ranoside (7) in DMF was treated with t-BuOK at room
temperature, yielding the expected product 8 in 80% isolated
yield (entry 4). Likewise, the rearranged product 10 was
obtained in quantitative yield from n-propyl 2,3-anhydro-
4,6-O-benzylidene-1-thio-â-D-mannopyranoside (9) (entry
5).13 All the substrates mentioned above were S-glycosides.
Hence, next, we examined O-glycosides in this rearrange-
ment. When a mixture of phenyl glycoside 11,14 t-BuOK,
and tetrabutylammonium bromide in DMF was heated at 90
°C, a reaction did occur, and unsaturated sugar 12 was
obtained in which the double bond was located between C-3
and C-4 in the carbohydrate, not between C-1 and C-2 (entry
6). When methyl glycoside 1315 was treated with t-BuOK
in DMF at 80 °C, a similar result was obtained, with
compound 1416 being in 64% isolated yield (entry 7). To
further investigate the scope of the rearrangement, two
furanosides were chosen as the substrates. As shown in Table
1, both p-tolyl 2,3-anhydro-1-thio-â-D-ribofuranoside (15)17,18
and p-tolyl 2,3-anhydro-1-thio-R-D-lyxofuranoside (17)18,19
produced the same furan derivative 16, presumably from
aromatization of the rearranged unsaturated sugar (entries 8
and 9).
Scheme 1. Synthesis of 2,3-Anhydro â-D-Allopyranoside 1
methanol (Scheme 1), was chosen as the substrate for
rearrangement (Scheme 2). Initially, when NaOH, K2CO3,
Scheme 2. Base-Induced Rearrangement of Sugar Epoxide 1 to
Unsaturated Sugar 2
The methyl glycosides 18,15b,c,20 19,15b,21 and 2022 (Figure
1) were also used as the substrates to test the rearrangement.
and tetrabutylammonium bromide were added to a solution
of epoxide 1 in toluene/DMSO/n-butanol (V/V/V ) 20/1/
0.4) at room temperature, the reaction proceeded very
smoothly to give the unsaturated sugar 2 in almost quantita-
tive yield. The structure of 2 was unambiguously determined
by its 1D and 2D NMR spectral analyses. When DMSO was
omitted, the reaction occurred slowly. However, this draw-
back could be overcome by raising the reaction temperature.
We also found that K2CO3 alone could not promote the
reaction and that K2CO3 was not even necessary for this
conversion. Thus, treatment of 1 with NaOH in toluene/n-
BuOH at reflux in the presence of tetrabutylammonium
bromide yielded, within 1 h, 2 in 99% isolated yield (Table
1, entry 1). After the success of this example, we next
examined other carbohydrate epoxide substrates in the
aforementioned rearrangement. All the 2,3-anhydro pyrano-
sides were prepared by a procedure similar to that used for
the preparation of 1. As illustrated in Table 1, p-tolyl 2,3-
anhydro-4,6-O-benzylidene-1-thio-â-D-mannopyranoside (3)
reacted under the same conditions to give to a similar
isomerized product 4 (82% isolated yield) (entry 2). When
p-tolyl 2,3-anhydro-4,6-O-benzylidene-1-thio-â-D-gulopyra-
noside (5) was reacted under these conditions, the reaction
occurred very slowly. However, the reaction speed increased
after a small amount of DMF was added, and the reaction
was complete within 0.5 h (entry 3). When thioglycoside
712 was used as a substrate under the above-mentioned
conditions, no isomerized product was detected. We therefore
changed the base and solvent. Eventually, a solution of
n-propyl 2,3-anhydro-4,6-O-benzylidene-1-thio-â-D-allopy-
Figure 1. Epoxides incapable of rearrangement under the same
conditions.
But under the above conditions, the reaction did not occur
for all three epoxide reactants. On the basis of these
(13) Compounds 7 and 9 are a chromatographically inseparable mixture;
therefore a mixture of 7 and 9 (ratio 1:1) was used for the rearrangement,
yielding 8 and 10. The yield of compound 10 is based on NMR analysis.
See also Supporting Information.
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7334. (c) Probert, M. A.; Zhang, J.; Bundle D. R. Carbohydr. Res. 1996,
296, 149-170.
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2899.
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3052.
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5774-5777.
(12) For the synthesis of pure compound 7, see Supporting Information.
(22) (a) Guthrie, R. D.; Liebmann, J. A. J. Chem. Soc., Perkin Trans. 1
1974, 6, 650-657. (b) Jesudason, M. V.; Owen, L. N. J. Chem. Soc., Perkin
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Org. Lett., Vol. 7, No. 25, 2005