Evgeniy G. Gordeev

Carboxylate Switch between Hydro- and Carbopalladation Pathways in Regiodivergent Dimerization of Alkynes

Experimental and theoretical investigation of the regiodivergent palladium-catalyzed dimerization of terminal alkynes is presented. Employment of N-heterocyclic carbene-based palladium catalyst in the presence of phosphine ligand allows for highly regio- and stereoselective head-to-head dimerization reaction. Alternatively, addition of carboxylate anion to the reaction mixture triggers selective head-to-tail coupling. Computational studies suggest that reaction proceeds via the hydropalladation pathway favoring head-to-head dimerization under neutral reaction conditions. The origin of the regioselectivity switch can be explained by the dual role of carboxylate anion. Thus, the removal of hydrogen atom by the carboxylate directs reaction from the hydropalladation to the carbopalladation pathway. Additionally, in the presence of the carboxylate anion intermediate, palladium complexes involved in the head-to-tail dimerization display higher stability compared to their analogues for the head-to-head reaction.

A solid acetylene reagent with enhanced reactivity: fluoride-mediated functionalization of alcohols and phenols

The direct vinylation of an OH group in alcohols and phenols was carried out utilizing a novel CaC2/KF solid acetylene reagent in a simple K2CO3/KOH/DMSO system. The functionalization of a series of hydroxyl-group-containing substrates and the post-modification of biologically active molecules were successfully performed using standard laboratory equipment, providing straightforward access to the corresponding vinyl ethers. The overall process developed involves an atom-economical addition reaction employing only inorganic reagents, which significantly simplifies the reaction set-up and the isolation of products. A mechanistic study revealed a dual role of the F− additive, which both mediates the surface etching/renewal of the calcium carbide particles and activates the CC bond towards the addition reaction. The development of the fluoride-mediated nucleophilic addition of alcohols eliminates the need for strong bases and may substantially extend the areas of application of this attractive synthetic methodology due to increasing functional group tolerance. As a replacement for dangerous and difficult to handle high-pressure acetylene, we propose the solid reagent CaC2/KF, which is easy to handle, does not require dedicated laboratory equipment and demonstrates enhanced reactivity of the acetylenic triple bond. Theoretical calculations have shown that fluoride-mediated activation of the hydroxyl group towards nucleophilic addition significantly reduces the activation barrier and facilitates the reaction.

Computational Study of a Model System of Enzyme-Mediated [4+2] Cycloaddition Reaction

A possible mechanistic pathway related to an enzyme-catalyzed [4+2] cycloaddition reac-tion was studied by theoretical calculations at density functional (B3LYP, O3LYP, M062X) and semiempirical levels (PM6-DH2, PM6) performed on a model system. The calculations were carried out for the key [4+2] cycloaddition step considering enzyme-catalyzed biosynthesis of Spinosyn A in a model reaction, where a reliable example of a biological Diels-Alder reaction was reported experimentally. In the present study it was demonstrated that the [4+2] cycloaddition reaction may benefit from moving along the energetically balanced reaction coordinate, which enabled the catalytic rate enhancement of the [4+2] cycloaddition pathway involving a single transition state. Modeling of such a system with coordination of three amino acids indicated a reliable decrease of activation energy by ~18.0 kcal/mol as compared to a non-catalytic transformation.

Novel [4 + 2] cycloaddition reactions of alkyne and enyne key-units: Direct access to bicyclic aromatic and heteroaromatic products. A theoretical mechanistic study

A new efficient approach was developed for the synthesis of aromatic and heteroaromatic compounds based on [4 + 2] cycloaddition of unsubstituted and heteroatom-substituted alkyne and enyne units. The developed approach provides a practical Green chemical route to several types of important bicyclic products (indane, cyclopentapyridines, indole, isoindole, indolizine, isophosphindole, benzofuran, benzothiophene, benzoselenophene and corresponding dihydro derivatives) starting from simple linear compounds. The mechanism of the reactions was revealed by theoretical calculations using different methods, including CCSD(T) and MP4(SDTQ) for energy calculations and B3LYP, M052X, B3PW91, BLYP and MP2 levels for evaluation of molecular structures.

[3 + 2]-Cycloaddition of in Situ Generated Nitrile Imines and Acetylene for Assembling of 1,3-Disubstituted Pyrazoles with Quantitative Deuterium Labeling

A novel synthetic methodology for the preparation of 1,3-disubstituted pyrazoles from in situ generated nitrile imines and acetylene is reported. The reactions are performed in a simple two-chamber reactor. One part of the reactor is loaded with hydrazonoyl chloride precursors of active nitrile imine species and a base. The other part is used to generate acetylene from CaC2 and water. Partitioning of the reactants improves the yields of desired pyrazoles up to 99% and simplifies their isolation to a simple procedure of solvent evaporation. The approach requires no complex equipment and utilizes inexpensive, safe, and easy to handle calcium carbide as a starting material. A model deuterium incorporation is carried out according to the developed methodology, producing a series of novel 4,5-dideuteropyrazoles with excellent deuterium enrichment. Theoretical calculations on reaction mechanism and characterization of possible intermediate structures were performed.

Analysis of 3D printing possibilities for the development of practical applications in synthetic organic chemistry

The possibility of rapid manufacturing of customized chemical labware and reactionware by three-dimensional (3D) printing is discussed. The advantages and disadvantages of this approach to the design of chemical equipment from different engineering plastics were demonstrated and the suitability of some materials for chemical applications was estimated: PP > PLA > > ABS > PETG (PP is polypropylene, PLA is polylactide, ABS is acrylonitrile butadiene styrene, and PETG is polyethylene terephthalate glycol). The procedure described is a powerful tool for the production of both typical and unique chemical labware; to date, the fused deposition modeling (FDM) method is already available for the everyday use in chemical laboratories. The examples of successful application of 3D-printed products were demonstrated: solvent resistance and impermeability were assessed, as well as Pd(OAc)2-catalyzed cross-coupling between p-bromotoluene and phenylboronic acid and Ni(acac)2-catalyzed hydrothiolation of alkyne with thiophenol were performed.

Improvement of quality of 3D printed objects by elimination of microscopic structural defects in fused deposition modeling

Additive manufacturing with fused deposition modeling (FDM) is currently optimized for a wide range of research and commercial applications. The major disadvantage of FDM-created products is their low quality and structural defects (porosity), which impose an obstacle to utilizing them in functional prototyping and direct digital manufacturing of objects intended to contact with gases and liquids. This article describes a simple and efficient approach for assessing the quality of 3D printed objects. Using this approach it was shown that the wall permeability of a printed object depends on its geometric shape and is gradually reduced in a following series: cylinder > cube > pyramid > sphere > cone. Filament feed rate, wall geometry and G-code-defined wall structure were found as primary parameters that influence the quality of 3D-printed products. Optimization of these parameters led to an overall increase in quality and improvement of sealing properties. It was demonstrated that high quality of 3D printed objects can be achieved using routinely available printers and standard filaments.

Switching the nature of catalytic centers in Pd/NHC systems by solvent effect driven non-classical R-NHC Coupling: Switching the nature of catalytic centers in Pd/NHC systems by solvent effect driven non-classical R-NHC coupling

A well‐established oxidative addition of organic halides (R‐X) to N‐heterocyclic carbene (NHC) complexes of palladium(0) leads to formation of (NHC)(R)PdII(X)L species, the key intermediates in a large variety of synthetically useful cross‐coupling reactions. Typical consideration of the cross‐coupling catalytic cycle is based on the assumption of intrinsic stability of these species, where the subsequent steps involve coordination of the second reacting partner. Thus, high stability of the intermediate (NHC)(R)PdII(X)L species is usually taken for granted. In the present study it is discussed that such intermediates are prone to non‐classical R‐NHC intramolecular coupling process (R = Me, Ph, Vinyl, Ethynyl) that results in removal of NHC ligand and generation of another type of Pd catalytic system. DFT calculations (BP86, TPSS, PBE1PBE, B3LYP, M06, wB97X‐D) clearly show that outcome of R‐NHC coupling process is not only determined by chemical nature of the organic substituent R, but also strongly depends on the type of solvent. The reaction is most favorable in polar solvents, whereas the non‐polar solvents render the products less stable.