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

Chapter 2 – Dearomatising additions to aryl oxazolines
2.4.2.b Radical trap
Internal radical traps are commonly used as mechanistic probes and may be attached to
either the nucleophile or the electrophile. They have often been used to measure the
rate of reaction (radical clocks), but since we are mainly interested in a qualitative
understanding of the reaction such studies will not be made. The radical trap must be
stable under the reaction conditions and the resulting radical should not propagate any
reaction; halogens or dithianes are often used to trap reaction intermediates, but would
also be likely to react under the conditions. Methylcyclopropanes are also often used
but their use as mechanistic probes has been discouraged since non-radical
intermediates have been reported to trigger ring opening. 92
Appending a probe to the oxazoline is preferred since it is synthetically easier, and a
broader range of aromatic substituents have been tolerated than have nucleophiles.
The group that seems best suited is the allyl group since its behaviour in the presence
of organolithiums has been thoroughly studied and its products should be stable and
readily characterised. Allyl ether 101j (Scheme 2.27) is well suited to the task. The
meta-anisole analogue 101c dearomatised in good yield and complete regioselectivity,
whilst O-allylphenol radical 133 is one of the fastest cyclisation probes, 93 with a halflife
determined by Ingold of 0.1 ns at 30 °C 94 (c. 10 ns at –80 °C). 95 Whilst the radical
anion intermediate is likely to be similar to that of benzene (Scheme 2.25), a useful
approximation of the rate of cyclisation of an alkyl radical is given by heptene radical
134. 96 Allyl ether 101j is preferred to the homoallyl analogue because it undergoes
cyclisation more rapidly 94 and it would be prone to benzylic lithiation which might
influence the reactivity of the aromatic system.
Ph
O
N
Ph
133
O
k = 6.3 x 10 9 s -1
t ½ ~0.1 ns
30 °C
O
t ½ ~10 ns
−80 °C
101j
O
134
k = 1.3 x 10 5 s -1
t ½ ~5 ms
25 °C
t ½ ~1 s
−80 °C
Scheme 2.27 – proposed allyl ether radical trap & rate of cyclisation 94
81