678
Published on the web May 28, 2011
¹
Electrochemically Generated ArS(ArSSAr)+B(C6F5)4
as an Activator of Thioglycosides for Glycosylation
Kodai Saito, Yoshihiro Saigusa, Toshiki Nokami, and Jun-ichi Yoshida*
Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering,
Kyoto University, Nishikyo-ku, Kyoto 615-8510
(Received March 30, 2011; CL-110265; E-mail: yoshida@sbchem.kyoto-u.ac.jp)
Electrochemically generated ArS(ArSSAr)+ was found to
Table 1. Effect of electrolytes
ArS(ArSSAr)+X-
(Ar = p-FC6H4)
(1.3 equiv)
be an effective activator for glycosylation of thioglycosides.
Efficiency of the reaction strongly depends on the nature of the
counter anion, and B(C6F5)4 was the most effective among
those examined. The method was applicable to various
glyocosyl donors including thiogalactosides and thiomannosides
and various acceptors including those having secondary hydroxy
groups.
BnO
BnO
BnO
BnO
BnO
¹
O
O
STol MeOH
(5.0 equiv)
BnO
Bu4NX
CH2Cl2
BnO
OMe
BnO
1a
2
-78 °C, 5 min
Entry
Counter anion
2 Yield/% [¡/¢]a
¹
1
2
3
4
5
BF4
60 [48/52]
N. R.
72 [14/86]
88 [38/62]
77 [32/68]b
¹
ClO4
OTf
Thioglycosides1 are widely utilized as glycosyl donors in
the chemical synthesis of oligosaccharides,2 because they are
stable and easy to handle. Continuous efforts have been made to
develop a new method for activating thioglycosides, which
might open many possibilities of chemical glycosylation.3
¹
¹
B(C6F5)4
B(C6F5)4
¹
aReactions were normally carried out with thioglycoside
(0.1 mmol) and a glycosyl acceptor (0.5 mmol) in Bu4NX/CH2Cl2
(X = BF4, ClO4, OTf: 0.3 M, X = B(C6F5)4: 0.1 M, 1 mL),
We have already reported that arylbis(arylthio)sulfonium
¹ 4
tetrafluoroborate [ArS(ArSSAr)+BF4
] generated by electro-
¹
ArS(ArSSAr)+X in CH2Cl2 (ca. 0.046 M, 2.9 mL, 0.13 mmol).
bThe reaction was carried out without adding Bu4NB(C6F5)4.
chemical oxidation of diaryldisulfide (ArSSAr) reacts with
thioacetals to generate alkoxycarbenium ions (indirect cation
pool method).5 We also found that electrochemically generated
Table 2. The effect of the subsituent on the Ar groupa
¹
ArS(ArSSAr)+B(C6F5)4 was effective for generation of glyco-
Entry
Ar
2 Yield/% [¡/¢]
syl cations or its equivalent from thioglycosides in the absence
of glycosyl acceptors.6 In the flow system, the resulting highly
reactive glycosyl cations are transferred to another location to be
used for the reaction with glycosyl acceptors. In this paper, we
report another method for glycosylation using thioglycoside and
ArS(ArSSAr)+, which involves generation of glycosyl cations in
the presence of glycosyl acceptors.
1
2
3
4
p-FC6H4
Ph
p-ClC6H4
Tol (p-MeC6H4)
88 [38/62]
60 [44/56]
66 [42/58]
55 [40/60]
aReactions were carried out with 1.3 equiv of ArS-
¹
(ArSSAr)+B(C6F5)4 and 5 equiv of MeOH at ¹78 °C.
At first we examined the effect of the counter anion
of ArS(ArSSAr)+. Thus, glycosyl donor 1a (0.1 mmol) was
additional amount of Bu4NB(C6F5)4 resulted in higher yield
¹
allowed to react with ArS(ArSSAr)+X (1.3 equiv) (Ar = p-
(compare Entry 4 and 5), although a solution of ArS-
¹
FC6H4), which was generated by the anodic oxidation of
ArSSAr using Bu4NX as a supporting electrolyte.7 Methanol
(5 equiv) was used as a glycosyl acceptor (Table 1). The use of
(ArSSAr)+B(C6F5)4 contains Bu4NB(C6F5)4 (ca. 0.05 M after
electrolysis). The reason is not clear at present.
Next, the effect of the substituent on the aryl group of
ArS(ArSSAr)+ was investigated (Table 2). As stated above the
use of ArS(ArSSAr)+ (Ar = p-FC6H4) gave 2 in 88% yield
(Entry 1). The use of Ph and p-ClC6H4 as an aryl substituent
resulted in the formation of 2 in 60% and 66% yield,
respectively (Entries 2 and 3). The use of p-MeC6H4 (Tol)
¹
¹
BF4 as X gave rise to the formation of methyl glycoside 2 in
60% yield (Entry 1). The glycosyl fluoride was also obtained in
33% yield,8 indicating that the glycosyl cation or the cation
¹
equivalent was trapped by fluoride derived from BF4 . To avoid
¹
the nucleophilic attack of the fluoride, the use of ClO4 as the
¹
counter anion was examined. However, ArS(ArSSAr)+ClO4
gave 2 in 55% yield (Entry 4). Thus, hereafter ArS-
¹
was not generated effectively by the anodic oxidation of ArSSAr
(ArSSAr)+B(C6F5)4 (Ar = p-FC6H4) was used as an activator
using Bu4NClO4 as a supporting electrolyte (Entry 2).9 On the
for glycosylation reactions.
¹
other hand, the use of OTf resulted in the formation of 2 in
The glycosylation was also carried out at higher reaction
temperature and there were no significant effects of reaction
temperature on glycosylation (See Supporting Informations for
details7). Thus, glycosylation reactions of various glycosyl
donors and acceptors were examined at ¹28 or 0 °C (Table 3).
Secondary alcohols such as c-C6H11OH could be used for the
glycosylation to afford the desired product 3 in 88% yield
(Entry 1). Glycosides 4 and 6 were effective as acceptors to give
72% yield (Entry 3). Interestingly, the ¢-selectivity was higher
¹
than that observed for BF4 , presumably because of the
formation of a glycosyl triflate10 as an intermediate. The use
¹
of B(C6F5)4 caused further increase in the yield of 2 (88%),
although the stereoselectivity decreased slightly (Entry 4). Thus,
¹
hereafter ArS(ArSSAr)+B(C6F5)4 was used as an activator for
glycosylation reactions. It is interesting that the use of the
Chem. Lett. 2011, 40, 678-679
© 2011 The Chemical Society of Japan