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

3.2 – Oxazoline removal
Ph
Ph
O
N
H
O
BnO
Conditions
BnO
BnO
OBn
OBn
BnO
OBn
OBn
226
Time / d
(total d)
[Oxalic Acid] [Substrate] Temperature
Remaining
oxazolidine* / %
6 (6) 0.5 0.05 rt 88
2 (8) 0.0001 0.05 rt 87
3 (11) 0.5 0.1 rt 80
2 (13) 0.5 0.1 50 °C 67
* calculated from ratio of SM:aldehyde signal in 1 H NMR
Table 3.12 – acid-catalysed hydrolysis of the oxazolidine
Bundgaard and co-workers have conducted comprehensive studies of the hydrolysis of
oxazolidines, finding that whilst hydrolysis occurs in the pH range 2-9, it is fastest
under neutral or slightly alkaline conditions, and also shows a strong dependence on
buffer concentration. 144,145 Buffer solutions of acetate (pH 8) and borate (pH 9), as
well as a silica/THF/water slurry were used with no observable improvement, similar
results were found in the hydrolysis of 222 (Table 3.11). Addition of chloral as a
‘sacrificial’ aldehyde to the original acid conditions gave no rate enhancement.
As expected, study of reaction progress at elevated temperatures (Table 3.13) shows a
significant increase in the rate of hydrolysis, reaching an acceptable speed at around 60
°C, with a half life estimated as 2 days. The reaction was repeated at this temperature
and deemed complete within 7 days in 85% yield, with no significant decomposition of
the aldehyde noted (Table 3.13).
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