Table 6 Catalyst and aglycone amount optimisation: dramatic effect
chromatography was performed on silica gel 60 (0.063–0.2 mm,
Macherey-Nagel). Reactions were monitored by TLC on silica
gel 60 UV254 (Macherey-Nagel) with detection by charring with
10% sulfuric acid in ethanol. Solvents were removed under
reduced pressure at < 50 ◦C.
of ionic liquid
Sc(OTf)3
amount
Isolated
yield
Ionic liquid
Octanol (eq)
a/b
[BMIM][OTf]
5 mol%
1 mol%
1 mol%
1 mol%
5
5
1.5
1
74
74
63
58
75/25
70/30
70/30
71/29
Instrumentation
1H NMR spectra and 13C NMR spectra were recorded at 25 ◦C
with a Jeol ECX 400 MHz spectrometer.
—
5 mol%
1 mol%
5
5
44
Traces
79/21
General procedure for glycosylation reaction
N
the polarity of [BMIM][OTf] (ET = 0.656) is similar to that
of ethanol.22 As suggested by the hydrogen bond basicity
(b-value) of [BMIM][OTf] (b = 0.464), we presume that OTf
anion might stabilise the oxocarbenium ion as a specific solvent–
solute interaction.23 As a matter of fact, the interaction of ionic
liquid triflate with the oxonium cation was clearly evidenced
in the glycosylation using trichloroacetamidates as activating
anomeric groups.24 Other activating groups were recently used
with [BMIM][OTf] as versatile glycosylation promoter. In each
case the reaction goes through the oxocarbenium ion.25
Another aspect we wanted to explore was the recyclability
of the ionic liquid. Reactions were carried out using D-glucose
with octanol. The crude reaction was then filtered through a
silica gel pad and eluted with MeOH/AcOEt mixture to afford
the mixture of a and b glycosides, free from octanol and ionic
liquid. The ionic liquid is recovered by elution with more MeOH.
It could be used at least three times without loss of yield and
selectivity. The process still needs chromatography; we are aware
of this inconvenience, but we must highlight that it allows a total
retrieval of the ionic liquid.
A suspension of carbohydrate (0.5 mmol) and Lewis acid
(0.05 eq) in alcohol (5 eq) with or without ionic liquid (0.5 mL)
was heated at 80 ◦C for 24 h. The crude reaction was then filtered
through a silica gel pad eluting with 0 to 15% MeOH in AcOEt
to afford the desired glycoside as an anomeric mixture and then
to recover the ionic liquid.
NMR characterisation
Identification of the glycopyranosides obtained was done by
NMR. Spectroscopic data were identical with those previously
reported in the literature. a/b selectivity was determined from
1H-NMR spectra after addition of D2O in NMR sample.
Conclusion
A new method has been established for the synthesis of
O-glycopyranosides from unprotected and unactivated carbo-
hydrates and alcohols using a metal triflate as a catalyst. When
glycosylation was conducted in 1-butyl-3-methylimidazolium
trifluoromethanesulfonate better yields were obtained. The
notable feature of this procedure is the reusability of the ionic
liquid which makes it an eco-friendly chemical process for
the synthesis of glycopyranosides of synthetic importance. The
possibility of drastically reducing the amount of aglycone is
promising for the synthesis of more elaborate O-glycosides
with a-selectivity. Pure a-anomer could then be obtained after
enzymatic hydrolysis using b-glycosidase.
Finally, we also tried to reduce the quantity of catalyst and
glycoside acceptor used for our model reaction. In a one gram
scale reaction we have shown that catalyst amount could be
reduced down to 1 mol% in [BMIM][OTf] (Table 6). It is
interesting to note that a further decrease of the amount of
the catalyst down to 0.1 mol% brings about the formation of
non-negligible amounts of glycofuranosides.
Noteworthy, the model reaction performed with only one
equivalent of octanol and 1 mol% of Sc(OTf)3 gave the desired
product with a still satisfactory 58% yield. Without liquid ionic
a huge decrease of yield occurs when decreasing the quantity of
alcohol or catalyst.
Acknowledgements
We acknowledge the Agence Nationale (French) pour la
Recherche (ANR), sustainable chemistry program (CP2D-
GLYCENLI Project) for financial support.
Experimental
References
General methods
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