A novel activating agents of 'disarmed' thioglycosides, combination of trityl tetrakis(pentafluorophenyl)borate, iodine and 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ)

Article abstract of DOI:10.1246/cl.2000.692

A combined use of trityl tetrakis(pentafluorophenyl) borate [TrB(C₆F₅)₄], iodine (I₂) and 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ) effectively activates disarmed thioglycosides to afford the corresponding disaccharides in high yields on treatment with several glycosyl acceptors.

Full text of DOI:10.1246/cl.2000.692

692
Chemistry Letters 2000
A Novel Activating Agents of 'Disarmed' Thioglycosides,
Combination of Trityl Tetrakis(pentafluorophenyl)borate, Iodine and
2,3-Dichloro-5,6-dicyano-p-benzoquinone (DDQ)
Kazuya Takeuchi, Takayuki Tamura, Hideki Jona, and Teruaki Mukaiyama
Department of Applied Chemistry, Faculty of Science, Science University of Tokyo, Kagurazaka, Shinjuku-ku, Tokyo 162-8601
(Received March 16, 2000; CL-000262)
A combined use of trityl tetrakis(pentafluorophenyl) borate
[TrB(C6F5)4], iodine (I2) and 2,3-dichloro-5,6-dicyano-p-benzo-
quinone (DDQ) effectively activates "disarmed" thioglycosides
to afford the corresponding disaccharides in high yields on
treatment with several glycosyl acceptors.
Thioglycosides are frequently employed in the synthesis of
complex carbohydrates1 since they are stable under most reaction
conditions and are activated by such reagents in combination
with TfOH-NIS2 or Lewis acids and NIS or NBS, or reagents as
6
MeOTf,3 DMTST,4 IDCP,5 and TrB(C6F5)4-NaIO4 and some
other promoters.7 Among these activating agents, the combina-
tion of NIS-TfOH effectively activates glycosyl donors to gener-
ate highly reactive key intermediate, an iodonium ion. Recently,
it was reported from our laboratery that the respective combina-
tions of catalytic amount of TrB(C6F5)4 and stoichiometric
amount of NIS or NBS were useful for activating "disarmed"
thioglycosides.8 A study on the above glycosylation was further
continued to confirm the co-product resulted from alkylthio moi-
ety left during the present reaction. As shown in Scheme 1,
dodecyl thioglycoside smoothly reacted with an acceptor in the
presence of NIS-TrB(C6F5)4 to afford the corresponding disac-
charide and didodesyldisulfide in high yields. This result indicat-
ed that dodesylsulfenyl iodide, formed by iodonium ion aciva-
tion, was rapidly converted to iodine and the corresponding disul-
fide. Based on this observation, generation of active iodonium
ion from iodine was then examined in order to establish the cat-
alytic cycle of the glycosylation using thioglycoside.
the active species should be an iodonium ion generated in situ
from I2 / DDQ. Interestingly enough, the addition of DDQ to
the above combination of TrB(C6F5)4 / I2 dramatically acceler-
ated the glycosylation reaction to afford the corresponding di-
saccharide in high yield (Entry 4). These observations promted
us to screen reaction conditions in detail and the results are
shown in Table 1. It was made thus clear that the coexistence
of the above three reagents was essential to the promotion of
the reaction while each combination such as I2 / DDQ,
TrB(C6F5)4 / DDQ, was not so effective (Entry 2, 3). Further, it
was observed that the effect of solvents was influential to the
present glycosylation and that use of pivalonitrile enhanced the
rate of the reaction (Entry 4, 5).
Next, the effects of the amount of activating agents were
examined for the optimization of reaction conditions. In the pres-
ence of 1 equiv each of I2 and DDQ, 5 mol% of TrB(C6F5)4 was
shown to be sufficient (Entry 6). It was further demonstrated that
the minimum requirement of DDQ was 55 mol% in the coexist-
ence of 5 mol% of TrB(C6F5)4 and 1 equiv. of I2 (Entry 7). The
amount of I2 was further examined in the coexistence of 5 mol%
of TrB(C6F5)4 and 55 mol% of DDQ, and it was shown that the
only 10 mol% of I2 was enough to promote the present glycosyla-
tion reaction (Entry 8). It is well-known that the rate of oxidation
reaction of using quinones increased when a catalytic amount of
protic acid was added. The conjugated acid, protonated DDQ,
was counted to be a stronger anion or electron acceptor compared
with DDQ. Consequently, it was considered that the reactivity of
the present glycosylation reaction was essentially determined by
both the reduction potential of quinones and the acidity of Lewis
acids. In order to prove the above hypothesis, combinations of
various quinones and Lewis acids were applied to the present
The iodine-based novel activating agents of thioglycosides
were studied by taking the reaction of ethyl 3,4,6-tri-O-acetyl-
2-deoxy-2-phthalimide-1-thio-β-D-glucopyranoside (1) with
methyl 2,3,4-tri-O-benzoyl-α-D-glucopyranoside (2) as a model
(Table 1). Firstly, a combination of TrB(C6F5)4 and I2 was
employed as an activating agent and the desired disaccharide
was obtained in moderate yield (Entry 1). Concerning this type
of iodine-based agent, R. A. Field reported the glycosylation of
simple alcohols using several glycosyl halides as donors by
using equimolar amounts of I2 / DDQ.9 Although the precise
mechanism of the I2 / DDQ-promoted glycosylation reaction
was not cleary described in the above paper, we assumed that
Copyright © 2000 The Chemical Society of Japan

Chemistry Letters 2000
693
reaction. As shown in Table 2, the rate of reaction revealed to
be dependent on the reduction potential of quinones10 in the
presence of 5 mol% of TrB(C6F5)4, 10 mol% of I2, 55 mol% of
several quinones.
Effects of various Lewis acid catalysts were further
screened in the glycosylation reaction by using 10 mol% of I2
and 55 mol% of DDQ. Significant difference of reactivity was
observed among various trityl salts screened (see Table 3): that
is, the corresponding disaccharide was obtained in poor yield in
the case of using 4-methoxytrityl tetrakis(pentafluorophenyl)-
boate, a less reactive Lewis acid catalyst, while TrB(C6F5)4 and
4,4',4"-trifluorotrityl tetrakis(pentafluorophenyl)borate gave
good results. It also became apparent that TrB(C6F5)4 gave
even better results than trityl tetrafluoroboarte because the former
had a highly stabilized counter anion, tetrakis(pentafluoro-
phenyl)borate. Of other Lewis acids and protic acids employed
in place of the trityl salts, trifluoromethanesulfonic acid
behaved relatively effective .
µmol). After the reaction mixture was stirred for 8 h at 0 °C, it
was quenched by adding saturated aqueous NaHCO3 (10 mL).
The mixture was filtered through Celite and extracted with
dichloromethane (3 times, each of 20 mL). The combined
organic layer was washed with brine (5 mL) and the resulted
organic layer was dried over Na2SO4. After filtration and evap-
oration, the resulted residue was purified by preparative TLC
(silica gel) to give the desired product (43.3 mg, 94%).
Thus, a novel activator composed of TrB(C6F5)4 / I2 /
DDQ, was effectively employed for the glycosylation of "dis-
armed" thioglycoside. It is noted that the experimental proce-
dure of the present glycosylation is quite simple and all
reagents are easily-available, stable, and nonhygroscopic.
The present research is partially supported by Grant-in-
Aids for Scientific Reaerch from the Ministry of Education,
Science, Sports, and Culture.
References
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glycosyl donors and acceptors was tried and the optimized reac-
tion conditions were summarized in Table 4. In each case, the
"disarmed" thioglycosides reacted with glycosyl acceptors,
methyl glucosides, to afford the corresponding β-glycosides in
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5
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6
7
The typical experimental procedure is as follows: to a stirred
suspension of trityl tetrakis(pentafluorophenyl)borate (2.3 mg,
2.5 µmol), DDQ (6.2 mg, 27.5 µmol) and Drierite (100 mg) in a
mixed solvent (pivalonitrile:dichloromethane = 2:1, 0.45 mL)
was successively added a solution (pivalonitrile:dichloromethane
= 2:1, 0.8 ml) of 1 (24.0 mg, 0.05 mmol) and 2 (32.9 mg, 0.065
mmol) at 0 °C, followed by addition of iodine (1.3 mg, 5.0
8
9
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