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

2.3 – Synthetic scope
The presence of the ortho substituent causes a significant movement in the chemical
shift of the oxazoline protons; all non-ortho substituted oxazolines have characteristic
1 H chemical shifts very close to 5.4 and 5.2 ppm (C5 and C4 respectively, identified by
correlation spectroscopy), always 0.20 ppm apart. In contrast those of anisole 103b
are 5.31 and 5.26 ppm, separated by only 0.05 ppm. Whilst the coupling constants and
13 C NMR chemical shifts are similar to other aryloxazolines, the change in proton
chemical shift might be indicative of a subtle change in the oxazoline environment.
However since few ortho-substituted aromatic systems have been treated, no
correlation with reactivity many be inferred.
It is surprising that the electron-rich anisole derivatives were readily dearomatised
whilst a number of less demanding aromatic systems were not. Strong π-donors such
as methoxy reduce the electrophilicity of the arene by raising the energy of the LUMO,
and would also destabilise a transition state with a developing negative charge.
Generally groups which are relatively π-neutral such as Ph and F would not be
expected to differ from the unsubstituted ring. Meyers only published reactions with
methoxynaphthalenes, and whilst these are synthetically very versatile, it may be
assumed that other aromatic substituents were tried and failed.
2.3.3 Electrophiles
Equally important to the utility of the final compounds is the range of electrophiles
tolerated and the regioselectivity of their addition. Upon addition of the electrophilic
quench, immediate decolourisation was seen, indicating that reaction is rapid.
Regioselectivity was found to be dependent upon the nature of the electrophile, and is
summarised below. The products are identified as α, γ, ε by the site of addition with
respect to C=N, and a brief rationalisation of the selectivity follows.
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