivities ranged
from 20:1 to 5:1, and with aldehydes a stereoselectivity of approximately 5:1 was observed at C7
in favor of the S-isomer. The stereochemical preference of these C-glycosylation reactions is
explained by the intermediacy of an R-oriented anomeric glycosyl samarium(III) compound that is
stabilized via chelation of the metal ion to the C2-acetamido group.
Sch em e 1
In tr od u ction
A well-known doctrine in classical glycoside synthesis
is the employment of an assisting group at C2 for the
stereocontrolled synthesis of 1,2-trans-O-glycosides.1 As
shown in Scheme 1 and as exemplified with a C2-acetate
substituent, their directing abilities are made possible
by evoking a stabilized carbocation intermediate 1, which
leads to direct SN2 substitution at the anomeric center
affording a â-O-glycoside. The groups typically used are
composed either of an ester (carbonate) linkage at the
C2 position or that of an amide (carbamate) linkage when
working with the corresponding amino sugars.
We have recently developed a mild and rapid entry to
1,2-trans-C-glycosides via the room-temperature reduc-
tive samariation of glycosyl 2-pyridyl sulfones of neutral
hexopyranoses in the presence of a carbonyl substrate,
which, contrary to O-glycoside synthesis, does not require
an assisting group at C2 (Scheme 2, eqs 1 and 2).2,3 The
success of this umpolung strategy to C-glycosides origi-
nates from the inherent stability of the intermediate
anomeric organosamarium toward â-elimination, when
a 1,2-trans spacial arrangement is assumed. In connec-
tion with our work in preparing analogous C-glycosides
of biologically important sugars,2b we were recently
confronted with the problem of having to prepare a
carbon mimic of N-acetyl-D-galactosamine linked to
serine in either anomeric configuration.4,5 We therefore
proceeded to examine whether our SmI2-promoted C-
glycoside methodology2 could likewise be extended to
galactosyl pyridyl sulfones bearing a C2-acetamide
Sch em e 2
† Present Address: Department of Chemistry, Aarhus University,
Langelandsgade 140, 8000 Aarhus C, Denmark.
(1) (a) Paulsen, H. Angew. Chem., Int. Ed. Engl. 1982, 21, 155. (b)
Schmidt, R. R. Angew. Chem., Int. Ed. Engl. 1986, 25, 212. (c) Toshima,
K.; Tatsuta, K. Chem. Rev. 1993, 93, 1503.
(2) (a) Maze´as, D.; Skrydstrup, T.; Beau, J .-M. Angew. Chem., Int.
Ed. Engl. 1995, 34, 909. (b) J arreton, O.; Skrydstrup, T.; Beau, J .-M.
J . Chem. Soc., Chem. Commun. 1996, 1661. (c) J arreton, O.; Skryd-
strup, T.; Beau, J .-M. Tetrahedron Lett. 1997, 36, 303. (d) Skrydstrup,
T.; J arreton, O.; Maze´as, D.; Urban, D.; Beau, J .-M. Chem. Eur. J ., in
press.
(3) For other reductive samariation approaches to C-glycosides,
see: (a) de Pouilly, P.; Che´nede´, A.; Mallet, J .-M.; Sinay¨, P. Bull. Soc.
Chim. Fr. 1993, 130, 256. (b) Hung, S.-C.; Wong, C.-H. Tetrahedron
Lett. 1996, 37, 4903. (c) Hung, S.-C.; Wong, C.-H. Angew. Chem., Int.
Ed. Engl. 1996, 35, 2671. (d) Vlahov, I. R.; Vlahova, P. I., Linhardt, R.
J . J . Am. Chem. Soc. 1997, 119, 1480.
(Scheme 2, eq 3). Although, a 1,2-trans-selectivity was
originally anticipated, we were skeptical as to the ef-
ficiency of these coupling reactions owing to the availibil-
S0022-3263(97)01727-1 CCC: $15.00 © 1998 American Chemical Society
Published on Web 03/21/1998

2508 J . Org. Chem., Vol. 63, No. 8, 1998
Urban et al.
Sch em e 3
ity of an acidic proton on the acetamido group. In a series
of elegant papers from the Kessler group,5a,g,h it was found
that for the low-temperature preparation of the corre-
sponding anomeric lithium reagent of N-acetyl-D-glu-
cosamine prepared via the reductive lithiation or trans-
metalation of an anomeric chloride or stannane, respec-
tively, prior deprotonation of the amide proton is neces-
sary to avoid competitive protonation at the anomeric
center.
In this paper, we show that such coupling reactions
are possible, but contrary to the previously observed
trans-selectivity, 1,2-cis-C-galactosamines are the pre-
dominant products. In addition, under the conditions
described the reaction of the intermediate organosa-
marium with a carbonyl substrate is preferred to proto-
nation from the acetamido group. These results point
out the opposing influence such an anchimeric assisting
group may have in the stereoselective synthesis of both
O- and C-glycosides.6
Resu lts a n d Discu ssion
P r ep a r a tion of th e P yr id yl Su lfon e of N-Acetyl-
ga la ctosa m in e. For the synthesis of the required
galactosyl pyridyl sulfone illustrated in Scheme 3, we
started from the known hemiacetal 2, easily obtained
from the azidonitration of tribenzyl-D-galactal and sub-
sequent hydrolysis of the anomeric nitrate formed.7 To
introduce the pyridyl sulfone moiety at the anomeric
position, we originally subjected hemiacetal 2 to the
conditions described by Williams with tri-n-butylphos-
phine and 2,2′-dipyridyl disulfide in CH2Cl2.8 This led
to the expected and chromatographically separable py-
ridyl sulfides R-3 and â-3 as a 1:3 anomeric mixture in
high yield. It was somewhat surprising that even with
an excess of Bu3P the azido group was not reduced under
the conditions employed.
was expected considering the above results. However,
upon heating the solution to reflux for 8 h followed by
the addition of 4 equiv of water and then acetylation
(pyridine/Ac2O), the sulfide R-4 could be obtained after
careful chromatographic separation from the closely
migrating triphenylphosphine oxide side product. Un-
fortunately, this separation was impossible with the
â-anomer after treatment of sulfide â-3 under identical
conditions, thus giving â-4 contaminated with consider-
able amounts of Ph3PO.10 Other azide reduction condi-
tions, such as the NiCl2/NaBH4 combination11 and
SmI2,12,13 followed by acetylation were less efficient,
affording yields of only approximately 50% of the desired
sulfide R-4 or â-4. Finally, the protocol described by
Bartra et al. (SnCl2/PhSH/NEt3)14 proved the most
effective, leading to the rapid reduction of the azide group
Different protocols for the transformation of the azide
functionality to an acetamido group were then attempted.
Treatment of R-3 with triphenylphosphine in THF9 did
not lead to any azide reduction at room temperature as
(4) For several reviews on the synthesis of C-glycosides: (a) Postema,
M. H. D. C-Glycoside Synthesis; CRC Press: Boca Raton, FL, 1995.
(b) Levy, D. E.; Tang, C. The Chemistry of C-Glycosides; Pergamon
Press: Exeter, U.K., 1995. (c) Casiraghi, G.; Zanardi, F.; Rassu, G.;
Spanu, P. Chem. Rev. 1995, 95, 1677. (d) Postema, M. H. D. Tetrahe-
dron 1992, 48, 8545. (e) Herscovici, J .; Antonakis, K. In Studies in
Natural Product Chemistry; Atta-ur-Rahman, Ed.; Elsevier: Amster-
dam, 1992; Vol. 10.
(5) For other syntheses of C-glycosyl analogues of 2-aminoglycosides
not discussed in the above reviews, see: (a) Hoffmann, M.; Kessler,
H. Tetrahedron Lett. 1994, 35, 6067. (b) Wei, A.; Haudrechy, A.; Audin,
C.; J un, H.-S.; Haudrechy-Bretel, N.; Kishi, Y. J . Org. Chem. 1995,
60, 2160. (c) Ayadi, E.; Czernecki, S.; Xie, J . Chem. Commun. 1996,
347. (d) J obron, L.; Leteux, C.; Veyrie`res, A.; Beau, J .-M. J . Carbohydr.
Chem. 1994, 13, 507. (e) Kim, K. H.; Hollingsworth, R. I. Tetrahedron
Lett. 1994, 35, 1031. (f) Mbongo, A.; Fre`chou, C.; Beaupe`re, D.; Uzan,
R.; Demailly, G. Carbohydr. Res. 1993, 246, 361. (g) Hoffmann, M.;
Burkhart, F.; Hessler, G.; Kessler, H. Helv. Chem. Acta 1996, 79, 1519.
(h) Burkhart, F.; Hoffmann, M.; Kessler, H. Angew. Chem., Int. Ed.
Engl. 1996, 35, 2671. (i) Burkhart, F.; Hoffmann, M.; Kessler, H.
Angew. Chem., Int. Ed. Engl. 1997, 36, 1191. (j) Rubinstenn, G.;
Esnault, J .; Mallet, J .-M.; Sinay¨, P. Tetrahedron: Asymmetry 1997, 8,
1327.
(6) Part of this work was previously published as a preliminary
communication. Urban, D.; Skrydstrup, T.; Riche, C.; Chiaroni, A.;
Beau, J .-M. J . Chem. Soc., Chem. Commun. 1996, 1883.
(7) (a) Lemieux, R. U.; Ratcliffe, R. M. Can. J . Chem. 1979, 57, 1244.
(b) Gauffeny, F.; Marra, A.; Shun, L. K. S.; Sinay¨, P.; Tabeur, C.
Carbohydr. Res. 1991, 219, 237.
(9) Vaultier, M.; Knouzi, N.; Carrie, R. Tetrahedron Lett. 1983, 24,
763.
(10) Likewise, the corresponding sulfones exhibited similar Rf values
as that of the sulfides making it impossible to separate the tri-
phenylphosphine oxide impurity at this stage. It is necessary that Ph3-
PO be removed from the sulfone as trace amounts were detrimental
for the coupling reactions discussed below.
(11) Paulsen, H.; Schnell, D. Chem. Ber. 1981, 114, 333.
(12) (a) Benati, L.; Montevecchi, P. C.; Nanni, D.; Spagnolo, P.; Volta,
M. Tetrahedron Lett. 1995, 36, 7313. (b) Goulaouic-Dubois, C.; Gug-
gisberg, A.; Hesse, M. Tetrahedron 1995, 51, 12035.
(13) For reviews on the use of SmI2 in organic synthesis, see: (a)
Molander, G. A.; Harris, C. R. Chem. Rev. 1996, 96, 307. (b) Molander,
G. A. In Comprehensive Organic Synthesis; Trost, B. M., Fleming, I.,
Schreiber, S., Eds.; Pergamon Press: Oxford, U.K., 1991; Vol. 1, p 251.
(c) Molander, G. A. In Organic Reactions; Paquette, L. A., Ed.; J ohn
Wiley: New York, 1994; Vol. 46, p 211. (d) Molander, G. A. Chem. Rev.
1992, 92, 29. (e) Curran, D. P.; Fevig, T. L.; J aspersen, C. P., Totleben,
M. L. Synlett 1992, 943. (f) Kagan, H. B.; Namy, J . L. Tetrahedron
1986, 42, 6573.
(8) Stewart, A. O.; Williams, R. M. J . Am. Chem. Soc. 1985, 107,
4289. See also: Mereyala, H. B.; Reddy, G. V. Tetrahedron 1991, 47,
6435.
(14) (a) Bartra, M.; Urpf, F.; Vilarrasa, J . Tetrahedron Lett. 1987,
47, 5941. (b) Bartra, M.; Romea, P.; Urpf, F.; Vilarrasa, J . Tetrahedron
1990, 46, 587.

Synthesis of R-C-Galactosamine Derivatives
J . Org. Chem., Vol. 63, No. 8, 1998 2509
Sch em e 4
Sch em e 5
and as well as their characteristically high anomeric
selectivities upon glycosylation. Hence, hemiacetal 2
could be converted stereoselectively to either the imidate
R-8 or â-8 under standard conditions described by
Schmidt (Scheme 5).1b Treatment of imidate R-8 with
2-mercaptopyridine and a catalytic amount of TMSOTf
or BF3‚Et2O in CH2Cl2 led to the sole production of the
â-pyridyl sulfide in high yield. In contrast, no selectivity
was obtained when subjecting the imidate â-8 to identical
conditions with TMSOTf. With the weaker Lewis acid,
BF3‚Et2O, a more favorable selectivity was observed
(approximately 3:1) in preference for the R-isomer.16
Examination of solvents other than CH2Cl2 led to lower
R:â selectivities. Although some improvement of the R,â-
selectivity would be desirable, the synthetic sequence to
pyridyl sulfone R-5 is still performant, providing an
overall yield of 58% from hemiacetal 2.
Sa m a r iu m Diiod id e-P r om oted Cou p lin g Rea c-
tion s. With a viable route to the pyridyl sulfone R-5,
the stage was now set for its samarium diiodide-promoted
coupling with carbonyl compounds. Upon combination
of a THF solution of R-5 and cyclohexanone (2 equiv) with
samarium diodide (2.2 equiv), an instantaneous reaction
ensued, resulting in the isolation of a chromatographi-
cally inseparable 10:1 anomeric mixture of C-glycosides
R-9 and â-9 in 75% yield (eq 1). That the C-glycosides
were themselves generated was itself noteworthy con-
sidering the need for protective metalation of the amide
proton in coupling reactions with the corresponding
anomeric lithium reagents.5a,g,h The 1-deoxy derivative
10 was only isolated in 18% yield.
and affording R-4 or â-4 in the respective yields of 99%
and 82% after acetylation.
Whereas R-4 could be cleanly converted to the corre-
sponding sulfone R-5 in 89% with m-CPBA in CH2Cl2,
we quickly discovered that this was not the case for â-4.
Under the same oxidizing conditions, this sulfide led to
a mixture of two compounds in which one was the
required sulfone â-5 (12%). The other component was
identified as the hemiacetal 6 (Scheme 4), whose forma-
tion during oxidation was surprising and unprecedented
from our previous work on the preparation of other
glycosyl pyridyl sulfones. The production of 6 could be
the result of the easier formation of an oxonium ion
intermediate i from â-4 than that for the R-anomer,
assisted by the proper positioning of the acetamide group
for displacement of the â-pyridyl sulfoxide or sulfone.
Subsequent hydrolysis then leads to the hemiacetal.
Another possibility would be for the â-sulfoxides, formed
after the first oxidation step, to undergo a Meisenheimer
rearrangement to the corresponding and unstable sul-
fenate esters, which are then hydrolyzed to 6 upon aque-
ous workup.15
With these results in hand, it became evident that a
more efficient synthesis of the sulfide R-3 was required
as the previous method to glycosylpyridylsulfides only led
to predominant â-sulfide formation. We initially exam-
ined the influence of temperature and solvent on the
introduction of the pyridyl sulfide from 2,2′-dipyridyl
disulfide. Neither the temperature nor the solvent (CH2-
Cl2, THF, CH3CN) greatly influenced the stereochemical
outcome at the anomeric center of R-3 with R:â selectivi-
ties of approximately 1:1.5, although the yields of the
sulfides were greater than 90%. The high reactivity of
both the cyclic oxonium ion intermediate and the pyridyl
thiolate generated under the reaction conditions is most
likely responsible for the nonselectivity observed at the
anomeric center.
Even more remarkable was the identification of the
major isomer as the R-anomer instead of the anticipated
â-isomer, which contradicts our previous results in 1,2-
trans-C-glycoside synthesis.2 This assignment was based
on the small coupling constants observed between
H1,H2 (1.3 Hz) for the major isomer in the 1H NMR
spectrum, clearly indicative of the R-orientation of the
C1-substituent. In addition, small coupling constants
were noted between all the other vicinal ring protons,
suggesting that the conformation of the R-C-glycoside
4
deviated considerably from that of the normal C1 chair
conformation. These spectral observations are in agree-
We next turned to the trichloroimidates as a potential
remedy to this problem owing to their ease in preparation
(16) It is somewhat surprising that, unlike in O-glycoside synthesis,
no general method exists for the synthesis of R-thioglycosides with high
stereoselectivity.
(15) Marichich, T. J .; Harrington. J . Am. Chem. Soc. 1972, 94, 5115.

2510 J . Org. Chem., Vol. 63, No. 8, 1998
Urban et al.
Ta ble 1. An ion ic Cou p lin g of P yr id yl Su lfon e 5a w ith
Ca r bon yl Com p ou n d s
ment with that of other R-C-glycosides obtained from
anionic condensations.2,5a,17 On the other hand, the minor
isomer was found to possess a large coupling constant
(J H1,H2 ) 9.7 Hz) characteristic of a â-C-glycoside (see
discussion below). A third minor component was also
isolated from the reaction mixture, whose structure
elucidation was based on the following spectral evidence.
Its 1H NMR spectrum revealed signals for a single
acetamido sugar moiety displaying similar proton cou-
pling constants as that observed for the major C-glyco-
side, though none for that of the aglycon moiety. On the
other hand, mass spectral data conformed with a struc-
ture whose mass was composed of two N-acetylgalac-
tosamine units. These data combined suggested that this
component was the symmetrical R,R-dimer 11, a class of
compounds that we have previously not observed in these
SmI2-promoted C-glycosylation reactions.2 Finally, it is
interesting to note the absence of the elimination product,
tribenzylgalactal, implying that â-elimination is not a
competing reaction. Coupling reactions with the corre-
sponding â-pyridyl sulfone â-5 led to similar results with
cyclohexanone, but because of the problems encountered
in its synthesis further work with this isomer was not
pursued.
was acetylated thus allowing for a chromatographic
separation of 11 and acetylated â-14. The â-configuration
of this minor component was deduced from the coupling
1
constants in the H NMR spectrum (e.g., J 1,2 ) J 2,3 ≈ 10
Hz), indicating an equatorial orientation of the newly
4
formed carbon-carbon bond in an expected C1 confor-
mation of the ring. Literature precedence has shown that
R-C-glycosides, formed from the coupling of C1-anions
with carbonyl substrates, deviate from this conformation
1
as indicated from their H NMR coupling constants.2,5a,17
In all cases, the â-anomers also displayed characteristic
chemical shifts. For example, the NH chemical shifts for
â-9 and 12-16 were typically found between 5.07 and
5.36 ppm, where for R-9, 12, 13 this peak could be located
between 6.92 and 7.03 ppm, and for R-14-16, between
6.27 and 6.54. This large chemical shift difference of the
NHAc group has also been reported for similar R- and
â-C-glycosides prepared in the N-acetylglucosamine
series.5g
Confirmation of the above results was provided by a
single-crystal X-ray structure of the major diastereoiso-
mer R-14 (mp 137-138 °C) obtained in entry 3 (Table 1,
Figure 1). Although it was found that all the R-C-
galactosamine derivatives possessed solution conforma-
tions that deviate considerably from the 4C1 conformation,
it was interesting to observe a chair conformation for R-14
in the solid state. The X-ray structure also assigns
unambiguously the configuration at the acyclic stereo-
center to be S. Hence, we assume that the major
diastereomer furnished from the other coupling reactions
also possesses this configuration (Table 1, entries 4 and
5). The predominant formation of the S-isomer parallels
earlier results obtained in the manno-series.2c
To determine the dominating factors leading to pref-
erential and unanticipated formation of the R-anomer
from pyridyl sulfone R-5, the above observations were
compared to results obtained with other galactosyl py-
ridyl sulfones with varying C2-substitutents (see Table
2). The condensation of the galactosyl pyridyl sulfone
17 with ketone substrates afforded C-galactosides pos-
sessing only the â-configuration at the anomeric center
(Table 2, entries 1 and 2).2d In contrast, the 2-deoxyga-
lactosyl derivative 18 led to a 1:1 anomeric mixture of
C-glycosides (Table 2, entry 3).2d With a galactosyl
The generality of this C-glycosylation method for the
selective construction of various R-C-galactosamine de-
rivatives is illustrated in Table 1. Comparable coupling
yields with other simple ketones and aldehydes (60-72%)
were obtained with R:â selectivities ranging from 5:1 to
20:1. With aldehydes, a stereoselectivity of approxi-
mately 5:1 was noted at the newly created acyclic
stereocenter C7.18 As with the previous condensation
employing cyclohexanone, the R- and â-C-glycosides
obtained from the ketones studied (Table 1, entries 1 and
2) were chromatographically inseparable. Like R-9, the
1H NMR coupling constants of the ring hydrogens in the
major coupling products deviated from those normally
4
found in a C1 conformation, which is clearly indicative
of the formation of R-C-glycosides. In contrast to the
ketones, it was possible to isolate the R-anomers by
careful column chromatography of the coupling products
furnished from the aldehyde substrates (Table 1, entries
3-5). However, the minor â-isomers comigrated with
dimer 11. In one case (Table 1, entry 3) this mixture
(17) (a) Wittman, V.; Kessler, H. Angew. Chem., Int. Ed. Engl. 1993,
32, 1091. (b) Lesimple, P.; Beau, J .-M. Bioorg. Med. Chem. 1994, 2,
1319.
(18) We were only able to detect one â-C-glycoside in the condensa-
tion of pyridyl sulfone R-5 with aldehyde substrates, although our limit
of detection was low owing to the high R,â-selectivities obtained in these
reactions. It does suggest, however, that some stereoselectivity is
achieved at C7 in the formation of the â-isomers.

Synthesis of R-C-Galactosamine Derivatives
J . Org. Chem., Vol. 63, No. 8, 1998 2511
a statistical mixture of anomeric dimers was obtained.21
Further one-electron transfer from the reducing species
then leads to the corresponding kinetic R-oriented Sm-
(III) species 23a . Rather than preferring a configura-
tional change to the thermodynamically more stable
â-anomer 24 as seen with other C2-equatorially-substi-
tuted glycosyl pyridyl sulfones (path a),2a,d,22 a strong six-
membered ring complex between the C1-metal ion and
the acetamido group disfavors this anomerization pro-
cess. It is possible that either the intermediate 23a
couples directly to the carbonyl substrate or instead
experiences a conformational change to a skew boat as
in 23b placing the C1-Sm bond in a thermodynamically
more stable equatorial position before the condensation
step. In both six-membered ring complexes, the NH bond
is likely pointing away from the C1-Sm bond, which
diminishs the rate of intramolecular deprotonation. Ap-
parently, the condensation rate of 23a or 23b to a
carbonyl substrate is sufficiently fast compared to the
rate of deprotonation whether it be inter- or intramo-
lecular, which is explained by the lower basicity and
higher oxophilicity of organolanthanide(III) reagents in
general. It is somewhat surprising though that the C2-
carbamate derivative is not synthetically useful (Table
2, entry 5), considering the important role this group has
been given in the SmI2-promoted intermolecular reduc-
tive couplings of R-(alkoxycarbonyl)amino ketones with
R,â-unsaturated esters.23 It may be that the expected
weaker O-Sm bond in this chelate complex compared
to 23a is not strong enough to prevent a C1-configura-
tional change, hence leading to a â-oriented organosa-
marium that subsequently undergoes protonation. There
is undoubtedly a fine balance between the energies of
complexation, anomerization, and sugar ring conforma-
tional changes.24
F igu r e 1. Single-crystal X-ray structure of C-glycoside R-14.
Ta ble 2. An ion ic Cou p lin g of P yr id yl Su lfon es 17-19
w ith Ca r bon yl Com p ou n d s
Finally, preliminary studies were conducted to employ
these results for the synthesis of a C-glycopeptide ana-
logue of the tumor-associated Tn-antigen,25 composed of
N-acetylgalactosamine unit linked to L-serine or L-
threonine (Figure 2). The elegant asymmetric amino acid
synthesis developed by Evans and co-workers26 served
(19) (a) Maze´as, D.; Skrydstrup, T.; Doumeix, O.; Beau, J .-M. Angew.
Chem., Int. Ed. Engl. 1994, 33, 1383. (b) Skrydstrup, T.; Maze´as, D.;
Elmouchir, M.; Doisneau, G.; Riche, C.; Chiaroni, A.; Beau, J .-M. Chem.
Eur. J . 1997, 8, 1342.
pyridyl sulfone possessing a C2-azido group as in 19,
attempted coupling with cyclohexanone gave only the
elimination product, tribenzylgalactal (Table 2, entry 4).
Apparently, the pyridyl sulfone group in 19 is reduced
faster in the presence of divalent samarium than the
azido functionality at C2. Finally, it was found that even
the exchange of the acetamido group with that of a
benzylcarbamoyl as in 20 did not afford a significant
amount of C-glycosides upon treatment with SmI2 in the
presence of cyclohexanone (Table 2, entry 5). These
results thus unveil an important directing effect dis-
played by C2-acetamido group in the intermediate gly-
cosyl organosamarium.
The R-selectivity displayed by pyridyl sulfone R-5 is
tentatively explained in Scheme 6. One-electron transfer
from SmI2 to the aryl sulfone moiety and subsequent
C1-S bond fragmentation generates the R-oriented ano-
meric radical 22.19,20 That this anomeric radical is formed
is seen from the isolation of the dimer 11 produced from
the dimerization of the glycosyl radical intermediate. It
is interesting to note the R,R-selectivity, whereas in the
few other examples reported on this type of dimerization
(20) (a) Dupuis, J .; Giese, B.; Ru¨egge, D.; Fischer, H.; Korth, H.-G.;
Sustmann, R. Angew. Chem., Int. Ed. Engl. 1984, 23, 896. (b) Korth,
H.-G.; Sustmann, R.; Dupuis, J .; Giese, B. J . Chem. Soc., Perkin Trans.
2 1986, 1453. (c) Chandra, H.; Symons, M. C. R. Tetrahedron Lett.
1987, 28, 1455. (d) Korth, H.-G.; Sustmann, R. J . Chem. Soc., Faraday
Trans. 1 1987, 95. (e) Korth, H.-G.; Sustmann, R.; Giese, B.; Ru¨ckert,
B.; Gro¨ninger, K. S. Chem. Ber. 1990, 123, 1891. (f) Giese, B.; Dupuis,
J .; Kro¨niger, K.; Hasskerl, T.; Nix, M.; Witzel, T. In Substituent Effects
in Radical Chemistry; Viehe, H. G., J anousek, Z., Merenyi, R., Eds.;
Reidel: Dordrecht, 1986; p 285. (g) Giese, B. Angew. Chem., Int. Ed.
Engl. 1989, 28, 969.
(21) (a) Giese, B.; Ru¨ckert, B.; Gro¨ninger, K. S.; Muhn, R.; Lindner,
H. J . Liebigs Ann. Chem. 1988, 997. (b) Collins, P. M.; Whitton, B. R.
J . Chem. Soc., Perkin Trans 1 1974, 1069.
(22) Little is known about the nature of this anomerization process,
although we have previously suggested the possibility that it may be
a unimolecular three-step process involving metal ion dissociation,
anion inversion, and association.2d
(23) Kawatsura, M.; Dekura, F.; Shirahama, H.; Matsuda, F. Synlett
1996, 373.
(24) Preliminary investigations with the corresponding pyridyl
sulfone of N-acetylglucosamine show that this compound does not
couple to carbonyl substrates. It is therefore apparent that the
stereochemistry at the C4 carbon is important for the C-glycosylation
event. Prehaps the energy barrier to the conformational change in the
organosamarium intermediate 23a is of lower energy than in the case
for the glucosamine derivative since the C4-substituent in 23a shifts
from an axial to equatorial orientation in 23b.

2512 J . Org. Chem., Vol. 63, No. 8, 1998
Urban et al.
Sch em e 6
Sch em e 7
F igu r e 2.
C-glycosides. Further work directed to the application
of this chemistry to prepare a C-glycoside analogue of
the Tn-antigen will be reported in due course.
as a suitable route for the construction of the aldehyde
partner 25, which was to be coupled with the pyridyl
sulfone R-5. With this approach in mind, we synthesized
the simple model oxazolidinone 26 and investigated its
ability to couple with R-5. Hence, ozonolysis of the easily
available alkene 27 furnished cleanly the crystalline
aldehyde 26 (mp 43 °C). Treatment of pyridyl sulfone
R-5 with 2 equiv of 26 and SmI2 then led to the formation
of a diastereomeric mixture of R-C-galactosamines (Scheme
7). However, instead of the expected C-galactosamine,
the lactones R-28 were obtained in 80% yield with an R:â
selectivity of 5:1, in which the condensation product had
undergone internal cyclization with expulsion of the
oxazolidine moiety. The preferential formation of the
lactone upon C-glycosylation was confirmed by subjecting
the mannosyl pyridyl sulfone 29, known for its high
yielding SmI2-promoted coupling reactions, to the same
conditions. This case, too, led to the production of a pair
of isomeric lactones 30 at C7 (ratio 3:1) as their R-ano-
mers in 65% yield.
In conclusion, we have presented a mild and rapid
method for the stereoselective synthesis of R-C-galac-
tosamine derivatives via chelation-controlled C-glycosy-
lation. The stereoselectivity observed at the anomeric
center contrasts earlier results seen with glucosyl, ga-
lactosyl, and mannosyl pyridyl sulfones where 1,2-trans-
C-glycosides were exclusively formed. These results
suggest the interesting dual role an anchimeric assisting
group may have at the C2 position of glycosyl donors for
the stereoselective synthesis of 1,2-trans-O- and 1,2-cis-
Exp er im en ta l Section
Gen er a l Con sid er a tion s. Unless otherwise stated, all
reactions were carried out under argon. THF was dried and
freshly distilled over sodium/benzophenone. Dichloromethane
was freshly distilled over P2O5. Reactions were monitored by
thin-layer chromatography (TLC) analysis. The following
compounds were prepared according to literature procedures:
2-azido-3,4,6-tri-O-benzyl-2-deoxy-D-galactopyranose (2),7 3,4,6-
tri-O-benzyl-2-O-(trimethylsilyl)-R-D-galactopyranosyl 2-py-
ridyl sulfone (17),2d and mannosyl pyridyl sulfone 29.2d
2-P yr id yl 2-Azid o-2-d eoxy-3,4,6-tr i-O-ben zyl-1-th io-r-
D-ga la ctop yr a n osid e (r-3). To a stirred solution of 2-azido-
3,4,6-tri-O-benzyl-2-deoxy-D-galactopyranose (2) (2.52 g, 5.3
mmol) and trichloroacetonitrile (3.2 mL, 32 mmol) in CH2Cl2
(25 mL) was added K2CO3 (1.1 g, 8.0 mmol). The mixture was
stirred for 6 h at 30 °C, after which it was filtered and
evaporated to dryness in vacuo. Purification of the residue
by flash chromatography (cyclohexane/EtOAc 5:1 containing
1% NEt3) provided the â-imidate as a colorless oil (2.76 g, 84%).
This compound was then redissolved in CH2Cl2 (140 mL), and
2-mercaptopyridine (1.17 g, 10.5 mmol) was added. The
stirred solution was cooled to -15 °C and BF3‚Et2O (131 µL,
1.1 mmol) was added. After being stirred at this temperature
for 1 h, the solution was washed with aqueous NaHCO3 (sat.)
(25) See: Toyokuni, T.; Dean, B.; Cai, S.; Boisin, D.; Hakamori, S.;
Singhal, A. K. J . Am. Chem. Soc. 1994, 116, 395 and references therein.
(26) Evans, D. A.; Britton, T. C.; Ellman, J . A.; Dorow, R. L. J . Am.
Chem. Soc. 1990, 112, 4011.

Synthesis of R-C-Galactosamine Derivatives
J . Org. Chem., Vol. 63, No. 8, 1998 2513
1
and then dried (Na2SO4) and evaporated to dryness in vacuo.
Purification by flash chromatography (cyclohexane/EtOAc 5:1)
provided first the R-anomer R-3 (1.61 g) and then the â-anomer
â-3 (0.62 g) in a combined yield of 88%: [R]D ) 142° (c ) 0.94,
yield of 99%: [R]D ) 115.6° (c ) 0.30, CHCl3); H NMR (250
MHz, CDCl3) δ 8.40 (dd, J ) 5.2, 2.0 Hz, 1 H, pyr), 7.50 (dd,
J ) 7.4, 2.0 Hz, 1 H), 7.45-7.20 (m, 16 H), 7.04 (dd, J ) 7.4,
5.2 Hz), 6.41 (d, J ) 5.2 Hz, 1 H), 5.22 (d, J ) 7.5 Hz, 1 H),
4.97 (d, J ) 11.7 Hz, 1 H), 4.92 (ddd, J ) 11.2, 7.5, 5.2 Hz, 1
H), 4.78 (d, J ) 11.7 Hz, 1 H), 4.63 (d, J ) 11.7 Hz, 1 H), 4.43
(d, J ) 11.7 Hz, 1 H), 4.40 (s, 2 H), 4.32 (dd, J ) 7.0, 5.2 Hz,
1 H), 4.12 (m, 1 H), 3.72 (dd, J ) 9.2, 7.0 Hz, 1 H), 3.60 (dd, J
) 11.2, 2.9 Hz, 1 H), 3.56 (dd, J ) 9.2, 5.2 Hz, 1 H), 1.88 (s, 3
H); 13C NMR (50 MHz, CDCl3) δ 170.3, 157.4, 149.2, 138.2,
137.7, 137.5, 136.7, 128.5, 128.2, 128.1, 128.0, 127.8, 127.7,
127.7, 127.6, 127.5, 123.0, 120.5, 84.9, 77.0, 74.5, 73.2, 72.2,
71.6, 71.1, 68.3, 49.4, 23.1; IR (neat) (cm-1) 3054, 2985, 1684,
1438, 1265; MS (CI, NH3) m/z 585 (M + 1), 474 (M + 1 -
HSPyr). Unsatisfactory elemental analyses were given for this
compound.
2-P yr id yl 2-Acet a m id o-2-d eoxy-3,4,6-t r i-O-b en zyl-1-
th io-â-D-ga la ctop yr a n osid e (â-4). The procedure described
for the obtention of R-4 was adopted, providing pyridyl sulfide
â-4 (89 mg, 82%) as a colorless syrup after purification by flash
chromatography (cyclohexane/EtOAc 1:3): [R]D ) 41.4° (c )
1.26, CHCl3); 1H NMR (250 MHz, CDCl3) δ 8.37 (broad d, J )
4.9 Hz, 1 H), 7.50 (dd, J ) 7.4, 2.0 Hz, 1 H), 7.41-7.24 (m, 17
H), 7.01 (ddd, J ) 6.0, 4.9, 2.7 Hz), 5.75 (d, J ) 8.2 Hz, 1 H),
5.69 (d, J ) 10.8 Hz, 1 H), 4.96 (d, J ) 11.7 Hz, 1 H), 4.74 (d,
J ) 11.7 Hz, 1 H), 4.63 (d, J ) 11.7 Hz, 1 H), 4.53 (d, J ) 11.7
Hz, 1 H), 4.48 (d, J ) 11.7 Hz, 1 H), 4.41 (d, J ) 11.7 Hz, 1 H),
4.26 (ddd, J ) 10.8, 10.2, 8.2 Hz, 1 H), 4.07 (d, J ) 2.9 Hz, 1
H), 4.01 (dd, J ) 10.2, 2.9 Hz, 1 H), 3.81 (dd, J ) 7.6, 5.3 Hz,
1 H), 3.63 (m, 2 H), 1.88 (s, 3 H); 13C NMR (50 MHz, CDCl3)
δ 170.5, 157.3, 149,1, 138.5, 138.0, 137.8, 136.6, 128.4, 128.3,
128.1, 128.0, 127.8, 127.7, 127.5, 123.9, 120.4, 82.8, 79.8, 77.6,
74.4, 73.3, 72.4, 71.8, 68.6, 51.7, 23.5; IR (neat) (cm-1) 3054,
2985, 1684, 1438, 1265; MS (CI, NH3) m/z 585 (M + 1), 474
(M + 1 - HSPyr). Unsatisfactory elemental analyses were
given for this compound.
1
CHCl3); H NMR (250 MHz, CDCl3) δ 8.46 (dd, J ) 4.8, 1.9
Hz, 1 H), 7.48 (dd, J ) 7.3, 1.9 Hz, 1 H), 7.42-7.17 (m, 16 H),
7.02 (dd, J ) 7.3, 4.8 Hz, 1 H), 6.54 (d, J ) 5.6 Hz, 1 H), 4.94
(d, J ) 11.5 Hz, 1 H), 4.77 (d, J ) 11.5 Hz, 1 H), 4.72 (d, J )
11.5 Hz, 1 H), 4.55 (d, J ) 11.5 Hz, 1 H), 4.52 (dd, J ) 10.8,
5.6 Hz, 1 H), 4.39 (d, J ) 11.5 Hz, 1 H), 4.33 (d, J ) 11.5 Hz,
1 H), 4.28 (dd, J ) 7.4, 5.8 Hz, 1 H), 4.06 (d, J ) 3.0 Hz, 1 H),
3.72 (dd, J ) 10.8, 3.0 Hz, 1 H), 3.64 (dd, J ) 9.2, 7.4 Hz, 1
H), 3.50 (dd, J ) 9.2, 5.8 Hz, 1 H); 13C NMR (50 MHz, CDCl3)
δ 155.9, 149.4, 138.0, 137.5, 137.1, 136.2, 128.2, 128.0, 128.0,
127.6, 127.5, 123.5, 120.3, 83.6, 79.3, 74.6, 73.0, 72.9, 71.9, 71.5,
68.0, 59.7; IR (neat) (cm-1) 3031, 2875, 2112, 1456. Anal. Calcd
for C32H32N4O4S: C, 67.59; H, 5.67; N, 9.85. Found: C, 67.77;
H, 5.72; N, 9.69.
2-P yr id yl 2-Azid o-2-d eoxy-3,4,6-tr i-O-ben zyl-1-th io-â-
D-ga la cto-p yr a n osid e (â-3). To a stirred solution of 2-azido-
3,4,6-tri-O-benzyl-2-deoxy-D-galactopyranose (2) (530 mg, 1.1
mmol) and trichloroacetonitrile (1.1 mL, 10.1 mmol) in CH2-
Cl2 (6 mL) was added DBU (82 µL, 0.55 mmol). The solution
was stirred for 1 h at 30 °C, after which time it was evaporated
to dryness in vacuo. Purification of the residue by flash
chromatography (cyclohexane/EtOAc 5:1 containing 1% NEt3)
provided the R-imidate as a colorless oil (516 g, 75%). The
R-imidate (500 mg, 0.81 mmol) was then redissolved in CH2-
Cl2 (26 mL), and 2-mercaptopyridine (270 mg, 2.43 mmol) and
4 Å molecular sieves (400 mg) were added. The stirred
solution was cooled to -20 °C and TMSOTf (10 µL, 0.052
mmol) was added dropwise. After being stirred at this
temperature for 1 h, the solution was filtered through Celite
and then washed with aqueous NaHCO3 (sat.), dried (Na2SO4),
and evaporated to dryness in vacuo. Purification by flash
chromatography (cyclohexane/EtOAc 5:1) provided the â-ano-
mer â-3 (526 mg) in 99% yield as a colorless solid. Recrystal-
lization from EtOAc/pentane provided colorless needles: mp
86 °C; [R]D ) 15.7° (c ) 0.85, CHCl3); 1H NMR (250 MHz,
CDCl3) δ 8.47 (dd, J ) 4.8, 1.9 Hz, 1 H), 7.50-7.25 (m, 17 H),
7.05 (dd, J ) 7.8, 4.8 Hz, 1 H), 5.40 (d, J ) 10.4 Hz, 1 H), 4.95
(d, J ) 11.2 Hz, 1 H), 4.81 (d, J ) 11.2 Hz, 1 H), 4.74 (d, J )
11.2 Hz, 1 H), 4.63 (d, J ) 11.2 Hz, 1 H), 4.49 (d, J ) 11.2 Hz,
1 H), 4.42 (d, J ) 11.2 Hz, 1 H), 4.09 (dd, J ) 10.4, 9.8 Hz, 1
H), 4.05 (d, J ) 3.0 Hz, 1 H), 3.75 (dd, J ) 7.2, 6.6 Hz, 1 H),
3.69-3.63 (m, 2 H), 3.59 (dd, J ) 9.8, 3.0 Hz, 1 H); 13C NMR
(50 MHz, CDCl3) δ 155.7, 149.1, 137.9, 137.4, 137.1, 136.2,
128.1, 128.0, 127.9, 127.7, 127.5, 127.4, 127.3, 123.1, 120.2,
82.6, 82.3, 77.1, 74.2, 73.0, 71.9, 71.8, 67.9, 61.5; IR (neat)
(cm-1) 3031, 2875, 2106, 1450, 1418. Anal. Calcd for
2-Aceta m id o-2-d eoxy-3,4,6-tr i-O-ben zyl-r-D-ga la ctop y-
r a n osyl 2-P yr id yl Su lfon e (r-5). m-CPBA of approximately
85% purity (735 mg, 2.13 mmol) was added to a stirred mixture
of sulfide R-4 (580 mg, 0.99 mmol) and NaHCO3 (584 mg, 6.95
mmol) in CH2Cl2 (10 mL) at 0 °C. Stirring was continued for
2.5 h at 0 °C, after which time the reaction mixture was diluted
with CH2Cl2 and then washed consecutively with a 50%
saturated solution of Na2S2O3, saturated NaCO3, and brine.
The organic phase was dried with Na2SO4 and concentrated
to dryness in vacuo. Flash chromatography (cyclohexane/
EtOAc 1:5) gave R-5 (545 mg, 89%) as a colorless solid.
Recrystallization from EtOAc/pentane provided colorless
1
needles: mp 151 °C; [R]D ) 95.0° (c ) 0.97, CHCl3); H NMR
(250 MHz, CDCl3) δ 8.64 (broad d, J ) 4.8 Hz, 1 H), 7.97 (broad
d, J ) 7.9 Hz, 1 H), 7.74 (dd, J ) 7.9, 1.7 Hz, 1 H), 7.42-7.18
(m, 16 H, 3Ph), 5.83 (d, J ) 8.0 Hz, 1 H), 5.60 (d, J ) 5.8 Hz,
1 H), 5.07 (ddd, J ) 10.8, 8.0, 5.8 Hz, 1 H), 4.86 (d, J ) 11.8
Hz, 1 H), 4.78 (d, J ) 11.8 Hz, 1 H), 4.68 (d, J ) 11.8 Hz, 1 H),
4.53 (d, J ) 11.8 Hz, 1 H), 4.52 (m, 1 H), 4.33 (d, J ) 11.8 Hz,
1 H), 4.27 (d, J ) 11.8 Hz, 1 H), 4.43 (dd, J ) 10.8, 2.8 Hz, 1
H), 4.08 (dd, J ) 3.0, 2.8 Hz, 1 H), 3.45 (dd, J ) 9.8, 6.2 Hz,
1 H), 3.35 (dd, J ) 9.8, 6.2 Hz, 1 H), 1.80 (s, 3 H); 13C NMR
(50 MHz, CDCl3) δ 170.7, 156.0, 137.9, 137.7, 137.7, 137.5,
128.5, 128.2, 128.1, 128.0, 127.9, 127.8, 127.6, 127.3, 123.3,
87.7, 75.1, 74.9, 74.1, 73.0, 72.1, 71.9, 67.9, 47.3, 23.0; IR (neat)
(cm-1) 3055, 2987, 1684, 1422, 1265. Anal. Calcd for
C
32H32N4O4S: C, 67.59; H, 5.67; N, 9.85. Found: C, 67.51; H,
5.71; N, 9.64.
P yr id yl Su lfid es r-3 a n d â-3 fr om 2-Azid o-2-d eoxy-
3,4,6-tr i-O-ben zyl-â-D-ga la ctop yr a n ose (2). Tributylphos-
phine (1.36 mL, 5.46 mmol) was added to a stirred solution of
hemiacetal 2 (2.0 g, 4.2 mmol) and 2,2′-dipyridyl disulfide (1.11
g, 5.0 mmol) in CH2Cl2 (65 mL). After being stirred for 1 h,
the solution was evaporated to dryness in vacuo. Purification
of the residue by flash chromatography (cyclohexane/EtOAc
5:1) provided first the R-anomer R-3 (614 mg) and then the
â-anomer â-3 (1.61 g) in a combined yield of 93%.
2-P yr id yl 2-Acet a m id o-2-d eoxy-3,4,6-t r i-O-b en zyl-1-
th io-r-D-ga la ctop yr a n osid e (r-4). To a stirred solution of
SnCl2 (341 mg, 1.79 mmol) in acetonitrile (10 mL) was added
consecutively thiophenol (740 µL, 7.22 mmol), triethylamine
(750 µL, 5.41 mmol), and azide R-3 (684 mg, 1.20 mmol). The
solution was stirred for 20 min, after which time it was diluted
with CH2Cl2 and washed with 2 N NaOH. The aqueous phase
was reextracted with CH2Cl2, and the combined organic phase
was then dried (Na2SO4) and evaporated to dryness in vacuo.
The residue was redissolved in pyridine (18 mL) and Ac2O (7
mL) and left standing overnight. The solution was evaporated
to dryness in vacuo and then coevaporated with toluene (3×).
Purification of the residue by flash chromatography (cyclo-
hexane/EtOAc 1:3) provided the acetamide R-4 (703 mg) in a
C
34H36N2O7S: C, 66.22; H, 5.89; N, 4.54. Found: C, 66.25; H,
6.05; N, 4.48.
2-Aceta m id o-2-d eoxy-3,4,6-tr i-O-ben zyl-â-D-ga la ctop y-
r a n osyl 2-P yr id yl Su lfon e (â-5). The procedure described
for the obtention of R-5 was adopted. Flash chromatography
(cyclohexane/EtOAc 1:5) gave â-5 (74 mg, 12%) as a colorless
syrup that was difficult to obtain in pure form: 1H NMR (250
MHz, CDCl3) δ 8.60 (dd, J ) 5.0, 2.0 Hz, 1 H), 8.04 (d, J ) 8.1
Hz, 1 H), 7.80 (ddd, J ) 8.1, 8.1, 2.0 Hz, 1 H), 7.41-7.11 (m,
16 H), 6.21 (d, J ) 7.1 Hz, 1 H), 5.60 (d, J ) 10.1 Hz, 1 H),
4.82 (d, J ) 11.5 Hz, 1 H), 4.68 (dd, J ) 10.8, 2.9 Hz, 1 H),
4.67 (d, J ) 11.5 Hz, 1 H), 4.57 (d, J ) 11.5 Hz, 1 H), 4.46 (d,
J ) 11.5 Hz, 1 H), 4.38 (s, 2 H), 4.08 (ddd, J ) 10.8, 10.1, 7.1

2514 J . Org. Chem., Vol. 63, No. 8, 1998
Urban et al.
Hz, 1 H), 3.88 (d, J ) 3.0 Hz, 1 H), 3.77 (dd, J ) 7.2, 5.5 Hz,
1 H), 3.40 (m, 2 H), 1.88 (s, 3 H); IR (neat) (cm-1) 3056, 1666,
1438, 1185; MS (CI, NH3) m/z 617 (M + 1), 474 (M + 1 - HSO2-
Pyr).
the R- and â-C-glycosides, as well as dimer 11 (see below) in
a ratio of 5.0:1.0:0.8, respectively, according to the 1H NMR
spectrum. This corresponded to a 60% yield for the C-
glycosylation step and an 8% yield for the dimer production.
The second fraction was identified as the 1-deoxy derivative
10 (4 mg, 10%). R-13: 1H NMR (200 MHz, CDCl3) δ 7.40-
7.24 (m, 15 H), 7.03 (d, J ) 4.8 Hz, 1 H), 4.81 (d, J ) 12.0 Hz,
1 H), 4.70 (d, J ) 12.0 Hz, 1 H), 4.62 (d, J ) 12.0 Hz, 1 H),
4.55 (d, J ) 12.1 Hz, 1 H), 4.52 (d, J ) 12.0 Hz, 1 H), 4.45 (d,
J ) 12.1 Hz, 1 H), 4.38 (ddd, J ) 9.5, 6.7, 2.1 Hz, 1 H), 4.27
(dd, J ) 3.3, 3.3 Hz, 1 H), 4.20 (dd, J ) 11.8, 9.5 Hz, 1 H),
4.05 (ddd, J ) 4.8, 3.3, 2.2 Hz, 1 H), 3.81 (dd, J ) 6.7, 3.3 Hz,
1 H), 3.78 (dd, J ) 11.8, 2.1 Hz, 1 H), 3.67 (d, J ) 2.1 Hz, 1
H), 1.97 (s, 3 H), 1.85-1.18 (m, 8 H); 13C NMR (50 MHz, CDCl3)
δ 170.7, 138.8, 137.8, 128.4, 128.3, 128.1, 128.0, 127.6, 127.5,
83.7, 75.3, 73.4, 73.3, 73.1, 72.6, 70.7, 69.1, 65.6, 51.2, 41.4,
34.4, 23.8, 23.6; IR (neat) (cm-1) 3054, 2987, 1422, 1265; MS
2-Aceta m id o-2-d eoxy-3,4,6-tr i-O-ben zyl-r-D-ga la ctop y-
r a n osyl-1-cycloh exa n ol (r-9). A 0.1 M solution of SmI2 in
THF (1.6 mL, 0.16 mmol) was added to a stirred solution of
sulfone R-5 (50 mg, 0.081 mmol) and cyclohexanone (17 µL,
0.17 mmol) in THF (0.5 mL) at 20 °C. After the mixture was
stirred for 10 min, saturated aqueous NH4Cl was added, and
the resulting mixture was then extracted twice with CH2Cl2.
The combined organic phases were washed twice with water,
dried, with Na2SO4, and evaporated to dryness. Flash chro-
matography (cyclohexane/EtOAc 1:3) afforded two fractions.
The first fraction (39 mg) contained a mixture of the R- and
â-C-glycosides, as well as dimer 11 (see below) in the ratio of
1
10.0:1.0:1.6, respectively, according to the H NMR spectrum.
This corresponded to a 75% yield for the C-glycosylation step
and a 9% yield for the dimer production. R-9: 1H NMR (250
MHz, CDCl3) δ 7.40-7.27 (m, 15 H), 6.92 (d, J ) 4.8 Hz, 1 H),
4.77 (d, J ) 12.3 Hz, 1 H), 4.67 (d, J ) 12.3 Hz, 1 H), 4.56 (d,
J ) 12.1 Hz, 1 H), 4.47 (d, J ) 12.1 Hz, 1 H), 4.47 (d, J ) 11.8
Hz, 1 H), 4.40 (d, J ) 11.8 Hz, 1 H), 4.39 (ddd, J ) 9.4, 6.7,
2.0 Hz, 1 H), 4.30 (dd, J ) 3.4, 3.4 Hz, 1 H), 4.21 (dd, J )
11.7, 9.4 Hz, 1 H), 4.06 (broad dd, J ) 4.8, 3.4 Hz, 1 H), 3.83
(dd, J ) 6.7, 3.4 Hz, 1 H), 3.80 (dd, J ) 11.7, 2.0 Hz, 1 H),
3.74 (bs, 1 H), 2.08 (s, 1 H), 1.94 (s, 3 H), 1.67-1.16 (m, 10 H);
13C NMR (50 MHz, CDCl3) δ 170.6, 138.8, 138.3, 137.9, 128.3,
128.2, 127.9, 127.8, 127.7, 127.5, 75.2, 73.3, 73.1, 73.1, 72.6,
70.6, 67.7, 65.7, 49.8, 36.9, 31.9, 25.4, 23.5, 21.6, 21.5; MS (CI,
NH3) m/z 574 (M + 1), 556 (M + 1 - H2O), 482 (M + 1 -
PhCH3); IR (neat) (cm-1) 3054, 2987, 2936, 2850, 1496, 1422,
1267. Characteristic signals for the â-isomer â-9 were seen
at δ 5.24 (d, J ) 8.5 Hz, 1 H), 4.92 (d, J ) 11.9 Hz, 1 H), 3.42
(d, J ) 9.7 Hz, 1 H), 1.89 (s, 3 H). The second fraction was
identified as the 1-deoxy derivative 10 (6 mg, 16%): 1H NMR
(250 MHz, CDCl3) δ 7.75-7.26 (m, 15 H), 5.18 (d, J ) 6.3 Hz,
1 H), 4.90 (d, J ) 11.7 Hz, 1 H), 4.75 (d, J ) 12.3 Hz, 1 H),
4.61 (d, J ) 11.7 Hz, 1 H), 4.52 (d, J ) 11.9 Hz, 1 H), 4.45 (d,
J ) 11.9 Hz, 1 H), 4.41 (d, J ) 12.3 Hz, 1 H), 4.26-4.15 (m, 2
H), 4.01 (d, J ) 3.0 Hz, 1 H), 3.66-3.46 (m, 4 H), 3.16 (dd, J
) 12.0, 12.0 Hz, 1 H), 1.87 (s, 3 H); MS (CI, NH3) m/z 494 (M
+ 18), 476 (M + 1), 384 (M + 1 - PhCH3).
2-Aceta m id o-2-d eoxy-3,4,6-tr i-O-ben zyl-r-D-ga la ctop y-
r a n osyl-3-p en ta n ol (r-12). The C-glycosides were prepared
according to the general procedure outlined for R-9. Flash
chromatography (cyclohexane/EtOAc 1:3) afforded two frac-
tions. The first fraction (40 mg) contained a mixture of the R-
and â-C-glycosides, as well as dimer 11 (see below) in a ratio
of 10.0:1.0:1.1, respectively, according to the 1H NMR spec-
trum. This corresponded to a 67% yield for the C-glycosylation
step and a 7% yield for the dimer production. The second
fraction was identified as the 1-deoxy derivative 10 (8 mg,
18%). R-12: 1H NMR (250 MHz, CDCl3) δ 7.40-7.24 (m, 15
H), 6.98 (d, J ) 4.8 Hz, 1 H), 4.82 (d, J ) 12.3 Hz, 1 H), 4.73
(d, J ) 12.3 Hz, 1 H), 4.58 (d, J ) 11.8 Hz, 1 H), 4.54 (d, J )
12.1 Hz, 1 H), 4.52 (d, J ) 11.8 Hz, 1 H), 4.43 (d, J ) 12.1 Hz,
1 H), 4.38 (ddd, J ) 9.4, 7.0, 2.1 Hz, 1 H), 4.30 (dd, J ) 3.4,
3.4 Hz, 1 H), 4.21 (dd, J ) 11.6, 9.4 Hz, 1 H), 4.05 (ddd, J )
4.8, 3.4, 3.0 Hz, 1 H), 3.81 (dd, J ) 7.0, 3.4 Hz, 1 H), 3.79 (d,
J ) 3.0 Hz, 1 H), 3.78 (dd, J ) 11.7, 2.1 Hz, 1 H), 1.97 (s, 3 H),
1.77-1.21 (m, 4 H), 0.79 (t, J ) 11.9 Hz, 6 H); 13C NMR (50
MHz, CDCl3) δ 170.8, 139.0, 138.4, 138.0, 128.5, 128.2, 127.9,
127.6, 75.3, 73.4, 73.3, 72.7, 70.8, 66.0, 65.9, 50.3, 28.6, 24.9,
23.7, 7.7; IR (neat) (cm-1) 3054, 2987, 1669, 1422, 1266; MS
(electrospray) m/z 582 (M + Na); HRMS m/e calcd for C34H41-
NNaO6 (M + Na) 582.2832, found 582.2843. Characteristic
signals for the â-isomer were seen at δ 5.36 (d, J ) 7.4 Hz, 1
H), 4.85 (d, J ) 11.6 Hz, 1 H), 1.90 (s, 3 H).
2-Aceta m id o-2-d eoxy-3,4,6-tr i-O-ben zyl-r-D-ga la ctop y-
r a n osyl-1-cycloh exylm eth a n ol (r-14). The C-glycosides
were prepared according to the general procedure outlined for
R-9. Flash chromatography (cyclohexane/EtOAc 1:3) afforded
two fractions (A and B), in which the first contained four
compounds (51 mg) according to its 1H NMR spectrum and
the latter (B) was the 1-deoxy derivative 10 (3 mg, 6%).
Subjection of the first fraction to flash chromatography
(toluene/EtOAc 7:2) led to two new fractions (C and D), the
first of which contained the isomeric R-C-glycosides in a ratio
of 6:1 (41 mg, 64%), whereas the other contained a mixture of
dimer 11 and the â-C-glycoside. Fraction C was then rechro-
matographed in cyclohexane/EtOAc (1:3), affording first a
mixture of the R-C-glycosides in favor of the minor isomer and
then the pure major isomer, which was recrystallized from
EtOAc/Et2O/pentane. R-14 (major C7-isomer): mp 137-138
°C; [R]D ) 15.1° (c ) 1.23, CHCl3); 1H NMR (250 MHz, CDCl3)
δ 7.37-7.24 (m, 15 H), 6.54 (d, J ) 5.9 Hz, 1 H), 4.77 (d, J )
11.8 Hz, 1 H), 4.70 (d, J ) 11.8 Hz, 1 H), 4.69 (d, J ) 12.0 Hz,
1 H), 4.54 (d, J ) 11.8 Hz, 1 H), 4.53 (d, J ) 12.0 Hz, 1 H),
4.44 (d, J ) 11.8 Hz, 1 H), 4.37 (ddd, J ) 9.4, 6.2, 2.4 Hz, 1
H), 4.23 (dd, J ) 11.3, 9.4 Hz, 1 H), 4.13 (dd, J ) 3.0, 2.9 Hz,
1 H), 4.07 (dd, J ) 3.4, 2.9 Hz, 1 H), 4.05 (ddd, J ) 5.9, 3.0,
2.9 Hz, 1 H), 3.78 (dd, J ) 6.2, 2.9 Hz, 1 H), 3.73 (dd, J )
11.3, 2.4 Hz, 1 H), 3.31 (ddd, J ) 7.2, 5.0, 3.4 Hz, 1 H), 2.41
(d, J ) 7.2 Hz, 1 H), 1.97 (s, 3 H), 1.80-1.07 (m, 11 H, CH,
5CH2); 13C NMR (50 MHz, CDCl3) δ 170.5, 138.7, 138.3, 137.9,
128.5, 128.4, 128.0, 127.7, 75.8, 75.2, 73.8, 73.6, 73.1, 72.6, 71.0,
65.8, 64.9, 51.8, 41.1, 29.8, 27.3, 26.4, 26.4, 26.1, 23.6; IR (neat)
(cm-1) 3429, 3054, 2987, 2929, 2856, 1675, 1497, 1454, 1422,
1372; MS (electrospray) m/z 610 (M + Na); HRMS m/e calcd
for C36H45NNaO6 (M + Na) 610.3145, found 610.3158. Char-
acteristic signals for the minor R-C-glycoside were seen at δ
7.37-7.24 (m, 15 H), 6.43 (d, J ) 6.8 Hz, 1 H), 4.72 (s, 2 H),
4.57 (s, 2 H), 4.54 (d, J ) 12.3 Hz, 1 H), 4.46 (d, J ) 12.3 Hz,
1 H), 4.37 (ddd, J ) 9.2, 6.8, 2.7 Hz, 1 H), 4.24 (ddd, J ) 6.8,
3.6, 2.5 Hz, 1 H), 4.18 (dd, J ) 11.8, 9.2 Hz, 1 H), 4.08 (dd, J
) 3.6, 3.6 Hz, 1 H), 3.94 (dd, J ) 5.5, 2.5 Hz, 1 H), 3.76 (dd, J
) 11.8, 2.7 Hz, 1 H), 3.75 (dd, J ) 6.8, 3.6 Hz, 1 H), 3.43 (ddd,
J ) 5.5, 5.5, 3.8 Hz, 1 H), 2.65 (d, J ) 3.8 Hz, 1 H), 2.00 (s, 3
H), 1.90-1.05 (m, 11 H). Fraction D was subjected to standard
acetylation conditions (Ac2O, pyridine) and then rechromato-
graphed in toluene/EtOAc (7:2), affording first a fraction
containing the acetylated â-C-glycosides (2 mg, 3%) contami-
nated with 11 and then dimer 11 (3 mg, 6%). â-Isomer: 1H
NMR (250 MHz, CDCl3) δ 7.40-7.22 (m, 15 H), 5.22 (d, J )
8.8 Hz, 1 H), 4.99 (d, J ) 11.6 Hz, 1 H), 4.73 (d, J ) 12.3 Hz,
1 H), 4.56 (d, J ) 11.6 Hz, 1 H), 4.53 (m, 1 H), 4.47 (s, 2 H),
4.46 (d, J ) 12.3 Hz, 1 H), 4.23 (ddd, J ) 10.0, 10.0, 8.8 Hz, 1
H), 4.01 (d, J ) 2.9 Hz, 1 H), 3.63-3.47 (m, 5 H), 2.03 (s, 3 H),
1.95 (s, 3 H), 1.86-1.05 (m, 11 H). Dimer 11: 1H NMR (250
MHz, CDCl3) δ 7.38-7.15 (m, 30 H), 6.88 (d, J ) 4.7 Hz, 2 H),
4.68 (d, J ) 11.9 Hz, 2 H), 4.62 (d, J ) 11.9 Hz, 2 H), 4.51 (d,
J ) 12.2 Hz, 2 H), 4.50 (d, J ) 12.0 Hz, 2 H), 4.44 (d, J ) 12.2
(electrospray) m/z 584 (M + Na); HRMS m/e calcd for C34H43
-
NNaO6 (M + Na), 584.2988, found 584.3015. Characteristic
signals for the â-isomer were seen at δ 5.24 (d, J ) 8.8 Hz, 1
H), 4.96 (d, J ) 11.7 Hz, 1 H), 3.57 (d, J ) 9.7 Hz, 1 H), 1.90
(s, 3 H), 0.88 (t, J ) 11.9 Hz, 6 H).
2-Aceta m id o-2-d eoxy-3,4,6-tr i-O-ben zyl-r-D-ga la ctop y-
r a n osyl-1-cyclop en ta n ol (r-13). The C-glycosides were
prepared according to the general procedure outlined for R-9.
Flash chromatography (cyclohexane/EtOAc 2:3) afforded two
fractions. The first fraction (30 mg) contained a mixture of

Synthesis of R-C-Galactosamine Derivatives
J . Org. Chem., Vol. 63, No. 8, 1998 2515
Hz, 2 H), 4.37 (ddd, J ) 9.5, 6.2, 2.0 Hz, 2 H), 4.34 (d, J )
12.0 Hz, 2 H), 4.34 (d, J ) 4.6 Hz, 2 H), 4.18 (dd, J ) 3.2, 3.2
Hz, 2 H), 4.15 (dd, J ) 12.1, 9.5 Hz, 2 H), 4.06 (dd, J ) 4.7,
4.6 Hz, 2 H), 3.76 (dd, J ) 6.2, 3.2 Hz, 2 H), 3.57 (dd, J )
12.1, 2.0 Hz, 2 H), 1.79 (s, 6 H); 13C NMR (50 MHz, CDCl3) δ
171.4, 138.5, 138.0, 137.9, 75.8, 73.7, 73.6, 73.5, 72.2, 71.4, 67.6,
66.2, 53.7, 23.3; IR (neat) (cm-1) 3054, 2987, 1419, 1266; MS
(CI, NH3) m/z 949 (M + 1).
3,4,6-Tr i-O-ben zyl-â-D-galactopyr an osyl-3-pen tan ol (21).
A 0.1 M solution of SmI2 in THF (2.2 mL, 0.22 mmol) was
added to a stirred solution of sulfone 172d (68 mg, 0.11 mmol)
and 3-pentanone (16 µL, 0.15 mmol) in THF (0.5 mL) at 20
°C. After the mixture was stirred for 10 min, saturated
aqueous NH4Cl was added, and the resulting mixture was then
extracted twice with CH2Cl2. The combined organic phases
were washed twice with water, dried (Na2SO4), and evaporated
to dryness. The residue was redissolved in THF (5 mL) and
cooled to 0 °C, and 1.0 M Bu4NF in THF (210 µL, 0.210 mmol)
was added. After the mixture was stirred for 5 min, water
and CH2Cl2 were added, and the organic phase was washed
twice with water, dried with Na2SO4, and evaporated to
dryness. Flash chromatography (cyclohexane/EtOAc 7:1-3:
1) gave first tribenzyl-D-galactal (12 mg, 29%) and then 21 (16
mg, 31%): 1H NMR (200 MHz, CDCl3) δ 7.40-7.24 (m, 15 H),
4.85 (d, J ) 11.6 Hz, 1 H), 4.73 (d, J ) 12.0 Hz, 1 H), 4.56 (d,
J ) 11.6 Hz, 1 H), 4.48 (d, J ) 12.0 Hz, 1 H), 4.48 (d, J ) 11.8
Hz, 1 H), 4.42 (d, J ) 11.8 Hz, 1 H), 4.21 (dd, J ) 9.4, 9.0 Hz,
1 H), 3.98 (d, J ) 2.8 Hz, 1 H), 3.73 (dd, J ) 6.5, 6.5 Hz, 1 H),
3.64-3.52 (m, 2 H), 3.44 (dd, J ) 9.0, 2.8 Hz, 1 H), 3.24 (d, J
) 9.4 Hz, 1 H), 2.99 (broad s, 1 H), 2.87 (broad s, 1 H), 1.83-
1.39 (m, 4 H), 1.89-1.74 (m, 6 H); 13C NMR (50 MHz, CDCl3)
δ 138.8, 137.8, 137.7, 128.6, 128.4, 128.2, 128.0, 127.8, 127.5,
84.4, 80.8, 75.7, 74.3, 73.5, 72.8, 71.8, 68.9, 68.2, 29.1, 28.0,
7.6, 7.1; IR (neat) (cm-1) 3054, 2986, 1419, 1263; MS (electro-
spray) m/z 543 (M + Na); HRMS m/e calcd for C32H40NaO6 (M
+ Na) 543.2723, found 543.2729.
2-Aceta m id o-2-d eoxy-3,4,6-tr i-O-ben zyl-r-D-ga la ctop y-
r a n osyl-2-m eth ylp r op a n ol (r-15). The C-glycosides were
prepared according to the general procedure outlined for R-9.
Flash chromatography (cyclohexane/EtOAc 1:2) afforded two
fractions. The first fraction (40 mg) contained a mixture of
two R-C-glycosides and one detectable â-C-glycoside, as well
as dimer 11 (see above) in the ratio of 10.0:2.0:1.0:0.8,
respectively, according to the 1H NMR spectrum. This cor-
responded to a 72% yield for the C-glycosylation step and a
4% yield for the dimer production. The second fraction was
identified as the 1-deoxy derivative 10 (2 mg, 4%). Further
careful purification of the first fraction afforded pure R-15
(major isomer) as a colorless syrup: [R]D ) 18.3° (c ) 0.93,
CHCl3); 1H NMR (250 MHz, CDCl3) δ 7.40-7.21 (m, 15 H),
6.37 (d, J ) 6.4 Hz, 1 H), 4.75 (d, J ) 11.9 Hz, 1 H), 4.69 (d,
J ) 11.9 Hz, 1 H), 4.59 (d, J ) 11.8 Hz, 1 H), 4.52 (d, J ) 12.0
Hz, 1 H), 4.50 (d, J ) 11.8 Hz, 1 H), 4.43 (d, J ) 12.0 Hz, 1 H),
4.36 (ddd, J ) 9.2, 6.5, 2.6 Hz, 1 H), 4.21 (dd, J ) 11.6, 9.2
Hz, 1 H), 4.12-4.05 (m, 2 H, H2), 4.00 (dd, J ) 4.7, 1.7 Hz, 1
H), 3.76 (dd, J ) 6.4, 2.6 Hz, 1 H), 3.71 (dd, J ) 11.3, 2.6 Hz,
1 H), 3.31 (broad dd, J ) 4.7, 4.7 Hz, 1 H), 2.54 (broad d, J )
4.7 Hz, 1 H), 1.99 (s, 3 H), 1.73 (m, 1 H), 0.97 (d, J ) 7.0 Hz,
3 H), 0.93 (d, J ) 7.0 Hz, 3 H); 13C NMR (50 MHz, CDCl3) δ
170.4, 138.6, 138.2, 137.8, 128.5, 128.4, 128.1, 127.9, 127.8,
127.7, 127.6, 75.9, 75.1, 73.9, 73.5, 73.0, 72.6, 71.0, 65.8, 65.6,
51.1, 30.9, 29.8, 23.5, 19.8, 16.6; IR (neat) (cm-1) 3054, 2987,
1675, 1496, 1422, 1267; MS (electrospray) m/z 570 (M + Na);
HRMS m/e calcd for C33H41NNaO6 (M + Na) 570.2832, found
570.2832. Characteristic signals for the minor R-C-glycoside
were seen at δ 6.46 (d, J ) 7.2 Hz, 1 H), 3.94 (dd, J ) 6.7, 2.2
Hz, 1 H), 3.42 (ddd, J ) 6.2, 6.2, 3.7 Hz, 1 H), 2.02 (s, 3 H),
1.90-1.05 (m, 11 H, CH, 5CH2), 0.89 (d, J ) 7.0 Hz, 3 H, Me),
0.83 (d, J ) 7.0 Hz, 3 H, Me). Characteristic signals for the
â-isomer were seen at δ 5.24 (d, J ) 7.7 Hz, 1 H), 4.92 (d, J )
11.7 Hz, 1 H), 1.95 (s, 3 H), 0.88 (t, J ) 11.9 Hz, 6 H), 1.04 (d,
J ) 7.0 Hz, 3 H), 0.97 (d, J ) 7.0 Hz, 3 H).
2-Azid o-2-d eoxy-3,4,6-tr i-O-ben zyl-â-D-ga la ctop yr a n o-
syl 2-P yr id yl Su lfon e (19). The procedure described for the
obtention of R-5 was adopted, providing pyridyl sulfone 19 (111
mg, 80%) as a colorless syrup after purification by flash
chromatography (cyclohexane/EtOAc 5:2): [R]D ) -46.3° (c )
1
0.90, CHCl3); H NMR (250 MHz, CDCl3) δ 8.65 (dd, J ) 4.9,
1.7 Hz, 1 H), 8.09 (d, J ) 7.8 Hz, 1 H), 7.88 (ddd, J ) 7.8, 7.8,
1.7 Hz, 1 H), 7.47-7.14 (m, 17 H), 4.85 (d, J ) 11.2 Hz, 1 H),
4.73 (s, 2 H), 4.64 (d, J ) 10.0 Hz, 1 H), 4.49 (d, J ) 11.2 Hz,
1 H), 4.47 (dd, J ) 10.0, 10.0 Hz, 1 H), 4.28 (s, 2 H), 3.89 (d,
J ) 2.9 Hz, 1 H), 3.59 (dd, J ) 7.1, 5.2 Hz, 1 H), 3.49 (dd, J )
10.0, 2.9 Hz, 1 H), 3.41 (m, 2 H); 13C NMR (50 MHz, CDCl3) δ
155.4, 150.1, 138.0, 137.6, 137.1, 128.6, 128.4, 128.2, 128.1,
127.9, 127.4, 124.2, 88.6, 81.9, 78.2, 74.4, 73.4, 72.7, 71.6, 68.0,
57.9. Anal. Calcd for C32H32N4O6S: C, 63.99; H, 5.37; N, 9.33.
Found: C, 64.11; H, 5.42; N, 9.21.
2-Aceta m id o-2-d eoxy-3,4,6-tr i-O-ben zyl-r-D-ga la ctop y-
r a n osyl-1-octa n ol (r-16). The C-glycosides were prepared
according to the general procedure outlined for R-9. Flash
chromatography (cyclohexane/EtOAc 2:3) afforded two frac-
tions. The first fraction (46 mg) contained a mixture of two
R-C-glycosides and one detectable â-C-glycoside as well as
dimer 11 (see above) in a ratio of 7.7:1.3:1.0:1.2, respectively,
according to the 1H NMR spectrum. This corresponded to a
69% yield for the C-glycosylation step and a 10% yield for the
dimer production. The second fraction was identified as the
1-deoxy derivative 10 (5 mg, 11%). R-15 (major C7-isomer):
1H NMR (200 MHz, CDCl3) δ 7.38-7.20 (m, 15 H), 6.27 (d, J
) 7.0 Hz, 1 H), 4.77 (d, J ) 12.2 Hz, 1 H), 4.68 (d, J ) 12.2
Hz, 1 H), 4.59 (d, J ) 12.0 Hz, 1 H), 4.54 (d, J ) 12.0 Hz, 1 H),
4.53 (d, J ) 12.0 Hz, 1 H), 4.45 (d, J ) 12.0 Hz, 1 H), 4.36
(ddd, J ) 9.3, 6.5, 2.3 Hz, 1 H), 4.22 (dd, J ) 11.1, 9.3 Hz, 1
H), 4.15 (ddd, J ) 7.0, 3.3, 2.5 Hz, 1 H), 4.06 (dd, J ) 3.8, 3.3
Hz, 1 H), 3.82 (dd, J ) 5.5, 2.5 Hz, 1 H), 3.77 (dd, J ) 6.5, 3.8
Hz, 1 H), 3.73 (dd, J ) 11.1, 2.3 Hz, 1 H), 3.57 (m, 1 H), 2.47
(broad d, J ) 5.2 Hz, 1 H), 1.97 (s, 3 H), 1.47-1.20 (m, 12 H),
0.97 (t, J ) 6.5 Hz, 3 H); 13C NMR (50 MHz, CDCl3) δ 170.2,
138.5, 138.3, 137.8, 128.5, 128.4, 128.0, 127.9, 127.8, 127.7,
75.2, 74.0, 73.4, 73.1, 72.7, 71.2, 71.0, 68.4, 65.6, 50.3, 33.3,
3-(4′-P en ten oyl)-2-oxa zolid in on e (27). To a stirred solu-
tion of 4-pentenoic acid (1.28 mL, 12.1 mmol) and triethyl-
amine (1.92 mL, 13.8 mmol) in THF (50 mL) at -78 °C was
added dropwise trimethylacetyl chloride (1.5 mL, 12.1 mmol).
After being stirred for 10 min at -78 °C and 30 min at 0 °C,
the suspension was recooled to -78 °C, and to this was added
a solution of metalated oxazolidinone (prepared by the addition
of 2.5 M BuLi in hexanes (4.6 mL, 1.84 mmol) to a -78 °C
stirred suspension of 2-oxazolidinone (1.00 g, 11.5 mmol) in
THF (50 mL), followed by warming to 20 °C). The mixture
was warmed to 0 °C and left stirring at this temperature for
1.5 h. The reaction mixture was quenched with aqueous NH4-
Cl and then extracted with CH2Cl2 (3×). The combined organic
phases were washed with 1 N NaOH and water and then dried
(Na2SO4) and evaporated to dryness in vacuo. Purification of
the residue by flash chromatography (cyclohexane/EtOAc 3:1)
afforded 27 as a colorless syrup (1.24 g, 73%). 1H NMR (250
MHz, CDCl3) δ 5.88 (ddt, J ) 17.0, 10.2, 6.5 Hz, 1 H), 5.10
(ddd, J ) 17.0, 3.4, 1.5 Hz, 1 H), 5.03 (dd, J ) 10.2, 1.5 Hz, 1
H), 4.39 (t, J ) 8.0 Hz, 2 H), 3.39 (t, J ) 8.0 Hz, 2 H), 3.02 (t,
J ) 7.0 Hz, 2 H), 2.40 (m, 2 H); 13C NMR (50 MHz, CDCl3) δ
172.1, 153.3, 136.5, 115.1, 61.9, 42.1, 34.0, 27.7; IR (neat)
(cm-1) 3057, 2987, 2925, 1782, 1700, 1612, 1481, 1387, 1268.
Anal. Calcd for C8H11NO3: C, 56.80; H, 6.55. Found: C, 56.65;
H, 6.53.
31.9, 29.8, 29.5, 29.3, 25.3, 23.5, 22.8, 14.2; IR (neat) (cm-1
)
3054, 2987, 1507, 1419, 1266; MS (electrospray) m/z 626 (M
+ Na); HRMS m/e calcd for C37H49NNaO6 (M + Na) 626.3458,
found 626.3460. Characteristic signals for the minor R-C-
glycoside were seen at δ 6.40 (d, J ) 7.0 Hz, 1 H), 1.99 (s, 3
H), 1.90-1.05 (m, 11 H). Characteristic signals for the
â-isomer were seen at δ 5.07 (d, J ) 7.7 Hz, 1 H), 4.92 (d, J )
11.7 Hz, 1 H), 1.90 (s, 3 H).
3-(4′-Oxobu ta n oyl)-2-oxa zolid in on e (26). Ozone was
bubbled through a solution of alkene 27 (155 mg, 0.92 mmol)
in CH2Cl2 (15 mL) at -78 °C until the solution turned blue.
Argon was then allowed to bubble though the solution for 20
min at the same temperature, after which time triphenylphos-
phine (362 mg, 1.38 mmol) was added, and the mixture was

2516 J . Org. Chem., Vol. 63, No. 8, 1998
Urban et al.
stirred for an additional 10 min. After evaporation to dryness
in vacuo, the residue was purified by flash chromatography
(cyclohexane/EtOAc 3:1), giving 26 as a colorless solid (143 mg,
91%). Recrystallization from EtOAc/Et2O/pentane afforded
colorless needles: mp 43 °C; 1H NMR (250 MHz, CDCl3) δ 9.72
(s, 1 H), 4.37 (t, J ) 8.0 Hz, 2 H), 3.94 (t, J ) 8.0 Hz, 2 H),
3.17-3.09 (t, 2 H), 2.80-2.72 (m, 2 H); 13C NMR (50 MHz,
CDCl3) δ 200.3, 171.8, 153.7, 62.4, 42.5, 37.6, 28.1; IR (neat)
(cm-1) 3054, 2987, 1783, 1700, 1422, 1388, 1267. Anal. Calcd
for C7H9NO4: C, 49.12; H, 5.30. Found: C, 48.99; H, 5.21.
r-C-Ga la ctosa m in e (r-28). The C-glycosides were pre-
pared from pyridyl sulfone R-5 according to the general
procedure outlined for R-9. Flash chromatography (cyclohex-
ane/EtOAc 1:3) afforded a fraction containing a mixture of two
R-C-glycosides and one detectable â-C-glycoside, as well as the
1-deoxy derivative 10 (see above) in the ratio of 3.5:1.5:1.0:
0.8, respectively, according to the 1H NMR spectrum. This
corresponded to an 80% yield for the C-glycosylation step and
a 10% yield for the 1-deoxy sugar formation. An approximately
2% yield of the dimer was also obtained. R-28 (major C7-
isomer): 1H NMR (250 MHz, CDCl3) δ 7.40-7.24 (m, 15 H),
5.71 (d, J ) 8.5 Hz, 1 H), 4.74 (d, J ) 11.7 Hz, 1 H), 4.68 (d,
J ) 11.7 Hz, 1 H), 4.61 (d, J ) 11.7 Hz, 1 H), 4.60 (m, 1 H),
4.48 (d, J ) 11.7 Hz, 1 H), 4.48 (d, J ) 12.3 Hz, 1 H), 4.43 (d,
J ) 12.3 Hz, 1 H), 4.40 (m, 1 H), 4.26 (m, 1 H), 4.22 (m, 1 H),
3.96 (dd, J ) 4.2, 3.5 Hz, 1 H), 3.90 (dd, J ) 6.8, 2.4 Hz, 1 H),
3.76 (dd, J ) 6.2, 3.5 Hz, 1 H), 3.75 (dd, J ) 11.6, 2.5 Hz, 1
H), 2.70-2.07 (m, 4 H), 2.00 (s, 3 H); charateristic peaks for
13C NMR (50 MHz, CDCl3) δ 176.5, 169.7, 75.5, 73.9, 72.3, 71.1,
67.7, 65.1, 48.2, 27.7, 24.4, 23.4; IR (neat) (cm-1) 3054, 2987,
1457, 1265; MS (electrospray) m/z 582 (M + Na); HRMS m/e
calcd for C33H37NNaO7 (M + Na) 582.2468, found 582.2473.
R-28 (minor C7-isomer): 1H NMR (250 MHz, CDCl3) δ 6.06
(d, J ) 7.2 Hz, 1 H), 4.78 (d, J ) 11.8 Hz, 1 H), 4.65 (d, J )
11.8 Hz, 1 H), 4.60 (m, 1 H), 4.59 (d, J ) 12.0 Hz, 1 H), 4.54
(d, J ) 12.0 Hz, 1 H), 4.54 (d, J ) 12.0 Hz, 1 H), 4.48 (d, J )
12.0 Hz, 1 H), 4.40 (m, 1 H1), 4.33 (ddd, J ) 9.4, 6.1, 3.1 Hz,
1 H), 4.14 (dd, J ) 11.4, 9.4 Hz, 1 H), 4.02 (dd, J ) 3.1, 3.1
Hz, 1 H), 4.01 (dd, J ) 2.5 Hz, 1 H), 3.81 (dd, J ) 6.1, 3.1 Hz,
1 H), 3.72 (dd, J ) 11.4, 3.1 Hz, 1 H), 2.70-2.07 (m, 4 H), 1.97
(s, 3 H); 13C NMR (50 MHz, CDCl3) δ 177.3, 170.6, 80.0, 74.9,
74.7, 73.2, 73.1, 72.5, 71.6, 68.1, 65.8, 51.2, 27.8, 25.4, 23.6.
Characteristic signals for the â-isomer were seen at δ 4.93 (d,
J ) 11.6 Hz, 1 H), 1.92 (s, 3 H).
outlined for R-9, affording the title compound as a colorless
syrup and as a 3:1 mixture of diastereomers (24 mg, 65%) after
flash chromatography (cyclohexane/EtOAc 7:1-1:1). Major
isomer: 1H NMR (250 MHz, CDCl3) δ 7.40-7.24 (m, 15 H),
4.82 (ddd, J ) 7.3, 5.5, 1.5 Hz, 1 H), 4.66 (d, J ) 11.7 Hz, 1
H), 4.51 (d, J ) 12.2 Hz, 1 H), 4.51 (d, J ) 11.7 Hz, 1 H), 4.51
(d, J ) 11.3 Hz, 1 H), 4.43 (d, J ) 12.2 Hz, 1 H), 4.43 (d, J )
11.3 Hz, 1 H), 4.27 (dd, J ) 9.4, 3.1 Hz, 1 H), 4.10 (ddd, J )
7.3, 5.4, 3.1 Hz, 1 H), 3.77 (dd, J ) 10.2, 7.3 Hz, 1 H), 3.76
(dd, J ) 9.4, 1.5 Hz, 1 H), 3.74 (dd, J ) 3.1, 3.1 Hz, 1 H), 3.62
(dd, J ) 3.1, 3.1 Hz, 1 H), 3.56 (dd, J ) 10.2, 5.4 Hz, 1 H),
2.82-2.67 (m, 4 H), 0.94 (s, 9 H), 0.18 (s, 3 H), 0.12 (s, 3 H);
13C NMR (50 MHz, CDCl3) δ 178.1, 138.3, 138.1, 128.5, 127.8,
127.7, 78.2, 77.8, 75.2, 74.5, 73.5, 73.0, 71.7, 68.5, 67.1, 28.5,
26.0, 23.8, 18.1, -4.0, -4.9; IR (neat) (cm-1) 2928, 2857, 1779,
1497, 1253; IR (neat) (cm-1) 3032, 2927, 2857, 1778, 1454,
1362; MS (electrospray) m/z 655 (M + Na); HRMS m/e calcd
for C37H48NaO6Si (M + Na) 655.3067, found 655.3074. Minor
isomer: 1H NMR (250 MHz, CDCl3) δ 7.38-7.23 (m, 15 H),
4.79 (ddd, J ) 8.3, 4.5, 3.7 Hz, 1 H), 4.67 (d, J ) 11.5 Hz, 1
H), 4.61 (d, J ) 11.9 Hz, 1 H), 4.55 (d, J ) 11.9 Hz, 1 H), 4.52
(d, J ) 11.3 Hz, 1 H), 4.51 (d, J ) 11.5 Hz, 1 H), 4.47 (d, J )
11.3 Hz, 1 H), 4.08 (dd, J ) 7.6, 2.5 Hz, 1 H), 4.04 (dd, J )
7.6, 3.7 Hz, 1 H), 3.94 (ddd, J ) 6.5, 5.5, 3.9 Hz, 1 H), 3.82
(dd, J ) 5.6, 3.9 Hz, 1 H), 3.76 (dd, J ) 10.2, 6.5 Hz, 1 H),
3.73 (dd, J ) 5.6, 2.5 Hz, 1 H), 3.70 (dd, J ) 10.2, 5.5 Hz, 1
H), 2.75-2.17 (m, 4 H), 0.93 (s, 9 H), 0.18 (s, 3 H), 0.07 (s, 6
H).
Ack n ow led gm en t. We are indebted to Claude Riche
and Ange`le Chiaroni from the Institut de Chimie des
Substances Naturelles, CNRS, Gif-sur-Yvette, France,
for the X-ray crystallographic analysis of our C-glyco-
side. We also thank Professor H. Kessler and M.
Hoffmann from the Technischen Universita¨t Mu¨nchen
for providing us with NMR spectra of their C-glycosides.
Su p p or tin g In for m a tion Ava ila ble: NMR peak assign-
ments (9-16, 21, 28 and 30) and X-ray crystallographic data
of R-14 (13 pages). This material is contained in libraries on
microfiche, immediately follows this article in the microfilm
version of the journal, and can be ordered from the ACS; see
any current masthead page for ordering information.
r-C-Ma n n osid e (30). The C-mannosides was prepared
from pyridyl sulfone 29 according to the general procedure
J O971727H