BiBr3-promoted activation of peracetylated glycosyl iodides: Straightforward access to synthetically useful 2-O-deprotected allyl glycosides

Article abstract of DOI:10.1002/ejoc.200800914

Substoichiometric amounts of BiBr₃ are able to promote anomeric activation of acetylated glycosyl iodides. This reactivity can be exploited for straightforward access to allyl glycosides unprotected at the O-2 position. The reported protocol appears to be convenient in comparison with the pre-existing ones in that shorter experimental times are needed and the use of strong acids is avoided. Suitable structural features of substrates (6-deoxy sugars or use of benzoyl or methoxycarbonyl 2-O-participating groups) switch the process to a preferential glycosidation without deprotection at the O-2 position. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.

Full text of DOI:10.1002/ejoc.200800914

FULL PAPER
DOI: 10.1002/ejoc.200800914
BiBr3-Promoted Activation of Peracetylated Glycosyl Iodides: Straightforward
Access to Synthetically Useful 2-O-Deprotected Allyl Glycosides
Antonello Pastore,[a] Matteo Adinolfi,[a] and Alfonso Iadonisi*[a]
Keywords: Protecting groups / Carbohydrates / Regioselectivity / Glycosylation
Substoichiometric amounts of BiBr3 are able to promote ano-
meric activation of acetylated glycosyl iodides. This reactivity
can be exploited for straightforward access to allyl glycosides
unprotected at the O-2 position. The reported protocol ap-
pears to be convenient in comparison with the pre-existing
ones in that shorter experimental times are needed and the
use of strong acids is avoided. Suitable structural features of
substrates (6-deoxy sugars or use of benzoyl or methoxycar-
bonyl 2-O-participating groups) switch the process to a pref-
erential glycosidation without deprotection at the O-2 posi-
tion.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2008)
These precursors can be rapidly prepared within a few min-
utes from the corresponding peracetylated sugars[3] and can
be employed as crude products after a simple extractive
workup for a wide range of transformations.[4] As expected,
substoichiometric amounts of InCl3 (a known activator of
glycosyl bromides)[5] are able to promote in high yield the
anomeric allylation of glucosyl iodide with the predicted
1,2-trans selectivity arising from the vicinal participation ef-
fect (Scheme 1).
Introduction
Chemical manipulation of monosaccharide functional
groups is frequently the fundamental initial stage for ac-
cessing the building blocks needed for oligosaccharide syn-
thesis or, more in general, for preparing useful precursors
of chiral synthetic targets. The desired differentiation of the
hydroxy groups of a sugar molecule often implies multiple
synthetic steps in which the appropriate variety of protect-
ing groups is installed and then suitably elaborated accord-
ing to the synthetic requirement. These processes can be
time consuming, as several synthetic operations and related
purifications should be performed. Therefore, over the last
year, some effort has been devoted towards the development
of expeditious synthetic procedures providing the rapid dif-
ferentiation of monosaccharide protecting groups through
multiple stages performed sequentially without any purifi-
cation of intermediates.[1] In this regard, herein we wish to
report a simple and rapid protocol for accessing monosac-
charides bearing the versatile allyl group at the anomeric
position, a free hydroxy group at C-2, and acetyl groups at
the other carbinolic positions. The approach relies on the
feasible activation of glycosyl iodides with substoichio-
metric amounts of BiBr3.
Scheme 1. InCl3-promoted activation of glycosyl iodide 2.
In searching for alternative catalytic reagents of higher
reactivity, we examined several bismuth(III) salts, whose
catalytic halophilic reactivity had been evidenced in some
useful synthetic transformations such as Friedel–Crafts al-
kylation.[6] When BiBr3 was used, the reaction outcome was
rather different, and a mixture of products was recovered
in which allyl glycoside 4, deprotected at the O-2 position,
predominated over minor, although not negligible, amounts
of peracetylated allyl glycoside 3 (Scheme 2).
Results and Discussion
The procedure was disclosed in the course of an investi-
gation aimed at finding catalytic activators of peracetylated
glycosyl iodides to be employed in glycosidation reactions.[2]
As shown in Scheme 2, the composition of the reaction
mixture was examined under a variety of conditions (reac-
tions at room temperature or in refluxing DCM, 2 or 4
equivalents of allyl alcohol used). The best yield of 2-O-
deprotected compound 4 (57%) was achieved with 4 equiv.
[a] Department of Organic Chemistry and Biochemistry, Univer-
sity of Naples “Federico II”,
via Cynthia 4, 80126 Naples, Italy
Fax: +39-081-674393
E-mail: iadonisi@unina.it
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BiBr3-Promoted Activation of Peracetylated Glycosyl Iodides
fucose were instead found to afford a large predominance
of the peracetylated 1,2-trans allyl glycosides (Table 1, en-
tries 9 and 10). Adoption of an alternative 2-O-acyl group
such as benzoyl (Table 1, entry 4) or methoxycarbonyl[10]
(Table 1, entry 7) suppressed, under otherwise identical
conditions, the process of deprotection at the O-2 position
and was effective in the exclusive generation of the corre-
sponding 1,2-trans glycosides. These latter results indicate
Table 1. BiBr3-promoted activation of glycosyl halides.[a]
Scheme 2. BiBr3-promoted activation of glycosyl iodide 2.
of allyl alcohol in refluxing DCM and in the presence of
freshly activated 4 Å molecular sieves. Remarkably, under
these conditions the reaction is sufficiently fast (ca. 90 min)
so that the whole synthetic sequence shown in Scheme 2
can be performed within a few hours. Other solvents (1,2-
dichloroethane, toluene, dioxane, acetonitrile) were also
tested, but lower yields were invariably obtained.
The anomeric profile of the obtained allylated products
was also interesting: whereas compound 4 was obtained
with some predominance of the α-anomer, peracetylated al-
lyl glycoside 3 was obtained with predominant, though not
exclusive, β-selectivity. Given that the allyl group is fre-
quently used for anomeric transient protection, the de-
scribed two-step sequence appeared of synthetic value, be-
cause it allowed the rapid chemical discrimination of the
anomeric, the O-2 position, and the remaining oxygenated
positions. From a literature survey it appeared that a similar
transformation can be carried out with a slightly improved
yield (63% of 4; β/α, 3:1) by treating β-penta-O-acetyl glu-
cose with allyl alcohol (4 equiv.) in the presence of a stoi-
chiometric excess of BF3·OEt2 (1.5 equiv.).[7] However, the
overall reaction requires a much longer reaction time (over-
night) than that required by the here-presented sequential
procedure. Equally prolonged times (and high tempera-
tures) were very recently reported to be required by several
zeolites for inducing similar transformations (glycosidation
with concomitant deprotection at the O-2 position) in the
coupling of β-configured peracetylated sugars with either
phenols or long-chain alcohols.[8] In contrast to the above-
mentioned BF3·OEt2-based procedure, the anomeric profile
observed in this latter approach was analogous to that ob-
tained under the here-described conditions. Further sparse
examples of glycosidations proceeding with deacetylation at
the O-2 position of the donor have been occasionally de-
scribed as minor side processes.[9]
Once the best reaction conditions were established, the
scope of the procedure was examined with a wide range of
alternative saccharide precursors (Table 1). With peracety-
lated galactose and mannose precursors, the yields of the
corresponding 2-OH allyl glycosides were again of synthetic
interest, albeit lower than those obtained with glucose
(Table 1, entries 5 and 8 vs. entry 1). Notably, a lower yield
of 2-O-deprotected product was obtained when commercial
acetobromogalactose was used in place of the correspond-
ing iodinated precursor (Table 1, entries 6 and 5, respec-
[a] General conditions: sugar, I2 (1.4 equiv.), Et3SiH (1.4 equiv.), re-
fluxing DCM. Extractive workup, then glycosyl iodide, allyl
alcohol (4 equiv.), 4 Å MS, BiBr3 (0.3 equiv.), DCM, reflux. [b] n-
Propanol was used in place of allyl alcohol. [c] n-Pentenyl alcohol
was used in place of allyl alcohol. [d] Tetracetylbromogalactose was
used in place of the corresponding iodide. [e] Isolated yield could
not be determined, as the anomeric products were contaminated
by inseparable 2,3,4,6-tetra-O-acetylmannopyranose. Estimated
tively). Acetylated 6-deoxy sugars such as -rhamnose or yield by NMR spectroscopy: ca 35% (α/β, ca. 1).
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A. Pastore, M. Adinolfi, A. Iadonisi
FULL PAPER
that BiBr3-promoted anomeric allylation without deprotec-
tion at the O-2 position can also be usefully achieved under
suitable structural conditions of the substrates, and this may
offer an alternative to protocols based on Fischer glycosida-
tions that require toxic and high-boiling allyl alcohol as the
solvent.
Use of alternative primary acceptors (n-propanol, n-pen-
tenyl alcohol) in place of allyl alcohol was also tested with
a gluco-configured acetylated precursor and did not result
in a remarkable difference in the reaction mixture composi-
tion (Table 1, compare entries 2 and 3 with entry 1), al-
though the best results in deprotection at the O-2 position
were obtained with allyl alcohol. An especially interesting
result was obtained with a disaccharide such as -lactose,
which afforded the 2-O-deprotected product in very good
overall yield and α-selectivity (Table 1, entry 11). It should
be noted that in previously reported approaches[7,8] of 2-
O-deprotective glycosidation no disaccharide was surveyed.
Additionally, only peracetylated β-configured galacto and
gluco sugars, more prone to acid-promoted anomeric acti-
vation, were used in those procedures, whereas the present
protocol can be generally independent of the anomeric con-
figuration of the starting compound, as the initial iodin-
ation step is efficient with both anomers.[3]
Scheme 3. BiBr3-promoted activation of orthoester 27.
After having established the scope and limitations of the
protocol, some experiments were performed to gain some
mechanistic information on the process. First, allyl 2,3,4,6-
tetra-O-acetylgalactopyranoside was exposed to the typical
reaction conditions above-described, and no appreciable
amount of deacetylation at the O-2 position was detected,
evidencing that the removal of the acetyl group does not
occur after allylation of the anomeric position. In a second
experiment, allyl orthoester 27 prepared via the corre-
sponding iodide 2[3] was exposed to BiBr3 and allyl alcohol
(Scheme 3). Interestingly, this treatment led to a mixture of
allylated compounds 3 and 4 within a short time period
even at room temperature with a larger relative predomi-
nance of deprotection at the O-2 position, but a lower α-
selectivity. The outcome of this experiment is highly sugges-
tive of an allylated orthoester as one of the feasible interme-
diates generated in the rate-determining step, in which
BiBr3 promotes the activation of the anomeric iodide. In
order to ascertain the origin of the aglycon moiety in the
final product, allyl orthoester 27 was treated under the same
conditions previously adopted but in the presence of meth-
anol rather than allyl alcohol as the external nucleophile.
The profile of products (Scheme 3) displayed a predomi-
nant, albeit not exclusive, content of methyl glycosides,
which implies that the aglycon can be provided from the
reaction medium and it is not necessarily incorporated into
the initial orthoester intermediate.
Scheme 4. Synthesis of donor 31 and its coupling with acceptor 32.
The Fmoc group was initially installed in compound 4,
and resulting compound 29 was submitted to a sequence of
anomeric deallylation and installation of the (N-phenyl)-
trifluoroacetimidate leaving group.[12] Bi(OTf)3-catalyzed
coupling[11] with model acceptor 32 smoothly afforded di-
saccharide 33 in good yield (70%).
Conclusion
We have shown that the sequence of anomeric iodination
and BiBr3-promoted activation of the intermediate glycosyl
iodides can afford, within short times, useful saccharidic
building-blocks unprotected at the 2-OH position and bear-
ing the selectively removable allyl anomeric group. Suitable
structural conditions of substrates (6-deoxy sugars or use
of benzoyl or methoxycarbonyl 2-O-participating groups)
switch the preferential process to a glycosidation without
concomitant deprotection at the O-2 position. Synthetically
useful elaborations of the obtained derivatives are currently
being investigated in our laboratory.
Due to our current interest in the search of 2-O-partici-
pating groups serving in Bi(OTf)3-promoted 1,2-trans glyco-
sidations[11] and amenable to selective removal in the pres-
ence of acetyls, we took advantage of the presented pro-
cedure for the straightforward access to 4, a useful precur-
sor of the 2-O-Fmoc trifluoroacetimidate donor 31
(Scheme 4).
Experimental Section
General: 1H and 13C NMR spectra were recorded in CDCl3 (in-
ternal standard CHCl3 at δ = 7.26 ppm). Assignment of proton
chemical shifts was based on decoupling experiments. Analytical
thin-layer chromatography (TLC) was performed on aluminium
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BiBr3-Promoted Activation of Peracetylated Glycosyl Iodides
plates precoated with Silica Gel 60 F254 as the adsorbent. Column
chromatography was performed on Kieselgel 60 (63–200 mesh).
9.6 Hz, 1 H, 2-H), 4.45 (d, 1 H, 1-H), 4.22 (dd, J6a,6b = 12.0 Hz,
J5,6a = 4.5 Hz, 1 H, 6a-H), 4.08 (dd, J5,6b = 2.2 Hz, 1 H, 6b-H),
3.85–3.74 (m, 1 H), 3.69–3.61 (m, 1 H, 5-H), 3.44–3.32 (m, 1 H),
2.04, 1.98, 1.97, 1.96 (4ϫs, 12 H, 4ϫ-COCH3), 1.6–1.4 (m, 2 H,
Typical Procedure for BiBr3-Promoted Allylation: To a solution of
peracetylated glucose (110 mg, 0.28 mmol) in dichloromethane
(4 mL) were sequentially added iodine (102 mg, 0.40 mmol) and
triethylsilane (62.5 µL, 0.40 mmol; caution: exothermic reaction).
After stirring for 5 min at reflux temperature, TLC analysis (petro-
leum ether/ethyl acetate, 6:4) displayed completion of the reaction.
After cooling to room temperature, the mixture was diluted with
dichloromethane and washed with a solution of saturated sodium
hydrogen carbonate containing a minimal amount of sodium thio-
sulfate for reducing the residual amount of iodine. The aqueous
phase was extracted with dichloromethane, and the collected or-
ganic phase was dried with sodium sulfate and concentrated in
vacuo. Freshly activated 4 Å molecular sieves were added to the
residue, and the mixture was suspended in anhydrous dichloro-
methane (4 mL). Allyl alcohol (4 equiv.) and BiBr3 (37 mg,
0.084 mmol) were then added, and the mixture was heated at reflux
until TLC analysis (petroleum ether/ethyl acetate, 4:6) displayed
complete consumption of the UV/Vis detectable glycosyl iodide (ca.
80 min). Some drops of pyridine were added, and the mixture was
filtered through a short pad of silica gel (ethyl acetate), and the
residue from the filtered liquor was chromatographed by silica gel
flash chromatography (petroleum ether/ethyl acetate, 6:4) to yield
peracetylated allyl glycoside 3 (40 mg, 37%; α/β, 1:10), and 2-O-
free allyl glycoside 4 (55 mg, 57%; α/β, 3:1).
3
-OCH2CH2CH3), 0.85 (t, J = 6.9 Hz, 3 H, -OCH2CH2CH3) ppm.
13C NMR (75 MHz, CDCl3): δ = 170.5, 170.1, 169.2, 169.1, 100.7
(C-1), 72.7, 71.6, 71.2, 70.2, 68.4, 61.9, 22.5, 20.5, 10.1 ppm.
C17H26O10 (390.39): calcd. C 52.30, H 6.71; found C 52.00, H 6.55.
n-Propyl 3,4,6-Tri-O-acetyl-D-glucopyranoside (6): Oil, yield 45%,
anomeric mixture (α/β, 2.7:1). Data for the α anomer: 1H NMR
(300 MHz, CDCl3): δ = 5.18 (t, J3,4 = J2,3 = 9.6 Hz, 1 H, 3-H),
4.95 (t, J4,5 = 9.6 Hz, 1 H, 4-H), 4.87 (d, J1,2 = 3.9 Hz, 1 H, 1-H),
4.21 (dd, J6a,6b = 12.3 Hz, J5,6a = 4.5 Hz, 1 H, 6a-H), 4.02 (dd, J5,6b
= 2.1 Hz, 1 H, 6b-H), 3.98–3.88 (m, 1 H, 5-H), 3.75–3.40 (m, 3 H,
2-H and -OCH2CH2CH3), 2.41 (d, J2,OH = 7.4 Hz, 1 H, 2-OH),
2.04, 2.03, 1.98 (3ϫs, 9 H, 3 ϫ-COCH3), 1.73–1.53 (m, 2 H,
3
-OCH2CH2CH3), 0.92 (t, J = 7.5 Hz, 3 H, -OCH2CH2CH3) ppm.
13C NMR (75 MHz, CDCl3): δ = 171.0, 170.6, 169.6, 98.1 (C-1),
73.4, 70.7, 70.4, 68.1, 67.5, 62.0, 22.6, 20.5, 10.5 ppm. Significant
signals for the β-anomer: 1H NMR (300 MHz, CDCl3): δ = 5.07
(t, J3,4 = J2,3 = 9.6 Hz, 1 H, 3-H), 4.97 (t, J4,5 = 9.6 Hz, 1 H, 4-H),
4.31 (d, J1,2 = 7.8 Hz, 1 H, 1-H) ppm. C15H24O9 (348.35): calcd. C
51.72, H 6.94; found C 51.45, H 6.75.
n-Pentenyl 2,3,4,6-Tetra-O-acetyl-β-D-glucopyranoside (7):[14] [α]2D5
=
–17.2 (c = 0.6, CHC13), m.p. 47 °C (light petroleum/diethyl ether).
1H NMR (300 MHz, CDCl3): δ = 5.86–5.67 (m, 1 H, -CH2CH=
Allyl 2,3,4,6-Tetra-O-acetyl-β-
D
-glucopyranoside (3):[7] Foam, yield
CH2), 5.18 (t, J3,4 = J2,3 = 9.4 Hz, 1 H, 3-H), 5.06 (t, J3,4 = J4,5
=
35%, anomeric mixture (α/β, 1:10). Data for the β-anomer: 1H
9.4 Hz, 1 H, 4-H), 4.99 (dd, 3J = 16.9 Hz, 2J = 1.8 Hz, 1 H,
NMR (300 MHz, CDCl3): δ = 5.94–5.74 (m, 1 H, -CH2CH=CH2), -CH2CH=CHcisHtrans), 4.96 (dd, J1,2 = 7.9 Hz, 1 H, 2-H), 4.95 (dd,
5.26 (dd, 3J = 17.4 Hz, 2J = 1.2 Hz, 1 H, -CH2CH=CHcisHtrans), 3J = 9.9 Hz, 2J = 1.8 Hz, 1 H, -CH2CH=CHcisHtrans), 4.47 (d, 1 H,
3
2
5.20 (t, J3,4 = J2,3 = 9.3 Hz, 1 H, 3-H), 5.19 (dd, J = 10.4 Hz, J
= 1.2 Hz, 1 H, -CH2CH=CHcisHtrans), 5.08 (t, J3,4 = J4,5 = 9.3 Hz,
1 H, 4-H), 5.01 (dd, J1,2 = 7.8 Hz, 1 H, 2-H), 4.55 (d, 1 H, 1-H),
1-H), 4.24 (dd, J6a,6b = 12.3 Hz, J5,6a = 4.8 Hz, 1 H, 6a-H), 4.11
(dd, J5,6b = 2.5 Hz, 1 H, 6b-H), 3.90–3.81 (dt, 3J = 6.1 Hz, 2J =
9.6 Hz, 1 H, -OCHaHbCH2CH2CH=CH2), 3.71–3.63 (m, 1 H, 5-
4.37–4.29 (dd, J = 4.8 Hz, J = 13.2 Hz, 1 H, -CHaHbCH=CH2), H), 3.53–3.43 (dt, 3J = 6.6 Hz, 2J = 9.6 Hz, 1 H, -OCHaHb-
3
2
4.25 (dd, J6a,6b = 12.0 Hz, J5,6a = 4.6 Hz, 1 H, 6a-H), 4.13 (dd, J5,6b
= 2.4 Hz, 1 H, 6b-H), 4.12–4.03 (dd, J = 6.0 Hz, J = 13.2 Hz, 1
CH2CH2CH=CH2), 2.06, 2.02, 2.00, 1.98 (4ϫs, 12 H, 4ϫ-
3
2
COCH3) ppm. 13C NMR (75 MHz, CDCl3): δ = 170.5, 170.2,
H, -CHaHbCH=CH2), 3.72–3.64 (m, 1 H, 5-H), 2.08, 2.04, 2.01, 169.3, 169.2, 137.7, 115.0, 100.8 (C-1), 72.9, 71.8, 71.4, 69.2, 68.6,
1.99 (4ϫs, 12 H, 4ϫ-COCH3) ppm. 13C NMR (75 MHz, CDCl3):
δ = 170.5, 170.1, 169.2, 169.1, 133.2, 117.5, 99.4 (C-1), 72.7, 71.6,
71.1, 69.8, 68.3, 61.8, 20.4 ppm. C17H24O10 (388.37): calcd. C 52.57,
H 6.23; found C 52.40, H 6.10.
62.0, 29.8, 28.6, 20.5 ppm. C19H28O10 (416.42): calcd. C 54.80, H
6.78; found C 54.53, H 6.65.
n-Pentenyl 3,4,6-Tri-O-acetyl-D-glucopyranoside (8): Oil, yield 43%,
anomeric mixture (α/β, 2.9:1). Data for the α-anomer: 1H NMR
(300 MHz, CDCl3): δ = 5.87–5.70 (m, 1 H, -CH2CH=CH2), 5.19
(t, J3,4 = J2,3 = 9.6 Hz, 1 H, 3-H), 5.02 (dd, 3J = 17.1 Hz, 2J =
Allyl 3,4,6-Tri-O-acetyl-
meric mixture (α/β, 3.0:1). Data for the α-anomer: 1H NMR
D
-glucopyranoside (4):[7] Oil, yield 57%, ano-
(300 MHz, CDCl3): δ = 6.00–5.80 (m, 1 H, -CH2CH=CH2), 5.30 1.8 Hz, 1 H, -CH2CH=CHcisHtrans), 5.02–4.90 (m, 2 H, -CH2CH=
(m, 3J = 17.1 Hz, 2J = 1.5 Hz, 1 H, -CH2CH=CHcisHtrans), 5.24
(m, J = 10.2 Hz, J = 1.5 Hz, 1 H, -CH2CH=CHcisHtrans), 5.22 (t,
J3,4 = J2,3 = 9.7 Hz, 1 H, 3-H), 4.99 (t, J4,5 = 9.7 Hz, 1 H, 4-H),
CHcisHtrans and 4-H), 4.87 (d, J1,2 = 3.6 Hz, 1 H, 1-H), 4.23 (dd,
J6a,6b = 12.3 Hz, J5,6a = 4.5 Hz, 1 H, 6a-H), 4.04 (dd, J5,6b = 2.4 Hz,
1 H, 6b-H), 3.97–89 (m, 1 H, 5-H), 3.78–3.69 (dt, J = 6.7 Hz, J
= 9.9 Hz, 1 H, -CHaHbCH2CH2CH=CH2), 3.69–3.59 (m, 1 H, 2-
H), 3.53–3.43 (dt, 3J = 6.4 Hz, 2J = 9.6 Hz, 1 H, -CHaHbCH2-
3
2
3
2
4.95 (d, J1,2
= 3.9 Hz, 1 H, 1-H), 4.36–4.01 (m, 2 H,
-CH2CH=CH2), 4.24 (dd, J6a,6b = 12.3 Hz, J5,6a = 4.5 Hz, 1 H, 6a-
H), 4.04 (dd, J5,6b = 2.1 Hz, 1 H, 6b-H), 3.99–3.93 (m, 1 H, 5-H), CH2CH=CH2), 2.60 (br. s, 1 H, 2-OH), 2.05 (ϫ2), 2.00 (3ϫs, 9 H,
3.71–3.62 (m, 1 H, 2-H), 2.23 (d, J2,OH = 7.5 Hz, 1 H, OH-2),
2.06, 2.04, 2.00 (3ϫs, 9 H, 3ϫ-COCH3) ppm. 13C NMR (75 MHz,
CDCl3): δ = 171.0, 170.5, 169.5, 132.9, 118.5, 97.3 (C-1), 73.3, 70.7,
69.0, 67.9, 67.6, 61.8, 20.7 ppm. Significant signals for the β-ano-
mer: 1H NMR (300 MHz, CDCl3): δ = 5.09 (t, J2,3 = J3,4 = 9.6 Hz,
1 H, 3-H), 4.39 (d, J1,2 = 8.1 Hz, 1 H, 1-H), 3.57 (m, 1 H, 2-H)
ppm. C15H22O9 (346.33): calcd. C 52.02, H 6.40; found C 51.80, H
6.31.
3ϫ-COCH3) ppm. 13C NMR (75 MHz, CDCl3): δ = 171.0, 170.5,
169.5, 137.6, 115.2, 98.3, 73.5, 70.8, 68.2 (ϫ2), 67.7, 62.1, 30.2,
28.4, 20.6 ppm. Significant signals for the β-anomer: 1H NMR
(300 MHz, CDCl3): δ = 5.09 (t, J3,4 = J2,3 = 9.9 Hz, 1 H, 3-H),
4.32 (d, J1,2 = 7.8 Hz, 1 H, 1-H) ppm. C17H26O9 (374.39): calcd. C
54.54, H 7.00; found C 54.32, H 6.87.
Allyl 2,3,4,6-Tetra-O-benzoyl-β-D
-glucopyranoside (10):[15] Foam.
[α]2D4 = +50.7 (c = 1.1, CHCl3). H NMR (300 MHz, CDCl3): δ =
8.30–7.20 (aromatic protons), 5.96 (t, J3,4 = J2,3 = 9.6 Hz, 1 H, 3-
H), 5.80–5.66 (m, 2 H, -CH2CH=CH2 and 4-H), 5.62 (t, 1 H, 2-
H), 5.24 (d, 3J = 17.4 Hz, 1 H, CH2CH=CHcisHtrans), 5.14 (d, 3J =
10.5 Hz, 1 H, -CH2CH=CHcisHtrans), 4.95 (d, J1,2 = 8.1 Hz, 1 H,
1
n-Propyl 2,3,4,6-Tetra-O-acetyl-D
-glucopyranoside (5):[13] Oil, yield
29%, anomeric mixture (α/β, 1:4.7). Data for the β-anomer: 1H
NMR (300 MHz, CDCl3): δ = 5.16 (t, J2,3 = J3,4 = 9.6 Hz, 1 H, 3-
H), 5.04 (t, J4,5 = 9.6 Hz, 1 H, 4-H), 4.94 (dd, J1,2 = 8.1 Hz, J2,3
=
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A. Pastore, M. Adinolfi, A. Iadonisi
FULL PAPER
1-H), 4.68 (dd, J6a,6b = 11.8 Hz, J5,6b = 2.8 Hz, 1 H, 6b-H), 4.60– Allyl 2,3,4-Tri-O-acetyl-β-
L
-fucopyranoside (20): Oil, yield 68%, 1H
4.05 (4 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 166.1, 165.8,
165.2, 165.1, 133.5, 133.3, 133.2 (ϫ2), 133.1, 129.8–128.3, 117.9,
NMR (300 MHz, CDCl3): δ = 5.83–5.68 (m, 1 H, -CH2CH=CH2),
5.23–5.05 (m, 4 H, -CH2CH=CH2, 4-H and 2-H), 4.93 (dd, J3,4
=
99.8 (C-1), 73.0, 72.2, 71.9, 70.1, 69.8, 63.2 ppm. C37H32O10 3.3 Hz, J2,3 = 10.5 Hz, 1 H, 3-H), 4.41 (d, J1,2 = 8.1 Hz, 1 H, 1-
(636.65): calcd. C 69.80, H 5.07; found C 69.65, H 5.21.
H), 4.32–4.20 (m, 3J
=
4.5 Hz, 2J
=
13.5 Hz,
1
H,
3
2
-CHaHbCH=CH2), 4.05–3.95 (m, J = 6.0 Hz, J = 13.5 Hz, 1 H,
-CHaHbCH=CH2), 3.73 (q, J5,6 = 6.6 Hz, 1-H, 5-H), 2.08, 1.96,
1.88 (3ϫs, 9 H, 3 ϫ-COCH3), 1.13 (d, 3 H, 6-CH3) ppm. 13C NMR
(75 MHz, CDCl3): δ = 170.4, 169.9, 169.2, 133.4, 117.0, 99.6 (C-
1), 71.1, 70.0, 69.5, 68.8, 68.7, 20.5, 20.4, 20.3, 15.8 ppm. C15H22O8
(330.33): calcd. C 54.54, H 6.71; found C 54.35, H 6.65.
Allyl 2,3,4,6-Tetra-O-acetyl-β-D-galactopyranoside (12):[16] 1H
NMR (300 MHz, CDCl3): δ = 5.90–5.70 (m, 1 H, -CH2CH=CH2),
5.35 (dd, J3,4 = 3.3 Hz, J4,5 = 1.0 Hz, 1 H, 4-H), 5.24 (dd, 3J =
2
17.1 Hz, J = 1.5 Hz, 1 H, -CH2CH=CHcisHtrans), 5.20 (dd, J1,2
=
7.5 Hz, J2,3 = 10.5 Hz, 1 H, 2-H), 5.17 (dd, 3J = 10.5 Hz, 2J =
1.5 Hz, 1 H, -CH2CH=CHcisHtrans), 4.99 (dd, 1 H, 3-H), 4.49 (d, 1
H, 1-H), 4.37–4.27 (m, 1 H), 4.15 (dd, J6a,6b = 12.6 Hz, 1 H, 6-H),
4.11–4.03 (m, 2 H), 3.87 (br. t, J5,6a = J5,6b = 6.6 Hz, 1 H, 5-H),
2.11, 2.02, 2.01, 1.94 (4ϫs, 12 H, 4ϫ-COCH3) ppm. 13C NMR
(75 MHz, CDCl3): δ = 170.2, 170.1, 170.0, 169.3, 133.2, 117.4, 99.9
(C-1), 70.8, 70.5, 69.9, 68.7, 66.9, 61.2, 20.5 ppm. C17H24O10
(388.37): calcd. C 52.57, H 6.23; found C 52.35, H 6.10.
Allyl 3,4-Di-O-acetyl-L-fucopyranoside (21): Oil, yield 30%, anom-
eric mixture (α/β, 2.4:1). Data for the α-anomer: 1H NMR
(300 MHz, CDCl3): δ = 5.95–5.80 (m, 1 H, -CH2CH=CH2), 5.35–
5.20 (m, 3 H, -CH2CH=CH2 and 4-H), 5.11 (dd, J3,4 = 3.3 Hz, J2,3
= 10.5 Hz, 1 H, 3-H), 4.94 (d, J1,2 = 3.6 Hz, 1 H, 1-H), 4,25–3.95
(m, 3 H, -CH2CH=CH2 and 5-H), 3.91 (br. dd, 1 H, 2-H), 2.61 (br.
s, 1 H, 2-OH), 2.12, 2.01 (2ϫs, 6 H, 2ϫ-COCH3), 1.10 (d, J5,6
=
Allyl 3,4,6-Tri-O-acetyl-D
-galactopyranoside (13):[17] Oil, yield 45%,
6.3 Hz, 3 H, 6-H3) ppm. 13C NMR (75 MHz, CDCl3): δ = 170.5
(ϫ2), 133.3, 118.0, 97.7 (C-1), 71.2 (ϫ2), 68.8, 66.9, 64.8, 20.8,
20.6, 15.8 ppm. Significant signals for the β-anomer: 1H NMR
(300 MHz, CDCl3): δ = 4.89 (dd, J3,4 = 3.3 Hz, J2,3 = 10.5 Hz, 1
H, 3-H), 4.34 (d, J1,2 = 8.1 Hz, 1 H, 1-H), 2.11, 2.01 (2ϫs, 6 H,
2ϫ-COCH3), 1.18 (d, J5,6 = 6.3 Hz, 3 H, 6-H3) ppm. C13H20O7
(288.30): calcd. C 54.16, H 6.91; found C 54.21, H 6.80.
anomeric mixture (α/β, 1.3:1). Data for the α-anomer: 1H NMR
(300 MHz, CDCl3): δ = 6.00–5.80 (m, 1 H, -CH2CH=CH2), 5.36
(dd, J3,4 = 3.0 Hz, J4,5 = 1.2 Hz, 1 H, 4-H), 5.29 (dd, 3J = 17.1 Hz,
2J = 1.2 Hz, 1 H, -CH2CH=CHcisHtrans), 5.22 (dd, 3J = 10.5 Hz, 2J
= 1.2 Hz, 1 H, -CH2CH=CHcisHtrans), 5.11 (dd, J2,3 = 10.5 Hz, 1
H, 3-H), 4.99 (d, J1,2 = 3.9 Hz, 1 H, 1-H), 4.30–4.00 (m, 5 H, 5-H,
6-H2 and -CH2CH=CH2), 3.80 (m, 1 H, 2-H), 2.70 (br. s, 1 H, 2-
OH), 2.10, 2.01 (ϫ2) (2ϫs, 9 H, 3ϫ-COCH3) ppm. 13C NMR
(75 MHz, CDCl3): δ = 170.6, 170.3, 170.0, 133.0, 118.3, 97.6 (C-1),
70.6, 68.9, 68.1, 66.9, 66.7, 61.7 (C-6), 20.6, 20.5 ppm. Significant
signals for the β-anomer: 1H NMR (300 MHz, CDCl3): δ = 4.89
(dd, J3,4 = 3.3 Hz, J2,3 = 10.5 Hz, 1 H, 3-H), 4.38 (d, J1,2 = 7.5 Hz,
1 H, 1-H) ppm. 13C NMR (75 MHz, CDCl3): δ = 101.9 (C-1) ppm.
C15H22O9 (346.33): calcd. C 52.02, H 6.40; found C 51.85, H 6.30.
Allyl 2,3,4-Tri-O-acetyl-L
-rhamnopyranoside (23):[19] Oil, yield
74%, anomeric mixture (α/β, 4.5:1). Data for the α-anomer: 1H
NMR (200 MHz, CDCl3): δ = 5.96–5.70 (m, 1 H, -CH2CH=CH2),
5.23 (dd, 3J = 17.2 Hz, 2J = 1.5 Hz, 1 H, -CH2CH=CHcisHtrans),
5.20 (dd, J2,3 = 3.4 Hz, J3,4 = 9.7 Hz, 1 H, 3-H), 5.18 (dd, J1,2
=
1.8 Hz, 1 H, 2-H), 5.15 (dd, 3J = 10.1 Hz, 2J = 1.5 Hz, 1 H,
-CH2CH=CHcisHtrans), 4.99 (t, J4,5 = 9.7 Hz, 1 H, 4-H), 4.70 (d, 1
H, 1-H), 4.18–3.88 (m, 2-H, -CH2CH=CH2), 3.88–3.74 (m, 1 H, 5-
H), 2.07, 1.98, 1.91 (3ϫs, 9 H, 3ϫ-COCH3), 1.15 (d, J5,6 = 6.2 Hz,
3 H, 6-CH3) ppm. 13C NMR (50 MHz, CDCl3): δ = 169.9, 169.8,
169.7, 133.1, 117.8, 96.3 (C-1), 70.9, 69.7, 68.9, 68.1, 66.2, 20.6
ppm. Data for the β-anomer: 1H NMR (300 MHz, CDCl3): δ =
5.92–5.77 (m, 1 H, -CH2CH=CH2), 5.44 (d, J2,3 = 3.0 Hz, 1 H, 2-
Allyl 3,4,6-Tri-O-acetyl-2-O-methoxycarbonyl-β-D-glucopyranoside
(15): Oil. [α]2D5 = +7.5 (c = 0.5, CHCl3). 1H NMR (300 MHz,
CDCl3): δ = 5.90–5.72 (m, 1 H, -CH2CH=CH2), 5.35 (br. s, 1 H,
4-H), 5.22 (m, 3J = 17.4 Hz, 2J = 1.2 Hz, 1 H, -CH2CH=CHcis
Htrans), 5.14 (m, J = 10.5 Hz, J = 1.2 Hz, 1 H, -CH2CH=CHcis
-
-
3
2
Htrans), 4.98–4.97 (m, overlapped signals, 2 H, 1-H and 3-H), 4.50
H), 5.24 (dd, 3J = 17.5 Hz, 2J = 1.5 Hz, 1 H, -CH2CH=CHcis
-
-
(dd, J1,2 = J2,3 = 3.9 Hz, 1 H, 1 H, 2-H), 4.35–4.00 (m, 4 H, 6-H2
and -CH2CH=CH2), 3.86 (t, J5,6a = J5,6b = 6.9 Hz, 1 H, 5-H), 3.75
(s, 3 H, -OCH l3), 2.08, 1.98, 1.93 (3ϫs, 9 H, 3ϫ-COCH3) ppm.
13C NMR (75 MHz, CDCl3): δ = 170.1, 170.0, 169.8, 154.7, 133.1,
117.4, 99.8 (C-1), 72.8, 70.6, 70.4, 70.0, 66.9, 61.0, 55.0, 20.4 ppm.
C17H24O11 (404.37): calcd. C 50.49, H 5.98; found C 50.25, H 6.04.
3
2
Htrans), 5.19 (dd, J = 10.5 Hz, J = 1.5 Hz, 1 H, -CH2CH=CHcis
Htrans), 5.03 (t, J3,4 = J4,5 = 10.2 Hz, 1 H, 4-H), 4.97 (dd, 1 H, 3-
H), 4.63 (s, 1 H, 1-H), 4.32 (dd, 3J = 4.8 Hz, 2J = 12.9 Hz, 1 H,
-CHaHbCH=CH2), 4.07 (dd, 3J = 6.3 Hz, 2J = 12.9 Hz, 1 H,
-CHaHbCH=CH2), 3.55–3.42 (m, 1 H, 5-H), 2.16, 2.03, 1.96 (3ϫs,
9 H, 3ϫ-COCH3), 1.26 (d, J5,6 = 6.0 Hz, 3 H, 6-CH3) ppm. 13C
NMR (75 MHz, CDCl3): δ = 170.1 (ϫ3), 133.2, 118.0, 96.9 (C-1),
71.1, 70.7, 70.5, 70.0, 69.1, 20.8, 20.7, 20.5, 17.4 ppm. C15H22O8
(330.33): calcd. C 54.54, H 6.71; found C 54.40, H 6.60.
Allyl 2,3,4,6-Tetra-O-acetyl-α-D
-mannopyranoside (17):[18] Oil, yield
25%, anomeric mixture (α/β, 3.7:1). Data for the α-anomer: 1H
NMR (300 MHz, CDCl3): δ = 6.00–5.80 (m, 1 H, -CH2CH=CH2),
5.35 (dd, J3,4 = 10.2 Hz, 1-H, 3-H), 5.29 (dd, 3J = 17.1 Hz, 2J =
1.2 Hz, 1 H, -CH2CH=CHcisHtrans), 5.27 (t, J4,5 = 10.2 Hz, 1 H, 4- Allyl 2,3,4,6-Tetra-O-acetyl-β-
D
-galactopyranosyl-(1Ǟ4)-2,3,6-tri-
-glucopyranoside (25):[20] Foam, yield 29%, anomeric
mixture (α/β, 1:6). Data for the β-anomer: 1H NMR (200 MHz,
3
2
H), 5.24 (dd, J2,3 = 3.1 Hz, 1 H, 2-H), 5.22 (dd, J = 10.5 Hz, J
= 1.2 Hz, 1 H, CH2CH=CHcisHtrans), 4.85 (d, J1,2 = 1.5 Hz, 1 H,
O-acetyl-D
1-H), 4.27 (dd, J6a,6b = 12.1 Hz, J5,6a = 5.2 Hz, 1 H, 6a-H), 4.22– CDCl3): δ = 5.93–5.70 (m, 1 H, -CH2CH=CH2), 5.31 (br. d, J3,4
=
4.12 (br. dd, 3J = 5.4 Hz, 2J = 13.2 Hz, 1 H, -CHaHbCH=CH2), 3.4 Hz, 1 H, 4Ј-H), 5.23 (dd, 3J = 17.3 Hz, 2J = 1.6 Hz, 1 H,
4.11–3.95 (m, 3 H, 6b-H, -CHaHbCH=CH2 and 5-H), 2.13, 2.09,
2.02, 1.97 (4ϫs, 12 H, 4ϫ-COCH3) ppm. 13C NMR (75 MHz,
CDCl3): δ = 170.6, 170.0, 169.7, 169.6, 132.9, 118.3, 96.5 (C-1),
-CH2CH=CHcisHtrans), 5.16 (t, J2,3 = J3,4 = 9.6 Hz, 1 H, 3-H), 5.15
(dd, 3J = 10.6 Hz, 2J = 1.6 Hz, 1 H, -CH2CH=CHcisHtrans), 5.07
(dd, J1,2 = 7.9 Hz, J2,3 = 10.4 Hz, 1 H, 2Ј-H), 4.92 (dd, 1 H, 3Ј-H),
4.89 (br. dd, J1,2 = 8.0 Hz, J2,3 = 9.6 Hz, 1 H, 2-H), 4.53–4.42
69.6, 69.0, 68.6, 68.5, 66.2, 62.4, 20.6 ppm. Significant signals for
1
the β-anomer: H NMR (300 MHz, CDCl3): δ = 5.48 (dd, J1,2
=
(2ϫd, 2 H, 1-H and 1Ј-H), 4.34–3.92 (m, 6 H), 3.84 (br. t, J5,6a =
0.9 Hz, J2,3 = 3.6 Hz, 1 H, 2-H), 5.26 (t, J3,4 = J4,5 = 9.6 Hz, 1 H, J5,6b = 6.8 Hz, 1 H, 5Ј-H), 3.77 (t, J3,4 = J4,5 = 9.3 Hz, 1 H, 4-H),
4-H), 5.04 (dd, 1-H, 3-H), 4.68 (d, 1 H, 1-H), 3.68–3.60 (m, 1 H, 3.63–3.50 (m, 1 H, 5-H), 2.11, 2.09, 2.02, 2.01 (ϫ2), 2.00, 1.92
5-H), 2.19, 2.09, 2.04, 1.99 (4ϫs, 12 H, 4ϫ-COCH3) ppm.
C17H24O10 (388.37): calcd. C 52.57, H 6.23; found C 52.35, H 6.15.
(7ϫs, 21 H, 7ϫ-COCH3) ppm. 13C NMR (50 MHz, CDCl3): δ =
170.2 (ϫ2), 170.0, 169.8, 169.6, 169.4, 168.8, 133.2, 117.5, 100.9
6210
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© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2008, 6206–6212

BiBr3-Promoted Activation of Peracetylated Glycosyl Iodides
(C-1Ј), 99.2 (C-1), 76.2, 72.8, 72.5, 71.6, 70.9, 70.6, 69.9, 69.1, 66.6,
62.0, 60.8, 20.6 ppm. C29H40O18 (676.62): calcd. C 51.48, H 5.96;
found C 51.13, H 5.78.
2-O-(Fluorenyl)methyloxycarbonyl-3,4,6-tri-O-acetyl-D-glucopyr-
anosyl (N-Phenyl)trifluoroacetimidate (31): To a solution of 30
(106 mg, 0.20 mmol) in acetone (4 mL) was sequentially added at
0 °C Cs2CO3 (74 mg, 0.23 mmol) and (N-phenyl)trifluoroacetimi-
doyl chloride (50 mL, 0.40 mmol). The mixture was allowed to
warm to room temperature and after 1 h from the start of the reac-
tion the solvent was removed in vacuo. The residue was purified by
column chromatography on neutral aluminium oxide (Brockman
grade 2, petroleum ether/ethyl acetate mixtures) to yield 31 (oil,
119 mg, yield 85%) as an anomeric mixture (α/β, 2.5:1). Data for
the α-anomer: 1H NMR (300 MHz, CDCl3): δ = 7.80–6.75 (aro-
matic protons), 6.74 (br. s, 1 H, 1-H), 5.66 (t, J2,3 = J3,4 = 9.9 Hz,
1 H, 3-H), 5.23 (t, J4,5 = 9.9 Hz, 1 H, 4-H), 5.05 (dd, J1,2 = 3.3 Hz,
1 H, 2-H), 4.50–4.10 (m, 6 H), 2.14, 2.11, 2.09 (3ϫs, 9 H, 3 ϫ
-COCH3) ppm. 13C NMR (75 MHz, CDCl3): δ = 170.3, 169.7,
169.4, 154.0, 143.0, 142.8, 141.2, 128.7, 127.9, 127.1, 125.0, 124.5,
120.0, 119.1, 91.8 (C-1), 73.0, 70.6, 67.6, 61.2, 46.3, 20.5 ppm. Sig-
Allyl 2,3,4,6-Tetra-O-acetyl-β-
D-galactopyranosyl-(1Ǟ4)-3,6-di-O-
acetyl-α-
D
-glucopyranoside (26): Oil. [α]2D5 = +62.3 (c = 1.2, CHCl3).
1H NMR (400 MHz, CDCl3): δ = 5.97–5.80 (m, 1 H, -CH2CH=
CH2), 5.37–5.15 (m, 4 H, 4Ј-H, -CH2CH=CH2, 3-H), 5.06 (dd, J1,2
= 7.6 Hz, J2,3 = 10.4 Hz, 1 H, 2Ј-H), 4.89 (dd, J3,4 = 3.3 Hz, 1 H,
3Ј-H), 4.86 (d, J1,2 = 3.4 Hz, 1 H, 1-H), 4.47 (d, 1 H, 1Ј-H), 4.40
(dd, J5,6a = 5.6 Hz, J6a,6b = 11.6 Hz, 1 H, 6a-H), 4.21–3.80 (m, 7
H, 6b-H, 6Ј-H2, 5-H, OCH2-CH=CH2 and 2-H), 3.64 (t, J3,4 = J4,5
= 9.6 Hz, 1 H, 4-H), 3.56–3.47 (br. t, J5,6a = J5,6b = 7.8 Hz, 1 H,
5Ј-H), 2.74 (br. s, 1 H, 2-OH), 2.11, 2.08 (ϫ2), 2.01 (ϫ2), 1.92
(6ϫs, 18 H, 6ϫ-COCH3) ppm. 13C NMR (50 MHz, CDCl3): δ =
170.6, 170.2, 170.1, 170.0, 169.9, 168.9, 133.0, 118.3, 100.8 (C-1Ј),
97.0 (C-1), 76.1, 73.2, 70.9, 70.3, 68.9 (ϫ2), 68.3, 66.5, 62.0, 60.7
(ϫ2), 20.7, 20.5 ppm. C27H38O17 (634.59): calcd. C 51.10, H 6.04;
found C 50.95, H 5.83.
1
nificant signals for the β-anomer: H NMR (300 MHz, CDCl3): δ
= 5.90 (br. s, 1 H, 1-H), 5.39 (t, J2,3 = J3,4 = 9.9 Hz, 1 H, 3-H) ppm.
13C NMR (75 MHz, CDCl3): δ = 94.2 (C-1) ppm. C35H32F3NO11
(699.63): calcd. C 60.09, H 4.61; found C 59.90, H 4.50.
Allyl 2-(Fluorenyl)methyloxycarbonyl-3,4,6-tri-O-acetyl-D-glucopyr-
anoside (29): To a solution of 4 (248 mg, 0.72 mmol) in anhydrous
DCM (8 mL) was sequentially added pyridine (0.64 mL, 8.0 mmol)
and FmocCl (259 mg, 1.0 mmol). When the reaction was complete
(ca. 3 h), the mixture was diluted with DCM and washed with
water. The aqueous phase was extracted with DCM, and the col-
lected organic phase was dried and concentrated under vacuo. The
residue was purified by silica-gel flash chromatography (petroleum
ether/ethyl acetate mixtures) to yield 29 (oil, 311 mg, 76% yield) as
Methyl 2-O-(Fluorenyl)methyloxycarbonyl-3,4,6-tri-O-acetyl-β-
D-
glucopyranosyl-(1Ǟ2)-3-O-benzyl-4,6-O-benzylidene-α- -glucopyr-
D
anoside (33): Donor 31 (35 mg, 0.05 mmol) and acceptor 32 (13 mg,
0.035 mmol) were coevaporated (3ϫ) in anhydrous toluene and
then dried in vacuo for 30 min. The mixture was then dissolved at
0 °C (ice bath) under an atmosphere of argon with anhydrous DCE
(1 mL) in the presence of freshly activated 4 Å AW molecular si-
eves. After stirring for 15 min, a solution of Bi(OTf)3 in dioxane
(17 mgmL–1, 135 µL, 3.5 µmol) was added. After a further 10 min
the ice bath was removed and the mixture was left whilst stirring
until TLC analysis displayed the consumption of the donor (ca.
90 min from the addition of the promoter). The reaction was
quenched with pyridine, and the mixture was filtered through a
short pad of silica gel. The residue from the filtered liquor was
submitted to silica-gel flash chromatography (toluene/acetone, 7:1)
to yield disaccharide 33 as a foam (21 mg, 70% yield). [α]2D5 = +29.3
(c = 1.1, CHCl3). 1H NMR (CDCl3, 300 MHz): δ = 7.70–7.20 (aro-
1
an anomeric mixture (α/β, 6:1). Data for the α-anomer: H NMR
(300 MHz, CDCl3): δ = 7.80–7.28 (aromatic protons), 5.97–5.82
(m, 1 H, -CH2CH=CH2), 5.59 (t, J2,3 = J3,4 = 9.7 Hz, 1 H, 3-H),
5.34 (dq, 3J = 17.2 Hz, 2J = 4J = 1.5 Hz, 1 H, -CH2CH=CHcis
3
2
4
Htrans), 5.22 (dq, J = 10.3 Hz, J = J = 1.5 Hz, 1 H, -CH2CH=
CHcisHtrans), 5.17 (d, J1,2 = 3.6 Hz, 1 H, 1-H), 5.09 (t, J3,4 = J4,5
=
9.7 Hz, 1 H, 4-H), 4.79 (dd, 1 H, 2-H), 4.44–4.01 (m, 8 H), 2.10,
2.04, 2.01 (3ϫs, 9 H, 3ϫ-COCH3) ppm. 13C NMR (75 MHz,
CDCl3): δ = 170.3, 169.8, 169.6, 154.1, 143.0, 142.9, 141.1 (ϫ2),
132.9, 127.8–119.9, 118.1, 94.6 (C-1), 73.8, 70.2, 69.9, 68.8, 68.5,
67.3, 61.7, 46.4, 20.5, 20.4 ppm. Significant signals for the β-
matic protons), 5.56 (s, 1 H, benzylidene acetal CH), 5.27 (t, J2,3
J3,4 = 9.7 Hz, 1 H, 3Ј-H), 5.09 (t, J4,5 = 9.7 Hz, 1 H, 4Ј-H), 4.97
=
anomer: 1H NMR (300 MHz, CDCl3): δ = 5.32 (t, J2,3 = J3,4
=
9.7 Hz, 1 H, 3-H), 5.11 (t, J4,5 = 9.7 Hz, 1 H, 4-H), 4.88 (br. dd,
J1,2 = 7.9 Hz, 1 H, 2-H), 4.64 (d, 1 H, 1-H), 3.76–3.68 (m, 1 H, 5-
H), 2.09, 2.03, 1.97 (3ϫs, 9 H, 3ϫ-COCH3) ppm. C30H32O11
(568.58): calcd. C 63.37, H 5.67; found C 63.14, H 5.75.
(d, J1,2 = 7.5 Hz, 1 H, 1Ј-H), 4.93 (dd, 1 H, 2Ј-H), 4.83 (d, J1,2
=
3.6 Hz, 1 H, 1-H), 4.72 (s, 2 H, benzyl CH2), 4.40 (dd, 3J = 7.8,
10.5 Hz, 1 H, Fmoc -OCH2CH), 4.32–4.06 (m, 5 H, overlapped
3
signals), 3.98 (t, J2,3 = J3,4 = 9.7 Hz, 1 H, 3-H), 3.86 (td, J = 4.5,
9.7 Hz, 1 H, 5-H), 3.80–3.70 (m, 2 H, 2-H, 6ax-H), 3.70–3.65 (m,
1 H, 5Ј-H), 3.60 (t, 1 H, 4-H), 3.42 (s, 3 H, -OCH3), 2.09, 2.03,
1.94 (3ϫs, 9 H, 3ϫ-COCH3) ppm. C NMR (CDCl3, 75 MHz):
δ = 170.4, 170.0, 169.2, 169.4, 154.1, 133.1, 143.2, 142.9, 141.2,
138.3, 137.4, 128.9–127.2, 126.0, 125.0, 129.0, 101.3 (ϫ2) (C-1Ј and
benzylidene acetal CH), 100.1 (C-1), 82.3, 79.5, 77.7, 77.2, 75.4,
75.2, 72.8, 71.9, 70.2, 69.1, 68.5, 62.2, 61.9, 55.4, 46.5, 20.6, 20.5
(ϫ2) ppm. C48H50O16 (882.91): calcd. C 65.30, H 5.71; found C
65.05, H 5.53.
2-(Fluorenyl)methyloxycarbonyl-3,4,6-tri-O-acetyl-D-glucopyranose
(30): To a solution of 29 (320 mg, 0.56 mmol) in DCM/MeOH (4:1,
5 mL) was added PdCl2 (13 mg, 0.07 mmol). The mixture was
stirred for 10 h at room temperature, concentrated, resuspended in
DCM/MeOH (95:5), and then filtered through a short pad of silica
gel. The filtered liquor was concentrated, and the residue was puri-
fied by silica-gel flash chromatography (petroleum ether/ethyl ace-
tate mixtures) to yield 30 (oil, 193 mg, 65% yield) as an anomeric
mixture (α/β 3.5). Data for the α-anomer: 1H NMR (300 MHz,
13
CDCl3): δ = 7.80–7.28 (aromatic protons), 5.61 (t, J2,3 = J3,4
=
9.7 Hz, 1 H, 3-H), 5.50 (br. s, 1 H, 1-H), 5.09 (t, J3,4 = J4,5 = 9.6 Hz,
1 H, 4-H), 4.78 (dd, J1,2 = 3.6 Hz, 1 H, 2-H), 4.40–4.04 (m, 6 H),
2.07, 2.02, 1.99 (3ϫs, 9 H, 3 ϫ-COCH3) ppm. 13C NMR (75 MHz,
CDCl3): δ = 170.8, 170.1, 169.7, 154.2, 143.0, 142.9, 141.1 (ϫ2),
127.8–120.0, 89.8 (C-1), 74.3, 70.2, 69.7, 68.4, 67.0, 61.8, 46.4,
20.6 ppm. Significant signals for the β-anomer: 1H NMR
(300 MHz, CDCl3): δ = 5.32 (t, J2,3 = J3,4 = 9.7 Hz, 1 H, 3-H),
3.79–3.71 (m, 1 H, 5-H) ppm. C27H28O11 (528.51): calcd. C 61.36,
H 5.34; found C 61.12, H 5.18.
Acknowledgments
NMR facilities of CIMCF (Centro Interdipartimentale di Metodo-
logie Chimico-Fisiche dell’Università Federico II di Napoli) are ac-
knowledged.
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Received: September 17, 2008
Published Online: November 14, 2008
6212
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© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2008, 6206–6212