Chemistry Reference
In-Depth Information
TABLE 5.1 Optimisation of the Click Reaction
Entry
Alkyne
DIPEA
Na Ascorbate
Catalyst
Solvent
Time
Yield
1
1 eq
3 eq
None
0.2 eq CuI
THF
2h
No reaction
2
1.2 eq
4 eq
None
0.2eq CuI
THF
4h
55%
3
1 eq
3 eq
None
2 eq CuI
CH
3
CN
1h
49%
4
1 eq
None
0.4 eq
0.2eq CuSO
4
sec
But
3h
No reaction
5
1 eq
None
0.4 eq
0.2eq CuSO
4
sec
But/H
2
O
1.1h
71%
6
1 eq
None
0.4 eq
0.2eq CuSO
4
DMF
2h
No reaction
7
1 eq
None
0.4 eq
0.2eq CuSO
4
DMF/H
2
O
1.5h
88%
commonly used in carbohydrate chemistry. Moreover, the reaction was conducted
at room temperature, using an equimolar ratio of reagents, and the corresponding
products were obtained in high yields. Due to the high solubility of protected sugars
in N,N-dimethylformamide (DMF), the addition of water to the solvent, up to 30%,
greatly accelerated the cycloaddition reaction between
17
and
18
(Table 5.1). Fur-
thermore, we changed the distance between the triazole-linked saccharide units by
the introduction of an appropriate spacer (Scheme 5.7).
The reaction between glycosyl azides and alkynyl glycosides can be acceler-
ated by the addition of Cu(II) sulfate pentahydrate and sodium ascorbate in 1:1
tert-Butanol/water, which results in the formation of triazole derivatives
33
and
35
in
78% and 85% yield, respectively (Scheme 5.8) [30].
Tripathi's group [31] synthesized 1,2,3-1
H
-triazolyl glycohybrids, such as
36
and
38
, by CuAAC coupling of glycosyl azides with 2,3-unsaturated alkynyl glycosides,
obtained by Ferrier's rearrangement of glycals (Scheme 5.9). Some of these products
(and others like
37
and
39
, containing coumarin residues) showed to be inhibitors of
-glucosidase, glycogen phosphorylase and glucose-6-phosphatase.
The reaction with internal alkynes, however, occurred only under thermal con-
ditions (refluxing toluene) and hence, mixtures of the regioisomers were obtained
(Scheme 5.10).
In an interesting approach to sustainable chemistry, the first study of a Cu(I)-
catalyzed azide-alkyne click reaction in ionic liquids, was reported by Marra et al.
[32]. The cycloaddition of a sugar azide with a sugar acetylene (Cu(I), DIPEA, 80
◦
C)
was achieved in high yields (up to 95%) using Ammoeng 110 and [C
8
dabco][N(CN)
2
]
among other ionic liquids (Scheme 5.11). The latter solvent was recycled in four
subsequent reactions without loss of reaction efficiency. The authors investigated the
role of DIPEA, used as an additive, whose presence seems to be crucial in the case
of non-basic ionic liquids.
Nitrogen donors including bases such as DIPEA, and some solvents such as
acetonitrile, have been reported to improve the reaction when Cu(I) is used as a
catalyst by helping to prevent degradation of Cu(I) by disproportionation or oxidation
[33].
A
-sialic acid azide derivative has been used as a substrate for the efficient
preparation of 1,2,3-triazole derivatives of sialic acid. These products would act as
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