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Y. Liu et al. / Tetrahedron Letters 57 (2016) 2758–2762
Table 2 (continued)
Entry
Nucleophile
Reaction time
30 min
Product
Yieldb (%)
a
:bc
HO
OAc
O
AcO
2n
OBn
FmocHN
O
O
14
15
75
>99:1
94:6
OBn
FmocH2HN
3n
OAc
O
O
OH
AcO
2o
O
3o
20 min
68
SH
OAc
O
2p
AcO
AcO
16
17
20 min
30 min
80
78
83:17
95:5
S
3p
SH
OAc
O
2q
S
3q
OH
OAc
O
O
O
AcO
O
2r
O
O
O
O
18
50 min
78
76
94:6
93:7
O
O
O
O
3r
O
OAc
O
HO
O
2s
AcO
O
O
O
19
30 min
O
O
O
O
O
3s
O
a
Reaction conditions: tri-O-acetyl-
D-glucal (200 mg, 0.73 mmol), EtOH (1.2 equiv), Hf(OTf)4 (10 mol %), solvent (5 mL), 40 °C.
b
c
Isolated yield by flash column chromatography on silica gel.
The anomeric ratio was determined by integration of the anomeric hydrogen in the 1H NMR spectra.
camphorsulfonic acid (CSA), TfOH-SiO2, 3,5-dinitro benzoic acid
(DNBA), and other catalysts13 such as iodonium dicollidinium per-
chlorate (IDCP), NIS, ceric(IV) ammonium nitrate (CAN), H2O2, Pd
(OAc)2, Zn, and pyridinium bromide salts. However, some of these
methods suffered from the drawbacks in terms of harsh reaction
conditions, excess amount of sensitive catalysts, and low yields.
Therefore, exploration of efficient promoters for this reaction is
still a challenge. Previous studies show that Hafnium(IV) triflate
was an efficient promoter in many reactions such as the
Friedel–Crafts acylation, Fries rearrangement, hydroamination,
thioacetalization, transthioacetalization, N-aminomethylation,
and Prins-type cyclization.14 Herein, we report a more practical
Ferrier rearrangement using Hafnium(IV) triflate as an efficient
Lewis acid catalyst.
To test the feasibility of this approach, various alcohols (2a–s)
were further applied under the optimized condition to the synthe-
sis of corresponding 2,3-unsaturated glycosides. The Ferrier rear-
rangement was performed between tri-O-acetyl
D-glucal(1)
(1 equiv) and various nucleophiles (1.2 equiv) at 40 °C, with
Hafnium(IV) triflate (10 mol %) as the catalyst and THF as the
solvent. As presented in Table 2, the substrate scope of various
linear alkyl alcohols (Table 2, entries 1–3) gave the products with
higher yields, while the branched alkyl alcohols (Table 2, entries
4, 5 and 8) with lower yields but higher stereoselectivity.
Functionalized alkyl alcohols (Table 2, entries 6 and 7) gave the
products with higher yield and better stereoselectivity, while
aromatic alcohols (Table 2, entries 10, 11 and 15) and adaman-
tanemethanol (Table 2, entry 12) with a higher steric hindrance
gave the products with higher stereoselectivity but lower yields.
The reactions of glucal with amino acids (Table 2, entries 13 and
14) were investigated. Interestingly, the glycosylated serine and
threonine building blocks were synthesized with almost a single
Our Initial studies started with tri-O-acetyl-D-glucal (1) as the
donor and EtOH as the nucleophile in a model system catalyzed
by Hf(OTf)4. As reaction medium has influence on the reaction,
we then paid efforts to screen the best reaction solvents among
CH3CN, CH2Cl2, THF, Et2O, dioxane, 1,2-dichloro ethane (DCE),
and toluene. As shown in Table 1, the ratio and the yield of desired
target compound varied. After stirring at 40 °C in THF and Et2O for
10 min, the corresponding 2,3-unsaturated glycoside was obtained
in an isolated yield of 96% and 90%, respectively.
a
configuration. Thio-phenol (Table 2, entry 16) and thiol (Table 2,
entry 17) were used as nucleophile to provide the corresponding
thioglycosides with satisfactory anomeric selectivity. For entry 9,
it was hypothesized that the catalyst was quenched by the
substrate, leading to the reactivity loss of Hf(OTf)4.