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

4.2 – Carbasugar synthesis
support to the formation of diene 284 – (Scheme 4.15) via a single deprotonation. Even
though this seems unlikely as the secondary alcohol might be expected to be both
kinetically and thermodynamically more acidic, it is consistent with the pKas of related
compounds in DMSO, and with the observation of the dienone in relatively neutral
condition (Table 4.2). Anion 284 – would receive additional stabilisation from
delocalisation of its charge; consistent with the strong hydrogen bonding seen in the IR
and 1 H NMR spectra of 276.
The formation of dienone 283 in the oxidation of the enol ether even under weakly
acidic conditions (entry b, Table 4.2), makes the absence of the diastereomeric epi-276
conspicuous; raising the possibility that the dienone formed under these conditions
comes from oxidation of the opposite face (285, Scheme 4.16). Further oxidation
might then take place under the reaction conditions or upon workup; below are the
equilibria present in the reaction, again intermediate 284 would be susceptible to
further oxidation.
Ox*
Ox*
[O]
Ox*
−H +
Ox*
+H +
OH
284
OH
O
283
OH
MeO
OH
OH
285
H
O
OH
−H +
Ox*
OH
O
epi-276
Scheme 4.16 – proposed in-situ oxidation of epi-276
Oxidation of olefins to α-diketones is known to occur under Upjohn conditions 176
although hemiacetal 285 – the product of disfavoured syn oxidation – would not be
amenable to further oxidation. Rapid hydrolysis of 285 would give epi-276, which is
not isolated, but might be even more sensitive to base than 276 (vide supra) and
readily tautomerise to diene 284, which might oxidise to the dienone under the reaction
conditions.
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