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

4.5 – Mannose synthesis
It is clear that if such an epoxide could be synthesised, selective hydrolysis would be
expected to yield an analogue of mannose with good regioselectivity. The next section
will discuss the synthesis of the diastereomeric epoxide by employing the lactonisation
previously discovered (section 4.2.8). This approach was chosen since it explores a
new method of oxazoline removal, and would complement the previous synthesis. It
should be noted that it would also possible to favour anti epoxidation by making the
silyl ether, 189 or by employing the Sharpless-Katsuki asymmetric epoxidation. 188
4.5.1 Strategy I: Lactonisation
It was recognised that lactonisation of diol 213 would leave only one hydrogen bond
donor to direct epoxidation in the newly formed bicycle 328 (Scheme 4.44). Simple
MM2 modelling indicates that whilst there is little to encumber the approach of the
oxidant to either face of the alkene, the pseudo-equatorial alcohol is well placed to
direct a hydrogen bonding reagent.
Ox*
MeOTf O
[O] O
O
OH
O
O
OH
OH
213 328 329
OH
Scheme 4.44 – proposed lactonisation-epoxidation & molecular model (MM2)
If successful, the resulting epoxide 329 should undergo diaxial hydrolysis to give an
analogue of mannose (Scheme 4.45). Whilst it might be possible to hydrolyse both the
epoxide and lactone in a single reaction, the resulting carboxylic acid would be
extremely polar and hard to isolate, instead a reduction-hydrolysis strategy is preferred.
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