Benzosiloxaboroles: Silicon Benzoxaborole Congeners with Improved Lewis Acidity, High Diol Affinity, and Potent Bioactivity

The
synthesis and physicochemical properties of benzosiloxaboroles,
the silicon analogues of an important class of heterocyclic compoundsbenzoxaborolesis
presented. They were prepared by halogen–lithium exchange reactions
of (2-bromophenyl)­boronates with n-BuLi followed
by the silylation or boronation of (2-lithiophenyl)­dimethylsilanes.
The cyclization of the resulting 2-(dimethylsilyl)­phenylboronates
apparently occurs through intramolecular dehydrogenative cyclization
reaction in the presence of water. Unlike the case for benzosiloxaborole,
the formation of its analogue containing a thiophene ring is thermodynamically
unfavorable, which was confirmed by theoretical calculations. The
presence of a B–O–Si linkage results in increased Lewis
acidity with respect to the analogous benzoxaboroles. The acidity
is strongly enhanced by fluorination or introduction of phenyl groups
at the silicon atom. Selected compounds show good antifungal activity,
and thus they are potential small-molecule therapeutic agents. They
can also serve as effective receptors for biologically relevant diols
under neutral pH conditions.