Intramolecular Transformations Research Articles

Recent Advances in the Catalytic Synthesis of the Cyclopentene Core.

Five-membered carbocycles are ubiquitously found in natural products, pharmaceuticals, and other classes of organic compounds. Within this category, cyclopentenes deserve special attention due to their prevalence as targets and as well as key intermediates for synthesizing more complex molecules. Herein, we offer an overview summarizing some significant recent advances in the catalytic assembly of this structural motif. A great variety of synthetic methodologies and strategies are covered, including transition metal-catalyzed or organocatalyzed processes. Both inter- and intramolecular transformations are documented. On this ground, our expertise in the application of C-H functionalization reactions oriented towards the formation of this ring and its subsequent selective functionalization is embedded.

Intramolecular transformations of derivatives of the Michael adduct of levoglucosenone and 2-(ethoxycarbonyl)cyclododecanone. 2. Ethylene ketal and its bromination—dehydrobromination products

Intramolecular transformations of derivatives of the Michael adduct of levoglucosenone and 2-(ethoxycarbonyl)cyclododecanone. 2. Ethylene ketal and its bromination—dehydrobromination products

Synthesis of Heterocycles from Donor-Acceptor Cyclopropanes: A Five-Year Recap

AbstractThis review discusses the utility of donor-acceptor cyclopropanes (DACs) for the construction of heterocycles. In addition to (3+2), (3+3), and (4+3) cycloaddition pathways, nucleophilic ring-opening reactions, intramolecular transformations, and cycloisomerizations in the presence of suitable catalysts pave the way for the generation of heterocycles from DACs. The mild reactions conditions employed and the variety of starting materials that can be used as reaction partners make the DAC route for heterocycle synthesis attractive. The literature covered in this review is from the period 2018 to 2023.1 Introduction2 Synthesis of Nitrogen Heterocycles2.1 By Annulations with Anthranils and Azadienes2.2 By Nucleophilic Attack of Anilines and Hydrazones2.3 By Reaction with Ureas and Thioureas2.4 By Annulation Reactions Using an Azomethine Imine2.5 By Reaction with Other Nitrogen Heterocycles2.6 By Other Transformations3 Synthesis of Oxygen Heterocycles3.1 By Intramolecular Transformations3.2 By Intermolecular Reactions4 Synthesis of Sulfur and Selenium Heterocycles4.1 By Reaction with Thiocarbonyl Substrates4.2 By Reaction with Thio- and Selenocyanates and Thiosulfonate Salts5 Synthesis of N–S and N–O Heterocycles6 Conclusions

Stereoselective Synthesis of Highly Functionalized Structures from α‐Bromo α’‐Sulfinyl Ketones

AbstractCrystallization‐Induced Diastereomer Transformation (CIDT) of α‐bromo‐α’‐(R)‐sulfinylketones is reported. The utility of these 1,2‐difunctionalized synthons is convincingly demonstrated by their facile conversion into cyanohydrins and bromohydrins. Furthermore, bromohydrins can be converted into complex arrangements of functionality and stereochemistry through SN2‐like inter and intramolecular transformations.

Transformations and antioxidative activities of lignans and stilbenes at high temperatures

Thermal transformations of polyphenols from the lignan and stilbene families were investigated at temperatures ranging from 200 °C to 250 °C, in polyethylene glycol (PEG-400), dimethylformamide (DMF) and in sunflower oil (SO). The polyphenols showed varying degrees of thermal stabilities and in some cases intramolecular transformations were observed. The formed products were isolated and characterized. Oligomerization of the polyphenols at thermo-oxidative conditions was also investigated. Finally, the antioxidative activity of the polyphenols against thermo-oxidative degradation α-linoleic acid was investigated at 200 °C. The results suggested that the studied substrates retained their antioxidative properties at elevated temperatures, with stilbenes showing most efficient protection against thermo-oxidative degradation of polyunsaturated fatty acids.

Recent Advances in 1,2-Amino(hetero)arylation of Alkenes.

Alkene amino(hetero)arylation presents a highly efficient and straightforward strategy for direct installation of amino groups and heteroaryl rings across a double bond simultaneously. An extensive array of practical transformations has been developed via alkene difunctionalization approach to access a broad range of medicinally valuable (hetero)arylethylamine motifs. This review presents recent progress in 1,2-amino(hetero)arylation of alkenes organized in three different modes. First, intramolecular transformations employing C, N-tethered alkenes will be introduced. Next, two-component reactions will be discussed with different combination of precursors, N-tethered alkenes and external aryl precursor, C-tethered alkenes and external amine precursor, or C, N-tethered reagents, and alkenes. Last, three-component intermolecular amino(hetero)arylation reactions will be covered.

Стереоконтролируемые внутримолекулярные превращения (-)-α сантонина

Chemical transformations of eudesmane sesquiterpene γ-lactones, leading to new biologically active compounds, have become an important direction in medicinal chemistry. This article discusses the stereoscopic intramolecular transformations of the sesquiterpene γ-lactone of the eudesmanic structure (-)-α santonin, a perspective natural compound characterized by a wide spectrum of biological activity.Stereoselective synthesis of new practically significant cis-condensed keto-eudesmane esters and ethylated santonin derivatives was carried out at room temperature in an argon atmosphere by the reaction of α-santonin with methyl and ethyl alcohols and alkyl halides in the presence of the Me3CONa-DMF base. It was revealed that, under the reaction conditions, the initial stage of santonin carbanion formation initiates subsequent stages of intramolecular electrophilic rearrangements with the formation of anenolate ion, which futhur interacts stereoselectively with nucleophilic and electrophilic reagents.It was shown that the synthesis of C4-α-ethyl-santonin with a six-membered ring configuration in the form of a distorted chair-chair can serve as a confirmation of the proposed mechanism of formation of practically valuable 6-keto-eudesmane ethers. In this article, the structure and spatial structure of the synthesized compounds is established using modern physicochemical and spectroscopic (1H NMR, 2D COZY NMR, NOESY, mass-spectrometry and X-ray structural analysis) research methods.

Compression Behavior and Vibrational Properties of New Energetic Material LLM-105 Analyzed Using the Dispersion-Corrected Density Functional Theory.

The 2,6-diamino-3,5-dinitropyrazine-1-oxide (LLM-105) is a newly energetic material with an excellent performance and low sensitivity and has attracted considerable attention. On the basis of the dispersion-corrected density functional theory (DFT-D), the high-pressure responses of vibrational properties, in conjunction with structural properties, are used to understand its intermolecular interactions and anisotropic properties under hydrostatic and uniaxial compressions. At ambient and pressure conditions, the DFT-D scheme could reasonably describe the structural parameters of LLM-105. The hydrogen bond network, resembling a parallelogram shape, links two adjacent molecules and contributes to the structure stability under hydrostatic compression. The anisotropy of LLM-105 is pronounced, especially for Raman spectra under uniaxial compression. Specifically, the red-shifts of modes are obtained for [100] and [010] compressions, which are caused by the pressure-induced enhance of the strength of the hydrogen bonds. Importantly, coupling modes and discontinuous Raman shifts are observed along [010] and [001] compressions, which are related to the intramolecular vibrational redistribution and possible structural transformations under uniaxial compressions. Overall, the detailed knowledge of the high-pressure responses of LLM-105 is established from the atomistic level. Uniaxial compression responses provide useful insights for realistic shock conditions.

Encapsulation of photochromic compounds possessing positive and negative photochromism

The photochromic compounds are of great interest due to their unique ability to undergo reversible intramolecular transformations under the influence of light, accompanied by changes in the absorption spectrum. The aim of the present work is the development of the polymer system for encapsulation of the photochromic compounds with maintaining the photochromic properties. The core–shell capsules were produced by a versatile one-step ultrasound treatment. The capsules possess positive or negative photochromic effects depending on the nature of the photochromic systems to be encapsulated. The capsules are demonstrated a noticeable photochromic reaction, which could find a broad application in various fields including information and biomedical technologies.

Advances in the synthesis of three-dimensional molecular architectures by dearomatizing photocycloadditions

The dearomatizing photocycloaddition reaction is a powerful and effective strategy for synthesizing complex, three-dimensional, polycyclic scaffolds from simple aromatic precursors. Generally, the dearomatizing photocycloaddition reaction is promoted by visible light and occurs via an energy transfer (EnT) process. This mini-review provides an overview of recent advances in this area (2018–2020), encompassing both intramolecular and intermolecular transformations. While the majority of the studies are centered on intramolecular processes due to their predictable regio- and stereo-selectivity, intermolecular transformations that show an exceptionally broad substrate scope are beginning to emerge.

Electrochemically Driven Radical Reactions: From Direct Electrolysis to Molecular Catalysis.

Organic radicals are versatile synthetic intermediates that provide reactivities and selectivities complementary to ionic species. Despite its long history, electrochemically driven radical reactions remain limited in scope. In the past few years, there have been dramatic increase in research activity in organic electrochemistry. We have been developing electrochemical and electrophotocatalytic methods for the generation and synthetic utilization of organic radicals. In our studies, various radical species such as alkene and arene radical cations and carbon- and heteroatom-centered radicals are generated from readily available precursors through direct electrolysis, molecular electrocatalysis or molecular electrophotocatalysis. These radical species undergo various inter- and intramolecular oxidative transformations to rapidly increase molecular complexity. The simultaneous occurrence of anodic oxidation and cathodic proton reduction allows the oxidative reactions to proceed through H2 evolution without external chemical oxidants.

Mannich-Type Reaction of α-Sulfanyl N-tert-Butanesulfinylimidates: Diastereoselective Access to α-Mercapto-β-amino Acid Derivatives.

A series of α-mercapto-β-amino acid derivatives were synthesized diastereoselectively in good yields through the aza-enolization of α-sulfanyl N-tert-butanesulfinylimidates, followed by their nucleophilic addition to N-tosyl imines via a Mannich-type reaction. The resulting derivatives bearing a β-sulfonylamino sulfide moiety participated in further inter- and intramolecular transformations involving episulfonium ion intermediates generated through neighboring-group participation.

The Application of Generalized Rayleigh Equation for Description of Periodic Intramolecular Rearrangements, Including Valence Tautomerism

In the paper, the possible application of the generalized Rayleigh equation for description of intramolecular periodic transformations, including valence tautomerism occurring in molecular multi-electron systems is discussed. This possibility is based on the fact that such a transformation is associated with a self-oscillating process, the parameters of which are selected using Prigogine - Lefever model. Such a self-oscillatory process is nothing but the periodic overcoming of the energy barrier separating the states between which the transitions take place. These states can be realized for molecular systems, the behavior of which at the level of the macroworld is connected with the manifestation of nonlinearity of intramolecular processes. Owing to such features of the structure and dynamics of a molecular, nonlinearities become possible that ensures periodicity in the change of a parameter characterizing behavior of the system. A qualitative analysis of the coefficient before the second term of the generalized Rayleigh equation shows that the oscillations can be stable in time with quite real energy barriers inherent in intramolecular motions. It is shown that coordination compounds containing atoms with unfilled 3d-, 4f- and 5f- shells can be used for this purpose.

Palladium-Catalyzed Enantioselective Cycloadditions of Aliphatic 1,4-Dipoles: Access to Chiral Cyclohexanes and Spiro [2.4] heptanes.

Design and exploration of new intermediates for chemo-, regio-, and stereoselective cycloadditions remain a formidable challenge in modern organic synthesis. Compared to the well-developed 1,3-dipolar cycloadditions, Pd-catalyzed1,4-dipolar cycloadditions are generally limited to specialized substrates due to the inherent nature of the thermodynamically driven intramolecular transformations and undesired isomerizations. Herein, we demonstrate the use of ligated palladium catalysts to control and modulate the intermolecular reactivity of aliphatic 1,4-dipoles, enabling two distinctive cycloaddition pathways with a broad scope of acceptors. This atom-economic process also features an eco-friendly in situ deprotonation strategy to generate the corresponding active palladium-mediated dipoles. Overall, a diverse array of chiral 6-membered rings and spiro [2.4] heptanes were prepared in high yield and selectivity. In addition, an unexpected property of cyano-stabilized carbanions was discovered and investigated, which can be useful in designing and predicting future transformations.

The Problem of Dynamic Process Manifestation in Identification of Organic Compounds by NMR Spectroscopy

The number, shape and position of NMR spectral lines depend on dynamic processes, and this creates certain difficulties in identification of pharmaceutical substances by NMR spectroscopy. The aim of the paper was to study instances of manifestation of intramolecular dynamic processes that affect identification of organic compounds by NMR, and to illustrate the potential of the methods used for their reduction, as well as associated problems.Materials and methods: 1H and 13C spectra of the following pharmaceutical substances: «buserelin acetate», «valsartan», «goserelin acetate», «iopromide», «clopidogrel hydrogensulfate», «omeprazole», «proroxan», «risperidone», «triptorelin acetate», and «enalapril maleate» were used to demonstrate negative effects of dynamic processes. The spatial structures of conformers were established by 1H-1H ROESY experiments. The quantum-chemical calculation of geometric and thermodynamic characteristics of different conformers was carried out by the PM3 method, and electronic characteristics—by the AM1 method with the help of the HyperChem software.Results: the authors analysed intramolecular dynamic processes which are most commonly encountered in expert work: pyramidal inversion of nitrogen in a heterocyclic compound (risperidone, proroxan, clopidogrel), rotation of molecular fragments around the amide bond (valsartan, iopromide, enalapril), prototropic rearrangements (buserelin, goserelin, omeprazole, triptorelin). The change in exchange rates was explained from the perspective of the change in the system of intra- and intermolecular nonvalent interactions.Conclusions: the use of traditional methods for increasing the rate of dynamic processes (increasing the temperature and changing the solvent) does not always eliminate the negative effects of intramolecular transformations. Methods of smoothing the spectral manifestations of dynamic processes have limited application due to strong intramolecular nonvalent interactions which prevent the conversion of the dynamic process rate into fast exchange. Experts and manufacturers should take into account the manifestation of dynamic processes during identification of pharmaceutical substances by NMR spectroscopy.

A constitutive model for block-copolymers based on effective temperature

Phase segregated copolymers such as elastomeric copolymers find myriad applications especially in impact resistant structures. When domains with varying relaxation characteristics are present, these polymers exhibit thermorheologically complex behaviour. The multiple relaxation processes are herein captured using the effective temperature based thermodynamics, used extensively in modelling thermo-mechanical response of metals and polymers. Specifically, we use two slowly evolving configurational subsystems and a fast evolving kinetic-vibration (K-V) subsystem. The two configurational subsystems represent the inter-molecular and intra-molecular meso-scale configurational transformations occurring within the two domains. The K-V subsystem represents the faster atomic vibrations. The configurational subsystems are weakly coupled with the K-V through heat exchange which accounts for structural relaxations of the individual domains towards the equilibrium microstructure. Based on this, we are able to capture strain rate dependence and strain induced softening of these materials under cyclic loads. In comparison with the existing formulations for such copolymers, ours is perhaps a more transparent approach, as it uses quantities such as volume fraction, glass transition temperatures of individual domains as material parameters. Indeed, our formulation could be readily adapted for non-elastomeric copolymers. It should also be potentially useful as a design tool for copolymers with increased glass transition range.

Divergent Synthesis of Densely Substituted Arenes and Pyridines via Cyclotrimerization Reactions of Alkynyl Triazenes.

Densely substituted fused aromatic triazenes can be prepared by [2 + 2 + 2] cyclotrimerization reactions of 1-alkynyl triazenes. The Cp*Ru-catalyzed cyclization proceeds well with both simple alkynyl triazenes and tethered 1-diynyl triazenes. Attractively, the methodology can be extended to pyridine synthesis by replacing an alkyne with a nitrile. The reaction is regioselective and yields the sterically more hindered product. The triazene group precisely installed on the synthesized aryl and pyridyl ring is a highly versatile moiety, which is effortlessly converted into the most important and frequently used functional aryl substituents, including fluorides. It is also suited for intramolecular transformations to afford a variety of valuable heterocycles. The coordination chemistry of alkynyl triazenes and Cp*RuCl was studied and led to the structural characterization of a Cp*RuCl(η2-alkyne) complex, a Cp*RuCl(η4-cyclobutadiene) complex, and an unusual dinuclear Ru complex with a bridging tetramethylfulvene ligand. Complexes of this type are potentially involved in catalyst deactivation pathways.

Gold-Catalyzed Homogeneous (Cyclo)Isomerization Reactions.

Gold is currently one of the most used metals in organometallic catalysis. The ability of gold to activate unsaturated groups in different modes, together with its tolerance to a wide range of functional groups and reaction conditions, turns gold-based complexes into efficient and highly sought after catalysts. Natural products and relevant compounds with biological and pharmaceutical activity are often characterized by complex molecular structures. (Cyclo)isomerization reactions are often a useful strategy for the generation of this molecular complexity from synthetically accessible reactants. In this review, we collect the most recent contributions in which gold(I)- and/or gold(III)-catalysts mediate intramolecular (cyclo)isomerization transformations of unsaturated species, which commonly feature allene or alkyne motifs, and organize them depending on the substrate and the reaction type.

On the mechanism for the photooxidation of aromatic azides containing a secondary N–H bond: A sequence of intramolecular transformations with the formation of heterocyclic oximes

During the photooxidation of aromatic azides containing a secondary N–H bond at the para-position, a sequence of intramolecular transformations of nitroso oxides led to the formation of heterocyclic oximes along with the corresponding nitroso and nitro compounds.

Chemiexcitation Efficiency of Intermolecular Electron-transfer Catalyzed Peroxide Decomposition Shows Low Sensitivity to Solvent-cavity Effects.

Intermolecular chemically initiated electron exchange luminescence (CIEEL) systems are known to possess low chemiluminescence efficiency; whereas, the corresponding intramolecular transformations are highly efficient. As the reasons for this discrepancy are not known, we report in this work our studies of the solvent-cavity effect on the efficiency of two intermolecular CIEEL systems, the catalyzed decomposition of diphenoyl peroxide and of a relatively stable 1,2-dioxetanone derivative, spiro-adamantyl-1,2-dioxetanone. The results indicate a very low medium viscosity effect on the quantum yields of these systems, a priori not compatible with these bimolecular transformations, showing also that their low efficiency cannot be due to solvent-cavity escape of intermediate radical ion pairs. In addition, the solvent-cage effect on the CIEEL efficiency, after the occurrence of the initial electron transfer, proved also to be very low, indicating the intrinsic low viscosity effect on the chemiexcitation step. Therefore, it is concluded that the low efficiency of these systems is intrinsic to the chemiexcitation step and cannot be improved by medium viscosity effects, being possibly due to sterical hindrance on charge-transfer complex formation in the initial step of the CIEEL.