Halogen bonding, the noncovalent interaction based on electrophilic halogen substituents, features very interesting properties, as illustrated by numerous applications continuously emerging in rece...

Catalysis of Organic Reactions through Halogen Bonding

Non-covalent molecular interactions on the basis of halogen and chalcogen bonding represent a promising, powerful catalytic activation mode. However, these "unusual" non-covalent interactions are typically employed in the solid state and scarcely exploited in catalysis. In recent years, an increased interest in halogen and chalcogen bonding has been awaken, as they provide profound characteristics that make them an appealing alternative to the well-explored hydrogen bonding. Being particularly relevant in the binding of "soft" substrates, the similar strength to hydrogen bonding interactions and its higher directionality allows for solution-phase applications with halogen and chalcogen bonding as the key interaction. In this mini-review, the special features, state-of-the-art and key examples of these so-called σ-hole interactions in the field of organocatalysis are presented.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/cctc.201901215

Frontiers in Halogen and Chalcogen‐Bond Donor Organocatalysis

Chalcogen bonding is the non-covalent interaction between Lewis acidic chalcogen substituents and Lewis bases. Herein, we present the first application of dicationic tellurium-based chalcogen bond donors in the nitro-Michael reaction between trans-β-nitrostyrene and indoles. This also constitutes the first activation of nitro derivatives by chalcogen bonding (and halogen bonding). The catalysts showed rate accelerations of more than a factor of 300 compared to strongly Lewis acidic hydrogen bond donors. Several comparison experiments, titrations, and DFT calculations support a chalcogen-bonding-based mode of activation of β-nitrostyrene.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/anie.201910639

Chalcogen Bonding Catalysis of a Nitro-Michael Reaction.

Asymmetric organocatalytic oxidations have been witnessed to an impressive development in the last years thanks to the establishment of important chiral hypervalent iodines(III/V). Many different a...

Chiral Hypervalent Iodines: Active Players in Asymmetric Synthesis.

The mechanism of the aryl iodide-catalyzed asymmetric migratory geminal difluorination of β-substituted styrenes (Banik et al. Science 2016, 353, 51) has been explored with density functional theory computations. The computed mechanism consists of (a) activation of iodoarene difluoride (ArIF2), (b) enantiodetermining 1,2-fluoroiodination, (c) bridging phenonium ion formation via SN2 reductive displacement, and (d) regioselective fluoride addition. According to the computational model, the ArIF2 intermediate is stabilized through halogen−π interactions between the electron-deficient iodine(III) center and the benzylic substituents at the catalyst stereogenic centers. Interactions with the catalyst ester carbonyl groups (I(III)+···O) are not observed in the unactivated complex, but do occur upon activation of ArIF2 through hydrogen-bonding interactions with external Bronsted acid (HF). The 1,2-fluoroiodination occurs via alkene complexation to the electrophilic, cationic I(III) center followed by C–F bond f...

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Mechanism and Origins of Chemo- and Stereoselectivities of Aryl Iodide-Catalyzed Asymmetric Difluorinations of β-Substituted Styrenes

Hypervalent iodine(III) derivatives are known as versatile reagents in organic synthesis, but there is only one previous report on their use as Lewis acidic organocatalysts. Herein, we present first strong indications for the crucial role of halogen bonding in this kind of catalyses. To this end, the solvolysis of benzhydryl chloride and the Diels-Alder reaction of cyclopentadiene with methyl vinyl ketone served as benchmark reactions for halide abstraction and the activation of neutral compounds. Iodolium compounds (cyclic diaryl iodonium species) were used as activators or catalysts, and we were able to markedly reduce or completely switch off their activity by sterically blocking one or two of their electrophilic axes. Compared with previously established bidentate cationic halogen bond donors, the monodentate organoiodine derivatives used herein are at least similarly active (in the Diels-Alder reaction) or even decidedly more active (in benzhydryl chloride solvolysis).

Iodine(III) Derivatives as Halogen Bonding Organocatalysts

In contrast to iodine(I)-based halogen bond donors, iodine(III)-derived ones have only been used as Lewis acidic organocatalysts in a handful of examples, and in all cases they acted in a monodentate fashion. Herein, we report the first application of a bidentate bis(iodolium) salt as organocatalyst in a Michael and a nitro-Michael addition reaction as well as in a Diels-Alder reaction that had not been activated by noncovalent organocatalysts before. In all cases, the performance of this bidentate XB donor distinctly surpassed the one of arguably the currently strongest iodine(I)-based organocatalyst. Bidentate coordination to the substrate was corroborated by a structural analysis and by DFT calculations of the transition states. Overall, the catalytic activity of the bis(iodolium) system approaches that of strong Lewis acids like BF 3 .

https://www.onlinelibrary.wiley.com/doi/pdf/10.1002/anie.202013172

A bidentate iodine(III)‐based halogen‐bond donor as a powerful organocatalyst

"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.

Hypervalent Iodine(III) Compounds as Biaxial Halogen Bond Donors

In recent years, the non-covalent interaction of halogen bonding (XB) has found increasing application in organocatalysis. However, reports of the activation of metal-ligand bonds by XB have so far been limited to a few reactions with elemental iodine or bromine. Herein, we present the activation of metal-halogen bonds by two classes of inert halogen bond donors and the use of the resulting activated complexes in homogenous gold catalysis. The only recently explored class of iodolium derivatives were shown to be effective activators in two test reactions and their activity could be modulated by blocking of the Lewis acidic sites. Bis(benzimidazolium)-based halogen bonding activators provided even more rapid conversion, while the non-iodinated reference compound showed little activity. The role of halogen bonding in the activation of metal-halogen bonds was further investigated by NMR experiments and DFT calculations, which support the mode of activation occurring via halogen bonding.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/ange.202005214

Activation of a Metal-Halogen Bond by Halogen Bonding

Motivated by the need to calculate liquid-phase free energies of species and equilibria involving halogen bonding, recent experimental data were used to optimize new Coulomb radii for Br and I for use in the SMD universal solvation model for calculating free energies of solvation The use of the SMD model with these parameters for Br and I and the SMD values of all other parameters is called SMD18 After parametrization, the SMD18 model was tested for data not used in the parametrization These data are standard-state free energies (equivalent to equilibrium constants) for 18 ionic equilibria involving Cl, Br, and I halogen bonding in acetonitrile, and the agreement of theory and experiment is satisfactory The SMD18 model is then used to compare hydrogen bonding to halogen bonding and to reassess the interpretation of recent experiments

Flemming Heinen

Papers

Iodine(III) Derivatives as Halogen Bonding Organocatalysts

A bidentate iodine(III)‐based halogen‐bond donor as a powerful organocatalyst

Hypervalent Iodine(III) Compounds as Biaxial Halogen Bond Donors

Activation of a Metal-Halogen Bond by Halogen Bonding

Refined SMD Parameters for Bromine and Iodine Accurately Model Halogen-Bonding Interactions in Solution.