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

3.2 – Oxazoline removal
Ph
Me
Ph
Me
Ph
Me
O
N
O
N
O
N
230
t ½ (pH 7.4)
0.08
0.3
30
min
t ½ (pH 1.0)
96
70
-
min
144
Scheme 3.37 – half-lives of some oxazolidines at 37 °C
This work clearly shows that a β-quaternary centre on the aldehyde clearly retards
hydrolysis, but the half lives reported are still shorter than those observed for alcohol
222 let alone benzyl ether 226. When looking at the role of amino alcohol substitution,
Bundgaard also found that substitution α to nitrogen led to significant retardation, with
geminal methyl groups causing a 50 times increase in half life than a simple
methylene. However, whilst they did not compare a phenyl group with a methyl
group, it is unlikely to be responsible for such a difference. In addition, recent
calculations by Walker based upon this research shows that cis substituted
oxazolidines hydrolyse more rapidly than their trans epimer, but do not quantify
this. 148
Whilst these combined effects might explain why the diphenyl oxazolidine with an
adjacent quaternary centre hydrolyses much more slowly than many apparently similar
oxazolidines, it does not explain the difference with the similarly substituted Meyers
oxazolidine. Furthermore, the reaction does not seem to share the same pH
dependence as Bungaard reported, meaning that it is possible that a change in
mechanism has occurred. Two pathways for hydrolysis are considered (Scheme 3.38).
126