The manifestation of isoindole-isoindoline tautomerism in condensed isoindoles was first described in the literature by two of us, after it had been studied on single (non-condensed) isoindoles. The quantitative ratio of the tautomers of simple isoindoles in organic solvent solutions was shown to depend on many factors as reported in many articles and reviews. Each new case of tautomerism must be demonstrated by proving the structure of both (or more) tautomeric forms and the existence of equilibrium between the tautomers in solution. Without this evidence, they can only be considered as isomers. In this paper are reported, for the first time, DFT calculations of the tautomerism in condensed isoindoles for which the existence of an equilibrium was also confirmed by 1H NMR. That is, we are talking about the study of a new type of tautomerism in condensed isoindoles, specifically for those structures where one can imagine the transfer of a hydrogen atom from the nitrogen atom of the neighboring heterocycle to the alpha position of the isoindole fragment. The objects of the study are isoindolo[2,1-a]quinazolin-5(11H)-ones and their heteroanalogs, as we have observed this phenomenon experimentally for some of them. The obtained results correlate well with literature data and with our experimental studies. The isoindoline tautomer is lower in energy than the isoindole tautomer. These calculations open prospects for a broader and deeper study of the remarkable and rare phenomenon of tautomerism in condensed isoindoles.

Phosphorus dendrimers are highly branched, monodisperse macromolecules built around a phosphorus core, and having phosphorus atoms at all branching points. Their modular architecture allows for precise control over size, shape, and surface functionality. When functionalized at the surface with heterocycles—organic rings containing one or more heteroatoms (e.g., nitrogen, oxygen, sulfur)—these dendrimers gain catalytic activity, in the materials or biological fields. This review is organized according to the type of heterocycles (including N, O, S, or combined heteroatoms) linked to the surface of phosphorus dendrimers and emphasizes their properties.

The reaction of 5-amino-11H-isoindolo[2,1-a]quinazolIne with maleimides is not a typical Michael reaction but proceeds through a more complex rearrangement. Depending on the type of control, the reaction with N-phenylmaleimide can follow two different pathways. Probable reaction mechanisms have been proposed for both kinetic and thermodynamic control. The structures of the reaction products were confirmed, in particular, by COSY and HMBC methods.

Two pairs of diastereomerically pure calix[4]arene phosphoric acid derivatives with ABHH and ABCH substitution patterns were synthesized via phosphorylation and phosphotropic rearrangement on the narrow rim. These new cone-shaped, inherently chiral calixarenes were tested as organocatalysts in the stereoselective aza-Diels–Alder reaction of imines with Danishefsky's diene, as well as in the stereoselective epoxide ring opening.

The binding properties of electron-rich M 4 L 2 metallacages with different cavity sizes, constructed through coordination-driven self-assembly of extended tetrathiafulvalene (exTTF)-based ligands, are evaluated and show a high size selectivity for different guest molecules.

Pillar[5]arene derivatives decorated with ten peripheral TTF or exTTF subunits were prepared and their electrochemical properties investigated. These electron-rich macrocyclic systems are suitable receptors for a fullerene guest.

Diversity-oriented approach to large artificial macrocycle libraries with a ring size of 13-18 atoms relying on the "build-couple-pair" strategy is disclosed. The "couple" phase included three one-pot steps including consequent amide coupling of N-Boc-monoprotected vicinal diamines with two alkenyl carboxylic acids, followed by ring-closing metathesis as the key "pair" step. The scope and limitations of the method were established for all three reagents. In particular, various acyclic, mono- and bicyclic aliphatic diamine derivatives with the N-C-C-N dihedral angle less than ca. 130 degrees appeared to be suitable substrates. The proposed approach was used to construct a virtual library of 1.8 . 10(5) macrocycles derived from 12,283 different scaffolds. More than 40 % of members of this library contained a protected amino function and hence can be suitable for the post-pairing modification, thus giving rise to at least a billion-size chemical space based on the REAL-type synthetic methodology. Validation of the approach under parallel synthesis conditions on a 383-member subset showed a 61 % success rate over the whole 4-5-step reaction sequence. Finally, the synthetic approach also worked on a gram scale (up to 8.0 g).

In this work, we have studied the dibenzofluorene derivative belonging to the KuQuinones family. We have investigated the structural, morphological and optical properties of this derivative, which is part of the new sub-class of dibenzofluorenes, due to its existence as a zwitterion, in contrast to other KuQuinones. The optimization of the dibenzofluorene derivative was performed using density functional theory (DFT) by the M06-2X/cc-pVTZ + PCM (CH3CN) method. The UV spectra were calculated using CAM-B3LYP/cc-pVTZ and W97X/cc-pVTZ + PCM (CH3CN) methods. Our theoretical results confirm and explain the obtained experimental data.

The development of methodologies to control on demand and reversibly supramolecular transformations from self-assembled metalla-structures requires the rational design of architectures able to answer to an applied stimulus. While solvent or concentration changes, light exposure or addition of a chemical have been largely explored to provide these transformations, the case of pH sensitive materials is less described. Herein, we report the first example of a pH-triggered dissociation of a coordination-driven self-assembled interlocked molecular link. It incorporates a pH sensitive benzobisimidazole-based ligand that can be selectively protonated on its bisimidazole moieties. This generates intermolecular electrostatic repulsions that reduces drastically the stability of the interlocked structure, leading to its dissociation without any sign of protonation of the pyridine moieties involved in the coordination bonds. Importantly, the dissociation process is reversible through addition of a base.

This work is dedicated to the study of structural, morphological, and optical properties of stable isoindole derivative, which keeps o-quinoid structure. Corresponding properties were studied using X-ray diffraction, SEM, and UV-Vis methods. The geometry of the target molecule was optimized using the M06-2x/cc-pVTZ method. Theoretical UV-Vis spectra were calculated using two methods: CAM-B3LYP/cc-pVTZ and W97X/cc-VTZ + PCM (CH3CN), and the obtained results sufficiently correlate with the experimental data.

A new exTTF-based ligand was synthesized and its coordination-driven self-assembly behavior with a square planar palladium complex was compared with a previously described regioisomer.

A M8L2 metalla-cage constructed through coordination-driven self-assembly from a quinonato bis-ruthenium complex and an electron-rich tetrathiafulvalene (TTF) tetrapyridyl ligand is depicted.

The synthesis of 2-(methoxymethyl)isoindolin-l-imine derivatives via an unusual Delepine reaction is reported. The substrate substituents' influence on the reaction course was studied, and a possible reaction mechanism proposed. The structure of 2-(methoxymethyl)isoindolin-1-imine was confirmed by X-ray diffraction analysis. (C) 2021 Elsevier Ltd. All rights reserved.

The Front Cover shows an irregular tetradecagon-shaped spaceship delivering large libraries of artificial macrocycles to the currently accessible chemical space. As many as 1.8⋅105 compounds derived from 12,283 scaffolds can be reached with the proposed diversity-oriented «build – couple – pair» approach; that exceeded the number of stars that can be observed with a naked eye from Earth. Invaluable help of Mr. Serhii Gula with artwork preparation is appreciated. More information can be found in the Full Paper by O. O. Grygorenko et al.

A convenient methodology for constructing 6,6-difluorospiro[3.3]heptane scaffold - a conformationally restricted isostere of gem-difluorocycloalkanes - is developed. Alarge array of novel 2-mono- and 2,2-bifunctionalized difluorospiro[3.3]heptane building blocks was obtained through the convergent synthesis strategy using a common synthetic precursor - 1,1-bis(bromomethyl)-3,3-difluorocyclobutane. The target compounds and intermediates were prepared by short reaction sequences (6-10 steps) on multigram scale (up to 0.47 kg).

Simple and efficient synthesis of 2-(1,2,4-oxadiazol-5-yl)-2,3-dihydro-4H-chromen-4-ones is elaborated. The method relies on CDI-mediated cyclocondensation of substituted 4-oxochromane-2-carboxylic acids and amidoximes. The protocol allows the preparation of 2-oxadiazolylchromanones decorated with two pharmacophores (2,3-dihydro-4H-chromen-4-one and 1,2,4-oxadiazole) that are in high demand in drug discovery.

Macrocycles represent previously unexplored promising drug candidates, that can be useful for treating protein-protein interactions. Atropoisomerism is an inherent feature of the natural macrocyclic peptides that is significant for their activity and selectivity, and, therefore, should be introduced into newly synthesized macrocycles. Synthesis of the libraries of artificial macrocycles faces many challenges due to their structure and size. Herein we report on the preparation of a 16-membered macrocycle containing 1,2,3-triazole ring, spiro-piperidine, and phenyl moieties, as well as a chiral carbon atom. Our approach to the macrocycle was inspired by the "build/couple/pair" (B/C/P) strategy, a part of diversity-oriented synthesis methodology. We have employed readily accessible starting materials and robust synthetic procedures which allowed us to obtain the target macrocycle in a high yield. Standard methods of amide bond formation were used for the coupling of macrocycle building blocks. Click chemistry azide-alkyne cycloaddition was exploited at the final ring closure step. The assignment of signals in 1H and 13C NMR spectra of the macrocycle was performed using a series of 2D NMR techniques. The macrocycle displayed planar chirality, which, in a combination with a stereocenter with the known configuration, was sufficient to propose possible structures of diastereomers. The diastereomers could differ by the relative position of triazole ring. Their racemization could occur through a "rope skipping" motion involving the cyclic chain crossing the plane of 1,2,3-triazole ring. The supposed structures of diastereomers were corroborated by means of a various NMR spectroscopy techniques and DFT calculations. Analysis of the amide NH chemical shift temperature coefficients coupled with the data on optimized geometries obtained by DFT convincingly demonstrated that the intramolecular hydrogen bonds play a major role in stabilization of the diastereomer structures. According to the variable temperature NMR experiment, the interconversion of two diastereomers did not occur even at heating up to 70 °C.

Selective chemical reactions create new possibilities for controlled synthesis of compounds with pre-designed properties for further use in medical chemistry, material science and other fields. This is especially useful for such synthetic methodology as [4+2] cycloaddition. Current work is dedicated to study of reactions between N-chiral maleinimides with cyclic dienes based on the pyridoisoindol. Pyrido[2,1-a]isoindol turned out to be the most practical object to study the first example of asymmetric variant of the Diels-Alder reaction involving condensed isoindols. Previously, we established that this heterocyclic system, in contrast to other azino- and azoloisoindols, upon undergoing cycloaddition with non-chiral maleinimides gives only rearranged adducts of the first type. This type of compounds have also interesting stereochemistry: in solid state they have twisted double bond (twist angle 7-10°), while in solution they exist as a mixture of athropodiastereomeres due to the asymmetric Carbon atom and hindered rotation around С–С bond between exocyclic double bond and 2-(α-pyridil)phenyl fragment. Initial expectation was that chiral induction would influence the ratio of corresponding athropodiastereomeres. Calculations show that there are four possible athropodiastereomeres due to the chiral center and sterically hindered chiral axis. In case of non-chiral dienophiles, reaction results in two major diastereomeres (for our purposes marked as A and B) with 70:30 ration and two minor isomers (marked С and D respectively), the latter constituting less than 5% of the total amount. Major and minor isomers are in constant complex equilibrium, controlled via slow rotation of around corresponding С-С bond on one hand (which is the reason for athropodiastereomeres between major forms A and B, shown via NMR spectra at different temperatures), and on the other hand – fast equilibrium due to the 1,5-sigmatropic shift (cause for the minor forms C and D). Target reaction was studied under standard conditions for this rearrangement and under the kinetic control in the inert atmosphere at -80°С using TiCl4 as catalyzer. We therefore show that reaction pathway is similar to our previous examples and results in rearranged adducts of the first type. Ratio of athropodiastereomeres (both major and minor forms) is different from previous examples using non-chiral 2-substituted maleimides. Asymmetric induction spontaneously transfers from influencing the Diels-Alder reaction to influencing synchronic sigmatropic rearrangement, which is the final stage in the formation of the rearranged adduct of the first type in condensed isoindol systems.

Developing methodologies for on-demand control of the release of a molecular guest requires the rational design of stimuli-responsive hosts with functional cavities. While a substantial number of responsive metallacages have already been described, the case of coordination-tweezers has been less explored. Herein, we report the first example of a redox-triggered guest release from a metalla-assembled tweezer. This tweezer incorporates two redox-active panels constructed from the electron-rich 9-(1,3-dithiol-2-ylidene)fluorene unit that are facing each other. It dimerizes spontaneously in solution and the resulting interpenetrated supramolecular structure can dissociate in the presence of an electron-poor planar unit, forming a 1:1 host-guest complex. This complex dissociates upon tweezer oxidation/dimerization, offering an original redox-triggered molecular delivery pathway.

An electroactive M2L2 metalla-macrocycle constructed through coordination driven self-assembly dimerizes upon oxidation and binds an electro-deficient substrate with a high association constant.