Stereoselective C-glycosidation of d-fucose derivatives directed by the protective groups

Article abstract of DOI:10.1016/j.carres.2014.04.005

Stereoselectivity in the C-glycosidation of lactones derived from d-fucose by following Kishi's method, which involves the addition of a nucleophile onto a carbohydrate-derived lactone and subsequent reduction of the lactol, was found to be reliant on the nature of the C2 and C3 protective groups. Lactones bearing TBDMS protecting groups selectively afford 1,3-trans products (α anomer), in which the stereoselective outcome is in apparent concordance with Woerpel's model. On the other hand, their benzylated congeners produce the 1,3-cis products (β anomer) as the major diastereoisomers. The latter results suggest an abnormal behavior during the stereoselective nucleophilic substitution at the anomeric position of the benzylated lactones.

Full text of DOI:10.1016/j.carres.2014.04.005

Accepted Manuscript
Stereoselective C-glycosidation of D-fucose derivatives directed by the protec-
tive groups
Omar Cortezano-Arellano, Camilo A. Meléndez-Becerra, Fernando Cortés,
Fernando Sartillo-Piscil, Alejandro Cordero-Vargas
PII:
S0008-6215(14)00155-4
DOI:
http://dx.doi.org/10.1016/j.carres.2014.04.005
CAR 6722
Reference:
Carbohydrate Research
To appear in:
Received Date:
Revised Date:
Accepted Date:
27 February 2014
31 March 2014
4 April 2014
Please cite this article as: Cortezano-Arellano, O., Meléndez-Becerra, C.A., Cortés, F., Sartillo-Piscil, F., Cordero-
Vargas, A., Stereoselective C-glycosidation of D-fucose derivatives directed by the protective groups, Carbohydrate
Research (2014), doi: http://dx.doi.org/10.1016/j.carres.2014.04.005
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Stereoselective C-glycosidation of D-fucose derivatives directed by the
protective groups
Omar Cortezano-Arellano,[a]† Camilo A. Meléndez-Becerra,[a] Fernando Cortés,[b]
Fernando Sartillo-Piscil[c] and Alejandro Cordero-Vargas[a]*
[a]
Instituto de Química, Universidad Nacional Autónoma de México. Circuito exterior s/n, Ciudad Universitaria, 04510, México,
D.F., Mexico
Fax: +52 55 56162217
*Corresponding autor, E-mail: acordero@unam.mx
[b]
[c]
†
Centro Conjunto de Investigación en Química Sustentable UAEMex-UNAM, carretera Toluca-Atlacomulco Km 14.5, Toluca,
Mexico, 50200.
Centro de Investigación de la Facultad de Ciencias Químicas, BUAP, 14 sur esq. San Claudio, San Manuel, 72570, Puebla,
Mexico.
Present adress: Centro de Investigación de la Facultad de Ciencias Químicas, BUAP, 14 sur esq. San Claudio, San Manuel, 72570,
Puebla, Mexico.
Abstract. Stereoselectivity in the C-glycosidation of lactones derived from D-fucose by following Kishi’s method, which
involves the addition of a nucleophile onto a carbohydrate-derived lactone and subsequent reduction of the lactol, was
found to be reliant on the nature of the C2 and C3 protective groups. Lactones bearing TBDMS protecting groups
selectively afford 1,3-trans products (α anomer), in which the stereoselective outcome is in apparent concordance with
Woerpel’s model. On the other hand, their benzylated congeners produce the 1,3-cis products (β anomer) as the major
diastereoisomers. The latter results suggest an abnormal behaviour during the stereoselective nucleophilic substitution at
the anomeric position of the benzylated lactones.
Keywords: Carbohydrates / Stereoselectivity / Lactones / Fucose derivatives
1. Introduction
Stereoselective C-glycosidation of furanose derivatives represents an important and useful tool for the
preparation of carbohydrate-derived molecules with biological activity.1 There are a number of available
methods for achieving C-glycosidation, including Friedel-Crafts type reactions,2,3 direct nucleophilic addition
to an activated carbohydrate4 or polarity inversion,5 amongst others.6 One of the most convenient C-
glycosidation methods is the 2-step protocol developed by Kishi.7 In this methodology, a carbohydrate
derived lactone (1) is treated with a suitable organometallic nucleophile, and the resulting hemiacetal (2) is
then reduced with triethylsilane and a Lewis acid to afford the desired C-glycoside 3 (Scheme 1).
Scheme 1. The Kishi method for the preparation of C-glycosides.
In furanoses, the stereoselective reduction of a lactol intermediary is usually explained by the Woerpel
model,8 which posits, that the oxocarbenium ion, generated by the Lewis acid generates an, which adopts two
folded conformations 2B and 2C, 2B being the most favored because the pseudo-axial orientation of the
alkoxy C3 substituent stabilizes the cation by electrostatic interactions. Further attack of the nucleophile (H-
for the case of the Kishi protocol) from the inside face of the oxocarbenium ion furnishes the 1,3-trans
product 3B as the major isomer.

Scheme 2. Woerpel’s model for nucleophilic substitution in lactol derived furanose cations.
2. Results and Discussion
During the course of a project directed towards the total synthesis of gilvocarcins,9,10 we found that the
stereoselectivity in the reduction of lactols 2A, derived from D-fucose, depends on the protective groups of
the carbohydrate motif. Whereas carbohydrates bearing TBDMS groups afford α-anomers (e.g. 3B, 1,3-
trans), in which the selectivity can be explained in terms of the Woerpel model, carbohydrates protected with
Bn groups invert the stereoselectivity, yielding the β-anomers (e.g. 3C, 1,3-cis) as the major products. This
paper accounts these observations, which, at the first glance, might be considered as abnormal relative to the
Woerpel model.
A new and promising strategy for the synthesis of gilvocarcins would be the treatment of lactone 5 with the
aryl lithium derived from 4 by treatment with nBuLi (Scheme 3). After some adjustment of the functional
groups, compound 6 would permit the construction of ring B of the natural product. Further standard
transformations wou ld culminate with the total synthesis of the gilvocarcin M.
Scheme 3. Proposed route to gilvocarcin M.
In the event, the reaction between compound 4 and n-butyllithiun followed by the addition of lactone 5a10b
(R=TBDMS) afforded the expected lactol 9, which was subjected immediately to the typical reduction
conditions (Et3SiH, BF3•OEt2, CH2Cl2, -78 °C). To our delight, the desired glycosylarene 10 was formed as a
single α-diastereoisomer; however, the reaction mixture contained considerable amounts of deprotected
products due to the acidic conditions. The crude reduction product was treated with TBAF, to thus obtain triol
10 in 63% overall yield (Scheme 4). The stereochemistry of 10 was determined by single-cristal X-ray
diffraction11 (Figure 1).

Scheme 4. Preparation of C-arylglycoside 10.
Figure 1. ORTEP drawing of compound 10.
In order to circumvent the problems concerning the liability of the TBDMS groups and because more robust
benzyl groups would presumably survive the entire route until completion of the total synthesis, we prepared
lactone 5b (see supporting information for details) and subjected it to the same reaction conditions as for 5a.
To our surprise, the major diastereoisomer formed was 11β (Scheme 5).
Scheme 5. Unexpected switch of diastereoselectivity for lactone 5b.
Stereochemical assignment of the major diastereoisomer 11β was made by chemical correlation of compound
10 into 11α, the minor component detected in the preparation of 11β (Scheme 6).
Scheme 6. Chemical correlation of 11α from 10.
The stereoselectivity reversal observed for lactone 5b was quite surprising because in most of the examples
reported for this type of reaction, benzyl ethers are the preferred protecting scheme and no changes in the
expected stereoselectivity have been observed. In addition, some reports have shown that the Woerpel product
is usually obtained with ribose derivatives12 (2,3-cis), and only a few examples, in which the C2 and C3

substituents are in a trans disposition, have been described. For example, Czernecki and coworkers13 reported
that arabinolactone derivative 12 is transformed into C-arylglycoside 14 by the treatment of the former with
phenyllithium followed by reduction with triethylsilane and BF3•OEt2. However, the authors stated that “one
isomer was isolated in 85% yield, but the anomeric configuration was not firmly established; it is written as β
for convenience of reading”. Similarly, the Wightman group14 treated arabinolactone 12 with either MeLi or
ethynyllithium followed by reduction of lactols 15a-b to afford stereoselectively compounds 16a-b in good to
moderate yields of the β-diastereoisomer (Scheme 7).
Scheme 7. C-Glycosidations of arabinose derivatives reported by Czerneki and Wightman.
Intrigued by our unexpected results in the formation of 11β, we sought to investigate the stereoselectivity
further. First we tested this sequence with other nucleophiles with the aim of verifying whether the reversal of
stereochemistry is due to the complexity of 4. Thus, the reaction sequence was performed with three different
arene nucleophiles (entries 1-6), trimethylsilylacetylide (entries 7 and 8) and methyllithium (entries 9 and 10).
The results for the sequence are shown in Table 1. In all of the cases, the employed methodology was the
same: i) addition of a lithium nucleophile and ii) reduction of the corresponding hemiacteal with Et3SiH and
BF3•OEt2. Due to the above-mentioned lability of the TBDMS groups, and for characterization purposes, in
some cases it was necessary to use an extra step for reprotection of the hydroxyl groups or for complete
deprotection.
Table 1. Synthesis of α or β C-furanosides from lactones 5a or 5b.
Entry
1
Nucleophile
Lactone
Product (yield)
α/β
5a
10 (63%, 3 steps)[d]
10:1
2
3
5b
5a
11 (70%, 2 steps)
1:8
4
only α

17
4
5b
1:7
5
5a
only α
6
18
5b
1:7
7
5a
only α
8
19
MeLi (20)
20
5b
5a
5b
1:10
only α
1:8
9
10
[a] nBuLi (1.4 eq.), THF, -78 °C, then 5a or 5b [b] MeLi (1.4 eq.), THF, -78 °C, then 5a or 5b; [c] Et3SiH (1.1 eq.), BF3•OEt2 (1.1 eq.),
CH2Cl2, -78 °C [d] after steps 1 and 2, the crude was treated with TBAF (6 eq.) in THF at r.t. [e] after steps 1 and 2, the crude was tretaed
with TBDMSCl (6 eq.) and imidazole (6 eq.) in DMF at r.t.
As seen in the Table, the reversal of stereoselectivity upon switching from TBDMS to Bn protecting groups is
general and does not depend on the structure of C1 R group. Complex arenes (entries 1 and 2) and more
simple ones (entries 3-6) afford the same selectivity for the products, which depends only on the nature of the
protective group. The same tendency was observed with TMS-alkynyl (entries 7 and 8) and methyl (entries 9
and 10). The stereochemistry of the products was verified by NOESY experiments, observing a NOE

interaction between H1 and H2 for the α- anomers (absent for the β anomers) and between H1 and H3 for the
β-anomers (absent for the α anomers).
Having established that the switch in stereoselectivity is caused by the protective groups on the carbohydrate
moiety, we proceeded to verify whether the selectivity also depends on the nucleophile strength and whether
it is the steric or electronic demand imposed by the substituents placed at C2 and C3 that is decisive. It is
important to note that Woerpel previously reported that the stereoselectivity is reinforced when substituents at
C2 and C3 are cis oriented (29) but eroded when both substituents are trans oriented (31) (Scheme 8).
Scheme 8. Reinforcement of selectivity with 2,3-cis substituted substrates observed by Woerpel.
Woerpel also observed a complete lack of stereoselectivity when the C2 and C4 substituents are cis oriented
(33).8d For example, allylation of 33 gives a 50:50 mixture of diastereoisomers due to the destabilizing 1,3-
diaxial interactions between substituents at C2 and C4 of conformer 34A, leading to a considerable population
of 34B. Attack of the allyl silane on the inside face of each conformer produces a nearly equimolar
distribution of diastereoisomers (Scheme 9).
Scheme 9. Complete loss of selectivity observed in arabinofuranoses.
On this basis, we decided to use allyltrimethylsilane as the nucleophile to see if a weak nucleophile15 gives the
same results. Lactones 5a-b were reduced with DIBAL to form the corresponding lactols 37a-b (Scheme 10).
When 37a-b were independently treated with allyltrimethylsilane and BF3•OEt2 at room temperature (the
reaction did not proceeded at -78 °C), diastereoselectivity dramatically dropped; however, the tendency
remained the same: lactone 5a produced the β anomer (d.r. 1:2) and lactone 5b the α anomer (d.r. 2:1). The
loss of diastereoselectivity is probably due to the increasing of the temperature (r.t.) or to the weaker
nucleophile.15

Scheme 10. Allylation of lactols 37a and 37b.
Finally, we decided to test whether reversal of the stereochemical outcome is observable when the protective
groups at C2 and C3 are not the same. Thus, lactone 42,16 bearing a TBDMS at C3 and a benzyl group at C2,
as well as its counterpart 44 (i.e. a benzyl group at C3 and a TBDMS at C2), were prepared from known D-
galactose derivative 4117 according to literature procedures16,18 and depicted in Scheme 11.
Scheme 11. Synthesis of lactones 42 and 44 bearing differentiated protective groups at C2 and C3.
With lactones 42 and 44 in hand, we proceeded to test them in the C-glycosidation reaction. When the
glycosidation sequence was carried out using lithium (trimethylsilyl)acetylide as the first nucleophile, and the
lactols reduced under the standard conditions at -78 °C, we were pleased to find out that the 1,3-trans product
(α anomers) were the only detectable diastereoisomer (45 and 46), (Scheme 12). In both cases, due to the
acidic media, the acetonide protection was hydrolysed, providing 45 for the former, and a mixture of
deprotection compounds 46a and 46b for the latter (46b is formed via silyl migration19). For characterization
purposes, crude 46a-b was treated with TBDMSCl, and compound 47 was isolated as the sole product in 30%
yield for 3 steps.
Scheme 12. C-glycosidations with lactones 44 and 45.

At this point, we cannot provide a plausible explanation for the reversed stereoselectivity when both groups,
at C2 and C3 positions of fucose derivatives are benzyl ethers. A detailed mechanistic study is currently in
progress. Furthermore, the above results indicate that: i) the stereoselectivity for the reduction of the lactols
can be modulated by the correct choice of the protecting groups, ii) lactols possessing TBDMS protective
groups afford the α-anomer, whereas their benzylated congeners provide the β-anomer; iii) this inversion is
observed in carbohydrate derivatives possessing 2,3-trans substituents; iv) the phenomenon is observed only
when the C2 and C3 protective groups are the same (both benzyl or both TBDMS).
3. Conclusions
In conclusion, we have demonstrated that the stereoselectivity of the C-glycosidation of lactones derived from
D-fucose by following Kishi’s method can be modulated by the carbohydrate’s protective groups. If the
carbohydrate is protected with TBDMS groups, the α anomer is obtained as nearly the only product. On the
other hand, perbenzylated carbohydrates afford the β anomer as the major product. Further experimental and
theoretical studies are in progress and will be reported soon.
4. Experimental Section
All reactions were carried under an inert atmosphere (Ar) unless is specified otherwise. Commercial reagents
were used as received without further purification. Flash column chromatography was carried out with silica
gel 60 (203-400 mesh ATSM) from Macherey-Nagel GmbH & Co. NMR spectra were recorded in CDCl3
with TMS as an internal standard at room temperature on Jeol Eclipse 300 MHz and Jeol Eclipse 400 MHz
spectrometers. Chemical shifts are reported in parts per million (δ / ppm). The peak patterns are indicated as
follows: s, singlet; d, doublet; dd, doublet of doublet; ddd, doublet of doublet of doublet; t, triplet; q, quartet;
m, multiplet; br, broad; bs, broad single . The coupling constants (J) are reported in Hertz (Hz). 13C NMR
spectra were recorded at 75 MHz and 100 MHz on the same instruments. Assignments of 13C spectra were
performed by DEPT experiments. Mass spectra were recorded on a Jeol JEMAX5065HA mass spectrometer
by Fast atom bombardment (FAB) ionization of low resolution. High resolution mass spectra (HRMS) were
recorded on a Jeol JMSSX-102A spectrometer. Melting points were determined by Reichert microscope
apparatus and were uncorrected.
4.1. General methods for the C-glycosidation
4.1.1. Conditions [a]. To a solution of the corresponding bromoarene or acetylene (1-1.2 mmol) in dry THF
(5 mL) at -78 °C under argon atmosphere was added dropwise nBuLi (1.4 mmol, 1.6 M solution in THF).
After stirring for 1h at -78 °C, a solution of lactone 5a or 5b (1 mmol) in dry THF (5 mL) was transferred to
the reaction flask and the solution was allowed to stir at -78 °C until complete consumption of the starting
material (usually 1.5-2 h, monitored by TLC). The reaction was quenched with saturated aqueous NH4Cl
solution, extracted with CH2Cl2, dried over Na2SO4, filtered and concentrated. The crude lactol was directly
used for the reduction step without further purification.
4.1.2 Conditions [b]. To a solution of MeLi (1 mmol, 1.6 M solution in diethyl ether) in dry THF (5 mL) at -
78 °C under argon atmosphere was added a solution of lactone 5a or 5b (1 mmol) in dry THF (5 mL). The
resulting solution was allowed to stir at -78 °C until complete consumption of the starting material (usually
1.5-2 h, monitored by TLC). The reaction was quenched with saturated aqueous NH4Cl solution, extracted
with CH2Cl2, dried over Na2SO4, filtered and concentrated. The crude lactol was directly used for the
reduction step without further purification.
4.1.3. Conditions [c] (reduction step). To a solution of the crude lactol (1 mmol) in dry CH2Cl2 at -78 °C
were added 2 mmol of Et3SiH, followed by BF3•OEt2 (2 mmol, added dropwise). The reaction mixture was
stirred at -78 °C for 2 h, neutralized (pH 6-7) with NEt3 and extracted with CH2Cl2. The combined organic
extracts were dried (Na2SO4), filtered and concentrated under reduced pressure. The residue was either
purified by flash column chromatography (for Bn protective groups) or subjected immediately to the
deprotection or reprotection reaction (TBDMS protections).

4.1.4. Conditions [d] (deprotection). To a solution of the crude C-glycoside (1 mmol) in THF (10 mL) at
room temperature was added TBAF (6 mmol of a 1M solution in THF) and the mixture was allowed to stir at
r.t. for 30 minutes. Water was then added and the reaction was extracted with ethyl acetate, the organic phase
was dried and concentrated. The residue was purified by flash column chromatography.
4.1.5. Conditions [e] (reprotection). To a solution of the crude C-glycoside (1 mmol) in DMF (4 mL) at r.t.
was added TBDMSCl (6 mmol) and imidazole (6 mmol). The mixture was stirred at r.t. for 24 h and then
extracted with ethyl acetate. The organic phase was washed with saturated aqueous NaCl, dried (Na2SO4),
filtered and concentrated under reduced pressure. The residue was purified by flash column chromatography .
4.2. 1-(2-(Benzyloxy)-5-(α-D-fucofuranosyl)phenyl ethanone (10). The title compound was obtained from
4 (0.5 g, 1.43 mmol) and lactone 5a (0.866 g, 1.72 mmol), following conditions [a], [c] and [d]. Purification
by flash chromatography (silica gel, hexane:ethyl acetate 1:1) afforded C-glycoside 10 in 63% (for 3 steps) as
colorless crystals (mp = 140-142 °C). 1H NMR (300 MHz, CDCl3): δ 7.7 (d, 1H, CH arom., J= 2.4 Hz), 7.58
(dd, 1H, CH arom., J= 8.6, 2.2 Hz), 7.47 (m, 2H, CH arom.), 7.40-7.30 (m, 3H, CH arom.), 7.16 (d, 1H, CH
arom., J= 8.8 Hz), 5.21 (s, 2H, OCH2Ph), 5.03 (d, 1H, H-1, J= 3.2 Hz), 4.09 (s,1H, H-3), 3.98 (dq, 1H, H-5,
J= 9.6, 6.4 Hz), 3.90 (d, 1H, H-2, J= 3.2 Hz), 3.69 (dd, 1H, H-4, J= 4.4, 2.4 Hz), 2.55 (s, 3H, COCH3), 1.31
(d, 3H, CH-CH3, J= 6.4 Hz). 13C NMR (75 MHz, CDCl3): δ 202.3 (C=O), 158.9 (C arom.-OBn), 138.01 (C
arom.), 134.2 (CH arom.), 131.08 (C arom.), 130.04 (CH arom.), 129.6 (CH arom.), 129.2 (CH arom.), 128.9
(CH arom.), 114.02 (CH arom.), 91.02 (C-4), 83.9 (C-1), 81.1 (C-2), 80.2 (C-3), 71.9 (CH2Ph), 69.15 (C-5),
32.15 (COCH3), 19.93 (CH3). IR (cm-1, KBr): 3344 (OH), 1679 (O=C-CH3). MS (EI+), m/z (%): 372 (M+, 3),
267 (9), 149 (8), 91 (100), 65 (6), 43 (7). HRMS (FAB+) calcd. for C21H24O6 372.1573, found 372.1581.
-86.5 (c = 1, CHCl3).
4.3. 1-(2-(Benzyloxy)-5-(2,3,5-tri-O-benzyl-β-D-fucofuranosyl)phenyl ethanone (11). Compound 11 was
prepared from 4 (1.43 mmol) and lactone 5b (0.74 g, 1.72 mmol) following conditions [a] and [c]. After flash
column chromatography (silica gel, hexane:ethyl acetate 95:5 to 9:1), 11 was isolated as an inseparable
mixture of diastereoisomers (yellow oil) in 70% yield (2 steps, only 11β is described). 1H NMR (300 MHz,
CDCl3): δ 7.8 (d, 1H, CH arom., J= 2.4 Hz), 7.5 (dd, 1H, CH arom., J= 8.6, 2.2 Hz), 7.44-7.17 (m, 20H, CH
arom.), 6.98 (d, 1H, CH arom., J= 8.4 Hz), 5.16 (s, 2H, OCH2Ph), 4.93 (d, 1H, H-1, J= 6.8 Hz), 4.67 (d, 1H,
OCHaPh, J= 11.6 Hz), 4.5 (d, 1H, OCHbPh, J= 11.4 Hz), 4.48-4.42 (m, 4H, 2(OCH2Ph)), 4.23 (t, 1H, H-3, J=
4.6 Hz), 4.13-4.1 (m, 2H, H-2, H-4), 3.71-3.64 (m, 1H, H-5), 2.6 (s, 3H, COCH3), 1.25 (d, 3H, CH-CH3, J=
6.4 Hz). 13C NMR (75 MHz, CDCl3): δ 199.5 (C=O), 157.6 (C arom.-OBn), 138.6 (C arom.), 137.9 (C arom.),
137.7 (C arom.), 136.1 (C arom.), 133.1 (C arom.), 131.8 (CH arom.), 128.6 (CH arom.), 128.3 (CH arom.),
128.2 (CH arom.), 127.8 (CH arom.), 127.7 (CH arom.), 127.7 (CH arom.), 127.5 (CH arom.), 112.9 (CH
arom.), 90.1 (CH), 85.3 (CH), 84.6 (CH), 82.8 (CH), 74.3 (CH), 72.3 (CH2Ph), 72.0 (CH2Ph), 71.1 (CH2Ph),
70.7 (CH2Ph), 32.0 (COCH3), 15.7 (CH3). IR (cm-1, film): 1675 (O=C-CH3). MS (FAB+), m/z (%): 641 (M-
H+, 3), 181 (13), 109 (15), 91 (100), 55 (86), 41 (70). HRMS (FAB+) [M-H]+ calcd. for C42H41O6 641.2903,
found 641.2897.
-20.6 (c = 1.2, CHCl3).
4.4. 1-(2-(Benzyloxy)-5-(2,3,5-tri-O-benzyl-α-D-fucofuranosyl)phenyl ethanone (11α). To a solution of
triol 10 (1.01 g, 2.7 mmol) in neat benzyl bromide (22 mL) was added nBuNI (0.11 g, 0.3 mmol). After
stirring for 20 minutes at room temperature, 3.7 g (16 mmol) of Ag2O were added to the reaction. The
resulting mixture was stirred at r.t. for 12 h, filtered over Celite, washed with ethyl acetate and the solvent was
evaporated. Purification by flash column chromatography (silica gel, hexane:ethyl acetate 9:1 to 8:2) afforded
1
11α as a yellow oil in 58% yield. H NMR (300 MHz, CDCl3): δ 7.78 (d, 1H, CH arom., J= 2.4 Hz), 7.58
(dd, 1H, CH arom., J= 8.7, 2.4 Hz), 7.45-7.20 (m, 19H, CH arom.), 6.99-6.95 (m, 2H, CH arom.), 5.16 (s,
2H, OCH2Ph), 5.0 (d, 1H, H-1, J= 3.6 Hz), 4.69 (s, 2H, OCH2Ph), 4.48 (s, 2H, OCH2Ph), 4.10 (ABq, 2H,
OCH2Ph, J= 12.3 Hz), 4.06-3.99 (m, 2H, H-3, H-4), 3.93 (dd, 1H, H-2, J= 3.8, 0.7 Hz), 3.89-3.81 (m, 1H, H-
5), 2.6 (s, 3H, COCH3), 1.24 (d, 3H, CH-CH3, J= 6.3 Hz). 13C NMR (75 MHz, CDCl3): δ 199.47 (C=O),
157.55 (C arom.-OBn), 138.82 (C arom.), 137.70 (C arom.), 137.67 (C arom.), 136.22 (CH arom.), 133.26
(CH arom.), 129.6 (C arom.), 128.63 (CH arom.), 128.38 (CH arom.), 128.23 (CH arom.), 128.16 (CH arom.),
127.77 (CH arom.), 127.75 (CH arom.), 127.47 (CH arom.), 127.4 (CH arom.), 127.36 (CH arom.), 112.54
(CH arom.), 86.3 (CH), 84.3 (CH), 83.9 (CH), 82.2 (CH), 74.4 (CH), 71.6 (CH2Ph), 71.4 (CH2Ph), 71.3
(CH2Ph), 70.7 (CH2Ph), 32.0 (COCH3), 15.9 (CH3). IR (cm-1, film):1673 (O=C-CH3). MS (FAB+), m/z (%):

641 (M-H+, 10), 181 (36), 154 (11), 91 (100), 77 (8), 57 (7). HRMS (FAB+) [M-H]+ calcd. for C42H41O6
641.2903, found 641.2910. -38.08 (c = 1.2, CHCl3).
4.5. 1-(Benzyloxy)-4-(α-D-fucofuranosil) benzene (21). The title compound was obtained from 4-
benzyloxybromobenzene 1721 (1 g, 3.8 mmol) and lactone 5a (2.1 g, 4.18 mmol), following conditions [a], [c]
and [d]. Purification by flash chromatography (silica gel, hexane:ethyl acetate 1:9) afforded C-glycoside 21 in
1
82% (for 3 steps) as a white solid (mp = 94-96 °C). H NMR (300 MHz, CDCl3): δ 7.43-7.29 (m, 7H, CH
arom.), 6.97 (d, 2H, CH arom., J= 8.7 Hz), 5.09 (d, 1H, H-1, J= 3 Hz), 5.04 (s, 2H, OCH2Ph), 4.19 (d, 1H, H-
3 J= 1.2 Hz), 4.03-3.98 (m, 1H, H-5), 3.91 (d, 1H, H-2 J= 2.4 Hz), 3.76 (dd, 1H, H-4, J= 3.3, 2.4 Hz), 3.04 (a,
3H, OH), 1.34 (d, 3H, CH-CH3, J= 6.3 Hz). 13C NMR (75 MHz, CDCl3): δ 158.54 (C arom.-OBn), 136.87 (C
arom.), 138.01 (C arom.), 128.5 (CH arom.), 128.15 (CH arom.), 127.97 (C arom.), 127.45 (CH arom.), 114.8
(CH arom.), 89.0 (CH), 82.7 (CH), 79.6 (CH), 79.3 (CH), 70.0 (CH2Ph), 68.2 (CH), 19.8 (CH3). IR (cm-1,
KBr): 3323 (OH), 1026 (C-O-C). MS (FAB+), m/z (%): 330 (M+, 8), 307 (15), 154 (100), 136 (99), 107 (50),
77 (60). HRMS (FAB+) calcd. for C19H22O5 330.1467, found 330.1472.
-71.8 (c = 1.2, CHCl3).
4.6. 1-(Benzyloxy)-4-(2,3,5-tri-O-benzyl-β-D-fucofuranosil) benzene (22). The title compound was
obtained from 4-benzyloxybromobenzene 1720 (1 g, 3.8 mmol) and lactone 5b (1.8 g, 4.2 mmol), following
conditions [a] and [c]. Purification by flash chromatography (silica gel, hexane:ethyl acetate 9:1 to 85:15)
1
afforded C-glycoside 22 in 60% (for 2 steps) as a yellow oil. H NMR (300 MHz, CDCl3): δ 7.45-7.15 (m,
22H, CH arom.), 6.95 (d, 2H, CH arom., J= 8.7 Hz), 5.07 (s, 2H, OCH2Ph), 4.90 (d, 1H, H-1, J= 6.9 Hz),
4.67 (d, 1H, OCHaPh, J= 11.7 Hz), 4.50 (d, 1H, OCHbPh, J= 12.3 Hz), 4.50 (d, 2H, OCH2Ph, J= 7.5 Hz), 4.40
(d, 2H, OCH2Ph, J= 6.6 Hz), 4.24 (t, 1H, H-3, J= 4.9 Hz), 4.14-4.05 (m, 2H, H-2, H-4), 3.73-3.65 (m, 1H, H-
5), 1.26 (d, 3H, CH-CH3, J= 6.3 Hz). 13C NMR (75 MHz, CDCl3): δ 158.52 (C arom.-OBn), 138.70 (C
arom.), 138.01 (C arom.), 137.86 (C arom.), 137.0 (C arom.), 133.0 (C arom.), 128.9 (C arom.), 128.5 (CH
arom.), 128.33 (CH arom.), 128.30 (CH arom.), 128.2 (CH arom.), 128.0 (CH arom.), 127.9 (CH arom.),
127.8 (CH arom.), 127.7 (CH arom.), 127.6 (CH arom.), 127.4 (CH arom.), 114.8 (CH arom.), 90.4 (CH),
85.1 (CH), 84.6 (CH), 83.3 (CH), 74.4 (CH), 72.2 (CH2Ph), 72.1 (CH2Ph), 71.1 (CH2Ph), 70.0 (CH2Ph), 15.9
(CH3). IR (cm-1, film): 1070 (C-O-C). MS (FAB+), m/z (%): 599 (M-H+, 5), 307 (20), 154 (65), 136 (40), 91
(100), 89 (9). HRMS (FAB+) [M-H]+ calcd. for C40H39O5 599.2797, found 599.2786.
CHCl3).
-21.15 (c = 1.2,
4.7. 1-(Methoxy)-4-(2,3,5-tri-O-tert-butyldimethylsilyl-α-D-fucofuranosil) benzene (23). This compound
was synthesized from commercially available 4-bromoanisole 18 (0.5 g, 2.67 mmol) and lactone 5a (1.34 g,
2.67 mmol) following conditions [a], [c] and [e]. After flash column chromatography (silica gel, hexane:ethyl
1
acetate 95:5 to 9:1), 23 was isolated as a yellow oil in 52% yield (3 steps). H NMR (300 MHz, CDCl3):
δ 7.22 (d, 2H, J=8.7), 6.76 (d, 2H, J=8.7 Hz), 4.91 (d, 1H, J=2.6 Hz), 4.07-3.97 (m, 1H), 3.96-3.94 (m, 1H),
3.72 (s, 3H), 3.71-3.68 (m, 2H), 1.15 (d, 3H, J=6.4 Hz), 0.85 (s, 9H), 0.84 (s, 9H), 0.65 (s, 9H), 0.06 (s, 6H),
0.05 (s, 3H), -0.23 (s, 3H), -057 (s, 3H). 13C NMR (75 MHz, CDCl3): δ -5.4, -5.0, -4.5, -4.3, -4.2, -4.0, 20.6,
25.8, 26.2, 55.5, 69.6, 92.12, 113.1, 129.1, 129.6, 159.1. MS (FAB+), m/z (%): 595 (M-H+, 1), 407 (2.5), 231
(10), 159 (10), 147 (26), 73 (100). HRMS (FAB+) [M-H]+ calcd. for C31H59O5Si3 595.3670, found 599.3669.
-35.5 (c = 1, CHCl3).
4.8. 1-(Methoxy)-4-(2,3,5-tri-O-benzyl-β-D-fucofuranosil) benzene (24). The title compound was obtained
from commercially available 4-bromoanisole 18 (0.5 g, 2.67 mmol) and lactone 5b (1.15 g, 2.67 mmol),
following conditions [a] and [c]. Purification by flash chromatography (silica gel, hexane:ethyl acetate 95:5 to
1
9:1) afforded C-glycoside 24 in 75% (for 2 steps) as a yellow oil. H NMR (400 MHz, CDCl3): δ 7.40-7.15
(m, 19H), 6.88 (d, 2H, J=8.7 Hz), 4.91 (d, 1H, J=6.8 Hz), 4.68 (d, 1H, J=12.0 Hz), 4.53 (d, 1H, J=11.8 Hz),
4.51 (d, 1H, J=11.8 Hz), 4.47 (d, 1H, J=11.8 Hz), 4.43 (d, 1H, J=12.0 Hz), 4.38 (d, 1H, J=11.8 Hz), 4.24 (t,
1H, J=5.0 Hz), 4.14-4.09 (m, 2H), 3.81 (s, 3H), 3.70 (qd, 1H, J=6.4, 4.6 Hz), 1.26 (d, 3H, J=6.4 Hz). 13C
NMR (100 MHz, CDCl3): δ 15.9, 55.4, 71.30, 71.2, 72.2, 72.4, 74.6, 83.4, 84.8, 85.2, 90.5, 114.0, 127.6,
127.8, 127.9, 128.0, 128. 1, 128.4, 128.5, 128.6, 133.0, 138.1, 138.2, 138.9, 159.5. HRMS (FAB+) calcd. for
C34H36O5 524.2563, found 524.2573.
-18.6 (c = 1, CHCl3).
4.9. 1-(Trimethylsilyl)-3-(2,3,5-tri-O-tert-butyldimethylsilyl-α-D-fucofuranosil) ethyne (25). This
compound was synthesized from commercially available ethylnyltrimethylsilane 19 (0.2 g, 2.03 mmol) and

lactone 5a (1.02 g, 2.03 mmol) following conditions [a], [c] and [e]. After flash column chromatography
(silica gel, hexane:ethyl acetate 98:2 to 95:5), 25 was isolated as a yellow oil in 48% yield (3 steps). 1H NMR
(300 MHz, CDCl3): δ 4.70 (d, 1H, J=2.8 Hz), 4.00 (qd, 1H, J=7.7, 6.3 Hz), 3.88 (t, 1H, J=1.1 Hz), 3.84 (dd,
1H, J=2.8, 1.1 Hz), 3.58 (dd, 1H, J=7.7, 1.1 Hz), 1.13 (d, 3H, J=6.3 Hz), 0.92 (s, 9H), 0.89 (s, 9H), 0.85 (s,
9H), 0.15 (s, 9H), -0.12 (s, 6H), -0.10 (s, 3H), -0.07 (s, 9H). 13C NMR (75 MHz, CDCl3): δ -4.7, -4.6, -4.5, -
4.4, -4.3, -4.0, -0.1, 20.6, 25.7, 26.0, 26.3, 69.2, 73.0, 79.3, 80.0, 92.1, 92.4, 101.8. MS (FAB+), m/z (%): 586
(M+, 1), 399 (1), 281 (7), 207 (12), 147 (50), 73 (100). HRMS (FAB+) [M-H]+ calcd. for C29H61O4Si4
585.3647, found 585.3652.
-12.0 (c = 1, CHCl3).
4.10. 1-(Trimethylsilyl)-3-(2,3,5-tri-O-benzyl-β-D-fucofuranosil) ethyne (26). The title compound was
obtained from commercially available ethynyltrimethylsilane 19 (0.2 g, 2.03 mmol) and lactone 5b (0.88 g,
2.03 mmol), following conditions [a] and [c]. Purification by flash chromatography (silica gel, hexane:ethyl
1
acetate 95:5 to 9:1) afforded C-glycoside 26 in 68% (for 2 steps) as a colorless oil. H NMR (300 MHz,
CDCl3): δ .18-7.03 (m, 15H), 4.53 (d, 1H, J= 4.7 Hz), 4.52 (d, 1H, J= 12.0 Hz), 4.43 (d, 1H, J= 11.8 Hz),
4.39 (d, 1H, J= 12.0 Hz), 4.34 (d, 1H, J= 12.0 Hz), 4.28 (d, 1H, J= 12.0 Hz), 4.24 (d, 1H, J= 12.0 Hz), 4.03
(dd, 1H, J= 4.7, 3.3 Hz), 3.90-3.83 (m, 2H), 3.47 (qd, 1H, J= 6.4, 3.5 Hz), 1.05 (d, 3H, J= 6.4 Hz), 0.0 (s,
9H). 13C NMR (75 MHz, CDCl3): δ 0.1, 15.9, 99.9, 71.3, 72.2, 72.4, 74.3, 84.3, 84.9, 89.1, 92.0, 103.3, 127.6,
127.7, 127.8, 127.9, 128.0, 128.4, 128.4, 128.6, 137.8, 138.1, 138.8. MS (FAB+), m/z (%): 515 (MH+, 1), 181
(20), 149 (20), 109 (10), 91 (100). HRMS (FAB+) [M+H]+ calcd. for C32H39O4Si 515.2618, found 515.2623.
-43.1 (c = 1, CHCl3).
4.11. 2,3,5-tri-O-tert-butyldimethylsilyl-α-D-fucofuranosilmethane (27). Compound 27 was prepared from
commercially available MeLi 20 (0.62 mL of a 1.6M solution in diethyl ether, 0.99 mmol) and lactone 5a (0.5
g, 0.99 mmol) following conditions [b] [c] and [e]. After flash column chromatography (silica gel,
1
hexane:ethyl acetate 98:2 to 95:5), 27 was isolated as a yellow oil) in 43% yield (3 steps). H NMR (400
MHz, CDCl3): δ 4.14 (qd, 1H, J=6.3, 2.6 Hz), 3.89 (qd, 1H, J=7.9, 6.3 Hz), 3.85 (sa, 1H), 3.65 (dd, 1H,
J=2.6, 0.9 Hz), 3.55 (dd, 1H, J=7.9, 0.9 Hz), 1.19 (d, 3H, J=6.3 Hz), 1.13 (d, 3H, J=6.3 Hz), 0.90 (s, 9H),
0.89 (s, 9H), 0.85, (s, 9H), 0.2-0.04 (m, 18H). 13C NMR (100 MHz, CDCl3): δ -4.8, -4.7, -4.41, -4.4, -4.3, -
4.1, 14.4, 17.9, 18.3, 18.5, 20.6, 25.8, 25.9, 26.1, 69.7, 77.1, 80.0, 80.1, 92.1. MS (ESI), m/z (%): 527
(MH+Na, 100), 504 (M+H, 50), 373 (20), 357 (10), 315 (5), 241 (20). HRMS (ESI) [M+H]+ calcd. for
C25H57O4Si3 505.3565, found 505.3555.
-24.3 (c = 1, CHCl3).
4.12. 2,3,5-tri-O-benzyl-α-D-fucofuranosilmethane (28). Compound 28 was prepared from commercially
available MeLi 20 (0.72 mL of a 1.6M solution in diethyl ether, 1.15 mmol) and lactone 5b (0.5 g, 1.15
mmol) following conditions [b] and [c]. After flash column chromatography (silica gel, hexane:ethyl acetate
95:5 to 9:1), 28 was isolated as an inseparable mixture of diastereoisomers (yellow oil) in 75% yield (2 steps,
only β anomer is described). 1H NMR (400 MHz, CDCl3): δ 7.37-7.22 (m, 15H), 4.65 (d, 1H, J=12.0 Hz),
4.56 (s, 2H), 4.51 (d, 1H, J=12.0 Hz), 4.49 (d, 2H, J=12.0 Hz), 4.16 (qd, 1H, J=6.4, 5.2), 4.09 (dd, 1H,
J=4.7, 3.6 Hz), 3.98 (t, 1H, J=4.7 Hz), 3.77 (dd, J=5.2, 3.6 Hz), 3.64 (qd, 1H, J=6.4, 4.7 Hz), 1.31 (d, 3H,
J=6.4 Hz), 1.22 (d, 3H, J=6.4 Hz). 13C NMR (100 MHz, CDCl3): δ 15.9, 19.3, 71.3, 72.0, 72.1, 74.7, 78.1,
84.9, 85.2, 89.7, 127.6, 127.78, 127.8, 127.9, 127.9, 128.3, 128.4, 128.5, 138.2, 138.3, 138.9. MS (ESI), m/z
(%): 456 (MH+Na, 45), 455 (M+Na, 100). HRMS (ESI) [M+Na]+ calcd. for C28H32O4Na 455.2198, found
455.2187.
-23.7 (c = 1, CHCl3).
4.13. 3-(2,3,5-tri-O-benzyl-β-D-fucofuranosil)-1-propene (38b). To a solution of lactone 5b (0.3 g, 0.69
mmol) in anhydrous CH2Cl2 (7 mL) at -78 °C and under argon, were added 2.8 mL of DIBAL-H (1M solution
in 2.77 mmol). After stirring at -78 °C for 30 minutes, methanol was carefully added and the solution was
stirred for further 10 min. The reaction mixture was allowed to warm at room temperature, partitioned
between Rochelle’s salt and dichloromethane and extracted. The organic phase was dried over Na2SO4,
filtered and concentrated in vacuo. The crude lactol was then dissolved in 3 mL of dry CH2Cl2, and cooled at -
78 °C. To this solution was dropwise added allyltrimethylsilane (0.17 mL, 1.04 mmol) and BF3•OEt2 (0.13
mL, 1.04 mmol). The reaction was stirred at room temperature for 1h, neutralized with triethylamine (pH 6-7)
and extracted with dichloromethane. The combined organic layers were dried (Na2SO4), filtered and the
solvent was evaporated in vacuo. The residue was purified by flash column chromatography (silica gel,
hexane:ethyl acetate 95:5 to 9:1) to afford compound 38b as an inseparable mixture of diastereoisomers (a:b

2.5:1) as a yellow oil (59% yield, 2 steps). Only a isomer (major) is described. 1H NMR (400 MHz, CDCl3): δ
7.37-7.20 (m, 15H), 5.89-5.87 (m, 1H), 5.15-5.02 (m, 2H), (4.65 (d, 1H, J=12.0), 4.61 (d, 1H, J=12.0 Hz),
4.55 (d, 1H, J=12.0 Hz), 4.50 (d, 2H, J=12.0 Hz), 4.40 (d, 1H, J=12.0 Hz), 3.98 (td, 1H, J= 6.7, 3.7 Hz),
3.96-3.91 (m, 2H), 3.81 (d, 1H, J=3.7 Hz), 3.73 (qd, 1H, J=6.4, 4.7 Hz), 2.57-2.47 (m, 2H), 1.15 (d, 3H, J =
6.4 Hz). 17.35. 13C NMR (100 MHz, CDCl3): δ 15.9, 33.2, 71.3, 71.5, 71.6, 74.5, 80.9, 83.1, 83.2, 86.8,
116.9, 127.5, 127.6, 127.8, 127.9, 127.9, 128.8, 128.5, 135.1, 138.1, 139.0. MS (FAB+), m/z (%): 457 (M-H+,
1), 315 (5), 181 (11), 91 (100), 73 (556). HRMS (FAB+) calcd. for C30H34O4 458.2457, found 458.2453.
4.14. 3-(α-D-fucofuranosyl)-1-propene (38c). To a solution of lactone 5a (0.3 g, 0.59 mmol) in anhydrous
CH2Cl2 (6 mL) at -78 °C and under argon, were added 0.7 mL of DIBAL-H (1M solution in 0.71 mmol).
After stirring at -78 °C for 30 minutes, methanol was carefully added and the solution was stirred for further
10 min. The reaction mixture was allowed to warm at room temperature, partitioned between Rochelle’s salt
and dichloromethane and extracted. The organic phase was dried over Na2SO4, filtered and concentrated in
vacuo. The crude lactol was then dissolved in 3 mL of dry CH2Cl2, and cooled at -78 °C. To this solution was
dropwise added allyltrimethylsilane (0.18 mL, 0.89 mmol) and BF3•OEt2 (0.09 mL, 0.71 mmol). The reaction
was stirred at room temperature for 1h, neutralized with triethylamine (pH 6-7) and extracted with
dichloromethane. The combined organic layers were dried (Na2SO4), filtered and the solvent was evaporated
in vacuo. The crude allylated product was dissolved in THF (9 mL) at r.t. and 3.56 mL of TBAF (3.56 mmol,
1M solution in THF) were added to this solution. After stirring at r.t. for 3 h, water was added and the reaction
was extracted with ethyl acetate. The organic phase was dried over Na2SO4 filtered and concentrated. The
residue was purified by flash column chromatography (silica gel, hexane:ethyl acetate 1:1) to afford
compound 38c as an inseparable mixture of diastereoisomers (α:β 1:2) as a yellow oil (25% yield, 3 steps).
1
Only α isomer (major) is described. H NMR (300 MHz, CD3OD): δ 5.93 (ddt, 1H, J= 17.2, 10.2, 6.9 Hz),
5.10 (dq, 1H, J=17.2, 1.6 Hz), 5.10 (ddt, 1H, J= 10.3, 2.3, 1.2 Hz), 4.00-3.97 (m, 1H), 3.85-3.79 (m, 3H),
3.55 (dd, 1H, J= 6.1, 5.1 Hz), 2.51-2.33 (m, 2H), 1.24 (d, 3H, J= 6.5 Hz). 13C NMR (75 MHz, CD3OD): δ
19.5, 38.5, 68.8, 79.7, 81.9, 83.3, 87.8, 117.5, 135.7. MS (FAB+), m/z (%): 189 (MH+, 45), 171 (12), 93 (100),
75 (20). HRMS (FAB+) [M+H]+ calcd. for C9H17O4 189.1127, found 189.1124.
4.15. 3-O-benzyl-2-O-tert-butyldimethylsilyl-5,6-O-isopropylidene-α-D-galactofuranose (44). To
a
solution of lactone 4318 (0.35 g, 1.05 mmol) in ethyl acetate (5.3 mL) at r.t. was added benzyl bromide (0.5
mL, 4.2 mmol). The solution was cooled at 0 °C and then Ag2O (1.0 g, 4.2 mmol) was added. The reaction
mixture was stirred at r.t. for 15h, filtered over celite and concentrated under vaccum. The residue was
purified by flash column chromatography (silica gel, hexane:ethyl acetate 5:1) to afford lactone 44 as a white
solid (mp = 72-74 °C) in 67% yield. 1H NMR (300 MHz, CDCl3): δ 7.41-7.30 (m, 5H), 4.84 (d, 1H, J= 11.4
Hz), 4.63 (d, 1H, J= 11.4 Hz), 4.55 (d, 1H, J= 7.6 Hz), 4.26-2.16 (m, 2H), 4.11 (dd, 1H, J= 7.6, 3.6 Hz), 3.99
(dd, 1H, J= 8.7, 6.6 Hz), 3.92 (dd, 1H, J= 8.7, 7.2 Hz), 1.40 (s, 3H), 1.35 (s, 3H), 0.96 (s, 9H), -0.21 (s, 3H), -
0.25 (s, 3H). 13C NMR (100 MHz, CDCl3): δ -5.1, -4.0, 18.4, 25.8, 25.9, 26.2, 65.2, 73.3, 74.4, 75.7, 78.0,
81.7, 110.3, 128.1, 128.4, 128.7, 137.1, 172.5. MS (FAB+), m/z (%): 423 (MH+, 8), 407 (7), 365 (7), 91 (100),
73 (60). HRMS (FAB+) [M+H]+ calcd. for C22H35O6Si 423.2203, found 423.2200.
CHCl3).
-47.0 (c = 0.2,
4.16. 1-(Trimethylsilyl)-3-(2-O-benzyl-α-D-galactofuranosil) ethyne (45). The title compound was
obtained from commercially available ethynyltrimethylsilane 19 (0.06 g, 0.59 mmol) and lactone 44 (0.25 g,
0.59 mmol), following conditions [a] and [c]. Purification by flash chromatography (silica gel, hexane:ethyl
1
acetate 1:1) afforded C-glycoside 46 in 55% (for 2 steps) as colorless oil. H NMR (300 MHz, CDCl3): δ
7.40-7.30 (m, 5H), 4.71 (d, 1H, J=3.2 Hz), 4.66 (d, 1H, J=11.5 Hz), 4.57 (d, 1H, J=11.5 Hz), 4.32 (dd, 1H,
J=5.6, 3.2 Hz), 4.00 (t, 1H, J=3.2 Hz), 3.99 (dd, 1H, J=5.6, 2.1 Hz), 3.79-3.70 (m, 3H), 2.57 (sa, 1H), 2.27
(sa, 1H), 0.88 (s, 9H), 0.18 (s, 3H), 0.08 (s, 3H), 0.07 (s, 3H). 13C NMR (75 MHz, CDCl3): δ -4.7, -4.4, 0.1,
17.9, 25.8, 53.6, 65.1, 70.3, 72.5, 72.9, 85.7, 90.2, 92.4, 102.5, 128.1, 128.2, 128.6, 137.2. MS (FAB+), m/z
(%): 465 (MH+, 3), 391 (2), 273 (5), 149 (18), 91 (100), 73 (95), 57 (32).
HRMS (FAB+) [M+H]+ calcd. for C24H41O5Si2 465.2493, found 465.2500.
-25.4 (c = 0.26, CHCl3).
4.17. 1-(Trimethylsilyl)-3-(3-O-benzyl-2,5,6--tri-O-tert-butyldimethylsilyl-α-D-galactofuranosil) ethyne
(47). This compound was synthesized from commercially available ethylnyltrimethylsilane 19 (0.035 g, 0.35
mmol) and lactone 45 (0.15 g, 0.35 mmol) following conditions [a], [c] and [e]. After flash column

chromatography (silica gel, hexane:ethyl acetate 98:2 to 95:5), 48 was isolated as a colorless oil in 30% yield
(3 steps). 1H NMR (400 MHz, CDCl3): δ 7.35-7.29 (m, 5H), 4.62 (d, 1H, J= 3.1 Hz), 4.61 (d, 1H, J=11.7 Hz),
4.53 (d, 1H, J=11.7 Hz), 4.15 (dd, 1H, J=3.3, 1.1 Hz), 3.97-3.87 (m, 3H), 3.77 (dd, 1H, J= 10.7, 2.7 Hz),
3.57 (d, 1H, J= 10.7, 4.8 Hz), 0.92 (s, 18H), 0.91 (s, 9H), 0.17 (s, 9H), 0.15-0.06 (m, 18H).
13C NMR (100 MHz, CDCl3): δ -5.1, -5.1, -4.9, -4.3, -4.3, -4.2, -0.1, 18.4, 18.5, 18.6, 26.0, 26.2, 26.2, 66.22,
71.6, 72.9, 74.3, 78.0, 85.5, 86.1, 92.3, 101.3, 127.7, 127.8, 128.5, 138.1. MS (ESI), m/z: 715 (M+Na+, 100),
601 (4). HRMS (ESI) [M+Na]+ calcd. for C36H68O5Si4Na 715.4042, found 715.4044.
0.32, CHCl3).
-+12.2 (c =
5. Supplementary data. Experimental details for the preparation of starting materials (compounds 4, 5b
and 44) and copies of the 1H NMR and 13C NMR spectra for all key intermediates are available on the WWW
under http://
6. Acknowledgments
We wish to thank the Instituto de Química, UNAM and DGAPA (project PAPIIT IB200912) for generous
financial support. O. Cortezano and C. Meléndez thank CONACYT for graduate scholarship (grants number
162040 and 403850). We thank Angeles Peña-González, Elizabeth Huerta-Salazar and Isabel Chávez-Uribe
for technical support (NMR). We also thank reviewers for helpful and detailed corrections.
7. References
1.
(a) Postema, M. H. D. C-Glycoside Synthesis; CRS: Boca Raton, FL, 1995; (b) Levy, D. E.; Tang, C. The Chemistry of C-
Glycosides; Pergamon: Oxford, 1995.
2.
a) Hurd, C. D.; Bonner, W. A. J. Am. Chem. Soc. 1945, 67, 1664; b) Kalvoda, L.; Farkaa, J.; Sorm, F. Tetrahedron Lett. 1970, 11,
2297; c) Stewart, A. O.; Williams, R. M. J. Am. Chem. Soc. 1985, 107, 4289; d) Matsumoto, T.; Katsuki, M.; Suzuki, K.
Tetrahedron Lett. 1970, 11, 2297; e) Martin, O. R.; Rao, S. P.; Kurz, K. G.; El-Shenawy, H. A. J. Am. Chem. Soc. 1988, 110,
8698; f) Hamamichi, N.; Misaka, T. J. Org. Chem. 1991, 56, 3771.
3.
For O→C transpositions, see: a) Matsumoto, T.; Hosoya, T.; Suzuki, K. Tetrahedron Lett. 1990, 31, 4629; b) Matsumoto, T.;
Katsuki, M.; Suzuki, K. Tetrahedron Lett. 1988, 29, 6935; c) Matsumoto, T.; Katsuki, M.; Hona, H.; Suzuki, K. Tetrahedron Lett.
1989, 30, 6185; d) Hosoya, T., Ohashi, Y.; Matsumoto, T.; Suzuki, K. Tetrahedron Lett. 1996, 37, 663; d) Matsumoto, T.; Katsuki,
H. Jona, K. Suzuki, J. Am. Chem. Soc. 1991, 113, 6892; e) T. Matsumoto, T. Sohma, H. Yamaguchi, S. Kurata, K. Suzuki, M.
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Graphical abstract
Stereoselective C-glycosidation of D-fucose derivatives directed by the
protective groups
Omar Cortezano-Arellano, Camilo Meléndez-Becerra, Fernando Cortés, Fernando Sartillo-
Piscil, Alejandro Cordero-Vargas*

Highlights
Stereoselectivity for the reduction of the lactols can be modulated by the correct choice of
protective groups.
Lactols possessing TBDMS protective groups afford the α-anomer, whereas their
benzylated congeners provide the β-anomer.
This change in stereoselectivity is observed in carbohydrate derivatives possessing 2,3-
trans substituents.
The phenomenon is observed only when the C2 and C3 protective groups are the same
(both benzyl or both TBDMS).