Heinen Flemming, Engelage Elric, Cramer Christopher J, Huber Stefan M
Fakultät für Chemie und Biochemie, Organische Chemie I, Ruhr-Universität Bochum, Universitätsstraße 150,44801 Bochum, Germany.
Department of Chemistry, Chemical Theory Center, and Minnesota Supercomputing Institute, University of Minnesota, 207 Pleasant Street SE, Minneapolis 55455-0431, Minnesota, United States.
J Am Chem Soc. 2020 May 13;142(19):8633-8640. doi: 10.1021/jacs.9b13309. Epub 2020 Apr 29.
"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 H 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.
“高价”碘（III）衍生物已被确立为有机转化中的强大试剂，但迄今为止，仅有少数研究涉及其作为卤素键合非共价路易斯酸的潜在用途。与基于碘（I）化合物的“经典”卤素键供体不同，碘（III）盐具有两个相互垂直的定向亲电轴。在此，我们展示了对溶液中此类路易斯酸双轴结合的首次系统研究。为此，通过核磁共振氢谱（¹H NMR）和等温滴定量热法，用包括二酯和二酰胺在内的各种底物滴定受阻和未受阻的碘鎓物种。在两个模型体系中获得了双轴结合的明确证据，且缔合强度增加了2个数量级。这些发现得到了密度泛函理论计算（该计算很好地重现了趋势，但低估了绝对结合常数）以及一个二酰胺与未受阻碘鎓化合物双轴配位的共晶体的证实。
