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

2.3 – Synthetic scope
Ph
O
Ph
NLi
R ≈
α
β
γ ε
δ
121
Scheme 2.16 – approximation of the HOMO of the azaenolate
However the hard protic quench of azaenolate 121 shows complete regioselectivity for
the ε position (entry e). This is be explained if proton addition is in equilibrium, since
102ε has the longest conjugated system; also explaining why α-protonation is not seen.
Unfortunately, protonation of para-substituted oxazolines (entries f, g) does not
support thermodynamic protonation, however a change in solvent and method of
protonation means that further experimentation would be necessary to gain further
insight.
This is consistent with the reaction of electrophiles with 2-oxazolinylnaphthalene
azaenolate 122, by Meyers. Whilst iodomethane also gave α addition, protonation
gave the thermodynamic product 124 in low yield, accompanied by rearomatisation. 26
Nu
122
O
N
Li
MeI
MeOH
Nu
Nu
O
N
Me
O
N
124
Nu = n-Bu 90%
= s-Bu 91%
= t-Bu 90%
Nu = n-Bu 18%
= t-Bu 31%
= Ph 74%
Scheme 2.17 – electrophilic quench of 2-oxazolinylnaphthalenes 26
Meyers observed regiospecific α addition to the azaenolates of 1-
oxazolinylnaphthalenes for a large range of electrophiles (section 1.3.2). This is most
likely because the HOMO is likely to be confined to the non-aromatic carbons;
although Ortiz 1 makes the unlikely suggestion that it is a complex-induced proximity
effect (CIPE). 38 Whilst the principle of least motion analysis is often applied to
rationalise the protonation of the hydrobenzene anion in the Birch reduction, it cannot
be applied to this situation since the resonance structures will not contribute equally.
72