Catalysis with Pnictogen,Chalcogen, and Halogen Bonds

Halogen‐ and chalcogen‐based σ‐hole interactions have recently received increased interest in non‐covalent organocatalysis. However, the closely related pnictogen bonds have been neglected. In this study, we introduce conceptually simple, neutral, and monodentate pnictogen‐bonding catalysts. Solution and in silico binding studies, together with high catalytic activity in chloride abstraction reactions, yield compelling evidence for operational pnictogen bonds. The depth of the σ holes is easily varied with different substituents. Comparison with homologous halogen‐ and chalcogen‐bonding catalysts shows an increase in activity from main group VII to V and from row 3 to 5 in the periodic table. Pnictogen bonds from antimony thus emerged as by far the best among the elements covered, a finding that provides most intriguing perspectives for future applications in catalysis and beyond.     

Catalysis with Chalcogen Bonds

Herein, we introduce catalysts that operate with chalcogen bonds. Compared to conventional hydrogen bonds, chalcogen bonds are similar in strength but more directional and hydrophobic, thus ideal for precision catalysis in apolar solvents. For the transfer hydrogenation of quinolines and imines, rate enhancements well beyond a factor of 1000 are obtained with chalcogen bonds. Better activities with deeper σ holes and wider bite angles, chloride inhibition and correlation with computed anion binding energies are consistent with operational chalcogen bonds. Comparable to classics, such as 2,2′‐bipyrroles or 2,2′‐bipyridines, dithieno[3,2‐b;2′,3′‐d]thiophenes (DTTs), particularly their diimides, but also wide‐angle cyclopentadithiazole‐4‐ones are identified as privileged motifs to stabilize transition states in the focal point of the σ holes on their two co‐facial endocyclic sulfur atoms.     

Substrate-Induced Dimerization Assembly of Chiral Macrocycle Catalysts toward Cooperative Asymmetric Catalysis

An artificial system of substrate-induced dimerization assembly of chiral macrocycle catalysts enables a highly cooperative hydrogen-bonding activation network for efficient enantioselective transformation. These macrocycles contain two thiourea and two chiral diamine moieties and dimerize with sulfate to form a sandwich-like assembly. The macrocycles then adopt an extended conformation and reciprocally complement the hydrogen-bonding interaction sites. Inspired by the guest-induced dynamic assembly, these macrocycles catalyze the decarboxylative Mannich reaction of cyclic aldimines containing a sulfamate heading group. The imine substrate can be activated toward nucleophilic attack of β-ketoacid by a cooperative hydrogen-bonding network enabled by sulfamate-induced dimerization assembly of the macrocycle catalysts. Highly efficient (>95 % yield in most cases) and enantioselective (up to 97.5:2.5 er) transformation of a variety of substrates using only 5 mol % macrocycle was achieved.     

A Combined Experimental/Quantum-Chemical Study of Tetrel,Pnictogen, and Chalcogen Bonds of Linear Triatomic Molecules

Linear triatomic molecules (CO₂, N₂O, and OCS) are scrutinized for their propensity to form perpendicular tetrel (CO₂ and OCS) or pnictogen (N₂O) bonds with Lewis bases (dimethyl ether and trimethyl amine) as compared with their tendency to form end-on chalcogen bonds. Comparison of the IR spectra of the complexes with the corresponding monomers in cryogenic solutions in liquid argon enables to determine the stoichiometry and the nature of the complexes. In the present cases, perpendicular tetrel and pnictogen 1:1 complexes are identified mainly on the basis of the lifting of the degenerate ν 2 bending mode with the appearance of both a blue and a red shift. Van ′t Hoff plots of equilibrium constants as a function of temperature lead to complexation enthalpies that, when converted to complexation energies, form the first series of experimental complexation energies on sp¹ tetrel bonds in the literature, directly comparable to quantum-chemically obtained values. Their order of magnitude corresponds with what can be expected on the basis of experimental work on halogen and chalcogen bonds and previous computational work on tetrel bonds. Both the order of magnitude and sequence are in fair agreement with both CCSD(T) and DFA calculations, certainly when taking into account the small differences in complexation energies of the different complexes (often not more than a few kJ mol⁻¹) and the experimental error. It should, however, be noted that the OCS chalcogen complexes are not identified experimentally, most probably owing to entropic effects. For a given Lewis base, the stability sequence of the complexes is first successfully interpreted via a classical electrostatic quadrupole–dipole moment model, highlighting the importance of the magnitude and sign of the quadrupole moment of the Lewis acid. This approach is validated by a subsequent analysis of the molecular electrostatic potential, scrutinizing the σ and π holes, as well as the evolution in preference for chalcogen versus tetrel bonds when passing to “higher” chalcogens in agreement with the evolution of the quadrupole moment. The energy decomposition analysis gives further support to the importance/dominance of electrostatic effects, as it turns out to be the largest attractive term in all cases considered, followed by the orbital interaction and the dispersion term. The natural orbitals for chemical valence highlight the sequence of charge transfer in the orbital interaction term, which is dominated by an electron-donating effect of the N or O lone-pair(s) of the base to the central atom of the triatomics, with its value being lower than in the case of comparable halogen bonding situations. The effect is appreciably larger for TMA, in line with its much higher basicity than DME, explaining the comparable complexation energies for DME and TMA despite the much larger dipole moment for DME.     

The Balance between Hydrogen Bonds,Halogen Bonds,and Chalcogen Bonds in the Crystal Structures of a Series of 1,3,4-Chalcogenadiazoles

In order to explore how specific atom-to-atom replacements change the electrostatic potentials on 1,3,4-chalcogenadiazole derivatives, and to deliberately alter the balance between intermolecular interactions, four target molecules were synthesized and characterized. DFT calculations indicated that the atom-to-atom substitution of Br with I, and S with Se enhanced the σ-hole potentials, thus increasing the structure directing ability of halogen bonds and chalcogen bonds as compared to intermolecular hydrogen bonding. The delicate balance between these intermolecular forces was further underlined by the formation of two polymorphs of 5-(4-iodophenyl)-1,3,4-thiadiazol-2-amine; Form I displayed all three interactions while Form II only showed hydrogen and chalcogen bonding. The results emphasize that the deliberate alterations of the electrostatic potential on polarizable atoms can cause specific and deliberate changes to the main synthons and subsequent assemblies in the structures of this family of compounds.     

Comparison between Hydrogen and Halogen Bonds in Complexes of 6-OX-Fulvene with Pnicogen and Chalcogen Electron Donors

Quantum chemical calculations are applied to complexes of 6-OX-fulvene (X=H, Cl, Br, I) with ZH₃/H₂Y (Z=N, P, As, Sb; Y=O, S, Se, Te) to study the competition between the hydrogen bond and the halogen bond. The H-bond weakens as the base atom grows in size and the associated negative electrostatic potential on the Lewis base atom diminishes. The pattern for the halogen bonds is more complicated. In most cases, the halogen bond is stronger for the heavier halogen atom, and pnicogen electron donors are more strongly bound than chalcogen. Halogen bonds to chalcogen atoms strengthen in the order O<S<Se<Te, whereas the pattern is murkier for the pnicogen donors. In terms of competition, most halogen bonds to pnicogen donors are stronger than their H-bond analogues, but there is no clear pattern with respect to chalcogen donors. O prefers a H-bond, while halogen bonds are favored by Te. For S and Se, I-bonds are strongest, followed Br, H, and Cl-bonds in that order.     

Highly Active Halogen Bonding and Chalcogen Bonding Chloride Transporters with Non-Protonophoric Activity

Synthetic anion transporters show much promise as potential anti-cancer agents and therapeutics for diseases associated with mis-regulation of protein anion channels. In such applications high activity and anion selectivity are crucial to overcome competing proton or hydroxide transport which dissipates cellular pH gradients. Here, highly active bidentate halogen bonding and chalcogen bonding anion carriers based on electron deficient iodo- and telluromethyl−triazole derivatives are reported. Anion transport experiments in lipid bilayer vesicles reveal record nanomolar chloride transport activity for the bidentate halogen bonding anion carrier, and remarkably high chloride over proton/hydroxide selectivity for the chalcogen bonding anionophore. Computational studies provide further insight into the role of sigma-hole mediated anion recognition and desolvation at the membrane interface. Comparison with hydrogen bonding analogues demonstrates the importance of employing sigma-hole donor motifs in synthetic anionophores for achieving both high transport activity and selectivity.     

Comparison of Bifurcated Halogen with Hydrogen Bonds

Bifurcated halogen bonds are constructed with FBr and FI as Lewis acids, paired with NH₃ and NCH bases. The first type considered places two bases together with a single acid, while the reverse case of two acids sharing a single base constitutes the second type. These bifurcated systems are compared with the analogous H-bonds wherein FH serves as the acid. In most cases, a bifurcated system is energetically inferior to a single linear bond. There is a larger energetic cost to forcing the single σ-hole of an acid to interact with a pair of bases, than the other way around where two acids engage with the lone pair of a single base. In comparison to FBr and FI, the H-bonding FH acid is better able to participate in a bifurcated sharing with two bases. This behavior is traced to the properties of the monomers, in particular the specific shape of the molecular electrostatic potential, the anisotropy of the orbitals of the acid and base that interact directly with one another, and the angular extent of the total electron density of the two molecules.     

Halogen and Chalcogen Bond Energies Evaluated Using Electron Density Properties

Halogen (X-bond) and chalcogen bond (Ch−bond) energies for 36 complexes have been obtained at the RI-MP2/def2−TZVP level of theory, involving the heavier halogen and chalcogen atoms (Br, I, Se, Te). We have explored the existence of linear relationships between the interaction energies and the local kinetic energy densities at the bond critical points that characterize the σ-hole interactions (both electronic G(r) and potential V(r) energy densities). Interestingly, we have found strong relationships for halogen and chalcogen bonding energies, especially for the V(r) energy density, thus allowing to estimate the interaction energy without computing the separate monomers. This is also useful to estimate the interaction in monomeric systems (intramolecular X/Ch-bonds), as illustrated using several examples. Remarkably, we have also found a good relationship when in the same representation both halogen and chalcogen atoms are included, thus allowing to use the same empirical correlation for both interactions.     

Halogen Bonds in Adenine-5-Bromouracil Complexes

Ab initio and density functional calculations were employed to investigate the bonding patterns in theadenine-5-bromouracil (AT+) complexes. It is shown that the Br atom in 5-bromouracil (T+) is involved in bonding both with the hydrogen atom of the amino group of adenine (A) and with N7(A) (or N1(A)). With this motif, the Br atom interacts with a nucleophile (H) in a "head-on" fashion and an electrophile(N) in a "side-on" fashion, forming both hydrogen and halogen bonds. Electrostatic attraction between the Br atom in T+ and N7 (or N1) of adenine was found via the electrostatic potential analysis. The existence of the Br···N interactions in the pairs was further conˉrmed by means of Bader's atoms in molecules theory. A bond critical point is identiˉed for the halogen bonds and the topological parameters at the bond critical point indicate the typical closed-shell interactions in the pairs. Natural bond orbital analysis suggests that the charge transfer from the lone pair of the nitrogen atom of adenine is mainly directed to the C-Br antibonding orbital. Finally, halogen bonds in the T+AT+A tetrads were also explored.     

Catalytic Enantioselective Synthesis of Lactams through Formal [4+2] Cycloaddition of Imines with Homophthalic Anhydride

An amide‐thiourea compound, operating through a novel ion pairing mechanism, is an efficient organocatalyst for the asymmetric reaction of homophthalic anhydride with imines. N ‐aryl and N ‐alkyl imines readily undergo formal [4+2] cycloaddition to provide lactams with high levels of enantio‐ and diastereoselectivity. The nature of the key chiral ion pair intermediate was elucidated by DFT calculations.     

Polymorphism,Halogen Bonding,and Chalcogen Bonding in the Diiodine Adducts of 1,3- and 1,4-Dithiane

Through variations in reaction solvent and stoichiometry, a series of S-diiodine adducts of 1,3- and 1,4-dithiane were isolated by direct reaction of the dithianes with molecular diiodine in solution. In the case of 1,3-dithiane, variations in reaction solvent yielded both the equatorial and the axial isomers of S-diiodo-1,3-dithiane, and their solution thermodynamics were further studied via DFT. Additionally, S,S’-bis(diiodo)-1,3-dithiane was also isolated. The 1:1 cocrystal, (1,4-dithiane)·(I₂) was further isolated, as well as a new polymorph of S,S’-bis(diiodo)-1,4-dithiane. Each structure showed significant S···I halogen and chalcogen bonding interactions. Further, the product of the diiodine-promoted oxidative addition of acetone to 1,4-dithiane, as well as two new cocrystals of 1,4-dithiane-1,4-dioxide involving hydronium, bromide, and tribromide ions, was isolated.     

Halogen Bonds of Halotetrafluoropyridines in Crystals and Co-crystals with Benzene and Pyridine

The structures of the three para-substituted halotetrafluoropyridines with chlorine, bromine, and iodine have been determined in the solid state (X-ray diffraction). The structures of these compounds and that of pentafluoropyridine were also determined in the gas phase (electron diffraction). Structures in the solid state of the bromine and iodine derivatives exhibit halogen bonding as a structure-determining motif. On the way to an investigation of halogen bond formation of halotetrafluoropyridines in the solid state with the stronger Lewis base pyridine, co-crystals of benzene adducts were investigated to gain an understanding of the influence of aryl–aryl interactions. These co-crystals showed halogen bonding only for the two heavier halotetrafluoropyridines. In the pyridine co-crystals halogen bonding was observed for all three para-halotetrafluoropyridines. The formation of homodimers and heterodimers with pyridine is also supported by quantum-chemical calculations of electron density topologies and natural bond orbitals.     

Chalcogen Bonding Catalysis of a Nitro‐Michael Reaction

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.     

Orthogonal Nanoparticle Catalysis with Organogermanes

Although nanoparticles are widely used as catalysts, little is known about their potential ability to trigger privileged transformations as compared to homogeneous molecular or bulk heterogeneous catalysts. We herein demonstrate (and rationalize) that nanoparticles display orthogonal reactivity to molecular catalysts in the cross‐coupling of aryl halides with aryl germanes. While the aryl germanes are unreactive in L_nPd⁰/L_nPd^II catalysis and allow selective functionalization of established coupling partners in their presence, they display superior reactivity under Pd nanoparticle conditions, outcompeting established coupling partners (such as ArBPin and ArBMIDA) and allowing air‐tolerant, base‐free, and orthogonal access to valuable and challenging biaryl motifs. As opposed to the notoriously unstable polyfluoroaryl‐ and 2‐pyridylboronic acids, the corresponding germanes are highly stable and readily coupled. Our mechanistic and computational studies provide unambiguous support of nanoparticle catalysis and suggest that owing to the electron richness of aryl germanes, they preferentially react by electrophilic aromatic substitution, and in turn are preferentially activated by the more electrophilic nanoparticles.     

Halogen and Hydrogen Bonds in Co-crystalline Ferrocenium Organotellurium Halide Salts

Russian Journal of Coordination Chemistry - The reactions of ferrocene and decamethylferrocene with vinyltellurium trichloride Ph(Cl)C= C(Ph)TeCl3 afford unusual co-crystalline salts...