Carbocatalytic Acetylene Cyclotrimerization: A Key Role of Unpaired Electron Delocalization

Gordeev E.G., Pentsak E.O., Ananikov V.P., J. Am. Chem. Soc., 2020, 142, 3784-3796.
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Development of sustainable catalysts for synthetic transformations is one of the most challenging and demanding goals. The high prices of precious metals and the unavoidable leaching of toxic metal species leading to environmental contamination make the transition metal-free catalytic systems especially important. Here we demonstrate that carbene active centers localized on carbon atoms at the zigzag edge of graphene represent an alternative platform for efficient catalytic carbon–carbon bond formation in the synthesis of benzene. The studied acetylene trimerization reaction is an efficient atom-economic route to build an aromatic ring—a step ubiquitously important in organic synthesis and industrial applications. Computational modeling of the reaction mechanism reveals a principal role of the reversible spin density oscillations that govern the overall catalytic cycle, facilitate the product formation, and regenerate the catalytically active centers. Dynamic π-electron interactions in 2D carbon systems open new opportunities in the field of carbocatalysis, unachievable by means of transition metal-catalyzed transformations. The theoretical findings are confirmed experimentally by generating key moieties of the carbon catalyst and performing the acetylene conversion to benzene.

Introducing tox‐Profiles of Chemical Reactions

Egorova K.S., Galushko A.S., Ananikov V.P., Angew. Chem. Int. Ed., 2020, 59, 22296-22305.
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In this Essay, we present a critical analysis of two common practices in modern chemistry—that is, of using speculations about the "greenness" and "nontoxicity" of developed synthesis procedures and of a priori labelling various compounds derived from natural sources as being environmentally safe. We note that every organic molecule that contains functional groups should be biologically active. Thus, analysis of the particular greenness and the potential environmental impact of a given chemical process should account for the biological activity of all its components in a measureable (rather than empirical) way. We highlight the necessity of clarifying discussions on biological activity and toxicity and propose possible ways of introducing tox‐Profiles as a reliable overview of the overall toxicity of chemical reactions.

Pd-Catalyzed Synthesis of Densely Functionalized Cyclopropyl Vinyl Sulfides Reveals the Origin of High Selectivity in a Fundamental Alkyne Insertion Step

Sahharova L.T., Gordeev E.G., Eremin D.B., Ananikov V.P., ACS Catal., 2020, 10, 9872–9888.
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Catalytic atom-economic hydrothiolation of cyclopropyl acetylenes was developed. Using Pd/NHC complex as a precatalyst, regioselective addition of thiols to cyclopropyl acetylenes was successfully performed, leading to densely functionalized compounds in excellent selectivity (up to 99:1) and high yields (up to 99%). Formation of Markovnikov-type products by insertion of alkyne into the Pd–S bond was confirmed experimentally. Molecular dynamics of the alkyne insertion into the Pd–S bond was performed computationally to identify key factors controlling the remarkable regioselectivity of this process. The fundamental question of how a small difference in activation energies can result in very high regioselectivity has been addressed by experimental methods combined with computational modeling. We show that the insertion of alkyne into the Pd–S bond proceeds by an asynchronous mechanism, which starts with metal–carbon binding and resolves into diverse transient structures. We further demonstrate that dynamic involvement of these structures ensures regioselectivity of the entire process, thus providing a mechanistic link that has long been missing. Alkyne insertion into the metal–heteroatom bond is a fundamental elementary step and a corner stone of catalysis and organometallic chemistry that works for a large variety of metals and heteroatoms. Mastering its Markovnikov vs anti-Markovnikov selectivity provides powerful opportunities for the design of selective functionalization routes.

Directing-Group-Free, Carbonyl Group-Promoted Catalytic C–H Arylation of Bio-Based Furans

Karlinskii B.Ya., Kostyukovich A.Yu., Kucherov F.A., Galkin K.I., Kozlov K.S., Ananikov V.P., ACS Catal., 2020, 10, 11466–11480.
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An efficient strategy was developed for directing-group-free C–H functionalization of biomass-derived C6 furanic building block. Palladium-catalyzed C–H functionalization of the low-reactive C3 position was successfully performed in 2,5-diformylfuran, an important derivative of the biobased platform chemical 5-(hydroxymethyl)furfural. The ligand-free catalytic arylation was carried out without using protecting or directing groups, which is of key importance for the studied area to achieve waste-minimized and step-economic biomass processing. The experimental results combined with density functional theory calculations revealed a reaction mechanism and indicated that the presence of the aldehyde group is essential for catalytic reaction. Enolization of the aldehyde group and Pd binding play an important role in governing the overall C–H functionalization pathway. One of the obtained arylated furanic compounds was tested as a model substrate for reduction and oxidation of carbonyl groups to highlight its versatile synthetic potential.

The Key Role of R-NHC Couplings (R = C, H, Heteroatom) and M-NHC Bond Cleavage in the Evolution of M/NHC Complexes and Formation of Catalytically Active Species

Chernyshev V. M., Denisova E.A., Eremin D. B., Ananikov V. P., Chem. Sci., 2020, 11, 6957-6977.
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Complexes of metals with N-heterocyclic carbene ligands (M/NHC) are typically considered the systems of choice in homogeneous catalysis due to their stable metal−ligand framework. However, it becomes obvious that even metal species with a strong M-NHC bond can undergo evolution in catalytic systems, and processes of M-NHC bond cleavage are common for different metals and NHC ligands. This review is focused on the main types of the M-NHC bond cleavage reactions and their impact on activity and stability of M/NHC catalytic systems. For the first time, we consider these processes in terms of NHC-connected and NHC-disconnected active species derived from M/NHC precatalysts and classify them as fundamentally different types of catalysts. Problems of rational catalyst design and sustainability issues are discussed in the context of the two different types of M/NHC catalysis mechanisms.

Selectivity Control in Thiol-yne Click Reactions via Visible Light Induced Associative Electron Upconversion

Burykina J.V., Shlapakov N.S., Gordeev E.G., König B., Ananikov V.P., Chem. Sci., 2020, 11, 10061-10070.
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An associative electron upconversion is proposed as a key step determining the selectivity of the thiol-yne coupling. The developed synthetic approach provided an efficient tool to access a comprehensive range of products - four types of vinyl sulfides were prepared in high yields and selectivity. Practically important, here we report the transition-metal-free regioselective thiol-yne addition and formation of the demanding Markovnikov-type product by radical photoredox reaction. The photochemical process was directly monitored by mass-spectrometry in a specially designed ESI-MS device with green laser excitation in the spray chamber. The proposed reaction mechanism is supported by experiments and DFT calculations.

Understanding Solubilization of Ca Acetylide with a New Computational Model for Ionic Pairs

Polynski M.V., Sapova M.D., Ananikov V.P., Chem. Sci., 2020, ASAP.
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The unique reactivity of the acetylenic unit in DMSO gives rise to ubiquitously developed synthetic methods. We theoretically consider CaC2 solubility and protolysis in DMSO and formulate a strategy for CaC2 activation in solution-phase chemical transformations. For this, we use a new strategy for the modeling of ionic compounds in strongly coordinating solvents combining Born-Oppenheimer molecular dynamics with DFTB3-D3(BJ) Hamiltonian and static DFT computations at the PBE0-D3(BJ)/pob-TZVP-gCP level. We modeled the thermodynamics of CaC2 protolysis under ambient conditions, taking into account its known heterogeneity and considering three polymorphs of CaC2. We give a theoretical basis for the existence of the elusive intermediate HC≡C-Ca-OH and show that CaC2 insolubility in DMSO is of thermodynamic nature. We confirm the unique role of water and specific properties of DMSO as unique activating agents for CaC2 and explain how the activation is realized. The implied strategy for the utilization of CaC2 in sustainable organic synthesis is outlined.

Controlled Natural Biomass Deoxygenation Allows the Design of Reusable Hot-Melt Adhesives Acting in a Multiple Oxygen Binding Mode

Kucherov F.A., Gordeev E.G., Kashin A.S., Ananikov V. P., ACS Appl. Mater. Interfaces, 2020, 12, 45394–45403.
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The present article describes a conceptual view on the design of reusable bioderived high-value-added materials. The translation of a highly complex irregular structure of natural biopolymer into a well-defined hierarchically organized molecular chain led to the discovery of unique adhesive properties enhanced by a novel multiple binding effect. For practical applications, biomass-derived furanic polyesters were found as reusable thermoplastic adhesives. Examined poly(ethylene-2,5-furandicarboxylate) (PEF) and poly(hexamethylene-2,5-furandicarboxylate) (PHF) showed strong adhesion to aluminum in single-lap shear tests (1.47 ± 0.1 and 1.18 ± 0.1 kN/cm2, respectively). After the separation, the joints could be easily restored by reheating of the metal parts. Three consecutive cycles of regluing were successfully performed without a significant drop in the adhesive strength. Strong adhesion of the biomass-derived polymers to glass surfaces was also observed (0.93 ± 0.11 kN/cm2 for PEF and 0.84 ± 0.06 kN/cm2 for PHF). An in-depth study of the surfaces after the shear tests, carried out by means of scanning electron microscopy, revealed predominantly cohesive failure in the case of aluminum samples and adhesive failure in the case of glass samples. Computational modeling revealed a multiple oxygen binding mode for the interaction of furanic polyester molecules with the glass surface and metal atoms. Only sustainable materials were used as a carbon source for the production of target polymers, which showed excellent compatibility with the practically most demanding constructing materials (a universal reusable hot-melt adhesive for copper, brass, Be-copper, Mn-bronze, zinc, aluminum, titanium, and glass).

Mechanistic Study of Pd/NHC‐Catalyzed Sonogashira Reaction: Discovery of NHC‐Ethynyl Coupling Process

Eremin D.B., Boiko D.A., Kostyukovich A.Yu., Burykina J.V., Denisova E.A., Anania M., Martens J., Berden G., Oomens J., Roithová J., Ananikov V.P, Chem. Eur. J., 2020, 67, 15672-15681.
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The product of a revealed transformation — NHC‐ethynyl coupling — was observed as a catalyst transformation pathway in the Sonogashira cross‐coupling, catalyzed by Pd/NHC complexes. The 2‐ethynylated azolium salt was isolated in individual from and fully characterized, including the X‐Ray analysis. A number of possible intermediates of this transformation with common formulae (NHC)xPd(C2Ph) (x = 1,2) were observed and subjected to collision‐induced dissociation (CID) and infrared multiphoton dissociation (IRMPD) experiments studies to elucidate their structure. Measured bond dissociation energies (BDEs) and IRMPD spectra were in an excellent agreement with quantum calculations for coupling product π‐complexes with Pd(0). Molecular dynamics simulations confirmed multiple observed CID fragmentation pathways. Performed study of catalyst evolution suggests the reported transformation to be considered in the development of new catalytic systems for alkyne functionalization reactions.

Preventing Pd-NHC Bond Cleavage and Switching from Nano-Scale to Molecular Catalytic Systems: Amines and Temperature as Catalyst Activators

Khazipov O. V., Shevchenko M. A., Pasyukov D. V., Chernenko A. Yu., Astakhov A. V., Tafeenko V. A., Chernyshev V. M., Ananikov V. P., Catal. Sci. Technol., 2020, 10, 1228-1247 .
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Many reactions catalyzed by Pd complexes with N-heterocyclic carbene (NHC) ligands are performed in the presence of amines which usually act as coupling reagents or mild bases. However, amines can react with Pd/NHC complexes in a number of ways: enhancing molecular catalysis, causing the catalyst deactivation or triggering the ligandless modes of catalysis by producing NHC-free active palladium species. This study gains insight into conditions required for the efficient use of amines as activators of molecular Pd/NHC catalysis and preventing the undesirable reductive cleavage of the Pd-NHC bond in catalytic systems. Reactions of Pd/NHC complexes with various amines within a temperature range of 25–140 °C and thermal stability of the resulting amino-complexes are examined. The results indicate the major influence of the amine structure and reaction temperature on the catalyst transformations. In particular, thermal decomposition of Pd/NHC complexes with aliphatic amine ligands predominantly leads to the reductive Pd-NHC bond cleavage, while deprotonation of the complexes with primary and secondary aliphatic amine ligands in the presence of strong bases at 25–60 °C promotes the activation of molecular Pd/NHC catalysis. Efficient Pd-PEPPSI complex – amine systems suitable for the strong-base-promoted C-S cross-coupling reactions between aryl halides and thiols are suggested on the basis of these findings.

Calcium Carbide Looping System for Acetaldehyde Manufacturing from Virtually any Carbon Source

Rodygin K.S., Lotsman K.A., Ananikov V. P., ChemSusChem, 2020, 13, 3679-3685.
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A vinylation/devinylation looping system for acetaldehyde manufacturing was evaluated. Vinylation of iso‐butanol with calcium carbide under solvent‐free conditions was combined with hydrolysis of the resulting iso‐butyl vinyl ether under slightly acidic conditions. Acetaldehyde produced by hydrolysis was collected from the reaction mixture by simple distillation, and the remaining alcohol was redirected to the vinylation step. All the inorganic co‐reagents can be looped as well, and the full sequence is totally sustainable. A complete acetaldehyde manufacturing cycle was proposed on the basis of the developed procedure. The cycle was fed with calcium carbide and produced the aldehyde as a single product in a total preparative yield of 97 %. No solvents, hydrocarbons, or metal catalysts were needed to maintain the cycle. As calcium carbide in principle can be synthesized from virtually any source of carbon, the developed technology represents an excellent example of biomass and waste conversion into a valuable industrial product.

Electron Microscopy Dataset for the Recognition of Nanoscale Ordering Effects and Location of Nanoparticles

Boiko D.A., Pentsak E.O., Cherepanova V.A., Ananikov V.P., Sci. Data, 2020, 7, 101.
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A unique ordering effect has been observed in functional catalytic nanoscale materials. Instead of randomly arranged binding to the catalyst surface, metal nanoparticles show spatially ordered behavior resulting in formation of geometrical patterns. Understanding of such nanoscale materials and analysis of corresponding microscopy images will never be comprehensive without appropriate reference datasets. Here we describe the first dataset of electron microscopy images comprising individual nanoparticles which undergo ordering on a surface towards the formation of geometrical patterns. The dataset developed in this study spans three levels of nanoscale organization: (i) individual nanoparticles (1–5 nm) and arrays of nanoparticles (5–20 nm), (ii) ordering effects (20–200 nm) and (iii) complex patterns (from nm to μm scales). The described dataset for the first time provides a possibility for the development of machine learning algorithms to study the unique phenomena of nanoparticles ordering and hierarchical organization.

Solid-State C–S Coupling in Nickel Organochalcogenide Frameworks as a Route to Hierarchical Structure Transfer to Binary Nanomaterials

Kashin A. S., Galushko A.S., Degtyareva E. S., Ananikov V. P., Inorg. Chem., 2020, 59, 10835–10844.
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In this work, the transfer of the flexible and easily tunable hierarchical structure of nickel organochalcogenides to different binary Ni-based nanomaterials via selective coupling of organic units was developed. We suggested the use of substituted aryl groups in organosulfur ligands (SAr) as traceless structure-inducing units to prepare nanostructured materials. At the first step, it was shown that the slight variation of the type of SAr units and synthetic procedures allowed us to obtain nickel thiolates [Ni(SAr) 2]n with diverse morphologies after a self-assembly process in solution. This feature opened the way for the synthesis of different nanomaterials from a single type of precursor using the phenomenon of direct transfer of morphology. This study revealed that various nickel thiolates undergo selective C–S coupling under high-temperature conditions with the formation of highly demanding nanostructured NiS particles and corresponding diaryl sulfides. The in situ oxidation of the formed nickel sulfide in the case of reaction in an air atmosphere provided another type of valuable nanomaterial, nickel oxide. The high selectivity of the transformation allowed the preservation of the initial organochalcogenide morphologies in the resulting products.

Application of Ni-Based Metal-Organic Framework as Heterogeneous Catalyst for Disulfide Addition to Acetylene

Degtyareva E. S., Erokhin K. S., Ananikov V. P., Catal. Commun., 2020, 146, 106119.
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Several recent studies have shown unique adsorption activity of metal organic frameworks (MOFs) towards unsaturated hydrocarbons. In the current article, we explored the application of Ni-MOFs for S-functionalization of acetylene. We showed that Ni-MOF-74 catalyzed the reaction of disulfide addition to gaseous acetylene with excellent selectivity. The prime advantage of the proposed Ni-MOF-74 over other examined catalysts was its easy separation and recycling possibility. Moreover, it demonstrated no leaching of Ni species into the solution. The work was supplemented with a study on the catalyst behavior in the course of the reaction by using SEM, EDX, XRD, and FT-IR methods.

Ambident Reactivity of Imidazolium Cations as Evidence of the Dynamic Nature of N‐Heterocyclic Carbene‐Mediated Organocatalysis

Galkin K.I., Karlinskii B.Ya., Kostyukovich A.Yu., Gordeev E.G., Ananikov V.P., Chem. Eur. J., 2020, 26, 8567-8571.
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This work reveals ambident nucleophilic reactivity of imidazolium cations towards carbonyl compounds at the C2 or C4 carbene centers depending on the steric properties of the substrates and reaction conditions. Such an adaptive behavior indicates the dynamic nature of organocatalysis proceeding via a covalent interaction of imidazolium carbenes with carbonyl substrates and can be explained by generation of the H‐bonded ditopic carbanionic carbenes.

Examining the Vinyl Moiety as a Protecting Group for Hydroxyl (-OH) Functionality under Basic Conditions

Voronin V.V., Ledovskaya M.S., Rodygin K.S., Ananikov V.P., Org. Chem. Front., 2020, 7, 1334-1342.
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A method for protection of alcohols with vinyl groups is suggested and studied in detail. The procedures of protection and deprotection via vinylation and devinylation reactions are evaluated. Vinylation reaction is performed using cheap and convenient calcium carbide reagent. Stability of the vinyl group under various conditions is examined. The vinyl group is found to be stable under basic conditions and labile under acidic conditions. The vinyl protecting group shows high tolerance to functional groups and good compatibility with common synthetic reagents. Applicability of the procedure in the Suzuki and Sonogashira catalytic reactions and its flexible utilization in the reaction with Grignard reagent are demonstrated.

Efficient Labeling of Organic Molecules Using 13C Elemental Carbon: Universal Access to 13C2-Labeled Synthetic Building Blocks, Polymers and Pharmaceuticals

Ledovskaya M.S., Voronin V.V., Rodygin K.S., Ananikov V.P., Org. Chem. Front., 2020, 7, 638-647.
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Among different types of labeling, 13C-labeled compounds are the most demanding in organic chemistry, life sciences and materials design. However, 13C-labeled organic molecules are very difficult to employ in practice due to extreme cost. The rather narrow range of labeled organic starting materials and the absence of universal synthetic building units further complicate the problem and make utilization of 13C-labeled molecules hardly possible in many cases. Here we report a versatile approach for 13C2-labeling of organic molecules starting with 13C elemental carbon: 13C carbon is applied for the synthesis of calcium carbide (Ca13C2), which is subsequently used to generate acetylene – a universal 13C2 unit for atom-economic organic transformations. Syntheses of labeled alkynes, O,S,N-functionalized vinyl derivatives, polymers and pharmaceutical substances were demonstrated. Elemental 13C carbon, as the chemically most simple source for 13C2-labeling, here was successfully combined with universal synthetic applicability of alkynes.

Primary Vinyl Ethers as Acetylene Surrogate: a Flexible Tool for Deuterium‐Labeled Pyrazole Synthesis

Ledovskaya M.S., Voronin V.V., Polynski M.V., Lebedev A.N., Ananikov V.P., Eur. J. Org. Chem, 2020, 2020, 4571-4580.
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A novel synthetic path to 1,3‐disubstituted pyrazoles and their deuterated derivatives was developed. It is based on the reaction of vinyl ethers with hydrazonoyl chlorides in the presence of triethylamine. The reaction mechanism, clarified by the joint experimental and computational study, involves 1,3‐dipolar cycloaddition of the in situ generated nitrile imines to vinyl ethers and subsequent cleavage of alcohol from the formed alkoxypyrazoline. The results highlight the possibility of using vinyl ethers as acetylene surrogate and provide a novel access to pyrazoles, 4,5‐dideuteropyrazoles and their regioselectively labeled derivatives, 5‐deuteropyrazoles.

Recent Advances in Applications of Vinyl Ether Monomers for Precise Synthesis of Custom-Tailored Polymers

Kirillov E., Rodygin K.S., Ananikov V.P., Eur. Polym. J., 2020, 136, 109872.
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This review highlights recent progress in the synthesis and application of vinyl ethers (VEs) as monomers for modern homo- and co-polymerization processes. VEs can be easily prepared using a number of traditional synthetic protocols including a more sustainable and straightforward manner by reacting gaseous acetylene or calcium carbide with alcohols. The remarkably tunable chemistry of VEs allows designing and obtaining polymers with well-defined structures and controllable properties. Both VE homopolymerization and copolymerization systems are considered, and specific emphasis is given to the novel initiating systems and to the methods of stereocontrol.

Assessing Possible Influence of Structuring Effects in Solution on Cytotoxicity of Ionic Liquid Systems

Egorova K.S., Posvyatenko A.V., Fakhrutdinov A.N., Kashin A.S., Ananikov V.P., J. Mol. Liquid., 2020, 297, 111751.
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During the last decades, micro-structuring phenomena, formation of polar domains and assembling of nano-scale heterogeneities in ionic liquids (ILs) have been discovered. Here we assess the influence of structuring effects in solution on biological activity of ionic systems. In the present work, we studied cytotoxicity of aqueous solutions of binary mixtures of common ILs and showed that it mostly did not comply with the concentration addition model thus suggesting the occurrence of toxicity-affecting interactions in the media. In most cases, antagonistic effects were observed in the studied systems. Micro-heterogeneous water structures were experimentally detected in the binary IL mixtures for the first time. By using a cytotoxicity assay, NMR spectroscopy and scanning electron microscopy, a novel research direction was explored dealing with a relationship between dynamic structuring effects in ILs and their cytotoxicity.

Widely accessible 3D printing technologies in chemistry, biochemistry and pharmaceutics: applications, materials and prospects

Gordeev E.G., Ananikov V.P., Russ. Chem. Rev., 2020, 89, 1507.
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Representative examples of the application of 3D printing in organic synthesis, biochemistry, biotechnology, analytical chemistry, pharmaceutics and chemical education are considered. It is shown that additive technologies open up new prospects for the development of these fields of science. The characteristics of widely used 3D printing methods (fused deposition modelling and stereolithography) are discussed in the context of chemical applications. It is noted that the key feature of these methods is the wide accessibility of technologies and materials.

The Increasing Value of Biomass: Moving From C6 Carbohydrates to Multifunctionalized Building Blocks via 5‐(hydroxymethyl)furfural

Galkin K.I, Ananikov V.P., ChemistryOpen, 2020, 9, 1135-1148.
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Recent decades have been marked by enormous progress in the field of synthesis and chemistry of 5‐(hydroxymethyl)furfural (HMF), an important platform chemical widely recognized as the "sleeping giant" of sustainable chemistry. This multifunctional furanic compound is viewed as a strong link for the transition from the current fossil‐based industry to a sustainable one. However, the low chemical stability of HMF significantly undermines its synthetic potential. A possible solution to this problem is synthetic diversification of HMF by modifying it into more stable multifunctional building blocks for further synthetic purposes.