Copper catalyzed reaction of hydrazones with polyhalogenated compounds. An efficient approach to alkenes and diazadienes

Catalytic olefination reaction represents new approach to the preparation of double C=C bond. N-unsubstituted hydrazones can be converted into alkenes by treatment with polyhalogenated alkanes in presence of a base and catalytic amounts of copper salts. The reaction has a wide synthetic scope allowing to prepare both alkyl and aryl substituted alkenes, including fluorinated and functionalized ones. We demonstrated also similar transformation with N-substituted hydrazones, as a result the new carbon-carbon bond forming reaction of N-monosubstituted hydrazones with polyhaloalkanes to produce 1,2-diazabuta-1,3-dienes has been developed. This highly efficient copper-catalyzed transformation features a broad scope with regard to all reaction components, as well as the possibility to perform the process in a much more convenient one-pot fashion starting with easily available aldehydes and hydrazines. The synthetic usefulness of the obtained halogenated azadienes was demonstrated in their reactions with O-, N-, S- and C-nucleophiles, which opened access to a variety of valuable acyclic and heterocyclic products. Mechanistic studies revealed that this Cu-catalyzed transformation proceeds via radical pathway.This work was supported by a research grant from RFBR grant 18-03-00791

In-Depth Assessment of the Palladium-Catalyzed Fluorination of Five-Membered Heteroaryl Bromides

A thorough investigation of the challenging Pd-catalyzed fluorination of five-membered heteroaryl bromides is presented. Crystallographic studies and density functional theory (DFT) calculations suggest that the challenging step of this transformation is C–F reductive elimination of five-membered heteroaryl fluorides from Pd(II) complexes. On the basis of these studies, we have found that various heteroaryl bromides bearing phenyl groups in the ortho position can be effectively fluorinated under catalytic conditions. Highly activated 2-bromoazoles, such as 8-bromocaffeine, are also viable substrates for this reaction.National Institutes of Health (U.S.) (GM46059)National Science Foundation (U.S.) (Predoctoral Fellowship 2010094243)Amgen Inc

Unsymmetrical Trifluoromethyl Methoxyphenyl β-Diketones: Effect of the Position of Methoxy Group and Coordination at Cu(II) on Biological Activity

Copper(II) complexes with 1,1,1-trifluoro-4-(4-methoxyphenyl)butan-2,4-dione (HL1) were synthesized and characterized by elemental analysis, FT-IR spectroscopy, and single crystal X-ray diffraction. The biological properties of HL1 and cis-[Cu(L1)2 (DMSO)] (3) were examined against Gram-positive and Gram-negative bacteria and opportunistic unicellular fungi. The cytotoxicity was estimated towards the HeLa and Vero cell lines. Complex 3 demonstrated antibacterial activity towards S. aureus comparable to that of streptomycin, lower antifungal activity than the ligand HL1 and moderate cytotoxicity. The bioactivity was compared with the activity of compounds of similar structures. The effect of changing the position of the methoxy group at the aromatic ring in the ligand moiety of the complexes on their antimicrobial and cytotoxic activity was explored. We propose that complex 3 has lower bioavailability and reduced bioactivity than expected due to strong intermolecular contacts. In addition, molecular docking studies provided theoretical information on the interactions of tested compounds with ribonucleotide reductase subunit R2, as well as the chaperones Hsp70 and Hsp90, which are important biomolecular targets for antitumor and antimicrobial drug search and design. The obtained results revealed that the complexes displayed enhanced affinity over organic ligands. Taken together, the copper(II) complexes with the trifluoromethyl methoxyphenyl-substituted β-diketones could be considered as promising anticancer agents with antibacterial properties. © 2021, MDPI. All rights reserved.This work was funded by RFBR and Sverdlovsk region (project numbers 20-43-660042 and 20-53-00006) and supported by the basic theme of the Russian Academy of Sciences (state registration no. AAAA-A19-119011790132-7 and project no. AAAA-A19-119012490006-1). XRD experiments and analytical studies were carried out using the equipment of the Center for Joint Use “Spectroscopy and Analysis of Organic Compounds” at the Postovsky Institute of Organic Synthesis UB RAS. X-ray study was supported by the U.S. National Science Foundation (Grant DMR-1523611 PREM). The cytotoxicity assay was carried out at the “Simbioz” Center for the Collective Use of Research Equipment in the Field of Physical–Chemical Biology and Nanobiotechnology at IBPPM RAS. This work has been supported by the RUDN University Strategic Academic Leadership Program

Impact of heterocirculene molecular symmetry upon two-dimensional

Peer reviewe

Stop-frame filming and discovery of reactions at the single-molecule level by transmission electron microscopy

We report an approach – named chemTEM – to follow chemical transformations at the single-molecule level with the electron beam of a transmission electron microscope (TEM) applied as both a tuneable source of energy and a sub-Angstrom imaging probe. Deposited on graphene, disk-shaped perchlorocoronene molecules are precluded from intermolecular interactions. This allows monomolecular transformations to be studied at the single-molecule level in real time and reveals chlorine elimination and reactive aryne formation as a key initial stage of multi-step reactions initiated by the 80 keV e-beam. Under the same conditions, perchlorocoronene confined within a nanotube cavity, where the molecules are situated in very close proximity to each other, enables imaging of intermolecular reactions, starting with the Diels-Alder cycloaddition of a generated aryne, followed by rearrangement of the angular adduct to a planar polyaromatic structure and the formation of a perchlorinated zigzag nanoribbon of graphene as the final product. ChemTEM enables the entire process of polycondensation, including the formation of metastable intermediates, to be captured in a one-shot ‘movie’. A molecule with a similar size and shape but with a different chemical composition, octathio[8]circulene, under the same conditions undergoes another type of polycondensation via thiyl biradical generation and subsequent reaction leading to polythiophene nanoribbons with irregular edges incorporating bridging sulphur atoms. Graphene or carbon nanotubes supporting the individual molecules during chemTEM studies ensure that the elastic interactions of the molecules with the e-beam are the dominant forces that initiate and drive the reactions we image. Our ab initio DFT calculations explicitly incorporating the e-beam in the theoretical model correlate with the chemTEM observations and give a mechanism for direct control not only of the type of the reaction but also of the reaction rate. Selection of the appropriate e-beam energy and control of the dose rate in chemTEM enabled imaging of reactions on a timeframe commensurate with TEM image capture rates, revealing atomistic mechanisms of previously unknown processes

2 H-Bis-1,2,3-triazolo-isoquinoline: Design, Synthesis, and Photophysical Study

An efficient three-step synthesis of a new heterocyclic system is described wherein the 2H-bis([1,2,3]triazolo)[5,1-a:4′,5′-c]isoquinoline ring system is elaborated using a simple synthetic strategy. The approach permits the preparation of target compounds in high yields using readily available arylhydrazines and o-alkynylbenzaldehydes as starting materials. The photophysical properties of the prepared heterocycles were studied to demonstrate that the prepared compounds are attractive blue-emitting fluorophores, exhibiting quantum yields up to 98% and Stokes shifts up to 67 nm. A strong effect of the steric hindrance on the absorption and emission spectra was revealed. Copyright © 2020 American Chemical Society