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

Chapter 2 – Dearomatising additions to aryl oxazolines
2.2 Optimisation of Reaction Conditions
Having established that this chemistry is novel, the reaction conditions were reviewed
to improve the yield of dearomatised adduct, and reduce side reactions. For most of
these studies the para-anisole aromatic system was be used since it showed more
ortho-lithiation than the phenyl ring – the main side-reaction – and its aromatic protons
are easily distinguished by 1 H NMR. Isopropyllithium was generally used for these
test reactions since it gives single diastereoisomers with characteristic diastereotopic
methyl signals.
2.2.1 Solvent system
DMPU is a key additive for dearomatising addition, yet it is unclear whether its role is
simply to deaggregate the organolithium, or to promote a specific reactivity. A direct
comparison of the crude 1 H NMR spectra of reactions in the presence of DMPU,
TMEDA and no co-solvent was made (Table 2.2). HMPA was not studied since
Meyers had not been able to achieve dearomatisation using it, and due to its toxicity, 65
but has recently been found by Karlubíková to make little difference. 66
Ox*
i) i-PrLi (1.5 eq), THF
co-solvent (n eq)
Ox*
Ox*
Me
OMe
101b
ii) MeI
OMe
102b
OMe
103b
Co-solvent (eq) 102b / % 103b / % SM / %
None 22 73 4
TMEDA (6 eq) 23 72 5
DMPU (6 eq) 67 20 4
Table 2.2 – crude ratios of addition with different co-solvent
57