Catalytic and stereoselective glycosylation with glycosyl fluoride using active carbocationic species paired with tetrakis(pentafluorophenyl)borate or trifluoromethanesulfonate

Article abstract of DOI:10.1246/cl.2001.224

Catalytic and stereoselective glycosylation with glycosyl fluoride using carbocationic species paired with tetrakis(pentafluorophenyl)borate [B(C₆F₅)₄^-] or trifluoromethanesulfonate (TfO^-) is investigated. When the glycosylation is carried out using the former catalyst in dichloromethane containing ^tBuCN, the major product is β-glycoside while α-selectivity is observed when the latter catalyst in dichloromethane containing Et₂O is used. In addition to the characteristic properties of the solvent, the nature of the counter anion such as B(C₆F₅)₄^- or TfO^- plays important roles in controlling the selectivity. Thus, an appropriate combination of catalyst and solvent leads to the formation of disaccharides.

Full text of DOI:10.1246/cl.2001.224

224
Chemistry Letters 2001
Catalytic and Stereoselective Glycosylation with Glycosyl Fluoride Using Active Carbocationic
Species Paired with Tetrakis(pentafluorophenyl)borate or Trifluoromethanesulfonate
Manabu Yanagisawa and Teruaki Mukaiyama*
Department of Applied Chemistry, Faculty of Science, Science University of Tokyo, Kagurazaka, Shinjuku-ku, Tokyo 162-8601
(Received December 19, 2000; CL-001143)
Catalytic and stereoselective glycosylation with glycosyl
fluoride using carbocationic species paired with tetrakis(penta-
fluorophenyl)borate [B(C6F5)4 ] or trifluoromethanesulfonate
syl fluoride by using carbocationic species either 1a or 2a and its
derivatives. It was recognized that the factors controlling the α-
and β-selectivities were influenced both by characteristic proper-
ties of the solvent and the nature of counter anion of the catalysts.
In the first place, the catalytic glycosylation of methyl 2,3,4-
tri-O-benzoyl-α-D-glucopyranoside (4) with 2,3,4,6-tetra-O-ben-
zyl-β-D-glucosyl fluoride (3) was examined by using a catalytic
amount of carbocationic species 1a, 2a or TrB(C6F5)4 (see Table
1).
–
(TfO–) is investigated. When the glycosylation is carried out
using the former catalyst in dichloromethane containing tBuCN,
the major product is β-glycoside while α-selectivity is observed
when the latter catalyst in dichloromethane containing Et2O is
used. In addition to the characteristic properties of the solvent,
the nature of the counter anion such as B(C6F5)4– or TfO– plays
important roles in controlling the selectivity. Thus, an appro-
priate combination of catalyst and solvent leads to the forma-
tion of disaccharides.
Development of stereoselective glycosylation reaction is one
of the most fundamental topics in carbohydrate chemistry and vari-
ous combinations of glycosyl donors and activators have been
studied1 in these two decades to establish efficient glycosylation
methods. Among them, the use of glycosyl fluoride proved to be
quite effective as it is a donor more stable than the corresponding
chloride or bromide, and has widely been used in the synthesis of
many complex oligosaccharides after our publication in 1981.2
Activation of glycosyl fluoride was successfully achieved by using
stoichiometric amounts of various Lewis acids most of which had
–
ClO4 or TfO– anions.3 However, only a few examples of catalytic
glycosylation using trimethylsilylated donors have been reported.
In 1998, the first example3 of catalytic glycosylation between gly-
cosyl fluoride and alcohols was presented in the glycosylation of
several alcohols and glucosides with glycosyl fluoride using a cat-
alytic amount of trityl tetrakis(pentafluorophenyl)borate
[TrB(C6F5)4]4 affording the corresponding disaccharides in high
t
yields with β-selectivities in dichloromethane containing BuCN.
However, α-selective catalytic glycosylation was not achieved by
using the carbocationic species such as TrB(C6F5)4.5
A typical experimental procedure is described for the reac-
tion of 3 with 4 using 2a as a catalyst in the co-existence of MS
5Å (Table 1; Entry 5): to a suspension of 2a (12.0 mg, 0.012
mmol) and powdered MS 5Å (60 mg) in a solvent (pivaloni-
trile/dichloromethane = 5/1, 0.5 mL) was added 2,3,4,6-tetra-O-
benzyl-β-D-glucosyl fluoride 3 (42.3 mg, 0.078 mmol) and
methyl 2,3,4-tri-O-benzoyl-α-D-glucopyranoside 4 (30.4 mg,
0.060 mmol) in the above solvent (2.5 mL) at 0 °C. The reac-
tion mixture was stirred for 1 h at 0 °C, then was quenched by
the addition of saturated aqueous sodium hydrogencarbonate (3
mL). The mixture was filtered through Celite pad and extracted
with ethyl acetate. The combined organic layer was washed
successively with water and brine and dried over MgSO4. After
filtration and evaporation, the resulting residue was purified by
preparative TLC, and methyl 2,3,4-tri-O-benzoyl-6-O-(2,3,4,6-
tetra-O-benzyl-D-glucopyranosyl)-D-glucopyranoside 5 (52.6
mg, 85% yield) was thus isolated. The ratio of anomers was
determined by 1H NMR analysis. Other examples of the glyco-
On the other hand, it was recently reported that the carbo-
–
cationic species paired with B(C6F5)4 (1a and 2a) smoothly
catalyzed the aldol reaction of aldehydes with silyl enol ethers6a
or enol esters6b similar to the case using a trityl cation. There
was also shown that the aldol reaction was promoted more
effectively by the electron-deficient cationic species 2a com-
pared with that of 1a. In this communication, we would like to
report on catalytic and stereoselective glycosylation with glyco-
Copyright © 2001 The Chemical Society of Japan

Chemistry Letters 2001
225
sylations with glycosyl fluoride by using different additives,
solvents and catalysts are shown in Table 1.
tivity of the produced glycosides decreased considerably when
reversed combinations of the catalyst and solvent system were
employed. The formation of α-glycoside was best achieved
when 2b and MS 5Å were used in dichloromethane containing
Et2O while β-glycoside was best obtained with 2a and MS 5Å
in dichloromethane containing tBuCN.
Some examples of the present glycosylation reaction are
illustrated in Table 3. In every case, the desired glycosides
were obtained in high yields and selectivities when the appro-
priate catalyst and solvent were combined.
When the glycosylation was carried out in dichloromethane
containing tBuCN, disaccharide 5 was obtained with high β-selec-
tivity (Entry 1–6). Cationic species 2a, a more active one,6b exhib-
ited higher catalytic activity than 1a did (Entry 1 vs 2 and Entry 4
vs 5) and the activity was also slightly higher than that of
TrB(C6F5)4 (Entry 5 vs 6) when the catalyst was used together with
MS 5Å. On the other hand, α-selectivity was not observed at all
when the preparation of α-disaccharide was tried in the solvent
containing Et2O expecting its solvent effect,7 (Entries 7–12).
In order to examine the effect of counter anions of the cata-
lyst, the carbocationic species 2b–2e were prepared by the fol-
lowing procedure as shown in Scheme 1, and were further
examined their effects on the stereoselectivities in detail.
It was clearly recognized that the resulting glycosides were
obtained with high stereoselectivities if the appropriate combi-
nations of catalyst and solvent system were chosen. For exam-
ple, when the reaction was carried out in dichloromethane con-
t
taining BuCN, β-glycoside was obtained by using the catalyst
such as 2a, 2c or 2d. On the other hand, disaccharide with α-
selectivity was obtained in dichloromethane containing Et2O by
using a catalyst either 2b or 2e. Interestingly, the stereoselec-
It is noted that the catalytic and stereoselective glycosylation
with glycosyl fluoride was carried out effectively by using several
–
cationic species paired with either B(C6F5)4 or TfO– in the co-
exsistence of MS 5Å or Drierite as a dehydrating agent. When the
reaction was performed in the solvent (tBuCN:CH2Cl2=5:1) by
using a catalytic amount of carbocationic species paired with a
–
counter anion as B(C6F5)4 , the major product was β-glycoside.
Contrary to the above result, α-glycoside was produced as a major
product when the same reaction was carried out in the solvent con-
taining Et2O using a catalytic amount of carbocationic species
paired with TfO–. These results suggest that the stereoselectivity
of the glycosylation is highly controlled by both the nature of a sol-
vent and that of a counter anion of the catalyst. And the study on
this topic is now in progress.
References and Notes
1
K. Toshima and K. Tatsuta, Chem. Rev., 93, 1503 (1993);
K. Suzuki and T. Nagasawa, J. Synth. Org. Chem. Jpn., 50,
378 (1992); G-J. Boons, Tetrahedron, 52, 1095 (1996).
T. Mukaiyama, Y. Murai, and S. Shoda, Chem. Lett., 1981,
431.
K. Takeuchi and T. Mukaiyama, Chem. Lett., 1998, 555,
and references cited therein.
J. C. W. Chien, W-M. Tsai, and M. D. Rausch, J. Am.
Chem. Soc., 113, 8570 (1991).
Recently, the α-selective catalytic glycosylation using a
protic acid such as TfOH was performed in our laboratory:
H. Jona, K. Takeuchi, and T. Mukaiyama, Chem. Lett.,
2000, 1278.
2
3
4
5
6
7
a) T. Mukaiyama, M. Yanagisawa, D. Iida, and I. Hachiya,
Chem. Lett., 2000, 606. b) M. Yanagisawa, T. Shimamura,
D. Iida, J. Matsuo, and T. Mukaiyama, Chem. Pharm.
Bull., 48, 1838 (2000).
G. Wulff and G. Röhle, Angew. Chem., Int. Ed. Engl., 13,
157 (1974)