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

Chapter 2 – Dearomatising additions to aryl oxazolines
Ox*
i) s-BuLi (1.5 eq)
−78 °C, DMPU (6 eq)
solvent
Ox*
Ox*
ii) MeI
R
R
R
101 102' 116'
Solvent R 102’ / % 116’ / % SM / %
THF H 81 0 5
PhMe H 66 5 20
THF OMe 71 7 5
PhMe OMe 50 10 20
Table 2.3 – isolated yields comparing toluene and THF as solvents
Although no ortho-lithiation was observed in toluene, less diene was isolated and a
significant amount of rearomatised adduct (116’). This is most likely due to proton
abstraction from the methyl group of the solvent which also explains the increased
amount of recovered starting material, since any ortho-lithiated oxazoline may simply
abstract a proton from the solvent. Whilst this in-situ regeneration of starting material
is appealing, it is more than offset by the losses in the formation of rearomatised 116’.
Other solvents such as DMPU, benzene and hexane, were tried but the reaction failed
either due to poor solvation, or freezing under the reaction conditions. Cumene
presents itself as a less acidic alternative to toluene but initial reactions have shown
little improvement. 66 The role of solvent and aggregation state is discussed in section
2.4.3.
59