Practical Synthesis of Hexopyranoses
145
Figure 2. Substrates and products.
manno- and gluco-type, were prepared as substrates. The results of the reductive ben-
zylidenation are shown in Table 1 (Figure 2).
To a solution of manno-type bromide 1 or 2 in acetonitrile was added 5 equiv of
sodium borohydride. The mixture was stirred for 30 min at reflux temperature to afford
1,2-O-benzylidene derivatives 5, 6 (entry 1, 2).a Under these conditions, gluco-type
bromides 3 or 4 were not converted to the corresponding 1,2-O-benzylidene derivatives
but gave complex mixtures.b Apparently, the oxocarbenium-ion intermediate, which is
necessary for the reductive acetalization, did not form when starting from 3 or 4, as it
did from the 1,2-cis glycosyl halide (entry 3,4). Addition of TBAI, which reacts with
the 1,2-cis glycosyl halide to give the 1,2-trans glycosyl halide, should be able to
promote the construction of a 1,2-O-benzylidene derivative from a 1,2-cis glycosyl
halide. However, using the previously reported conditions (NaBH4 1.5 mol, n-Bu4NI
0.5 mol, acetonitrile), the 1,2-O-benzylidene group was not produced at all and starting
materials 3 and 4 were recovered (entry 5, 6).c We thought that excess NaBH4 trapped
the iodide ion necessary for the halogen exchange of 1,2-cis glycosyl halide. This
hypothesis was supported by results of carrying out the reaction using excess TBAI
(entry 7, 8). Use of potassium iodide (KI) as an inexpensive iodide ion source was
much more effective for this reaction (entry 9, 10). In the reactions using KI, manno-
type glycosyl bromide 1 or 2 were converted at room temperature to the corresponding
1,2-O-benzylidene 5 and 6 in a satisfactory yield, respectively (entry 11, 12).
1
The structures of 1,2-O-benzylidene derivatives 5 and 6 were confirmed by H
NMR. A NOE was observed between H-2 and the methine proton of the benzylidene
aSelected spectral data for 3,4,6-tri-O-p-methoxybenzoyl-1,2-O-p-methoxybenzylidene-a-D-man-
nopyranose 6: 1H NMR (CDCl3) d 6.12 (dd, J3,4 = 10.1, J4,5 = 9.9 Hz, H-4), 5.95 (s, ben-
zylidene), 5.67 (dd, J2,3 = 3.5, J3,4 = 10.1 Hz, H-3), 5.58 (d, J1,2 = 1.8 Hz, H-1), 4.80 (dd, H-2),
4.65 (dd, J5,6a = 2.2, J6a,6b = 12.3 Hz, H-6a), 4.36 (dd, J5,6b = 3.3 Hz, H-6b), 4.10 (ddd, H-5);
3,4,6-tri-O-p-methoxybenzoyl-1,2-O-p-methoxybenzylidene-a-D-glucopyranose 8(R): 1H NMR
(CDCl3) d 5.92 (s, benzylidene), 5.87 (d, J1,2 = 5.1 Hz, H-1), 5.71 (dd, J2,3 = 2.9, J3,4 = 1.8
Hz, H-3), 5.50 (ddd, J2,4 = 1.1, J4,5 = 8.8 Hz, H-4), 4.62 (dd, J5,6a = 2.6, J6a,6b = 11.7 Hz,
H-6a), 4.52 (m, H-5), 4.45 (m, H-2), 4.41 (dd, J5,6b = 5.1 Hz, H-6b).
bAll of glycosyl bromides underwent decomposition, and the products were not isolated.
cA small amount of the glycal, 2,3,4,6-tetra-O-benzoyl-D-glucal was obtained in the heating
condition.