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

Chapter 2 – Dearomatising additions to aryl oxazolines
2.1.1 Summary of initial reactions
Whilst the dearomatising addition of organolithiums was possible with three of the five
oxazolines, the anti-diphenyl oxazoline is clearly best at promoting the
dearomatisation. Failure of the cis oxazoline (109) after repeated attempts shows that
the trans geometry is key, whilst the benzylic lithiation of the Meyers (104) and
norephedrine (110) oxazolines indicate that the diphenyl system may be successful due
to the mutual hindrance of C4 and C5. Mechanistically, the pseudo-C 2 nature of
oxazolines 101 offers a very appealing rationale for the high levels of
diastereoselectivity observed, although equally high diastereoselectivity was seen with
anti-oxazolines 104 and 110.
The other key component in the reaction is the DMPU co-solvent. DMPU has been
used extensively in organolithium chemistry, largely as a less toxic substitute for
HMPA. 65 It is a Lewis basic ligand for lithium, donating electron density through its
oxygen lone pairs, purportedly making the organolithium more reactive through
deaggregation, which is discussed at the end of the chapter.
Oxazolines are traditionally used to direct ortho-metalation, and Scheme 2.3 shows
that it might be possible to tune the reactivity of the aromatic ring, permitting
functionalisation before dearomatisation. Addition of a range of Grignard reagents
was also attempted to anisole 101b, but neither dearomatisation nor nucleophilic
aromatic substitution were observed and only starting material was isolated. Finally,
Table 2.1 shows that the six reactions in which dearomatisation occurred had similar
opaque brown/green solutions such as that shown below.
Scheme 2.6 – crystal structure and reaction solution of 102b
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