"The properties of organic molecules are defined by their shape and
functionality. However, the creation of such molecules with control
over both of these features is highly challenging. This proposal
describes novel methodology for simultaneous C-C bond formation with control
over shape (stereochemistry). In particular it focuses
on the stereoselective replacement of boron (which is easy to
introduce) to halides and other heteroatoms, and new ways for
cross-coupling to aromatics without the need for transition metals.
In order to promote the electrophilic halogenation of a boronic
ester, we envisaged the reaction of boronate complex with a halogen electrophile. In preliminary experiments such processes have already
been found to be viable and occur with complete stereoinversion.
Through tuning the nature of the aryl lithium one could envisage
selective halogenation of a broad range of substrates, giving access
to a myriad of stereodefined secondary alkyl halides, including
fluorides. Moreover, alcohols, amines derivatives, thioethers and
selenoethers could all be accessible by the reaction of these new
activated boronic ester ate complexes with suitable electrophiles.
The final part will focus on the (transition metal-free) cross
coupling of secondary alkylboronic esters. We present a conceptually new
approach to this challenging problem by considering the reaction of a
secondary boronic ester with an aryl lithium reagent. Following ate
complex formation, one-electron oxidation would result in
dearomatization leading to a radical cation which would trigger a
1,2-migration/rearomatization sequence. High stereointegrity can be
expected for such a process from the stereospecificity of the
1,2-sigmatropic rearrangement. Preliminary results have shown that
the concept is again viable but needs substantial optimization. This methodology will be applied to
challenges in synthesis."
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