Hypervalent Iodine(III) Compounds as Biaxial Halogen Bond Donors

Flemming, H.; Engelage, E.; Cramer, C. J.; Huber, S. M.
J. Am. Chem. Soc. 2020, 142, 8633 (doi:10.1021/jacs.9b13309).

"Hypervalent" iodine(III) derivatives have been established as powerful reagents in organic transformations, but so far only few studies have addressed their use as halogen-bonding noncovalent Lewis acids. In contrast to "classical" halogen bond donors based on iodine(I) compounds, iodine(III) salts feature two electrophilic axes. Herein we present the first systematic investigation on biaxial binding to such Lewis acids in solution. Hindered and unhindered iodolium species were titrated with various substrates, including diesters and diamides, via ¹H-NMR spectroscopy and ITC. Clear evidence for biaxial binding was obtained in two model systems and the association strengths increased by two orders of magnitude. These findings were corroborated by DFT calculations (which reproduced the trend well but underestimated the absolute binding constants) and a co-crystal featuring biaxial coordination of a diamide to the unhindered iodolium compound.