Cyclization Reactivity Research Articles

Synthesis of New Structural Analogues of Natural Integrastatins with a Basic Epoxybenzo[7,8]oxocine Skeleton: Combined Experimental and Computational Study

AbstractIn this work, the cyclization reactivity of various 3-acetyl-2-methylpyridines (including 3-acetyl-2-methylquinoline) containing both electron donor and acceptor substituents with salicylaldehyde into epoxybenzooxocino[4,3-b]pyridine derivatives was studied. The reactions were carried out in mild (under room temperature or reflux in 2-propanol) and harsh (in a sealed glass ampoule) conditions. It was shown that 3-acetyl-2-methylpyridines with an aryl substituent in the 4-position do not react with salicylaldehyde either under normal convection heating conditions or under more severe conditions. This effect was explained by the steric hindrance of the substituents using quantum chemical calculations. It was found that electron donor substituents in 3-acetyl-2-methylpyridines significantly facilitate cyclization in epoxybenzooxocino[4,3-b]pyridines. The presence of electron acceptor substituents (NO2 group for example) in the 5-position of pyridine prevents cyclization under normal conditions, but gives a rather high conversion to oxocinopyridines under more specific conditions. This effect is quantum-chemically explained by the decrease in the basicity of pyridine. Pyridines with two pairs of methyl groups in ortho-positions to the acetyl group are capable to form mixtures of regioisomeric epoxybenzooxocinopyridines. Further, epoxybenzooxocinopyridines with methyl and acetyl groups can form a mixture of diastereomeric bisoxocins under more specific conditions. All 17 initial pyridines were studied quantum-chemically in order to understand what features of their structure and properties affect the success of the cyclization reaction and the yield of the target product. The pyridine molecules were calculated by the DFT RB3LYP/6-311++G(d,p) method taking into account the alcohol solvent within the CPCM model using Gaussian-2016 program. It was shown that the absence of steric hindrances in the form of bulky substituents in 4-position of pyridines is the main factor affecting the success of the cyclization reaction. Also, the yield of the target product is affected by the CH-acidity of the methyl group in 2-position, which, in turn, is affected by electron-donating and electron-withdrawing substituents in the 5- and 6-positions.

Precursor synthesis strategy for polycyclic aromatic conjugated polymers on the application of supercapacitors

Polycyclic aromatics (PCAs) possess excellent photoelectric properties, but the construction of such compounds has been a quite challenging subject of study, mainly due to very low solubility. Herein we report a precursor synthesis strategy for polycyclic aromatic conjugated polymers. A soluble precursor polymer, that containing fusible “double U-shaped aromatic” (DUA) and perylenetetracarboxydiimide (PDI) units, was firstly synthesized by Suzuki coupling. The stereo aromatic units in polymer backbone were found to be converted into polycyclic aromatic units, i.e. hexa-peri-hexabenzocoronene (HBC), by chemical or electrochemical oxidation, which resulted in a formation of insoluble polycyclic aromatic conjugated polymers. The electrochemical oxidations that occurred at the interface of electrode and solution exhibited higher cyclization reactivity and leads to the formation of high quality films on the electrode surface. Characterization by Raman and UV-visible (UV-Vis) spectroscopy validated the successful formation of this HBC structure. Some potential applications of such thin films are being explored, and here we focus on the characteristics of supercapacitors based on their excellent electrochemical properties.

From Osmium Hydrido Vinylidene to Osmacycles: The Key Role of Osmabutadiene Intermediates

Osmium hydrido vinylidene 1 shows diverse cyclization reactivity with activated terminal alkynes. Treatment of 1 with HC≡CCOR' (R'=OEt and Me) gave osmafurans 3a and 3b via osmium alkenyl/vinylidenes 2a and 2b. In addition, 1 reacted with HC≡CCH(OH)C≡CH to yield osmabenzene 4, in which the alkynol acted as a C(5) fragment to cyclize with 1. Mechanistic analysis indicates that these reactions and the previous formal [3+3] cycloadditions between 1 and HC≡CCH(OH)R (R=Ph, Et, and vinyl) or HC≡CCH(OEt)(2) all go through similar osmabutadiene intermediates. Subsequently, the intermediates either took a "coordination and cyclization" process or a "carbon-carbon coupling" path to cyclization, depending on the coordination ability of substituents on the terminal alkenyl carbon atom.

Serendipitous synthesis of 3-hydroxy tetrahydrofurans from tin catalyzed sulfonylation of acyclic 1,2,4-triols

The reaction of syn-1,2,4-triols under sulfonylation conditions catalyzed by Bu2SnO (5mol%) results in cyclization and the formation of 3-hydroxy tetrahydrofurans (56–85%) while the anti-1,2,4-triols react to give C1-O-sulfonyl derivatives in good yields (66–83%) and the cyclization product in poor yield (5–12%). A mechanism that justifies these observations is proposed to occur via the tosylation of the primary hydroxyl followed by an intramolecular tin acetal rearrangement to a 1,3-stannylene which then undergoes a 5-exo-tet-cyclization. The difference in rates of cyclization reactivity is due to the energetically more stable tin acetals of syn-1,3-diols compared to those of anti-1,3-diols.

Ring-Construction/Stereoselective Functionalization Cascade: Total Synthesis of Pachastrissamine (Jaspine B) through Palladium-Catalyzed Bis-cyclization of Propargyl Chlorides and Carbonates

Palladium(0)-catalyzed cyclization of bromoallenes, propargyl chlorides, and carbonates bearing hydroxy and benzamide groups as internal nucleophiles stereoselectively provides functionalized tetrahydrofuran. Cyclization reactivity is dependent on the relative configuration of the benzamide and leaving groups, and on the nature of the leaving groups. This bis-cyclization was used as the key step in a short total synthesis of pachastrissamine, which is a biologically active marine natural product.

Structure Modulated Electronic Contributions to Metalloenediyne Reactivity: Synthesis and Thermal Bergman Cyclization of MLX2 Compounds

The synthesis of novel metalloendiyne complexes MLRX(2) (where L = 1,4-dibenzyl/diethyl-1,4-diaza-cyclododec-8-ene-6,10-diyne, X = halogen) are reported with their X-ray crystal structures and thermal Bergman cyclization temperatures. Two distinct types of constructs are obtained; the Zn(II) compounds are tetrahedral, while the Cu(II) and the Pd(II) compounds are all distorted- or square-planar. Each possesses structurally similar enediyne conformations and critical distances (3.75-3.88 A). The tetragonal Cu(II) species all exhibit Bergman cyclization temperatures between 140 and 150 degrees C in the solid state, while the square-planar Pd(II) analogues possess similar critical distances but cyclize at significantly higher temperatures (205-220 degrees C). In contrast, the Zn(II) derivatives show a marked halogen dependence, with X = Cl having the highest Bergman cyclization temperature, which is comparable to the Pd(II) square-planar set, while the ZnLX(2) compound with X = I shows the lowest Bergman cyclization temperature (144 degrees C), similar to the Cu(II) derivatives. Moreover, for the planar constructs, the R group has little influence on the cyclization temperatures; however, for the tetrahedral ZnLX(2) compounds, the steric influence of the R group plays a more significant role in the cyclization reaction coordinate by influencing the stability of the precyclized intermediate. This complex set of results is best interpreted by a combination of steric contributions and electronic interactions between the halogen through space (in the case of Zn(II)) and through bonds (in the case of Pd(II)) and the pi orbitals of the endiyne fragment. In contrast, for Cu(II) systems, the distorted square-planar geometry permits neither direct through space nor symmetry-allowed through bond communication between the orbital partners, and thus little variation in Bergman cyclization reactivity is observed.

Metalloenediynes: Advances in the Design of Thermally and Photochemically Activated Diradical Formation for Biomedical Applications

The remarkable discovery of the enediyne antitumor antibiotics almost two decades ago has led to significant developments in the systematic design and study of simple synthetic enediyne constructs and their Bergman cyclization reactivities. Advances in understanding both the geometric and electronic factors that are important in influencing the activation barrier to formation of the potent 1,4-phenyl diradical intermediate in simple organic enediynes have been made as a first step to the development of synthetic agents for biomedical uses. Progress in these areas has also served as a benchmark and guideline for a new wave of inorganic metalloenediyne constructs that display variable and wide-ranging reactivity or stability depending upon the geometric or electronic structure of the resulting complex. In general, metal sites offer additional structural flexibilities over their carbocyclic or acyclic organic analogues, which contributes greatly to their intriguing Bergman cyclization reactivities. This is true not only for thermal cyclization of metal-bound enediyne ligands in which the metal acts as a scaffold or Lewis acid, but also for photoelectronic or photothermal Bergman cyclization which can be achieved via metal-ligand charge transfer excited states. These reactivity developments parallel new protein targeting strategies for simple enediynes constructs, suggesting that a combined approach of controlled initiation and site specific targeting may allow enediynes to truly reach their full potential in biomedical applications.

Dynamic Monte Carlo Simulation of Gelation with Extensive Cyclization

Recent investigations have implicated cagelike precursors in the unusually high gelation conversion (∼82%) of acid-catalyzed tetraethoxysilane. However, the statistical models used so far cannot capture kinetic or composition-dependent features of alkoxysilane polycondensation. Here we take a first step toward unified modeling of the kinetics and structure of silica gelation. Dynamic Monte Carlo simulations [Šomvársky, J.; Dušek, K. Polym. Bull. 1994, 33, 369] are developed which permit competition between extensive cyclization and growth. The model includes well-established kinetic trends (hydrolysis preequilibrium and first-shell substitution effects). As a first approximation, unimolecular-like terms for cyclization reactivity follow the experimental pattern of bimolecular rate coefficients. The present simulations allow unlimited formation of three-site rings, giving rise to many structures that are not those of real silicates (where four-site rings dominate). However, the level of cyclization (both cycles per molecule and per site) is consistent with that of real silicates and is enough to delay gelation to 82% conversion or higher. These simulations also display a broader range of gelation behavior than prior kinetic models. At high to moderate monomer concentrations, competition between cyclization and growth causes the expected delay of gelation. Upon further dilution, we discover a third regime, absent from prior kinetic gelation models but important for siloxanes: formation of a distribution of polycyclic precursors that still retain enough functionality to gel.

Cyclizations of 5-Hexenyl, 6-Heptenyl, 7-Octenyl, and 8-Nonenyl Radicals. The Kinetic and Regiochemical Impact of Fluorine and Oxygen Substituents

Using competition kinetic methodology, rate constants for cyclizations of a series of hydrofluorocarbon (HFC) and ether 5-hexenyl, 6-heptenyl, and 7-octenyl radicals have been determined. Remarkably large rate constants (>107 s-1) have been observed for 6-exo-cyclizations of 1,1,2,2-tetrafluoro- and 1,1,2,2,3,3,4,4,-octafluoro-6-heptenyl radicals (>103 those of analogous hydrocarbon radicals), whereas HFC hexenyl and heptenyl ethers exhibit lower cyclization reactivity, as do HFC 7-octenyl radical systems, which cyclize in an endo manner. HFC 8-nonenyl radicals were not observed to cyclize. The results can be rationalized in terms of transition state polar influences, though other factors may also play significant roles.

ChemInform Abstract: Remarkable Cyclization Reactivities of Partially Fluorinated 6‐Heptenyl Radicals.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Remarkable Cyclization Reactivities of Partially-Fluorinated 6-Heptenyl Radicals

Remarkable Cyclization Reactivities of Partially-Fluorinated 6-Heptenyl Radicals

ChemInform Abstract: Cyclization Reactivities of Fluorinated Hex‐5‐enyl Radicals

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Cyclization reactivities of fluorinated hex-5-enyl radicals

A kinetic study of the effect of fluorine substitution on the rates and regiochemistry of hex-5-enyl radical cyclization is reported. One or more fluorines on or proximate to the double bond of the radical have relatively little electronic effect on either rate or regiochemistry, whereas fluorines substituted at the radical end can have a dramatic impact on both. The relative reactivities of such partially-fluorinated hex-5-enyl radicals can be understood largely in terms of polar effects on the transition state, but radical pyramidalization and, to a lesser extent, addition thermodynamics play a role. The relationship between these fluorine substituent effects and the cyclopolymerizations of fluorinated α,ω-dienes are discussed.

Studies on hetero-cage compounds—VI : Transannular cyclizations in pentacyclo[6.2.1.0. 2,70. 4,100 5,9]undecan-3,6-dione system

Several 4-oxa- and -aza-bird-cage compounds were prepared by transannular cyclizations of pentacyclo[6.2.1.0. 2,70. 4,100 5,9]undecan-3,6-dione ( 3). Diol derivatives of 3 cyclized to afford the corresponding 4-oxa-bird-cage derivatives such as 9, 16a and 16b. The corresponding 3-keto-6-ol derivatives ( 6, 10a and 10b) did not cyclize transannularly, while 3-imino-6-ol, 3-keto-6-amino, and 3- imino-6-amino type derivatives cyclized to afford 3-substituted 4-oxa- and -aza-bidr-cage compounds such as 12, 14 and 18. The transannular cyclization reactivity in the 3 system has been compared with that in the bicyclo[3.3.1]nona-3,7-dione system ( 1).

Viscoelastic properties of epoxy resin. I. Effect of prepolymer structure on viscoelastic properties

AbstractThe intermolecular cyclization reaction is investigated in highly crosslinked epoxy systems, where diepoxides with different mobilities between terminal epoxy groups were crosslinked with ethylene diamine. Based on the measured values of the Clash‐Berg 10‐sec modulus in the rubbery region, the correlation between the mobility and the cyclization reactivity of the diepoxides is discussed. The epoxide with higher mobility is found to have a higher rubbery modulus than that with lower mobility, as was expected. This is tentatively explained by the difference in the reactivity of the formation of the 11‐membered ring. Dynamic mechanical measurements were also run on a forced vibration apparatus. The higher β‐transition peak of the polymer of bisphenol‐A diglycidyl ether was interpreted in terms of its higher free volume as well as lower density and lower glassy modulus. The higher modulus in the glassy region of ethylene glycol diglycidyl ether–ethylenediamine was explained on the basis of hydrogen bonding.