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

4.2 – Carbasugar synthesis
As well as the expected oxazolidine, an almost equivalent amount of lactone 307 was
seen when the alkylation reaction was left overnight before reduction. This
unexpected product is clearly produced by base catalysed hydrolysis of the ammonium
salt 308 before reduction (Scheme 4.33) and is only possible due to the 1,4-cis
relationship between the oxazoline and the free alcohol. The bicyclic structure of 307
is corroborated by a 1 Hz 4 J H4-H6 “W-coupling”.
Ph
Ph
O
O
N
OH
216
OH
Ph
O
Ph
OH
H N O
O
OH
308
Scheme 4.33 – lactonisation of oxazoline 216
O
O
O
307
OH
The increase of lactone 307 with time shows that hydrolysis occurs under the
alkylation conditions rather than the mildly basic reduction. The hydrolysis is likely
catalysed by trace water which would facilitate proton transfers and is basic enough to
deprotonate the final protonated lactone. Hydrolysis of oxazolidine 306 proceeded
smoothly returning epoxycabasugar 309 in excellent yield over three steps. The rate of
reaction was consistent with the hydrolysis of earlier oxazolidines with the cis-1,4
pattern discussed.
O
Ph
O
N
OH
216
Ph
OH
MeOTf, 2 hr
then NaBH 4
O
Ph
H
H
O
OH
306
Ph
NMe
OH
i) (CO 2 H) 2 , THF/water
17 hr, 50 °C
ii) NaBH 4 , MeOH
O
HO
OH
OH 83%
3 steps
309
Scheme 4.34 – oxazolidine hydrolysis facilitated by 1,4-cis-hydroxyl group
156