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

Chapter 4 – Synthesis of carbasugars
O
Ox*
OH
216
OH
Conditions
X
HO
HO
Ox*
OH
333
OH
Entry Conditions Result
a KOH (1M, aq) THF, Δ 22 hr nr
b KOH (3M, aq) THF, Δ 36 hr nr
c KOH (3M, aq) dioxane, Δ 36 hr nr
d KOH, d 6 -DMSO, rt, 2 hr nr
e KOH, d 6 -DMSO, 50 °C, 1 hr no isolable product
f KOH, d 6 -DMSO, 18-crown-6, rt, 2 hr no isolable product
g HCl (3M) THF, Δ 24 hr polymerised
h HCl (1M) THF, rt, 1 hr nr
i HCl (1M) THF, rt, 18 hr polymerised
j H 2 SO 4 (1M), THF, rt, 5 hr nr
k H 2 SO 4 (1M), THF, rt, 28 hr polymerised
m HClO 4 (1M), dioxane, rt, 28 hr 20% ester *
* rest SM, see section 3.2.4
Table 4.8 – attempted epoxide hydrolysis (route D)
Initial work attempted to repeat the above hydrolysis using the original and more
forcing conditions (entries a-c). The nucleophilicity of potassium hydroxide is
enhanced by the use of DMSO 208 which solvates potassium 185 making the counter ion
more reactive. At ambient temperature (entries d-f), no reaction was observed when
followed by 1 H NMR, however raising the temperature caused rapid decomposition of
the oxazoline ring. Similar degradation occurred when 18-crown-6 was added to the
reaction at ambient temperature.
Upon treatment with acid, the epoxyoxazoline rapidly turned to baseline salts (c. 10
min), and reverted back to starting material upon workup. This is most likely due to
protonation of the oxazoline which has previously been shown to be susceptible to acid
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