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Despite the large variety of modified nucleosides that have been reported, the preparation of constrained 4′‐spirocyclic adenosine analogues has received very little attention. We discovered that the [2+2]‐cycloaddition of dichloroketene on readily available 4′‐exo‐methylene furanose sugars efficiently results in the diastereoselective formation of novel 4′‐spirocyclobutanones. The reaction mechanism was investigated via density functional theory (DFT) and found to proceed either via a non‐synchronous or stepwise reaction sequence, controlled by the stereochemistry at the 3′‐position of the sugar substrate. The obtained dichlorocyclobutanones were converted into nucleoside analogues, providing access to a novel class of chiral 4′‐spirocyclobutyl adenosine mimetics in eight steps from commercially available sugars. Assessment of the biological activity of designed 4′‐spirocyclic adenosine analogues identified potent inhibitors for protein methyltransferase target PRMT5. [ABSTRACT FROM AUTHOR]

Abstract: An efficient metal‐free cascade reaction between 1‐dibromovinyl‐2‐nitro‐substituted arenes and secondary amines results in the formation of polycyclic pseudoindoxyls in a single step. The reaction mechanism leading to these fused ring systems was investigated, and is believed to involve the initial formation of nitroarylated ynamines/ynamides. These intermediates cycloisomerize towards N‐alkenyl‐tethered 2‐aminoisatogens via a carbene intermediate as demonstrated by QTAIM (quantum theory of atoms in molecules) and ELF (electron localization function) analysis. A subsequent intramolecular dipolar cycloaddition afforded the title compounds. [ABSTRACT FROM AUTHOR]

Abstract: An efficient metal‐free cascade reaction between 1‐dibromovinyl‐2‐nitro‐substituted arenes and secondary amines results in the formation of polycyclic pseudoindoxyls in a single step. The reaction mechanism leading to these fused ring systems was investigated, and is believed to involve the initial formation of nitroarylated ynamines/ynamides. These intermediates cycloisomerize towards N‐alkenyl‐tethered 2‐aminoisatogens via a carbene intermediate as demonstrated by QTAIM (quantum theory of atoms in molecules) and ELF (electron localization function) analysis. A subsequent intramolecular dipolar cycloaddition afforded the title compounds. [ABSTRACT FROM AUTHOR]

The chalcogen bond has been acknowledged as an influential noncovalent interaction (NCI) between an electron‐deficient chalcogen (donor) and a Lewis base (acceptor). This work explores the main features of chalcogen bonding through a large‐scale computational study on a series of donors and acceptors spanning a wide range in strength and character of this type of bond: (benzo)chalcogenadiazoles (with Ch = Te/Se/S) versus halides and neutral Lewis bases with O, N, and C as donor atoms. We start from Pearson's hard and soft acids and bases (HSAB) principle, where the hard nature of the chalcogen bond is quantified through the molecular electrostatic potential and the soft nature through the Fukui function. The σ‐holes are more pronounced when going down in the periodic table and their directionality matches the structural orientation of donors and acceptors in the complexes. The Fukui functions point toward an n→σ*‐type interaction. The initial conjectures are further scrutinized using quantum mechanical methods, mostly relating to the systems' electron density. A Ziegler–Rauk energy decomposition analysis shows that electrostatics plays a distinctly larger role for the soft halides than for the hard, uncharged acceptors, associated with the softness matching within the HSAB principle. The natural orbital for chemical valence analysis confirms the n→σ* electron donation mechanism. Finally, the electron density and local density energy at the bond critical point in the quantum theory of atoms in molecules study and the position of the spikes in the reduced density gradient versus density plot in the NCI theory situate the chalcogen bond in the same range as strong hydrogen bonds. © 2017 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

In the last decade, halogen bonds, noncovalent interactions formed between positive regions in the electrostatic potential on halogen atoms, often referred to as σ-holes, and electron-rich sites, have gained a lot of interest. Recently, this interest has been expanded towards interactions with Group V and Group VI elements, giving rise to pnicogen and chalcogen bonds. Although chalcogen bonds have already shown some promising results for applications in crystallography and catalysis, experimental results characterising these noncovalent interactions remain scarce. In this combined experimental and theoretical study, original data allowing the characterization of S⋅⋅⋅O chalcogen bonds is obtained by studying the 1:1 molecular complexes between 2,2,4,4-tetrafluoro-1,3-dithiethane (C2F4S2) and dimethyl ether (DME). Ab initio calculations of the C2F4S2⋅DME dimer yield two stable chalcogen-bonded isomers, the difference being the presence or absence of secondary F⋅⋅⋅H interactions. Liquid-krypton solutions containing C2F4S2 and DME were studied using FTIR and Raman spectroscopy. Upon subtraction of rescaled monomer spectra, clear complex bands are observed. The observed complexation shifts agree favourably with the ab initio calculated shifts of the chalcogen-bonded complexes. The 1:1 stoichiometry of the complex is confirmed and a complexation enthalpy of −13.5(1) kJ mol−1 is found, which is in good agreement with the calculated values. A Ziegler-Rauk energy decomposition analysis revealed that electrostatic interactions prominently dominate over orbital interactions. Nevertheless, significant charge transfer occurs from the oxygen in DME to one of the sulfur atoms in C2F4S2 and the carbon along the extension of the chalcogen bond. [ABSTRACT FROM AUTHOR]

The contributions of covalent and noncovalent interactions to the formation of classical adducts of bulky Lewis acids and bases and frustrated Lewis pairs (FLPs) were scrutinized by using various conceptual quantum chemical techniques. Significantly negative complexation energies were calculated for fourteen investigated Lewis pairs containing bases and acids with substituents of various sizes. A Ziegler-Rauk-type energy decomposition analysis confirmed that two types of Lewis pairs can be distinguished on the basis of the nature of the primary interactions between reactants; dative-bond formation and concomitant charge transfer from the Lewis base to the acid is the dominant and most stabilizing factor in the formation of Lewis acid-base adducts, whereas weak interactions are the main thermodynamic driving force (>50 %) for FLPs. Moreover, the ease and extent of structural deformation of the monomers appears to be a key component in the formation of the former type of Lewis pairs. A Natural Orbital for Chemical Valence (NOCV) analysis, which was used to visualize and quantify the charge transfer between the base and the acid, clearly showed the importance and lack of this type of interaction for adducts and FLPs, respectively. The Noncovalent Interaction (NCI) method revealed several kinds of weak interactions between the acid and base components, such as dispersion, π-π stacking, CH ⋅⋅⋅π interaction, weak hydrogen bonding, halogen bonding, and weak acid-base interactions, whereas the Quantum Theory of Atoms in Molecules (QTAIM) provided further conceptual insight into strong acid-base interactions. [ABSTRACT FROM AUTHOR]

In this study, the rate of photopolymerization ( Rp) of 21 alkyl methacrylates is correlated with the chemical properties of their monomeric radicals by making use of the enthalpic and polar effects of these radicals. Based on these properties, a general non-linear expression is derived by optimizing the radicals and evaluating both their stability and polar effects, via the radical electrophilicity, using density functional theory. The expression performs quite well in predicting Rp for 16 of the 21 methacrylates with an R2 value of 0.9384, but does not hold for too unstable and/or too nucleophilic radicals. Increasing the stability or decreasing the nucleophilicity of the monomeric radical results in a higher polymerization rate; in addition, the influence of the polar effects becomes larger for more stable radicals. Methacrylates containing a pendant phenyl, where π-π stacking plays an important role, are experimentally found to have a higher polymerization rate than predicted. [ABSTRACT FROM AUTHOR]

Theoretical design can be an important aid in the discovery of valuable stable radical systems. In this study, inverse molecular design was applied to thiadiazinyl radicals to maximize two fundamental electronic properties in chemistry, namely electrophilicity and nucleophilicity. We discovered that the thiadiazinyl structure can be made moderately nucleophilic or highly electrophilic, depending on the electronic character of its substituents. The most electrophilic thiadiazinyl radical displays the highest electrophilic character encountered so far for uncharged radical systems. The accumulated data relating to the influence of different substituents at the various sites has allowed us to propose thiadiazinyl radicals that are intrinsically stable and as electrophilic or nucleophilic as possible. Although the nucleophilicity optimum fulfills the additional requirement of being stable, a significant drop from highly to merely moderately electrophilic is observed for the new electrophilicity optimum. [ABSTRACT FROM AUTHOR]

A list of participants for the current issue is presented which includes Hassan Abdallah, Luis Francisco Acosta, Andrew Adamczyk.