Additive-controlled stereoselective glycosylations of oxazolidinone- protected glucosamine and galactosamine thioglycoside donors based on preactivation protocol

Article abstract of DOI:10.1055/s-0030-1258557

Based on a pre-activation protocol, the stereoselectivity of oxazolidinone-protected amino sugar thioglycoside donors towards glycosylations can be controlled by additives. Either - or -selectivity could be obtained by changing additives. 2,4,6-Tri-tert-butylpyrimidine (TTBP) was the best -directing additive, while thiophene worked as the best -directing additive. The bifunctional additives such as tetrabutyl ammonium iodide (TBAI) afforded either - or -selectivity depending on the amount added. Poor -selectivity of some glycosylations without any additives was greatly improved by adding TBAI or thiophene. Georg Thieme Verlag Stuttgart New York.

Full text of DOI:10.1055/s-0030-1258557

2506
LETTER
Additive-Controlled Stereoselective Glycosylations of Oxazolidinone-
Protected Glucosamine and Galactosamine Thioglycoside Donors Based on
Preactivation Protocol
Glycosylations of
i
O
xazol
q
idinone-Prot
u
ected Thiogly
n
c
oside
D
onors Geng, Xin-Shan Ye*
State Key Laboratory of Natural and Biomimetic Drugs, Peking University, and School of Pharmaceutical Sciences, Peking University,
Xue Yuan Rd No.38, Beijing 100191, P. R. of China
Fax +86(10)82802724; E-mail: xinshan@bjmu.edu.cn
Received 1 June 2010
AcO
Abstract: Based on a pre-activation protocol, the stereoselectivity
of oxazolidinone-protected amino sugar thioglycoside donors to-
wards glycosylations can be controlled by additives. Either a- or b-
selectivity could be obtained by changing additives. 2,4,6-Tri-tert-
butylpyrimidine (TTBP) was the best b-directing additive, while
thiophene worked as the best a-directing additive. The bifunctional
additives such as tetrabutyl ammonium iodide (TBAI) afforded ei-
ther a- or b-selectivity depending on the amount added. Poor a-
selectivity of some glycosylations without any additives was greatly
improved by adding TBAI or thiophene.
O
AcO
O
ROH
ROH
N
Ac
BSM, Tf2O
OR
OR
O
AcO
AcO
CH2Cl2, –73 °C
BSM, TTBP, Tf2O
O
STol
O
AcO
AcO
NAc
1
O
O
O
CH2Cl2, –73 °C
NAc
O
Key words: glycosylation, stereoselectivity, preactivation, addi-
tive, carbohydrate
Scheme 1 Stereoselectivity-controllable glycosylation of donor 14d
OAc
OAc
O
Anomeric control in glycosylations is one of the major
challenges in the synthesis of complex oligosaccharides
and glycoconjugates with biological importance.1,2 Gen-
erally, the 1,2-trans-linked glycosides are constructed by
means of a participating neighboring group at the C-2 po-
sition of a glycosyl donor, while the formation of 1,2-cis-
linked glycosides remains a difficult task.3 Introduction of
a nonparticipating neighboring group at C-2 is insufficient
to guarantee stereoselective cis-glycosylation reactions
and often leads to mixtures of anomers. Recently, 2,3-
trans-oxazolidinone developed first by Kerns as a special
nonparticipating group for glucosamine donors attract
particular attention.4 It is a good stereodirecting group for
the formation of either a- or b-glycosidic linkages. In our
own work,4d the hindered base 2,4,6-tri-tert-butylpyrimi-
dine (TTBP)5 was found to be a crucial factor in the ste-
reoselectivity-controllable glycosylations of 4,6-di-O-
STol
O
NAc
O
2
Figure 1 Galactosamine donor 2
and 2 (Figure 1) under pre-activation conditions, and our
findings are reported herein.
Enlightened by the mechanistic studies done by Kerns,8a
Oscarson,8b and Ito,8c a reasonable explanation for the
controllable stereoselectivity is as follows: after pre-acti-
vation by the combination of benzenesulfinyl morpholine
(BSM) and triflic anhydride (Tf2O)9 donor 1 is converted
into a-triflate intermediate,10 and the glycosyl acceptor at-
tacks in a SN2-like fashion to form the b-glycoside; in situ
anomerization of the b-glycoside under acidic conditions
leads to formation of the a-glycoside. TTBP functions as
an acid scavenger to hinder the anomerization and make
the stereoselectivity controllable. According to this postu-
lation, based on the pre-activation protocol, the good b-
anomeric selectivity seems to arise from the triflate anion.
To testify it and find other ways to control the stereoselec-
tivity, we choose some molecules which might influence
or change the status of intermediate as new potential addi-
tives.11 On the one hand, the nature of the counterion in
the promoter system was found to have an influence on
the stereoselectivity in some glycosylations,12 so we want-
ed to examine the effect of other types of anion. Because
of the similarity of halide anion,13 such as I– to triflate an-
ion, quaternary ammonium salts which are soluble in or-
ganic solvents were chosen as the alternative of triflate
anion. On the other hand, since it was reported that thio-
acetyl-N-acetyl oxazolidinone protected donor
1
(Scheme 1). Based on a pre-activation protocol,6,7 either
excellent a- or b-stereoselectivity was obtained by means
of the addition of TTBP or the absence of it.
These results open a new avenue to modulate the stereo-
selectivity by changing additives in glycosylation reac-
tions. To investigate the effect of other additives on the
stereochemistry outcomes of glucosamine donor 1 and to
further extend the stereoselectivity-controllable pattern to
the galactosamine case, our attention was paid to explor-
ing additives in glycosylations of amino sugar donors 1
SYNLETT 2010, No. 16, pp 2506–2512
x
x
.x
x
.2
0
1
0
Advanced online publication: 03.09.2010
DOI: 10.1055/s-0030-1258557; Art ID: W08710ST
© Georg Thieme Verlag Stuttgart · New York

LETTER
Glycosylations of Oxazolidinone-Protected Thioglycoside Donors
2507
ethers could improve a-selectivity in the glycosylation ed to the reaction system. Hence, adding 1 equivalent of
reactions
of
2-azido-2-deoxyglucosyl
trichloro- TBAI gave rise to b-selectivity (entry 4), while adding 0.5
acetimidates14 via the b-sulfonium ion intermediate,15 we or even 0.1 equivalent of TBAI afforded a-selectivity (en-
decided to check if thioethers have a similar effect on the tries 5 and 6). Dimethyl sulfide showed similar effects
oxazolidinone protected thioglycoside donors.
(entries 11–14). In addition, the amount of TBAI and
TBAB should not be more than 1 equivalent, because an
excess of them resulted in a lower yield, and only trace
amount of products were obtained when 2 equivalents of
additives were used (entries 3 and 7). These interesting re-
sults gave us an important hint that other additives besides
TTBP could dramatically control the stereoselectivity of
donor 1 towards glycosylations.
Firstly, four additives, tetrabutyl ammonium iodide
(TBAI),16 tetrabutyl ammonium bromide (TBAB),13 di-
methyl sulfide, and thiophene, were examined in the gly-
cosylations of donor 1 with acceptor 3, which were carried
out in the pre-activation manner.17 Donor 1 was pre-acti-
vated at –73 °C in anhydrous dichloromethane using
BSM–Tf2O. After disappearance of donor 1 by TLC de-
tection, the additive and acceptor were added separately to Since in the absence of any additives the glycosylation of
the reaction mixture, with a time interval of 15 minutes. donor 1 with acceptor 3 was also a-selective (entry 1,
The reaction was then warmed to room temperature to fur- Table 1), it was important to know if the good a-selectiv-
nish the glycosidic bond formation, and the results are list- ity really comes from the effect of additives. For the mod-
ed in Table 1. The yields were high and all the el reaction, there is no evidence to testify whether the
glycosylations proceeded with excellent stereoselectivity additives lead to a-selectivity or they just have no effect at
(only a-anomer or only b-anomer). Both the a- and b- all. So we next checked the effect of these additives on
products are known compounds, and the NMR data of two glycosylations with poor a-selectivity reported in our
them are identical to those reported previously.4d As it was previous work (entries 1–20, Table 2).4d As displayed in
shown, TTBP (entry 2) was a good b-directing additive, Table 2, glycosylation of donor 1 with acceptor 4 under
both TBAB (entries 7–10) and thiophene (entries 15–18) pre-activation conditions without any additives provided
were good a-directing additives. However, the effects of a mixture of a- and b-anomers, the anomeric ratio (a/b)
TBAI and dimethyl sulfide depended on the amounts add- was 3:1 (entry 1). Adding the a-directing additives such as
Table 1 Effect of Additives on the Stereoselective Glycosylation of Donor 1 with Acceptor 3
O
Ph
NAc
O
O
O
O
BnO
Ph
O
O
OMe
O
O
AcO
HO
AcO
AcO
O
BnO
OMe
O
AcO
STol
BSM, Tf2O
additives
3
O
or
NAc
1
CH2Cl2, –73 °C
O
Ph
O
AcO
AcO
O
BnO
O
O
O
O
NAc
OMe
O
Entry
Additive
none
Equiv
2
Isolated yield (%)
Anomeric ratio (a/b)
a only
1
2
82
85
TTBP
b only
3
4
5
6
TBAI
TBAI
TBAI
TBAI
2
1
0.5
0.1
trace
87
87
–
b only
a only
a only
95
7
8
9
TBAB
TBAB
TBAB
TBAB
2
1
0.5
0.1
trace
78
81
–
a only
a only
a only
10
90
11
12
13
14
Me2S
Me2S
Me2S
Me2S
2
1
0.5
0.1
86
95
94
94
b only
b only
a only
a only
15
16
17
18
thiophene
thiophene
thiophene
thiophene
2
1
0.5
0.1
81
85
83
83
a only
a only
a only
a only
Synlett 2010, No. 16, 2506–2512 © Thieme Stuttgart · New York

2508
Y. Geng, X.-S. Ye
LETTER
Table 2 Additive-Controlled Stereoselective Glycosylations of Donor 1 with Acceptors 4–6
AcO
O
AcO
OR
O
NAc
AcO
AcO
O
O
additives
BSM, Tf2O
ROH
STol
or
O
CH2Cl2, –73 °C
NAc
1
AcO
AcO
O
O
N
O
OR
Ac
O
Entry
ROH
Additive
Equiv
Yield (%)
a/b Ratio
1
2
3
4
5
6
7
8
9
none
TTBP
TBAI
–
2
1
0.1
1
0.1
1
0.1
1
81
87
87
85
98
88
96
95
84
81
3:1
b only
b only
a only
b only
a only
b only
a only
a only
a only
OH
O
TBAI
BnO
BnO
TBAB
TBAB
Me2S
Me2S
thiophene
thiophene
BnO
OMe
4
10
0.1
11
12
13
14
15
16
17
18
19
20
none
TTBP
TBAI
87
98
96
82
50
84
87
79
82
80
1.5:1
b only
1:8
a only
1:5
a only
1:5
a only
a only
a only
2
1
0.1
1
0.1
1
0.1
1
0.1
TBAI
Ph
O
O
TBAB
TBAB
Me2S
Me2S
thiophene
thiophene
O
OMe
HO
OBn
5
21
22
23
24
25
26
27
28
29
30
none
TTBP
TBAI
84
87
96
87
70
73
87
85
75
80
a only
1:5
1:3
a only
1:3
a only
1:3
a only
a only
a only
2
1
0.1
1
0.1
1
0.1
1
0.1
TBAI
Ph
O
O
O
TBAB
TBAB
Me2S
Me2S
thiophene
thiophene
OMe
BnO
OH
6
thiophene (entries 9 and 10) greatly improved the a-selec- other hand, in this reaction, although the addition of 1
tivity. Other additives, like 0.1 equivalents of TBAI (entry equivalent of TBAI (entry 13), TBAB (entry 15), or di-
4), TBAB (entry 6), or dimethyl sulfide (entry 8) were methyl sulfide (entry 17) increased the b-selectivity,
able to improve the a-selectivity too. Thus, these a-direct- TTBP was the best b-directing additive (entry 12). Then
ing additives did have an effect on the stereochemical out- the effects of these additives on glycosylation of donor 1
come.
with acceptor 6 (entries 21–30), which was the only reac-
tion with moderate b-selectivity in our previous work,
were checked. The similar results were obtained. These
new b-directing additives improved the b-stereoselectivi-
ty, but none of them exceeded TTBP. The addition of
TTBP afforded an anomeric ratio of 1:5 (entry 22), where-
as the addition of 1 equivalent of TBAI (entry 23), TBAB
(entry 25), or dimethyl sulfide (entry 27) only afforded the
a/b ratio of 1:3.
Meanwhile, the b-selectivity was obtained not only by
adding TTBP (entry 2), but also by the addition of 1
equivalent of TBAI (entry 3), TBAB (entry 5), or dimeth-
yl sulfide (entry 7). It is noteworthy that the effect of
TBAB on this reaction was not consistent with the glyco-
syl coupling of donor 1 and acceptor 3 (entries 5 and 6,
Table 2 vs. entries 8 and 10, Table 1). Another glycosyla-
tion of donor 1 with acceptor 5 with poor a-selectivity was
also checked. Again, the poor anomeric ratio of 1.5:1 (en- After the above-mentioned investigations, the conclusion
try 11) was significantly improved by adding thiophene about the effects of the additives was summarized.
(entries 19 and 20), or 0.1 equivalents of TBAI (entry 14), Among them, TTBP was the best b-directing additive and
TBAB (entry 16), or dimethyl sulfide (entry 18). On the thiophene was the best a-directing additive, while TBAI
Synlett 2010, No. 16, 2506–2512 © Thieme Stuttgart · New York

LETTER
Glycosylations of Oxazolidinone-Protected Thioglycoside Donors
2509
and dimethyl sulfide were the bifunctional additives, cat- diate after activation is a-triflate, leading to b-glycosides
alytic amount of TBAI or dimethyl sulfide led to a-selec- at first; subsequent anomerization of the b-glycosides
tivity, stoichiometric amount of them led to b-selectivity. could give rise to the a-glycosides. Different even oppo-
These interesting findings drove us to conduct some site stereoselectivities conducted by these additives might
mechanism studies. To investigate the effects of different arise from their effects on the anomerization course. To be
additives on changing the status of the intermediates dur- sure, TTBP as an acid scavenger suppresses anomeriza-
ing glycosylation reactions, we did some low-temperature tion and gives rise to good b-selectivity. On the other
1H NMR experiments18 to detect the intermediate upon hand, TBAB or dimethyl sulfide can change the interme-
activation of donor 1 and addition of different additives diates in the glycosylations, different stereoselectivities
(Figure 2). As shown, in the case of TTBP as the additive, might arise from different intermediates.
1H NMR signals demonstrated that donor 1 was converted
To further investigate the generality of these rules, the
into a-triflate [1H NMR (400 MHz, CD2Cl2): d = 6.97 (s,
glycosylation of galactosamine donor 2 was checked. Do-
H-1)] immediately upon activation. While in the case of
nor 2 was synthesized following the preparative route of
no additives, donor 1 turned into both a-glucosamine
thioglycoside [1H NMR (400 MHz, CD2Cl2): d = 6.08 (d,
H-1, J = 4.4 Hz)] through anomerization and a-triflate in-
termediate [d = 6.94 (d, H-1, J = 2.4 Hz)]. A similar phe-
nomenon was observed when TBAI or thiophene was
added after activation of donor 1, and unexpectedly, none
of other intermediates, such as glycosyl iodide or sulfo-
nium ion, was detected. However, when TBAB was used
as the additive, proportionate signal attributed to b-triflate
[1H NMR (400 MHz, CD2Cl2): d = 6.52 (d, H-1, J = 7.6
Hz)] also appeared, indicating that TBAB can change the
status of the intermediate. When dimethyl sulfide was
added, no signals for triflates were detected, instead, the
signal of b-sulfonium ion [1H NMR (400 MHz, CD2Cl2):
d = 5.91 (d, H-1, J = 8.8 Hz)] appeared. Based on these
observations, it seems that a conclusion about the influ-
ences of different additives on the stereochemistry out-
comes in the glycosylation reactions of donor 1 can be
deduced. In the case of no additives or when TTBP,
thiophene, or TBAI was used as the additive, the interme-
donor 14d,8b (see Supporting Information). It was glycosy-
lated with four representative acceptors 3, 4, 7, and 8, af-
fording a-glycosides 9,19 11, 13, 15 and/or b-glycosides
10,20 12, 14, 16 (Table 3). Additives TTBP, thiophene,
and TBAI were separately added to the glycosylation re-
actions under the pre-activation conditions, and the results
are listed in Table 3. Generally, the yields were high, and
the rules of the additive-controlled stereoselectivity were
well kept, either excellent a-selectivity or moderate to
good b-selectivity could be obtained simply by modulat-
ing the additives.21 The a-directing additive thiophene af-
forded good to excellent a-selectivity in all glycosylations
(entries 5, 10, 15, and 20). The b-directing additive TTBP
afforded good b-selectivity in glycosylations with accep-
tors 3, 4, and 7 (entries 2, 7, and 12), but poor b-selectivity
in the glycosylation with acceptor 8 (entry 17). The bi-
functional additive TBAI afforded either a- (entries 3, 8,
13, and 18) or b-selectivity (entries 4, 9, 14, and 19) by
virtue of its amount added into the reactions, but its a-
selectivity was not superior to that of thiophene and the
Figure 2 Investigations to the status of intermediates after activation of donor 1 and addition of different additives by low temperature NMR
spectroscopy. The anomeric protons of b-thioglycoside (a), a-thioglycoside (b), a-triflate (c), b-triflate (d), and b-sulfonium ion (e) are assigned.
Synlett 2010, No. 16, 2506–2512 © Thieme Stuttgart · New York

2510
Y. Geng, X.-S. Ye
LETTER
b-selectivity was not superior to that of TTBP. It is note- ties were greatly changed by adding either the a-directing
worthy that couplings of donor 2 with acceptors 4, 7, and additive thiophene or the b-directing additive TTBP.
8 in the absence of any additives provided a mixture of a-
and b-anomers (entries 6, 11, and 16). The poor selectivi-
Table 3 Additive-controlled stereoselective glycosylations of donor 2 with acceptors 3, 4, 7 and 8
OAc
OAc
OAc
OAc
O
OAc
O
OAc
O
additives
BSM, Tf2O
ROH
or
STol
OR
O
O
O
CH2Cl2, –73 °C
NAc
OR
NAc
NAc
O
O
O
2
9–16
Entry
ROH
Additive
Product
Isolated yield (%) Anomeric ratio (a/b)
O
Ph
O
O
O
O
BnO
NAc
OMe
O
O
OAc
1
2
3
4
5
no
TTBP
TBAI (0.1 equiv)
TBAI (1 equiv)
thiophene
76
87
75
87
75
a only
1:9
a only
1:7
OAc
O
Ph
O
O
9
HO
BnO
OMe
Ph
OAc
O
O
a only
3
O
OAc
O
O
BnO
OMe
O
NAc
O
10
OAc
OAc
O
O
N
Ac
BnO
BnO
O
O
O
BnO
6
7
8
9
10
no
TTBP
TBAI (0.1 equiv)
TBAI (1 equiv)
thiophene
75
78
75
77
77
2:1
OMe
OH
O
b only
a only
1:20
11
BnO
BnO
BnO
OMe
OAc
OAc
O
a only
4
O
N
Ac
BnO
BnO
O
O
O
BnO
OMe
12
OAc
OAc
O
O
N
O
Ac
OBn
O
O
BnO
BnO
11
12
13
14
15
no
TTBP
TBAI (0.1 equiv)
TBAI (1 equiv)
thiophene
90
87
84
85
77
1.5:1
1:5
2:1
1:4
> 20:1
OH
OBn
O
OMe
13
BnO
BnO
OMe
OAc
OAc
O
7
OBn
O
O
O
NAc
BnO
O
BnO
OMe
14
Synlett 2010, No. 16, 2506–2512 © Thieme Stuttgart · New York

LETTER
Glycosylations of Oxazolidinone-Protected Thioglycoside Donors
2511
Table 3 Additive-controlled stereoselective glycosylations of donor 2 with acceptors 3, 4, 7 and 8 (continued)
OAc
OAc
OAc
OAc
O
OAc
O
OAc
O
additives
BSM, Tf2O
ROH
or
STol
OR
O
O
O
CH2Cl2, –73 °C
NAc
OR
NAc
NAc
O
O
O
2
9–16
Entry
ROH
Additive
Product
Isolated yield (%) Anomeric ratio (a/b)
Ph
O
O
O
BnO
O
O
OMe
NAc
OAc
O
O
OAc
16
17
18
19
20
no
TTBP
TBAI (0.1 equiv)
TBAI (1 equiv)
thiophene
83
84
85
87
83
3:1
1:1.5
3:1
1:1
4:1
O
Ph
O
15
O
BnO
HO
OMe
Ph
O
O
O
8
BnO
O
OAc
OAc
O
OMe
O
NAc
O
16
(4) (a) Benakli, K.; Zha, C.; Kerns, R. J. J. Am. Chem. Soc. 2001,
123, 9461. (b) Boysen, M.; Gemma, E.; Lahmann, M.;
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Chem. Int. Ed. 2004, 43, 5221. (b) Huang, L.; Wang, Z.; Li,
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In summary, based on pre-activation protocol, not only
hindered base TTBP but also some other additives can
significantly influence the stereochemistry outcomes of
glycosylations of 4,6-di-O-acetyl-N-acetyl oxazolidinone
protected glucosamine donor 1 and galactosamine donor
2. Generally, good to excellent b-anomeric selectivity was
obtained by adding TTBP, whereas excellent a-anomeric
selectivity was obtained by adding thiophene. The amount
of bifunctional additives such as TBAI gave rise to com-
pletely different stereoselectivity, catalytic amount af-
forded a-selectivity while stoichiometric amount led to b-
selectivity. The additive-controlled stereoselective gly-
coslylations may find wide applications to the oligosac-
charide assembly. Further exploration of new additives
which may modulate the stereoselectivity of glycosyla-
tions and extension of this protocol to other sugars are un-
der investigation.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synlett.
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Acknowledgment
This work was financially supported by the National Natural Sci-
ence Foundation of China (Grant No. 20732001) and the grant
(2009ZX09501-011) from the Ministry of Science and Technology
of China.
(9) Wang, C.; Wang, H.; Huang, X.; Zhang, L.-H.; Ye, X.-S.
Synlett 2006, 2846.
(10) (a) Crich, D.; Sun, S. J. Am. Chem. Soc. 1997, 119, 11217.
(b) Crich, D.; Cai, W. J. Org. Chem. 1999, 64, 4926.
(c) Crich, D.; Smith, M. J. Am. Chem. Soc. 2001, 123, 9015.
(11) Although participating solvents such as Et2O or MeCN can
influence the intermediate of glycosylations, they cannot be
used as additives because a large excess of them are needed.
About the solvent effect, see: (a) Wulff, G.; Rohle, G.
Angew. Chem., Int. Ed. Engl. 1974, 13, 157. (b) Vankar, D.;
Vankar, P. S.; Behrendt, M.; Schmidt, R. R. Tetrahedron
1992, 47, 9985; and references cited therein.
References and Notes
(1) Boltje, T. J.; Buskas, T.; Boons, G. J. Nat. Chem. 2009, 1,
611.
(2) Zhu, X. M.; Schmidt, R. R. Angew. Chem. Int. Ed. 2009, 48,
1900.
(3) Demchenko, A. V. Synlett 2003, 1225.
Synlett 2010, No. 16, 2506–2512 © Thieme Stuttgart · New York

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Y. Geng, X.-S. Ye
LETTER
(12) Mukaiyama, T. Angew. Chem. Int. Ed. 2004, 43, 5590; and
references cited therein.
(13) Lemieux, R. U.; Hendriks, K. B.; Stick, R. V.; James, K.
J. Am. Chem. Soc. 1975, 97, 4056; and references cited
therein.
(14) Park, J.; Kawatkar, S.; Kim, J. H.; Boons, G. J. Org. Lett.
2007, 9, 1959.
(15) Sulfonium ion observation: (a) West, A. C.; Schuerch, C.
J. Am. Chem. Soc. 1973, 95, 1333. (b) Kim, J. H.; Yang, H.;
Park, J.; Boons, G. J. J. Am. Chem. Soc. 2005, 127, 12090.
(c) Nokami, T.; Shibuya, A.; Manabe, S.; Ito, Y.; Yoshida, J.
Chem. Eur. J. 2009, 15, 2252.
NMR was recorded. Subsequently the temperature of the
probe was raised in 10 °C steps with monitoring by 1H
NMR.
(19) Product 9 was purified by column chromatography on silica
gel (PE–EtOAc, 3:1); Rf = 0.3 (PE–EtOAc, 1.5:1). 1H NMR
(400 MHz, CDCl3): d = 7.59–7.61 (m, 2 H), 7.33–7.40 (m, 8
H), 6.25 (d, 1 H, J = 2.8 Hz, H-1¢), 5.55 (s, 1 H), 5.30 (s, 1
H), 4.70 (d, 1 H, J = 3.6 Hz, H-1), 4.64 (d, 1 H, J = 11.6 Hz),
4.53 (d, 1 H, J = 11.6 Hz), 4.11–4.34 (m, 6 H), 3.77–3.84 (m,
2 H), 3.72 (t, 1 H, J = 10.0 Hz), 3.51–3.56 (m, 2 H), 3.37 (s,
3 H), 2.40 (s, 3 H), 2.08 (s, 3 H), 2.04 (s, 3 H). 13C NMR (100
MHz, CDCl3): d = 170.38 (2 C), 169.35, 152.90, 137.54,
137.11, 128.80, 128.62, 128.54, 128.47, 128.05, 126.29,
126.20, 101.14, 97.94, 95.01, 82.39, 78.38, 72.98, 72.07,
72.00, 68.87, 68.03, 65.80, 61.77, 61.54, 56.06, 55.17,
23.80, 20.58, 20.54. ESI-MS: m/z = 686 [M + H]+, 703 [M +
NH4]+, 708 [M + Na]+. Anal. Calcd for C34H39NO14: C,
59.56; H, 5.73; N, 2.04. Found: C, 59.30; H, 5.69; N, 1.97.
(20) Product 10 was purified by column chromatography on
silica gel (PE–EtOAc, 1.5:1); Rf = 0.1 (PE–EtOAc, 1.5:1).
1H NMR (400 MHz, CDCl3): d = 7.48–7.50 (m, 2 H), 7.31–
7.38 (m, 8 H), 5.59 (s, 1 H), 5.56 (s, 1 H), 5.08 (d, 1 H,
J = 7.6 Hz, H-1¢), 4.64 (d, 1 H, J = 11.8 Hz), 4.54 (d, 1 H,
J = 3.6 Hz, H-1), 4.52 (d, 1 H, J = 12.0 Hz), 4.32 (dd, 1 H,
J = 7.6, 12.0 Hz), 4.15–4.24 (m, 3 H), 3.95–4.08 (m, 3 H),
3.63–3.79 (m, 4 H), 3.30 (s, 3 H), 2.38 (s, 3 H), 2.10 (s, 3 H),
1.98 (s, 3 H). 13C NMR (100 MHz, CDCl3): d = 171.25,
170.28, 169.33, 153.54, 137.91, 137.35, 128.86, 128.56,
128.18, 128.03, 127.45, 126.04, 103.01, 100.85, 98.25,
80.63, 78.79, 77.23, 76.33, 72.98, 72.23, 68.84, 64.06,
62.53, 61.33, 57.55, 55.22, 25.08, 20.59, 20.56. ESI-MS:
m/z = 686 [M + H]+, 703 [M + NH4]+, 708 [M + Na]+, 724
[M + K]+. Anal. Calcd for C34H39NO14: C, 59.56; H, 5.73; N,
2.04. Found: C, 59.34; H, 5.67; N, 1.96.
(16) Hadd, M. J.; Gervay, J. Carbohydr. Res. 1999, 320, 61.
(17) General Procedures for Glycosylations of Donors 1 or 2
with Acceptors 3–8
Tf2O (8.7 mL, 0.052 mmol, 1.3 equiv) was added to a stirred
mixture of donors 1 or 2 (21.2 mg, 0.048 mmol, 1.2 equiv),
BSM (11.1 mg, 0.052 mmol, 1.3 equiv), and activated 4 Å
MS (300 mg, powder) in CH2Cl2 (3 mL) at –73 °C under
nitrogen atmosphere. The reaction mixture was stirred for 5
min, after loss of the donor detected by TLC, the additive
(0.1–2.0 equiv) was added to the mixture. After stirring for
15 min, a solution of the acceptor 3 (15.0 mg, 0.040 mmol,
1.0 equiv) or other acceptors in CH2Cl2 (0.2 mL) was added
dropwise to the reaction mixture. The mixture was stirred
and warmed up to r.t. slowly, quenched by Et3N (0.1 mL).
The precipitate was filtered off, and the filtrate was
concentrated. The residue was purified by column
chromatography on silica gel to give the products.
(18) Representative Procedures for Detecting Intermediates
after Activation of Donor 1 by Variable Temperature
NMR Spectroscopy
To a solution of donor 1 (8.7 mg, 0.02 mmol), BSM (5.1 mg,
0.024 mmol) in CD2Cl2 (0.5 mL) in a NMR tube at –60 °C,
under an argon atmosphere, was added 1.2 equiv of Tf2O
(0.024 mmol, 4.1 mL). The NMR tube was immediately
transferred to the pre-cooled NMR probe (–60 °C), and 1H
(21) The a-anomers and b-anomers were identified by their
1H NMR coupling constants for anomeric protons. For a-
anomers, J1,2 = 2.4–2.8 Hz; for b-anomers, J1,2 = 7.2–7.6 Hz.
Synlett 2010, No. 16, 2506–2512 © Thieme Stuttgart · New York