A Route to Carbasugar Analogues - Jonathan Clayden - The ...

4.2 – Carbasugar synthesis
Ox*
Ox*
Ox*
NaBH 4
O
OH
T °C
OH
OH
OH
OH
quant.
276 213
287
Entry T Conditions Reaction time 213 : 287
a rt + CeCl 3 .7H 2 O 10 min 8 : 1
b 0 + CeCl 3 .7H 2 O 20 min 10 : 1
c –60 + CeCl 3 .7H 2 O 60 min 5 : 1
d 0 – 30 min 10 : 1
e 0 – 6 hr > 20 : 1
Table 4.3 – borohydride reduction of the hydroxyenone
The stereoselectivity of the reductions do not correlate with either reagent or
temperature, but instead correlate strongly with the time of the reaction. Whilst this
was initially puzzling, it was found that enone 276 does not visualise well under either
UV irradiation or permanganate stain, but only under the molybdenate-based PMA
stain. When reactions were monitored using PMA stain, it was found that the reaction
was considerably slower than previously believed. Since sodium borohydride only
decomposes slowly in aqueous ammonium chloride, 183 which had been used to quench
the reactions, it is believed that unreacted borohydride species were responsible for the
loss of diastereoselectivity upon warming in entries a-d. When appropriate, future
reductions were quenched with acetic acid.
Under the mildly basic Luche conditions (entries a-c) it was found that the enone was
prone to oxidation to small amounts of dienone 283 (Scheme 4.15). This could be
countered by conducting the reaction at lower pH, which has been shown have little
effect on the regioselectivity. 178
The structure of 213 was confirmed by x-ray
diffraction.
146