Stereospecific synthesis of α- and β-C-glycosides from glycosyl sulfoxides: Scope and limitations

Article abstract of DOI:10.1021/jo0014515

C-Glycosides derived from α-L-fuco-, α-D-gluco-, β-D-gluco-, and α-D-mannopyranose have been synthesized from the corresponding glycosyl phenyl sulfoxide through phenylsulfinyl-lithium exchange, to generate an anomeric carbanion, and subsequent reaction with a carbon electrophile. The reactions were stereospecific and proceeded with retention of the configuration at the anomeric center. Improved yields of C-glycosides were obtained by an inverse addition protocol. Trapping of the anomeric carbanion with aldehydes gave best results. Reaction with ketones, chloroformates, nitriles, and alkyl halides was also explored. Mechanistic aspects of the reaction are discussed.

Full text of DOI:10.1021/jo0014515

1768
J . Org. Chem. 2001, 66, 1768-1774
Ster eosp ecific Syn th esis of r- a n d â-C-Glycosid es fr om Glycosyl
Su lfoxid es: Scop e a n d Lim ita tion s
Mercedes Carpintero, Ine´s Nieto, and Alfonso Ferna´ndez-Mayoralas*
Instituto de Quı´mica Orgcinica General, CSIC, J uan de la Cierva 3, 28006 Madrid, Spain
Iqofm68@fresno.csic.es
Received October 9, 2000
C-Glycosides derived from R-L-fuco-, R-D-gluco-, â-D-gluco-, and R-D-mannopyranose have been
synthesized from the corresponding glycosyl phenyl sulfoxide through phenylsulfinyl-lithium
exchange, to generate an anomeric carbanion, and subsequent reaction with a carbon electrophile.
The reactions were stereospecific and proceeded with retention of the configuration at the anomeric
center. Improved yields of C-glycosides were obtained by an inverse addition protocol. Trapping of
the anomeric carbanion with aldehydes gave best results. Reaction with ketones, chloroformates,
nitriles, and alkyl halides was also explored. Mechanistic aspects of the reaction are discussed.
Sch em e 1
In tr od u ction
Over the past two decades a considerable amount of
work has been devoted to the synthesis of C-glycosides.1
These compounds are important not only because they
are structural subunits of a variety of natural products2
but they can also be regarded as mimics of biologically
relevant O-glycosides, in which a methylene group re-
places the exo-anomeric oxygen.3 This modification
makes C-glycosides resistant to acid and enzymatic
hydrolysis, and, thus, they can be studied as stable drugs.
In contrast to O-glycosides, C-glycosides do not suffer an
exo-anomeric effect, providing structures of great value
for studies about the conformation around the glycosidic
linkage.4
Many synthetic approaches have been devised for the
preparation of C-glycosides.1,5 A good number of synthetic
strategies including anomeric carbocations, carbanions,
radicals, and carbenes have been intensively exploited.
Despite this, there is as yet no general synthetic strategy
for a direct and stereocontrolled route to a large variety
of these compounds.
(from glycosyl stannanes). We recently described12 a new
method to synthesize C-fucopyranosides from easily
accessible fucopyranosyl phenyi sulfoxides, based on the
generation of a glycosyl carbanion through a phenyl-
sulfinyl-lithium exchange (Scheme 1). This method
was shown to be stereospecific: C-fucopyranosides were
obtained from the corresponding fucopyranosyl phenyl
sulfoxide with retention of the configuration at the
anomeric center. In the present work we examine the
potential of this method for the synthesis of C-glycosyl
derivatives by using a variety of electrophiles and gly-
cosyl sulfoxides. Some practical considerations and mecha-
nistic aspects are discussed.
Resu lts a n d Discu ssion
Among the approaches that use nucleophilic glycosyl
donors,6 nonstabilized anomeric carbanions bearing oxy-
genated substituents at position 2 have been generated
by sequential two-electron transfer with either lithium
naphthalenide7 (from glycosyl chlorides) or samarium
diiodide (from glycosyl sulfones,8 phosphates9 or chlo-
rides10) or by lithium exchange with n-butyllithium11
To optimize the reaction conditions, the sulfinyl-
lithium exchange was first examined with the fucosyl
phenyl sulfoxide 1 quenching with CD3OD (Scheme 2).
Compound 1 was prepared efficiently from L-fucose
following a procedure described by us.12b To prevent
1,2-elimination, the 2-hydroxyl must be deprotonated
before anomeric lithiation. The same lithiating reagent
t-BuLi could serve as base to remove the proton. How-
ever, it has been shown13 that t-BuLi reacts faster at
sulfur (affording tert-butyl phenyl sulfoxide) than it
removes a proton from an alcohol. This difference of
(1) Du, Y.; Linhardt, R. J . Tetrahedron 1998, 54, 9913-9959.
(2) Nicotra, F. Top. Curr. Chem. 1997, 187, 55-83.
(3) Carbohydrate Mimics. Concepts and Methods; Chapleur, Y., Ed.;
Wiley-VCH: Weinheim, 1998.
(4) (a) Goekjian, P. G.; Wu, T.-C.; Kishi, Y. J . Org. Chem. 1991, 56,
6412-6422. (b) Espinosa, J . F.; Can˜ada, F. J .; Asensio, J . L.; Mart´ın-
Pastor, M.; Dietrich, H.; Mart´ın-Lomas, M.; Schmidt, R. R.; J ime´nez-
Barbero, J . J . Am. Chem. Soc. 1996, 118, 10862-10871.
(5) The Chemistry of C-glycosides; Levy, D. E., Tang, P. C., Eds.;
Pergamon: Oxford, 1995.
(9) Hung, S.-C.; Wong, C.-H. Angew. Chem., Int. Ed. Engl. 1996,
35, 2671-2674.
(10) Hung, S.-C.; Wong, C.-H. Tetrahedron Lett. 1996, 37, 4903-
4906.
(6) Beau, J .-M.; Gallagher, T. Top. Curr. Chem. 1997, 187, 1-54.
(7) Wittman, V.; Kessler, H. Angew. Chem., Int. Ed. Engl. 1993, 32,
1091-1093.
(8) (a) Skrydstrup, T.; J arreton, O.; Maze´as, D.; Urban, D.; Beau,
J .-M. Chem. Eur. J . 1998, 4, 655-671. (b) Vlahov, I. R.; Vlahova, P.
I.; Linhardt, R. J . J . Am. Chem. Soc. 1997, 119, 1480-1481. (c) de
Pouilly, P.; Che´nede´, A.; Mallet, J .-M.; Sinay¨, P. Bull. Soc. Chim. Fr.
1993, 130, 256-265.
(11) (a) Frey, O.; Hoffmann, M.; Wittmann, V.; Kessler, H.; Uhl-
mann, P.; Vasella, A. Helv. Chim. Acta 1994, 77, 2060-2069. (b)
Lesimple, P.; Beau, J .-M. Bioorg. Med. Chem. 1994, 2, 1319-1330.
(12) (a) J aramillo, C.; Corrales, G.; Ferna´ndez-Mayoralas, A. Tetra-
hedron Lett. 1998, 39, 7783-7786. (b) Carpintero, M.; J aramillo, C.;
Ferna´ndez-Mayoralas A. Eur. J . Org. Chem. 2000, 1285-1296.
(13) Park, G.; Okamura, W. H. Synth. Commun. 1991, 21, 1047-
1054.
10.1021/jo0014515 CCC: $20.00 © 2001 American Chemical Society
Published on Web 02/10/2001

Stereospecific Synthesis of R- and â-C-Glycosides
J . Org. Chem., Vol. 66, No. 5, 2001 1769
Sch em e 2a
Ta ble 1. Rea ction of 1 w ith Differ en t Electr op h iles
(Sch em e 3)
yield (%) of
C-glycoside C-glycoside (a:b) C-glycoside:3
ratioc of
electrophile
iPrCHOa
iPrCHOb
4a
5a ,b
5a ,b
6a ,b
6a ,b
7a ,b
8a ,bd
9
57
61 (2:1)
16
44 (1:1)
49 (2:1)
50 (1.3:1)
19
2.3:1
4.0:1
0.4:1
1.2:1
1.6:1
n.d.e
0.7:1
0.6:1
1.8:1
4b
PhCHOb
PhCNb
Melb
cyclohexanoneb
EtOCOClb
10
11
28
42
a
b
Using the direct addition procedure. Using the inverse
addition procedure. c Determined by H NMR spectroscopy of the
1
crude mixture. After reduction and acetylation. e n.d., not deter-
d
mined.
changing the protocol was more than a 2-fold increase
in yield, affording the C-disaccharide 6 with R-stereo-
selectively in 44% yield.
The other electrophiles were tested using only the
inverse addition. With benzaldehydesan aromatic
aldehydesthe yield was lower than with isobutyralde-
hyde. A clean reaction, however, was obtained with
benzonitrile, which after hydrogenation to reduce the
generated imine and subsequent acetylation afforded the
acetamide 8 in 50% overall yield. This is an interesting
result since it offers the possibility of obtaining amino-
C-glycosides as potential enzyme inhibitors16 in a straight-
forward manner. With less reactive electrophiles, MeI
and cyclohexanone, the yield of C-glycoside was low. As
a general feature we observed that the lower the reactiv-
ity of the electrophile the higher the ratio of protonated
species 3. This suggests that with electrophiles of low
reactivity a certain amount of glycosyl carbanion could
remain at the time that the reaction is quenched by
addition of ammonium chloride, giving protonated prod-
uct. With ethoxycarbonyl chloride the reaction afforded
an interesting compound, 11, containing the carboxylate
group at the anomeric position that can be further
manipulated for the preparation of other C-glycosides.
Concerning the stereoselectivity of the process at the
anomeric carbon, the C-glycosides 5-11 showed in their
1H NMR spectra a J 1,2 value in the range of 1-4 Hz,
corresponding to a 1,2-cis configured fucopyranosyl moi-
ety. Therefore, the reactions proceeded with retention of
the configuration at the anomeric center. With regard to
the diastereomeric ratio at the newly generated chiral
center in the reactions with aldehydes, in some conden-
sations we observed a slight excess of one diastereoisomer
(see Table 1, a:b ratio). Nevertheless, the attack on the
aldehyde by the lithiated anomeric species was basically
unselective.
a
Conditions: (A) (i) 1, t-BuLi, THF, -78 °C; (ii) CD3OD, -78
°C; (B) (i) 1, MeLi‚LiBr, THF, -78 °C, then t-BuLi; (ii) CD3OD,
-78 °C; (C) (i) t-BuLi, THF, -78 °C, then, a solution of 1 and
MeLi‚LiBr in THF (inverse addition); (ii) CD3OD, -78 °C.
reactivity could lead to the formation of the 1,5-anhydro-
fucitol 3 by an intramolecular proton transfer from the
hydroxyl HO-2 to the newly generated anomeric carban-
ion. Indeed, a high proportion of 3 was obtained in our
previous experiments when sulfoxide 1 was treated with
an excess of t-BuLi followed by quenching with deuter-
ated methanol (conditions A in Scheme 2). In accordance
with the above arguments, the percentage of protonation
was substantially decrease when sulfoxide 1 was previ-
ously treated with MeLi‚LiBr (conditions B), a base that
has been successfully used in deprotonation of glycosyl
stannane.14 We have now enhanced the deuterium con-
tent by inverse addition of the reagents.13,15 In this
modification the t-BuLi was first added dropwise to THF
at -78 °C in order to remove the trace moisture in THF.
To this solution is added the glycosyl sulfoxide, previously
treated with MeLi‚LiBr, dissolved in a minimum amount
of THF. When the anomeric carbanion so generated was
trapped with CD3OD, the ratio of deuterated/protonated
products increased to 8:1.
The reaction was next examined with a variety of
carbon electrophiles, which furnished C-fucopyranoside
compounds (Scheme 3). Table 1 summarizes the results.
With isobutyraldehyde and the aldehyde derived from
D-galactose 4, the reaction was assayed using the condi-
tions described previously12 (in THF instead of Et2O) and
the inverse addition protocol. We were pleased to observe
that the yield of the corresponding C-glycoside was
improved using the inverse addition. With this protocol
the amount of protonation is substantially reduced which
in turn leads to higher yields of C-glycosidation. Thus,
in the reaction with sugar aldehyde 4 the effect of
The procedure was next tested with sulfoxides by
varying the nature of the glycosyl moiety. We prepared
sulfoxides derived from â-glucopyranoside (12) and R-
mannopyranoside (13) (Scheme 4) by controlled oxidation
of the corresponding 1-thio-glycopyranosides, prepared
as described previously.17 The R-glucopyranosyl deriva-
tive 14 was obtained from the ortho ester 15. Acid
hydrolysis of 15 gave a mixture of 1- and 2- acetates,
(14) Hoffmann, M.; Kessler, H. Tetrahedron Lett. 1997, 38, 1903-
1906.
(15) Inverse addition of the reagents has been used in different
sulfinyl-lithium exchage reactions to prevent protonation, see ref 13
and Satoh, T.; Kobayashi, S.; Nakanishi, S.; Horiguchi, K.; Irisa, S.
Tetrahedron 1999, 55, 2515-2528.
(16) A similar amino-C-glucopyranose was found to be a potent
â-glucosidase inhibitor, see: Schmidt, R. R.; Dietrich, H. Angew. Chem.,
Int. Ed. Engl. 1991, 30, 1328-1329.
(17) Skrydstrup, T.; Maze´as, D.; Elmouchir, M.; Doisneau, G.; Riche,
C.; Chiaroni, A.; Beau, J .-M. Chem. Eur. J . 1997, 3, 1342-1356.

1770 J . Org. Chem., Vol. 66, No. 5, 2001
Carpintero et al.
Sch em e 3
Sch em e 4a
Sch em e 5a
a
Reagents and conditions: (a) AcOH, rt; (b) NaOMe, MeOH,
rt, 81% (2 steps); (c) (PhS)2, Bu3P, 0 °C, 25%; (d) mCPBA, NaHCO3,
97%.
which was subsequently treated with NaOMe to afford
the 1,2-diol 16. Thioglycosidation was performed by
applying to 16 a method described by Fu¨rstner18 for the
synthesis of thioglycosides from hexoses and pentoses
having free the anomeric position. In this manner the
R-thioglycoside 17 was obtained with moderate stereo-
selectivity (R:â, 3:1).
As in the case of the fucopyranosyl sulfoxide, we first
examined the stereoselectivity of the sulfinyl-lithium
exchange by quenching the anomeric carbanion with
deuterated methanol (Scheme 5). The reactions of sul-
foxides 12, 13, and 14 using the inverse addition protocol
gave deuterated 1,5-anhydroalditols 18, 21, and 24,
respectively, but in low deuteration/protonation ratios
(18/19, 7:3; 21/22, 3:2; 24/25, 2:3). Nevertheless, in all
a
Reagents and conditions: (a) (i) MeLi‚LiBr, THF, -78 °C, then
t-BuLi (inverse addition); (ii) CD3OD, -78 °C; (b) (i) Ibid.; (ii)
iPrCHO, -78 °C.
cases we detected only deuterated 1,5-anhydroalditols
with the deuterium on the same side as the leaving
sulfinyl, indicating that the process took place with
retention of configuration at this center. More dis-
appointing results were obtained when the lithiation of
the sugars was followed by reaction with a carbon
electrophile (Scheme 5). In the presence of isobutyralde-
hyde as electrophile, the reactions of 12, 13, and 14 led
to low yields of C-glycosides (10, 21, and 37% yields,
respectively), together with 1,5-anhydro-alditols and
decomposition products. We hypothesized that under the
basic conditions used the benzylic hydrogens could be
deprotonated, giving, in this way, decomposition. To test
(18) Fu¨rstner, A. Liebigs Ann. Chem. 1993, 1211.

Stereospecific Synthesis of R- and â-C-Glycosides
J . Org. Chem., Vol. 66, No. 5, 2001 1771
Sch em e 6a
Sch em e 7
Sch em e 8a
a
Reagents and conditions: (a) MeI, KOH, THF, reflux, 61%;
(b) PhSH, MeNO2, 100 °C, 42 %; (c) NaOMe, MeOH, rt, 91%; (d)
mCPBA, NaHCO3, 86%; (e) MeLi‚LiBr, THF, -78 °C, then t-BuLi
(inverse addition), then iPrCHO, 50%.
this hypothesis experimentally, we prepared the phenyl
â-D-glucopyranosyl sulfoxide 31 having methyl instead
of benzyl groups (Scheme 6). The synthesis of 31 was
carried out by following a sequence of reactions similar
to that for 12. The lithiation of 31 by inverse addition
and subsequent treatment with isobutyraldehyde gave
a cleaner reaction than that with the benzylated sulfox-
ides, allowing the isolation of the C-glycoside 32 in 50%
yield. Again the product 32 retained the configuration
at the anomeric center. Although the conditions of the
reactions limit the use of protecting groups to those
resistant to strong basic media, we showed that the
method can be applied to different glycopyranosyl sul-
foxides, affording stereospecific C-glycosidations.
Mech a n istic Con sid er a tion s. Phenyl tert-butyl sul-
foxide was always present in the mixtures analyzed at
the end of the reactions, indicating that the process takes
place through ligand exchange. On the basis of the
mechanism proposed for similar reactions,19 this would
involve attack of the t-BuLi on the sulfur atom, generat-
ing a σ-sulfurane (Scheme 7), with the sulfur in the center
of a trigonal bypyramid. By a pseudorotation process
different complexes are formed with the ligands occupy-
ing equatorial and apical positions. The complex that has
the more electronegative group occupying the apical
position is the more stable and the one which results in
bond rupture. In our case, the glycosyl ligand is the more
electronegative group, and thus, the anomeric carbanion
is formed which is configurationally stable at -78 °C.
a
Reagents and conditions: (a) MeLi‚LiBr, THF, -78 °C, then
t-BuLi (inverse addition), then iPrCHO.
electronic properties of the aromatic ligand. To evaluate
this factor we performed the sulfinyl-lithium exchange
on two aryl fucopyranosyl sulfoxides having an electron-
donating and an electron-withdrawing group in the
aromatic ring (Scheme 8). Compounds 33 and 35 were
obtained by following the procedure used to prepare 1.
The reaction of 33 with t-BuLi and subsequent trapping
with isobutyraldehyde gave the C-glycoside 5 isolated in
only 22% yield. The presence of the methoxy substituent
in the para position to the sulfinyl must decrease the
electrophilicity of the latter toward attack of t-BuLi. In
addition, a mixture of products derived from coupling of
the aldehyde to the aromatic ring of the sulfoxide was
also formed from which the major isomer 3420 could be
isolated in 21% yield. The formation of 34 can be
explained by metalation ortho-directed by the methoxy
group, through a lithium-oxygen coordination, followed
by coupling to the aldehyde. On the other hand, the
reaction of the p-nitrophenyl sulfoxide 35 led to the
In view of this mechanism, the nucleophilic attack of
the t-BuLi to the sulfinyl group and the subsequent
progress of the reaction will be influenced by the stereo-
(19) Oae, S.; Kawai, T.; Furukawa, N. Tetrahedron Lett. 1984, 25,
69-72.

1772 J . Org. Chem., Vol. 66, No. 5, 2001
Carpintero et al.
mmol) and CH3I (103 µL, 1.656 mmol) were added and the
reaction was allowed to proceed at reflux temperature for 7 h.
The reaction mixture was cooled to room temperature, diluted
with CH2Cl2 (10 mL), and washed with H2O (3 × 5 mL),
saturated NaHCO3 (2 × 5 mL), and H2O (5 mL). The organic
layer was dried (Na2SO4) and concentrated. The residue was
purified by FC (hexane/EtOAc, 4:1 f 1:1 f 1:2) to give 28 (47
mg, 61%): mp 73-75 °C; [R]D +122.8° (c 1.0, CHCl3); 1H NMR
(300 MHz, CDCl3) δ 5.66 (d, J ) 5.3 Hz, 1 H), 4.35 (ddd, J )
1.0, 3.3, 5.3 Hz, 1 H), 3.68-3.62 (m, 3 H), 3.46 (s, 3 H), 3.43
(s, 3 H), 3.38, (s, 3 H), 3.32 (dd, J ) 1.0, 3.3 Hz, 1 H), 3.25 (s,
3H), 1.64 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 121.16, 97.44,
79.43, 76.78, 57.68, 50.73, 20.53. Anal. Calcd for C12H22O7: C,
51.79; H, 7.97. Found: C, 51.32; H, 7.61.
P h en yl 2-O-Acetyl-3,4,6-tr i-O-m eth yl-1-th io-â-D-glu co-
p yr a n osid e (29). Thiophenol (308 µL, 3.021 mmol) was added
to a solution of 28 (280 mg, 1.007 mmol) in CH3NO2 (2 mL),
warmed to 100 °C, and stirred for 24 h. After this time, the
reaction mixture was cooled to room temperature, diluted with
CH2Cl2 (10 mL), and washed with saturated NaHCO3 (5 mL)
and H2O (2 mL). The organic layer was dried (Na2SO4) and
concentrated. The residue was purified by FC (hexane/EtOAc,
3:1) to give 29 (150 mg, 42%): mp 60-62 °C; [R]D +2.6° (c 0.9,
CHCl3); 1H NMR (200 MHz, CDCl3) δ 7.50-7.28 (m, 5 H), 4.89
(t, J ) 10.1 Hz, 1 H), 4.58 (d, J ) 10.0 Hz, 1 H), 3.65-3.22 (m,
5 H), 3.53 (s, 6 H), 3.39 (s, 3 H), 2.13 (s, 3 H). 13C NMR (50
MHz, CDCl3) δ 169.65, 132.03, 128.93, 128.41, 86.05, 79.30,
79.12, 71.80, 71.40, 60.56, 59.52, 21.14. Anal. Calcd for
displacement of the aromatic group by the tert-butyl
group, giving glycosyl tert-butyl sulfoxide 3621 as the
main product isolated in 57% yield. This result supports
the mechanism described in Scheme 7. In the σ-sulfurane
derived from 35, the p-nitrophenyl is now the group that
can best carry a negative charge, and the one which
results in bond rupture.
Con clu sion s. There are few methods reported in the
literature to synthesize C-glycosides in a stereospecific
manner. In the present work we show that the sulfinyl-
lithium exchange on different glycosyl sulfoxides and the
subsequent reaction with carbon electrophiles proceeds
with retention of configuration at the anomeric center.
In addition, the sulfoxide substrates are readily accessible
in both anomeric configurations. By application of this
method we have obtained a C-disaccharide and other
functionalyzed C-glycosides of utility for enzymatic22 and
conformational studies. Manipulation of the obtained
glycosides, as well as studies aimed to further improve
reaction conditions, are currently underway.
Exp er im en ta l Section
Gen er a l Meth od s. The methods described12b previously
were applied.
C
17H24O6S: C, 57.28; H, 6.79. Found: C, 57.61; H, 7.03.
P h en yl 3,4,6-Tr i-O-m eth yl-1-th io-â-D-glu cop yr a n osid e
3,4,6-Tr i-O-ben zyl-r,â-D-glu cop yr a n ose (16). A suspen-
sion of 1517 (100 mg, 0.197 mmol) in 60% aqueous AcOH (2
mL) was stirred at room temperature for 2 h. After this time
the reaction mixture was concentrated, and the residue was
purified by FC (hexane/EtOAc 7:1 f 5:1 f 3:1) to give a
mixture of 1-O-acetyl- and 2-O-acetyl-3,4,6-tri-O-benzyl-R,â-
D-glucopyranoses (84 mg) which was treated with a solution
of NaOMe in MeOH (25 mM, 6 mL) at room temperature for
90 min. Then, the reaction was neutralized with Amberlyst
IR-120 (H+), filtered and concentrated. The residue was
purified by FC (hexane/EtOAc 7:1 f 5:1 f 2:1) to give 16 (72
mg, 81%, R:â 2.5:1): mp 80-82 °C; [R]D +56.6° (c 1.0, CHCl3);
1H NMR (200 MHz, CDCl3) δ 7.39-7.16 (m, 15 H), 5.27 (t, J
) 3.4 Hz,), 4.85 (m), 4.55-4.47 (m), 4.06 (dt, J ) 3.4, 9.7 Hz),
3.81 (t, J ) 9.0 Hz), 3.35 (d, J ) 3.2 Hz), 2.43 (br s), 2.22 (d,
J ) 3.4 Hz), 1.61 (br s). 13C NMR (50 MHz, CDCl3) δ 138.05,
137.77, 133.27, 128.48, 128.39, 127.99, 127.92, 127.75, 92.40,
82.47, 77.69, 75.29, 74.83, 73.50, 72.77, 70.56, 68.81. Anal.
Calcd for C27H30O6: C, 71.98; H, 6.71. Found: C, 72.21; H, 7.09.
P h en yl 3,4,6-Tr i-O-ben zyl-1-th io-r-D-glu cop yr a n osid e
(17). To a mixture of 16 (500 mg, 1.11 mmol), CH3CN (10 mL),
and PhSSPh (291 mg, 1.33 mmol) was added Bu3P (558 µL,
2.22 mmol) at 0 °C, and the solution was stirred for 4 h. The
reaction mixture was cooled, diluted with CH2Cl2 (5 mL),
washed with H2O (10 mL), and dried (Na2SO4) and the solvent
was evaporated. The residue was purified by FC (hexane/
EtOAc 10:1 f 7:1 f 5:1 f 2:1) to give 17 (151 mg, 25%): mp
(30). 29 (125 mg, 0.350 mmol) was treated with a solution of
NaOMe in MeOH (50 mM, 1.5 mL) at room temperature for 4
h. Then, the reaction mixture was neutralized with Amberlyst
IR-120 (H+), filtered, and concentrated. The residue was
purified by FC (hexane/EtOAc 1:1) to give 30 (100 mg, 91%)
as a syrup: [R]D -29.7° (c 0.7, CHCl3); 1H NMR (300 MHz,
CDCl3) δ 7.55-7.52 (m, 2 H), 7.31-7.26 (m, 3 H), 4.47 (d, J )
9.7 Hz, 1 H), 3.68-3.56 (m, 4 H), 3.65 (s, 3 H), 3.52 (s, 3 H),
3.40, (s, 3 H), 3.35 (m, 1 H), 3.19 (m, 1 H); 13C NMR (75 MHz,
CDCl3) δ 132.56. 132.17, 128.91, 127.92, 88.32, 87.47, 79.16,
79.02, 72.23, 71.25, 60.89, 60.36, 59.35. Anal. Calcd for
C
15H22O5S: C, 57.30; H, 7.05; S, 10.20. Found: C, 57.31; H,
7.17; S, 9.89.
p-Meth oxyph en yl 3,4-O-Isopr opyliden e-1-th io-r-L-fu co-
p yr a n osid e (37). To a solution of L-fucose (1 g, 6.10 mmol) in
DMF (3 mL) containing Et3N (5 mL), cooled to 0 °C, was added
dropwise TMSCl (4.5 mL, 35.5 mmol). The mixture was
warmed to room temperature and stirred for 2 h. Then the
reaction was quenched with H2O/ice (3 × 40 mL), dried (Na2-
SO4), and concentrated to give a residue which was dissolved
in CH2Cl2 (15 mL) and treated with TMSI (0.88 mL, 6.47
mmol), at room temperature for 1 h. The reaction was then
cooled to 5 °C, and a solution of p-methoxy-thiophenol (793
µL, 6.45 mmol) and 2,6-di-tert-butyl-4-methylpyridine (1.13
mg, 5.49 mmol) in CH2Cl2 (15 mL) was added. After 21 h,
MeOH (30 mL) was added, and stirring was continued for 30
min. Evaporation of the solvent gave a crude which was
dissolved in Me2CO (30 mL) and treated with 2,2-dimethoxy-
propane (1.5 mL, 12.2 mmol) and pTsOH‚H2O (60 mg, 0.31
mmol). After 2 h, the reaction mixture was neutralized with
Et3N and concentrated to give a residue which was purified
by FC (hexane/EtOAc, 6:1), giving the title compound (1.25 g,
1
123-125 °C; H NMR (200 MHz, CDCl3) δ 7.55-7.16 (m, 20
H), 5.65 (d, J ) 5.3 Hz, 1 H), 4.94-4.40 (m, 6 H), 4.40-4.30
(m, 1 H), 4.90-3.90 (m, 1 H), 3.84 (dd, J ) 5.9, 9.0 Hz, 1 H),
3.74-3.62 (m, 3 H). Anal. Calcd for C33H34O5S: C, 73.04, H,
6.31, S, 5.91. Found: C, 73.32, H, 6.53, S, 5.59.
3,4,6-Tr i-O-m eth yl-r-D-glu copyr an ose 1,2-(Meth yl or th o-
a ceta te) (28). 27 (100 mg, 0.276 mmol) was solved in THF
(4 mL), and KOH (206 mg, 3.671 mmol) and CH3I (103 µL,
1.656 mmol) were added. The reaction mixture was stirred at
reflux temperature for 4 h. Then, more KOH (206 mg, 3.671
1
63%): mp 119-120 °C; [R]D -246.7° (c 0.9, CHCl3); H NMR
(300 MHz, CDCl3) δ 7.40-7.39 (m, 2 H), 6.84-6.81 (m, 2 H),
5.34 (d, J ) 4.9 Hz, 1 H), 4.55 (qd, J ) 2.2, 6.7 Hz, 1 H), 4.12
(t, J ) 5.0 Hz, 1 H), 4.08 (dd, J ) 2.2, 5.8 Hz, 1 H), 4.01 (q, J
) 5.8 Hz, 1 H), 3.77 (s, 3 H), 2.50 (d, J ) 6.2 Hz, 1 H) 1.48 (s,
3H), 1.33 (s, 3 H), 1.32 (d, J ) 6.6 Hz, 3 H); 13C NMR (75 MHz,
CDCl3) δ 159.64, 134.54, 123.89, 114.70, 109.37, 89.37, 76.98,
76.12, 69.85, 65.30, 55.29, 27.81, 25.84, 16.23. Anal. Calcd for
(20) Selected 1H NMR (200 MHz, CDCl3) data for 34: δ 7.64 (m, 2H),
7.05 (d, J ) 8.4 Hz, 1H), 5.52 (br s, 1H), 4.65 (m, 2H), 4.40 (m, 2H),
4.19 (dd, J ) 1.1, 7.5 Hz, 1H), 3.91 and 3.90 (2s, OMe), 2.05 (m, 1H),
1.2-1.4 (m, (CH3)2C), 0.9-1.00 (m, CH3Fuc).
(21) Selected 1H NMR (200 MHz, CDCl3) data for 36: δ 5.42 (d, J )
4.9 Hz, 1H), 4.51 (m, 1H), 4.02 (dd, J ) 2.4, 5.1 Hz, 1H), 1.54 (s, 3H),
1.39 (s, 9H), 1.35 (s, 3H), 1.33 (d, J ) 6.7 Hz, 3H).
C
16H22O5S: C, 58.87; H, 6.79; S, 9.82. Found: C, 58.51; H, 6.97;
S, 10.18.
Oxid a tion of P h en yl 1-Th io-glycop yr a n osid es. Gen -
(22) A full description about the activity of some of the C-glycosides
as R-fucosidase and R-fucosyltransferase inhibitors will be described
elsewhere.
er a l P r oced u r e. To a mixture of the aryl 1-thio-glycopyrano-
side (0.33 mmol), CH2Cl2 (8 mL), and NaHCO3 (33 mg, 0.40

Stereospecific Synthesis of R- and â-C-Glycosides
J . Org. Chem., Vol. 66, No. 5, 2001 1773
mmol) at -78 °C was added a solution of m-CPBA (63 mg,
0.36 mmol) in CH2Cl2 (1.5 mL). The reaction mixture was
stirred for 5 h and, then, heated to room temperature. The
mixture was diluted with CH2Cl2 (5 mL) and washed with 20%
Na2S2O3 (5 mL) and saturated NaHCO3 (5 mL). The organic
layer was dried (Na2SO4) and concentrated. The residue was
purified by FC (hexane/EtOAc 4:1 f 3:1 f 2:1 f 1:2) to give
the sulfoxide.
H), 3.11 (dd, J ) 10.3, 11.1 Hz, 1 H), 1.53 (s, 3 H), 1.37 (s, 3
H), 1.36 (d, J ) 6.6 Hz, 3 H). (1S)-1,5-Anhydro-3,4,6-tri-O-
benzyl-(1-2H1)-D-glucitol (18): δ 7.37-7.15 (m, 15 H), 5.00-
4.50 (m, 6 H), 3.70-3.65 (m, 1 H), 3.68-3.64 (m, 2 H), 3.56
(dd, J ) 8.7, 9.4 Hz, 1 H), 3.45 (t, J ) 8.6 Hz, 1 H), 3.39 (ddd,
J ) 2.7, 3.8, 9.4 Hz, 1 H), 3.20 (d, J ) 10.3 Hz, 1 H). (1R)-
1,5-Anhydro-3,4,6-tri-O-benzyl-(1-2H1)-D-mannitol (21): δ 7.39-
7.16 (m, 15 H), 4.09 (d, J ) 2.0 Hz, 1 H), 4.0 (dd, J ) 2.0, 3.3
Hz, 1 H), 3.73 (t, J ) 9.3 Hz, 1 H), 3.69 (dd, J ) 2.0, 10.6 Hz,
1 H), 3.62 (dd, J ) 5.5, 10.6 Hz, 1 H), 3.43 (dd, J ) 3.4, 9.0
Hz, 1 H), 3.35 (ddd, J ) 2.0, 5.5, 9.7 Hz, 1 H). (1R)-1,5-
Anhydro-3,4,6- tri-O-benzyl-(1-2H1)-D-glucitol (24): δ 7.37-7.15
(m, 15 H), 4.50-5.00 (m, 6 H), 4.02 (d, J ) 5.3 Hz, 1 H), 3.7
(m, 1 H), 3.64-3.68 (m, 2 H), 3.56 (dd, J ) 8.7, 9.4 Hz, 1 H),
3.45 (t, J ) 8.6 Hz, 1 H), 3.39 (ddd, J ) 2.7, 3.8, 9.4 Hz, 1 H).
C-Glycosyla tion . Gen er a l P r oced u r e. A solution of the
glycosyl sulfoxide (0.320 mmol) and MeLi‚BrLi (1.1 M in Et2O,
0.350 mmol) in a minimun amount of dry THF was added
dropwise to a solution fo tBuLi (1.64 M in hexanes, 1.60 mmol)
in dry THF (2 mL) at -78 °C. After 5 min electrophile (0.96
mmol) was added, and the mixture was stirred for 5 min at
-78 °C and then quenched with a saturated aqueous solution
of NH4Cl (1 mL). After partitioning between water and CH2Cl2,
the organic layer was dried (Na2SO4) and concentrated. The
residue was purified by FC (hexane/EtOAc 10:1 f 5:1 f 2:1).
P h en yl 3,4,6-Tr i-O-ben zyl-â-D-glu cop yr a n osyl Su lfox-
id e (12). Following the general procedure phenyl 3,4,6-tri-O-
benzyl-1-thio-â-D-glucopyranoside17 was oxidized to give 12
(95%) as 2:1 diastereomeric mixture (12a /12b): [R]D +28.0° (c
1
1.0, CHCl3); H NMR (200 MHz, CDCl3) δ 5.05 (d, J ) 11.0
Hz, 12a ), 4.95 (d, J ) 11.0 Hz, 12b), 4.87 (d, J ) 11.3 Hz,
12a ), 4.81 (d, J ) 11.0 Hz, 12b), 4.81 (d, J ) 11.3 Hz, 12a ),
4.56 (d, J ) 10.8 Hz, 12a ), 4.52 (s, 12a ). Anal. Calcd for
C
33H34O6S: C, 70.95; H, 6.13; S, 5.74. Found: C, 70.84; H, 6.22;
S, 5.76.
P h en yl 3,4,6-Tr i-O-ben zyl-r-D-m a n n op yr a n osyl Su l-
foxid e (13). Following the general procedure phenyl 3,4,6-
tri-O-benzyl-L-thio-R-D-mannopyranoside17 was oxidized to give
13 (93%) as a solid: mp 125-128 °C; [R]D +15.6° (c 1.0, CHCl3);
1H NMR (200 MHz, CDCl3) δ 7.67-7.18 (m, 20 H), 4.80 (d,
J ) 11.5 Hz, 1 H), 4.79 (d, J ) 11.0 Hz, 1 H), 4.75 (d, J ) 11.5
Hz, 1 H), 4.68-4.63 (m, 2 H), 4.57 (d, J ) 12.0 Hz, 1 H), 4.49
(d, J ) 11.0 Hz, 1 H), 4.46 (d, J ) 12.0 Hz, 1 H), 4.20 (dd, J )
3.0, 7.9 Hz, 1 H), 4.16 (ddd, J ) 2.3, 5.4, 9.4 Hz, 1 H), 3.84
(dd, J ) 7.9, 9.4 Hz, 1 H), 3.76 (dd, J ) 2.3, 10.9 Hz, 1 H),
3.65 (dd, J ) 5.4, 10.9 Hz, 1 H); 13C NMR (50 MHz, CDCl3) δ
137.96, 137.85, 137.61, 131.33, 129.14, 128.59, 128.42, 128.36,
128.06, 127.88, 127.85, 127.76, 127.66, 124.51, 96.69, 79.23,
77.05, 74.49, 74.15, 73.44, 72.69, 69.22, 65.67. Anal. Calcd for
C33H34O6S: C, 70.95; H, 6.13; S, 5.74. Found: C, 71.24; H, 6.48;
S, 5.51.
4,8-An h yd r o-6,7-O-isop r op ylid en e-2-C-m eth yl-1,2,9-tr i-
d eoxy-L-th r eo-D-gu lo-n on itol (5a ) a n d 4,8-An h yd r o-6,7-
O-isop r op ylid en e-2-C-m et h yl-1,2,9-t r id eoxy-L-th r eo-D-
id o-n on itol (5b). Using the general procedure sulfoxide 1 was
treated with isobutyraldehyde as electrophile to give separated
5a (40%) and 5b (21%). 5a : mp 92-95 °C; [R]D -57.2° (c 0.9,
1
CHCl3); H NMR (300 MHz, CDCl3) δ 4.29 (qd, J ) 1.5, 6.7
Hz, 1 H), 4.21 (dd, J ) 2.1, 8.8 Hz, 1 H), 4.17 (ddd, J ) 0.6,
1.5, 7.2 Hz, 1 H), 4.01 (t, J ) 1.2 Hz, 1 H), 3.81 (m, 1 H), 3.31
(t, J ) 9.1 Hz, 1 H), 2.29 (d, J ) 9.8 Hz, 1 H), 1.92 (m, 1 H),
1.58 (s, 1 H), 1.48 (s, 3 H), 1.35 (s, 3 H), 1.29 (d, J ) 6.6 Hz, 3
H), 1.01 (d, J ) 6.7 Hz, 3 H), 0.94 (d, J ) 6.8 Hz, 3 H); 13C
NMR (50 MHz, CDCl3) δ 109.51, 80.73, 73.63, 72.27, 66.88,
66.19, 31.42, 28.27, 26.32, 19.16, 18.72, 18.27. Anal. Calcd for
P h en yl 3,4,6-Tr i-O-ben zyl-â-D-glu cop yr a n osyl Su lfox-
id e (14). Following the general procedure compound 17 was
oxidized to give 14 (97%) as a syrup: [R]D +7.4° (c 1.0, CHCl3);
1H NMR (200 MHz, CDCl3) δ 7.73-7.18 (m, 20 H), 4.96 (d, J
) 11.2 Hz, 1 H), 4.82-4.68 (m, 2 H), 4.67 (d, J ) 4.5 Hz, 1 H),
4.51 (d, J ) 11.2 Hz, 1 H), 4.45 (d, J ) 12.0 Hz, 1 H), 4.38 (d,
C
13H24O5: C, 60.21; H, 8.94. Found: C, 60.64; H, 9.28. 5b: mp
J ) 12.0 Hz, 1 H), 4.34-4.18 (m, 3 H), 3.65-3.56 (m, 3 H); 13
C
78-83 °C; [R]D -38.3° (c 0.5, CHCl3); 1H NMR (300 MHz,
CHCl3) δ 4.35 (qd, J ) 1.3, 6.6 Hz, 1 H), 4.22 (dd, J ) 2.1, 7.7
Hz, 1 H), 4.18 (d, J ) 7.6 Hz, 1 H), 4.02-3.97 (m, 2 H), 3.58
(dt, J ) 3.1, 9.2 Hz, 1 H), 2.70 (d, J ) 9.8 Hz, 1 H), 1.84 (m, 1
H), 1.56 (s, 1 H), 1.48 (s, 3 H), 1.35 (s, 3 H), 1.32 (d, J ) 6.6
Hz, 3 H), 1.07 (d, J ) 6.5 Hz, 3 H), 0.90 (d, J ) 6.7 Hz, 3 H);
13C NMR (50 MHz, CDCl3) δ 108.79, 79.99, 14 75.18, 73.47,
68.83, 68.34, 66.07, 29.79, 26.69, 23.99, 19.78, 18.66, 18.34.
Anal. Calcd. for C13H24O5: C, 60.21; H, 8.94. Found: C, 60.03;
H, 9.10.
NMR (50 MHz, CDCl3) δ 138.49, 137.89, 131.64, 129.78,
129.17, 128.39, 128.04, 127.96, 127.90, 127.81, 127.69, 124.40,
93.16, 85.42, 73.42, 76.16, 75.44, 75.18, 74.30, 73.35, 68.54.
Anal. Calcd for C33H34O6S: C, 70.95; H, 6.13; S, 5.74. Found:
C, 70.67; H, 6.07; S, 5.98.
P h en yl 3,4,6-Tr i-O-m eth yl-â-D-glu cop yr a n osyl Su lfox-
id e (31). Following the general procedure compound 30 was
oxidized to give 31 (86%) as a syrup: [R]D +49.0° (c 1.0, CHCl3);
1H NMR (300 MHz, CDCl3) δ 5.34-5.28 (m, 1 H), 4.88-4.18
(m, 6 H), 3.52 (m, 3 H), 3.44 (s, 3 H), 3.40 (s, 3 H). Anal. Calcd
for C15H22O6S: C, 54.53; H, 6.71. Found: C, 54.81; H, 6.93.
p-Meth oxyp h en yl 3,4-O-Isop r op ylid en e-r-L-fu cop yr a n -
osyl Su lfoxid e (33). Following the general procedure com-
pound 37 was oxidized to give 33 (99%): mp 155-157 °C; [R]D
+85.6° (c 1.1, CHCl3); 1H NMR (300 MHz, CDCl3) δ 7.64-7.61
(m, 2 H), 7.06-7.03 (m, 2 H), 5.95 (d, J ) 4.4 Hz, 1 H), 4.59
(qd, J ) 1.5, 6.6 Hz, 1 H), 4.50-4.42 (m, 3 H), 4.18 (dd, J )
1.4, 7.7 Hz, 1 H), 3.86 (s, 3 H), 1.36 (s, 3 H), 1.31 (s, 3 H), 1.26
(d, J ) 6.5 Hz, 3 H); 13C NMR (75 MHz, CDCl3) δ 162.30,
130.54, 126.94, 114.81, 109.54, 92.15, 74.57, 73.85, 68.88,
65.00, 55.49, 26.19, 24.20, 16.63. Anal. Calcd for C16H22O6S:
C, 56.12; H, 6.48; S, 9.36. Found: C, 56.36; H, 6.75; S, 9.08.
Deu ter a tion Exp er im en t. A solution of the glycosyl
sulfoxide (0.320 mmol) and MeLi‚BrLi (1.1 M in Et2O, 0.350
mmol) in a minimun amount of dry THF was added dropwise
to a solution fo tBuLi (1.64 M in hexanes, 1.60 mmol) in dry
THF (2 mL) at -78 °C. After 5 min, CD3OD (5 equiv) was
added and the mixture was stirred for 5 min at -78 °C and,
then, quenched with saturated aqueous solution of NH4Cl (1
mL). After partitioning between water and CH2Cl2, the organic
layer was dried (Na2SO4) and concentrated. The crude mixture
was analyzed by 1H NMR (200 MHz, CDCl3). (1S)-1,5-Anhydro-
3,4-O-isopropylidene-(1-2H1)-L-fucitol (2): δ 4.03 (dd, J ) 2.2,
5.5 Hz, 1 H), 3.98-3.80 (m, 3 H), 3.76 (qd, J ) 2.2, 6.6 Hz, 1
(6R a n d 6S)-6-C-(3,4-O-Isop r op ylid en e-r-L-fu cop yr a n -
osyl)-1,2:3,4-di-O-isopr opyliden e-r-D-galactopyr an ose (6).
Using the general procedure sulfoxide 1 was treated with
galactopyranose aldehyde 4 as electrophile to give 6 (44%) in
approximately a 1:1 diastereomeric mixture: mp 57-59 °C; [R]D
1
-76.1° (c 0.5, CHCl3); H NMR (200 MHz, CDCl3) δ 5.57 (d,
J ) 5.0 Hz), 4.61 (dd, J ) 2.4, 7.9 Hz), 4.46 (s), 4.42-4.31 (m),
4.27 (dd, J ) 2.3, 7.7 Hz), 4.19-3.96 (m), 2.89 (br s), 1.54 (s),
1.48 (s), 1.43(s), 1.35 (s), 1.30 (s), 1.24 (d, J ) 6.6 Hz); 13C NMR
(50 MHz, CDCl3): δ 109.34, 109.03, 108.85, 96.44, 75.61, 74.30,
74.06, 70.92, 70.83, 70.80, 70.69, 68.09, 66.98, 66.06, 26.65,
25.93, 25.86, 25.09, 24.20, 24.13, 18.11. Anal. Calcd for
C
21H34O10: C, 56.62; H, 7.47. Found: C, 56.91; H, 7.71.
2,6-An h yd r o-7-d eoxy-4,5-O-isop r op ylid en e-1-C-p h en yl-
L-th r eo-D-gu lo-h ep titol a n d 2,6-An h yd r o-7-d eoxy-4,5-O-
isop r op ylid en e-1-C-p h en yl-L-th r eo-D-id o-h ep titol (7a ,b).
Using the general procedure sulfoxide 1 was treated with
benzaldehyde as electrophile to give about a 2:1 diastereomeric
mixture of 7a /7b (49%) as crystals: mp 126-128 °C; [R]D
-69.3° (c 1.1, CHCl3); 1H NMR (300 MHz, CDCl3) δ 7.39-7.28
(m, 5 H), 4.87 (t, J ) 4.9 Hz, 7b), 4.47 (q, J ) 6.7 Hz, 7a ), 4.34
(q, J ) 6.6 Hz, 7b), 4.01 (d, J ) 2.2 Hz, 7a ), 3.77 (d, J ) 2.0
Hz, 7b), 3.67 (s, 7a ), 3.10 (d, J ) 2.4 Hz, 7a ), 3.03 (d, J ) 2.7
Hz, 7b), 1.47 (s, 7b), 1.44 (s, 7a ), 1.38 (d, J ) 6.6 Hz, 3H),

1774 J . Org. Chem., Vol. 66, No. 5, 2001
Carpintero et al.
1.33 (s, 7b), 1.30 (s, 7a ). Anal. Calcd for C16H22O5: C, 65.29;
H, 7.53. Found: C, 65.65; H, 7.80.
110.01, 75.13, 72.29, 71.49, 67.82, 66.69, 53.63, 26.68, 24.30,
23.59, 21.03, 17.76. Anal. Calcd for C20H27NO6: C, 63.64; H,
7.21; N, 3.71. Found: C, 63.89; H, 7.16; N, 3.70. 8b: mp 81-
83 °C; [R]D -1.5° (c 1.0, CHCl3); lH NMR (300 MHz, CDCl3) δ
7.29-7.19 (m, 5 H), 6.33 (d, J ) 7.2 Hz, 1 H), 5.07 (dd, J )
7.5, 8.8 Hz, 1 H), 4.67 (t, J ) 3.0 Hz, 1 H), 4.30 (dd, J ) 3.1,
8.8 Hz, 1 H), 4.22 (dd, J ) 3.0, 7.3 Hz, 1 H), 4.11-4.06 (m, 2
H), 2.01 (s, 3 H), 1.96 (s, 3 H), 1.47 (s, 3 H), 1.30 (d, J ) 6.5
Hz, 3 H), 1.29 (s, 3 H); 13C NMR (75 MHz, CDCl3) δ 169.62,
169.23, 139.06, 128.73, 127.83, 127.06, 109.71, 74.75, 71.91,
71.68, 68.12, 66.58, 54.17, 26.47, 24.23, 23.38, 20.82, 17.25.
Anal. Calcd for C20H27NO6: C, 63.64; H, 7.21; N, 3.71. Found:
C, 63.82; H, 6.96; N, 3.72.
2,6-An h yd r o-1,7-d id eoxy-4,5-O-isop r op ylid en e-L-glyc-
er o-D-glu co-h ep titol (9). Using the general procedure sul-
foxide 1 was treated with methyl iodide as electrophile to give
9 (19%) as crystals: mp 79-84 °C; [R]D -61.8° (c 0.7, CHCl3);
1H NMR (300 MHz, CDCl3) δ 4.22 (dd, J ) 3.4, 6.9 Hz, 1 H),
4.16 (qd, J ) 3.0, 6.8 Hz, 1 H), 4.14-4.08 (m, 2 H), 3.68 (q,
J ) 3.3 Hz, 1 H), 1.97 (d, J ) 4.3 Hz, 1 H), 1.51 (s, 3 H), 1.35
(s, 3 H), 1.30 (d, J ) 6.5 Hz, 3 H), 1.21 (d, J ) 6.9 Hz, 3 H);
13C NMR (300 MHz, CDCl3) δ 108.96, 75.24, 75.17, 70.51,
67.40, 64.79, 27.14, 24.80, 17.76, 15.59. Anal. Calcd for
C10H18O4: C, 59.39; H, 8.97. Found: C, 59.59; H, 9.12.
1-C-(3,4-O-Isop r op ylid en e-r-L-fu cop yr a n osyl)-cyclo-
h exa n -1-ol (10). Using the general procedure sulfoxide 1 was
treated with cyclohexanone as electrophile to give 10 (28%)
as crystals: mp 69-71 °C; [R]D -56.1° (c 0.8, CHCl3); 1H NMR
(200 MHz, CDCl3) δ 6.61 (s, 1 H), 4.31 (qd, J ) 1.4, 6.6 Hz, 1
H), 4.24 (dd, J ) 2.1, 7.8 Hz, 1 H), 4.16 (dd, J ) 1.1, 7.7 Hz,
1 H), 4.02 (t, J ) 1.8 Hz, 1 H), 3.64 (d, J ) 1.4 Hz, 1 H), 2.41
(s, 1 H), 1.48 (s, 3 H), 1.35 (s, 3 H), 1.94-1.38 (m, 10 H), 1.30
(d, J ) 6.5 Hz, 3 H); 13C NMR (50 MHz, CDCl3) δ 108.64, 75.24,
78.80, 73.29, 72.36, 67.85, 66.19, 35.51, 32.23, 25.58, 21.54,
21.28, 26.23, 23.86, 18.14. Anal. Calcd for C15H26O5: C, 62.91;
H, 9.15. Found: C, 63.18; H, 9.42.
4,8-An h yd r o-6,7,9-tr i-O-ben zyl-1,2-d id eoxy-2-C-m eth yl-
D-er yth r o-L-ta lo-n on itol a n d 4,8-An h yd r o-6,7,9-tr i-O-ben -
zyl-1,2-d id eoxy-2-C-m et h yl-D-er yth r o-L-ga la cto-n on it ol
(20). Using the general procedure sulfoxide 12 was treated
with isobutyraldehyde as electrophile to give 20 (13%) in
approximately a 1:1 diastereomeric mixture: [R]D +18.0° (c
1
0.95, CHCl3); H NMR (400 MHz, CDCl3) δ 7.33-7.17 (m, 15
H), 3.78 (dd, J ) 7.8, 8.5 Hz), 3.68 (t, J ) 7.8 Hz), 3.58 (t, J )
9.2 Hz), 3.53 (t, J ) 8.9 Hz), 2.07 (m), 1.87 (m), 1.03 (d, J )
6.7 Hz), 0.96 (d, J ) 6.9 Hz), 0.90 (d, J ) 6.7 Hz), 0.88 (d, J )
6.9 Hz). Anal. Calcd for C31H38O6: C, 73.49; H, 7.56. Found:
C, 73.63; H, 7.31.
E t h yl 2,6-An h yd r o-7-d eoxy-3-et h oxyca r b on yl-4,5-O-
isop r op ylid en e-L-glycer o-D-glu co-h ep ta te (11). Using the
general procedure sulfoxide 1 was treated with ethoxycarbonyl
chloride as electrophile to give 11 (42%) as a syrup: [R]D -27.20
4,8-An h yd r o-6,7,9-tr i-O-ben zyl-1,2-d id eoxy-2-C-m eth yl-
D-er yth r o-L-m a n n o-n on itol a n d 4,8-An h yd r o-6,7,9-tr i-O-
b en zyl-1,2-d id eoxy-2-C-m et h yl-D-er yth r o-L-a llo-n on it ol
(23). Using the general procedure sulfoxide 13 was treated
with isobutyraldehyde as electrophile to give 23 (41%) in
approximately a 1:1 diastereomeric mixture: [R]D +5.0° (c 0.6,
CHCl3); 1H NMR (200 MHz, CHCl3) δ 7.24-7.37 (m, 15 H),
4.50-4.68 (m, 6H), 3.64-3.96 (m, 6H), 2.58 (br s,), 2.35 (br s),
2.02-2.18 (m), 1.65-1.84 (m), 0.99 (d, J ) 6.8 Hz), 0.95 (d,
J ) 6.6 Hz), 0.94 (d, J ) 6.8 Hz), 0.91 (d, J ) 6.8 Hz); 13C
NMR (75 MHz, CDCl3) δ 78.33, 78.16, 76.30, 74.35, 74.08,
73.40, 73.31, 73.27, 73.21, 72.95, 72.79, 72.77, 72.45, 68.55,
68.28, 65.43, 30.70, 28.58, 19.52, 19.47, 17.92, 14.70. Anal.
Calcd for C31H38O6: C, 73.49; H, 7.56. Found: C, 73.42; H, 7.71.
4,8-An h yd r o-1,2-d id eoxy-6,7,9-tr i-O-m eth yl-2-C-m eth -
yl-D-er yth r o-L-ta lo-n on itol a n d 4,8-An h yd r o-1, 2-d id eoxy-
6,7,9-t r i-O-m et h yl-2-C-m et h yl-D-er yth r o-L-ga la cto-n on i-
tol (32). Using the general procedure sulfoxide 31 was treated
with isobutyraldehyde as electrophile to give 32 (50%) in
approximately a 1:1 diastereomeric mixture: [R]D +18.3° (c 0.6,
1
(c 0.8, CHCl3); H NMR (200 MHz, CDCl3) δ 5.30 (t, J ) 3.8
Hz, 1 H), 4.72 (d, J ) 4.4 Hz, 1 H), 4.45 (dd, J ) 3.4, 7.2 Hz,
1 H), 4.28-4.11 (m, 6 H), 1.56 (s, 3 H), 1.51 (s, 3 H), 1.38-
1.11 (m, 9 H); 13C NMR (50 MHz, CDCl3) δ 169.43, 153.92,
110.26, 74.89, 71.63, 61.19, 71.06, 64.65, 61.17, 26.49, 24.86,
16.72, 14.13, 14.08. Anal. Calcd for C15H24O8: C, 54.21; H, 7.28.
Found: C, 53.98; H, 6.93.
1-Ace t a m id o-2,6-a n h yd r o-1,7-d id e oxy-4,5-O-isop r o-
p ylid en e-1-C-p h en yl-L-th r eo-D-gu lo-h ep t it ol (8a ) a n d
1-Acet a m id o-2,6-a n h yd r o-1,7-d id eoxy-4,5-O-isop r op yl-
id en e-1-C-p h en yl-L-th r eo-D-id o-h ep titol (8b). A solution of
sulfoxide 1 (0.32 mmol) and MeLi‚BrLi (1.5 M, 0.350 mmol)
in a minimun amount of dry THF was added dropwise to a
solution fo tBuLi (1.4 M in hexanes, 1.60 mmol) in dry THF
(2.0 mL) at -78 °C. After 5 min PhCN (1.6 mmol) was added,
and the mixture was stirred for 5 min at -78 °C. Then MeOH
(1.0 mL) and NaBH4 (60 mg, 1.6 mmol) were added, and the
reaction was allowed to proceed at room temperature for 2 h.
After this time AcOH (1.0 mL) was added and the solvents
were evaporated. The residue was solved in pyridine (0.5 mL)-
and treated with Ac2O (0.25 mL), and the mixture was stirred
at room temperature for 24 h and concentrated. The residue
was purified by FC (hexane/EtOAc 10:1) to give separated 8a
(33 mg, 28%) and 8b (26 mg, 22%). 8a : mp 59-60 °C; [R]D
-6.3° (c 0.6, CHCl3); 1H NMR (300 MHz, CDCl3) δ 7.34-7.19
(m, 5 H), 6.33 (d, J ) 7.6 Hz, 1 H), 5.20-5.08 (m, 2 H), 4.36
(dd, J ) 2.5, 7.3 Hz, 1 H), 4.20 (dd, J ) 2.5, 7.6 Hz, 1 H), 4.12-
4.02 (m, 2 H), 1.89 (s, 3 H), 1.83 (s, 3 H), 1.49 (s, 3 H), 1.31 (s,
3 H), 1.22 (d, J ) 6.5 Hz, 3 H); 13C NMR (75 MHz, CDCl3) δ
170.08, 169.33, 140.13, 128.92, 128.62, 128.35, 128.08, 127.65,
1
CHCl3); H NMR (200 MHz, CDCl3) δ 3.68 (s), 3.67 (s), 3.55
(s), 3.53 (s), 3.39 (s), 3.37 (s), 2.88 (d), 2.82 (br s), 2.10 (m),
1.88 (m), 1.01 (d, J ) 6.7 Hz), 0.98 (d, J ) 7.1 Hz), 0.91 18 (d,
J ) 6.7 Hz), 0.89 (d, J ) 6.8 Hz). Anal. Calcd for C13H26O6: C,
56.09; H, 9.41. Found: C, 56.42; H, 9.71.
Ack n ow led gm en t. We are gratefully indebted to
Dr. Carlos J aramillo for helpful discussions. This work
was supported by DGES (Grants PB96-0828 and PB96-
0833), Comunidad de Madrid (to M.C.), and Fundacio´n
Segundo Gil Davila (to I.N.)
J O0014515