Hypervalent Iodine(III) Compounds as Biaxial Halogen Bond Donors

“Hypervalent”
iodine­(III) derivatives have been established as powerful reagents
in organic transformations, but so far only a handful of studies have
addressed their potential use as halogen-bonding noncovalent Lewis
acids. In contrast to “classical” halogen-bond donors
based on iodine­(I) compounds, iodine­(III) salts feature two directional
electrophilic axes perpendicular to each other. Herein we present
the first systematic investigation on biaxial binding to such Lewis
acids in solution. To this end, hindered and unhindered iodolium species
were titrated with various substrates, including diesters and diamides,
via 1H NMR spectroscopy and isothermal titration calorimetry.
Clear evidence for biaxial binding was obtained in two model systems,
and the association strengths increased by 2 orders of magnitude.
These findings were corroborated by density functional theory calculations
(which reproduced the trend well but underestimated the absolute binding
constants) and a cocrystal featuring biaxial coordination of a diamide
to the unhindered iodolium compound.