Glycosyl fluorides from n-pentenyl-related glycosyl donors-application to glycosylation strategies

Article abstract of DOI:10.1139/cjc-2012-0285

n-Pentenyl glycosides (NPGs) and n-pentenyl orthoesters (NPOEs) have been transformed into glycosyl fluorides by a variety of methods. In the case of NPGs, Barluenga's reagent, bis(pyridinium)iodonium(I)tetrafluoroborate (IPy ₂BF₄),

Full text of DOI:10.1139/cjc-2012-0285

51
Glycosyl fluorides from n-pentenyl-related glycosyl
donors — Application to glycosylation strategies
Bert Fraser-Reid, J. Cristobal Lopez, Paloma Bernal-Albert, Ana M. Gomez,
Clara Uriel, and Juan Ventura
Abstract: n-Pentenyl glycosides (NPGs) and n-pentenyl orthoesters (NPOEs) have been transformed into glycosyl fluorides
by a variety of methods. In the case of NPGs, Barluenga’s reagent, bis(pyridinium)iodonium(I)tetrafluoroborate (IPy2BF4),
gives good yields of glycosyl fluorides when HF–pyridine complex is used as an additional fluoride source. NPOEs can
be activated either by a combination of electrophilic iodonium (Barluenga’s reagent) and HBF4 or by the action of
HF–pyridine complex. The ensuing glycosyl fluorides form a semiorthogonal pair of glycosyl donors when confronted with NPGs.
Key words: pentenyl glycosides, glycosyl fluorides, pentenyl orthoesters, glycosylation, orthogonal.
Résumé : Les glycosides de n-pentényle (GNP) et les orthoesters de n-pentényle (OENP) peuvent être transformés en
fluorures de glycosyles par diverses méthodes. Dans les cas des GNP, le réactif de Barluenga, le tétrafluoroborate de
bis(pyridinium)iodonium(I) (IPy2BF4) permet d’obtenir de bons rendements de fluorures de glycosyles si on utilise le
complexe de HF–pyridine comme source additionnelle de l’ion fluorure. Les OENP peuvent être activés soit par une
combinaison d’iodonium électrophile (tel le réactif de Barluenga) et de l’acide HBF4 ou par l’action du complexe
HF–pyridine. Les fluorures de glycosyles qui en résultent conduisent a la formation d’une paire semi-orthogonale de
`
donneurs glycosyles lorsqu’ils sont confrontés a des glycosides de pentényle, GNP.
`
Mots-clés : glycosides de pentényle, fluorures de glycosyle, orthoesters de pentényle, glycosylation, orthogonal.
[Traduit par la Rédaction]
Prior to these developments, the concept of orthogonal
glycosylation had been introduced by Ogawa and co-workers5
in 1994. The strategy involves the coupling of two potential
donors with different leaving groups, one of which can be
activated without disturbing the other, which can then become
an acceptor. Glycosyl fluorides were one of the donors fea-
tured in the original experiments and, since their emergence in
1981,6 have proven to be valuable in glycosylation strategies.7
The interest in these glycosyl donors, because of their en-
hanced stability compared with other glycosyl halides, has
continued to flourish over the last two decades,8 and a variety
of methods are now available for their activation.9
Introduction
Biologically active oligosaccharides are rarely simple
uniform linear structures such as those found in other
biopolymers.1 Branched motifs are frequently encountered,
and these substructures convey biological information and
therefore cannot be ignored in view of their biological signif-
icance. These complex oligosaccharides present multiple
challenges to laboratory synthesis because issues of regiose-
lectivity, chemoselectivity, and stereoselectivity must be ad-
dressed.2 Frush and Isbell’s3 discovery of neighboring group
participation 71 years ago showed how the last of these three
selectivities, 1,2-trans stereoselectivity, could be optimized in
donor–acceptor coupling.
Results and discussion
Regio- and chemo-selectivities are principles of interest to
our groups in view of their potential for reducing the time-
consuming, and frequently frustrating, demands of protect–
deprotect synthetic strategies. Regioselectivity requires that a
donor be induced to display a preference for one of several
available hydroxyls of an acceptor, thereby reducing the need
to protect all hydroxyls except the targeted one. Chemoselec-
tivity is required when two (or more?) donors are prone to the
same activation process, but one must be preferably triggered.
The 20-year-old armed–disarmed strategy is a case in point.4
Glycosyl fluorides from n-pentenyl glycosides
In view of these properties, the preparation of glycosyl
fluorides continues to be a topic of interest. n-Pentenyl glyco-
syl donors are ready precursors of other donors, e.g., glycosyl
bromides10 and trichloroacetimidates,11 hence, we were inter-
ested in adding glycosyl fluorides to this list. n-Pentenyl do-
nors are usually triggered by halonium ions4d and (or) acids.12
In view of the latter, the Barluenga reagent, bis(pyridinium)
iodonium(I)tetrafluoroborate (IPy2BF4), was of interest as a
possible electrophilic agent.13,14 In this connection, it should
Received 24 July 2012. Accepted 28 August 2012. Published at www.nrcresearchpress.com/cjc on 2 January 2013.
B. Fraser-Reid. Natural Products and Glycotechnology Research Institute Inc. (NPG), 595F Weathersfield Road, Pittsboro, NC 27312, USA.
J.C. Lopez, P. Bernal-Albert, A.M. Gomez, C. Uriel, and J. Ventura. Instituto de Química Orgánica General (IQOG-CSIC), Juan de
la Cierva 3, Madrid 28006, Spain.
Corresponding authors: Bert Fraser-Reid (e-mail: dglucose@aol.com) and J. Cristobal Lopez (e-mail: jc.lopez@csic.es).
Can. J. Chem. 91: 51–65 (2013)
doi:10.1139/cjc-2012-0285
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Can. J. Chem. Vol. 91, 2013
Scheme 1. Attempted activation–glycosylation of 2 with NPG 1.
Table 1. IPy2BF4/HBF4 mediated transformation of n-pentenyl
glycosides to glycosyl fluorides in CH2Cl2.
Temp. (°C)
Entry
Substrate
(time)
Product
Yield (%)
be noted that Clausen and Madsen15 previously converted
n-pentenyl glycosides (NPGs) to glycosyl fluorides.
This interest was sparked by attempts to glycosylate accep-
tor 2 with donor 1 using the Barluenga reagent, along with an
equimolar amount of HBF4 to neutralize nucleophilic pyridine
that is released during the reaction. As shown in Scheme 1, the
hoped-for disaccharide (3) was obtained in a 35% yield; how-
ever, the formation of twice as much glycosyl fluoride (4)
indicated that fluoride ion was competing strongly for the
donor (1).
The 2:1 formation of products 4 and 3 indicated the poten-
tial of the process as a route to glycosyl fluorides.16 The
chances of improving glycosyl fluoride formation should be
enhanced by removing the acceptor 2 and increasing fluoride
ion supply.
Accordingly, a collection of NPGs, Table 1 (1, 5–8), armed
and disarmed, with diverse protecting groups, was treated
at Ϫ40 °C with 1 equiv of IPy2BF4 and a slight excess of
HBF4. Entries i–v of Table 1 showed that the formation of
fluorides 4 and 10–13, respectively, was usually complete in
10–40 min (TLC), with very good to excellent results. Nota-
bly, silyl protecting groups were compatible with the reaction
conditions, as is clear from the conversion of NPG 6b to
glycosyl fluoride 11b (Table 1, entry iii).
The reaction of the NPG tetrabenzoate 8 (Table 1, entry v)
requires special comment. Under the indicated conditions of
Table 1, but with a temperature of –78 °C, the starting material
(8) disappeared after 30 min to give a stable substance. Ex-
posing the latter to BF3·OEt2 for 20 min led to the tetrabenzoyl
glycosyl fluoride 13. The intermediacy of the orthoacyl fluo-
ride 9 was indicated, with this possibility being supported by
the prior work of Griffith and Hindsgaul.17
Our interest in the use of partially protected NPG donors for
regioselective glycosylations prompted us to examine the syn-
thesis of comparable glycosyl fluoride donors (Table 2). Ac-
cordingly, the partially protected NPG mannoside 14 was
treated with 2 equiv of an IPy2BF4/HBF4 mixture at –55 °C for
10 min. As seen from entry i (Table 2), the desired fluoride
(16) was obtained in a 42% yield, but was accompanied by 15%
of disaccharide 17. The gluco analog 15 gave an equal distribu-
tion of products, 18 and 19 (40% and 15%, respectively). Obvi-
ously the concentration of nucleophilic fluoride was not enough
to preclude self-coupled formation of the disaccharides.
The HF–pyridine complex (or Olah’s reagent) has been
used as a source of nucleophilic fluoride,18,19 so it was a
logical choice as a partner for the Barluenga reagent in our
efforts to enhance the formation of glycosyl fluorides.20 Ac-
cordingly, NPGs 14 and 15 were exposed to IPy2BF4 in the
presence of an excess of Olah’s reagent at low temperature.
Indeed, the use of a 2:10 ratio of IPy2BF4/HF (Table 2, entry
iii) on mannoside 14 gave a considerable increase in the yield
of the desired fluoride, 16. However, this was accompanied by
a substantial amount of compound 20, resulting from
iodofluorination of the olefinic residue of the precursor. Low-
ering the ratio of the fluoride source by 50% to 2:5 (Table 2,
entry iv) had the desired effect in that the yield of fluoride 16
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Fraser-Reid et al.
53
Table 2. IPy2BF4/HBF4 and IPy2BF4/HF–pyridine mediated transformation of
partially unprotected n-pentenyl glycosides to glycosyl fluorides.
had increased to 85%. Unfortunately, the iodofluorination
product 20 was still produced in a substantial amount.
With the gluco NPG 15 (Table 2, entry v), the desired
fluoride 18 was obtained in a 94% yield with no evidence of
the corresponding iodofluorination product. Notably, this re-
sult was obtained even though the ratio of reagents (IPy2BF4/HF,
2:10) was very favorable for iodofluorination (Table 2, entries iii
and iv).
Reversing the roles of orthogonal donor and acceptor re-
quired a source of iodonium ions for activating the NPG
donor. Iodonium dicollidine perchlorate (IDCP),21 which has
served us well in the past,22 was chosen for coupling glycosyl
fluoride acceptors 22 and 23 with armed gluco (1, Scheme 2c)
and manno (6a and 6b, Scheme 2d and 2e, respectively)
donors. Products 25, 26a, and 26b were obtained in excellent
yields of 90%, 88%, and 72%, respectively, albeit as ␣/␤
mixtures. The result in Scheme 2e is noteworthy because of
the survival of the silyl protecting group under the reaction
conditions.
The donors in Scheme 2c–2e, were armed; however, the
disarmed counterpart, 8, (Scheme 2f) failed to give 27 with
IDCP as the electrophile. The use of N-iodosuccinimide (NIS)
with BF3·OEt2 proved better, although product 27 was ob-
tained in only in a 25% yield. Because of these facts, the
glycosyl fluoride – NPG couple could be best described as a
semiorthogonal donors pair of donors.23
Glycosyl fluorides and n-pentenyl glycosides as
semiorthogonal glycosyl donors
With the availability of glycosyl fluorides and NPGs, the
possibility of orthogonal coupling between both was now
explored (Scheme 2). To activate the glycosyl fluoride as a
donor, ytterbium triflate (Yb(OTf)3) was chosen as the fluo-
rophilic agent. Schemes 2a and 2b record the results of cou-
pling armed and disarmed donors 12a and 12b, respectively,
with the NPG 21 as acceptor. Disaccharides 24a and 24b were
obtained in encouraging yields of 68% and 75%, respectively.
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Can. J. Chem. Vol. 91, 2013
Scheme 2. n-Pentenyl glycosides (NPGs) and glycosyl fluorides as a pair of semiorthogonal donors.
n-Pentenyl orthoesters (NPOEs) are ~15 kcal (1 cal ϭ 4.184 J)
more reactive than the corresponding NPG,24 and on that
basis, they should serve as better progenitors of glycosyl
fluorides. This possibility was tested by presenting acceptor 2
(1 equiv) to equimolar amounts of NPOE 28 and the armed
fluoride 16 along with NIS (2 equiv) and BF3·OEt2. After
20 min at Ϫ30 °C, glycosylation had occurred by the NPOE
only to give the tetrabenzoylated disaccharide 29 in a 96%
yield (Scheme 3a), with the glycosyl fluoride being recovered
to the extent of 85%.
This result suggested that the NPOE was the superior donor
under the conditions used in Scheme 3a. Attempts were made
to enforce glycosylation of acceptor 2 by armed glycosyl
fluoride 16, in the presence of NPOE 28, by the use of various
fluorophilic agents, but all failed to produce disaccharide 30
(Scheme 3b). These experiments confirmed that activation of
a glycosyl fluoride in the presence of an NPOE is highly unlikely.
Accordingly, chemoselective coupling of NPOE 28 with the
glycosyl fluoride acceptor 23 went smoothly (Scheme 3c) to
give disaccharide 31 in a 94% yield.
In view of the foregoing results, a one-pot synthesis using
three reactants (21, 23, and 28), each of which is a potential
donor, and two of which (21 and 23) are potential acceptors, is
shown in Scheme 4. Thus, glycosyl fluoride 23 served as
acceptor to NPOE donor 28 under NIS/BF3·OEt2 activation
at Ϫ20 °C. After 2 h, NPG 21 was presented, as an acceptor,
for glycosylation by the putative disaccharide under activation
by Yb(OTf)3 at room temperature. After 10 min, the
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Fraser-Reid et al.
55
Scheme 3. Competition experiments for the chemoselective activation of n-Pentenyl orthoesters (NPOEs) in the presence of glycosyl fluorides.
Scheme 4. One-pot synthesis of trisaccharide 32.
n-pentenyl trisaccharide 32 was obtained in a 72% yield as a
single (␣,␣,␣) isomer.
Glycosyl fluorides from furanosyl 1,2-orthoesters
We were interested to see whether the previously discussed
transformations of pyranosyl NPOEs could be extended to
recently described furanosyl counterparts.25,26
Along this line, and taking full advantage of the knowledge
gained in this work, a further extension could be made to the
one-pot synthesis in Scheme 4. Thus, in Scheme 5, methyl
glucoside 33 was added (to 23 and 21) as a third acceptor,
which resulted in the one-pot synthesis of linear tetrasaccha-
ride 34 (obtained as an ␣/␤ mixture). The low yield in this
transformation was ascribed to the poor reactivity of ace-
tylated acceptor 33 towards the intermediate n-pentenyl trisac-
charide donor. In this sense, a considerable amount of
hemiacetal arising from the trisaccharide was observed in the
reaction mixture.
Our exploratory work revealed the need for a different
operational procedure than that used with the pyranose sys-
tems because the furanosyl substrates are much more acid-
sensitive. It is crucial that a solution of the furanosyl orthoester
in CH2Cl2 be added to the reaction mixture of HF–pyridine in
CH2Cl2 rather than in the reverse order. Otherwise, with
NPOE 36, for example, rearrangement to the corresponding
alkyl glycoside 35 was an important reaction course compared
with that of the desired glycosyl fluoride 37 (Scheme 6).
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Can. J. Chem. Vol. 91, 2013
Scheme 5. One-pot synthesis of tetrasaccharide 34.
Scheme 6. Transformation of 1,2-orthoester 36 to furanosyl fluoride 37 by treatment with HF–pyridine complex. (a) Addition of
HF–pyridine complex to a solution of 36 in CH2Cl2. (b) Addition of 36 to a precooled solution of HF–pyridine in CH2Cl2.
With this precaution implemented, the ribo-NPOE 38a gave
the fluoride 44 quantitatively in ~10 min (Table 3, entry i). The
dibenzoyl and dibenzyl arabino substrates, 39a and 40a, re-
spectively, behaved similarly, affording fluorides 45 and 46 in
95% and 91% yields, respectively (Table 3, entries ii and iii).
These results suggested that the nature of the protecting groups
at O3 and O5 did not have a major effect on the formation of
the glycosyl fluorides.
The partially protected analogs with a free C3–OH gave
distinctly different results. The arabino-NPOE 41 was con-
verted to the fluoride 47 in a 91% yield (Table 3, entry vii). In
contrast, the ribo counterpart 42 gave only a 53% yield of
fluoride 48 (Table 3, entry viii).
Not surprisingly, a free C5–OH was unacceptable. Thus,
diol 43 furnished the 1,5-anhydro derivative 49 upon treatment
with HF–pyridine (Table 3, entry ix).
The use of these furanosyl fluorides with other donors for
orthogonal coupling leading to oligofuranosides was tested as
shown in Scheme 7. Glycosyl fluoride 47, when presented to
NPOE 38a under activation with NIS/Yb(OTf)3, gave a prod-
uct that was presumed to be disaccharide 50. This was directly
treated with NPG 51 under activation of BF3·OEt2, which led
to trisaccharide 52.
electrophilic iodonium and nucleophilic fluoride. In the case of
NPGs, Barluenga’s reagent gives good yields of glycosyl
fluorides when HF–pyridine complex is used as an additional
fluoride source. NPOEs can be activated by a combination of
electrophilic iodonium (Barluenga’s reagent) and HBF4 or by
action of HF–pyridine complex in which acidic triggering of
the pentenyl moiety is accompanied by the fluoride nucleo-
phile present in Olah’s reagent. Furthermore, the ensuing
glycosyl fluorides form a semiorthogonal pair of glycosyl
donors when confronted with NPGs.
Experimental section
1H NMR, 13C NMR, and 19F NMR spectra were obtained for
solutions in CDCl3 using either a 300, 400, or a 500 MHz
1
spectrometer. H and 13C NMR spectra were assigned with the
assistance of two-dimensional (2D) correlation spectroscopy
(COSY) and 2D heteronuclear single quantum correlation
(HSQC) experiments. Optical rotations were determined for so-
lutions in chloroform at 25 °C. Column chromatography was
performed on silica gel (230Ϫ400 mesh). TLC was conducted
in precoated Kiesel gel 60 F254 (Merck). Detection was first by
UV light (254 nm), then charring with a 1:20:4 solution of
sulfuric acid / acetic acid / H2O. All solvents were purified by
distillation over drying agents or by elution through a PURE
SOLV purification system. A time-of-flight (TOF) mass analyzer
was used for the HR-MS. Reactions requiring anhydrous condi-
tions were performed under argon. Anhydrous magnesium
Conclusion
NPGs and NPOEs can be transformed into glycosyl fluo-
rides by a variety of methods, which involve the use of
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Fraser-Reid et al.
57
Table 3. Reaction of 1,2-orthoesters 38Ϫ43 with HF–pyridine
complex in CH2Cl2.
chromatography (hexane/EtOAc, 8:2 to 1:1) to provide fluo-
ride 429 (72 mg, 60%) and disaccharide 3 (27 mg, 35%).
HF–pyridine
(equiv)
Yield
(%)
Methyl 2,3,4-tri-O-methyl-6-O-(2,3,4,6-tetra-O-benzyl-␣-D-
glucopyranosyl)-␣-D-glucopyranoside (3)
Entry
Substrate
Product
1H NMR (300 MHz) ␦: 7.34Ϫ7.15 (m, 20H), 5.02 (d, J ϭ
11.1 Hz, 1H), 4.91 (d, J ϭ 10.8 Hz, 1H), 4.84 (d, J ϭ 11.4 Hz,
1H), 4.82 (d, J ϭ 9.9 Hz, 1H), 4.75 (d, J ϭ 11.3 Hz, 1H), 4.62
(d, J ϭ 12.1 Hz, 1H), 4.56 (d, J ϭ 12.1 Hz, 1H), 4.54 (d, J ϭ
10.9 Hz, 1H), 4.48 (m, 1H), 4.20 (m, 1H), 3.78–3.37 (m,
12H), 3.62 (s, 3H), 3.50 (s, 3H), 3.47 (s, 3H), 3.36 (s, 3H).
13C NMR (75 MHz) ␦: 138.5, 138.4, 138.2, 138.1, 128.4 (ϫ2),
128.3 (ϫ6), 128.0 (ϫ2), 127.9 (ϫ2), 127.8 (ϫ2), 127.7 (ϫ2),
127.6 (ϫ2), 127.5 (ϫ2), 103.9, 97.3, 84.8, 83.4, 82.1, 81.7,
79.8, 77.9, 75.7, 75.0 (ϫ2), 74.9, 73.4, 69.8, 69.0, 68.8, 60.8,
60.4, 58.9, 55.1. Anal. calcd for C44H54O11 (758.37): C 69.64,
H 7.17; found: C 69.30, H 7.35.
2,3,4,6-Tetra-O-benzyl-␣-D-glucopyranosyl fluoride (4)
[␣]D ϩ10.7 (c 0.53, CHCl3). 1H NMR (300 MHz) ␦: 7.15–
7.31 (m, 20H), 5.56 (dd, J ϭ 53.2, 2.6 Hz, 1H), 4.98–4.45 (m,
8H), 3.99 (t, J ϭ 9.6 Hz, 1H), 3.94 (m, 1H) 3.79 (m, 1H), 3.65
(m, 1H), 3.57 (ddd, J ϭ 25.7, 9.6, 2.6 Hz, 1H). Atmospheric
pressure ionization and electrospray ionization (API–ES) pos-
itive: 565.2 (M ϩ Na)ϩ. Anal. calcd for C34H35O5F (542.65):
C 75.26, H 6.50; found: C 75.3, H 6.64.
General procedure A — IPy2BF4-mediated
transformation of NPGs to glycosyl fluorides
A solution of IPy2BF4 (44.6 mg, 0.12 mmol) in dry CH2Cl2
(1 mL) under argon and cooled to Ϫ40 °C was treated with
tetrafluoroboric acid (13 ␮L, 0.12 mmol). After 5 min, a
solution of the NPG or orthoester (0.10 mmol) dissolved in dry
CH2Cl2 (2 mL) was added. When all the starting material
disappeared, the reaction mixture was diluted with CH2Cl2
(30 mL) and washed with 10% aqueous sodium thiosulfate
containing sodium bicarbonate, saturated sodium bicarbonate,
and water. The organic layer was then dried and concentrated
and the residue was purified by flash chromatography.
Note: R ϭ n-pentenyl for series a; R ϭ Me for series b.
General procedure B — Reaction of partially
unprotected NPGs with IPy2BF4/HBF4
sulfate was used for drying solutions. (NPGs) 1, 5–8, 14–15,
and 21, pyranose orthoester 28, and furanose orthoesters 36
and 38–43 were prepared following previously described pro-
cedures.27 The exchange of substituents at the different hy-
droxyl groups was carried out following routine procedures.28
A solution of IPy2BF4 (44.6 mg, 0.12 mmol) in dry CH2Cl2
(1 mL) under argon and cooled to Ϫ40 °C was treated with
tetrafluoroboric acid (13 ␮L, 0.12 mmol). After 5 min, a
solution of the NPG (0.10 mmol) dissolved in dry CH2Cl2
(2 mL) was added. When all the starting material disappeared,
the reaction mixture was diluted with CH2Cl2 (30 mL) and
washed with 10% aqueous sodium thiosulfate containing so-
dium bicarbonate, saturated sodium bicarbonate, and water.
The organic layer was then dried and concentrated and the
residue was purified by flash chromatography.
Attempted glycosylation of compound 2 with NPG 1,
mediated by IPy2BF4
A solution of IPy2BF4 (74.4 mg, 0.24 mmol) in dry CH2Cl2
(2 mL) under argon and cooled to Ϫ78 °C was treated with
tetrafluoroboric acid (27 ␮L, 0.24 mmol). After 5 min, a
solution of the NPG 1 (122 mg, 0.23 mmol) and the glycosyl
acceptor 2 (23.6 mg, 0.11 mmol) dissolved in CH2Cl2 (2 mL)
was added. The reaction mixture was stirred at Ϫ78 °C for
30 min after which time it was allowed to warm to Ϫ30 °C and
then stirred for an additional 2 h. The reaction mixture was
then diluted with dichloromethane (30 mL) and washed with
10% aqueous sodium thiosulphate containing sodium bicar-
bonate and water. The organic layer was dried and concen-
trated and the ensuing residue was purified by flash
General procedure C — IPy2BF4/HF–pyridine-mediated
transformation of partially unprotected NPGs to glycosyl
fluorides
A solution of IPy2BF4 (74.2 mg, 0.2 mmol) in dry CH2Cl2
(3 mL) was cooled to Ϫ40 °C. HF–pyridine complex (5, 10, or
20 mmol) was then added and the resultant solution was stirred
for 5 min. A solution of the NPG (0.1 mmol) in dry CH2Cl2
(2 mL) was then added dropwise. The resultant solution was
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Can. J. Chem. Vol. 91, 2013
Scheme 7. Stepwise synthesis of trisaccharide 52.
stirred for 20 min at Ϫ40 °C. The reaction was then diluted
with methylene chloride (20 mL) and the resultant solution
was carefully added to an aqueous solution containing
NaHCO3 and Na2S2O3. The resulting layers were separated
and the aqueous layer was extracted with methylene chloride.
The combined organic layers were washed with saturated
aqueous NaCl. The resultant organic phase was dried over
Na2SO4, filtered, and concentrated. Purification by flash chro-
matography (hexane/EtOAc) afforded the corresponding gly-
cosyl fluorides.
2,3,4,6-Tetra-O-methyl-␣-D-mannopyranosyl fluoride (11a)
This compound was prepared according to General proce-
dure
A
from n-pentenyl 2,3,4,6-tetra-O-methyl-␣-D-
mannopyranoside (6a; 60.8 mg, 0.2 mmol). Silica gel chro-
matography (hexane/EtOAc, 7:3) provided 11a (45 mg, 94%).
1
[␣]D ϩ28.7 (c 1.5, CHCl3). H NMR (300 MHz) ␦: 5.65 (dd,
J ϭ 1.6, 50.2 Hz, 1H), 3.76Ϫ3.58 (m, 6H), 3.51 (s, OMe, 3H),
3.50 (s, OMe, 3H), 3.49 (s, OMe, 3H), 3.39 (s, OMe, 3H).
13C NMR (75 MHz) ␦: 105.5 (d, J ϭ 220.8 Hz), 80.4 (d, J ϭ
2.0 Hz), 75.8 (d, J ϭ 34.6 Hz), 75.4, 73.6 (d, J ϭ 2.5 Hz),
60.6, 59.5, 59.2, 58.0. API-ES positive: 477.3 (2M ϩ H)ϩ,
261.1 (M ϩ Na)ϩ. Anal. calcd for C10H19O5F (238.12): C
50.41, H 8.04; found: C 50.17, H 7.96.
General procedure D — HF–pyridine mediated
transformation of 1,2-orthoesters to glycosyl fluorides
A solution of the 1,2-orthoester (1 equiv) in dry CH2Cl2
(5 mL/mmol) was added to a solution of HF–pyridine
(20 equiv unless otherwise specified) in dry CH2Cl2 (1 mL/mmol)
under argon and cooled to Ϫ40 °C. After 5Ϫ10 min, when all the
starting material had disappeared, the reaction mixture was diluted
with CH2Cl2 (30 mL) and quenched by saturated aqueous NaHCO3.
The layers were separated, the aqueous phase was extracted
with CH2Cl2, and the combined organic layers were washed
with saturated aqueous NaCl. The resultant organic phase
was dried over MgSO4, filtered, and concentrated. The
residue was purified by silica gel flash column chromatog-
raphy eluting with a mixture of hexane and ethyl acetate to
afford the pure products.
6-O-tert-Butyldiphenylsilyl-2,3,4-O-tri-O-methyl-␣-D-
mannopyranosyl fluoride (11b)
This compound was prepared according to General proce-
dure
A
from n-pentenyl 6-O-tert-butyldimethylsilyl-
2,3,4-O-tri-O-methyl-␣-D-mannopyranoside (6b; 53 mg,
0.1 mmol). Silica gel chromatography (hexane/EtOAc, 8:2)
provided 11b (39.3 mg, 85%). [␣]D ϩ26.5 (c 1.2, CHCl3).
1H NMR (300 MHz) ␦: 7.75Ϫ7.69 (m, 5H), 7.43–7.35 (m, 5H),
5.72 (dd, J ϭ 50.5, 1.9 Hz, 1H), 3.97 (dd, J ϭ 11.5, 3.4 Hz,
1H), 3.85 (t, J ϭ 9.5 Hz, 1H), 3.85 (dd, J ϭ 11.5, 1.7 Hz, 1H),
3.74 (m, 1H), 3.67Ϫ3.63 (m, 1H), 3.57 (s, 3H), 3.56 (m, 1H),
3.55 (s, 3H), 3.54 (s, 3H), 1.07 (s, 9H). 13C NMR (75 MHz) ␦:
135.9 (ϫ2), 135.6 (ϫ2), 133.8, 133.3, 129.5 (ϫ2), 127.6 (ϫ2),
127.5 (ϫ2), 105.6 (d, J ϭ 219.4 Hz), 80.4, 75.9, 75.0, 74.8,
62.3, 60.7, 58.9, 57.9, 26.7 (ϫ3), 19.4. API-ES positive: 480.3
(M ϩ NH4)ϩ, 485.3 (M ϩ Na)ϩ. Anal. calcd for C25H35O5FSi
(462.22): C 64.9, H 7.63; found: C 65.02, H 7.58.
2,3,4,6-Tetra-O-methyl-␣-D-glucopyranosyl fluoride (10)
This compound was prepared according to General procedure A
from n-pentenyl 2,3,4,6-tetra-O-methyl-␣-D-glucopyranose (5;
60.8 mg, 0.2 mmol). Silica gel chromatography (hexane/EtOAc, 7:3)
provided pure 10 (50 mg, quantitative yield). 1H NMR (300 MHz)
␦: 5.66 (dd, J ϭ 53.3, 2.6 Hz, 1H), 3.80–3.75 (m, 1H), 3.64 (s, OMe,
3H), 3.62–3.38 (m, 3H), 3.54 (s, OMe, 3H), 3.53 (s, OMe, 3H), 3.40
(s, OMe, 3H), 3.28 (t, J ϭ 9.4 Hz, 1H), 3.19 (ddd, J ϭ 25.6, 9.4,
2.6 Hz, 1H). 13C NMR (75 MHz) ␦: 104.9 (d, J ϭ 224.8 Hz), 82.7,
81.2 (d, J ϭ 24.6 Hz), 78.2, 72.3 (J ϭ 4.0 Hz), 70.2, 60.9, 60.5, 59.1
(ϫ2). API-ES positive: 477.3 (2M ϩ H)ϩ. Anal. calcd for
C10H19O5F (238.12): C 50.41, H 8.04; found: C 50.30, H 8.28.
2,3,4,6-Tetra-O-benzyl-␣-D-mannopyranosyl fluoride (12a)
This compound was prepared according to General proce-
dure
A
from n-pentenyl 2,3,4,6-tetra-O-benzyl-␣-D-
mannopyranoside (7a; 60.8 mg, 0.1 mmol). Silica gel
chromatography (hexane/EtOAc, 9:1) provided pure 12a (51 mg,
94%).30 [␣]D ϩ25.9 (c 0.56, CHCl3). 1H NMR (300 MHz) ␦:
7.35–7.18 (20H, m), 5.60 (d, J ϭ 50.6 Hz, 1H), 4.88 (d, J ϭ
Published by NRC Research Press

Fraser-Reid et al.
59
10.8 Hz, 1H), 4.81 (d, J ϭ 12.3 Hz, 1H), 4.70–4.63 (4H, m),
4.56–4.53 (2H, m), 4.08 (t, J ϭ 9.7 Hz, 1H), 3.93–3.88 (3H,
m), 3.79 (dd, J ϭ 11.0, 4.5 Hz, 1H), 3.72 (d, J ϭ 10.9 Hz, 1H).
API-ES positive: 565.3 (M ϩ Na)ϩ. Anal. calcd for
C34H35FO5: C 75.26, H 6.50; found: C 75.16, H 6.45.
217.3 Hz), 79.0 (d, J ϭ 1.8 Hz), 75.2, 73.5, 73.3 (d, J ϭ
2.9 Hz), 73.2, 72.4, 68.2, 67.1 (d, J ϭ 39.7 Hz). 19F NMR
(376 MHz) ␦: Ϫ141.0 (d, J ϭ 49.4 Hz). API-ES positive:
475.1 (M ϩ Na)ϩ. Anal. calcd for C27H29O5F (452.51):
C 71.66, H 6.46; found: C 71.54, H 6.34.
2-O-Benzoyl-3,4,6-O-tri-O-benzyl-␣-D-mannopyranosyl
fluoride (12b)
3,4,6-Tri-O-benzyl-2-O-(3,4,6-tri-O-benzyl-D-
mannopyranosyl)-␣-D-mannopyranosyl fluoride (17)
[␣]Hg (435 nm) ϩ38.2 (c 0.6, CHCl3). 1H NMR (300 MHz)
␦: 7.25Ϫ7.08 (m, 30H), 5.63 (dd, J ϭ 50.4, 1.3 Hz, 1H), 5.05
(bs, 1H), 4.87Ϫ4.48 (m, 14H), 4.11 (m, 2H), 3.91Ϫ3.72 (m,
8H). Anal. calcd for C54H57O10F (884.39): C 73.28, H 6.49;
found: C 73.14, H 6.34.
This compound was prepared according to General proce-
dure
A
from n-pentenyl 2-O-benzoyl-3,4,6-O-tri-O-benzyl-
␣-D-mannopyranoside (7b; 44.6 mg, 0.12 mmol). Silica gel
chromatography (hexane/EtOAc, 9:1) provided 12b (50 mg,
1
90%). H NMR (300 MHz) ␦: 8.08Ϫ8.06 (m, 2H), 8.05 (m,
1H), 7.56Ϫ7.19 (m, 17H), 5.75 (dd, J ϭ 49.3, 1.7 Hz, 1H),
5.74 (t, J ϭ 2.4 Hz, 1H), 4.89 (d, J ϭ 10.5 Hz, 1H), 4.81 (d,
J ϭ 11.1 Hz, 1H), 4.73 (d, J ϭ 12.0 Hz, 1H), 4.61 (d, J ϭ
11.4 Hz, 1H), 4.57 (d, J ϭ 10.8 Hz, 1H), 4.55 (d, J ϭ 12.0 Hz,
1H), 4.21Ϫ3.96 (m, 3H), 3.91 (dd, J ϭ 11.2, 3.6 Hz, 1H), 3.80
(dd, J ϭ 11.2, 1.5 Hz, 1H). 13C NMR (75 MHz) ␦: 165.3,
138.1, 138.0, 137.5, 133.4, 129.9 (ϫ2), 128.5 (ϫ2), 128.4
(ϫ5), 128.3 (ϫ3), 128.0 (ϫ2), 127.9 (ϫ2), 127.8, 127.7, 127.5
(ϫ2), 105.5 (d, J ϭ 219.3 Hz), 77.2, 75.3, 73.9 (d, J ϭ
2.5 Hz), 73.4, 73.2, 71.8, 68.3, 67.2 (d, J ϭ 40.0 Hz). API-ES
positive: 579 (M ϩ Na)ϩ. Anal. calcd for C34H33O6F
(556.23): C 73.36, H 5.98; found: C 73.54, H 5.86.
Reaction of n-pentenyl 3,4,6-tri-O-benzyl-␣-D-
glucopyranose (15)
Application of General procedure B to partially protected
NPG 15 (77.8 mg, 0.15 mmol) followed by flash chromatog-
raphy (hexane/EtOAc, 8:2) afforded glycosyl fluoride 18
(27 mg, 40%) followed by disaccharide 19 (20 mg, 15%).
When NPG 15 (38.9 mg, 0.075 mmol) was subjected to the
General procedure C with 10 equiv of HF–pyridine followed
by flash chromatography (hexane/EtOAc, 8:2), glycosyl fluo-
ride 18 was exclusively obtained (32 mg, 94%).
3,4,6-Tri-O-benzyl-␣-D-glucopyranosyl fluoride (18)
2,3,4,6-Tetra-O-benzoyl-␣-D-mannopyranosyl fluoride (13)
A solution of IPy2BF4 (55.8 mg, 0.15 mmol) in dry CH2Cl2
(1 mL) was cooled to Ϫ78 °C and HBF4 (16 ␮L, 0.15 mmol)
was added. After 5 min of stirring, a solution of n-pentenyl
2,3,4,6-tetra-O-benzoyl-␣-D-mannopyranoside (8; 66.4 mg,
0.1 mmol) in dry CH2Cl2 (3 mL) was added. The stirring was
maintained at Ϫ78 °C for 30 min before BF3·OEt2 (13 ␮L,
0.1 mmol) was added. The reaction mixture was then warmed
to room temperature over 20 min and washed with 10%
aqueous sodium thiosulfate containing sodium bicarbonate,
saturated sodium bicarbonate, and water. The organic layer
was then dried and concentrated and the residue was purified
by flash chromatography (hexane/EtOAc, 8:2) to provide pure
13 (45 mg, 75%). [␣]D Ϫ29.7 (c 1.6, CHCl3). 1H NMR (300 MHz)
␦: 8.14Ϫ7.26 (m, 20H), 6.22 (t, J ϭ 10.1 Hz, 1H), 5.96Ϫ5.86
(m, 2H), 5.86 (dd, J1,2 ϭ 43.1, 1.8 Hz, 1H), 4.79 (dd, J ϭ 12.3,
2.2 Hz, 1H), 4.61 (m, 1H), 4.49 (dd, J ϭ 12.3, 3.8 Hz, 1H).
API-ES positive: 622.1 (M ϩ Na)ϩ. Anal. calcd for
C34H27O9F (598.57): C 68.22, H 4.55; found: C 68.14, H 4.43.
[␣]D ϩ71.3 (c 0.5, CHCl3). 1H NMR (300 MHz) ␦:
7.28Ϫ7.08 (m, 15H), 5.54 (dd, J ϭ 53.8, 2.3 Hz, 1H), 4.84 (d,
J ϭ 11.3 Hz, 1H), 4.75 (d, J ϭ 11.1 Hz, 2H), 4.55 (d, J ϭ
12.1 Hz, 1H), 4.47 (d, J ϭ 11.8 Hz, 1H), 4.52 (d, J ϭ 12.2 Hz,
1H), 3.98 (m, 1H), 3.81Ϫ3.76 (m, 4H), 3.70 (dd, J ϭ 10.8,
1.8 Hz, 1H). 13C NMR (75 MHz) ␦: 138.2, 137.8, 137.6, 128.5
(ϫ2), 128.4 (ϫ3), 127.9 (ϫ3), 127.84 (ϫ3), 127.81 (ϫ3),
127.7, 107.1 (d, J ϭ 224.0 Hz), 81.9, 76.6, 75.4, 74.9, 73.5,
73.0 (d, J ϭ 3.4 Hz), 72.3 (d, J ϭ 25.6 Hz), 67.7. 19F NMR
(376 MHz) ␦: Ϫ151.2 (dd, J ϭ 53.8, 24.6 Hz). API-ES
positive: 475.1 (M ϩ Na)ϩ. Anal. calcd for C27H29O5F
(452.51): C 71.66, H 6.46; found: C 71.60, H 6.48.
3,4,6-Tri-O-benzyl-2-O-(3,4,6-tri-O-benzyl-␣-D-
glucopyranosyl)-␣-D-glucopyranosyl fluoride (19)
1H NMR (300 MHz) ␦: 7.37Ϫ7.07 (m, 30H), 5.76 (dd, J ϭ
53.5, 1.5 Hz, 1H), 5.07 (d, J ϭ 2.1 Hz, 1H), 4.93 (d, J ϭ
11.2 Hz, 1H), 4.87 (d, J ϭ 11.0 Hz, 1H), 4.84 (d, J ϭ 10.7 Hz,
1H), 4.83 (d, J ϭ 10.4 Hz, 1H), 4.82 (d, J ϭ 10.9 Hz, 1H),
4.76 (d, J ϭ 10.5 Hz, 1H), 4.62 (d, J ϭ 12.1 Hz, 1H), 4.55 (d,
J ϭ 12.1 Hz, 1H), 4.54 (d, J ϭ 10.7 Hz, 1H), 4.50 (d, J ϭ
12.1 Hz, 1H), 4.47 (d, J ϭ 10.9 Hz, 1H), 4.34 (d, J ϭ 12.1 Hz,
1H), 3.97Ϫ3.90 (m, 3H), 3.84Ϫ3.68 (m, 7H), 3.47 (dd, J ϭ
11.1, 2.8 Hz, 1H), 3.40 (dd, J ϭ 10.7, 1.2 Hz, 1H). 13C NMR
(75 MHz) ␦: 138.5, 138.4, 137.9, 137.8, 137.6 (ϫ2), 128.5 (ϫ4),
128.4 (ϫ2), 128.3 (ϫ2), 128.3 (ϫ2), 128.2 (ϫ2), 128.1 (ϫ2),
128.0 (ϫ2), 127.9 (ϫ4), 127.8, 127.8, 127.7 (ϫ2), 127.7 (ϫ2),
127.6 (ϫ2), 127.6, 127.5, 104.1 (d, J ϭ 226.6 Hz), 96.5, 82.9,
79.8, 77.1, 76.1, 75.2, 75.1, 74.9 (d, J ϭ 26.5 Hz), 74.8, 73.5,
73.3, 72.9 (d, J ϭ 3.6 Hz), 72.6, 70.8, 67.8, 67.7. API-ES
positive: 886.3 (M ϩ H)ϩ. Anal. calcd for C54H57O10F
(884.39): C 73.28, H 6.49; found: C 73.2, H 6.48.
Reaction of n-pentenyl 3,4,6-tri-O-benzyl-␣-D-
mannopyranoside (14)
Application of General procedure B to partially protected
NPG 14 (77.8 mg, 0.15 mmol) followed by flash chromatog-
raphy (hexane/EtOAc, 8:2) afforded glycosyl fluoride 16
(28.5 mg, 42%) followed by disaccharide 17 (19.5 mg, 15%).
3,4,6-Tri-O-benzyl-␣-D-mannopyranosyl fluoride (16)
[␣]D ϩ9.3 (c 1.3, CHCl3). 1H NMR (400 MHz) ␦:
7.29Ϫ7.29 (m, 15H), 5.59 (dd, J ϭ 49.4, 1.6 Hz, 1H), 4.75 (d,
J ϭ 10.8 Hz, 1H), 4.66 (d, J ϭ 11.5 Hz, 1H), 4.62 (d, J ϭ
11.4 Hz, 1H), 4.58 (d, J ϭ 12.2 Hz, 1H), 4.46 (d, J ϭ 10.8 Hz,
1H), 4.45 (d, J ϭ 12.2 Hz, 1H), 4.03 (m, 1H), 3.91Ϫ3.78 (m,
3H), 3.70 (dd, J ϭ 10.9, 3.4 Hz, 1H), 3.62 (dd, J ϭ 10.9,
1.4 Hz, 1H). 13C NMR (100 MHz) ␦: 138.0, 137.9, 137.5,
128.6 (ϫ2), 128.4 (ϫ2), 128.3 (ϫ2), 128.1, 127.9 (ϫ2),
127.88 (ϫ2), 127.85 (ϫ2), 127.7, 127.6, 107.2 (d, J ϭ
4-Fluor-5-iodo-pentyl 3,4,6-tri-O-benzyl-␣-D-
mannopyranoside (20)
1
Mixture of diastereomers (1:1). H NMR (300 MHz) ␦:
7.30Ϫ7.08 (m, 15H), 4.82 (d, J ϭ 1.5 Hz, 1H), 4.75 (d, J ϭ
Published by NRC Research Press

60
Can. J. Chem. Vol. 91, 2013
10.8 Hz, 1H), 4.65 (d, J ϭ 11.9 Hz, 1H), 4.57 (d, J ϭ 12.1 Hz,
1H), 4.46 (d, J ϭ 11.9 Hz, 1H), 4.43 (d, J ϭ 10.8 Hz, 1H),
4.39 (m, 1H), 3.94 (m, 1H), 3.82Ϫ3.61 (m, 5H), 3.42Ϫ 3.34
(m, 1H), 3.24 (d, J ϭ 5.4 Hz, 1H), 3.18 (d, J ϭ 5.4 Hz, 1H),
1.85Ϫ1.52 (m, 4H). 13C NMR (75 MHz) ␦: 138.4 (ϫ2), 138.1,
128.8 (ϫ2), 128.6 (ϫ2), 128.5 (ϫ2), 128.2 (ϫ2), 128.1 (ϫ2),
128.0 (ϫ3), 127.9, 127.8, 99.5, 99.4, 93.3, 90.9, 80.4, 75.4,
74.5, 73.7, 72.3, 71.4, 69.2, 68.6, 67.2, 32.0, 31.7, 25.0, 6.9,
6.6. Anal. calcd for C32H38O6FI (664.54): C 57.84, H 5.76;
found: C 57.73, H 7.64.
67.0, 66.7, 60.8, 58.8, 57.5, 30.3, 28.6. API-ES positive: 844.3
(M ϩ NH4)ϩ, 872 (M ϩ 2Na)ϩ. Anal. calcd for C48H58O12
(826.39): C 69.71, H 7.07; found: C 69.61, H 6.94.
2,3,4-Tri-O-methyl-6-O-(2,3,4,6-tetra-O-benzyl-D-
glucopyranosyl)-␣- and -␤-D-glucopyranosyl fluoride (25)
To a stirred solution of pentenyl-2,3,4,6-tetra-O-benzyl-␣-
D-glucopyranoside (1; 122 mg, 0.2 mmol) and 2,3,4-tri-O-
methyl-␣-D-glucopyranosyl fluoride (22; 34.8 mg, 0.15 mmol)
in CH2Cl2 (6 mL) under argon was added IDCP (234 mg,
0.5 mmol) in one portion. The solution was stirred for 2 h and
then the mixture was quenched by washing with a mixture of
aqueous sodium bicarbonate and aqueous sodium thiosulfate
solution. The separated organic extract was dried, filtered, and
concentrated. Purification by flash chromatography (hexane/
EtOAc, 8:2 to 1:1) gave disaccharide 25␣ (51 mg, 45%)
followed by disaccharide 25␤ (50 mg, 45%). ␣-Anomer:
[␣]D ϩ37.5 (c 0.35, CHCl3). 1H NMR (300 MHz) ␦:
7.30Ϫ7.05 (m, 20H), 5.48 (dd, J ϭ 53.3, 2.7 Hz, 1H), 4.98 (d,
J ϭ 17.4 Hz, 1H), 4.96 (d, J ϭ 10.1 Hz, 1H), 4.84 (d, J ϭ
10.8 Hz, 1H), 4.81 (d, J ϭ 10.8 Hz, 1H), 4.66 (d, J ϭ 16.7 Hz,
1H), 4.61 (d, J ϭ 17.2 Hz, 1H), 4.54 (d, J ϭ 12.1 Hz, 1H),
4.42 (bs, 1H), 4.40 (d, J ϭ 12.1 Hz, 1H), 3.91 (t, J ϭ 9.2 Hz,
1H), 3.80Ϫ3.39 (m, 9H), 3.56 (s, 3H), 3.48 (s, 3H), 3.38 (s,
3H), 3.24 (t, J ϭ 9.5 Hz, 1H), 2.93 (ddd, J ϭ 25.7, 9.5, 2.7 Hz,
1H). 13C NMR (75 MHz) ␦: 138.8, 138.5, 138.2, 137.9, 128.3
(ϫ5), 127.9 (ϫ3), 127.8 (ϫ3), 127.7 (ϫ3), 127.6 (ϫ2), 127.5
(ϫ2), 127.3 (ϫ2), 104.9 (d, J ϭ 226.3 Hz), 94.4, 82.9, 81.8,
81.2 (d, J ϭ 24.8 Hz), 80.1, 78.4, 77.5, 75.6, 75.1, 73.4, 72.3,
72.4 (d, J ϭ 3.5 Hz), 70.3, 68.4, 66.0, 60.8, 60.6, 59.1. API-ES
positive: 764.3 (M ϩ NH4)ϩ, 769.2 (M ϩ Na)ϩ. Anal. calcd
for C43H51FO10 (746.86): C 69.15, H 6.88; found: C 69.35, H
6.65. ␤-Anomer: [␣]D ϩ17.5 (c 0.45, CHCl3). 1H NMR (300 MHz)
␦: 7.29Ϫ7.08 (m, 20H), 5.60 (dd, J ϭ 53.3, 2.6 Hz, 1H), 4.90
(d, J ϭ 11.0 Hz, 1H), 4.84 (d, J ϭ 10.8 Hz, 1H), 4.74 (d, J ϭ
10.8 Hz, 1H), 4.72 (d, J ϭ 9.3 Hz, 1H), 4.69 (d, J ϭ 11.0 Hz,
1H), 4.55 (d, J ϭ 12.2 Hz, 1H), 4.49 (d, J ϭ 12.2 Hz, 1H),
4.47 (d, J ϭ 10.8 Hz, 1H), 4.37 (d, J ϭ 7.7 Hz, 1H), 4.13 (dd,
J ϭ 11.0, 1.7 Hz, 1H), 3.83 (ddd, J ϭ 10.0, 4.5, 1.6 Hz, 1H),
3.70Ϫ3.40 (m, 8H), 3.56 (s, 3H), 3.47 (s, 3H), 3.39 (s, 3H),
3.18 (t, J ϭ 9.6 Hz, 1H), 3.11 (ddd, J ϭ 25.7, 9.6, 2.7 Hz, 1H).
13C NMR (75 MHz) ␦: 138.5, 138.3, 138.1, 137.9, 128.4 (ϫ2),
128.33 (ϫ2), 128.32 (ϫ2), 128.31 (ϫ2), 128.0 (ϫ2), 127.9
(ϫ2), 127.8 (ϫ2), 127.7, 127.6 (ϫ2), 127.57, 127.56, 127.55,
104.8 (d, J ϭ 226.4 Hz), 103.7, 84.8, 82.8, 81.9, 81.3 (d, J ϭ
24.8 Hz), 78.5, 77.8, 75.7, 75.0, 74.9, 74.8, 73.4, 72.2 (d, J ϭ
3.9 Hz), 68.9, 68.1, 60.9, 60.5, 59.1. API-ES positive: 769.2
(M ϩ Na)ϩ. Anal. calcd for C43H51FO10 (746.86): C 69.15, H
6.88; found: C 69.3, H 6.93.
n-Pentenyl 2,3,4-tri-O-methyl-6-O-(2,3,4,6-tetra-O-benzyl-
␣-D-mannopyranosyl)-␣-D-mannopyranoside (24a)
To a stirred solution of fluoride 12a (54.2 mg, 0.1 mmol),
NPG 21 (29 mg, 0.1 mmol), and 4 Å molecular sieves (50 mg)
in CH2Cl2 (5 mL) was added ytterbium(III) trifluorometh-
anesulfonate (62 mg, 0.1 mmol). Stirring was maintained for
10 min, then the reaction mixture was diluted with CH2Cl2
(15 mL) and washed with saturated aqueous sodium bicarbon-
ate. The organic extract was dried over Na2SO4, filtered, and
concentrated. The residue was purified by flash chromatogra-
phy (hexane/EtOAc, 7:3) to give disaccharide 24a (55.2 mg,
1
68%). [␣]D ϩ37.6 (c 1.5, CHCl3). H NMR (300 MHz) ␦:
7.32Ϫ7.06 (m, 20H), 5.71 (ddt, J ϭ 17.1, 10.4, 6.6 Hz, 1H),
5.04 (s, 2H), 4.86Ϫ4.96 (m, 1H), 4.81 (d, J ϭ 10.9 Hz, 1H),
4.73 (bs, 1H), 4.65 (s, 2H), 4.61 (d, J ϭ 12.2 Hz, 1H), 4.53 (d,
J ϭ 12.2 Hz, 1H), 4.51 (d, J ϭ 12.2 Hz, 1H), 4.46 (d, J ϭ
12.1 Hz, 1H), 4.43 (d, J ϭ 10.9 Hz, 1H), 3.85Ϫ3.26 (m, 14H),
3.42 (s, 3H), 3.41 (s, 3H), 3.36 (s, 3H), 2.06Ϫ1.97 (m, 2H),
1.61Ϫ1.52 (m, 2H). 13C NMR (75 MHz) ␦: 138.7, 138.6,
138.5, 138.4, 137.9, 128.3 (ϫ2), 128.2 (ϫ6), 127.8 (ϫ2),
127.7 (ϫ2), 127.6 (ϫ2), 127.5 (ϫ2), 127.4 (ϫ2), 127.3 (ϫ2),
114.9, 98.0, 96.6, 81.4, 79.9, 77.1, 76.1, 74.9, 74.8 (ϫ2), 73.2,
72.3, 71.8, 71.7, 71.4, 69.2, 66.9, 65.9, 60.8, 58.8, 57.6, 30.3,
28.5. API-ES positive: 830.5 (M ϩ NH4)ϩ, 835.2 (M ϩ Na)ϩ,
859.5 (M ϩ 2Na)ϩ. Anal. calcd for C48H60O11 (812.98):
C 70.91, H 7.44; found: C 71.06, H 7.37.
n-Pentenyl 2,3,4-tri-O-methyl-6-O-(2-O-benzoyl-,3,4,6-tri-
O-benzyl-␣-D-mannopyranosyl)-␣-D-mannopyranoside
(24b)
To a stirred solution of fluoride 12b (27.8 mg, 0.05 mmol),
NPG 21 (14.5 mg, 0.05 mmol), and 4 Å molecular sieves
(25 mg) in CH2Cl2 (3 mL) was added ytterbium(III) trifluo-
romethanesulfonate (62 mg, 0.1 mmol). Stirring was main-
tained for 10 min, then the reaction mixture was diluted with
CH2Cl2 (15 mL) and washed with saturated aqueous sodium
bicarbonate. The organic extract was dried over Na2SO4, fil-
tered, and concentrated. The residue was purified by flash
chromatography (hexane/EtOAc, 7:3) to give disaccharide 24b
1
(31 mg, 75%). [␣]D ϩ13.2 (c 1.3, CHCl3). H NMR (300 MHz)
2,3,4-Tri-O-methyl-6-O-(2,3,4,6-tetra-O-methyl-D-
␦: 8.09Ϫ8.06 (m, 2H), 7.57Ϫ7.17 (m, 18H), 5.80 (ddt, J ϭ
16.8, 10.2, 6.6 Hz, 1H), 5.73 (m, 1H), 5.09 (d, J ϭ 1.8 Hz,
1H), 5.05Ϫ4.95 (m, 2H), 4.88 (d, J ϭ 1.5 Hz, 1H), 4.87 (d,
J ϭ 10.8 Hz, 1H), 4.80 (d, J ϭ 12.3 Hz, 1H), 4.76 (d, J ϭ
12.9 Hz, 1H), 4.54 (m, 3H), 4.12Ϫ4.10 (m, 1H), 3.96 (m, 1H),
3.91 (dd, J ϭ 10.8, 3.6 Hz, 1H), 3.81Ϫ3.57 (m, 8H), 3.51 (s,
6H), 3.51 (s, 3H), 3.46Ϫ3.37 (m, 2H). 13C NMR (75 MHz) ␦:
165.4, 138.6, 138.5, 138.0, 137.9, 132.9, 130.0, 129.9 (ϫ3),
128.3 (ϫ2), 128.29 (ϫ2), 128.24 (ϫ2), 128.21 (ϫ2), 128.1
(ϫ2), 127.8 (ϫ2), 127.6, 127.5 (ϫ2), 127.4, 114.9, 98.1, 96.5,
81.4, 78.3, 76.3, 75.1, 74.2, 73.3, 71.5, 71.4, 71.0, 69.0, 68.7,
mannopyranosyl)-␣- and -␤-D-mannopyranosyl fluoride (26a)
To a stirred solution of fluoride 23 (22 mg, 0.1 mmol), NPG
6a (30 mg, 0.1 mmol), and 4 Å molecular sieves (25 mg) in
CH2Cl2 (3 mL) was added I(coll)2ClO4 (117 mg, 0.25 mmol).
Stirring was maintained for 1 h, then the reaction mixture was
diluted with CH2Cl2 (15 mL) and washed with 10% aqueous
sodium thiosulfate containing sodium bicarbonate, saturated
aqueous sodium bicarbonate, and water. The organic extract
was dried over Na2SO4, filtered, and concentrated. The residue
was purified by flash chromatography (hexane/EtOAc, 2:8)
Published by NRC Research Press

Fraser-Reid et al.
61
to give disaccharide 26a␣ (20 mg, 44%) followed by
disaccharide 26a␤ (19 mg, 44%). ␣-Anomer: [␣]D ϩ26.8 (c 0.15,
CHCl3). H NMR (300 MHz) ␦: 5.65 (dd, J ϭ 50.4, 2.1 Hz,
(44.8 mg, 0.2 mmol), and 4 Å molecular sieves (25 mg) in
anhydrous CH2Cl2 (3 mL) was stirred under argon for 10 min
at room temperature. Then the reaction was cooled to Ϫ30 °C
and BF3OEt2 (15 ␮L, 0.12 mmol) was added. After 30 min,
the reaction was diluted with CH2Cl2 (10 mL), washed with
10% aqueous Na2S2O3 and saturated aqueous NaHCO3
(10 mL), extracted with CH2Cl2, dried over Na2SO4, filtered,
and concentrated. The obtained residue was a complex mixture
of compounds from which disaccharide 27 could be purified
by flash chromatography (hexane/AcOEt, 7:3; 20 mg, 25%).
1
1H), 5.03 (d, J ϭ 1.8 Hz, 1H), 3.91 (dd, J ϭ 12.0, 4.5 Hz, 1H),
3.74Ϫ3.70 (m, 2H), 3.67Ϫ3.65 (m, 3H), 3.61 (m, 1H), 3.56 (s,
3H), 3.53 (s, 3H), 3.52 (s, 3H), 3.49 (s, 3H), 3.46 (s, 3H), 3.40
(s, 3H), 3.58Ϫ3.44 (m, 6H). 13C NMR (75 MHz) ␦: 105.4 (d,
J ϭ 221.3 Hz), 97.3, 81.1, 80.6 (d, J ϭ 1.6 Hz), 76.8, 76.3,
75.7 (d, J ϭ 34.1 Hz), 75.1, 73.7 (d, J ϭ 2.2 Hz), 71.6, 71.3,
65.9, 60.9, 60.6, 59.4, 59.2, 58.8, 57.9, 57.7. API-ES positive:
465.2 (M ϩ Na)ϩ. Anal. calcd for C19H35FO10 (442.47):
C 51.57, H 7.97; found: C 51.64, H 8.03. ␤-Anomer:
[␣]D Ϫ20.1 (c 0.15, CHCl3). 1H NMR (300 MHz) ␦: 5.66 (dd,
J ϭ 50.4, 1.8 Hz, 1H), 4.48 (bs, 1H), 4.22 (dd, J ϭ 11.1,
1.5 Hz, 1H), 3.87Ϫ3.82 (m, 1H), 3.73Ϫ3.70 (m, 2H), 3.65 (s,
3H), 3.52 (s, 3H), 3.51 (s, 6H), 3.49 (s, 3H), 3.48 (s, 3H), 3.41
(s, 3H), 3.67Ϫ3.25 (m, H), 3.18 (dd, J ϭ 8.7, 3.3 Hz, 1H).
API-ES positive: 465.2 (M ϩ Na)ϩ. Anal. calcd for
C19H35FO10 (442.47): C 51.57, H 7.97; found: C 51.39,
H 8.15.
1
[␣]D Ϫ2.3 (c 0.9, CHCl3). H NMR (300 MHz) ␦: 8.0Ϫ7.15
(m, 20H), 6.04 (t, J ϭ 10.0 Hz, 1H), 5.87 (dd, J ϭ 10.1,
3.3 Hz, 1H), 5.70 (dd, J ϭ 3.2, 1.8 Hz, 1H), 5.64 (dd, J ϭ 50.3,
1.8 Hz, 1H), 5.14 (d, J ϭ 1.6 Hz, 1H), 4.67Ϫ4.58 (m, 1H),
4.47Ϫ4.39 (m, 2H), 3.96 (dd, J ϭ 11.5, 5.3 Hz, 1H),
3.87Ϫ3.78 (m, 2H), 3.67 (m, 1H), 3.54 (s, 3H), 3.48 (s, 3H),
3.46 (s, 3H), 3.53Ϫ3.42 (m, 2H). 13C NMR (75 MHz) ␦:
166.2, 165.4 165.3, 165.2, 133.4 (ϫ2), 133.1, 133.0, 129.9,
129.8 (ϫ4), 129.7 (ϫ2), 129.6 (ϫ2), 129.4, 129.1, 128.9,
128.5 (ϫ2), 128.4 (ϫ2), 128.3 (ϫ2), 128.2 (ϫ2), 105.3 (d,
J ϭ 220.8 Hz), 98.0, 80.5, 75.5 (d, J ϭ 34.0 Hz), 75.4, 73.7,
70.3, 69.9, 68.8, 67.1, 66.9, 62.8, 60.9, 59.4, 57.8. API-ES
positive: 825.2 (M ϩ Na)ϩ. Anal. calcd for C43H43FO14
(802.79): C 64.33, H 5.40; found: C 64.47, H 5.49.
6-O-tert-Butyldiphenylsilyl-2,3,4-tri-O-methyl-6-O-(2,3,4,6-
tetra-O-methyl-D mannopyranosyl-␣- and -␤-D-
mannopyranosyl fluoride (26b)
To a stirred solution of fluoride 23 (22 mg, 0.1 mmol), NPG
6b (52.8 mg, 0.1 mmol), and 4 Å molecular sieves (25 mg) in
CH2Cl2 (3 mL) was added I(coll)2ClO4 (117 mg, 0.25 mmol).
Stirring was maintained for 1 h, then the reaction mixture was
diluted with CH2Cl2 (15 mL) and washed with 10% aqueous
sodium thiosulfate containing sodium bicarbonate, saturated
aqueous sodium bicarbonate, and water. The organic extract
was dried over Na2SO4, filtered, and concentrated. The residue
was purified by flash chromatography (hexane/AcOEt, 1:1) to
give disaccharide 26b␣ (32 mg, 48%) followed by disaccha-
ride 26b␤ (16 mg, 24%). ␣-Anomer: [␣]D ϩ43.5 (c 1.0,
CHCl3). 1H NMR (300 MHz) ␦: 7.76Ϫ7.71 (m, 4H),
7.42Ϫ7.34 (m, 6H), 5.66 (dd, J ϭ 50.4, 1.5 Hz, 1H), 5.05 (d,
J ϭ 1.2 Hz, 1H), 3.95Ϫ3.83 (m, 4H), 3.76Ϫ3.66 (m, 4H),
3.57Ϫ3.46 (m, H), 3.53 (s, 6H), 3.51 (s, 3H), 3.50 (s, 3H), 3.49
(s, 3H), 3.48 (s, 3H), 1.06 (s, 9H). 13C NMR (75 MHz) ␦:
135.9 (ϫ2), 135.6 (ϫ2), 134.1, 133.6, 129.4 (ϫ2), 127.5 (ϫ2),
127.4 (ϫ2), 105.4 (d, J ϭ 220.9 Hz), 96.8, 81.2, 80.5 (d, J ϭ
1.6 Hz), 76.7, 76.1, 75.6 (d, J ϭ 34.0 Hz), 75.2, 73.8 (d, J ϭ
2.0 Hz), 73.0, 65.5, 63.3, 60.9, 60.6, 59.3, 58.3, 57.9, 57.6,
26.7 (ϫ3), 19.4. API-ES positive: 684.3 (M ϩ NH4)ϩ. Anal.
calcd for C34H51FO10Si (666.85): C 61.24, H 7.71; found:
C 61.09, H 7.65. ␤-Anomer: [␣]D Ϫ9.5 (c 0.9, CHCl3).
1H NMR (300 MHz) ␦: 7.78Ϫ7.70 (m, 4H), 7.42Ϫ 7.35 (m,
6H), 5.69 (dd, J ϭ 50.4, 1.8 Hz, 1H) 4.48 (bs, 1H), 4.25 (dd,
J ϭ 11.1, 1.8 Hz, 1H), 3.95 (dd, J ϭ 11.1, 5.1 Hz, 1H),
3.91Ϫ3.85 (m, 1H), 3.76 (d, J ϭ 3.3 Hz, 1H), 3.72 (m, 1H),
3.65 (s, 3H), 3.62Ϫ3.55 (m, 1H), 3.53 (s, 3H), 3.50 (s, 3H),
3.49 (s, 3H), 3.48 (s, 6H), 3.44 (t, J ϭ 9.3 Hz, 1H), 3.25Ϫ3.22
(m, 1H), 3.19 (dd, J ϭ 9.3, 3.0 Hz, 1H), 1.05 (s, 9H). API-ES
positive: 684.3 (M ϩ NH4)ϩ. Anal. calcd for C34H51FO10Si
(666.85): C 61.24, H 7.71; found: C 61.15, H 7.84.
Methyl 2,3,4-tri-O-methyl-6-O-(2,3,4,6-tetra-O-benzoyl-␣-
D-mannopyranosyl)-␣-D-glucopyranoside (29)
A stirred solution of 28 (57.5 mg, 0.087 mmol), 16 (47 mg,
0.087 mmol), and 2 (20 mg, 0.087 mmol) in CH2Cl2 (4 mL)
under argon was cooled to Ϫ30 °C and then NIS (38.7 mg,
0.173 mmol) and BF3·OEt2 (1.1 ␮L, 0.0087 mmol) were
added. The solution was stirred for 20 min and then quenched
by washing with a mixture of aqueous sodium bicarbonate and
aqueous sodium thiosulfate solution. The separated organic
extract was dried, filtered, and concentrated. Purification by
flash chromatography (hexane/EtOAc, 3:2 to 1:1) gave recov-
ered 16 (40 mg, 85%) and disaccharide 29 (68 mg, 96%).
[␣]D ϩ4.3 (c 3.2, CHCl3). 1H NMR (300 MHz) ␦: 8.05Ϫ7.17
(m, 20H), 6.02 (t, J ϭ 10.0 Hz, 1H), 5.85 (dd, J ϭ 10.0,
3.2 Hz, 1H), 5.67 (dd, J ϭ 3.1, 1.8 Hz, 1H), 5.14 (d, J ϭ
1.4 Hz, 1H), 4.74 (d, J ϭ 3.5 Hz, 1H), 4.68 (dd, J ϭ 11.9,
2.0 Hz, 1H), 4.48 (ddd, J ϭ 9.9, 4.3, 2.0 Hz, 1H), 4.39 (dd,
J ϭ 11.9, 4.6 Hz, 1H), 3.91 (dd, J ϭ 11.0 Hz, 5.4 Hz, 1H),
3.79 (dd, J ϭ 10.9, 1.4 Hz, 1H), 3.69Ϫ3.63 (m, 1H), 3.57 (s,
3H), 3.53 (s, 3H), 3.49 (m, 1H), 3.46 (s, 3H), 3.42 (s, 3H), 3.11
(dd, J ϭ 9.7, 3.7 Hz, 1H), 3.05 (m, 1H). 13C NMR (75 MHz)
␦: 166.4, 165.7, 165.6, 165.5, 133.7 (ϫ2), 133.4, 133.3, 130.2,
130.1 (ϫ2), 129.9 (ϫ6), 129.6 (ϫ2), 129.3 (ϫ4), 129.2 (ϫ2),
128.8, 128.7, 128.6, 97.7, 97.5, 83.8, 82.0, 79.8, 70.6, 70.2,
70.0, 69.2, 67.2, 66.8, 63.1, 61.1, 60.8, 59.3, 55.4. API-ES
positive: 837.2 (M ϩ Na)ϩ. Anal. calcd for C44H46O15
(814.83): C 64.86, H 5.69; found: C 65.02, H 5.73.
2,3,4-Tri-O-methyl-6-O-(2,3,4,6-tetra-O-benzoyl-␣-D-
mannopyranosyl)-␣-D-glucopyranosyl fluoride (31)
A stirred solution of NPOE 28 (66.4 mg, 0.1 mmol) and
fluoride 23 (22.4 mg, 0.1 mmol) in CH2Cl2 (4 mL) under
argon was cooled to Ϫ20 °C and then NIS (44.8 mg,
0.2 mmol) and Yb(OTf)3 (62 mg, 0.1 mmol) were added. The
solution was stirred for 1 h and then quenched by washing
with a mixture of aqueous sodium bicarbonate and aqueous
sodium thiosulfate solution. The separated organic extract was
2,3,4-Tri-O-methyl-6-O-(2,3,4,6-tetra-O-benzoyl-␣-D-
mannopyranosyl)-␣-D-glucopyranosyl fluoride (27)
A solution of n-pentenyl 2,3,4,6-tetra-O-benzoyl-␣-D-
mannopyranoside (8; 79.7 mg, 0.12 mmol), 2,3,4-tri-O-methyl-
␣-D-mannopyranosyl fluoride (23; 22.4 mg, 0.1 mmol), NIS
Published by NRC Research Press

62
Can. J. Chem. Vol. 91, 2013
dried, filtered, and concentrated. Purification by flash chroma-
tography (hexane/EtOAc, 3:2 to 1:1) gave disaccharide 31
(75 mg, 94%). [␣]D Ϫ2.3 (c 0.9, CHCl3). 1H NMR (300 MHz)
␦: 8.0Ϫ7.15 (m, 20H), 6.04 (t, J ϭ 10.0 Hz, 1H), 5.87 (dd,
J ϭ 10.1, 3.3 Hz, 1H), 5.70 (dd, J ϭ 3.2, 1.8 Hz, 1H), 5.64 (dd,
J ϭ 50.3, 1.8 Hz, 1H), 5.14 (d, J ϭ 1.6 Hz, 1H), 4.67Ϫ4.58
(m, 1H), 4.47Ϫ4.39 (m, 2H), 3.96 (dd, J ϭ 11.5, 5.3 Hz, 1H),
3.87Ϫ3.78 (m, 2H), 3.67 (m, 1H), 3.54 (s, 3H), 3.48 (s, 3H),
3.46 (s, 3H), 3.53Ϫ3.42 (m, 2H). 13C NMR (75 MHz) ␦:
166.2, 165.4, 165.3, 165.2, 133.4 (ϫ2), 133.1, 133.0, 129.9,
129.8 (ϫ4), 129.7 (ϫ2), 129.6 (ϫ2), 129.4, 129.1, 128.9,
128.5 (ϫ2), 128.4 (ϫ2), 128.3 (ϫ2), 128.2 (ϫ2), 105.3 (d,
J ϭ 220.8 Hz), 98.0, 80.5, 75.5 (d, J ϭ 34.0 Hz), 75.4, 73.7, 70.3,
69.9, 68.8, 67.1, 66.9, 62.8, 60.9, 59.4, 57.8. API-ES positive:
825.2 (M ϩ Na)ϩ. Anal. calcd for C43H43FO14 (802.79): C
64.33, H 5.40; found: C 64.47, H 5.49.
30 min, the acceptor 33 (32 mg, 0.1 mmol) in CH2Cl2 (3 mL)
was added and the reaction was cooled to Ϫ30 °C. Then NIS
(24.6 mg, 0.11 mmol) and BF3(OEt)2 (3.8 ␮L, 0.03 mmol)
were added. After 12 h, the reaction was quenched by washing
with a mixture of aqueous sodium bicarbonate and aqueous
sodium thiosulfate solution. The separated organic extract was
dried, filtered, and concentrated. Purification by flash chroma-
tography (hexane/EtOAc, 2:8) yielded tetrasaccharide 34
1
(32.6 mg, 25%). Major isomer, selected signals: H NMR
(300 MHz) ␦: 5.25 (d, J ϭ 1.8 Hz, 1H), 5.11 (d, J ϭ 1.8 Hz,
1H), 4.93 (d, J ϭ 2.5 Hz, 1H), 4.91 (bs, 1H), 3.58 (s, 3H), 3.54
(s, 3H), 3.50 (s, 6H), 3.47 (s, 3H), 3.44 (s, 3H), 3.35 (s, 3H),
2.06 (s, 3H), 2.01 (s, 3H), 1.99 (s, 3H). 13C NMR (75 MHz) ␦:
97.7, 96.9, 96.8, 96.6. Electrospray ionization (ESI)-HR-MS:
1324.5055 (M ϩ NH4)ϩ, 1329.4602 (M ϩ Na)ϩ. Anal. calcd
for C65H78O28 (1306.46): C 59.72, H 6.01, O 34.27; found: C
59.88, H 6.09.
One-pot assembly of trisaccharide 32
A mixture of NPOE 28 (73 mg, 0.11 mmol), 2,3,4-
tri-O-methyl-␣-D-mannopyranosyl fluoride (23; 22.4 mg,
0.1 mmol), and 4 Å molecular sieves in CH2Cl2 (4 mL) was
stirred under argon at Ϫ20 °C for 10 min. Then NIS (24.6 mg,
0.11 mmol) and Yb(OTf)3 (68.2 mg, 0.11 mmol) were added.
The reaction mixture was stirred at Ϫ20 °C for 1 h, after
which n-pentenyl-2,3,4-tri-O-methyl-␣-D-mannopyranoside
(21; 26.1 mg, 0.09 mmol) in CH2Cl2 (2 mL) was added. The
reaction was allowed to warm to room temperature and then
Yb(OTf)3 (68.2 mg, 0.11 mmol) was added. Upon stirring for
10 min, the reaction was quenched by washing with a mixture
of aqueous sodium bicarbonate and aqueous sodium
thiosulfate solution. The separated organic extract was dried,
filtered, and concentrated. Purification by flash chromatogra-
phy (hexane/EtOAc, 1:1) gave trisaccharide 32 (69 mg, 72%).
[␣]D Ϫ2.3 (c 0.9, CHCl3). 1H NMR (300 MHz) ␦: 8.31Ϫ7.79
(m, 8H), 7.61Ϫ7.22 (m, 12H), 6.10 (t, J ϭ 9.9 Hz, 1H), 5.96
(dd, J ϭ 10.2, 3.3 Hz, 1H), 5.77 (ddt, J ϭ 17.1, 10.5, 6.6 Hz,
1H), 5.76 (m, 1H), 5.26 (d, J ϭ 1.8 Hz, 1H), 5.12 (d, J ϭ
1.0 Hz, 1H), 5.03Ϫ4.92 (m, 2H), 4.88 (bs, 1H), 4.71Ϫ4.68 (m,
1H), 4.57Ϫ4.47 (m, 2H), 4.05Ϫ3.97 (m, 2H), 3.91Ϫ3.87 (m,
1H), 3.81Ϫ3.35(m, 11H), 3.58 (s, 3H), 3.56 (s, 3H), 3.49 (s,
3H), 3.48 (s, 3H), 3.47 (s, 3H), 3.45 (s, 3H), 2.11Ϫ2.04 (m,
2H), 1.69Ϫ1.60 (m, 2H). 13C NMR (75 MHz) ␦: 166.2, 165.4,
165.2, 165.1, 137.9, 133.3, 133.2, 132.9, 129.9, 129.8 (ϫ2),
129.77 (ϫ2), 129.73 (ϫ2) 129.6 (ϫ2), 129.5, 129.2, 129.0,
128.5 (ϫ2), 128.4 (ϫ2), 128.3 (ϫ2), 128.2 (ϫ2), 114.9, 97.6,
96.9, 96.6, 81.39, 81.38, 77.1, 76.6, 76.3, 75.8, 71.4, 71.1,
70.4, 69.9, 68.7, 67.1, 67.0 (ϫ2), 66.0, 62.9, 60.8, 60.7, 58.7,
58.6, 57.5, 57.4, 30.3, 28.6. API-ES positive: 1090.3
(M ϩ NH4)ϩ, 1095.4 (M ϩ Na)ϩ. Anal. calcd for C57H68O20
(1073.14): C 63.80, H 6.39; found: C 63.93, H 6.51.
Methyl 3,5-di-O-benzyl-2-O-benzoyl-␤-D-ribofuranoside
(35)
To a solution of 1,2-orthoester 36 (80 mg, 0.18 mmol) in dry
CH2Cl2 (3 mL) at Ϫ40 °C under argon was added a solution
of HF–pyridine (10.27 mL, 1.78 mmol) in dry CH2Cl2 (2 mL).
After 10 min, when all the starting material had disappeared,
the reaction mixture was diluted with CH2Cl2 (30 mL) and
quenched by saturated aqueous NaHCO3. The layers were
separated, the aqueous phase was extracted with CH2Cl2, and
the combined organic layers were washed with saturated aque-
ous NaCl. The resultant organic phase was dried, filtered, and
concentrated. The residue was purified by flash silica gel
column chromatography (hexane/EtOAc, 8:2) to yield fluoride
37 (33 mg, 42%) followed by methyl glycoside 35 (19 mg,
24%). For 35: [␣]D ϩ32.0 (c 0.2, CHCl3). 1H NMR
(300 MHz) ␦: 8.10Ϫ8.07 (m, 3H), 7.61Ϫ7.23 (m, 12H), 5.45
(d, J ϭ 4.3 Hz, 1H), 5.04 (s, 1H), 4.63 (d, J ϭ 11.7 Hz, 1H),
4.60 (d, J ϭ 11.7 Hz, 1H), 4.55 (d, J ϭ 12.3 Hz, 1H), 4.45 (d,
J ϭ 11.7 Hz, 1H), 4.36 (m, 1H), 4.24 (m, 1H), 3.61 (ddd, J ϭ
16.6, 10.5, 4.6 Hz, 2H), 3.38 (s, 3H, OMe). 13C NMR
(75 MHz) ␦: 165.6, 138.2, 137.4, 133.3, 129.9 (ϫ2), 129.6,
128.4 (ϫ2), 128.3 (ϫ4), 128.0 (ϫ2), 127.8, 127.6 (x 2), 127.5,
106.3, 80.5, 77.9, 74.2, 73.2, 73.0, 71.2, 55.1. API-ES posi-
tive: 471.5 (M ϩ Na)ϩ.
3,5-Di-O-benzyl-2-O-benzoyl-␤-D-ribofuranosyl fluoride
(37)
Following General procedure D, a solution of HF–pyridine
(40 equiv, 6 mmol, 0.9 mL) was treated with orthoester 36
(70 mg, 0.16 mmol) to afford, after flash chromatography
(hexane/EtOAc, 9:1), compound 37 (72 mg, quantitative
yield) as a colorless oil. [␣]D ϩ44.2 (c 1.0, CHCl3). 1H NMR
(300 MHz) ␦: 8.10Ϫ8.07 (m, 3H), 7.61Ϫ7.23 (m, 12H), 5.85
(d, J ϭ 61.9 Hz, 1H), 5.60 (t, J ϭ 4.0 Hz, 1H), 4.63 (d, J ϭ
11.7 Hz, 1H), 4.60 (d, J ϭ 11.7 Hz, 1H), 4.55 (d, J ϭ 12.3 Hz,
1H), 4.45 (d, J ϭ 11.7 Hz, 1H), 4.48Ϫ4.40 (m, 1H),
4.35Ϫ4.30 (m, 1H), 3.74 (dd, J ϭ 11.0, 3.2 Hz, 1H), 3.60 (dd,
J ϭ 11.0, 5.4 Hz, 1H). 13C NMR (75 MHz) ␦: 165.5, 134.0,
133.9, 133.5 (ϫ2), 130.1 (ϫ2), 130.0 (ϫ4), 128.8 (ϫ2), 128.7
(ϫ2), 128.6 (ϫ2), 112.6 (d, J ϭ 225.2 Hz, C-1), 82.8 (d, J ϭ
2.3 Hz, C-3), 75.1, 74.6, 71.2, 64.2, 29.9. 19F NMR (376 MHz)
␦: 115.1 (m). API-ES positive: 459.2 (M ϩ Na)ϩ. Anal. calcd
for C26H25FO5 (436.47): C 71.55, H 5.77; found: C 71.43,
H 5.64.
One-pot assembly of tetrasaccharide 34
A mixture of NPOE 28 (88.4 mg, 0.133 mmol), 2,3,4-tri-
O-methyl-␣-D-mannopyranosyl fluoride (23; 27.1 mg,
0.12 mmol), and 4 Å molecular sieves in CH2Cl2 (4 mL) was
stirred under argon at Ϫ20 °C for 10 min. Then NIS (29.8 mg,
0.133 mmol) and Yb(OTf)3 (82.5 mg, 0.133 mmol) were
added. The reaction mixture was stirred at Ϫ20 °C for 1 h,
after which n-pentenyl-2,3,4-tri-O-methyl-␣-D-mannopyranoside
(21;31.9 mg, 0.11 mmol) in CH2Cl2 (3 mL) was added. The
reaction was allowed to warm to room temperature and then
Yb(OTf)3 (41.2 mg, 0.066 mmol) was added. Upon stirring for
Published by NRC Research Press

Fraser-Reid et al.
63
2,3,5-Tri-O-benzoyl-␣-D-arabinofuranosyl fluoride (44)31
Following General procedure D, a solution of HF–pyridine
(3.0 mmol, 0.45 mL) was treated with orthoester 38a (80 mg,
0.15 mmol) to afford, after flash chromatography (hexane/
EtOAc, 8:2), compound 12 (66 mg, 95%) as a colorless oil. In
a different run, orthoester 38b (80 mg, 0.17 mmol) was sub-
jected to the same reaction conditions to obtain fluoride 44
(62 mg, 79%). [␣]D Ϫ53.6 (c 1.0, CHCl3). 1H NMR
(300 MHz, CDCl3) ␦: 8.03Ϫ7.90 (m, 5H), 7.56, 7.17 (m,
10H), 5.95 (d, J ϭ 58.4 Hz, 1H), 5.63 (bd, J ϭ 6.1 Hz, 1H),
5.52 (m, 1H), 4.80Ϫ4.74 (m, 2H), 4.62 (dd, J ϭ 12.9, 6.5 Hz,
1H). 13C NMR (75 MHz, CDCl3) ␦: 166.6, 166.1, 165.0,
133.8, 133.7, 133.1, 129.9 (ϫ2), 129.8 (ϫ2), 129.7 (ϫ2),
129.4, 128.6 (ϫ3), 128.5 (ϫ2), 128.4, 128.3 (ϫ2), 112.4 (d,
J ϭ 226.5 Hz, C-1), 84.4, 80.8 (d, J ϭ 40.0 Hz, C-2), 76.5,
63.4. 19F NMR (376 MHz, CDCl3) ␦: Ϫ124.7 (dd, J ϭ 58.5,
6.0 Hz). API-ES positive: 487.3 (M ϩ Na)ϩ. Anal. calcd for
C26H21FO7 (464.44): C 67.24, H 4.56; found: C 67.18, H 4.43.
2,5-Di-O-benzoy1-␣-D-arabinofuranosyl fluoride (47)
Following General procedure D, a solution of HF–pyridine
(3.06 mmol, 0.45 mL) was treated with orthoester 41 (34 mg,
0.09 mmol) to afford, after flash chromatography (hexane/
EtOAc, 8:2), compound 47 (29 mg, 91%). [␣]D ϩ52.1 (c 0.8,
CHCl3). 1H NMR (300 MHz) ␦: 8.09Ϫ8.04 (m, 4H),
7.59Ϫ7.41 (m, 6H), 6.00 (d, J ϭ 60.0 Hz, 1H), 5.32 (dd, J ϭ
10.9, 2.6 Hz, 1H), 4.72Ϫ4.50 (m, 3H), 4.33 (dd, J ϭ 5.8,
2.6 Hz, 1H). 13C NMR (75 MHz) ␦: 166.8, 166.4, 134.2,
133.5, 130.1 (ϫ2), 130.0 (ϫ2), 129.7, 128.9 (ϫ2), 128.8,
128.6 (ϫ2), 113.2 (d, J ϭ 223.9 Hz, C-1), 86.1 (d, J ϭ
39.0 Hz, C-2), 84.3, 77.0, 63.5, 30.0. 19F NMR (376 MHz)
␦: Ϫ121.9 (dd, J ϭ 59.8, 11.3 Hz). API-ES positive: 383.4
(M ϩ Na)ϩ. Anal. calcd for C19H17FO6 (360.33): C 63.33, H
4.76; found: C 63.17, H 4.51.
2,5-Di-O-benzoyl-1-␤-D-ribofuranosyl fluoride (48)
Following General procedure D, a solution of HF–pyridine
(1.82 mmol, 0.27 mL) was treated with orthoester 42 (57 mg,
0.15 mmol) to afford, after flash chromatography (hexane/
EtOAc, 8:2), compound 48 (29 mg, 53%). [␣]D ϩ30.4 (c 0.6,
CHCl3). 1H NMR (300 MHz) ␦: 8.03Ϫ8.00 (m, 2H),
7.65Ϫ7.30 (m, 8H), 6.01 (d, J ϭ 59.7 Hz, 1H), 5.32 (dd, J ϭ
10.9, 2.6 Hz, 1H), 4.69 (m, 2H), 4.54 (m,1H), 4.33 (dd, J ϭ
5.8, 2.6 Hz, 1H). 13C NMR (75 MHz) ␦: 166.5, 166.2, 132.9,
132.0, 128.9 (ϫ2), 128.7 (ϫ2), 127.7 (ϫ2), 127.4 (ϫ2), 111.9
(d, J ϭ 223.9 Hz, C-1), 84.8 (d, J ϭ 39.0 Hz, C-2), 82.8, 75.9,
62.2, 28.7. 19F NMR (376 MHz) ␦: Ϫ115.7 (bd, J ϭ 60.7 Hz).
API-ES positive: 383.3 (M ϩ Na)ϩ. Anal. calcd for
C19H17FO6 (360.33): C 63.33, H 4.76; found: C 63.21, H 4.63.
2,3,5-Tri-O-benzoyl-␤-D-ribofuranosyl fluoride (45)
Following General procedure D, a solution of HF–pyridine
(3.0 mmol, 0.45 mL) was treated with orthoester 39a (80 mg,
0.15 mmol) to afford, after flash chromatography (hexane/
EtOAc, 8:2), compound 45 (70 mg, quantitative yield) as a
colorless oil. In a different run, orthoester 39b (80 mg,
0.17 mmol) was subjected to the same reaction conditions to
obtain fluoride 45 (77 mg, quantitative yield). [␣]D ϩ105.9 (c
1
1.0, CHCl3). H NMR (300 MHz, CDCl3) ␦: 8.10Ϫ7.87 (m,
5H), 7.63Ϫ7.31 (m, 10H), 5.98 (d, J ϭ 61.0 Hz, 1H),
5.93Ϫ5.86 (m, 2H), 4.87 (m, 1H), 4.78 (dd, J ϭ 12.1, 3.8 Hz,
1H), 4.59 (dd, J ϭ 12.1, 5.0 Hz, 1H). 13C NMR (75 MHz,
CDCl3) ␦: 166.4, 165.5, 165.2, 134.0, 133.9, 133.5, 130.1
(ϫ2), 130.4 (ϫ2), 130.2 (ϫ2), 129.7, 128.9, 128.8 (ϫ3), 128.7
(ϫ2), 128.6 (ϫ2), 112.3 (d, J ϭ 226.3 Hz, C-1), 81.1 (d, J ϭ
2.7 Hz, C-3), 74.9 (d, J ϭ 36.2 Hz, C-2), 71.2, 64.2.
19F NMR (376 MHz, CDCl3) ␦: Ϫ116.0 (bd, J ϭ 65.0 Hz).
API-ES positive: 487.3 (M ϩ Na)ϩ. Anal. calcd for
C26H21FO7 (464.44): C 67.24, H 4.56; found: C 67.13, H 4.49.
1,5-Anhydro-2-O-benzoyl-␤-D-ribofuranose (49)
Following General procedure D, a solution of HF–pyridine
(40 equiv, 8.8 mmol, 1.31 mL) was treated with orthoester 43
(60 mg, 0.22 mmol) to afford, after flash chromatography
(hexane/EtOAc, 1:1), compound 49 (21 mg, 40%). [␣]D Ϫ27.9
1
(c 1.4, CHCl3). H NMR (300 MHz) ␦: 8.09Ϫ8.04 (m, 2H),
7.63Ϫ7.44 (m, 3H), 5.35 (d, J ϭ 4.6 Hz, 1H), 5.13 (s, 1H),
4.95 (m, 1H), 4.02 (m, 2H), 3.83 (m, 1H), 2.16 (d, 1H, OH).
13C NMR (75 MHz) ␦: 166.2, 133.6, 129.8 (ϫ2), 129.3, 128.5
(ϫ2), 104.5, 82.7, 77.2, 69.7, 66.6. API-ES positive: 473.3
(2M ϩ H)ϩ, 495.3 (2M ϩ Na)ϩ. Anal. calcd for C12H12O5
(236.22): C 61.01, H 5.12; found: C 60.87, H 4.98.
3,5-Di-O-benzyl-2-O-benzoyl-␣-D-arabinofuranosyl fluoride
(46)
Following General procedure D, a solution of HF–pyridine
(3.6 mmol, 0.53 mL) was treated with orthoester 40a (60 mg,
0.12 mmol) to afford, after flash chromatography (hexane/
EtOAc, 8:2), compound 46 (51 mg, 91%) as a colorless oil. In
a different run, orthoester 40b (40 mg, 0.09 mmol) was sub-
jected to the same reaction conditions to obtain fluoride 46
(39 mg, 93%). [␣]D ϩ14.4 (c 1.0, CHCl3). 1H NMR
(300 MHz) ␦: 7.98Ϫ7.95 (m, 3H), 7.64Ϫ7.28 (m, 12H), 5.90
(d, J ϭ 59.0 Hz, 1H, 1-H), 5.54 (dd, J ϭ 7.1, 1.1 Hz, 1H, 2-H),
4.84 (d, J ϭ 12.3 Hz, 1H, –OCH2Ph), 4.65 (d, J ϭ 12.3 Hz,
1H, –OCH2Ph), 4.61Ϫ4.58 (m, 1H, 4-H), 4.12 (dd, J ϭ 4.6,
1.1 Hz, 1H, 3-H) 3.68 (dd, J ϭ 10.8, 4.5 Hz, 1H, 5a-H), 3.62
(dd, J ϭ 10.8, 6.0 Hz, 1H, 5b-H). 13C NMR (75 MHz) ␦:
165.4, 137.9, 137.5, 133.9, 130.1 (ϫ2), 129.2, 128.8 (ϫ2)
128.7 (ϫ2), 128.6 (ϫ2), 128.2 (ϫ3), 128.0, 127.9 (ϫ2), 113.2
(d, J ϭ 225.4 Hz, 1-C), 85.4, 82.3, 80.7 (d, J ϭ 39.2 Hz, 2-C),
73.7, 72.6, 69.1. 19F NMR (376 MHz) ␦: Ϫ123.5 (dd, J ϭ
59.1, 7.0 Hz). API-ES positive: 459.2 (M ϩ Na)ϩ. Anal. calcd
for C26H25FO5 (436.47): C 71.53, H 5.77; found: C 71.39,
H 5.59.
2,5-Di-O-benzoyl-3-O-(2,3,5-tri-O-benzoyl-␣-D
-arabino-furanosyl)-␣-D-arabinofuranosyl fluoride (50)
A stirred solution of NPOE 38a (100 mg, 0.198 mmol) and
fluoride 47 (74 mg, 0.20 mmol) in CH2Cl2 (4 mL) under argon
was cooled to 0 °C and then NIS (85.5 mg, 0.38 mmol) and
Yb(OTf)3 (58.9 mg, 0.10 mmol) were added. The solution was
stirred for 1 h and then quenched by washing with a
mixture of aqueous sodium bicarbonate and aqueous sodium
thiosulfate solution. The separated organic extract was dried,
filtered, and concentrated. Purification by flash chromatogra-
phy (hexane/EtOAc, 8:2) gave disaccharide 50 (86 mg, 61%).
[␣]D Ϫ6.3 (c 1.0, CHCl3). 1H NMR (400 MHz) ␦: 8.13Ϫ7.93
(m, 10H), 7.60Ϫ7.21 (m, 15H), 6.00 (d, J ϭ 58.1 Hz, 1H,
1-H), 5.72 (s, 1H, 1=-H), 5.63 (s, 1H, 2-H), 5.59 (d, J ϭ 1.6 Hz,
1H, 3=-H), 5.57 (d, J ϭ 6.6 Hz, 1H, 2-H), 4.78Ϫ4.53 (m, 7H).
13C NMR (100 MHz) ␦: 166.1, 166.0, 165.6, 165.3, 165.2,
133.7, 133.6, 133.5, 133.2, 133.1, 130.0 (ϫ4), 129.9 (ϫ2),
129.8, 129.7 (ϫ2), 129.6 (ϫ2), 129.5, 129.3, 128.9, 128.8,
Published by NRC Research Press

64
Can. J. Chem. Vol. 91, 2013
(4) (a) Mootoo, D. R.; Date, V.; Fraser-Reid, B. J. Am. Chem. Soc.
1988, 110 (8), 2662. doi:10.1021/ja00216a057; (b) Fraser-Reid,
B.; Konradsson, P.; Mootoo, D. R.; Udodong, U. J. Chem. Soc.
Chem. Commun. 1988, (12): 823. doi:10.1039/c39880000823;
(c) Mootoo, D. R.; Konradsson, P.; Udodong, U.; Fraser-Reid,
B. J. Am. Chem. Soc. 1988, 110 (16), 5583. doi:10.1021/
ja00224a060; (d) Fraser-Reid, B.; Udodong, U. E.; Wu, Z.;
Ottosson, H.; Merritt, J. R.; Rao, C. S.; Roberts, C.; Madsen, R.
Synlett 1992, 1992 (12), 927. doi:10.1055/s-1992-21543.
(5) Kanie, O.; Ito, Y.; Ogawa, T. J. Am. Chem. Soc. 1994, 116 (26),
12073. doi:10.1021/ja00105a066.
128.7 (ϫ2), 128.6 (ϫ2), 128.5 (ϫ2), 128.4 (ϫ2), 128.3 (ϫ2),
112.6 (d, J ϭ 225.2 Hz), 105.6, 84.2, 82.2, 81.7, 81.3 (d, J ϭ
40.2 Hz), 79.9, 77.4, 63.7, 63.0. API-ES positive: 827.5
(M ϩ Na)ϩ. Anal. calcd for C45H37O13F (804.77): C 67.16, H
4.63; found: C 67.07, H 4.39.
n-Pentenyl-2,3-di-O-benzyl-5-O-[2,5-di-O-benzoyl-3-O-
(2,3,5-tri-O-benzoyl-␣-D-arabino-furanosyl)-␣-D-
arabino-furanosyl]-␣-D-arabino-furanoside (52)
To a stirred solution of fluoride 50 (8 mg, 0.01 mmol) and
NPG 51 (8 mg, 0.02 mmol) in CH2Cl2 (2 mL) cooled
to Ϫ20 °C was added BF3·Et2O (0.9 ␮L, 0.00710 mmol). The
reaction was allowed to warm to Ϫ10 °C and then stirred for
an additional 4 h after which time it was diluted with CH2Cl2
(15 mL) and washed with saturated aqueous sodium bicarbon-
ate. The organic extract was dried, filtered, and concentrated.
The residue was purified by flash chromatography (CH2Cl2) to
give trisaccharide 52 (9 mg, 75%). [␣]D ϩ22.2 (c 0.7, CHCl3).
1H NMR (500 MHz) ␦: 8.13Ϫ7.93 (m, 10H), 7.60Ϫ7.15 (m,
25H), 5.75 (m, 1H), 5.72 (s, 1H, 1-H), 5.60 (d, J ϭ 1.5 Hz, 1H,
2=-H), 5.53 (dd, J ϭ 3.9, 0.7 Hz, 1H, 1-H), 5.45 (d, J ϭ 1 Hz,
1H, 2Љ-H), 5.34 (s, 1H, 1-H), 4.98 (d, J ϭ 1.3 Hz, 1H), 4.91
(m, 2H), 4.74Ϫ4.42 (m, 11H), 4.21 (dt, J ϭ 6.6, 4.2 Hz, 1H,
4-H), 4.04 (dd, J ϭ 6.6, 3.4 Hz, 1H, 3-H), 3.99 (dd, J ϭ 3.4,
1.5 Hz, 1H, 2-H), 3.90 (dd, J ϭ 11.2, 4.6 Hz, 1H, 5-H), 3.75
(dd, J ϭ 11.2, 3.9 Hz, 1H), 3.68 (m, 1H), 3.34 (m, 1H), 2.06
(m, 2H), 1.60 (m, 2H). 13C NMR (125 MHz) ␦: 166.1 (d),
166.0, 165.6, 165.3, 165.2, 138.2, 137.9, 137.6, 133.5, 133.4,
133.3, 133.1, 132.9, 130.0, 129.9, 129.8, 129.7, 129.6, 129.5,
129.4, 129.2, 129.1, 128.4 (ϫ2), 128.3 (ϫ2), 128.2, 128.1,
127.9, 127.8, 127.7, 127.6, 114.7, 106.1, 106.0, 105.0, 88.2,
83.4, 82.0, 81.9, 81.6, 81.1, 80.6, 80.0, 77.7, 77.6, 72.2, 71.9,
66.9, 66.3, 63.7, 63.2, 30.3, 28.7. HR-MS: 1205.4127 (M ϩ Na)ϩ.
Anal. calcd for C69H66O18 (1182.42): C 70.04, H 5.62; found:
C 69.94, H 5.49.
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2000, 327 (1–2), 15. doi:10.1016/S0008-6215(99)00325-0.
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10.1016/S0008-6215(99)00324-9.
(9) Mukaiyama, T. Angew. Chem. Int. Ed. 2004, 43 (42), 5590.
doi:10.1002/anie.200300641.
(10) Konradsson, P.; Fraser-Reid, B. J. Chem. Soc. Chem. Commun.
1989, (16): 1124. doi:10.1039/c39890001124.
(11) (a) Lu, J.; Jayaprakash, K. N.; Schlueter, U.; Fraser-Reid, B. J.
Am. Chem. Soc. 2004, 126, 7450. doi:10.1021/ja038807p; (b)
Lu, J.; Fraser-Reid, B. Chem. Commun. (Camb.) 2005, (7): 862.
doi:10.1039/b413694b; (c) Jayaprakash, K. N.; Lu, J.; Fraser-Reid,
B. Angew. Chem. Int. Ed. 2005, 44 (36), 5894. doi:10.1002/
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(12) Fraser-Reid, B.; López, J. C. Orthoesters and Related Deriva-
tives. In Handbook of Chemical Glycosylation: Advances in
Stereoselectivity and Therapeutic Relevance; Demchenko,
A. V., Ed.; Wiley-VCH: New York, 2008; Chapter 5.1.
(13) (a) Barluenga, J.; González, J. M.; Campos, P. J.; Asensio, G.
Angew. Chem. Int. Ed. Engl. 1985, 24, 319. doi:10.1002/
anie.198503191.(b) Barluenga, J. Pure Appl. Chem. 1999, 71 (3),
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Org. Chem. 1991, 56 (6), 2234. doi:10.1021/jo00006a050.
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Acknowledgements
B.F.R. thanks the National Science Foundation (grant No.
CHE 0717702) for financial support. This research has been
supported with funds from the Ministerio de Ciencia e Inno-
vación and Comunidad de Madrid (grant Nos. CTQ2009-
10343 and S2009/PPQ-1752, respectively). We also thank
Ms. M. Rodríguez (Instituto de Química Orgánica General
(IQOG)) for skillful technical support.
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