2-(Dimethyl (2-naphthylmethyl)silyl) ethoxy carbonate (NSEC) as a new mode of hydroxyl group protection

Article abstract of DOI:10.1081/CAR-200067008

2-[Dimethyl(2-naphthylmethyl)silyl]ethoxy carbonate (NSEC) is a novel protecting group to mask hydroxyl groups. NSECCl is available in three steps from chlorodimethylvinylsilane and 2-(bromomethyl)naphthalene. Introduction and removal of the NSEC group ar

Full text of DOI:10.1081/CAR-200067008

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2‐[Dimethyl(2‐naphthylmethyl)silyl]ethoxy
Carbonate (NSEC) as a New Mode of
Hydroxyl Group Protection
Simone Bufali a , Alexandra Hölemann a & Peter H. Seeberger a
a Laboratory for Organic Chemistry , ETH Zürich , Zürich,
Switzerland
Published online: 16 Aug 2006.
To cite this article: Simone Bufali , Alexandra Hölemann & Peter H. Seeberger (2005)
2‐[Dimethyl(2‐naphthylmethyl)silyl]ethoxy Carbonate (NSEC) as a New Mode of Hydroxyl Group
Protection , Journal of Carbohydrate Chemistry, 24:4-6, 441-462
To link to this article: http://dx.doi.org/10.1081/CAR-200067008
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Journal of Carbohydrate Chemistry, 24:441–462, 2005
Copyright # Taylor & Francis, Inc.
ISSN: 0732-8303 print 1532-2327 online
DOI: 10.1081/CAR-200067008
2-[Dimethyl
(2-naphthylmethyl)silyl]
ethoxy Carbonate (NSEC)
as a New Mode of Hydroxyl
Group Protection
Simone Bufali, Alexandra Ho¨lemann, and Peter H. Seeberger
Laboratory for Organic Chemistry, ETH Zu¨rich, Zu¨rich, Switzerland
2-[Dimethyl(2-naphthylmethyl)silyl]ethoxy carbonate (NSEC) is a novel protecting
group to mask hydroxyl groups. NSECCl is available in three steps from chlorodimethyl-
vinylsilane and 2-(bromomethyl)naphthalene. Introduction and removal of the NSEC
group are performed easily and rapidly in the presence of most protecting groups
currently used in carbohydrate chemistry. The removal of NSEC can be carried out
under mild conditions in the presence of various ether and ester protecting groups.
Additionally, the NSEC group is stable to glycosylation conditions using glycosyl phos-
phates. The synthesis of disaccharide 18 containing NSEC has been accomplished.
Keywords Carbonate, Carbohydrates, Deprotection, Glycosylation, Oligosaccharides,
Silyl protecting group
INTRODUCTION
The synthesis of complex, branched carbohydrates requires an orthogonal
protecting group pattern that masks hydroxyl groups that serve as connecting
points. Since each monosaccharide presents up to four functional groups with
similar reactivity, the differential protection of these functional groups remains
a major challenge in the assembly of large carbohydrate structures. In addition
to protecting group orthogonality, the steric and electronic nature of the protecting
Received January 3, 2005; accepted March 1, 2005.
In memory of Professor Jacques H. van Boom
Address correspondence to Peter H. Seeberger, Laboratory for Organic Chemistry,
¨
¨
Eidgenossische Technische Hochschule Zu¨rich, ETH Honggerberg, HCI F315,
Wolfgang-Pauli-Strasse 10, CH-8093 Zu¨rich, Switzerland. E-mail: seeberger@org.
chem.ethz.ch
441

S. Bufali, A. Ho¨lemann, and P. H. Seeberger
442
groups are important because they influence the reactivity of the building blocks
and the outcome of the glycosylation reactions. A variety of different protecting
groups that can be removed selectively has been disclosed.[1] Benzyl ethers are
typically used as permanent protecting groups, which mask hydroxyl groups
during the entire synthesis and are removed at the late stages of oligosaccharide
assembly. Various esters, silyl ethers, and allyl ethers commonly are employed as
temporary protecting groups. The choice of an orthogonal protecting group
pattern represents a key issue in planning and executing the synthesis of the
target molecule. Silyl ether-based protecting groups have achieved great popular-
ity in organic synthesis.
Silyl-based modes of protection are relatively stable under basic or neutral
conditions, and many silyl-based groups even tolerate weak acidic reaction
conditions. In addition, a range of cleavage conditions for silyl ether bonds is
available.[2] The removal of silyl groups by fluoride ions has been used
commonly, because the formation of the Si-F bond is energetically favored.
The use of silyl ethers has already been established for solid-phase oligo-
nucleotide[3] and oligosaccharide[4] syntheses.
UV-active protecting groups have been applied to solid support oligosac-
charide synthesis since real-time monitoring of coupling reactions is of
particular utility for automated oligosaccharide assembly. Therefore, the
9-fluorenylmethoxycarbonyl (Fmoc) group has been used as a temporary
protecting group in the automated synthesis of Lewis antigens.[5] The UV-
active dibenzofulvene moiety released after Fmoc cleavage allows for real-
time monitoring of the reaction progress.[6]
The trimethylsilylethoxy carbonate (Teoc) group is a useful protecting
group for hydroxyl[7] and amino groups in peptide[8] and oligonucleotide[9,10]
assembly. It is readily introduced in good yields using mild basic conditions.
Facile, selective removal of Teoc in the presence of other carbonate-based pro-
tecting groups such as Fmoc has been achieved by treatment with acetic acid-
buffered TBAF solutions.[11]
Here, we present 2-[dimethyl(2-naphthylmethyl)silyl]ethoxy carbonate
(NSEC) as a novel, silyl-based, temporary protecting group (Fig. 1). NSEC
combines the advantages of a silyl-based protecting group—facile and selective
cleavage—with the use of a highly UV-sensitive chromophoric tag for UV moni-
toring during automated synthesis.
Figure 1: Design of a UV active, silyl-based protecting group.

New Mode of Hydroxyl Group Protection
443
RESULTS AND DISCUSSION
2-[Dimethyl(2-naphthylmethyl)silyl]ethyl chloroformate (NSECCl) was syn-
thesized in three steps (Sch. 1). Preparation of the Grignard reagent 2-naphtyl-
methyl magnesium bromide and addition to chlorodimethylvinylsilane
afforded vinylsilane 1 in 69% yield. A hydroboration-oxidation protocol
followed by reaction of the resulting alcohol with phosgene led to the desired
chloroformate 2 (NSECCl) in good yield.
To test the stability of the NSEC group under conditions used to cleave
standard hydroxyl protecting groups, NSEC protected glucose 5 containing a
free hydroxyl group in C2 was prepared (Sch. 2). Introduction of the NSEC
group at the C6 hydroxyl position of the 1,2-anhydrosugar 3[12] proceeded
smoothly under mild basic conditions using DMAP to give 4 (98% yield).
Epoxidation of the double bond with dimethyldioxirane (DMDO) and opening
of the epoxide with methanol yielded 81% of the desired glucose building
block 5.
The introduction of different ester and carbonate protecting groups at the
C2 hydroxyl group of 5 was achieved in the presence of the NSEC protecting
group and furnished fully protected monosaccharides 6a–e (Table 1).
Unfortunately, ether protecting groups like allyl and p-methoxybenzyl
(PMB) could not be introduced successfully. Treatment of 5 with sodium
hydride and allyl bromide in DMF at 08C gave only 18% of the desired
product 6f, as cleavage of NSEC under these basic conditions occured. Allyla-
tion in the presence of allyl trichloroacetimidate[13] (AllTCA) allows for protec-
tion of hydroxyl groups under acidic conditions. However, the reaction of 5 and
AllTCA promoted by TfOH in CH2Cl2/hexanes[13] or by TMSOTf yielded only
24% and 19% of 6f, respectively, due to incomplete conversion.
To prepare the C2 O-allyl and O-PMB-protected glucose derivatives, a
different synthetic route was chosen (Sch. 3). The C6 hydroxyl group of 3
was protected with TIPS before epoxidation with DMDO and epoxide
opening with methanol afforded 7.[14] The C2 hydroxyl group of 7 was then
protected using p-methoxybenzyl chloride or allyl bromide and sodium
hydride to give monosaccharides 8a and 8b. Desilylation with TBAF and C6
hydroxyl protection with NSECCl in the presence of DMAP yielded the
desired monosaccharides 9 and 6f.
Scheme 1: (a) Mg, Et2O, 3 hr, then chlorodimethylvinylsilane, Et2O, reflux, 69%; (b) 1. 9-BBN,
THF, 1 hr; 2. H2O2, NaOH, H2O, THF, reflux, 1.5 hr, 60%; 3. phosgene, Et2O,2158C to rt, 2.5 hr, 63%.

S. Bufali, A. Ho¨lemann, and P. H. Seeberger
444
Scheme 2: (a) NSECCl, DMAP, CH2Cl2, rt, 15 hr, 98%; (b) 1. DMDO, CH2Cl2, 08C, 1 hr; 2. MeOH,
CH2Cl2, rt, 15 hr, 81% (2 steps).
To evaluate if NSEC is useful even at hindered hydroxyl groups, two mono-
saccharides with free C2 hydroxyl group were prepared (Sch. 4). Epoxidation of
10 with DMDO followed by opening of the epoxide with methanol and sub-
sequent NSEC protection gave 11, albeit in low yield. Benzylated thioglycoside
12[14] was NSEC protected to provide 13 (59% yield). These results indicate
that the NSEC group may be difficult to introduce in sterically demanding
positions.
A method for the removal of the NSEC group was developed using
monosaccharides 6a–f and 9 (Table 2). Treatment with TBAF at 08C allowed
for NSEC cleavage in the presence of most hydroxyl protecting groups.
Esters, including levulinoyl, benzoyl, pivaloyl, and acetyl esters, but also
allyl and PMB ethers are not affected under these conditions, and monosac-
charides 14a–d and 8a,b were obtained in excellent yield.
However, the NSEC group cannot be selectively removed in the presence of
Fmoc. Reaction of 6e with HF-pyridine fails to remove NSEC even after 7 d.
Treatment with TBAF/acetic acid results in Fmoc cleavage, as a mixture of 5
(38%) and the monosaccharide diol (41%) was obtained.
Table 1: Protection of 5 with common hydroxyl protecting groups in the presence
of NSEC.
Yield
Product
R
Conditions
(%)
6a
6b
6c
6d
6e
6f
Lev
Bz
Piv
Ac
Fmoc
All
LevOH, DIPC, DMAP, CH2, Cl2, 08C to rt, 15 hr
BzCl, DMAP, CH2Cl2, 08C to rt, 1.5 hr
PivCl, DMAP, CH2Cl2, 08C to rt, 3 hr
AcCl, DMAP, CH2Cl2, 08C to rt, 3 hr
FmocCl, pyridine, rt, 2 d
90
86
86
93
66
24
AllTCA,a TfOH, CH2, Cl2, hexanes, rt, 5 hr
aAllyl trichloroacetimidate.[13]

New Mode of Hydroxyl Group Protection
445
Scheme 3: (a) R ¼ PMB: 1. PMBCl, NaH, DMF, 08C to rt, 1 hr, 88%; 2. TBAF, AcOH, THF, 1 hr, 66% (2
steps); R ¼ All: 1. AllBr, NaH, DMF, 08C to rt, 1 hr;2. TBAF, THF, 1 hr, 99% (2 steps); (b) NSECCl, DMAP,
CH2Cl2, rt, 15 hr, 66% (R ¼ PMB); 58% (R ¼ All).
The stability of the NSEC group under conditions commonly used to cleave
other modes of protection was studied. The NSEC group is not affected under
deprotection conditions that facilitate the removal of levulinoyl (Lev), Fmoc,
allyl, and PMB groups (Table 3). Monosaccharide alcohol 5 was obtained in
good yield in all cases. For ester-type protecting groups (Bz, Piv, Ac) selective
deprotection was not possible. These groups are usually cleaved under
strongly basic conditions that also cleave the NSEC carbonate, thus leading
to the monosaccharide diol.
With effective protocols to place and remove the NSEC group in hand, we
used the new protecting group in the assembly of a disaccharide (Sch. 5).
The phosphate glycosylating agent 15 was prepared via a one-pot procedure
from the corresponding NSEC protected glucal 4 by epoxidation, subsequent
epoxide opening with dibutyl phosphate, and benzoylation.[15] Protection of
the C2 hydroxyl group proved difficult and furnished 15 in 20 to 47% yield.
The C2 unprotected glycosyl phosphate was isolated as a byproduct in about
20% yield. Coupling of 15 with 4-penten-1-ol proceeded smoothly in the
Scheme 4: (a) 1. DMDO, CH2Cl2, 08C, 1 hr; 2. MeOH, CH2Cl2, rt, 15 hr; 3. NSECCl, DMAP,
pyridine, CH2Cl2, rt, 2d, 25% (3 steps); (b) NSECCl, DMAP, Et3N, CH2Cl2, rt, 1d, 59%.

S. Bufali, A. Ho¨lemann, and P. H. Seeberger
446
Table 2: Removal and functional group compatibility of NSEC protected
monosaccharides.
Starting
material
Yield
(%)
Product
R
6a
6b
6c
6d
6e
6f
14a
14b
14c
14d
14e
8b
Lev
Bz
Piv
Ac
Fmoc
All
quanta
85a
91a
93a
b
—
92a
95a
9
8a
PMB
aTBAF, THF, 08C;
bAcetic acid-buffered TBAF was used. These conditions resulted in loss of Fmoc.
presence of TBSOTf to give 16 in 70% yield. Removal of the NSEC group with
TBAF (96%) and subsequent glycosylation of 17 with phosphate 15 using
TBSOTf yielded the desired disaccharide 18 in 83% yield.
CONCLUSION
In conclusion, a novel silyl-based protecting group to mask hydroxyl groups—2-
[dimethyl(2-naphthylmethyl)silyl]ethoxy carbonate (NSEC)—is reported. This
group can be readily introduced and removed in the presence of most commonly
Table 3: Stability of NSEC protected monosaccharides under various conditions.
Starting
material
Yield
(%)
R
Conditions
6a
6e
6f
Lev
Fmoc
All
NH2NH2-HOAc, MeOH, CH2Cl2, rt,1 hr
20% piperidine in DMF, rt, 30 min
PdCl2, H2O, AcOH, NaOAc, 808C, 40 min
DDQ, CH2Cl2, H2O, rt, 3 hr
quant
95
83
9
PMB
72

New Mode of Hydroxyl Group Protection
447
Scheme 5: (a) 1. DMDO, CH2 Cl2, 08C, 30 min; 2. HOP(O)(OBu)2, CH2 Cl2,2788C, 30 min; 3.
BzCl, DMAP, 08C, 3 hr, 47% (3 steps); (b) 4-Penten-1-ol, TBSOTf, CH2 Cl2, 2788 to 2308C, 3 hr, 70%;
(c) TBAF, THF, 08C, 50 min, 96%; (d) 15, TBSOTf, CH2Cl2, 2788 to 2308C, 2 hr, 83%.
used hydroxyl protecting groups. The NSEC group can be selectively removed
using TBAF in the presence of various ester and ether protecting groups. Other
carbonates such as Fmoc are also cleaved under these conditions. The NSEC
group is stable under a range of deprotection conditions, but strongly basic con-
ditions result in the removal of the NSEC group.
The NSEC carbonate is compatible with glycosylation conditions using
glycosyl phosphates and should find application in the synthesis of complex
carbohydrates and combinatorial oligosaccharide libraries. This protecting
group should be particularly useful for automated assembly of oligosacchar-
ides, as its cleavage can be followed by UV.
EXPERIMENTAL
General
All chemicals were reagent grade and used as supplied unless otherwise
noted. Dichloromethane (CH2Cl2), tetrahydrofuran (THF), diethyl ether
(Et2O), and toluene were purified by a J. C. Meyer Solvent Dispensing
System (two packed columns of neutral alumina, or in the case of toluene,
one packed column of alumina followed by one packed column of Q5 reactant,
i.e., a copper oxide oxygen scavenger). Solvents for chromatography and work-
up procedures were distilled from commercially available technical grade
solvents. Analytical thin-layer chromatography was performed on E. Merck
silica gel 60 F254 plates (0.25 mm). Compounds were visualized by UV or by
dipping the plates in a cerium sulfate-ammonium molybdate solution
followed by heating. Liquid column chromatography was performed using
forced flow of the indicated solvent on Fluka silica gel 60 (40–63 mm). 1H
NMR spectra were recorded using a Varian Mercury XL 300 spectrometer
(300 MHz) and a Bruker DRX2500 spectrometer (500 MHz) and are reported

S. Bufali, A. Ho¨lemann, and P. H. Seeberger
448
in ppm (d) relative to CHCl3 (7.25 ppm) as an internal reference. Coupling
constants (J) are reported in Hz. 13C NMR spectra were obtained using a
Varian Mercury XL 300 spectrometer (75 MHz) and a Bruker DRX2500 spec-
trometer (125 MHz) and are reported in d relative to CDCl3 (77.0 ppm) as an
internal reference. 31P NMR spectra were obtained using a Varian Mercury XL
300 spectrometer (121 MHz) and are reported in d relative to H3PO4 (0.0 ppm)
as an external reference. Optical rotations were measured on a Perkin-Elmer
241 polarimeter or a Jasco DIP-370 polarimeter (10 cm, 1 mL cell). IR spectra
were obtained on a Perkin-Elmer 1600 FT-IR spectrophotometer. High-resolution
mass spectral (HRMS) analyses were performed by the MS-service at the Labora-
tory for Organic Chemistry at ETH Zu¨rich. ESI-MS, EI-MS, and MALDI-MS were
obtained on an IonSpec Ultra instrument. In the case of MALDI-MS, 2,5-dihy-
droxybenzoic acid (DHB) served as the matrix.
General Procedures
Protection of Alcohols with Acyl Chlorides: General Procedure A
To a solution of alcohol 5 in anhydrous CH2Cl2 (ca 14 mL/mmol) DMAP (2.2
to 2.3 equiv.) was added, followed by addition of the corresponding acyl chloride
(1.9 to 2.1 equiv) at 08C. The solution was stirred for 5 min at 08C and then at rt
until TLC analysis showed complete conversion. The mixture was diluted with
hexanes/EtOAc (1 : 1) and filtered through a plug of silica gel. The solvents
were evaporated and the crude product was purified by flash silica gel
column chromatography.
NSEC Deprotection: General Procedure B
To a solution of the carbonate (1.0 equiv.) in THF (ca 20 mL/mmol) at 08C a
solution of TBAF in THF (1 M, 1.2 to 1.3 equiv) was added and the mixture was
stirred at 08C until TLC analysis showed complete conversion. Ethyl acetate
was added and the organic layer was washed with saturated aqueous
NaHCO3 solution and water. The organic phase was dried with MgSO4,
filtered, and evaporated. The residue was purified by flash silica gel column
chromatography.
Dimethyl(2-naphthylmethyl)vinylsilane (1). The glassware was dried in
the oven just before use. Magnesium (1.09 g, 45.2 mmol) was poured in a round
bottom flask and diethyl ether (100 mL) was added. A few pellets of iodine were
added several times until the brownish color persisted. 2-(Bromomethyl)-
naphthalene (8.33 g, 37.7 mmol) was added and the solution was warmed in a
water bath until boiling started. After 2 hr, chlorodimethylvinylsilane (5.70 g,
45.5 mmol) was added and the suspension was refluxed for 24 hr. The
reaction was quenched with aqueous NH4Cl solution (0.5 M) and the aqueous

New Mode of Hydroxyl Group Protection
449
phase was extracted with diethyl ether. The combined organic layers were
dried over Na2SO4, filtered, and concentrated. The crude product was
purified by flash silica gel column chromatography (hexanes/EtOAc 20 : 1) to
give 1 (5.92 g, 69%) as a colorless oil; Rf ¼ 0.50 (hexanes/EtOAc 20 : 1). 1H
NMR (300 MHz, CDCl3) d 7.80–7.70 (m, 3 H), 7.46–7.37 (m, 3 H), 7.19 (dd,
J ¼ 1.6, 8.5 Hz, 1 H), 6.23–5.95 (m, 2 H), 5.74–5.65 (m, 1 H), 2.32 (s, 2 H),
0.09 (s, 6 H). 13C NMR (75 MHz, CDCl3) d 138.4, 137.9, 134.0, 132.6, 131.3,
128.2, 127.8, 127.7, 127.2, 126.0, 125.6, 124.6, 26.4, 23.4. IR (CHCl3): vmax
cm21 3155, 2253, 1793, 1630, 1598, 1466, 1380, 1097. EI-MS: m/z (Mþ) calcd
226.1178, obsd 226.1171.
2-[Dimethyl(2-naphthylmethyl)silyl]ethyl chloroformate (2). A solution
of silane 1 (4.79 g, 21.2 mmol) in THF (15 mL) was added to a solution of 9-BBN
in THF (0.5 M, 43 mL, 21.2 mmol) at rt under nitrogen.[16] After 1 hr, ethanol
(5 mL), water (2 mL), and an aqueous NaOH solution (3 M, 18 mL) were
added. H2O2 (30%, 0.45 mL) was added dropwise at rt and the solution was
heated to reflux. After 1 hr, the mixture was cooled to rt, diluted with
aqueous NaHCO3 solution, and extracted with diethyl ether. The combined
organic layers were dried over Na2SO4, filtered, and concentrated. Purification
by flash silica gel column chromatography (hexanes/EtOAc 3 : 2) gave
2-[dimethyl(2-naphthylmethyl)silyl]ethanol (3.02 g, 12.4 mmol, 58%) as a color-
less oil, which was azeotroped with toluene three times and dried under high
vacuum for 30 min. The compound was dissolved in diethyl ether (50 mL)
and slowly cannulated into a solution of phosgene in toluene (20%, 13 mL,
24.8 mmol) at 2158C. After addition, the solution was warmed to rt under
argon. After 2.5 hr, the solution was degassed with nitrogen, equipping the
system with an exhaust line into an alkaline bath. After 30 min, the solvent
was evaporated and the residue was purified by flash silica gel column chrom-
atography (hexanes/EtOAc 3 : 1) to yield 2 (2.40 g, 37%, 3 steps) as a colorless
1
oil; Rf ¼ 0.75 (hexanes/EtOAc 3 : 1). H NMR (300 MHz, CDCl3) d 7.80–7.71
(m, 3 H), 7.46–7.36 (m, 3 H), 7.15 (d, J ¼ 6.5 Hz, 1 H), 4.40–4.34 (m, 2 H),
2.31 (s, 2 H), 1.19–1.13 (m, 2 H), 0.09 (s, 6 H). 13C NMR (75 MHz, CDCl3) d
150.7, 136.9, 134.0, 131.4, 128.2, 127.8, 127.8, 127.3, 126.2, 125.6, 124.9,
71.0, 26.0, 16.0, 23.1. IR (CHCl3): vmax cm21 3158, 2253, 1768, 1632, 1466,
1374, 1149, 1092, 913. EI-MS: m/z (Mþ - CO2) calcd 262.0945, obsd 262.0941.
3,4-Di-O-benzyl-6-O-f2-[dimethyl(2-naphthylmethyl)silyl]ethoxycarbonylg-
D-glucal (4). A solution of NSECCl (1.00 g, 3.26 mmol) in CH2Cl2 (10 mL) was
added to a solution of 3,4-di-O-benzyl-D-glucal 3 (1.00 g, 3.06 mmol) in CH2Cl2
(10 mL), followed by DMAP (0.560 g, 4.59 mmol) before the reaction was stirred at
rt overnight. After 15 hr, the solution was diluted with ethyl acetate (60 mL) and
washed with HCl (5% aqueous, 60 mL), saturated aqueous NaHCO3 solution
(60 mL), and brine (2 ꢀ 60 mL). The combined organic layers were dried over

S. Bufali, A. Ho¨lemann, and P. H. Seeberger
450
MgSO4, filtered, and concentrated. The residue was purified by flash silica gel
column chromatography (hexanes/EtOAc 6 : 1) to yield 4 (1.78 g, 98%) as a colorless
oil; Rf ¼ 0.67 (hexanes/EtOAc 3 : 1); [a]D þ0.34 (c 0.85, CHCl3). 1H NMR (500 MHz,
CDCl3) d 7.78–7.71 (m, 3 H), 7.44–7.29 (m, 13 H), 7.16 (dd, J ¼ 1.8, 6.6 Hz, 1 H),
6.40 (dd, J ¼ 1.2, 5.0 Hz, 1 H), 4.91 (dd, J ¼ 2.8, 3.4 Hz, 1 H), 4.86 (d, J ¼ 11.3 Hz,
1 H), 4.64–4.69 (m, 2 H), 4.56 (d, J ¼ 11.7 Hz, 1 H), 4.45–4.43 (m, 2 H), 4.25–
4.21 (m, 3 H), 4.15–4.12 (m, 1 H), 3.82–3.79 (m, 1 H), 2.30 (s, 2 H), 1.12–1.08
(m, 2 H), 0.07 (s, 6 H). 13C NMR (125 MHz, CDCl3) d 155.0, 144.4, 138.2, 137.9,
137.1, 133.8, 131.1, 128.5, 128.5, 128.0, 127.9, 127.8, 127.7, 127.7, 127.6, 127.0,
125.9, 125.3, 124.5, 100.0, 75.1, 74.9, 74.0, 73.6, 70.4, 66.2, 65.8, 25.8, 15.9, 23.4.
IR (CHCl3): vmax cm21 2964, 1739, 1646, 1251, 1067. ESI-MS: m/z (M þ Na)þ
calcd 619.2486, obsd 619.2477.
Methyl 3,4-di-O-benzyl-6-O-f2-[dimethyl(2-naphthylmethyl)silyl]ethoxy-
carbonylg-b-D-glucopyranoside (5). Glucal 4 (0.740 g, 1.24 mmol) was
coevaporated with toluene three times, dried under high vacuum for 1 hr,
and was then dissolved in anhydrous CH2Cl2 (10 mL). The solution was
cooled to 08C and dimethyldioxirane (33 mL of a 0.08 M solution in acetone,
2.64 mmol) was added. After 1 hr, the solution was concentrated and the
product dried for 10 min under high vacuum. CH2Cl2 (10 mL) followed by
methanol (10 mL) were added at 08C, and the solution was warmed to rt and
stirred overnight. After 15 hr, the solvent was removed and the crude
product was purified by flash silica gel column chromatography (hexanes/
EtOAc 3 : 1 to 3 : 2) to yield 5 as a colorless solid (0.683 g, 81%); mp. 83–848C;
Rf ¼ 0.30 (hexanes/EtOAc 3 : 2); [a]D þ2.52 (c 0.95, CHCl3). 1H NMR
(500 MHz, CDCl3) d 7.78–7.70 (m, 3 H), 7.44–7.27 (m, 13 H), 7.16 (dd,
J ¼ 1.6, 6.9 Hz, 1 H), 4.95–4.85 (m, 3 H), 4.61 (d, J ¼ 10.9 Hz, 1 H), 4.44–
4.42 (m, 1 H), 4.24–4.18 (m, 4 H), 3.61–3.53 (m, 7 H), 2.30–2.29 (m, 3 H),
1.11–1.08 (m, 2 H), 0.07 (s, 1 H). 13C NMR (125 MHz, CDCl3) d 155.2, 138.7
137.9, 137.3, 134.0, 131.3, 128.7, 128.3, 128.2, 128.1, 128.0, 127.9, 127.8,
127.2, 126.1, 125.6, 124.8, 103.8, 84.6, 77.5, 75.3, 75.3, 74.8, 73.4, 66.5, 66.4,
57.4, 26.0, 16.1, -3.1. IR (CHCl3): vmax cm21 3067, 1741, 1600, 1269, 1224,
1112. ESI-MS: m/z (M þ Na)þ calcd 667.2698, obsd 667.2707.
Methyl 3,4-di-O-benzyl-2-O-levulinoyl-6-O-f2-[dimethyl(2-naphthylmethyl)-
silyl]ethoxycarbonylg-b-D-glucopyranoside
(6a).
Levulinic
acid
(0.016 mL, 0.15 mmol) and DMAP (0.020 g, 0.161 mmol) were dissolved in
CH2Cl2 (1 mL) and the solution was cooled to 08C. DIPC (0.023 mL,
0.15 mmol) was added under vigorous stirring. After 10 min, a solution of
glucose 5 (0.094 g, 0.146 mmol) in CH2Cl2 (1 mL) was added dropwise and the
reaction was stirred at rt overnight. After 15 hr, the solution was diluted
with ethyl acetate, the precipitate was filtered through Celite, and the
solution was concentrated. The residue was diluted with hexanes/EtOAc

New Mode of Hydroxyl Group Protection
451
(3 : 2), filtered through a silica pad, and concentrated to yield 6a (0.096 g, 90%)
as a colorless oil; Rf ¼ 0.31 (hexanes/EtOAc 3 : 2); [a]D 25.52 (c 1.15, CHCl3).
1H NMR (500 MHz, CDCl3) d 7.78–7.70 (m, 3 H), 7.44–7.26 (m, 13 H), 7.16
(dd, J ¼ 1.8, 8.5 Hz, 1 H), 5.00–4.96 (m, 1 H), 4.84 (d, J ¼ 10.9 Hz, 1 H), 4.78
(d, J ¼ 11.5 Hz, 1 H), 4.73 (d, J ¼ 11.5 Hz, 1 H), 4.59 (d, J ¼ 10.9 Hz, 1 H),
4.43 (dd, J ¼ 2.1, 11.6 Hz, 1 H), 4.30–4.20 (m, 4 H), 3.72–3.69 (m, 1 H), 3.63–
3.60 (m, 1 H), 3.58–3.55 (m, 1 H), 3.45 (s, 3 H), 2.72–2.68 (m, 2 H), 2.58–2.46
(m, 2 H), 2.30 (s, 2 H), 2.16 (s, 3 H), 1.11–1.08 (m, 2 H), 0.07 (s, 6 H). 13C
NMR (125 MHz, CDCl3) d 206.4, 171.7, 155.2, 138.3, 137.8, 137.3, 128.7, 128.6,
128.3, 128.2, 128.1, 128.0, 128.0, 127.9, 127.8, 127.2, 126.1, 125.6, 124.8, 101.9,
83.0, 77.1, 75.3, 75.2, 73.6, 73.3, 66.4, 66.3, 57.0, 38.1, 30.0, 28.2, 26.0, 16.1,
23.1. IR (CHCl3): vmax cm21 3054, 2896, 1747, 1718, 1455, 1359, 1241, 1152,
1073. ESI-MS: m/z (M þ Na)þ calcd 765.3065, obsd 765.3056.
Methyl
2-O-benzoyl-3,4-di-O-benzyl-6-O-f2-[dimethyl(2-naphthyl-
(6b). Following
methyl)silyl]ethoxycarbonylg-b-D-glucopyranoside
General Procedure A, alcohol 5 (0.090 g, 0.14 mmol), DMAP (0.038 g,
0.31 mmol), and benzoyl chloride (0.032 mL, 0.28 mmol) were reacted in
CH2Cl2 (2 mL) for 90 min at rt. Purification by flash silica gel column chromato-
graphy (hexanes/EtOAc 4 : 1) gave 6b (0.090 g, 86%) as a colorless oil; Rf ¼ 0.25
(hexanes/EtOAc 4 : 1); [a]D þ28.7 (c 0.46, CHCl3). 1H NMR (300 MHz, CDCl3): d
8.01 (d, J ¼ 7.4 Hz, 2 H), 7.77–7.68 (m, 3 H), 7.56 (t, J ¼ 7.4 Hz, 1 H), 7.45–7.24
(m, 10 H), 7.16–7.10 (m, 6 H), 5.25 (dd, J ¼ 7.8, 9.2 Hz, 1 H), 4.86
(d, J ¼ 10.8 Hz, 1 H), 4.73 (d, J ¼ 11.1 Hz, 1 H), 4.66 (d, J ¼ 11.1 Hz, 1 H),
4.60 (d, J ¼ 10.8 Hz, 1 H), 4.48–4.43 (m, 2 H), 4.30–4.18 (m, 3 H), 3.84
(t, J ¼ 9.1 Hz, 1 H), 3.71–3.59 (m, 2 H), 3.43 (s, 3 H), 2.29 (s, 2 H), 1.12–1.06
(m, 2 H), 0.06 (s, 6 H). 13C NMR (75 MHz, CDCl3): d 165.0, 154.8, 137.5,
137.4, 137.0, 133.6, 133.0, 131.0, 129.7, 129.7, 128.4, 128.2, 128.2, 128.0,
127.9, 127.8, 127.7, 127.6, 127.5, 127.4, 126.9, 125.8, 125.2, 124.4, 101.7,
82.7, 77.5, 75.1, 75.0, 73.5, 73.1, 66.2, 66.1, 56.8, 25.9, 15.9, 23.2. IR (CHCl3):
vmax cm21 3036, 2995, 1733, 1451, 1395, 1318, 1256, 1092, 1067. ESI-MS:
m/z (M þ Na)þ calcd 771.2965, obsd 771.2969.
Methyl
3,4-di-O-benzyl-6-O-f2-[dimethyl(2-naphthylmethyl)silyl]-
(6c). Following
ethoxycarbonylg-2-O-pivaloyl-b-D-glucopyranoside
General Procedure A, alcohol 5 (0.090 g, 0.14 mmol), DMAP (0.038 g, 0.31 mmol)
and pivaloyl chloride (0.034 mL, 0.27 mmol) were reacted in CH2Cl2 (2 mL) for
3 hr at rt. Flash silica gel column chromatography (hexanes/EtOAc 4 : 1) gave
6c (0.086 g, 86%) as a colorless solid; mp 82–838C; Rf ¼ 0.20 (hexanes/EtOAc
4 :1); [a]D 23.5 (c 0.49, CHCl3). 1H NMR (300 MHz, CDCl3): d 7.74–7.65
(m, 3 H), 7.40–7.18 (m, 13 H), 7.11 (dd, J ¼ 1.7, 8.3 Hz, 1 H), 5.01 (dd,
J ¼ 7.9, 8.9 Hz, 1 H), 4.78 (d, J ¼ 10.8 Hz, 1 H), 4.71 (d, J ¼ 11.1 Hz, 1 H),
4.66 (d, J ¼ 11.1 Hz, 1 H), 4.53 (d, J ¼ 10.8 Hz, 1 H), 4.40 (dd, J ¼ 2.0,

S. Bufali, A. Ho¨lemann, and P. H. Seeberger
452
11.5 Hz, 1 H), 4.27–4.14 (m, 4 H), 3.71–3.50 (m, 3 H), 3.41 (s, 3 H), 2.25 (s, 2 H),
1.16 (s, 9 H), 1.09–1.01 (m, 2 H), 0.02 (s, 6 H). 13C NMR (75MHz, CDCl3): d
176.9, 155.0, 137.9, 137.6, 137.1, 133.8, 131.1, 128.5, 128.4, 128.0, 127.9,
127.8, 127.6, 127.6, 127.5, 127.4, 127.0, 125.9, 125.3, 124.5, 102.0, 83.1, 77.3,
75.0, 74.8, 73.1, 72.9, 66.2, 66.1, 56.8, 38.8, 27.0, 25.8, 15.8, 23.4. IR (CHCl3):
vmax cm21 2954, 1739, 1456, 1395, 1359, 1262, 1139, 1092. ESI-MS: m/z
(M þ Na)þ calcd 751.3278, obsd 751.3262.
Methyl 2-O-acetyl-3,4-di-O-benzyl-6-O-f2-[dimethyl(2-naphthylmethyl)-
silyl]ethoxycarbonylg-b-D-glucopyranoside (6d). Following General Pro-
cedure A, alcohol 5 (0.080 g, 0.12 mmol), DMAP (0.033 g, 0.27 mmol), and acyl
chloride (0.018 mL, 0.25 mmol) were stirred in CH2Cl2 (2 mL) for 90 min at rt.
Flash silica gel column chromatography (hexanes/EtOAc 4 : 1) yielded 6d
(0.079 g, 93%) as a colorless oil; Rf ¼ 0.25 (hexanes/EtOAc 4 : 1); [a]D þ5.4 (c
1
0.24, CHCl3). H NMR (300 MHz, CDCl3): d 7.77–7.68 (m, 3 H), 7.44–7.24
(m, 13 H), 7.14 (dd, J ¼ 1.9, 8.3 Hz, 1 H), 4.97 (dd, J ¼ 8.2, 8.6 Hz, 1 H), 4.83
(d, J ¼ 10.8 Hz, 1 H), 4.78 (d, J ¼ 11.4 Hz, 1 H), 4.67 (d, J ¼ 11.4 Hz, 1 H),
4.58 (d, J ¼ 10.8 Hz, 1 H), 4.43 (dd, J ¼ 2.1, 11.4 Hz, 1 H), 4.29–4.17 (m, 4
H), 3.70–3.49 (m, 3 H), 3.43 (s, 3 H), 2.28 (s, 2 H), 1.97 (s, 3 H), 1.11–1.05
(m, 2 H), 0.05 (s, 6 H). 13C NMR (75 MHz, CDCl3): d 169.4, 154.8, 137.8,
137.3, 137.0, 133.7, 131.0, 128.4, 128.3, 128.0, 127.9, 127.7, 127.5, 127.4,
126.9, 125.8, 125.2, 124.4, 101.5, 82.9, 77.6, 75.1, 75.0, 73.0, 72.8, 66.2, 66.0,
56.7, 25.9, 21.0, 15.9, 23.2. IR (CHCl3): vmax cm21 2964, 2933, 1728,
1456, 1380, 1272, 1128, 1072. ESI-MS: m/z (M þ Na)þ calcd 709.2809, obsd
709.2812.
Methyl 3,4-di-O-benzyl-2-O-(9-fluorenylmethoxycarbonyl)-6-O-f2-[di-
methyl(2-naphthylmethyl)silyl]ethoxycarbonylg-b-D-glucopyranoside
(6e). To a solution of 5 (0.100 g, 0.155 mmol) in anhydrous pyridine (3 mL)
FmocCl (0.080 g, 0.31 mmol) was added at 08C and the white suspension was
stirred at rt. After 24 hr, additional FmocCl (0.040 g, 0.15 mmol) was added.
The clear solution was diluted with ethyl acetate (40 mL) after an additional
24 hr, washed with HCl (3% aqueous, 2 ꢀ 30 mL), saturated aqueous
NaHCO3 solution (2 ꢀ 30 mL) and brine (2 ꢀ 30 mL), dried over MgSO4,
filtered, and evaporated. The residue was purified by flash silica gel column
chromatography (hexanes/EtOAc 3 : 1, then toluene/EtOAc 40 : 1) to yield 6e
(0.089 g, 66%) as a colorless oil; Rf ¼ 0.30 (toluene/EtOAc 25 : 1); [a]D 26.3
1
(c 0.16, CHCl3). H NMR (300 MHz, CDCl3): d 7.80–7.71 (m, 5 H), 7.64–7.57
(m, 2 H), 7.46–7.22 (m, 17 H), 7.17 (dd, J ¼ 1.6, 8.4 Hz, 1 H), 4.88–4.72 (m, 4
H), 4.61 (d, J ¼ 11.0 Hz, 1 H), 4.54–4.20 (m, 8 H), 3.77 (t, J ¼ 9.0 Hz, 1 H),
3.67–3.55 (m, 2 H), 3.50 (s, 3 H), 2.31 (s, 2 H), 1.14–1.08 (m, 2 H), 0.08 (s, 6
H). 13C NMR (75 MHz, CDCl3): d 154.9, 154.4, 143.4, 143.2, 141.3, 137.8,
137.4, 137.1, 133.8, 131.1, 128.5, 128.3, 128.1, 128.0, 127.8, 127.8, 127.8,

New Mode of Hydroxyl Group Protection
453
127.7, 127.7, 127.6, 127.6, 127.1, 127.0, 125.9, 125.3, 125.1, 125.0, 124.5, 120.0,
101.5, 82.7, 77.5, 77.4, 75.2, 75.1, 73.1, 70.1, 66.2, 65.9, 56.9, 46.7, 25.8, 15.8,
23.4. IR (CHCl3): vmax cm21 3005, 1749, 1446, 1385, 1256, 1087, 1072.
ESI-MS: m/z (M þ Na)þ calcd 884.4, obsd 884.2.
Methyl
2-O-allyl-3,4-di-O-benzyl-6-O-f2-[dimethyl(2-naphthylmethyl)-
silyl]ethoxycarbonylg-b-D-glucopyranoside (6f). Procedure 1: Glucose 5
(0.049 g, 0.075 mmol) and freshly prepared allyl trichloroacetimidate[13]
(0.079 g, 0.39 mmol) were dissolved in CH2Cl2 (2 mL). The solution was
cooled to 08C and TMSOTf (0.008 mL, 0.038 mmol) was added. The reaction
was warmed to rt and stirred overnight. After 15 hr, a second aliquot of allyl tri-
chloroacetimidate (0.070 g, 0.35 mmol) and TMSOTf (0.010 mL, 0.040 mmol) was
added at 08C. The reaction was then warmed to rt. After 1 hr, a few drops of Et3N
were added, the reaction mixture was concentrated, and the residue was purified
by flash silica gel column chromatography (hexanes/EtOAc 3 : 1) to give 6f
(10 mg, 19%) as a colorless oil.
Procedure 2: Glucose 5 (40 mg, 0.062 mmol) and allyl trichloroacetimi-
date[13] (0.049 g, 0.124 mmol) were dissolved in CH2Cl2 (1 mL), and hexanes
(2 mL) and triflic acid (0.005 mL, 0.06 mmol) were added. The reaction was
stirred at rt overnight. After 15 hr, the reaction mixture was filtered and the
filtrate was washed with saturated aqueous NaHCO3 solution and water,
dried over MgSO4, filtered, and concentrated. Flash silica gel column chro-
matography (hexanes/EtOAc 3 : 1) gave 6f (10 mg, 24%) as a colorless oil.
Procedure 3: A solution of NSECCl (0.174 g, 0.52 mmol) in CH2Cl2 (3 mL)
was added to a solution of 8b (0.154 g, 0.37 mmol) in CH2Cl2 (5 mL) followed
by DMAP (0.068 g, 0.56 mmol) and the reaction was stirred at rt overnight.
After 15 hr, the solution was diluted with ethyl acetate (20 mL) and washed
with HCl (5% aqueous, 40 mL), saturated aqueous NaHCO3 solution (40 mL),
and brine (40 mL). The combined organic layers were dried over MgSO4,
filtered, and concentrated. The residue was purified by flash silica gel
column chromatography (hexanes/EtOAc 6 : 1 to 3 : 1) to yield 6f (0.144 g,
58%) as a colorless oil; Rf ¼ 0.78 (hexanes/EtOAc 3 : 2); [a]D 22.19 (c 3.2,
1
CHCl3). H NMR (500 MHz, CDCl3) d 7.71–7.63 (m, 3 H), 7.37–7.10 (m, 13
H), 7.09 (dd, J ¼ 1.7, 8.5 Hz, 1 H), 5.91–5.83 (m, 1 H), 5.24–5.23 (m, 1 H),
5.20 (m, 1 H), 5.11–5.09 (m, 1 H), 4.90 (d, J ¼ 10.9 Hz, 1 H), 4.80
(d, J ¼ 10.9 Hz, 1 H), 4.72 (d, J ¼ 10.9 Hz, 1 H), 4.51 (d, J ¼ 10.9 Hz, 1 H),
4.35–4.30 (m, 2 H), 4.19–4.09 (m, 6 H), 3.56 (t, J ¼ 8.9 Hz, 1 H), 3.45–3.41
(m, 5 H), 3.25–3.22 (m, 1 H), 2.23 (s, 2 H), 1.04–1.00 (m, 2 H), 0.06 (s, 6 H).
13C NMR (125 MHz, CDCl3) d 155.2, 138.7, 138.0, 137.3, 135.2, 134.0, 131.3,
128.7, 128.6, 128.3, 128.2, 128.1, 128.0, 127.9, 127.9, 127.8, 127.2, 126.1,
125.6, 124.8, 117.2, 104.6, 84.8, 82.1, 77.7, 75.9, 75.3, 73.8, 73.1, 66.6, 66.3,
57.3, 26.0, 16.1, 23.1. IR (CHCl3): vmax cm21 3415, 3025, 2390, 1739, 1523,
1451, 1251, 1066, 1046. ESI-MS: m/z (M þ Na)þ calcd 707.3011, obsd 707.3021.

S. Bufali, A. Ho¨lemann, and P. H. Seeberger
454
Methyl 3,4-di-O-benzyl-6-O-tri-isopropylsilyl-b-D-glucopyranoside (7).
3,4-Di-O-benzyl-D-Glucal[17] (0.348 g, 1.07 mmol) was dissolved in DMF. Imida-
zole (0.145 g, 2.14 mmol) followed by TIPSCl (0.28 mL, 1.28 mmol) were added;
and the reaction was stirred at rt overnight. After 23 hr, water was added
(60 mL) and the solution was extracted with ethyl acetate (2 ꢀ 60 mL). The
combined organic layers were washed with saturated aqueous NaHCO3
solution (70 mL), water (70 mL), and brine (70 mL), dried over MgSO4,
filtered, and concentrated. Flash silica gel column chromatography
(hexanes/EtOAc 3 : 2) gave the TIPS protected glycal as a colorless oil
(0.502 g), which was coevaporated with toluene three times and dried under
high vacuum for 1 hr. The glycal was dissolved in CH2Cl2 (10 mL) and the
solution was cooled to 08C. Dimethyldioxirane (26 mL of a 0.08 M solution in
acetone, 2.1 mmol) was added. After 1 hr, the solvents were removed and the
product was dried for 10 min under high vacuum. CH2Cl2 (10 mL) followed
by methanol (10 mL) were added at 08C, and the solution was warmed to rt
and stirred overnight. After 15 hr, the solvent was removed and the crude
product was purified by flash silica gel column chromatography (hexanes/
EtOAc 3 : 2) to give 7 (0.538 g, 95%, 3 steps) as a colorless solid. The spectral
data are consistent with previously reported data.[18]
Methyl 3,4-di-O-benzyl-2-O-para-methoxybenzyl-b-D-glucopyranoside
(8a). Glucose 7 (0.198 g, 0.37 mmol) was dissolved in DMF (5 mL) and the
solution was cooled to 48C. NaH (0.030 g of a 60% suspension in mineral oil,
0.74 mmol) and p-methoxybenzyl chloride (0.080 mL, 0.56 mmol) were added
and the solution was warmed to rt. After 1 hr, the reaction was quenched by
addition of water (20 mL) at 08C and the aqueous layer was extracted with
ethyl acetate (3 ꢀ 20 mL). The combined organic layers were washed with satu-
rated aqueous NaHCO3 solution (50 mL), dried over MgSO4, filtered, and con-
centrated. The residue was purified by flash silica gel column chromatography
(hexanes/EtOAc 3 : 2 to 2 : 3) to give methyl 3,4-di-O-benzyl-2-O-para-methoxy-
benzyl-6-O-triisopropylsilyl-b-D-glucopyranoside (0.211 g). The product was
dissolved in THF (5mL) and TBAF (0.70 mL of a 1 M solution in THF,
0.64 mmol) was added at rt. After 10 min, acetic acid (0.020 mL, 0.32 mmol)
was added and the solution was stirred for 1 hr. Water (20 mL) was added and
the aqueous phase was extracted with ethyl acetate (3 ꢀ 20 mL). The combined
organic layers were washed with saturated aqueous NaHCO3 solution (40 mL),
dried over MgSO4, filtered, and concentrated. Flash silica gel column chromato-
graphy (hexanes/EtOAc 3 : 2 to 2 : 3) gave 8a (0.118 g, 66%, 2 steps) as a colorless
oil. Characterization data were consistent with literature data.[19]
Methyl 2-O-allyl-3,4-di-O-benzyl-b-D-glucopyranoside (8b). Glucose 7
(0.185 g, 0.35 mmol) was dissolved in DMF (5 mL) and the solution was
cooled to 48C. NaH (0.030 g of a 60% suspension in mineral oil, 0.70 mmol)

New Mode of Hydroxyl Group Protection
455
and allyl bromide (0.050 mL, 0.52 mmol) were added and the solution was
warmed to rt. After 1 hr, the reaction was quenched by addition of water
(20 mL) at 08C. After extraction with ethyl acetate (3 ꢀ 20 mL), the organic
layers were washed with saturated aqueous NaHCO3 solution (50 mL), dried
over MgSO4, filtered and concentrated. The residue (0.205 g) was dissolved in
THF (5 mL), TBAF (0.80 mL of a 1 M solution in THF, 0.74 mmol) was added
at rt, and the reaction was stirred for 1 hr. Water (20 mL) was added and the
aqueous phase was extracted with CH2Cl2 (3 ꢀ 30 mL). The combined
organic layers were dried over MgSO4, filtered, and concentrated to give 8b
as a colorless oil (0.144 g, 99%). Characterization data were consistent with
literature data.[19]
Methyl 3,4-di-O-benzyl-2-O-para-methoxybenzyl-6-O-f2-[dimethyl(2-
naphthylmethyl)silyl]ethoxycarbonylg-b-D-glucopyranoside (9).
A
solution of NSECCl (0.140 g, 0.33 mmol) in CH2Cl2 (1 mL) was added to a
solution of 8a (0.118 g, 0.24 mmol) in CH2Cl2 (5 mL), followed by addition of
DMAP (0.044 g, 0.36 mmol), and the reaction was stirred at rt overnight.
After 15 hr, the solution was diluted with ethyl acetate (20 mL) and washed
with HCl (5% aqueous, 40 mL), saturated aqueous NaHCO3 solution (40 mL),
and brine (40 mL). The combined organic layers were dried over MgSO4,
filtered, and concentrated. Purification by flash silica gel column chromato-
graphy (hexanes/EtOAc 6 : 1) gave 9 (0.122 g, 66%) as a colorless oil;
Rf ¼ 0.27 (hexanes/EtOAc 3 : 1); [a]D þ15.7 (c 2.8, CHCl3). 1H NMR
(500 MHz, CDCl3) d 7.71–7.64 (m, 3 H), 7.37–7.18 (m, 12 H), 7.09 (dd,
J ¼ 1.8, 8.4 Hz, 1 H), 6.78–6.76 (m, 2 H), 4.87 (d, J ¼ 11.1 Hz, 1 H), 4.79
(d, J ¼ 10.8 Hz, 1 H), 4.76 (d, J ¼ 10.7 Hz, 1 H), 4.71 (d, J ¼ 11.1 Hz, 1 H),
4.56 (d, J ¼ 10.7 Hz, 1 H), 4.51 (d, J ¼ 10.8 Hz, 1 H), 4.34–4.33 (m, 1 H),
4.24–4.14 (m, 4 H), 3.73 (s, 3 H), 3.72–3.57 (m, 1 H), 3.49 (s, 3 H), 3.46–3.33
(m, 1 H), 2.23 (s, 2 H), 1.04–1.01 (m, 2 H), 0.07 (s, 6 H). 13C NMR (125 MHz,
CDCl3) d 159.5, 155.2, 138.8, 138.0, 130.0, 128.7, 128.6, 128.3, 128.1, 128.0,
128.0, 127.9, 127.8, 127.8, 127.2, 126.1, 125.6, 124.8, 114.0, 104.9, 84.8, 82.1,
76.9, 75.8, 75.3, 74.6, 73.1, 66.6, 66.4, 57.3, 55.5, 26.1, 16.1, 23.1. IR (CHCl3):
vmax cm21 3008, 1741, 1513, 1454, 1067. ESI-MS: m/z (M þ Na)þ calcd
787.3273, obsd 787.3285.
Methyl 2-O-f2-[dimethyl(2-naphthylmethyl)silyl]ethoxycarbonylg-3,4-
di-O-benzyl-6-O-levulinoyl-b-D-glucopyranoside (11). Glucal 10[20]
(0.360 g, 0.85 mmol) was coevaporated with toluene three times, dried under
high vacuum for 1 hr and then dissolved in CH2Cl2 (10 mL). The solution
was cooled to 08C and dimethyldioxirane (21 mL of a 0.08 M solution in
acetone, 1.70 mmol) was added. After 1 hr, the solvent was removed under
reduced pressure and the product was dried for 10 min under high vacuum.
CH2Cl2 (7 mL) followed by methanol (7 mL) were added at 08C and the

S. Bufali, A. Ho¨lemann, and P. H. Seeberger
456
solution was stirred for 3 hr. The solvent was removed and the residue was
purified by flash silica gel column chromatography (hexanes/EtOAc 3 : 2 to
2 : 3) to give methyl 3,4-di-O-benzyl-6-O-levulinoyl-b-D-glucopyranoside
(0.333 g). An aliquot of the obtained compound (0.049 g) was redissolved in
CH2Cl2 (2 mL), and pyridine (0.5 mL) and DMAP (0.050 g, 0.41 mmol) were
added. The solution was stirred for 1 hr, and then a solution of NSECCl
(0.130 g, 0.41 mmol) in CH2Cl2 (0.5 mL) was added. The reaction was stirred
for 2 d, diluted with ethyl acetate (10 mL), and washed with HCl (5%
aqueous, 10 mL), saturated aqueous NaHCO3 solution (10 mL), and brine
(10 mL). The combined organic layers were dried over MgSO4, filtered, and
concentrated. Flash silica gel column chromatography (hexanes/EtOAc 2 : 3)
gave 11 (0.024 g, 25%, 3 steps) as a colorless oil; Rf ¼ 0.26 (hexanes/EtOAc
1
2 : 3); [a]D 22.67 (c 4.5, CHCl3). H NMR (300 MHz, CDCl3) d 7.78–7.69 (m, 3
H), 7.44–7.25 (m, 13 H), 7.15 (dd, J ¼ 1.7, 8.4 Hz, 1 H), 4.85–4.74 (m, 4 H),
4.60 (d, J ¼ 10.8 Hz, 1 H), 4.38 (dd, J ¼ 2.2, 11.9 Hz, 1 H), 4.33 (d, J ¼ 9.6 Hz,
1 H), 4.28–4.20 (m, 3 H), 3.74–3.70 (m, 1 H), 3.64–3.58 (m, 1 H), 3.54–3.51
(m, 1 H), 3.48 (s, 3 H), 2.77–2.72 (m, 2 H), 2.60 (t, J ¼ 6.5 Hz, 2 H), 2.29
(s, 2 H), 2.19 (s, 3 H), 1.09–1.05 (m, 2 H), 0.06 (d, J ¼ 3.0 Hz, 6 H). 13C NMR
(125 MHz, CDCl3)
d 206.5, 172.6, 154.5, 138.8, 137.8, 137.3, 134.0,
131.3, 128.7, 128.6, 128.4, 128.2, 128.0, 128.0, 127.9, 127.9, 127.8, 127.2,
126.1, 125.6, 124.8, 101.9, 83.3, 77.6, 77.4, 75.5, 75.3, 73.3, 66.7, 63.1, 57.2,
38.1, 30.1, 28.1, 25.9, 16.0, 23.2, 23.2. IR (CHCl3): vmax cm21 3035,
1744, 1251, 1159, 1067, 1026. ESI-MS: m/z (M þ Na)þ calcd 765.3065, obsd
765.3080.
Thioethyl 2-O-f2-[dimethyl(2-naphthylmethyl)silyl]ethoxycarbonylg-
3,4,6-tri-O-benzyl-b-D-glucopyranoside (13). Glucose 12[14] (0.050 g,
0.10 mmol) was dissolved in CH2Cl2 (1.5 mL). A solution of NSECCl (0.070 g,
0.20 mmol) in CH2Cl2 (1 mL) followed by Et3 N (0.021 mL, 0.15 mmol) and
DMAP (0.0024 g, 0.02 mmol) was added, and the solution was stirred at rt.
After 24 hr, the reaction was diluted with ethyl acetate (20 mL) and washed
with HCl (5% aqueous, 20 mL), saturated aqueous NaHCO3 solution (20 mL),
and brine (20 mL). The combined organic layers were dried over MgSO4,
filtered, and concentrated. Flash silica gel column chromatography
(hexanes/EtOAc 6 : 1 to 3 : 1) gave product 13 (0.045 g, 59%) as a colorless oil;
Rf ¼ 0.42 (hexanes/EtOAc 3 : 1); [a]D þ0.75 (c 10.7, CHCl3). 1H NMR
(300 MHz, CDCl3) d 7.80–7.71 (m, 3 H), 7.47–7.15 (m, 19 H), 4.89–4.75 (m, 4
H), 4.66–4.55 (m, 3 H), 4.44 (d, J ¼ 10.0 Hz, 1 H), 4.28–4.22 (m, 2 H), 3.81–
3.69 (m, 4 H), 3.54–3.50 (m, 1 H), 2.80–2.69 (m, 2 H), 2.30 (s, 2 H), 1.30
(t, J ¼ 7.4 Hz, 3 H), 1.12–1.06 (m, 2 H), 0.07 (s, 6 H). 13C NMR (125 MHz,
CDCl3) d 154.1, 138.0, 138.0, 137.7, 137.0, 133.7, 131.0, 128.9, 128.3, 128.3,
128.2, 128.1, 127.9, 127.8, 127.7, 127.6, 127.6, 127.5, 127.5, 126.9, 125.8,
125.2, 124.5, 84.5, 83.4, 79.4, 77.6, 75.9, 75.4, 75.1, 73.5, 68.8, 66.6, 25.9,

New Mode of Hydroxyl Group Protection
457
24.2, 15.9, 15.1, 23.2. IR (CHCl3): vmax cm–1 3008, 1748, 1600, 1451, 1359,
1251, 1087. ESI-MS: m/z (M þ Na)þ calcd 787.3095, obsd 787.3100.
Methyl 3,4-di-O-benzyl-2-O-para-methoxybenzyl-b-D-glucopyranoside
(8a). Following General Procedure B, 9g (0.026 g, 0.034 mmol) was treated
with TBAF (0.040 mL of a 1 M solution in THF, 0.040 mmol) in THF (1 mL)
for 45 min. Purification by flash silica gel chromatography (hexanes/EtOAc
3 : 2) gave 8a (0.015 g, 95%) as a colorless oil. The spectroscopic data are consist-
ent with those reported above.
Methyl 2-O-allyl-3,4-di-O-benzyl-b-D-glucopyranoside (8b). Following
General Procedure B, 6j (0.029 g, 0.042 mmol) was treated with TBAF
(0.050 mL of a 1 M solution in THF, 0.051 mmol) in THF (1 mL) for 40 min.
Purification by flash silica gel chromatography (hexanes/EtOAc 3 : 2 to 2 : 3)
gave 8b (0.016 g, 92%) as a colorless oil. The spectroscopic data are consistent
with those reported above.
Methyl 3,4-di-O-benzyl-2-O-levulinoyl-b-D-glucopyranoside (14a). Fol-
lowing General Procedure B, 6a (0.046 g, 0.060 mmol) was treated with
TBAF (0.075 mL of a 1 M solution in THF, 0.070 mmol) in THF (1.2 mL) for
30 min. Purification by flash silica gel chromatography (hexanes/EtOAc 2 : 3)
gave 14a (0.028 g, quantitative yield) as a colorless oil. Characterization data
were consistent with literature data.[19]
Methyl 2-O-benzoyl-3,4-di-O-benzyl-b-D-glucopyranoside (14b). Follow-
ing General Procedure B, 6b (0.035 g, 0.047 mmol) was treated with TBAF
(0.060 mL of a 1 M solution in THF, 0.060 mmol) for 30 min. Flash silica gel
column chromatography (hexanes/EtOAc 3 : 2) gave 14b (0.019 g, 85%) as a col-
orless solid; mp 94–958C. Characterization data were consistent with litera-
ture data.[21]
Methyl 3,4-di-O-benzyl-2-O-pivaloyl-b-D-glucopyranoside (14c). Follow-
ing General Procedure B, 6c (0.080 g, 0.11 mmol) was treated with TBAF
(0.14 mL of a 1 M solution in THF, 0.14 mmol) for 45 min. Flash silica gel column
chromatography (hexanes/EtOAc 3 : 1) gave 14c (0.047 g, 91%) as a colorless
solid; mp 73–748C. Characterization data were consistent with literature data.[18]
Methyl 2-O-acetyl-3,4-di-O-benzyl-b-D-glucopyranoside (14d). Following
General Procedure B, 6d (0.062 g, 0.090 mmol) was treated with TBAF
(0.11 mL of a 1 M solution in THF, 0.11 mmol) for 45 min. Flash silica gel
column chromatography (hexanes/EtOAc (2 : 1) gave 14d (0.035 g, 93%) as a
colorless solid; mp 79–808C. Characterization data were consistent with litera-
ture data.[21]

S. Bufali, A. Ho¨lemann, and P. H. Seeberger
458
Removal of the levulinoyl group: Methyl 3,4-di-O-benzyl-6-O-f2-
[dimethyl (2-naphthylmethyl)silyl]ethoxycarbonylg-b-D-glucopyrano-
side (5). A solution of hydrazine acetate in methanol (0.3 M) was prepared and
an aliquot (0.10 mL, 0.030 mmol) was added to a solution of glucose 6a (0.020 g,
0.027 mmol) in CH2Cl2 (1 mL). After 1.5 hr, the reaction was quenched by
addition of a few drops of acetone, diluted with CH2Cl2, and concentrated. Flash
silica gel column chromatography (hexanes/EtOAc 3 : 1) gave 5 (0.039 g, quanti-
tative yield). Spectroscopic data are consistent with the data reported above.
Removal of the Fmoc group: Methyl 3,4-di-O-benzyl-6-O-f2-[dimethyl-
(2-naphthylmethyl)silyl]ethoxycarbonylg-b-D-glucopyranoside (5). A
solution of 6e (0.036 g, 0.042 mmol) in anhydrous DMF (1.6 mL) and piperdine
(0.4 mL) was stirred for 30 min at rt. Water (2 mL) was added and the mixture
was extracted with diethyl ether (5 ꢀ 10 mL). The combined organic layers
were washed with water (2 ꢀ 10 mL) and brine (10 mL), dried with MgSO4,
filtered, and evaporated. Purification by flash silica gel column chromato-
graphy (hexanes/EtOAc 5 : 1 to 2 : 1) yielded 5 (0.026 g, 95%). Spectroscopic
data are consistent with the data reported above.
Removal of the allyl ether group: Methyl 3,4-Di-O-benzyl-6-O-f2-
[dimethyl(2-naphthylmethyl)silyl]ethoxycarbonylg-b-D-glucopyrano-
side (5). Glucose 6j (0.041 g, 0.060 mmol) was dissolved in AcOH/H2O (9 : 1,
4 mL). PdCl2 (0.030 g, 0.15 mmol) followed by NaOAc (0.030 g, 0.36 mmol) were
added and the solution was heated to 808C. After 40 min, the reaction was
cooled to rt, diluted with ethyl acetate, and washed with saturated aqueous
NaHCO3 solution (3 ꢀ 30 mL), brine (30 mL), and water (30 mL). The combined
organic layers were dried over MgSO4, filtered, and concentrated to yield 5
(0.032 g, 83%). Spectroscopic data are consistent with the data reported above.
Removal of the PMB ether group: Methyl 3,4-di-O-benzyl-6-O-f2-
[dimethyl(2-naphthylmethyl)silyl]ethoxycarbonylg-b-D-glucopyrano-
side (5). Glucose 8g (0.010 g, 0.013 mmol) was dissolved in CH2Cl2 (1 mL).
Water (0.060 mL) followed by DDQ (0.0046 g, 0.020 mmol) were added and
the reaction was stirred for 3 hr. A solution of ascorbic acid sodium salt
(0.1 M, 5 mL) in water was added to quench excess DDQ. The solution was
diluted with CH2Cl2 (10 mL) and washed with aqueous ascorbic acid solution
(0.1 M, 2 ꢀ 20 mL) and brine (20 mL). The combined organic layers were
dried over MgSO4, filtered, and concentrated. Purification by flash silica gel
column chromatography (hexanes/EtOAc 3 : 1 to 3 : 2) gave 5 (0.006 g, 72%).
Spectroscopic data are consistent with the data reported above.
Dibutyl
2-O-benzoyl-3,4-di-O-benzyl-6-O-f2-[dimethyl(2-naphthyl-
methyl)silyl]ethoxycarbonylg-b-D-glucopyranosyl phosphate (15).

New Mode of Hydroxyl Group Protection
459
Glycal 4 (0.400 g, 0.670 mmol) was azeotroped with toluene (5 ꢀ 5 mL) and then
dried under vacuum overnight. A solution of the glycal in anhydrous CH2Cl2
(8 mL) was cooled to 08C and dimethyldioxirane (13 mL of a 0.08 M solution
in acetone, 1.0 mmol) was added. After 30 min at 08C, the volatiles were
removed under vacuum and the resulting oil was dried for 30 min. The
residue was redissolved in anhydrous CH2Cl2 (23 mL) and cooled to 2788C.
A solution of dibutyl phosphate (0.155 g, 0.737 mmol) in anhydrous CH2Cl2
(2 mL) was added dropwise within 5 min. After 30 min, the reaction was
warmed to 08C, and DMAP (0.327 g, 2.68 mmol) followed by benzoyl chloride
(0.16 mL, 1.4 mmol) was added. The mixture was stirred for 3 hr, while
warming to rt and then diluted with ethyl acetate. The precipitate was
filtered through a plug of silica gel and the solvents were removed under
vacuum. The residue was purified by flash silica gel column chromatography
(deactivated with 1% Et3N for loading, hexanes/EtOAc 5 : 1 to 3 : 1 to 1 : 1) to
yield phosphate 15 (0.290 g, 47%) as a colorless oil; Rf ¼ 0.40 (hexanes/
1
EtOAc 1 : 1); [a]D þ22.7 (c 0.37, CHCl3). H NMR (300 MHz, CDCl3): d 8.01
(d, J ¼ 7.6 Hz, 2 H), 7.77–7.69 (m, 3 H), 7.56 (t, J ¼ 7.6 Hz, 1 H), 7.45–7.24
(m, 10 H), 7.17–7.09 (m, 6 H), 5.39–5.29 (m, 2 H), 4.88–4.60 (m, 4 H), 4.46
(dd, J ¼ 1.4, 11.5 Hz, 1 H), 4.28–4.16 (m, 3 H), 4.08–3.91 (m, 2 H), 3.86–3.59
(m, 5 H), 2.29 (s, 2 H), 1.62–1.53 (m, 3 H), 1.42–1.21 (m, 4 H), 1.11–0.91
(m, 3 H), 0.85 (t, J ¼ 7.4 Hz, 3 H), 0.66 (t, J ¼ 7.3 Hz, 3 H), 0.06 (s, 6 H). 13C
NMR (75 MHz, CDCl3): d 164.9, 154.7, 137.2, 136.9, 133.7, 133.2, 131.0,
129.7, 129.2, 128.4, 128.3, 128.2, 128.0, 128.0, 127.9, 127.7, 127.5, 127.4,
126.9, 125.8, 125.2, 124.4, 96.4 (d, 3JP ¼ 5.0 Hz), 82.0, 82.0, 76.9, 75.2, 73.7,
73.2 (d, 2JP ¼ 8.6 Hz), 67.9 (d, 2JP ¼ 6.3 Hz), 67.8 (d, 2JP ¼ 6.3 Hz), 66.2,
65.4, 32.0 (d, 3JP ¼ 7.5 Hz), 31.8 (d, 3JP ¼ 7.3 Hz) 25.8, 18.6, 18.3, 15.9, 13.6,
13.4, –3.2. 31P NMR (121 MHz, CDCl3): d 22.2. IR (CHCl3): vmax cm21 3005,
2954, 1733, 1600, 1451, 1262, 1097, 1031. ESI-MS: m/z (M þ Na)þ calcd
949.3724, obsd 949.3721.
Pent-4-enyl 2-O-benzoyl-3,4-di-O-benzyl-6-O-f2-[dimethyl(2-naph-
thylmethyl)silyl]ethoxycarbonylg-b-D-glucopyranoside (16). Phosphate
15 (0.110 g, 0.119 mmol) was azeotroped with anhydrous toluene (3 ꢀ 5 mL)
and dried under vacuum overnight. Pent-4-en-1-ol (0.025 mL, 0.24 mmol) and
CH2Cl2 (2 mL) were added, the solution was cooled to 2788C, and TBSOTf
(0.030 mL, 0.13 mmol) was added. The mixture was stirred for 3 hr while
slowly warming to 2308C and then neutralized by addition of Et3N. The
solvents were evaporated and purification by flash silica gel column chromato-
graphy (hexanes/EtOAc 7 : 1) gave 16 (0.067 g, 70%) as a colorless oil; Rf ¼ 0.14
(hexanes/EtOAc 7 : 1); [a]D þ19.6 (c 0.75, CHCl3). 1H NMR (300 MHz, CDCl3): d
8.03 (d, J ¼ 7.4 Hz, 2 H), 7.79–7.71 (m, 3 H), 7.58 (t, J ¼ 7.4 Hz, 1 H), 7.47–7.27
(m, 10 H), 7.18–7.16 (m, 6 H), 5.65–5.62 (m, 1 H), 5.28 (dd, J ¼ 7.9, 9.3 Hz, 1
H), 4.89 (d, J ¼ 10.9 Hz, 1 H), 4.84–4.67 (m, 3 H), 4.72 (d, J ¼ 8.4 Hz, 1 H),
4.63 (d, J ¼ 10.9 Hz, 1 H), 4.51 (d, J ¼ 7.9 Hz, 1 H), 4.47 (dd, J ¼ 2.0, 11.5 Hz,

S. Bufali, A. Ho¨lemann, and P. H. Seeberger
460
1 H), 4.31–4.21 (m, 3 H), 3.89–3.81 (m, 2 H), 3.73–3.60 (m, 2 H), 3.44 (ddd,
J ¼ 6.2, 7.1, 9.6 Hz, 1 H), 2.31 (s, 2 H), 2.01–1.87 (m, 2 H), 1.67–1.48
(m, 2 H), 1.14–1.09 (m, 2 H), 0.08 (s, 6 H). 13C NMR (75 MHz, CDCl3): d
165.1, 155.0, 137.9, 137.6, 137.5, 137.1, 133.8, 133.1, 131.1, 129.9, 129.7,
128.5, 128.3, 128.2, 128.1, 128.0, 127.8, 127.7, 127.6, 127.5, 127.0, 125.9,
125.3, 124.5, 114.7, 101.0, 82.7, 77.6, 75.1, 75.0, 73.6, 73.1, 69.0, 66.2, 29.7,
28.5, 25.8, 15.8, 23.4. IR (CHCl3): vmax cm21 3035, 2892, 1733, 1446, 1313,
1262, 1092, 1021. ESI-MS: m/z (M þ Na)þ calcd 825.3435, obsd 825.3417.
Pent-4-enyl 2-O-benzoyl-3,4-di-O-benzyl-b-D-glucopyranoside (17). Fol-
lowing General Procedure B, 16 (0.063 g, 0.078 mmol) was treated with TBAF
(0.10 mL of a 1 M solution in THF, 0.10 mmol) in THF (1.5 mL) for 50 min. Flash
silica gel column chromatography (hexanes/EtOAc 5 : 1 to 1 : 1) gave 17
(0.040 g, 96%) as a colorless solid; mp 58–58.58C; Rf ¼ 0.20 (hexanes/EtOAc
3 : 1); [a]D þ11.5 (c 0.26, CHCl3). 1H NMR (300 MHz, CDCl3): d 8.01
(d, J ¼ 7.4 Hz, 2 H), 7.57 (t, J ¼ 7.4 Hz, 1 H), 7.46–7.41 (m, 2 H), 7.38–7.27
(m, 5 H), 7.13 (s, 5 H), 5.68–5.55 (m, 1 H), 5.24 (dd, J ¼ 8.0, 9.3 Hz, 1 H),
4.87 (d, J ¼ 10.9 Hz, 1 H), 4.84–4.74 (m, 4 H), 4.68 (d, J ¼ 10.9 Hz, 1 H), 4.54
(d, J ¼ 8.0 Hz, 1 H), 3.93–3.70 (m, 5 H), 3.49–3.41 (m, 2 H), 2.02–1.84 (m, 3
H), 1.65–1.49 (m, 2 H). 13C NMR (75 MHz, CDCl3): d 165.2, 137.8, 137.7,
133.1, 129.9, 129.7, 128.5, 128.4, 128.3, 128.1, 128.0, 127.7, 114.8, 101.2,
82.5, 77.7, 75.3, 75.1, 75.0, 73.8, 69.2, 61.9, 29.7, 28.5. IR (CHCl3): vmax cm21
3005, 2872, 1728, 1451, 1359, 1267, 1087, 1026. ESI-MS: m/z (M þ Na)þ
calcd 555.2359, obsd 555.2345.
Pent-4-enyl 2-O-benzoyl-3,4-di-O-benzyl-6-O-f2-[dimethyl(2-naphthyl-
methyl)silyl]ethoxycarbonylg-b-D-glucopyranosyl-(1 ! 6)-2-O-benz-
oyl-3,4-di-O-benzyl-6-b-D-glucopyranoside (18). Phosphate 15 (0.073 g,
0.079 mmol) and 17 (0.035 g, 0.066 mmol) were coevaporated with anhydrous
toluene (5 ꢀ 5 mL) and then dried under vacuum overnight. Anhydrous
CH2Cl2 (2 mL) was added, the solution was cooled to 2788C and TBSOTf
(0.019 mL, 0.083 mmol) was added. The mixture was stirred for 2 hr while
slowly warming to 2308C, and then neutralized with Et3N and concentrated.
Purification by silica gel column chromatography (toluene/EtOAc 10 : 1) gave
disaccharide 18 (0.069 g, 83%) as a colorless oil; Rf ¼ 0.35 (toluene/EtOAc
1
10 : 1); [a]D þ17.6 (c 0.33, CHCl3). H NMR (300 MHz, CDCl3): d 7.99–7.95
(m, 4 H), 7.78–7.69 (m, 3 H), 7.55 (t, J ¼ 7.4 Hz, 1 H), 7.50 (t, J ¼ 7.4 Hz, 1
H), 7.44–7.26 (m, 15 H), 7.20–7.08 (m, 13 H), 5.63–5.50 (m, 1 H), 5.33 (dd,
J ¼ 7.8, 9.0 Hz, 1 H), 5.16 (d, J ¼ 7.8, 9.2 Hz, 1 H), 4.88 (d, J ¼ 10.8 Hz, 1 H),
4.80–4.57 (m, 9 H), 4.51–4.45 (m, 2 H), 4.35–4.14 (m, 4 H), 4.31
(d, J ¼ 7.9 Hz, 1 H), 3.84 (t, J ¼ 8.9 Hz, 1 H), 3.75–3.41 (m, 7 H), 3.19–3.12
(m, 1 H), 2.29 (s, 2 H), 1.86–1.78 (m, 2 H), 1.45–1.27 (m, 2 H), 1.11–1.06
(m, 2 H), 0.06 (s, 6 H). 13C NMR (75 MHz, CDCl3): d 164.9, 164.8, 154.8,

New Mode of Hydroxyl Group Protection
461
137.8, 137.6, 137.6, 137.4, 137.4, 137.0, 133.6, 133.0, 132.8, 131.0, 129.8, 129.6,
129.6, 129.5, 128.4, 128.3, 128.2, 128.2, 128.1, 128.0, 128.0, 127.8, 127.7, 127.7,
127.6, 127.5, 127.5, 126.9, 125.8, 125.2, 125.2, 124.4, 114.5, 100.8, 100.7, 82.7,
82.6, 77.9, 77.5, 75.1, 75.0, 74.8, 74.8, 73.6, 73.5, 73.2, 68.4, 67.9, 66.2, 66.1,
29.8, 28.5, 25.8, 15.9, 23.2. IR (CHCl3): vmax cm21 3015, 2882, 1728, 1451,
1262, 1092, 1067. ESI-MS: m/z (M þ Na)þ calcd 1271.5164, obsd 1271.5165.
ACKNOWLEDGMENTS
We gratefully acknowledge financial support of the Swiss National Science
Foundation (Grant Nr. 200021–101593 “Automated Solid-Phase Synthesis of
Oligosaccharides”), the ETH Zu¨rich, and the Deutsche Forschungsge-
meinschaft (Emmy Noether fellowship for A. H.).
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