posted on 2021-06-24, 21:04authored byM. Zain
H. Kazmi, Jason P. G. Rygus, Hwee Ting Ang, Marco Paladino, Matthew A. Johnson, Michael J. Ferguson, Dennis G. Hall
Boron-containing
heterocycles are important in a variety of applications
from drug discovery to materials science; therefore a clear understanding
of their structure and reactivity is desirable to optimize these functions.
Although the boranol (B–OH) unit of boronic acids behaves as
a Lewis acid to form a tetravalent trihydroxyborate conjugate base,
it has been proposed that pseudoaromatic hemiboronic acids may possess
sufficient aromatic character to act as Brønsted acids and form
a boron oxy conjugate base, thereby avoiding the disruption of ring
aromaticity that would occur with a tetravalent boronate anion. Until
now no firm evidence existed to ascertain the structure of the conjugate
base and the aromatic character of the boron-containing ring of hemiboronic
“naphthoid” isosteres. Here, these questions are addressed
with a combination of experimental, spectroscopic, X-ray crystallographic,
and computational studies of a series of model benzoxazaborine and
benzodiazaborine naphthoids. Although these hemiboronic heterocycles
are unambiguously shown to behave as Lewis acids in aqueous solutions,
boraza derivatives possess partial aromaticity provided their nitrogen
lone electron pair is sufficiently available to participate in extended
delocalization. As demonstrated by dynamic exchange and crossover
experiments, these heterocycles are stable in neutral aqueous medium,
and their measured pKa values are consistent
with the ability of the endocyclic heteroatom substituent to stabilize
a partial negative charge in the conjugate base. Altogether, this
study corrects previous inaccuracies and provides conclusions regarding
the properties of these compounds that are important toward the methodical
application of hemiboronic and other boron heterocycles in catalysis,
bioconjugation, and medicinal chemistry.