Stereoselective synthesis of carba- and C-glycosyl analogs of fucopyranosides

Article abstract of DOI:10.1002/1099-0690(200004)2000:7<1285::AID-EJOC1285>3.0.CO;2-Z

Fucopyranoside analogs with methylene groups instead of endo- or exo- anomeric oxygens, carba- and C-fucopyranosides, respectively, were synthesized. For the synthesis of 5a-carba-L-fucose (1) two approaches were studied, which shared a common cyclitol bu

Full text of DOI:10.1002/1099-0690(200004)2000:7<1285::AID-EJOC1285>3.0.CO;2-Z

FULL PAPER
Stereoselective Synthesis of carba- and C-Glycosyl Analogs of Fucopyranosides
[a]
Mercedes Carpintero,[a] Carlos Jaramillo,[a][°] and Alfonso Fernandez-Mayoralas*
´
Dedicated to Professor Pierre Sinay¨ on the ocassion of his 62nd birthday
Keywords: Carbocycles / Carbohydrates
Fucopyranoside analogs with methylene groups instead of
endo- or exo-anomeric oxygens, carba- and C-fucopyranos- trolled by substitution on the substrate. For the synthesis of
ides, respectively, were synthesized. For the synthesis of 5a-
1-C-fucopyranosides (37, 38, and 42) a new method based on
carba- -fucose (1) two approaches were studied, which the use of fucosyl phenyl sulfoxides (35 and 41) was em-
shared a common cyclitol building block (8), obtained from
a SmI2-promoted carbocyclization of a -mannitol derivative.
and stereoselective hydrogenation of a double bond, con-
L
ployed. An anomeric carbanion is generated through phenyl-
sulfinyl-lithium exchange, which reacted with electrophiles
with retention of configuration at the anomeric center. The
D
The first route made use of a Stork radical cyclization onto a
conduritol derivative 13 as the key step, which failed to give
the silyl ether ring. The second route furnished the target 1,
and involved regioselective elimination of a cyclic sulfate 9,
required fucosyl sulfoxides were prepared from
L-fucose by
highly stereoselective thioglycosylation reactions.
Introduction
them[8a][8b] make use of a cyclization of acyclic carbohydrate
derivatives; other approaches employ cyclitols as starting
materials, and a recent report,[8f] describes the desymmetriz-
ation of a dienylsilane. In the present work, we explored
new routes to synthesize 5a-carba--fucose from a readily
available -mannitol derivative, through an SmI2-promoted
carbocyclization and further functional group manipula-
tion. Our approaches make use of symmetry elements;[6a]
this significantly simplifies the synthesis.
The synthesis of C-glycosides has been an active field of
research over the last years. Several approaches have been
published, including ones via anomeric carbocations and
radicals.[9] For the synthesis of 1-C-fucosyl glycosides, we
employed a strategy based on the reaction of an anomeric
carbanion with a carbon electrophile. We recently commun-
icated[6b] a new method to generate anomeric carbanions
from easily accessible glycosyl sulfoxides, and their stereose-
lective reaction with electrophiles with retention of config-
uration at the anomeric center. Full details of the applica-
tion of this method for the stereoselective synthesis of C-
fucosides is now described.
Research on carbohydrates has grown considerably over
the last years and promises to be a major focus led by drug
discovery.[1] Oligosaccharides on the cell-surface mem-
branes play an important role in processes such as fertiliza-
tion, immune defense, parasitic infection, cell growth, cell–
cell adhesion, and inflammation.[2] However, the use of oli-
gosaccharides as new drug candidates is hampered by their
susceptibility to hydrolysis by glycosidases, enzymes that are
ubiquitous in tissue. This limitation has stimulated the syn-
thesis of more stable oligosaccharide analogs and mi-
metics.[3] In this context, 5a-carbapyranoses, also named
pseudosugars, and 1-C-glycopyranosides, analogs in which
the endo- and the exo-anomeric oxygen, respectively, are re-
placed by a methylene group, have attracted considerable
interest owing to their inherent stability to the hydrolytic
activity of glycosidases. Inhibitors of glycosidases and gly-
cosyltransferases, enzymes involved in oligosaccharide-
chain biosynthesis, have been prepared on the basis of these
structures,[4] thus expanding their potential applications.
Apart from that, little has been done with regard to study-
ing the conformation around the glycosidic linkage in the
5a-carba- and 1-C-glycosides, and comparing it with the
parent glycosides; this may shed light on the influence of
the exo-anomeric effect.
Results and Discussion
Synthesis of 5a-Carba-α-l-fucopyranose
Within a project[5,6] on the synthesis of LewisX trisac-
charide analogs,[7] we were interested in the preparation of 5a-
carba--fucose and 1-C-fucosyl glycosides. Several syn-
theses of 5a-carba--fucose have been published.[8] Two of
Two routes, depicted in Scheme 1, were designed for the
preparation of 5a-carba-α--fucopyranose (1) from -man-
nitol derivative VIII through a common intermediate cycli-
tol VII obtained by a SmI2-promoted carbocyclization. To
introduce the methyl group into the cyclitol ring, we first
tried to apply the Stork radical cyclization on a conduritol
derivative V (route 1, Scheme 1). A second approach in-
volved the generation of a ketone VI by regioselective elim-
ination of the cyclic sulfate derived from cyclitol VII; this
was followed by a Wittig reaction and stereoselective hydro-
[a]
´
´
Instituto de Quımica Organica General, CSIC,
Juan de la Cierva 3, E-28006 Madrid, Spain
Fax: (internat.) ϩ 34-91/564-4853
E-mail: iqofm68@fresno.csic.es
[°]
Present address: Lilly S. A.,
Avda. de la Industria 30, 28108 Alcobendas (Madrid), Spain
Eur. J. Org. Chem. 2000, 1285Ϫ1296
WILEY-VCH Verlag GmbH, D-69451 Weinheim, 2000
1434Ϫ193X/00/0407Ϫ1285 $ 17.50ϩ.50/0
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´
M. Carpintero, C. Jaramillo, A. Fernandez-Mayoralas
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Scheme 2. Reagents and conditions: (a) TBDPSCl, ImH, DMAP,
DMF, 66%; (b) BnBr, NaH, DMF, 95%; (c) H2, Pd/C, EtOAc, 61%
(R ϭ TBDPS), or pTsOH, EtOAc/MeOH, 84% (R ϭ Bn); (d)
Swern oxidn.; (e) SmI2, tBuOH, THF, –60 °C, 91% (R ϭ TBDPS),
or 82% (R ϭ Bn)
Scheme 1. Retrosynthetic analysis of the two routes to 1
genation of the exo-methylene double bond in IV (route
2, Scheme 1).
The carbocyclization key step was carried out with the
use of the sequence of oxidation and samarium diiodide-
promoted pinacol coupling[10] on two differently substituted
diols 5 and 6 prepared from 1,6-di-O-trityl-3,4-O-isopropyl-
idene--mannitol (2, Scheme 2). The diastereoselectivity of
the cyclization was found[6a] to be dependent on the pro-
tecting group R at the vicinal position of the primary alco-
hol.
Once the cyclitol was formed, its transformation into the
target 5a-carba-α--fucopyranose was first tried by route 1
depicted in Scheme 1. Conversion of trans-diol 7 (R ϭ TBS)
into the corresponding conduritol by dihydroxy elimination
turned out to be difficult due to both the diequatorial con-
figuration of the diol system and the lability of the silyl
protecting groups. We then focused our attention on cis-
diol 8 (R ϭ Bn), which could be converted into protected
conduritol 10 by the Corey–Winter method[11] or, more
conveniently, by treatment of its cyclic sulfate 9 with sodium
hydrogen telluride (Scheme 3). Debenzylation of 10 by the
Birch reduction furnished conduritol 11 which was partially
Scheme 3. Reagents and conditions: (a) SOCl2, Et3N, CH2Cl2; (b)
NaIO4, RuCl3, MeCN, CCl4, H2O, 86% (2 steps); (c) NaTeH,
DMF, 95%; (d) Im2C(S), PhMe, 77%; (e) P(OEt)3, 165 °C, 76%; (f)
Na, NH3, –78 °C, 56%; (g) vinyl acetate, CH2Cl2, PS lipase, 66%;
(h) Me2SiCH2BrCl, CH2Cl2, Et3N; (i) Bu3SnH, AIBN, PhMe
acetylated to give 12 by
a lipase-catalyzed transes- that is, bromomethyldimethylsilylation of the free hydroxyl
terification with vinyl acetate in an organic solvent.[12] Of group and radical cyclization, followed by protodesilyl-
the different organic solvents tested (THF, acetonitrile, and ation. Although the silyl ether derivative 13 was cleanly
toluene), dichloromethane gave the highest ratio of mono/ formed,[14] several attempts to perform the cyclization, even
diacetyl derivatives.
with different protecting groups on the cyclitol ring, by
The regio- and stereoselective hydromethylation of the treatment with Bu3SnH, were unfruitful, leading to com-
double bond of 12 was tried with the Stork procedure,[13] plex mixtures of by-products.
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carba- and C-Glycosyl Analogs of Fucopyranosides
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We then began to explore the second route outlined in Table 1. Catalytic hydrogenation of 17 and 18
Scheme 1. The formation of an α-deoxyketone from a cis-
cyclohexanediol derivative VII was first required. We rea-
soned that the treatment of the cyclic sulfate 9 (Scheme 4)
with a base should lead to regioselective elimination by ab-
straction of the proton that is trans-diaxially disposed to
the sulfate leaving group. Thus, the treatment of 9 with
KOtBu led to the formation of a new product with a lower
Rf on TLC, presumably the vinyl bisulfate 15,[15] which,
after acidification, afforded the expected ketone 16 in 86%
yield. The reaction proceeded cleanly and no other product
was detected. Finally, Wittig olefination of 16 with
PPh3MeBr/KHMDS furnished exo-methylenecyclohexane
17.
[a]
Simultaneous hydrogenolysis of benzyl groups occurred to give
1 and 21.
the carba--galacto- and -altropyranose derivatives 22 and
23 in the ratio 17:83, from which 23 was isolated in 57%
yield. Under similar conditions, diol 18 gave the carba--
galacto- and -altropyranose derivatives 24 and 25 in 92:8
ratio, 24 being isolated in 71% yield.
Scheme 4. Reagents and conditions: (a) tBuOK, THF; (b) H2SO4,
H2O, THF, 86% (2 steps); (c) PPh3MeBr, [Me3Si]2NK, THF, 85%;
(d) CF3COOH, MeOH, 98%
Hydrogenation of the double bond was expected to pro-
ceed stereoselectively anti to the benzyloxy group at the ad-
jacent position, to afford the desired pseudo--fucopyr-
anose compound. However, the reaction of the isopropylid-
ene derivative 17 and the diol 18 under different conditions
gave mainly the isomeric -configured pseudosugar. Table 1
Scheme 5. Reagents and conditions: (a) BH3 THF, THF; (b) H2O2
(30%), NaOH (3 ), 69% (for 17) and 77% (for 20)
Although transformation of 24 to the pseudo--fucopyr-
summarizes the results of the hydrogenations with Pd, Rh, anose 1 is feasible, we decided to reexamine the hydrogena-
and Ni catalysts. It is noteworthy that the reaction of 17 tion of exo-methylenecyclohexanes derived from 18 by
with Raney nickel gave the 6-deoxy-5a-carba--altropyr- changing the substituents at the C-2 and C-3 positions. We
anose derivative 20 as sole product, isolated in 87% yield. hypothesized that changing the conformation into a form
Only with the diol 18 and with the Rh complex as catalyst with the substituent at C-3 in the axial orientation, the ste-
did the reaction lead to a slight excess of pseudo--fuco reochemistry of the process should be the opposite. Thus,
derivative 19. Nevertheless, it can be seen that with a given we prepared compound 26 in which the presence of two
catalyst the relative amount of 19 is always higher in the bulky tert-butyldimethylsilyl groups at C-2 and C-3 posi-
hydrogenation of 18 than in that of 17.
tions makes the cyclohexane ring adopt the conformation
We also evaluated the diastereoselectivity of the hydro- with the two silyl groups trans-diaxially disposed
boration of 17 and 18 (Scheme 5). In this case the fine tun- (Scheme 6).[16] When 26 was hydrogenated in the presence
ing of the protecting groups resulted in a drastic change in of Pd–C (Scheme 7), a mixture of pseudo-sugars 27 and 28
diastereoselectivity: treatment of isopropylidene derivative (ratio 27/28, 7:93) was obtained. Therefore, hydrogenation
17 with BH3 and subsequent oxidation gave a mixture of on 26 took place selectively on the β-face of the cyclohex-
Eur. J. Org. Chem. 2000, 1285Ϫ1296
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´
M. Carpintero, C. Jaramillo, A. Fernandez-Mayoralas
FULL PAPER
ane ring. Deprotection of 28 furnished the target carba-5a- with a 2-OH group free, from which the corresponding sul-
α--fucopyranose (1), whose 1H NMR spectrum was in fones and sulfoxides can be obtained.
agreement with the previously reported one.[8e]
The synthesis of the β-thioglycoside 29 was carried out
by a classical route (Scheme 8) involving thioglycosidation
of -fucose tetraacetate; this was followed by deacetylation
and isopropylidenation (four steps, 69% overall yield). Al-
ternatively, a shorter route to 29 was also achieved by direct
sulfenylation[22] of -fucose with (PhS)2/Bu3P and sub-
sequent isopropylidenation. Of the solvents tested for the
sulfenylation step, acetonitrile gave the best results in terms
of yield and stereoselectivity (β:α ϭ 91:9). By the two-step
procedure, 29 was obtained in 60% yield.
Scheme 6. Proposed conformations of 17 and 26
Scheme 8. Reagents and conditions: (a) Ac2O, Py; (b) PhSH, SnCl4,
CH2Cl2; (c) NaOMe, MeOH; (d) 2,2-DMP, pTsOH, Me2CO, 69%
(4 steps); (e) (PhS)2, Bu3P, CH3CN, then step d, 59% (2 steps);
(f) TMSCl, Et3N, DMF; (g) TMSI, CH2Cl2; (h) PhSH, DTBMP,
CH2Cl2, 5 °C; (i) MeOH, room temp.; (j) 2,2-DMP, pTsOH,
Me2CO, 77% (5 steps)
Scheme 7. Reagents and conditions: (a) TBDMSOTf, iPr2EtN,
CH2Cl2, 89%; (b) H2, Pd/C (10%), EtOAc, 96%; (c) Bu4NF,
CH2Cl2, 51%.
The preparation of the α-thioglycoside was tried by a
procedure described for the α-thioglucopyranoside,[23] but
only a small excess of desired α-thioglycoside was obtained
(α:β, 60:40) in low yield (38%). This result confirmed the
difficulties often encountered when preparing α--thiofuco-
pyranosides.[24] Eventually, the α-thioglycoside 30 could be
stereoselectively prepared by an original route (Scheme 8),
whose thioglycosylation step was performed by a modified
procedure for the synthesis of α-fucopyranosides,[25] in 77%
overall yield. Remarkably, all of the five steps are performed
In conclusion, we found a stereoselective route to
pseudo--fucopyranose 1 from -mannitol to afford, in ad-
dition to the target carbasugar 1, epimeric pseudosugars.
These can be prepared by hydrogenation or hydroboration
of a common exo-methylenecyclitol, the stereoselectivity of
which can be controlled by the substitution on the cyclitol.
Synthesis of 1-C-Fucopyranosides
Our approach to the synthesis of these compounds re- in the same flask. Control of the temperature during the
quired the preparation of a nucleophilic glycosyl donor. thioglycosylation step was crucial for achieving α-stereo-
Nonstabilized anomeric carbanions bearing oxygenated selectivity (the ratios α/β were 95:5 and 66:33 at 5 and 20
substituents at position 2 were previously generated by se- °C, respectively).
quential two-electron transfer with either lithium naph-
From the 1-thio-β--fucopyranoside derivative 29, the
thalenide[17] (from glycosyl chlorides) or samarium diiodide corresponding sulfone 31 was obtained (Scheme 9), and was
(from glycosyl sulfones,[18] phosphates[19] or chlorides[20]), submitted to reductive lithiation with lithium naphthalenide
or by lithium exchange with n-butyllithium[21] (from glyco- (LN).[26] The reaction of the oxyanion of 31 with lithium
syl stannanes). We investigated new methods to generate naphthalenide in the presence of isobutyraldehyde as elec-
anomeric carbanions; these methods are based on the use of trophile at –78 °C did not afford the desired C-glycoside.
glycosyl sulfones and their reductive lithiation, or glycosyl Instead, the main products were the dimer 32[27] and the
sulfoxides through a sulfinyllithium exchange. Direct C-1- 1,5-anhydro--fucitol 33, isolated in 36% and 29% yields,
lithiation of sugars generally leads to the β-elimination of respectively. The selective formation of 32 with an α,α-con-
functional groups in the 2-position; this was prevented by figuration at the anomeric carbons suggests that the α-rad-
leaving the 2-hydroxyl group unprotected.[17] Therefore, we ical intermediate was generated upon one-electron transfer
first prepared the phenyl 1-thio-β- and α-fucopyranosides, from lithium naphthalenide to the phenylsulfonyl group
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carba- and C-Glycosyl Analogs of Fucopyranosides
FULL PAPER
and subsequent C(1)–S fragmentation. The second electron it was the sole diastereoisomer formed, and its relative con-
transfer onto the anomeric position, to form a carbanion, figuration was not determined. Deprotonation and phenyl-
seems to be slower than dimerization or proton abstraction, sulfinyllithium exchange on 35 was performed by treatment
probably due to the presence of the oxyanion at C-2.
with tBuLi. The dianion intermediate was quenched with
deuterated methanol, and a mixture of the corresponding
α-deuterated and protonated 1,5-anhydrofucitols 36 and 33,
respectively, plus recovered starting material (Scheme 10)
formed. The best yields of metallation were obtained in
THF and Et2O, and in the presence of MeLi LiBr[30] prior
1
to tBuLi treatment (Table 2). The H NMR spectra of the
crude mixtures showed, in all experiments, that only the
above-mentioned products were present. No β-deuterated
1,5-anhydrofucitol could be detected; this indicates that the
deuteration is completely stereoselective. Hence, the anom-
eric carbanion seems to be configurationally stable. This
was further supported by the results obtained from the re-
action of the fucopyranosyllithium, generated in this way
with isobutyraldehyde, which led to a diastereomeric mix-
ture of the α-configured C-glycosides 37/38 (Scheme 11).
1
Again, no β-C-glycoside could be detected by H NMR.
The structures of diastereoisomers 37/38 were confirmed by
Scheme 9. Reagents and conditions: (a) mCPBA, NaHCO3,
CH2Cl2, room temp., 90%; (b) BuLi, THF, –78 °C; (c) LN,
iPrCHO, –78 °C, 65% (2 steps)
Table 2. Phenylsulfinyllithium exchange of 35
Exp. Solvent Equiv./t (min)[b] Equiv./t (min)[c] Yield (%)[a] 36:33
All attempts, with different amounts of lithium naph-
thalenide and with different lengths of time, to get the C-
fucopyranoside from the reaction of the fucosyl sulfone 31,
for the reductive lithiation, failed. Hence, we focused our
attention on the fucosyl sulfoxides and the possibility of
performing a phenylsulfinyllithium exchange, which has
been used for the generation of oxiranyl carbanions and its
further reaction with electrophiles,[28] and for the prepara-
tion of glycals.[29]
1
2
3
THF
THF
Et2O
5/0.5
5/5
3/0.5
6/5
61
80
63
54
77
2.3:1
2:1
3.3:1
8.0:1
6.7:1
5/5
6/5
4[d] Et2O
5[d] Et2O
5/5
5/20
6/5
6/5
[a] Yields and ratio of 36: 33 were determined by 1H NMR spectro-
scopy. – [b] Equiv. means equivalents of tBuLi; t: time of metalation
[c]
step. – Equiv. means equivalents of CD3OD; t: time of deutera-
[d]
tion step. –
1 equiv. of MeLi LiBr was added prior to tBuLi
)
Since phenylsulfinyllithium exchange would proceed, in treatment (ref.[30]
principle, with retention of configuration,[28] sulfoxide 35
would be the appropriate anomer for the generation of an
α-oriented anomeric carbanion (Scheme 10). Compound 35
was prepared by partial oxidation of 30 at low temperature;
Scheme 10. Reagents and conditions: (a) mCPBA, NaHCO3,
CH2Cl2, –78 °C, 96%; (b) tBuLi, THF, –78 °C; (c) CD3OD (see
Table 2)
Scheme 11. Reagents and conditions: (a) MeLi LiBr, –78 °C, then,
tBuLi, Et2O; (b) iPrCHO, 81% (2 steps); (c) 2,2-DMP, pTsOH,
Me2CO
Eur. J. Org. Chem. 2000, 1285Ϫ1296
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M. Carpintero, C. Jaramillo, A. Fernandez-Mayoralas
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their transformation into the diacetals 39 and 40, which preliminary experiment, only one equiv. of the more valu-
gave further information[31] about the new chiral center cre- able aldehyde was used and, after acetylation, a mixture of
ated during the C-glycosylation.
diastereomeric C-disaccharides 46/47 was obtained[33] in
Additional evidence for the stereospecificity of the pro- 23% (not optimized) combined yield. We are currently in-
cess was obtained from the reaction of fucosyl phenyl sulf- vestigating the scope and limitation of this new method to
oxide 41, prepared analogously to 35 from phenyl thiogly- generate anomeric carbanions from different sugars and
coside 29 (Scheme 12). In this case, phenylsulfinyllithium electrophiles.
exchange was slower, and the corresponding β-configured
fucopyranosyllithium species proved to be less efficient in
the C-glycosylation, although it afforded only the corres-
ponding β-C-glycosides 42, whose structures were again se-
cured after acetylation to 43 and 44 (Scheme 12).
Conclusion
This paper describes an original route to the preparation
of 5a-carba-α--fucopyranose (1) from -mannitol, which
allows the stereoselective synthesis of other related carba-
sugars, and a new method for the preparation of C-glycos-
ides on the basis of glycosyl sulfoxides. The key steps for
the synthesis of 1 were the SmI2-promoted carbocyclization,
the regioselective elimination of a cyclic sulfate, and the
stereoselective hydrogenation of a double bond, controlled
by substitution on the substrate. The synthesis of 1-C-fuco-
pyranosides was carried out stereospecifically by the gen-
eration of an anomeric carbanion through phenylsulfinylli-
thium exchange. The required fucosyl phenyl sulfoxides
were efficiently prepared from -fucose by highly stereose-
lective thioglycosylation reactions. These fucopyranoside
analogs are useful compounds for the synthesis of fucosid-
ase and fucosyltransferase inhibitors and for conforma-
tional studies around the anomeric center. Our future stud-
ies will focus on these areas.
Experimental Section
General Methods: Separation and purification of all synthesized
compounds were carried out by flash chromatography (FC) with
silica gel (Merck, 230–400 mesh). The eluent used is indicated, and
solvent ratios refer to volume. – TLC was performed with the TLC
plates GF234 Merck (0.2 mm); detection was done with 5% PMA
in EtOH or 5% H2SO4 in EtOH. Solvents were dried and distilled
as follows: THF, PhMe, and Et2O (Na/benzophenone), MeCN and
Scheme 12. Reagents and conditions: (a) mCPBA, NaHCO3,
CH2Cl2, –78 °C, 89%; (b) MeLi LiBr, –78 °C, then, tBuLi, Et2O;
(c) iPrCHO, 69% (2 steps); (d) 2,2-DMP, p-TsOH, Me2CO
˚
CH2Cl2 (CaH2), DMF (3A molecular sieves), pyridine (NaOH). –
Melting points were determined in a Kofler hot-stage apparatus
and are not corrected. – 1H NMR and 13C NMR spectra were
measured on a Varian XL-300 (300 MHz and 75 MHz, respect-
ively) spectrometer, or on a Bruker AM-200 (200 MHz and
50 MHz, respectively) spectrometer, in CDCl3 or in the solvent in-
dicated. Chemical shifts (δ) refer to TMS, which was used as an
internal reference. – Optical rotations were measured at room
temp., in quartz cells (d ϭ 1 dm), in a Perkin–Elmer 241 MC po-
larimeter, with Na 589 light, at the concentration indicated, in
CHCl3 or in the solvent indicated. – Elemental analysis were deter-
mined in a Perkin–Elmer 240 analyzer. The preparation of com-
pounds 3–8 is described in ref.[6a]
An attempt to widen the scope of the C-glycosylation to
more complex aldehydes was carried out (Scheme 13) by
reaction of the fucopyranosyllithium generated from 35
with the aldehyde 45[32] derived from -galactose. In this
2,5-Di-O-benzyl-1,6-O-isopropylidene-D-allo-inositol
3,4-Cyclic
Sulfate (9): To a solution of Et3N (140 µL, 1.0 mmol) in CH2Cl2
(0.9 mL) was added 8 (R ϭ Bn) (100 mg, 0.25 mmol); the mixture
was stirred at 0 °C for 10 min. A solution of thionyl chloride (29
µL, 0.400 mmol, 1.6 equiv.) in dry CH2Cl2 (65 µL) was then slowly
added (20 min), and the mixture was further stirred for 10 min at
0 °C. The reaction was then diluted with cold Et2O (1 mL), washed
with H2O (1 mL), dried (Na2SO4), and concentrated. The residue
Scheme 13. Synthesis of compounds 46/47
1290
Eur. J. Org. Chem. 2000, 1285Ϫ1296

carba- and C-Glycosyl Analogs of Fucopyranosides
was dissolved in CCl4 (0.5 mL), CH3CN (0.5 mL) and H2O H), 4.57 (dd, J ϭ 3.8 Hz, J ϭ 4.9 Hz, 1 H), 4.08 (dd, J ϭ 3.6 Hz,
FULL PAPER
(1.0 mL) and cooled to 0 °C. Ruthenium trichloride (13 mg,
J ϭ 10.0 Hz, 1 H), 3.95 (dd, J ϭ 3.6 Hz, J ϭ 10.0 Hz, 1 H), 2.27
(d, J ϭ 2.0 Hz, 1 H), 2.09 (s, 3 H), 1.48 (s, 3 H), 1.45 (s, 3 H). –
0.05 mmol, 0.2 equiv.) and NaIO4 (107 mg, 0.50 mmol, 2.0 equiv.)
were added, while stirring continued vigorously at 0 °C for 1 h. 13C NMR (50 MHz): δ ϭ 177.06, 132.14, 127.67, 110.67, 73.81,
After this time period, the mixture was diluted with Et2O (5 mL),
filtered through a pad of celite, and washed with H2O (2 mL). The
organic layer was dried (Na2SO4), concentrated and purified by FC
(hexane/EtOAc, 100:1) to give 9 (99 mg, 86%): m.p. 107–109 °C. –
[α]D ϭ –62.0 (c ϭ 0.50). – 1H NMR (200 MHz): δ ϭ 7.37–7.18 (m,
10 H), 4.95 (dd, J ϭ 1.9 Hz, J ϭ 6.7 Hz, 1 H), 4.86 (d, J ϭ 4.4 Hz,
1 H), 4.85 (d, J ϭ 5.6 Hz, 1 H), 4.81 (d, J ϭ 6.1 Hz, 1 H), 4.65 (d,
J ϭ 12.8 Hz, 1 H), 4.61 (d, J ϭ 11.7 Hz, 1 H), 4.43 (dd, J ϭ 2.9 Hz,
J ϭ 6.7 Hz, 1 H), 4.39 (t, J ϭ 2.4 Hz, 1 H), 4.28 (dd, J ϭ 2.0 Hz,
J ϭ 4.6 Hz, 1 H), 3.94 (dd, J ϭ 2.0 Hz, J ϭ 10.0 Hz, 1 H), 1.43 (s,
3 H), 1.42 (s, 3 H). – 13C NMR (50 MHz): δ ϭ 137.42, 136.95,
128.59, 128.29, 127.88, 127.75, 112.06, 81.69, 80.77, 75.18, 74.72,
73.30, 72.61, 72.10, 70.65, 26.87, 26.71.
71.51, 66.07, 64.51, 35.31, 26.74. – C11H16O5 (228.24): calcd. C
57.87, H 7.07; found C 58.14, H 7.42.
(2R,3R,4R,5R)-2,5-Di-benzyloxy-3,4-(isopropylidendioxy)cyclo-
hexan-1-one (16): Compound 9 (450 mg, 1 mmol) was dissolved in
THF (22 mL) and this solution was treated with tBuOK (353 mg,
3.15 mmol, 2.8 equiv.) at room temp. for 90 min. Then the mixture
was treated with THF/H2SO4/H2O (300:3:1, 3.5 mL) at room temp.
for 30 min. The reaction was diluted with CH2Cl2 (30 mL), washed
with sat. NaHCO3 solution (20 mL), dried (Na2SO4) and concen-
trated to give a residue which was purified by FC (hexane/EtOAc
20: 1), giving 16 (320 mg, 86%): m.p. 91–94 °C. – [α]D ϭ –4.0 (c ϭ
1.0). – 1H NMR (300 MHz): δ ϭ 7.30–7.17 (m, 10 H), 4.73 (d, J ϭ
12.0 Hz, 1 H), 4.63 (d, J ϭ 11.7 Hz, 1 H), 4.56 (d, J ϭ 12.0 Hz, 1
H), 4.51 (d, J ϭ 11.7 Hz, 1 H), 4.49 (d, J ϭ 2.4 Hz, 1 H), 4.22 (dd,
J ϭ 2.6 Hz, J ϭ 10.0 Hz, 1 H), 4.19 (m, 1 H), 4.15 (dd, J ϭ 2.8 Hz,
J ϭ 10.0 Hz, 1 H), 2.77 (dd, J ϭ 3.9 Hz, J ϭ 15.2 Hz, 1 H), 2.46
(ddd, J ϭ 1.1 Hz, J ϭ 2.6 Hz, J ϭ 15.2 Hz, 1 H), 1.45 (d, J ϭ
11.7 Hz, 6 H). – 13C NMR (50 MHz): δ ϭ 204.61, 138.14, 137.85,
128.39, 128.31, 127.37, 127.61, 127.56, 127.35, 111.78, 82.14, 75.29,
75.06, 72.82, 72.62, 70.75, 41.91, 26.83, 26.76. – C23H26O5 (382.46):
calcd. C 72.23, H 6.85; found C 72.89, H 6.81.
1,4-Di-O-benzyl-2,3-O-isopropylidene-L-conduritol E (10): A sus-
pension of tellurium powder (50 mg, 0.39 mmol, 4.0 equiv.) and
NaBH4 (18 mg, 0.48 mmol, 5.0 equiv.) in dry DMF (1 mL) con-
taining tBuOH (10 µL) was heated at 80 °C under argon without
stirring; after 10 min, the solution was stirred at this temperature
for another 45 min. The purple solution was cooled at room tem-
perature, a solution of 9 (45 mg, 0.10 mmol, 1 equiv.) in pyridine/
DMF/benzene (9 µL/0.4 mL/130 µL) was added, and the mixture
was stirred at room temp. for 10 min. Then Et2O (2 mL) was added,
and the mixture was filtered through Celite and washed with
EtOAc, CH2Cl2 and MeOH. The combined filtrates were washed
with NaCl (1 mL), and H2O (4 ϫ 1 mL), dried (Na2SO4) and con-
centrated. The residue was purified by FC (hexane/EtOAc, 30:1) to
give 10 (35 mg, 95%): m.p. 60–62 °C. – [α]D ϭ ϩ90.0 (c ϭ 0.70). –
1H NMR (200 MHz): δ ϭ 7.37–7.30 (m, 10 H), 5.91 (m, 2 H), 4.99
(d, J ϭ 11.7 Hz, 2 H), 4.65 (d, J ϭ 11.7 Hz, 2 H), 4.35 (m, 2 H),
4.21 (m, 2 H), 1.55 (s, 6 H). – 13C NMR (50 MHz): δ ϭ 139.20,
129.55, 128.44, 127.80, 127.66, 110.90, 75.00, 73.58, 72.13, 27.03. –
C23H26O4 (366.46): calcd. C 75.38, H 7.15; found C 75.17, H 7.19.
(1R,2R,3R,4R)-1,4-Di-benzyloxy-2,3-isopropylidenedioxy-5-
methylenecyclohexane (17): To a suspension of PPh3MeBr (1.46 g,
4.1 mmol) in dry THF (5.0 mL) under argon at –78 °C was added
KHMDS (0.5 , 6.8 mL, 3.4 mmol). The temperature was raised
to 0 °C and the mixture was stirred for 1 h. Then the reaction was
cooled at –40 °C, a solution of 16 (434 mg, 1.14 mmol) in dry THF
(5.0 mL) was added dropwise, and stirring was continued for 30 h
at 5 °C. The mixture was then quenched with NH4Cl (10 mL) and
was extracted with CH2Cl2 (20 mL). The organic layer was dried
(Na2SO4) and concentrated, and the residue was purified by FC
(hexane/EtOAc, 30:1) to give 17 (373 mg, 85%): m.p. 30–31 °C. –
[α]D ϭ ϩ14.1 (c ϭ 0.62). – 1H-NMR (300 MHz, [D6]acetone): δ ϭ
7.37–7.24 (m, 10 H), 5.14 (m, 1 H), 5.08 (m, 1 H), 4.61 (d, J ϭ
12.1 Hz, 1 H), 4.58 (d, J ϭ 12.2 Hz, 1 H), 4.52 (d, J ϭ 12.2 Hz, 1
H), 4.38 (d, J ϭ 2.7 Hz, 1 H), 4.29 (dd, J ϭ 2.4 Hz, J ϭ 10.0 Hz,
1 H), 4.15 (q, J ϭ 2.8 Hz, 1 H), 4.08 (dd, J ϭ 2.7 Hz, J ϭ 9.9 Hz,
1 H), 2.47 (m, 2 H), 1.39 (s, 3 H), 1.38 (s, 3 H). – 13C NMR
(50 MHz): δ ϭ 141.18, 139.00, 138.65, 128.19, 127.59, 127.21,
127.15, 118.40, 109.83, 79.67, 75.92, 75.72, 72.68, 72.10, 70.31,
34.72 26.85, 26.79. – C24H28O4 (380.48): calcd. C 75.76, H 7.42;
found C 74.51, H 7.32.
2,3-O-Isopropylidene-L-conduritol E (11): Sodium metal (52 mg,
1.184 mmol, 8 equiv.) was added to a solution of liquid ammonia
(3 mL) cooled at –70 °C until a deep color persisted for 30 min.
Then, a solution of 10 (100 mg, 0.27 mmol, 1 equiv.) in Et2O
(1 mL) was added and the reaction was stirred for 2 h. Then sat.
aq. NH4Cl (1 mL) was added, and the ammonia was allowed to
evaporate at room temp. The residue was purified by FC (hexane/
EtOAc, 1:1) to give 11 (28 mg, 56%) and recovered 10 (18 mg,
15%).
11: M.p. 142–144 °C. – [α]D ϭ –251.8 (c ϭ 0.90). – 1H NMR
(200 MHz): δ ϭ 6.04 (dd, J ϭ 1.4 Hz, J ϭ 3.2 Hz, 2 H), 4.55 (s, 2
H), 3.98 (dd, J ϭ 1.2 Hz, J ϭ 1.8 Hz, 2 H), 2.39 (d, J ϭ 2.0 Hz, 2
H), 1.50 (s, 6 H). – 13C NMR (50 MHz): δ ϭ 130.46, 107.52, 73.37,
64.83, 26.89. – C9H14O4 (186.21): calcd. C 58.04, H 7.58; found C
57.95, H 7.45.
(1R,2R,3R,4R)-1,4-Di-benzyloxy-5-methylenecyclohexane-2,3-diol
(18): To a solution of 17 (64 mg, 0.17 mmol) in MeOH (2 mL) was
added dropwise CF3COOH (6.5 µL, 0.85 mmol, 5 equiv.); the mix-
ture was stirred at room temp. for 30 min. The solvents were then
removed to give a residue which was purified by FC (hexane/EtOAc
2:1), affording 18 (59 mg, 98%): m.p. 49–50 °C. – [α]D ϭ –2.6 (c ϭ
1.00). – 1H NMR (300 MHz, [D6]acetone): δ ϭ 7.40–7.22 (m, 10
H), 5.08 (s, 1 H), 5.02 (s, 1 H), 4.61 (d, J ϭ 6.1 Hz, 2 H), 4.57 (d,
J ϭ 12.1 Hz, 1 H), 4.45 (d, J ϭ 12.1 Hz, 1 H), 4.13 (d, J ϭ 3.2 Hz,
1 H), 4.01 (ddd, J ϭ 2.8 Hz, J ϭ 4.7 Hz, J ϭ 8.2 Hz, 1 H), 3.92
(td, J ϭ 3.2 Hz, J ϭ 6.8 Hz, 1 H), 3.82 (q, J ϭ 3.2 Hz, 1 H), 3.59
1-O-Acetyl-2,3-O-isopropylidene-L-conduritol E (12): To a solution
of 11 (75 mg, 0.40 mmol) in dry CH2Cl2 (15 mL) was added vinyl
˚
acetate (171 µL, 2.02 mmol, 5 equiv.), 4 A molecular sieves (1 g),
and lipase PS (0.63 g). The mixture was stirred at 30 °C and at
250 rpm in an orbital shaker for 4 h, and then it was filtered
through celite. The filtrate was concentrated, and the residue frac-
tionated by FC (hexane/EtOAc, 8:1Ǟ 2:1Ǟ1:1) to give 12 (61 mg, (d, J ϭ 5.1 Hz, 1 H), 3.48 (d, J ϭ 5.1 Hz, 1 H), 2.50 (dd, J ϭ
66%): m.p. 110–114 °C. – [α]D ϭ –313.4, (c ϭ 0.60). – 1H NMR
(200 MHz): δ ϭ 6.11 (dd, J ϭ 5.0 Hz, J ϭ 9.6 Hz, 1 H), 6.00 (dd,
6.0 Hz, J ϭ 13.6 Hz, 1 H), 2.44 (dd, J ϭ 3.7 Hz, J ϭ 13.6 Hz, 1
H). – 13C NMR (75 MHz): δ ϭ 140.59, 138.19, 138.0, 128.41,
J ϭ 5.2 Hz, J ϭ 9.7 Hz, 1 H), 5.64 (dd, J ϭ 3.7 Hz, J ϭ 5.0 Hz, 1 128.39, 127.71, 127.61, 127.61, 116.37, 80.98, 76.52, 72.56, 72.18,
Eur. J. Org. Chem. 2000, 1285Ϫ1296 1291

´
M. Carpintero, C. Jaramillo, A. Fernandez-Mayoralas
FULL PAPER
71.09, 70.12, 32.37. – C21H24O4 (340.42): calcd. C 74.09, H 7.11;
found C 74.62, H 7.38.
70.77, 31.94, 29.76, 18.44. – C21H26O4 (342.43): calcd. C 73.66, H
7.65; found C 73.51, H 7.59.
1,4-Di-O-benzyl-2,3-isopropylidene-5a-carba-β-D-altropyranose (23):
Catalytic Hydrogenation of 17 and 18 with Pd/C. – Method a: A
solution of 17 or 18 (0.08 mmol) in EtOAc (1.5 mL), was hydrogen-
ated in the presence of 10% Pd/C (3 mg, 0.002 mmol, 0.05 equiv.)
at room temperature for 10 min. The mixture was filtered and con-
centrated to give a mixture of 1 and 21, whose ratio (see Table 1)
was determined by 1H NMR (200 MHz, D2O): 1, see below;
21,[8a][8e] 3.92–3.88 (m, 3 H), 3.41 (dd, J ϭ 1.5 Hz, J ϭ 10.6 Hz, 1
H), 1.92–1.62 (m, 1 H), 1.52–1.43 (m, 1 H) 1.33 (q, J ϭ 12.4 Hz, 1
H),0.89 (d, J ϭ 6.95 Hz, 3 H). – Method b: To a solution of 18
(0.08 mmol) in MeOH (1.0 mL) was added pyridine (3 µL,
0.04 mmol, 0.5 equiv.); this mixture was hydrogenated in the pres-
ence of 10% Pd/C (8 mg, 0.008 mmol, 0.1 equiv.) at room temper-
ature for 48 h. The mixture was filtered and concentrated to give a
residue which was purified by FC (hexane/EtOAc 7:1) to give 19
(11 mg, 41%) and 20 (14 mg, 51%).
To a solution of BH3 THF (1 , 287 µL, 0.287 mmol, 3 equiv.) in
dry THF (362 µL), cooled at 0 °C, was added, dropwise, a solution
of 17 (37 mg, 0.096 mmol) in dry THF (362 µL). The mixture was
stirred at room temp. for 2 h and then 3  NaOH (108 µL,
0.324 mmol, 3.4 equiv.) and 30% H2O2 (108 µL, 0.105 mmol, 1.1
equiv.) were added dropwise; stirring was continued for 30 min. The
mixture was then diluted with CH2Cl2 (1 mL), washed with sat.
aq. NaCl (1 mL), dried (Na2SO4), and concentrated. FC (hexane /
EtOAc, 5:1) gave 23 (21 mg, 57%): m.p. 81–83 °C. – [α]D ϭ ϩ5.4
1
(c ϭ 1.3). – H NMR (300 MHz, [D6]benzene): δ ϭ 7.38–7.08 (m,
10 H), 4.90 (d, J ϭ 11.9 Hz, 1 H), 4.85 (d, J ϭ 11.9 Hz, 1 H), 4.55
(d, J ϭ 11.9 Hz, 1 H), 4.46 (d, J ϭ 11.9 Hz, 1 H), 4.42 (dd, J ϭ
2.3 Hz, J ϭ 10.3 Hz, 1 H), 4.18 (m, 1 H), 4.14 (dd, J ϭ 2.3 Hz,
J ϭ 8.9 Hz, 1 H), 3.88 (q, J ϭ 2.5 Hz, 1 H), 3.52–3.36 (m, 2 H),
2.03 (m, 1 H), 1.73 (dd, J ϭ 4.7 Hz, J ϭ 11.7 Hz, 1 H), 1.66 (ddd,
J ϭ 3.2 Hz, J ϭ 6.9 Hz, J ϭ 15.1 Hz, 1 H), 1.47 (s, 3 H), 1.45 (s,
3 H). – 1H NMR (300 MHz): δ ϭ 7.29–7.20 (m, 10 H), 4.89 (d,
J ϭ 11.8 Hz, 1 H), 4.83 (d, J ϭ 11.9 Hz, 1 H), 4.55 (d, J ϭ 11.6 Hz,
1 H), 4.46 (d, J ϭ 11.9 Hz, 1 H), 4.24 (dd, J ϭ 2.4 Hz, J ϭ 10.1 Hz,
1 H), 4.14–4.05 (m, 3 H), 3.61–3.52 (m, 2 H), 2.65 (dd, J ϭ 5.0 Hz,
J ϭ 7.1 Hz, 1 H), 2.16–2.13 (m, 1 H), 1.94 (ddd, J ϭ 3.0 Hz, J ϭ
7.1 Hz, J ϭ 15.1 Hz, 1 H), 1.71 (d br, J ϭ 13.9 Hz, 1 H), 1.49 (s,
6 H). – 13C NMR (50 MHz): δ ϭ 139.06, 138.27, 129.80, 128.26,
127.62, 127.36, 108.99, 76.57, 76.18, 74.86, 74.12, 73.31, 73.07,
65.79, 42.58, 29.50, 26.86. – C21H26O5 (358.43): calcd. C 70.37, H
7.31; found C 70.17, H 7.02.
With Rhodium from 17: A solution of 17 (30 mg, 0.08 mmol) in
MeOH (1.0 mL) was hydrogenated in the presence of Rh(PPh3)Cl
(10 mg, 0.01 mmol, 0.1 equiv.) at room temperature for 24 h.
CF3COOH (3 µL, 0.03 mmol, 0.5 equiv.) was then added. The mix-
ture was concentrated to give a residue which was purified by FC
(hexane/EtOAc, 7:1), to give 19 (7 mg, 25%) and 20 (18 mg, 66%). –
From 18: A solution of 18 (27 mg, 0.08 mmol) in MeOH (1.0 mL)
was hydrogenated in the presence of Rh(PPh3)Cl (10 mg,
0.01 mmol, 0.1 equiv.) at room temperature for 24 h and then at 60
°C for 8 h. The mixture was concentrated and the residue was puri-
fied by FC (hexane/EtOAc, 7:1) to give 19 (14 mg, 51%) and 20
(13 mg, 48%).
1,4-Di-O-benzyl-5a-carba-α-L-galactopyranose (24): This com-
pound was prepared from 18 (50 mg, 0.15 mmol) under the same
conditions as described for 23. The residue was purified by FC
(hexane/EtOAc, 2:1) to give 24 (37 mg, 71%). – [α]D ϭ –24.7 (c ϭ
0.60). – 1H NMR (300 MHz): δ ϭ 7.29–7.18 (m, 10 H), 4.88 (d,
J ϭ 11.6 Hz, 1 H), 4.62 (d, J ϭ 11.5 Hz, 1 H), 4.57 (d, J ϭ 11.6 Hz,
1 H), 4.38 (d, J ϭ 11.6 Hz, 1 H), 4.00 (m, 1 H), 3.86 (q, J ϭ 2.7 Hz,
1 H), 3.77–3.74 (m, 2 H), 3.51 (d, J ϭ 5.6 Hz, 2 H), 2.40–2.34 (br
s, 1 H), 2.30–2.22 (br s, 2 H), 1.98–1.88 (m, 1 H), 1.74 (m, J ϭ
1.0 Hz, J ϭ 3.8 Hz, J ϭ 14.6 Hz, 1 H), 1.57 (dt, J ϭ 2.2 Hz, J ϭ
15.1 Hz, 1 H). – 13C NMR (50 MHz): δ ϭ 138.13, 129.79, 128.48,
127.99, 127.82, 127.78, 127.58, 76.80, 76.36, 74.27, 72.52, 76.80,
71.33, 64.19, 37.14, 25.02. – C21H26O5 (358.43): calcd. C 70.37, H,
7.31; found C 70.61, H, 7.22.
With Raney Nickel from 17: A solution of 17 (30 mg, 0.08 mmol) in
MeOH (1.0 mL) was hydrogenated in the presence of Raney nickel
(100 mg) at room temperature for 30 min. CF3COOH (3 µL,
0.03 mmol, 0.5 equiv.) was then added, and the solution was separ-
ated by decantation and concentrated to give a residue which was
purified (see above), to give 20 (24 mg, 87%). – From 18: A solution
of 18 (27 mg, 0.08 mmol) in MeOH (1 mL) was hydrogenated in
the presence of Raney nickel (100 mg) at room temperature for
16 h. The reaction mixture was concentrated and the residue was
purified by FC (hexane/EtOAc, 7:1) to give 19 (4 mg, 14%) and 20
(13 mg, 48%).
1,4-Di-O-benzyl-5a-carba-α-L-fucopyranose (19): – [α]D ϭ –4.4 (c ϭ
1.0). – 1H NMR (300 MHz): δ ϭ 7.39–7.30 (m, 10 H), 4.86 (d, J ϭ
11.6 Hz, 1 H), 4.68 (d, J ϭ 5.8 Hz, 1 H), 4.64 (d, J ϭ 5.8 Hz, 1 H),
4.45 (d, J ϭ 11.6 Hz, 1 H), 3.86 (q, J ϭ 2.7 Hz, 1 H), 3.79 (m, 2
H), 3.73 (m, 1 H), 2.32–2.26 (br s, 2 H), 2.09–1.95 (m, 1 H), 1.75
(dtd, J ϭ 0.8 Hz, J ϭ 2.8 Hz, J ϭ 14.4 Hz, 1 H), 1.62 (dt, J ϭ
2.0 Hz, J ϭ 14.4 Hz, 1 H), 1.03 (d, J ϭ 6.8 Hz, 3 H). – 13C NMR
(50 MHz): δ ϭ 139.21, 138.36, 128.31, 127.90. 127.71, 127.53,
127.50, 81.82, 77.21, 75.34, 74.38, 72.50, 71.25, 30.31, 29.99,
17.67. – C21H26O4 (342.43): calcd. C 73.66, H 7.65; found C 73.17,
H 7.91.
(1R,2R,3R,4R)-1,4-Di-benzyloxy-2,3-(tert-butyldimethyl)silyloxy-5-
methylenecyclohexane (26): To a solution of 18 (150 mg, 0.44 mmol)
in CH2Cl2 (1.5 mL) and iPr2EtN (226 µL, 0.017 mmol, 0.05 equiv.)
was added, dropwise, tert-butyldimethylsilyl triflate (258 µL,
1.0 mmol, 2.4 equiv.); the mixture was stirred at room temp. for
5 min. The mixture was then diluted with CH2Cl2 (2 mL) and
washed with H2O (3 mL). The organic layer was dried (Na2SO4)
and concentrated, giving a residue which was purified by FC (hex-
ane/EtOAc 100:1) to give 26 (225 mg, 89%). – [α]D ϭ –3.8 (c ϭ
0.95). – 1H NMR (300 MHz, [D6]acetone): δ ϭ 7.40–7.24 (m, 10
H), 4.92 (m, 1 H), 4.67 (d, J ϭ 12.4 Hz, 1 H), 4.55 (m, 2 H), 4.54
1,4-Di-O-benzyl-6-deoxy-5a-carba-α-D-altropyranose (20): m.p. 81–
83 °C. – [α]D ϭ ϩ29.5 (c ϭ 0.52). – 1H NMR (300 MHz): δ ϭ (d, J ϭ 12.7 Hz, 1 H), 4.18 (d, J ϭ 1.8 Hz, 1 H), 4.09–4.00 (m, 2
7.39–7.29 (m, 10 H), 4.64 (d, J ϭ 11.2 Hz, 1 H), 4.58 (d, J ϭ H), 3.68 (ddd, J ϭ 2.3 Hz, J ϭ 5.0 Hz, J ϭ 6.8 Hz, 1 H), 2.50 (ddd,
2.3 Hz, 2 H), 4.51 (d, J ϭ 11.2 Hz, 1 H), 4.25 (m, 2 H), 3.83 (ddd, J ϭ 0.9 Hz, J ϭ 4.5 Hz, J ϭ 12.0 Hz, 1 H), 2.40 (t, J ϭ 12.3 Hz,
J ϭ 2.4 Hz, J ϭ 4.7 Hz, J ϭ 11.4 Hz, 1 H), 3.39 (dd, J ϭ 2.3 Hz,
J ϭ 10.2 Hz, 1 H), 2.34–2.24 (m, 2 H), 1.98–1.84 (m, 1 H), 1.79
(dt, J ϭ 4.1 Hz, J ϭ 12.9 Hz, 1 H), 1.51 (c, J ϭ 12.1 Hz, 1 H), 1.04
1 H) 0.84 (s, 9 H), 0.81 (s, 9 H), 0.07–0.04 (m, 12 H). – 13C NMR
(50 MHz): δ ϭ 141.71, 139.00, 138.96, 128.20, 127.49, 127.38,
127.29, 108.05, 77.90, 76.43, 74.05, 72.97, 71.70, 70.70, 34.01,
(d, J ϭ 6.6 Hz, 3 H). – 13C NMR (50 MHz): δ ϭ 138.31, 138.13, 25.78, 25.76, 18.10, 18.06, –4.40, –4.51, –5.04, –5.12. – C33H52O4Si2
128.48, 127.90, 127.77, 127.60, 81.73, 75.11, 70.09, 68.68, 71.94, (568.94): calcd. C 69.67, H 9.22; found C 69.67, H 8.98.
1292
Eur. J. Org. Chem. 2000, 1285Ϫ1296

carba- and C-Glycosyl Analogs of Fucopyranosides
2,3-(tert-Butyldimethyl)silyloxy-5a-carba-α- -fucopyranose (28): A
FULL PAPER
L
diphenyldisulfide (1.73 g, 7.92 mmol, 1.3 equiv.) and Bu3P
mixture of 26 (200 mg, 0.350 mmol), EtOAc (8 mL), and 10% Pd/ (3.00 mL, 2.44 g, 12.0 mmol, 2.0 equiv.) at 0 °C. The temperature
C (26 mg, 0.017 mmol, 0.05 equiv.), was hydrogenated at room was raised to room temp., and the reaction was allowed to proceed
temp. for 4 h. The reaction mixture was then diluted with EtOAc
(20 mL), filtered, and concentrated to give a residue which was
purified by FC (hexane/EtOAc, 100:1) to give, first, 27 (8 mg,
for 24 h. Then the solvent was evaporated to give a residue which
was cromatographed (hexane/EtOAc, 2:1 Ǟ 1:1 Ǟ EtOAc), giving
crude phenyl 1-thio-α- and -β--fucopyranoside, which were dis-
solved in Me2CO (30 mL) and treated with 2,2-dimethoxypropane
1
7%): – H NMR (300 MHz): δ ϭ 3.88–3.83 (m, 3 H), 3.32 (t, J ϭ
9.7 Hz, 1 H), 1.69–1.61 (m, 2 H), 1.29–1.24 (m, 1 H), 1.01 (d, J ϭ (2.90 mL, 2.46 g, 23.6 mmol, 3.9 equiv.) and pTsOH H2O (250 mg,
6.2 Hz, 3 H), 0.92 (s, 9 H), 0.91 (s, 9 H), 0.05 (s, 6 H), 0.04 (s, 6 1.31 mmol, 0.22 equiv.). After 24 h, the reaction was neutralized
H). Further elution gave 28 (125 mg, 89%): m.p. 92–95 °C. –
[α]D ϭ –36.72 (c ϭ 0.50). – H NMR (300 MHz): δ ϭ 3.86–3.85 was purified by FC (hexane/EtOAc, 5:1 Ǟ 3:1), giving 29 (1.06 g,
with Et3N (1.0 mL) and was concentrated to give a residue which
1
(m, 1 H), 3.76–3.72 (m, 2 H), 3.69–3.67 (m, 1 H), 2.46 (br s, 1 H), 59%) (whose physical properties were identical to the material de-
2.30 (br s, 1 H), 2.04–1.99 (m, 1 H), 1.64–1.63 (m, 1 H), 1.60–1.59
(m, 1 H), 1.03 (d, J ϭ 6.9 Hz, 3 H), 0.90 (s, 18 H), 0.09–0.03 (m,
12 H). – 13C NMR (50 MHz): δ ϭ 75.09, 73.98, 73.32, 70.53, 31.50,
28.34, 26.08, 18.00, 18.06, 17.21, –4.59, –4.64. – C19H42O4Si2
(390.71): calcd. C 58.41, H 10.85; found C 58.23, H 10.31.
scribed above) and 30 (105 mg, 6%).
Phenyl 3,4-O-Isopropylidene-1-thio-α-
L-fucopyranoside (30): To a
solution of -fucose (4.00 g, 24.4 mmol) in DMF (12.0 mL) con-
taining Et3N (20 mL, 14.5 g, 14 mmol, 5.9 equiv.), cooled to 0 °C,
was added, dropwise, TMSCl (18.0 mL, 15.4 g, 142 mmol, 5.8
equiv.). The mixture was warmed to room temp. and stirred for
2 h. Then the reaction was quenched with H2O/ice (160 mL) and
extracted with pentane (400 mL). The organic phase was washed
with H2O/ice (3 ϫ 120 mL), dried (Na2SO4), and concentrated to
give a residue which was dissolved in CH2Cl2 (60 mL) and treated
with TMSI (3.52 mL, 5.17 g, 25.9 mmol, 1.1 equiv.) at room temp.
for 1 h. The reaction was then cooled to 5 °C, and a solution of
PhSH (2.64 mL, 2.85 g, 25.8 mmol, 1.1 equiv.) and 2,6-di-tert-bu-
tyl-4-methylpyridine (5.00 g, 24.3 mmol, 1.0 equiv.) in CH2Cl2
(60 mL) was added. After 21 h, MeOH (120 mL) was added, and
stirring was continued for 30 min. Evaporation of the solvent gave
crude phenyl 1-thio-α- and -β--fucopyranoside, which was dis-
solved in Me2CO (120 mL) and treated with 2,2-dimethoxypropane
(6.00 mL, 5.08 g, 48.8 mmol, 2.0 equiv.) and pTsOH H2O (240 mg,
1.26 mmol, 0.052 equiv.). After 90 min, the reaction was neutral-
ized with Et3N (4.00 mL) and concentrated to give a residue which
was purified by FC (hexane/EtOAc, 6:1 Ǟ 3:1 Ǟ 1:1), giving 29
(340 mg, 4%) (see above physical and spectroscopic data) and 30
(5.55 g, 77%): m.p. 72–74 °C. – [α]D ϭ –278.0 (c ϭ 1.1, MeOH). –
1H NMR (200 MHz): δ ϭ 7.52–7.47 (m, 2 H), 7.30–7.27 (m, 3 H),
5.55 (d, J ϭ 4.7 Hz, 1 H), 4.57 (dt, J ϭ 2.0 Hz, J ϭ 6.7 Hz, 1 H),
4.20–4.04 (m, 3 H), 2.65 (d, J ϭ 5.8 Hz, 1 H), 1.53 (s, 3 H), 1.37
(s, 3 H), 1.35 (d, J ϭ 6.7 Hz, 3 H). – 13C NMR (50 MHz): δ ϭ
134.16, 131.31, 129.02, 127.26, 109.42, 88.24, 76.27, 75.73, 69.98,
65.35, 27.90, 25.92, 16.22. – C15H20O4S (296.38): calcd. C 60.79, H
6.80, S 10.82; found C 60.59, H 7.01, S 10.87.
5a-Carba-α-L-fucopyranose (1): To a solution of 28 (85 mg,
0.22 mmol) in THF (7 mL) was added Bu4NF (224 mg, 0.87 mol,
4 equiv.); the reaction mixture was stirred at room temp. for 2 h.
The solvent was then evaporated and the residue was purified by
FC (CH2Cl2/MeOH 10:1) to give a mixture which was purified by
filtration through florisil and eluted with CH2Cl2/MeOH (5:1) to
give 1 (19 mg, 51%): m.p. 112–115 °C (ref.[8a,8e] 115 °C). – [α]D
ϭ
–49.9 (c ϭ 0.40, EtOH) (ref.[8a,8e] [α]D ϭ –58). – 1H NMR (300 MHz,
D2O): 4.07 (q, J ϭ 3.0 Hz, 1 H), 3.88 (t, J ϭ 2.6 Hz, 1 H), 3.76
(dd, J ϭ 3.0 Hz, J ϭ 10.3 Hz, 1 H), 3.69 (dd, J ϭ 3.0 Hz, J ϭ
10.3 Hz, 1 H, H-3), 2.03–1.94 (m, 1 H), 1.61 (m, 2 H), 0.99 (d, J ϭ
6.95 Hz, 3 H). – 13C NMR (50 MHz): δ ϭ 75.47, 72.65, 72.11,
70.81, 33.67, 29.83, 17.75.
Phenyl 3,4-O-Isopropylidene-1-thio-β-
L-fucopyranoside (29).
–
Method a: A suspension of -fucose (5.00 g, 30.5 mmol) in pyridine
(15 mL) was treated with Ac2O (60 mL, 64.9 g, 636 mmol, 21
equiv.) and was heated to 100 °C for 1 h. The mixture was cooled
to room temp. and was concentrated (coevaporating with PhMe,
2 ϫ 50 mL) to give a residue which was dissolved in CH2Cl2
(100 mL) and cooled to –20 °C. PhSH (3.68 mL, 3.97 g, 36.0 mmol,
1.2 equiv.) and SnCl4 (3.65 mL, 8.12 g, 31.2 mmol, 1.0 equiv.) were
added dropwise, and the temperature was raised to 0 °C within 1 h.
After 2 h, the temperature was raised to room temp., and the mix-
ture was diluted with CH2Cl2 (100 mL) and washed with 1  H2SO4
(75 mL), sat. NaHCO3 (75 mL), and H2O (75 mL). Evaporation of
the solvent gave a residue which was dissolved in MeOH (100 mL)
and treated with NaOMe (0.7  in MeOH, 10 mL) at room temp.
for 20 h. The reaction was then neutralized with Amberlyst IR-120
(Hϩ), filtered and concentrated to give crude phenyl 1-thio-α- and -
β--fucopyranoside. This mixture was dissolved in Me2CO
(100 mL) and treated with 2,2-dimethoxypropane (15.0 mL, 12.7 g,
122 mmol, 4.0 equiv.) and pTsOH H2O (580 mg, 3.05 mmol, 0.10
equiv.). After 12 h, the reaction was neutralized with Et3N
(1.00 mL) and concentrated to give a residue which was purified
by FC (hexane/EtOAc, 5:1 Ǟ 3:1), giving 29 (6.30 g, 69%) and 30
(331 mg, 4%). – 29: M.p. 82–83 °C. – [α]D ϭ ϩ35.1 (c ϭ 1.0,
MeOH). – 1H NMR (200 MHz): δ ϭ 7.55–7.51 (m, 2 H), 7.30–
7.26 (m, 3 H), 4.40 (d, J ϭ 10.3 Hz, 1 H), 4.07–3.99 (m, 2 H), 3.85
(dt, J Ͻ 1 Hz, J ϭ 6.4 Hz, 1 H), 3.52 (ddd, J ϭ 2.3 Hz, J ϭ 6.5 Hz,
J ϭ 10.3 Hz, 1 H), 2.58 (d, J ϭ 2.3 Hz, 1 H), 1.41 (d, J ϭ 6.4 Hz,
3 H), 1.40 (s, 3 H), 1.32 (s, 3 H). – 13C NMR (50 MHz): δ ϭ 132.58,
132.12, 128.90, 127.94, 109.81, 87.76, 79.04, 76.25, 72.71, 71.22,
28.08, 26.30, 16.90. – C15H20O4S (396.38): calcd. C 60.79, H 6.80,
S 10.82; found C 60.59, H 6.97, S 10.73. – Method b: To a suspen-
Phenyl
1,1-Dioxo-3,4-O-isopropylidene-1-thio-β-L-fucopyranoside
(31): To a solution of 29 (805 mg, 2.72 mmol) in CH2Cl2 (25 mL)
was added NaHCO3 (550 mg, 6.55 mmol, 2.4 equiv.) and 86%
mCPBA (1.30 g, 6.46 mmol, 2.4 equiv.) at room temp. After 2 h,
CH2Cl2 (25 mL) was added and the solution was washed with sat.
NaHCO3 (3 ϫ 25 mL). The organic layer was dried (Na2SO4) and
concentrated to give a residue which was purified by FC (hexane/
EtOAc, 4:1 Ǟ 3:1 Ǟ 1:1), affording 31 (800 mg, 90%): m.p. 141–
143 °C. – [α]D ϭ –33.0 (c ϭ 1.1). – 1H NMR (200 MHz): δ ϭ 7.97–
7.93 (m, 2 H), 7.72–7.55 (m, 3 H), 4.16 (d, J ϭ 9.9 Hz, 1 H), 4.11
(dd, J ϭ 5.5 Hz, J ϭ 6.3 Hz, 1 H), 3.99 (dd, J ϭ 5.5 Hz, J ϭ
2.0 Hz, 1 H), 3.87 (ddd, J ϭ 1.7 Hz, J ϭ 6.3 Hz, J ϭ 9.9 Hz, 1 H),
3.84 (dt, J ϭ 2.0 Hz, J ϭ 6.4 Hz, 1 H), 2.58 (d, J ϭ 1.7 Hz, 1 H),
1.33 (s, 3 H), 1.32 (d, J ϭ 6.4 Hz, 3 H), 1.31 (s, 3 H). – 13C NMR
(50 MHz): δ ϭ 135.30, 134.25, 129.76, 128.86, 110.06, 91.20, 78.79,
75.41, 73.24, 68.64, 27.77, 26.23, and 16.46. – C15H20O6S (328.38):
calcd. C 54.86, H 6.14; found C 54.84, H 5.98.
Reaction of 31 with Lithium Naphthalenide: To a solution of 31
sion of -fucose (1.00 g, 6.09 mmol) in MeCN (15 mL) was added (50 mg, 0.15 mmol) in THF (1 mL), cooled to –78 °C, was added
Eur. J. Org. Chem. 2000, 1285Ϫ1296 1293

´
M. Carpintero, C. Jaramillo, A. Fernandez-Mayoralas
FULL PAPER
BuLi (1.38  in THF, 0.11 mL, 0.152 mmol, 1.0 equiv.). After
0.16 mmol, 1.1 equiv.). After 5 min, tBuLi (1.64  in pentane, 740
30 min, isobutyraldehyde (43 µL, 34.0 mg, 0.47 mmol, 3.1 equiv.) µL, 1.21 mmol, 8.1 equiv.) was added dropwise, and after another
and lithium naphthalenide (1  in THF, 0.80 mL, 0.8 mmol, 5.3
equiv.) were added, and stirring was continued for an additional
30 min. Then the reaction was quenched with 20% AcOH in THF
20 min, isobutyraldehyde (70 µL, 55.3 mg, 0.767 mmol, 5.1 equiv.)
was added. After 100 additional min, the reaction was quenched
at –78 °C with sat NH4Cl (0.50 mL), was warmed to room temp.,
(1.00 mL), warmed to room temp., diluted with CH2Cl2 (20 mL), diluted with H2O (5 mL), and washed with CH2Cl2 (3 ϫ 20 mL).
and washed with H2O (10 mL). The organic layer was dried
(Na2SO4) and concentrated to give a residue which was purified by
FC. Elution with hexane/EtOAc (8:1) afforded 32 (10.2 mg, 36%),
The combined organic layers were dried (Na2SO4) and concen-
trated to give a residue which was purified by FC. Elution with
hexane/EtOAc 10:1 gave first 37 (12.2 mg, 31%), then 38 (11.1 mg,
which was characterized as its diacetate 34: m.p. 131–134 °C. – 28%) and 33 (4 mg, 22%). To a solution of 37 (12 mg) in acetone
[α]D ϭ –111.1, (c ϭ 1.0). – 1H NMR (400 MHz, [D6]benzene): δ ϭ
(1.2 mL) was added dimethoxypropane (30 µL) and pTsOH H2O
5.37 (dd, J ϭ 3.0 Hz, J ϭ 3.2 Hz, 1 H), 4.32 (d, J ϭ 2.4 Hz, 1 H), (1 mg). After 24 h, the reaction mixture was neutralized with Et3N
4.18 (dd, J ϭ 3.9 Hz, J ϭ 7.2 Hz, 1 H), 4.09 (dt, J ϭ 1.8 Hz, J ϭ
and concentrated. The residue was purified by FC (hexane/EtOAc,
6.6 Hz, 1 H), 3.74 (dd, J ϭ 1.8 Hz, J ϭ 7.2 Hz, 1 H), 1.76 (s, 3 H), 20:1) to give 39 as an oil. – [α]D ϭ –19.7 (c ϭ 1.1). – 1H NMR
1.49 (s, 3 H), 1.28 (d, J ϭ 6.5 Hz, 3 H), 1.17 (s, 3 H). – 13C NMR (200 MHz): δ ϭ 4.30 (dt, J ϭ 1.4 Hz, J ϭ 6.7 Hz, 1 H), 4.27 (dd,
(50 MHz): δ ϭ 169.85, 109.52, 75.86, 73.35, 70.69, 70.33, 66.94,
J ϭ 2.7 Hz, J ϭ 7.9 Hz, 1 H), 4.11 (ddd, J ϭ 1.4 Hz, J ϭ 7.9 Hz,
27.05, 24.91, 18.06. – MS (FAB, m-NBA); m/z: 459.3 [M ϩ 1]ϩ. – 1 H), 3.98 (t, J ϭ 2.7 Hz, 1 H), 3.73 (dd, J ϭ 1.4 Hz, J ϭ 2.5 Hz,
C22H34O10 (458.50): calcd. C 57.63, H 7.47; found C 57.21, H 7.48.
1 H), 3.16 (dd, J ϭ 1.4 Hz, J ϭ 9.4 Hz, 1 H), 2.09 (dtt, J ϭ 6.7 Hz,
J ϭ 6.7 Hz, J ϭ 9.4 Hz, 1 H), 1.49 (s, 3 H), 1.41 (s, 6 H), 1.36 (s,
Further elution with hexane/EtOAc (2:1) gave 33 (8.3 mg, 29%):
1
m.p. 82–86 °C. – [α]D ϭ –68.8 (c ϭ 1.0). – H NMR (200 MHz): 3 H), 1.23 (d, J ϭ 6.7 Hz, 3 H), 0.95 (d, J ϭ 6.7 Hz, 3 H), 0.92 (d,
δ ϭ 4.05 (dd, J ϭ 5.4 Hz, J ϭ 2.2 Hz, 1 H), 3.96 (dd, J ϭ 5.4 Hz,
J ϭ 6.5 Hz, 3 H). – 13C NMR (50 MHz): δ ϭ 108.27, 98.03, 75.73,
J ϭ 6.3 Hz, 1 H), 3.94 (dd, J ϭ 5.3 Hz, J ϭ 11.0 Hz, 1 H), 3.84 74.54, 72.23, 76.84, 75.93, 61.49, 29.09, 27.15, 23.72, 23.60, 18.57,
(dddd, J ϭ 3.6 Hz, J ϭ 5.3 Hz, J ϭ 6.3 Hz, J ϭ 9.9 Hz, 1 H), 3.78 18.35, 17.55, 16.86. – C16H28O5 (280.32): calcd. C 63.97, H 9.40;
(dt, J ϭ 2.2 Hz, J ϭ 6.5 Hz, 1 H), 3.12 (dd, J ϭ 9.9 Hz, J ϭ
11.0 Hz, 1 H), 2.14 (d, J ϭ 3.6 Hz, 1 H), 1.54 (s, 3 H), 1.38 (s, 3 to the method described for 39 and the residue was purified by FC
H), 1.37 (d, J ϭ 6.5 Hz, 3 H). – 13C NMR (50 MHz): δ ϭ 119.46,
(hexane/EtOAc, 20:1) to give 40: m.p. 40–42 °C. – [α]D ϭ ϩ27.3
79.64, 76.24, 72.35, 69.36, 68.15, 28.20, 26.24, 16.84. – C9H16O4 (c ϭ 1.1). – H NMR (200 MHz): δ ϭ 4.86 (dd, J ϭ 2.7 Hz, J ϭ
found C 63.56, H 9.66. – A solution of 38 was treated according
1
(188.22): calcd. C 57.43, H 8.57; found C 57.14, H 8.41.
7.5 Hz, 1 H), 4.13 (dd, J ϭ 5.3 Hz, J ϭ 2.7 Hz, 1 H), 4.11–4.00 (m,
2 H), 4.08 (dd, J ϭ 5.3 Hz, J ϭ 8.4 Hz, 1 H), 3.34 (dd, J ϭ 8.4 Hz,
J ϭ 5.4 Hz 1 H), 1.82 (dtt, J ϭ 5.4 Hz, J ϭ 6.5 Hz, 1 H), 1.51 (s,
3 H), 1.37 (s, 3 H), 1.36 (s, 3 H), 1.31 (s, 3 H), 1.18 (d, J ϭ 6.4 Hz,
3 H), 1.00 (d, J ϭ 6.8 Hz, 3 H), 0.93 (d, J ϭ 6.7 Hz, 3 H). – 13C
NMR (50 MHz): δ ϭ 109.16, 100.86, 74.01, 73.43, 72.93, 72.74,
65.26, 63.99, 30.48, 26.21, 24.77, 24.21, 23.66, 18.93, 17.47, 16.37. –
C16H28O5 (280.32): calcd. C 63.97, H 9.40; found C 64.22, H 9.68.
Phenyl 1-Oxo-3,4-O-isopropylidene-1-thio-α- -fucopyranoside (35):
L
A solution of 30 (1.55 g, 3.88 mmol) in CH2Cl2 (70 mL) containing
NaHCO3 (390 mg, 4.64 mmol, 1.2 equiv.) was cooled to –78 °C
and treated with a solution of 85% mCPBA (780 mg, 3.84 mmol,
0.99 equiv.) in CH2Cl2 (20 mL). After 60 min, the reaction was
warmed to room temp., diluted with CH2Cl2 (75 mL), and washed
with Na2S3O3 (50 mL) and NaHCO3 (50 mL). The organic layer
was dried (Na2SO4) and concentrated to give a residue which was
purified by FC (hexane/EtOAc, 3:1Ǟ2:1Ǟ1:2), affording 35
(1.16 g, 96%): m.p. 122–125 °C. – [α]D ϭ –86.3 (c ϭ 1.0). – 1H
NMR (200 MHz): δ ϭ 7.73–7.69 (m, 2 H), 7.59–7.54 (m, 3 H),
5.75 (br. s, 1 H), 4.64 (dt, J ϭ 1.4 Hz, J ϭ 6.5 Hz, 1 H), 4.55 (d,
J ϭ 3.0 Hz, 1 H), 4.49 (t, J ϭ 3.0 Hz, 1 H), 4.45 (dd, J ϭ 3.0 Hz,
J ϭ 7.5 Hz, 1 H), 4.21 (dd, J ϭ 1.4 Hz, J ϭ 7.5 Hz, 1 H), 1.36 (s,
3 H), 1.31 (s, 3 H), 1.30 (d, J ϭ 6.5 Hz, 3 H). – 13C NMR
(50 MHz): δ ϭ 140.11, 131.36, 129.05, 125.29, 109.61, 93.15, 74.54,
73.87, 68.87, 64.27, 26.15, 24.22, 16.49. – C15H20O5S (312.38):
calcd. C 57.67, H 6.45; found C 57.37, H 6.39.
Phenyl 1-Oxo-3,4-O-isopropylidene-1-thio-β-L-fucopyranoside (41):
A solution of 29 (3.75 g, 12.7 mmol) in CH2Cl2 (150 mL) con-
taining NaHCO3 (1.20 g, 14.3 mmol, 1.1 equiv.) was cooled to –78
°C and treated with a solution of 85% mCPBA (2.39 g, 11.8 mmol,
0.93 equiv.) in CH2Cl2 (50 mL). After 30 min, the reaction was
warmed to room temp. and was washed with Na2S3O3 (100 mL)
and NaHCO3 (100 mL). The organic layer was dried (Na2SO4) and
concentrated to give a residue which was purified by FC (hexane/
EtOAc, 1:1 Ǟ EtOAc), affording 41 (3.54 g, 89%): m.p. 97–101
1
°C. – [α]D ϭ –80.4 (c ϭ 1.0, CHCl3). – H NMR (200 MHz): δ ϭ
7.75–7.67 (m, 2 H), 7.56–7.52 (m, 3 H), 4.37 (ddd, J ϭ 1.7 Hz, J ϭ
5.9 Hz, J ϭ 8.2 Hz, 1 H), 4.29 (d, J ϭ 1.7 Hz, 1 H), 4.14 (t, J ϭ
5.9 Hz, 1 H), 4.05 (dd, J ϭ 2.2 Hz, J ϭ 5.9 Hz, 1 H), 3.99 (d, J ϭ
8.2 Hz, 1 H), 3.79 (dt, J ϭ 2.2 Hz, J ϭ 6.5 Hz, 1 H), 1.60 (s, 3 H),
1.38 (s, 3 H), 1.34 (d, J ϭ 6.5 Hz, 3 H). – 13C NMR (50 MHz):
δ ϭ 141.95, 131.46, 128.95, 124.72, 119.95, 94.11, 77.00, 74.95,
71.52, 68.58, 27.14, 25.50, 16.37. – C15H20O5S (312.38): calcd. C
57.67, H 6.45; found C 57.36, H 6.50.
Deuteration Experiments (Table 2): Under argon, a solution of 35
(0.033 ) in dry solvent at –78 °C was treated with MeLi LiBr (1.5
 in Et2O, 1.1 equiv.), followed by slow addition of tBuLi (1.64 
in hexanes, 5 equiv.). After 20 min, CD3OD (5 equiv.) was added,
the mixture was stirred for 5 min at –78 °C, and it was then
quenched with saturated aqueous solution of NH4Cl. After separ-
ating the water and CH2Cl2 layers, the organic layer was dried
(Na2SO4) and concentrated. The crude mixture was analyzed by
4,8-Anhydro-3,5:6,7-di-O-isopropylidene-2-C-methyl-1,2,9-trideoxy-
1
1H NMR (200 MHz). – H NMR (200 MHz, selected data): δ ϭ
L-threo-D-galacto- and -L-threo-D-talo-nonitol (43 and 44): To a sus-
4.20 (dd, J4,5 ϭ 1.5 Hz, J3,4 ϭ 7.5 Hz, H-4 of 36), 4.05 (dd, J4,5
2.2 Hz, J3,4 ϭ 7.5 Hz, H-4 36 and 33), 3.12 (dd, J1ax,2 ϭ 9.9 Hz,
J1ax,1eq ϭ 11.0 Hz, H-1ax of 33).
ϭ
pension of 41 (47 mg, 0.15 mmol) in Et2O (4.5 mL), cooled to
–78 °C, was added, dropwise, MeLi LiBr (1.5  in Et2O, 105 µL,
0.158 mmol, 1.1 equiv.). After 5 min, tBuLi (1.64  in pentane, 740
µL, 1.21 mmol, 8.1 equiv.) was added dropwise, and after another
20 min, isobutyraldehyde (70 µL, 55.3 mg, 0.78 mmol, 5.1 equiv.)
was added. After an additional 100 min, the reaction was quenched
at –78 °C with sat. NH4Cl (0.50 mL); it was warmed to room temp.,
4,8-Anhydro-3,5:6,7-di-O-isopropylidene-2-C-methyl-1,2,9-trideoxy-
L-threo-
D-ido and L-threo-D-gulo-nonitol (39 and 40): To a suspen-
sion of 35 (47 mg, 0.15 mmol) in Et2O (4.5 mL), cooled to –78 °C,
was added, dropwise, MeLi LiBr (1.5
1294
 in Et2O, 105 µL,
Eur. J. Org. Chem. 2000, 1285Ϫ1296

carba- and C-Glycosyl Analogs of Fucopyranosides
FULL PAPER
D. E. Levy, C. Tang, The Chemistry of C-Glycosides, Pergamon,
[9]
diluted with H2O (5 mL), and washed with CH2Cl2 (3 ϫ 20 mL).
The combined organic layers were dried (Na2SO4) and concen-
trated to give a residue which was chromatographed (hexane/
EtOAc, 5:1 Ǟ 2:1) to remove remaining 41. The diastereomeric
mixture of C-glycosides, which contained 33, were treated with iso-
propylidene according to the method described for 39 afforded 43
and 44, which were separated by FC. Elution with hexane/EtOAc
(50:1) gave 43 (8.6 mg, 19%): m.p. 145–147 °C. – [α]D ϭ –43.3 (c ϭ
1.1). – 1H NMR (200 MHz): δ ϭ 4.11–3.99 (m, 2 H), 3.84 (dt, J ϭ
1.9 Hz, J ϭ 6.6 Hz, 1 H), 3.71 (dd, J ϭ 7.0 Hz, J ϭ 9.7 Hz, 1 H),
3.60 (dd, J ϭ 3.4 Hz, J ϭ 9.4 Hz, 1 H), 2.89 (t, J ϭ 9.6 Hz, 1 H),
1.96 (dtt, J ϭ 3.4 Hz, J ϭ 6.8 Hz, J ϭ 7.0 Hz, 1 H), 1.56 (s, 3 H),
1.49 (s, 3 H), 1.41 (s, 3 H), 1.37 (d, J ϭ 6.6 Hz, 3 H), 1.36 (s, 3 H),
0.96 (d, J ϭ 7.0 Hz, 3 H), 0.90 (d, J ϭ 6.8 Hz, 3 H). – 13C NMR
(50 MHz): δ ϭ 109.306, 101.81, 76.57, 76.37, 74.80, 72.70, 72.09,
29.27, 28.65, 28.45, 26.28, 19.31, 18.86, 16.83, 16.10. – C16H28O5
(300.39): calcd. C 63.97, H 9.40; found C 64.02, H 9.41. – Further
elution with hexane/EtOAc 20:1 gave 44 (10.7 mg, 24%): m.p. 75–
Exeter, 1995.
[10]
For samarium diiodide promoted pinacol coupling of related
[10a]
carbohydrate derivatives, see:
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(m, 2 H), 3.78 (dt, J ϭ 2.3 Hz, J ϭ 6.7 Hz, 1 H), 3.66 (dd, J ϭ
8.6 Hz, J ϭ 9.6 Hz, 1 H), 3.42 (dd, J ϭ 6.3 Hz, J ϭ 9.5 Hz, 1 H),
3.19 (dd, J ϭ 6.3 Hz, J ϭ 9.6 Hz, 1 H), 2.04 (dtt, J ϭ 6.5 Hz, J ϭ
6.7 Hz, J ϭ 9.5 Hz, 1 H), 1.56 (s, 3 H), 1.41 (s, 3 H), 1.37 (d, J ϭ
6.6 Hz, 3 H), 1.35 (s, 3 H), 1.33 (s, 3 H), 0.94 (d, J ϭ 6.7 Hz, 3 H),
0.94 (d, J ϭ 6.5 Hz, 3 H). – 13C NMR (50 MHz): δ ϭ 109.32,
99.31, 77.00, 76.62, 76.31, 74.99, 74.42, 70.87, 28.52, 27.08, 26.31,
25.17, 22.94, 19.30, 16.75. – C16H28O5 (300.39): calcd. C 63.97, H
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(2:1) gave 33 (7.4 mg, 26%), whose physical properties were ident-
ical to the material described above.
[14]
[15]
The formation of 13 was evidenced by the presence of a singlet
at δ ϭ 4.04, assigned to the methylene of the bromomethylsilyl
1
group, in its H NMR (CDCl3) spectrum.
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This was evidenced by comparison of the coupling constants
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Scheme 6).
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Acknowledgments
Financial support by DGES (Grants No. PB96–0828 and PB96–
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ledged. We also thank Prof. M. Bernabe for helpful discussions.
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1
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´
Dimer 32 was characterized as its diacetate 34, the H NMR
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of which showed signals for an α-configured fucopyranosyl
unit (J1,2 ϭ 3.0 Hz), but no signals were observed for an agly-
con moiety. The mass spectral data agreed with a structure
whose mass was composed of two fucopyranosyl units.
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A. Fernandez-Mayoralas, C. Jaramillo, J. Org. Chem. 1997, 62,
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fucopyranosyl ring of 39 and 40 has a skew conformation. The
small J1,7 for 39 (1.4 Hz) was indicative of the R configuration
at C-7 with a boat conformation of the dioxane ring. On the
other hand, the large J1,7 (8.4 Hz) for 40 agreed with the S
configuration at C-7 with a chair conformation of the diox-
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Eur. J. Org. Chem. 2000, 1285Ϫ1296
1295

´
M. Carpintero, C. Jaramillo, A. Fernandez-Mayoralas
FULL PAPER
[33]
Selected 1H NMR (200 MHz) data for 46: δ ϭ 5.50 (d, J ϭ
(t, J ϭ 2.6 Hz, 1 H), 4.60 (dd, J ϭ 2.2, 7.9 Hz, 1 H), 4.40 (dd,
J ϭ 1.9, 7.9 Hz, 1 H), 4.38 (dd, J ϭ 2.7, 8.6 Hz, 1 H), 4.29 (dd,
J ϭ 2.3, 5.0 Hz, 1 H), 4.26 (dd, J ϭ 2.7, 7.6 Hz, 1 H), 4.16 (dd,
J ϭ 1.7, 5.0 Hz, 1 H), 2.08 (s, 3 H), 2.00 (s, 3 H).
Received September 6, 1999
5.1 Hz, 1 H), 5.32 (dd, J ϭ 8.0, 4.0 Hz, 1 H), 5.11 (dd, J ϭ
3.9, 4.3 Hz, 1 H), 4.60 (dd, J ϭ 3.0, 7.5 Hz 1 H), 4.53 (dd, J ϭ
4.7, 3.9 Hz, 1 H), 4.34 (dd, J ϭ 7.7, 1.7 Hz, 1 H), 3.96 (dd, J ϭ
Ͻ 1.0, 7.9 Hz, 1 H), 2.09 (s, 3 H), 2.05 (s, 3 H). For 47: δ ϭ
5.53 (d, J ϭ 5.0 Hz, 1 H), 5.42 (dd, J ϭ 5.0, 8.5 Hz, 1 H), 5.21
[O99508]
1296
Eur. J. Org. Chem. 2000, 1285Ϫ1296