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

2.3 – Synthetic scope
2.3 Synthetic Scope
Until now, most reactions have used secondary organolithiums isopropyllithium and
sec-butyllithium, only two aromatic substituents and iodomethane as electrophilic
quench. For the reaction to be synthetically useful, it should be general to a number of
nucleophiles, electrophiles and tolerate a number of aryl groups.
2.3.1 Organolithiums
2-Phenyl oxazoline 101a was treated with a number of commercially available
organolithiums. The results are summarised below.
Ox*
i) NuLi (1.5 eq),
THF, DMPU (6eq)
−78 °C 5 min
Ox*
Nu
ii) MeI
101a 102a
Entry Nu 102a (SM) / % Lithiated Colour
a n-Bu < 5 (95) 0 Electric blue
b 64 Me < 5 (95) 0 –
c † Me 3 SiCH 2 1 (45) 22 Electric blue
d s-Bu 81 * (1) 8 Dark green
e i-Pr 70 (12) 6 Dark green
f 70 t-Bu 17 (12) 17 Dark green
g 64 PhLi < 5 (95) 0 –
† addition to 101b (Scheme 2.9) * 3:1 exocyclic d.r.
Table 2.7 – survey of organolithium nucleophiles
Primary alkyllithiums (entries a-c) show little or no dearomatisation, indeed diene was
only isolated from addition of (trimethylsilyl)methyllithium (Scheme 2.9). This
reaction saw mainly benzylic lithiation, previously unseen for these oxazolines,
predominantly at the aza-allylic C4 position (117). Diene 102b” is tentatively
assigned by 1 H, COSY and mass spectroscopic data, similar results were seen when
solvated in toluene.
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