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

Chapter 2 – Dearomatising additions to aryl oxazolines
viewed as evidence of an SET reaction. One could dispute that rather than
representing a kinetic resolution of the s-BuLi in solution, that addition of both s-butyl
enantiomers is equally likely and that the bond rotation occurs in the butyl radical
before RC.
2.4.3 Aggregation in organolithium chemistry
Whilst the mechanistic studies are inconclusive, another area that might shed light on
understanding the dearomatising chemistry is the role of aggregates which are
implicated by the sensitivity of the reaction to the order of addition and solvent.
Aggregates form since a monodentate alkyl ligand is unable to adequately stabilise its
lithium counterpart, which is normally tetracoordinate. These aggregates can shift to
their entropically favoured state by the addition of Lewis bases, such as THF, TMEDA
and DMPU, which displace organic ligands around the cation. Deaggregation is often
associated with making organolithiums more reactive since the organic portion no
longer coordinates as many lithium centres, but this has been hard to prove. Indeed,
Collum has authored a critique of the triad of strong solvation, lower aggregation and
higher reactivity, by discussing examples of the behaviour of TMEDA in
organolithium reactions. 109
Collum highlights that the lower aggregation means higher reactivity assumption is
fundamentally flawed since by stabilising lower aggregates of organolithiums, one is
lowering the ground state energy of the reactants without necessarily lowering the
energy of the transition state. Since it is the transition state we hope to stabilise
observed increases in reaction rate cannot be used to infer lower aggregation. Indeed,
a stronger ligand binding lithium would be less labile and the cation disinclined to
coordinate the substrate.
Transition state stabilisation seems especially important when we consider that under
normal conditions, dearomatisation is a very unfavourable process and it is likely that
dearomatised intermediates require significant stabilisation. Hence the subtleties of
how stabilisation takes place are important, and might explain why only certain cosolvents
were found to assist dearomatisation. An example of a similarly solventspecific
effect was observed by Streitwieser who found that the aromatic enolate of p-
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