“Triply Activated” Phenyl 3-Iodopropiolates: Halogen-Bond Donors with Remarkable σ-Hole Potentials

Abstract

The ability of halogen-bond donors to form strong and directional intermolecular interactions remains integral to their prospects of becoming reliable synthetic tools for the bottom-up assembly of functional materials. An activation strategy involving three different electron-withdrawing groups in parallel, was employed in order to develop new halogen-bond donors possessing some of the highest σ-hole potentials reported to date.

Halogen-Bonded Supramolecular Parallelograms: From Self-Complementary Iodoalkyne Halogen-Bonded Dimers to 1:1 and 2:2 Iodoalkyne Halogen-Bonded Cocrystals

“…16,17 We also demonstrated the formation of halogen-bonded parallelogram-shaped self-complementary dimers from appropriately oriented pyridylsubstituted polyfluoro iodobenzenes. 18,19 In this study, we focus on iodoalkynes that are excellent halogen bond donors, 20,21 with the caveat that they are, however, occasionally somewhat more fugitive during preparation. 22 Accordingly, we report here the formation of parallelogram-shaped dimers featuring iodoalkynes as the halogen bond donor and further extend this to the intentional formation of 1:1 and 2:2 cocrystals that feature parallelogramshaped supramolecular macrocycles using deliberate combinations of bis-iodoalkynes and bipyridines.…”

Principles and Applications of CF2X Moieties as Unconventional Halogen Bond Donors in Medicinal Chemistry, Chemical Biology, and Drug Discovery

“…Halogen bonds (XB) are highly directional interactions between the electropositive region on the halogen (X = Cl, Br, I), the σ-hole, and a nucleophilic interaction partner (B), typically an atom containing one or more nonbonding electron pairs, a π-system, or an anion . Aryl halides with an sp 2 -hybridized carbon–halogen (C­(sp 2 )–X) moiety or ethynyl halide species (C­(sp)–X) form halogen bonds, which are well studied in organocatalysis, − crystal engineering, − biological systems, − and medicinal chemistry. − …”

N−X⋅⋅⋅O−N Halogen Bonds in Complexes of N‐Haloimides and Pyridine‐N‐oxides: A Large Data Set Study

“…However, the significance of X•••O(carbonyl/ether) interactions has been demonstrated in protein-drug complexes [54,55] and crystal engineering. [56][57][58][59][60][61][62][63][64] These X•••O interactions can be classified as weak and moderate XBs with interaction energies 0.5-20 kJ mol À 1 and ~20-60 kJ mol À 1 , respectively. Compared to XB research on X•••N, X•••O systems that utilize pyridine N-oxides (PyNOs), the oxidised products of the parent pyridines, as the XB acceptors in CÀ I••• À OÀ N + or NÀ I••• À OÀ N + systems is surprisingly scarce.…”

“…Compared to the much more explored C−I⋅⋅⋅N XB systems, [44] oxygen atom as an XB acceptor has not attracted so much intention due to its lower nucleophilicity and inherent polydentate nature and electron ′′push‐pull′′ property (Figure 2). However, the significance of X⋅⋅⋅O(carbonyl/ether) interactions has been demonstrated in protein‐drug complexes [54,55] and crystal engineering [56–64] . These X⋅⋅⋅O interactions can be classified as weak and moderate XBs with interaction energies 0.5–20 kJ mol −1 and ~20–60 kJ mol −1 , respectively.…”