Revisit of the phenol O-glycosylation with glycosyl imidates, BF 3·OEt2 is a better catalyst than TMSOTf

Article abstract of DOI:10.1016/j.carres.2012.09.025

With BF₃·OEt₂ as the catalyst, the glycosylation of phenols with glycosyl trichloroacetimidates (or N-phenyl trifluoroacetimidates) bearing 2-O-participating groups leads to the desired 1,2-trans-O-glycosides in generally excellent yields without formation of the 1,2-cis-anomers. However, with TMSOTf as the catalyst, the outcomes of the corresponding phenol O-glycosylation are highly dependent on the nucleophilicity of the phenols; less nucleophilic is the phenol, higher amounts of the 1,2-cis-O-glycoside together with more side-products are generated. 1,2-Orthoesters have been found to be the major products at a low temperature (<-70 °C) in all these phenol O-glycosylation reactions, which are transformed into the final products at a higher temperature. BF ₃·OEt₂ is an effective catalyst to promote the conversion of 1,2-orthoesters into the corresponding 1,2-trans-O-glycosides. However, the 1,2-orthoesters could be converted into the dioxolenium triflate and glycosyl triflate in the presence of TMSOTf, these intermediates which might be in equilibrium with the glycosyl oxocarbenium related species lead to the final mixture of the α/β-O-glycosides and side-products.

Full text of DOI:10.1016/j.carres.2012.09.025

Carbohydrate Research 363 (2012) 14–22
Contents lists available at SciVerse ScienceDirect
Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
Revisit of the phenol O-glycosylation with glycosyl imidates, BF3ꢀOEt2 is a
better catalyst than TMSOTf
Yali Li a,b, Huaping Mo a, Gaoyan Lian a, Biao Yu a,
⇑
a State Key Laboratory of Bio-organic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai
200032, China
b School of Chemical Engineering and Technology, Tianjin University, 92 Weijin Road, Tianjin 300072, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 21 August 2012
Received in revised form 27 September 2012
Accepted 29 September 2012
Available online 6 October 2012
With BF3ꢀOEt2 as the catalyst, the glycosylation of phenols with glycosyl trichloroacetimidates (or N-phe-
nyl trifluoroacetimidates) bearing 2-O-participating groups leads to the desired 1,2-trans-O-glycosides in
generally excellent yields without formation of the 1,2-cis-anomers. However, with TMSOTf as the cata-
lyst, the outcomes of the corresponding phenol O-glycosylation are highly dependent on the nucleophi-
licity of the phenols; less nucleophilic is the phenol, higher amounts of the 1,2-cis-O-glycoside together
with more side-products are generated. 1,2-Orthoesters have been found to be the major products at a
low temperature (<ꢁ70 °C) in all these phenol O-glycosylation reactions, which are transformed into
the final products at a higher temperature. BF3ꢀOEt2 is an effective catalyst to promote the conversion
of 1,2-orthoesters into the corresponding 1,2-trans-O-glycosides. However, the 1,2-orthoesters could
be converted into the dioxolenium triflate and glycosyl triflate in the presence of TMSOTf, these interme-
diates which might be in equilibrium with the glycosyl oxocarbenium related species lead to the final
Keywords:
Phenol O-glycosylation
Glycosyl imidates
BF3ꢀOEt2
TMSOTf
mixture of the a/b-O-glycosides and side-products.
Ó 2012 Elsevier Ltd. All rights reserved.
1. Introduction
glycosylation of aliphatic alcohols with glycosyl trichloroacetimi-
dates as donors.13 Few reports mentioned that the use of BF3ꢀOEt2
instead of TMSOTf as the catalyst led to better yields of the desired
phenol O-glycosides,4,20 yet no explanation for this phenomenon
has been provided. This phenomenon has also puzzled us for a long
time during our own experience with the synthesis of various phe-
nol O-glycosides.14–24 Herein we confirm unambiguously that
BF3ꢀOEt2 is indeed a better catalyst than TMSOTf for the phenol O-
glycosylation with glycosyl trichloroacetimidates (or N-phenyl tri-
fluoroacetimidates) as donors and provide a rationale for this
conclusion.
Aromatic O-glycosides occur widely in nature and many of them
have significant biological activities. Chemical O-glycosylation of
phenols to synthesize these compounds has become a common
practice.1,2 In fact, the first recorded O-glycosidic bond formation
reaction is a phenol O-glycosylation, that in 1879 Michael reported
the substitution of peracetyl glucopyranosyl chloride with potas-
sium phenolate.3 Compared to the alkyl O-glycosylation, there are
two major problems associated with phenol O-glycosylation.1 First,
phenols, especially those bearing electron-withdrawing substitu-
ents, are less nucleophilic than aliphatic alcohols, thus are more dif-
ficult to be glycosylated. Second, phenols bearing electron-donating
substituents are ambident nucleophiles, thus C-glycosylation
competes with O-glycosylation. A comprehensive review on phenol
O-glycosylation has been provided by Ellervik and co-workers in
2006.1 It concludes that the predominant methods applied for
phenol O-glycosylation have been those with glycosyl acetates, ha-
lides, and trichloroacetimidates as donors, among them glycosyla-
tion with glycosyl trichloroacetimidates under the catalysis of a
Lewis acid generally gives better yields. Interestingly, BF3ꢀOEt2
has been the predominant catalyst used for phenol O-glycosyla-
tion,4–12 although TMSOTf is much more frequently used for the
2. Results and discussion
2.1. Comparison of BF3ꢀEt2O and TMSOTf as catalyst for the
phenol O-glycosylation with peracyl glycopyranosyl imidates as
donors
Apanelof13phenols(2a–2m)wasselectedforglycosylationcom-
paratively with peracyl glycosyl trichloroacetimidates (or N-phenyl
trifluoroacetimidates) as donors. Phenols 2a–2k bear mono-substitu-
entatthe para-ormeta-position, thusonlythenucleophilicity,butnot
the steric hindrance, affects their capability for glycosidation. Their
nucleophilicity is differentiated by the electronic effect of the
substituents, which correlates well to their base strength,25–28 with
pKa values ranging from 10.20 (for p-methoxyphenol 2a) to 7.15
⇑
Corresponding author. Fax: +86 21 64166128.
E-mail address: byu@mail.sioc.ac.cn (B. Yu).
0008-6215/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.carres.2012.09.025

Y. Li et al. / Carbohydrate Research 363 (2012) 14–22
15
(for p-nitrophenol 2k).29,30 p-(Methoxycarbonyl)phenol (2i), o-meth-
oxy-p-(methoxycarbonyl)phenol (2l), and o,o-bismethoxy-p-
(methoxycarbonyl)phenol (2m) possess similar pKa values (8.47,
8.30, and 8.70, respectively), yet have disparate steric effects for gly-
cosidation. Glycosylation ofthesephenolswithperacetylglucopyran-
osyl trichloroacetimidate (1) was carried out under identical
conditions (CH2Cl2, 4 Å MS, 0 °C, 3 h) with either BF3ꢀEt2O or TMSOTf
as the catalyst (0.1 equiv). The outcomes are listed in Table 1.
respectively (entries 11, 14, and 15). Increasing the amount of
TMSOTf to 1.0 equiv, the coupling of 1 and 2k was reported to give
the
a
anomer of 3k as the major product (
a
/b = 3.4:1) in ꢂ50%
yield.31 In contrast, the corresponding BF3ꢀEt2O-catalyzed reactions
gave glycosides 3i, 3j, and 3k in >87% yields without detection of
the
a
-anomers. BF3ꢀEt2O was also proven to be a much better cata-
lyst than TMSOTf when catalyzing the glycosylation of phenols with
steric hindrance. Thus, the TMSOTf-catalyzed glycosylation of o-
methoxy-p-(methoxycarbonyl)phenol (2l) and o,o-bismethoxy-p-
(methoxycarbonyl)phenol (2m) gave glycosides 3l and 3m in
It is very clear that the BF3ꢀEt2O-catalyzed glycosylation of these
phenols (2a–2m) with imidate 1 led to the desired b-O-glucosides
(3ab–3mb) in excellent yields (87%-100%) and complete stereose-
ꢂ75% yields with the
a/b ratios of 1:5.5 and 1:10, respectively;
lectivity. No
a-glucosides were detected in all these reactions. In
while the BF3ꢀEt2O-catalyzed couplings were much cleaner, leading
only to the b-O-glycosides in ꢂ90% yields (entries 16 and 17). Addi-
tionally, the replacement of TMSOTf with HOTf as the catalyst did
not improve the glycosylation yields and stereoselectivity (entries
2 and 12); and TBSOTf (tert-butyldimethylsilyltrifluoromethane
sulfonate) was proven to be a poor catalyst for the present phenol
O-glycosylation (entries 3 and 13).
contrast, the outcomes of the corresponding TMSOTf-catalyzed gly-
cosylation were highly dependent on the nucleophilicity and steric
hindrance of the phenols. The coupling with p-methoxyphenol 2a
(pKa = 10.20) gave the b-glucoside 3ab exclusively in quantitative
yield (entry 1). However, a trace amount of the
a-anomer 3ba
(ꢂ5%) was detected when coupling with p-methylphenol 2b
(pKa = 10.19, entry 4). Along with the decrease of the nucleophilic-
To examine if the thermodynamically favorable
a-glycosides
ity of the phenols, the amounts of the
a
-glycosylation products in-
(especially those bearing electron-withdrawing aglycones) were
produced via the anomerization of the corresponding b-anomers
under the action of TMSOTf (which is a stronger Lewis acid than
BF3ꢀEt2O), b-O-glycosides 3ib and 3kb were treated with 0.1 equiv
TMSOTf under the above glycosylation conditions (CH2Cl2, 4Å
creased accordingly. Thus, coupling with m-methylphenol 2c,
phenol 2d, p-phenylphenol 2e, p-chlorophenol 2f, m-iodophenol
2g, and m-chlorophenol 2h (pKa = 10.09, 9.95, 9.51, 9.38, 9.17, and
9.02, respectively) under the catalysis of TMSOTf led to the coupled
O-glycosides 3c–3h with the
a/b ratio of 1:14, 1:12, 1:11, 1:6, 1:5,
MS, 0 °C, 3 h). No
a-anomers (3ia or 3ka, respectively) were de-
and 1:4, respectively (entries 5–10). When the poorly nucleophilic
phenols p-(methoxycarbonyl)phenol 2i, m-nitrophenol 2j, and
p-nitrophenol 2k (pKa = 8.47, 8.39, and 7.15, respectively) were
used to glycosidation, the reactions turned out to be rather com-
plex, with the desired O-glycosides (3i, 3j, and 3k) being isolated
tected, thus ruling out this possibility.
Next, p-methoxyphenol (2a) and p-(methoxycarbonyl)phenol
(2i), representing the highly and poorly nucleophilic phenols,
respectively, were paired up to examine the effect of TMSOTf and
BF3ꢀEt2O on their O-glycosidation with a variety of the peracyl gly-
cosyl imidates (4–10) (Table 2). The glycosylation of p-methoxy-
in only 74–84% yields, and the a/b ratios were 1:2, 1:1.5, and 1:1,
Table 1
TMSOTf- or BF3ꢀEt2O-catalyzed glycosylation of phenols 2a–2m with peracetyl glucopyranosyl trichloroacetimidate (1)
OAc
OAc
O
OAc
O
OH
TMSOTf o rBF3OEt2
(0.1 equiv)
O
AcO
AcO
AcO
AcO
AcO
O
O
CCl3
+
+
AcO
CH2Cl2, 0 oC, 4A MS, 3h
AcO
R
OAc
OAc
O
NH
R
R
1
2a-2m
3aα-3mα
3aβ-3mβ
29
Entry
R
pKa
TMSOTf
BF3ꢀOEt2
Yielda (%)
a
/b Ratiob
Yielda (%)
a
/b Ratiob
1
p-OCH3 (2a)
2a
2a
10.20
100
88
50
96
100
90
100
100
92
100
79
3a
3a
3a
a
a
a
/3ab = 0:1
/3ab = 0:1
/3ab = 0:1
100
3a /3ab = 0:1
a
2c
3d
4
p-CH3 (2b)
m-CH3 (2c)
H (2d)
p-C6H5 (2e)
p-Cl (2f)
m-I (2g)
m-Cl (2h)
p-COOCH3 (2i)
2i
10.19
10.09
9.95
9.51
9.38
9.17
9.02
8.47
3b
a
/3bb = 1:18
100
96
89
90
91
98
95
100
3ba
/3bb = 0:1
5
6
7
8
3ca
/3cb = 1:14
3ca/3cb = 0:1
3d
a
/3db = 1:12
/3eb = 1:11
/3fb = 1:6
3d
3ea
3f
a
/3db = 0:1
/3eb = 0:1
a/3fb = 0:1
3e
a
3f
a
9
3g
3h
a
a
/3gb = 1:5
/3hb = 1:4
3ga/3gb = 0:1
10
11
12c
13d
14
15
16
3h
a/3hb = 0:1
3i
3i
3i
3j
a
/3ib = 1:2
3i
a/3ib = 0:1
81
17
84
74
a
a
a
/3ib = 1:2.5
/3ib = 1:2.5
/3jb = 1:1.5
2i
m-NO2 (2j)
p-NO2 (2k)
o-CH3O–
p-COOCH3 (2l)
8.39
7.15
8.30
87
90
92
3j
a/3jb = 0:1
3k
a
/3kb = 1:1
3k
a/3kb = 0:1
74
3l
a
/3lb = 1:5.5
3l
a/3lb = 0:1
17
o,o-Bis-CH3O-p-COOCH3 (2m)
8.70
75
3ma
/3mb = 1:10
90
3ma/3mb = 0:1
a
b
c
Isolated yields for the
a/b-O-glycosides.
The
a
/b ratios were determined by 1H NMR measurement.
HOTf (0.1 equiv) was used instead of TMSOTf.
TBSOTf (0.1 equiv) was used instead of TMSOTf.
d

16
Y. Li et al. / Carbohydrate Research 363 (2012) 14–22
phenol (2a) with peracetyl glucopyranosyl N-phenyl trifluoroace-
timidate (4),32,33 perbenzoyl glucopyranosyl trichloroacetimidate
(5), peracetyl galactopyranosyl trichloroacetimidate (6), and per-
the stereoselectivity a/b = 1:5.5 to 1:1.8) eroded considerably with
TMSOTf as the catalyst. Peracetyl allopyranosyl trichloroacetimi-
date (8, which bears a 3-axial substituent) was shown to be a poor
donor to couple with phenols 2a and 2i with either BF3ꢀEt2O or
acetyl
ysis of both BF3ꢀEt2O and TMSOTf led to the 1,2-trans-O-glycosides
(3ab, 11ab, 12ab, and 13a ) only and in high yields (entries 1–4).
L-arabinopyranosyl trichloroacetimidate (7) under the catal-
TMSOTf as the catalyst (a/b = 1:3.5; entry 5). When coupling with
a
the poorly nucleophilic 2i in the presence of TMSOTf, the 1,2-cis-b-
The only surprise was that the reaction with galactosyl imidate 6
as the donor in the presence of TMSOTf was rather complex, lead-
ing to the desired b-galactoside 12ab in only 76% yield. In contrast
to the glycosylation of p-methoxyphenol (2a), similar glycosylation
of p-(methoxycarbonyl)phenol (2i) was clean only with BF3ꢀEt2O as
the catalyst (>87%, b only), otherwise both the yields (70–77%) and
anomer 14i even became the major product /b = 2.6:1).
a
(a
However, glycosylation of the hindered phenols 2l and 2m with
allopyranosyl trichloroacetimidate 8 (or its N-phenyl trifluoroace-
timidate counterpart) led to the corresponding b-glycosides only
and in high yields.15 Peracetyl manno- and rhamnopyranosyl tri-
chloroacetimidates (9 and 10) were excellent donors for coupling
Table 2
TMSOTf- or BF3ꢀEt2 O-catalyzed glycosylation of p-methoxyphenol (2a) and p-(methoxycarbonyl)phenol (2i) with peracetyl and perbenzoyl glycosyl imidates 4–10
TMSOTf or BF3OEt2
O
(0.1 equiv)
O
X
O
R
R
+
HO
(PO)n
(PO)n
CH2Cl2, 0 oC, 4A MS, 3h
3aα/β, 11aα/β-16aα/β
3iα/β, 11iα/β-16iα/β
4-10
2a R = OMe
2i R = COOMe
Entry
Donor
Phenol 2a
BF3ꢀOEt2
Phenol 2i
TMSOTf
TMSOTf
BF3ꢀOEt2
Yield (
a
/b)a,b
Yield (
a
/b)a,b
Yield (
a
/b)a,b
Yield (
a
/b)a,b
OAc
O
AcO
AcO
O
CF3
NPh
94%
80%
70%
88%
(3ia/3ib = 0:1)
1
2
(3aa
/3ab = 0:1)
(3aa
/3ab = 0:1)
(3i
a
/3ib = 1:3.5)
OAc
4
OBz
O
BzO
BzO
O
CCl3
NH
100%
(11a
95%
(11a
75%
(11i
87%
(11i
a/11ab = 0:1)
a
a
a
/11ab = 0:1)
a
a
a
/11ib = 1:5.5)
a
a
a
/11ib = 0:1)
O5Bz
OAc
AcO
AcO
O
O
O
CCl3
NH
76%
(12a
96%
(12a
77%
(12i
99%
(12i
3
4
5
a
/12ab = 0:1)
/13ab = 1:0)
/14ab = 1:1.8)
/12ab = 0:1)
/13ab = 1:0)
/12ib = 1:1.8)
/13ib = 5.5:1)
/14ib = 2.6:1)
/12ib = 0:1)
/13ib = 1:0)
/14ib = 1:3.5)
OAc
6
OAc
O
CCl3
NH
100%
(13a
90%
(13a
77%
(13i
90%
(13i
AcO
a
OAc
7
OAc
O
O
CCl3
NH
AcO
95%
(14a
86%
(14a
71%
(14i
95%
(14i
a
a/14ab = 1:3.5)
a
a
a
OAc
OAc
8
AcO
AcO
AcO
OAc
O
O
CCl3
NH
87%
(15a
83%
(15a
94%
(15i
87%
(15i
6
7
a
/15ab = 1:0)
/16ab = 1:0)
a
/15ab = 1:0)
/16ab = 1:0)
/15ib = 1:0)
/16ib = 1:0)
a
/15ib = 1:0)
/16ib = 1:0)
9
NH
CCl3
O
O
AcO
100%
(16a
100%
(16a
100%
(16i
100%
(16i
AcO
a
a
a
a
OAc
10
a
Isolated yields for the
a
/b glycosides.
b
The
a
/b ratios were determined by 1H NMR measurement.

Y. Li et al. / Carbohydrate Research 363 (2012) 14–22
17
6
OAc
O
δ+
TMSOTf or BF3OEt2
(0.1 equiv)
4
5
O
1
+
Et3N
-O
R
AcO
AcO
1
2O
7
CH2Cl2, -78 oC, 4A MS
3
2a or 2i
O
O
O
O
R
δ+
2i
2a
A
8
17 R = OMe (55%)
18 R = COOMe (57%)
TMSOTf or BF3OEt2
(0.1equiv)
CH2Cl2, -78 oC, 4A MS
Et3N
17 only, no 18
Scheme 1. Formation of the orthoesters 17 and 18 and their transesterification at ꢁ78 °C.
OAc
O
OAc
O
AcO
AcO
AcO
AcO
O
COOMe
O
O
OAc
O
OAc
O
AcO
δ+
3iβ
AcO
AcO
OTf
AcO
AcO
TMSOTf (1.0 eq)
B
+
OAc
O
-25 o
C
+
CD2Cl2, -70 o
C
O
O
AcO
OAc
O
D
AcO
AcO
O
COOMe
AcO
AcO
18
AcO
COOMe
O
AcO
3iα
OTf
C
Scheme 2. Conversion of orthoester 18 into O-glycosides 3ib and 3ia in the presence of TMSOTf.
with phenols, all the reactions with either BF3ꢀEt2O or TMSOTf as
the catalyst led to the 1,2-trans-O-glycosides (15a , 15i , 16a
and 16i ) only and in excellent yields (entries 6 and 7).
Additionally, treatment of the 1,2-orthoesters (e.g., 17 and 18)
with BF3ꢀEt2O or TMSOTf at 0 °C (CH2Cl2, 4 Å MS) led to similar re-
sults as those obtained from treatment of the glycosyl imidates and
phenols as shown in Tables 1 and 2. These results confirmed unam-
biguously that the 1,2-orthoesters were the precursors to the cor-
responding O-glycosides (and the side products as well)37–41 in the
phenol O-glycosylation with glycosyl imidates as donors. This pro-
cess was then monitored by NMR measurement. The use of ortho-
esters instead of the imidates and phenols as starting materials
facilitated the deciphering of the NMR spectra.
a
a
a,
a
2.2. 1,2-Orthoesters were determined to be the intermediates
The naturally occurring phenolic O-glycosides, except those of 2-
deoxy-glycosides, are mostly in 1,2-trans-glycosidic linkages.
Therefore, neighboring group participation is always exploited in
the phenol O-glycosylation, such as in the present glycosylation
with peracyl glycosyl imidates as donors.34,35 In the glycosylation
involving neighboring group participation, a competitive reaction
pathway is the formation of the 1,2-orthoesters.36–41 Occasionally,
orthoesters have been reported to be the precursors to the final
O-glycosides.42–45 In the present phenol O-glycosylation, the corre-
sponding 1,2-orthoesters were found as the major product at
ꢁ78 °C. In fact, when the reactions with peracetyl glucopyranosyl
imidate 1 or 4 as donor were quenched at this temperature, the cor-
responding orthoesters were isolated in good yields. As example,
treatment of p-methoxyphenol (2a) or p-(methoxycarbonyl)phenol
(2i) with trichloroacetimidate 1 (or with trifluoroacetimidate 4) in
the presence of either BF3ꢀEt2O or TMSOTf (0.1 equiv) at ꢁ78 °C
(CH2Cl2, 4 Å MS) led to the orthoesters 17 or 18 cleanly as moni-
tored by TLC or 1H NMR measurement (with CD2Cl2 as the solvent).
Quenching the reaction with Et3N at this temperature and usual
workup provided 17 and 18 in ꢂ60% yields (Scheme 1). The lower
yields as opposed to the TLC and NMR observation were due to par-
tial decomposition of the 1,2-orthoesters during workup and puri-
fication. The formation of the 1,2-orthoesters from dioxolenium
intermediate A and phenols is a reversible process in the presence
of BF3ꢀEt2O or TMSOTf.46–49 Thus, treatment of the p-(methoxycar-
bonyl)phenoxyorthoacetate 18 with p-methoxyphenol (2a) under
the similar conditions for the formation of 18 led to the p-methoxy-
phenoxyorthoacetate 17 exclusively, while 17 was the only product
upon similar treatment of 17 with p-methoxycarbonyphenol (2i).
Obviously, the highly nucleophilic p-methoxyphenol (2a) com-
peted favorably against the poorly nucleophilic p-methoxycarbony-
phenol (2i) for the dioxolenium intermediate A.
2.3. BF3ꢀEt2O is more effective than TMSOTf for conversion of
1,2-orthoesters into the corresponding 1,2-trans-O-glycosides
The addition of either BF3ꢀEt2O or TMSOTf (1.0 equiv) into a
CD2Cl2 solution of orthoester 17 at ꢁ70 °C led immediately to the
disappearance of the starting material and the presence of the O-
glycoside 3ab, as monitored by 1H NMR measurement.50 When
1.0 equiv of BF3ꢀEt2O or TMSOTf was added, this process took place
at around ꢁ70 °C, with no intermediate being detected by NMR.
Similar results were observed upon treatment of orthoester 18
with BF3ꢀEt2O, resulting in O-glycoside 3ib without detection of
any intermediate. Nevertheless, intermediates were detected when
18 was treated with TMSOTf (Scheme 2 and Fig. 1). Thus, to a
CD2Cl2 solution of 18 (0.16 M) in a NMR tube was added TMSOTf
(1.0 equiv) at ꢁ70 °C, the mixture was then warmed up at a rate
of 5 °C/5 min and monitored by 1H and 13C NMR measurements.
Immediately after the addition of TMSOTf, the dioxolenium triflate
B (dH-1 = 7.32 ppm, J = 7.0 Hz; dC-1 = 112.1 ppm)51,52 was detected.
At around ꢁ50 °C, the glycosyl
a-triflate C (dH-1 = 6.25 ppm,
J = 3.0 Hz; dC-1 = 103.4 ppm)51,53–55 was observed. In this case, the
ꢁOTf (from TMSOTf) behaves as a competitive nucleophile (cf.
the p-(methoxycarbonyl)phenol anion from 18). The triflates B
and C disappeared at around ꢁ25 °C, meanwhile, a complex mix-
ture containing the
a- and b-O-glycosides resulted. It should be
noted that stoichiometric amount of BF3ꢀEt2O or TMSOTf was used
here to facilitate detection of the possible intermediates.51–55 Nev-
ertheless, the conclusions could be extrapolated to the catalyzed

18
Y. Li et al. / Carbohydrate Research 363 (2012) 14–22
Figure 1. The 1H and 13C NMR spectra of the mixture starting from orthoester 18 and TMSOTf in CD2Cl2 at temperatures from ꢁ70 to ꢁ8 °C.
process, because comparable yields and b/
tained in the presence of 1.0 and 0.1 equiv of the promoter in these
reactions.
a
selectivities were at-
that the configuration of the C3-substituent of pyranose donors ex-
erts a dramatic effect on the glycosylation processes. (2) With
TMSOTf as the catalyst, the corresponding phenol O-glycosylation
is highly dependent on the nucleophilicity of the phenols; less
nucleophilic is the phenol, higher amounts of the undesired 1,2-
cis-O-glycoside together with more side-products are formed. (3)
1,2-Orthoesters are formed predominantly at a low temperature
(<ꢁ70 °C) in all these phenol O-glycosylation reactions, which are
converted into the final products at a higher temperature. (4)
BF3ꢀEt2O is an effective catalyst to promote the conversion of 1,2-
orthoesters into the corresponding 1,2-trans-O-glycosides; the
reaction is so quick that no intermediate could be detected by
NMR measurement. (5) The 1,2-orthoesters could be converted
into dioxolenium triflate B and glycosyl triflate C in the presence
3. Conclusion
Based on the present studies, the following conclusions can be
drawn for the phenol O-glycosylation with glycosyl trichloroace-
timidates (or N-phenyl trifluoroacetimidates) as donors: (1) With
BF3ꢀEt2O as the catalyst, the glycosylation of phenols with glycosyl
imidates bearing 2-O-participating groups leads to the desired 1,2-
trans-O-glycosides in high yield (generally >90%) without forma-
tion of the 1,2-cis-anomers. The only exception is the coupling of
unhindered phenols with allosyl imidate 8 as the donor, indicating

Y. Li et al. / Carbohydrate Research 363 (2012) 14–22
19
of TMSOTf, those intermediates which might be in equilibrium
4.4. 3-Chlorophenyl 2,3,4,6-tetra-O-acetyl-
(3h
a-D-glucopyranoside
with the oxocarbenium related species lead to a mixture of
a
-
a)
and b-glycosides and relevant side-products.
White solid: ½a 2D5
ꢃ
95.8 (c 0.4, CHCl3); 1H NMR (400 MHz, CDCl3)
d 7.26–7.22 (m, 1H), 7.14 (s, 1H), 7.07–7.05 (m, 1H), 7.00–6.98 (m,
1H), 5.72 (d, J = 3.6 Hz, 1H), 5.70 (t, J = 10.0 Hz, 1H), 5.16 (t,
J = 9.6 Hz, 1H), 5.05 (dd, J = 3.6, 10.4 Hz, 1H), 4.27 (dd, J = 4.4,
11.6 Hz, 1H), 4.11–4.04 (m, 2H), 2.07 (s, 3H), 2.06 (s, 6H), 2.05 (s,
3H); 13C NMR (100 MHz, CDCl3) d 170.6, 170.2, 169.6, 156.7,
135.1, 130.5, 123.4, 117.3, 114.9, 94.4, 70.3, 69.9, 68.3, 68.2, 61.7,
20.7, 20.6 (2C); HRMS (ESI) calcd for C20H23ClO10Na [M+Na]+
481.0872, found 481.0887.
4. Experimental section
A typical procedure for the phenol O-glycosylation with glyco-
syl imidates as donors in the presence of BF3ꢀEt2O or TMSOTf (Ta-
bles 1 and 2).
A mixture of imidate 1 (100 mg, 0.2 mmol), phenol 2i (26 mg,
0.17 mmol), and freshly activated 4 Å molecular sieve in anhydrous
CH2Cl2 (5 mL) was stirred under Ar at 0 °C for 10 min, TMSOTf
(2
l
L, 0.02 mmol) or BF3ꢀEt2O (1
lL, 0.02 mmol) was then added
4.5. 3-Nitrophenyl 2,3,4,6-tetra-O-acetyl-
a-D-glucopyranoside
through a syringe. The stirring continued for 3 h, Et3N (1 mL) was
then added, and the resulting mixture was filtered through Celite.
The filtrate was concentrated. The residue was purified by silica gel
column chromatography to give phenol glycoside 3iA (22 mg, 26%)
and 3ib (43 mg, 53%) or 3ib only (82 mg, 100%).
(3ja
)
White solid: ½a 2D5
ꢃ
162.5 (c 0.2, CHCl3); 1H NMR (400 MHz,
CDCl3) d 7.99–7.95 (m, 2H), 7.52 (t, J = 8.0 Hz, 1H), 7.44 (dd,
J = 1.2, 8.4 Hz, 1H), 5.82 (d, J = 3.6 Hz, 1H), 5.72 (t, J = 9.6 Hz, 1H),
5.19 (t, J = 9.6 Hz, 1H), 5.09 (dd, J = 3.2, 10.4 Hz, 1H), 4.27 (dd,
J = 4.8, 12.0 Hz, 1H), 4.11–4.04 (m, 2H), 2.08 (s, 3H), 2.07 (s, 3H),
2.05 (s, 3H), 2.04 (s, 3H); 13C NMR (100 MHz, CDCl3) d 170.5,
170.1, 169.5, 156.5, 149.2, 130.4, 122.9, 118.1, 111.8, 94.7, 70.2,
69.7, 68.5, 68.2, 61.6, 20.7, 20.6 (2C); HRMS (ESI) calcd for
The resulting phenol glycosides 3ab,56 3ba 57
3cb,60 3da 61 3db,62 3eb,63 3fa 64 3gb,65 3hb,66 3ia 67
3ka 31 3kb,69 3lb,15 3mb,15 12ab,70 13aa 71 15aa 72
and 16a
are known compounds.
,
3bb,58 3ca 59
3ib,63 3jb,68
7373
,
,
,
,
,
,
,
a
C
20H23NO12Na [M+Na]+ 492.1112, found 492.1130.
4.1. 4-Biphenylyl 2,3,4,6-tetra-O-acetyl-
a-D-glucopyranoside
(3e
a
)
4.6. 2-Methoxy-4-(methoxycarbonyl)phenyl 2,3,4,6-tetra-O-
acetyl- -glucopyranoside (3l
a
-D
a)
White solid: ½a 2D5
ꢃ
108.4 (c 0.3, CHCl3); 1H NMR (400 MHz,
White solid: ½a 2D5
ꢃ
135.4 (c 2.0, CHCl3); 1H NMR (300 MHz,
CDCl3) d 7.48 (d, J = 6.8 Hz, 4H), 7.38 (t, J = 7.6 Hz, 2H), 7.28–
7.24 (m, 1H), 7.10 (d, J = 8.8 Hz, 2H), 5.72 (d, J = 3.6 Hz, 1H),
5.68 (t, J = 9.6 Hz, 1H), 5.13 (t, J = 9.6 Hz, 1H), 5.01 (dd,
J = 10.0 Hz, 1H), 4.22 (dd, J = 4.8, 12.4 Hz, 1H), 4.11 (m, 1H), 4.03
(dd, J = 1.6, 12.0 Hz, 1H), 2.01 (s, 3H), 2.00 (s, 3H), 1.98 (s, 6H);
13C NMR (100 MHz, CDCl3) d 170.6, 170.2, 169.6, 155.6, 140.4,
136.3, 128.8, 128.4, 127.1, 126.9, 116.9, 94.3, 70.5, 70.1, 68.4,
68.1, 61.6, 20.7 (2C), 20.6 (2C); HRMS (ESI) calcd for C26H28O10Na
[M+Na]+ 523.1575, found 523.1585.
CDCl3) d 7.62–7.59 (m, 2H), 7.10 (d, J = 8.1 Hz, 1H), 5.80 (d,
J = 3.9 Hz, 1H), 5.78–5.71 (m, 1H), 5.18 (t, J = 9.9 Hz, 1H), 5.04
(dd, J = 3.6, 10.2 Hz, 1H), 4.36–4.24 (m, 2H), 4.09–4.04 (m, 1H),
3.91 (s, 3H), 3.89 (s, 3H), 2.11 (s, 3H), 2.06 (s, 6H), 2.05 (s, 3H);
13C NMR (100 MHz, CDCl3) d 170.5, 170.2, 170.0, 169.6, 166.4,
150.4, 148.8, 126.1, 122.8, 118.6, 113.4, 95.5, 70.5, 69.8, 68.3,
68.2, 61.6, 55.9, 52.2, 20.7, 20.6 (3C); HRMS (MALDI) calcd for
C
22H28O13Na [M+Na]+ 535.1422, found 535.1427.
4.7. 2,6-Dimethoxy-4-(methoxycarbonyl)phenyl 2,3,4,6-tetra-O-
acetyl- -glucopyranoside (3m
4.2. 4-Chlorophenyl 2,3,4,6-tetra-O-acetyl-b-
(3fb)
D-glucopyranoside
a
-D
a)
White solid: ½a 2D5
ꢃ
84.2 (c 0.2, CHCl3); 1H NMR (400 MHz, CDCl3)
White solid: ½a 2D5
ꢃ
ꢁ16.0 (c 0.8, CHCl3); 1H NMR (400 MHz,
d 7.28 (d, J = 6.4 Hz, 2H), 5.78–5.73 (m, 2H), 5.17 (t, J = 10.4 Hz, 1H),
5.01 (dd, J = 3.6, 10.4 Hz, 1H), 4.90–4.86 (m, 1H), 4.32 (dd, J = 4.0,
12.0 Hz, 1H), 4.06 (dd, J = 2.4, 12.4 Hz, 1H), 3.91 (s, 3H), 3.84 (s,
6H), 2.14 (s, 3H), 2.08 (s, 3H), 2.05 (s, 3H), 2.04 (s, 3H); 13C NMR
(100 MHz, CDCl3) d 170.8, 170.3, 170.1, 169.3, 166.5, 152.8,
137.8, 126.6, 106.6, 96.8, 70.8, 69.8, 68.5, 68.4, 61.8, 56.0, 52.3,
20.8, 20.7 (2C); HRMS (MALDI) calcd for C24H30O14Na [M+Na]+
565.1528, found 565.1522.
CDCl3) d 7.27 (d, J = 8.8 Hz, 2H), 6.94 (d, J = 9.2 Hz, 2H), 5.32–
5.23 (m, 2H), 5.18 (t, J = 9.6 Hz, 1H), 5.05 (d, J = 7.2 Hz, 1H), 4.30
(dd, J = 5.6, 12.4 Hz, 1H), 4.18 (dd, J = 2.0, 12.4 Hz, 1H), 3.87–
3.83 (m, 1H), 2.08 (s, 3H), 2.06 (s, 3H), 2.05 (s, 3H), 2.04 (s,
3H); 13C NMR (100 MHz, CDCl3) d 170.5, 170.2, 169.4, 169.3,
155.4, 129.5, 128.6, 118.5, 99.2, 72.6, 72.1, 71.1, 68.2, 61.9, 20.7,
20.6 (3C); HRMS (ESI) calcd for
481.0872, found 481.0896.
C
20H23ClO10Na [M+Na]+
4.8. 4-(Methoxy)phenyl 2,3,4,6-tetra-O-benzoyl-b-
glucopyranoside (11ab)
D-
4.3. 3-Iodophenyl 2,3,4,6-tetra-O-acetyl-
a-D-glucopyranoside
(3ga)
White solid: ½a 2D5
ꢃ
17.5 (c 1.1, CHCl3); 1H NMR (400 MHz, CDCl3)
White solid: ½a 2D5
ꢃ
ꢁ7.7 (c 1.6, CHCl3); 1H NMR (400 MHz,
d 8.04–7.84 (m, 8H), 7.59–7.28 (m, 12H), 6.96 (dd, J = 2.4, 7.2 Hz,
2H), 6.68 (dd, J = 2.0, 6.4 Hz, 2H), 6.00 (t, J = 10.0 Hz, 1H), 5.79–
5.68 (m, 2H), 5.28 (d, J = 8.0 Hz, 1H), 4.69 (dd, J = 3.2, 12.0 Hz,
1H), 4.57 (dd, J = 6.4, 12.0 Hz, 1H), 4.31–4.26 (m, 1H), 3.71 (s,
3H); 13C NMR (100 MHz, CDCl3) d 166.1, 165.9, 165.4, 165.2,
155.8, 151.0, 133.6, 133.4, 133.4, 133.3, 129.9, 129.8 (2C), 129.6,
129.1, 128.7, 128.6, 128.5 (3C), 128.4, 119.0, 114.5, 100.9, 72.9,
72.5, 71.8, 69.8, 63.2, 55.6; HRMS (MALDI) calcd for C41H34O11Na
[M+Na]+ 725.1993, found 725.1983.
CDCl3) d 7.41 (s, 1H), 7.35 (d, J = 7.6 Hz, 1H), 7.00–6.94 (m, 2H),
5.64 (d, J = 3.2 Hz, 1H), 5.62 (t, J = 10.0 Hz, 1H), 5.09 (t,
J = 10.0 Hz, 1H), 4.98 (dd, J = 4.0, 10.4 Hz, 1H), 4.20 (dd, J = 4.4,
12.0 Hz, 1H), 4.04–3.97 (m, 2H), 2.00 (s, 6H), 1.98 (s, 3H), 1.97
(s, 3H); 13C NMR (100 MHz, CDCl3) d 170.6, 170.2, 169.4, 169.3,
157.2, 132.5, 130.9, 125.9, 116.6, 98.8, 94.1, 72.6, 72.2, 71.1,
68.3, 62.1, 20.8, 20.6 (2C), 20.5; HRMS (ESI) calcd for C20H23IO10-
Na [M+Na]+ 573.0228, found 573.0246.

20
Y. Li et al. / Carbohydrate Research 363 (2012) 14–22
4.9. 4-(Methoxycarbonyl)phenyl 2,3,4,6-tetra-O-benzoyl-
a
-D
-
4.14. 4-(Methoxycarbonyl)phenyl 2,3,4-tri-O-acetyl-
a-L-
glucopyranoside (11i
a)
arabinopyranoside (13i
a)
White solid: ½a 2D5
ꢃ
68.1 (c 0.6, CHCl3); 1H NMR (400 MHz, CDCl3)
White solid: ½a 2D5
ꢃ
9.9 (c 0.7, CHCl3); 1H NMR (400 MHz, CDCl3) d
d 7.92–7.82 (m, 10H), 7.50–7.13 (m, 14H), 6.36 (t, J = 10.0 Hz, 1H),
6.04 (d, J = 7.2 Hz, 1H), 5.69 (t, J = 9.6 Hz, 1H), 5.45 (dd, J = 3.6,
10.0 Hz, 1H), 4.47–4.38 (m, 3H), 3.82 (s, 3H); 13C NMR (100 MHz,
CDCl3) d 165.4, 165.0, 164.8 (2C), 164.3, 158.5, 132.6, 132.3,
132.2, 130.6, 128.9 (2C), 128.8, 128.7 (2C), 128.4, 128.0, 127.6
(2C), 127.5 (2C), 127.4, 127.3, 123.8, 115.3, 93.1, 70.4, 69.2, 68.2,
67.9, 61.8, 51.0; HRMS (MALDI) calcd for C42H34O12Na [M+Na]+
753.1942, found 753.1943.
8.01 (d, J = 8.8 Hz, 2H), 7.04 (d, J = 8.8 Hz, 2H), 5.45 (dd, J = 2.0,
8.0 Hz, 1H), 5.34–5.33 (m, 1H), 5.20–5.17 (m, 2H), 4.14 (dd,
J = 4.4, 12.8 Hz, 1H), 3.89 (s, 3H), 3.80 (dd, J = 2.4, 12.8 Hz, 1H),
2.15 (s, 3H), 2.10 (s, 3H), 2.09 (s, 3H); 13C NMR (100 MHz, CDCl3)
d 170.2, 170.1, 169.4, 166.5, 160.1, 131.6, 124.8, 116.1, 97.9, 69.5,
68.8, 66.9, 62.5, 52.0, 20.9, 20.7 (2C); HRMS (ESI) calcd for
C
19H22O10Na [M+Na]+ 433.1105, found 433.1126.
4.15. 4-Methoxyphenyl 2,3,4,6-tetra-O-acetyl-
allopyranoside (14a
a-D-
4.10. 4-(Methoxycarbonyl)phenyl 2,3,4,6-tetra-O-benzoyl-b-
glucopyranoside (11ib)
D-
a)
White solid: ½a 2D5
ꢃ
101.3 (c 0.5, CHCl3); 1H NMR (400 MHz, CDCl3)
White solid: ½a 2D5
ꢃ
29.7 (c 0.6, CHCl3); 1H NMR (400 MHz, CDCl3)
d 6.94 (d, J = 9.2 Hz, 2H), 6.68 (d, J = 9.2 Hz, 2H), 5.67 (t, J = 3.2 Hz,
1H), 5.48 (d, J = 4.4 Hz, 1H), 5.00–4.96 (m, 2H), 4.42–4.38 (m,
1H), 4.23 (dd, J = 4.8, 12.4 Hz, 1H), 4.09 (dd, J = 2.0, 12.0 Hz, 1H),
3.71 (s, 3H), 2.15 (s, 3H), 2.01 (s, 3H), 1.97 (s, 3H), 1.96 (s, 3H);
13C NMR (100 MHz, CDCl3) d 169.6 (2C), 168.8, 168.2, 154.4,
149.7, 117.4, 113.6, 94.2, 66.2 (2C), 64.7, 63.4, 61.0, 54.7, 19.9,
19.7, 19.6, 19.5; HRMS (ESI) calcd for C21H26O11Na [M+Na]+
477.1367, found 477.1379.
d 8.02 (d, J = 8.8 Hz, 2H), 7.96–7.93 (m, 4H), 7.87 (d, J = 8.8 Hz, 4H),
7.60–7.26 (m, 12H), 7.04 (d, J = 9.6 Hz, 2H), 6.04 (t, J = 9.6 Hz, 1H),
5.85 (dd, J = 7.6, 9.2 Hz, 1H), 5.74 (t, J = 9.6 Hz, 1H), 5.51 (d,
J = 7.2 Hz, 1H), 4.71 (dd, J = 3.2, 12.0 Hz, 1H), 4.55 (dd, J = 7.2,
12.4 Hz, 1H), 4.41–4.36 (m, 1H), 3.88 (s, 3H); 13C NMR (100 MHz,
CDCl3) d 166.4, 166.0, 165.8, 165.3, 165.1, 160.2, 133.6, 133.5,
133.4 (2C), 131.5, 129.9, 129.8 (3C), 129.7, 129.4, 128.9, 128.6
(2C), 128.5 (3C), 128.4, 125.0, 116.4, 98.7, 72.8, 72.7, 71.6, 69.5,
63.1, 52.0; HRMS (MALDI) calcd for
753.1942, found 753.1946.
C
42H34O12Na [M+Na]+
4.16. 4-Methoxyphenyl 2,3,4,6-tetra-O-acetyl-b-
allopyranoside (14ab)
D-
4.11. 4-(Methoxycarbonyl)phenyl 2,3,4,6-tetra-O-acetyl-
a-D-
White solid: ½a 2D5
ꢃ
ꢁ12.0 (c 2.4, CHCl3); 1H NMR (400 MHz,
galactopyranoside (12i
a)
CDCl3) d 6.93 (d, J = 9.2 Hz, 2H), 6.77 (d, J = 9.2 Hz, 2H), 5.67 (t,
J = 2.8 Hz, 1H), 5.18 (d, J = 8.0 Hz, 1H), 5.06 (dd, J = 3.2, 8.4 Hz,
1H), 4.99 (dd, J = 2.4, 9.6 Hz, 1H), 4.18–4.11 (m, 3H), 3.71 (s, 3H),
2.08 (s, 3H), 2.02 (s, 3H), 1.99 (s, 3H), 1.95 (s, 3H); 13C NMR
(100 MHz, CDCl3) d 170.7, 169.8, 169.1 (2C), 155.7, 151.1, 118.7,
114.5, 98.4, 70.4, 68.9, 68.5, 66.2, 62.4, 55.7, 20.8, 20.7, 20.6,
20.5; HRMS (ESI) calcd for C21H26O11Na [M+Na]+ 477.1367, found
477.1389.
White solid: ½a 2D5
ꢃ
145.5 (c 0.9, CHCl3); 1H NMR (400 MHz,
CDCl3) d 8.02 (d, J = 8.4 Hz, 2H), 7.12 (d, J = 8.4 Hz, 2H), 5.86 (d,
J = 3.6 Hz, 1H), 5.59 (dd, J = 2.8, 10.8 Hz, 1H), 5.53 (m, 1H), 5.33
(dd, J = 3.6, 10.8 Hz, 1H), 4.31 (t, J = 6.4 Hz, 1H), 4.14–4.03 (m,
2H), 3.90 (s, 3H), 2.18 (s, 3H), 2.08 (s, 3H), 2.04 (s, 3H), 1.93 (s,
3H); 13C NMR (100 MHz, CDCl3) d 170.4, 170.3, 170.2, 170.0,
166.5, 159.8, 131.6, 124.8, 116.2, 94.5, 67.8, 67.6, 67.5, 67.4, 61.4,
52.0, 20.7, 20.6 (2C), 20.5; HRMS (ESI) calcd for C22H26O12Na
[M+Na]+ 505.1316, found 505.1337.
4.17. 4-(Methoxycarbonyl)phenyl 2,3,4,6-tetra-O-acetyl-
a-D-
allopyranoside (14i
a
)
4.12. 4-(Methoxycarbonyl)phenyl 2,3,4,6-tetra-O-acetyl-b-
galactopyranoside (12ib)
D-
White solid: ½a 2D5
ꢃ
141.6 (c 1.4, CHCl3); 1H NMR (400 MHz,
CDCl3) d 7.95 (d, J = 8.8 Hz, 2H), 7.05 (d, J = 9.2 Hz, 2H), 5.68–5.66
(m, 2H), 5.06 (t, J = 3.6 Hz, 1H), 5.01 (dd, J = 3.2, 10.8 Hz, 1H),
4.31–4.28 (m, 1H), 4.22 (dd, J = 4.8, 12.0 Hz, 1H), 4.06–4.01 (m,
1H), 3.83 (s, 3H), 2.17 (s, 3H), 2.00 (s, 3H), 1.95 (s, 3H), 1.94 (s,
3H); 13C NMR (100 MHz, CDCl3) d 170.6, 170.5, 169.8, 169.2,
166.6, 160.1, 131.6, 131.5, 124.6, 116.3, 116.2, 93.7, 67.1, 67.0,
65.5, 64.9, 61.7, 52.0, 20.9, 20.7, 20.6, 20.5; HRMS (ESI) calcd for
White solid: ½a 2D5
ꢃ
1.7 (c 0.8, CHCl3); 1H NMR (400 MHz, CDCl3) d
8.01 (d, J = 8.8 Hz, 2H), 7.03 (d, J = 8.8 Hz, 2H), 5.54–5.47 (m, 2H),
5.14–5.11 (m, 2H), 4.25–4.09 (m, 3H), 3.90 (s, 3H), 2.19 (s, 3H),
2.07 (s, 6H), 2.02 (s, 3H); 13C NMR (100 MHz, CDCl3) d 170.4,
170.2, 170.1, 169.4, 166.5, 160.2, 131.6, 125.1, 116.2, 98.8, 71.3,
70.7, 68.5, 66.8, 61.4, 52.1, 20.7, 20.6 (3C); HRMS (ESI) calcd for
C
22H26O12Na [M+Na]+ 505.1316, found 505.1336.
C
22H26O12Na [M+Na]+ 505.1316, found 505.1335.
4.18. 4-(Methoxycarbonyl)phenyl 2,3,4,6-tetra-O-acetyl-b-
allopyranoside (14ib)
D-
4.13. 4-(Methoxycarbonyl)phenyl 2,3,4-tri-O-acetyl-b-
arabinopyranoside (13ib)
L-
White solid: ½a 2D5
ꢃ
ꢁ16.5 (c 1.9, CHCl3); 1H NMR (400 MHz,
White solid: ½a 2D5
ꢃ
174.3 (c 0.4, CHCl3); 1H NMR (400 MHz,
CDCl3) d 8.02 (d, J = 8.8 Hz, 2H), 7.06 (d, J = 8.8 Hz, 2H), 5.76 (t,
J = 2.4 Hz, 1H), 5.46 (d, J = 8.0 Hz, 1H), 5.20 (dd, J = 2.8, 8.4 Hz,
1H), 5.07 (dd, J = 2.4, 9.6 Hz, 1H), 4.31–4.20 (m, 3H), 3.90 (s, 3H),
2.18 (s, 3H), 2.09 (s, 3H), 2.05 (s, 3H), 2.04 (s, 3H); 13C NMR
(100 MHz, CDCl3) d 170.6, 169.7, 169.1 (2C), 166.5, 160.4, 131.6,
124.9, 116.2, 96.5, 70.6, 68.7, 68.3, 66.1, 62.3, 52.1, 20.7 (2C),
20.6, 20.5; HRMS (ESI) calcd for C22H26O12Na [M+Na]+ 505.1316,
found 505.1339.
CDCl3) d 8.02 (d, J = 8.8 Hz, 2H), 7.10 (d, J = 8.8 Hz, 2H), 5.85 (d,
J = 3.6 Hz, 1H), 5.59 (dd, J = 3.2, 10.8 Hz, 1H), 5.42 (s, 1H), 5.37
(dd, J = 3.6, 10.8 Hz, 1H), 4.02 (d, J = 12.8 Hz, 1H), 3.90 (s, 3H),
3.78 (d, J = 12.0 Hz, 1H), 2.18 (s, 3H), 2.07 (s, 3H), 2.06 (s, 3H);
13C NMR (100 MHz, CDCl3) d 170.4, 170.3, 170.1, 166.6, 159.9,
131.7, 124.7, 116.0, 94.8, 68.7, 67.8, 67.0, 61.5, 52.0, 20.9, 20.7;
HRMS (ESI) calcd for
433.1122.
C
19H22O10Na [M+Na]+ 433.1105, found

Y. Li et al. / Carbohydrate Research 363 (2012) 14–22
21
4.19. 4-(Methoxycarbonyl)phenyl 2,3,4,6-tetra-O-acetyl-
a
-
D
-
added through a syringe, and the stirring continued at the same
temperature. The starting orthoester 18 was completely consumed
after 1 h as monitored by TLC analysis. Et3N (1 mL) was then added
and the resulting mixture was filtered through a pad of Celite. The
filtrate was concentrated, and the residue was purified by silica gel
column chromatography to give orthoester 17.
mannopyranoside (15i
a)
White solid: ½a 2D5
ꢃ
72.7 (c 1.5, CHCl3); 1H NMR (400 MHz, CDCl3)
d 8.02 (d, J = 8.8 Hz, 2H), 7.14 (d, J = 8.8 Hz, 2H), 5.60 (d, J = 1.2 Hz,
1H), 5.57 (dd, J = 3.2, 10 Hz, 1H), 5.46–5.45 (m, 1H), 5.39 (t,
J = 9.6 Hz, 1H), 4.30 (dd, J = 6.0, 12.8 Hz, 1H), 4.07–4.03 (m, 2H),
3.90 (s, 3H), 2.21 (s, 3H), 2.05 (s, 3H), 2.04 (s, 3H), 2.02 (s, 3H);
13C NMR (100 MHz, CDCl3) d 190.5, 170.0, 169.9, 169.7, 166.5,
159.0, 131.6, 124.9, 116.0, 95.5, 69.5, 69.2, 68.7, 65.8, 62.0, 52.1,
20.8, 20.7, 20.6 (2C); HRMS (ESI) calcd for C22H26O12Na [M+Na]+
505.1316, found 505.1316.
4.24. A typical procedure for the NMR monitoring of the
conversion of 1,2-orthoesters into O-glycosides
A
CD2Cl2 (0.5 mL) solution of 1,2-orthoester 18 (40 mg,
0.08 mmol) was added to an NMR tube. The NMR tube was then
cooled to -70 °C in the NMR spectrometer. After 15 min, the first
1H and 13C NMR was measured at this temperature. Then the
NMR tube was taken out and put into dry ice quickly to keep below
4.20. 4-(Methoxycarbonyl)phenyl 2,3,4-tri-O-acetyl-
rhamnopyranoside (16i
a-L-
a)
-70 °C, and TMSOTf (8 lL, 0.08 mmol) was added quickly to the
White solid: ½a 2D5
ꢃ
ꢁ59.3 (c 0.7, CHCl3); 1H NMR (400 MHz,
tube. The NMR tube was then put back into the NMR spectrometer
immediately, and was then warmed up at a rate of 5 °C/5 min. The
1H and 13C NMR measurements were taken every 5 min.
CDCl3) d 8.02 (d, J = 9.2 Hz, 2H), 7.12 (d, J = 8.8 Hz, 2H), 5.54 (d,
J = 1.2 Hz, 1H), 5.52 (dd, J = 3.2, 10.0 Hz, 1H), 5.44–5.43 (m, 1H),
5.18 (t, J = 9.6 Hz, 1H), 3.96–3.92 (m, 1H), 3.90 (s, 3H), 2.20 (s,
3H), 2.06 (s, 3H), 2.04 (s, 3H); 13C NMR (100 MHz, CDCl3) d 170.1,
170.0, 166.6, 159.3, 131.6, 124.6, 115.9, 95.3, 70.8, 69.5, 68.8,
67.5, 52.0, 20.9, 20.8, 20.7, 17.4; HRMS (ESI) calcd for C20H24O10Na
[M+Na]+ 447.1262, found 447.1271.
Acknowledgments
Financial support from the National Basic Research Program of
China
(2010CB529706) and the National Natural Science
Foundation of China (20932009 and 20921091) are gratefully
acknowledged.
4.21. A typical procedure for the preparation of sugar 1,2-
orthoesters. 3,4,6-Tri-O-acetyl-1,2-O-[p-methoxybenzylidene]-
a-D-glucopyranose (17)
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