Ene Moiety Research Articles

A theoretical view on the stereochemistry of 1,3-benzoxazol-2-(3H)-ylidenes obtained from double vinylic substitution.

2-(1,3-Benzoxazol-2(3H)-ylidene)-3-oxo-3-phenylpropanenitrile (1) and methyl-2-(1,3-benzoxazol-2(3H)-ylidene)(cyano)acetate (2) are observed as single isomers by NMR spectroscopy. A theoretical study was carried out to investigate if this is due to the exclusive presence of the most stable diastereoisomer or if the ene moiety undergoes fast rotation, thereby allowing for the observation of an average conformer. Indeed, the pronounced stabilization of the E stereoisomer, attributed to intramolecular hydrogen bonding, makes it the single obtained product.

Thiol-Ene Photo-Click Hydrogels with Tunable Mechanical Properties Resulting from the Exposure of Different -Ene Moieties through a Green Chemistry.

Temperature and light responsiveness are widely exploited stimuli to tune the physico-chemical properties of double network hydrogels. In this work, new amphiphilic poly(ether urethane)s bearing photo-sensitive moieties (i.e., thiol, acrylate and norbornene functionalities) were engineered by exploiting the versatility of poly(urethane) chemistry and carbodiimide-mediated green functionalization procedures. Polymers were synthesized according to optimized protocols maximizing photo-sensitive group grafting while preserving their functionality (approx. 1.0 × 1019, 2.6 × 1019 and 8.1 × 1017 thiol, acrylate and norbornene groups/gpolymer), and exploited to prepare thermo- and Vis-light-responsive thiol-ene photo-click hydrogels (18% w/v, 1:1 thiol:ene molar ratio). Green light-induced photo-curing allowed the achievement of a much more developed gel state with improved resistance to deformation (ca. 60% increase in critical deformation, γL). Triethanolamine addition as co-initiator to thiol-acrylate hydrogels improved the photo-click reaction (i.e., achievement of a better-developed gel state). Differently, L-tyrosine addition to thiol-norbornene solutions slightly hindered cross-linking, resulting in less developed gels with worse mechanical performances (~62% γL decrease). In their optimized composition, thiol-norbornene formulations resulted in prevalent elastic behavior at lower frequency compared to thiol-acrylate gels due to the formation of purely bio-orthogonal instead of heterogeneous gel networks. Our findings highlight that exploiting the same thiol-ene photo-click chemistry, a fine tuning of the gel properties is possible by reacting specific functional groups.

Well defined and responsive amphiphilic block copolymers synthesized using TEMPO initiated thiol-ene reaction

Well defined and responsive amphiphilic block copolymers based on poly(N-isopropyl acrylamide)-b-poly(isobornyl acrylate) (PNIPAM-b-PiBoA), poly(styrene)-b-poly(acrylic acid) (PS-b-PAA) and poly(isobornyl acrylate)-b-poly(acrylic acid) (PiBoA-b-PAA) were synthesized using 2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO) initiated thiol-ene reaction under ambient conditions. The preparation of two blocks for conjugation via TEMPO initiated thiol-ene reaction was carried out through Reversible Addition-Fragmentation Chain Transfer (RAFT) and high-temperature polymerization. RAFT polymerization of NIPAM, styrene and AA followed by aminolysis resulted in thiol-functionalized PNIPAM, PS and PAA. The high-temperature polymerization of iBoA resulted in PiBoA functionalized with Ene moiety. The characterization of the synthesized homopolymers was performed using 1H NMR spectroscopy, UV–vis spectroscopy, Fourier-transform infrared (FT-IR) spectroscopy and size exclusion chromatography (SEC). In order to synthesize amphiphilic block copolymers, TEMPO initiated thiol-ene reaction was utilized for the conjugation of a thiol-functionalized block with an Ene functionalized block. The progress of thiol and ene conjugation was monitored via1H NMR spectroscopy. Based on 1H NMR results, quantitative conversions were obtained in 16 h under ambient conditions. The synthesized amphiphilic block copolymers were characterized using variety of techniques, for example, 1H NMR spectroscopy, UV–vis spectroscopy, SEC, FT-IR spectroscopy, Atomic force microscopy (AFM), X-ray photoelectron spectroscopy (XPS), Zeta potential and dynamic light scattering (DLS).

An acyclic enediyne anticancer compound attributed to a Bergman cyclization at physiological temperature

Enediyne cytotoxic drugs have attracted much attention because of their unique structure and potent anticancer activity. However, acyclic enediynes are long considered as inactive at physiological temperature due to their long C1-C6 distance. By adjusting the steric bulkiness of the functional groups at the alkynyl termini and the electron-withdrawing effect at the ene moiety, herein, a simple acyclic enediyne was designed and synthesized to achieve the onset of thermal Bergman cyclization at physiological temperature in polar solvents. The spontaneous generation of diradical intermediates was confirmed through EPR analysis and further supported by spin trapping experiment, radical indicator experiment, and high resolution MS analysis. The reactive diradicals generated in aqueous media induced single and double stranded cleavage of DNA, and showed high cytotoxicity to Hela cells. The IC50 value of the enediyne compound is comparable to many clinical used anti-tumor agents.

Enantioselective carbonyl-ene-type cyclization of α-ketoester and 2-substituted vinylsilane catalyzed by a chiral Cu-BOX complex

We developed an enantioselective carbonyl-ene-type cyclization using 2-substituted vinylsilane as a nucleophilic ene moiety catalyzed by a chiral copper-BOX complex. This reaction is the first example of enantioselective carbonyl-ene cyclization using a 1,2-disubstituted olefin. This methodology gave chiral indenols with a tetrasubstituted carbon.

Thiol-ene polymer microbeads prepared under high-shear and their successful utility as a heterogeneous photocatalyst via C60-capping

A series of thiol-ene (1.1:1 equiv) polymer microbeads (PMBs) were prepared via a high-shear suspension photopolymerization method to explore the physical properties of the networks as a function of composition. 1,3,5-triallyl-1,3,5-triazine-2,4,6(1H, 3H, 5H)-trione (TTT) and pentaerythritol tetrakis (3-mercaptopropionate) (PETMP) PMBs were selected for the synthesis of a heterogeneous photocatalyst. Particle size was characterized using DLS and OM, and thermal stability and Tg were assessed using TGA and DSC. PMBs produced from higher functionality monomers produce smaller particles, and Tg increased with monomer rigidity. TTT-PETMP PMBs were derivatized with C60 to demonstrate the accessibility and reactivity of the residual thiols, successful inclusion of C60 as the reactive ene moiety, and overall PMB utility as a scaffold material. Upon capping with C60, the Tg of the composite particles increased significantly. Most importantly, the C60-capped PMBs produced singlet oxygen in direct and indirect chemical assays, and the efficiency did not decrease after recycling.

Synthesis and biological activity of novel deoxycholic acid derivatives

We report the synthesis and biological activity of new semi-synthetic derivatives of naturally occurring deoxycholic acid (DCA) bearing 2-cyano-3-oxo-1-ene, 3-oxo-1(2)-ene or 3-oxo-4(5)-ene moieties in ring A and 12-oxo or 12-oxo-9(11)-ene moieties in ring C. Bioassays using murine macrophage-like cells and tumour cells show that the presence of the 9(11)-double bond associated with the increased polarity of ring A or with isoxazole ring joined to ring A, improves the ability of the compounds to inhibit cancer cell growth.

Catalytic [2 + 2 + 2] cycloaddition of benzothiophene dioxides with α,ω-diynes for the synthesis of condensed polycyclic compounds.

A Rh-catalyzed intermolecular [2 + 2 + 2] cycloaddition of the 2,3-double bond of benzothiophene dioxides with α,ω-diynes gave sulfone-containing cycloadducts in high yields. This is the first example of a catalytic [2 + 2 + 2] cycloaddition that uses the 2,3-double bond of a heterole as an ene moiety. The consecutive reaction of benzodithiophene tetraoxide with 2,3-naphthylene-tethered 1,7-diyne gave an 11-ring condensed polycyclic compound in one pot.

DFT study of the mechanism and stereochemistry of the Rh(I)-catalyzed Diels-Alder reactions between electronically neutral dienes and dienophiles.

Diels-Alder reaction between electronically neutral dienes and dienophiles is usually sluggish under thermal conditions and has to be catalyzed by transition metal catalysts. We report here our DFT study of the mechanism and stereochemistry of the Rh-catalyzed Diels-Alder reaction between electronically neutral dienes and dienophiles (alkenes and alkynes), finding that this reaction includes a reaction sequence of oxidative cyclization between diene and alkene/alkyne and a reductive elimination step. The alkyne's oxidative cyclization is much faster than alkene's due to the additional coordination of alkyne to the Rh center in the oxidative cyclization transition state. For both intermolecular and intramolecular reactions, the reductive elimination step in the catalytic cycle is rate-determining. The different reactivity of ene-diene and yne-diene substrates can be rationalized by the model that reductive elimination to form a C(sp(2))-C(sp(3)) bond is easier than that for the formation of a C(sp(3))-C(sp(3)) bond, due to the additional coordination of the double bond to the Rh center in the transition state in the former. We also uncovered the reasons for the high para-selectivity of the intermolecular Diels-Alder reaction of dienes and alkynes. In addition, DFT calculations aiming to understand the high diastereoselectivity of an intramolecular [4 + 2] reaction of ene-dienes with substituents adjacent to the diene and ene moieties of the substrates found that the substituents in the substrates favor staying away from the Rh center in the oxidative cyclization transition states. This preference leads to the generation of the final [4 + 2] products with the substituents and the bridgehead hydrogen atoms in a cis-configuration.

Photo-initiated thiol-ene “click” hydrogels from RAFT-synthesized poly(N -isopropylacrylamide)

Despite the efficiency and robustness of the widely used copper-catalyzed 1,3-dipolar cycloaddition reaction, the use of copper as a catalyst is often not attractive, particularly for materials intended for biological systems. The use of photo-initiated thiol-ene as an alternative “click” reaction to synthesize “model networks” is investigated here. Poly(N-isopropylacrylamide) precursors were synthesized by reversible addition fragmentation chain transfer (RAFT) polymerization and were designed to have trithiocarbonate moieties as end groups. This structure design provides opportunity for subsequent end-group modifications in preparation for thiol-ene “click.” Two reaction routes have been proposed and studied to yield thiol and ene moieties. The advantages and disadvantages of each reaction path were investigated to propose a simple but efficient route to prepare copper-free “click” hydrogels. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 4626–4636

Evaluation of fracture toughness and mechanical properties of ternary thiol–ene–methacrylate systems as resin matrix for dental restorative composites

ObjectiveStudy and evaluation of fracture toughness, flexural and dynamic mechanical properties, and crosslink density of ternary thiol–ene–methacrylate systems and comparison with corresponding conventional methacrylate system were considered in the present study. MethodsUrethane tetra allyl ether monomer (UTAE) was synthesized as ene monomer. Different formulations were prepared based on combination of UTAE, BisGMA/TEGDMA and a tetrathiol monomer (PETMP). The photocuring reaction was conducted under visible light using BD/CQ combination as photoinitiator system. Mechanical properties were evaluated via measuring flexural strength, flexural modulus and fracture toughness. Scanning electron microscopy (SEM) was utilized to study the morphology of the fractured specimen's cross section. Viscoelastic properties of the samples were also determined by dynamic mechanical thermal analysis (DMTA). The same study was performed on a conventional methacrylate system. The data were analyzed and compared by ANOVA and Tukey HSD tests (significance level=0.05). ResultsThe results showed improvement in fracture toughness of the specimens containing thiol–ene moieties. DMTA revealed a lower glass transition temperature and more homogenous structure for thiol–ene containing specimens in comparison to the system containing merely methacrylate monomer. The flexural modulus and flexural strength of the specimens with higher thiol–ene content were lower than the neat methacrylate system. The SEM micrographs of the fractured surface of specimens with higher methacrylate content were smooth and mirror-like (shiny) which represent brittle fracture. SignificanceThe thiol–ene–methacrylate system can be used as resin matrix of dental composites with enhanced fracture toughness in comparison to the methacrylate analogous.

Photochemical C2−C6 Cyclization of Enyne−Allenes: Detection of a Fulvene Triplet Diradical in the Laser Flash Photolysis

A series of enyne-allenes, with and without benzannulation at the ene moiety and equipped with aromatic and carbonyl groups as internal triplet sensitizer units at the allene terminus, was synthesized. Both sets, the cyclohexenyne-allenes and benzenyne-allenes, underwent thermal C(2)-C(6) cyclization exclusively to formal ene products. In contrast, the photochemical C(2)-C(6) cyclization of enyne-allenes provided formal Diels-Alder and/or ene products, with higher yields for the benzannulated systems. A raise of the temperature in the photochemical cyclization of enyne-allene 1b' led to increasing amounts of the ene product in relation to that of the formal Diels-Alder product. Laser flash photolysis at 266 and 355 nm as well as triplet quenching studies for 1b,b' indicated that the C(2)-C(6) cyclization proceeds via the triplet manifold. On the basis of a density functional theory (DFT) study, a short-lived transient (tau = 30 ns) was assigned as a triplet allene, while a long-lived transient (tau = 33 micros) insensitive to oxygen was assigned as fulvene triplet diradical. An elucidation of the reaction mechanism using extensive DFT computations allowed rationalization of the experimental product ratio and its temperature dependence.

Effect of the heteroatomic substituent on the pi-facial diastereoselectivity in Lewis acid catalyzed carbonyl ene reaction: A theoretical study

Quantum chemical investigation on the optimized transition structures of intermolecular ene reaction containing various heteroatomic substituents at the α-carbon atom reveal that, the electrostatic effect produced by the ene moiety plays a crucial role in controlling the conformation of the transition structure. The stereoselectivity calculated from the proposed model agreed nicely with the reported experimental results.

3‐Methylcyclopropene‐3‐carbonitrile as a New Enophile of the Alder‐ene Reaction.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

3-Methylcyclopropene-3-carbonitrile as a new enophile of the Alder-ene reaction

By the reactions of 3-methylcyclopropene-3-carbonitrile with methylenecyclohexane, α-methylstyrene and β-pinene products of their cyclopropanation have been obtained, the formation of the latter proceeding by the Alder-ene addition scheme. A DFT study of the reaction mechanism shows that most favourable are exo transition states with syn configuration of the CN group and the ene moiety.

マイクロスケールＣｒｏｓｓ Ｍｅｔａｔｈｅｓｉｓ／ＣＤ・ＦＤＣＤプロトコルによる新規天然物絶対配置決定法

A micro-scale chemical/CD (FDCD) exciton chirality protocol has been realized for determining the absolute configuration of C=C double bond containing compounds. This method is based on the conversion of the preexisting and/or introduced double bonds into the p-substituted styrenoid chromophores and/or fluorophores via cross olefin metathesis, that function as the new CD and FDCD reporter groups. The method has been applied to a variety of natural and synthetic compounds, i.e., (i) allylic alcohols and amines, (ii) macro-cyclic molecules, (iii) unstable alcohols where acylation by Mosher's acid fail, (iv) chiral molecules bearing no other functional groups than ene moieties, in which other methods are not accessible, (v) substrates bearing the sterically hindered hydroxyls, and (vi) large compounds where two hydroxyls are separated by a long distance. Based on the established method, the configurational assignment of gymnocin-B, a new polyether marine natural product containing 15 contiguous polyether skeleton, has been realized.

Novel Oxa-di-π-methane and Norrish Type I Reactions in the S2 (π,π*) Excited State of a Series of β,γ-Unsaturated Ketones

[reaction: see text] Beta,gamma-unsaturated methyl ketones with electron-withdrawing groups at the gamma-position of the ene moiety undergo ODPM rearrangements and Norrish type I reactions on direct irradiation at 254 nm. The results are consistent with the involvement of alkene S(2) (pi,pi*) as reactive excited states in these processes.

Synthesis of carbo- and aza-bicyclo[4.3.0] and [4.4.0] compounds by Ti(II)-mediated cyclization of 2,7- or 2,8-enynyl-1-ol derivatives

The reaction of 2,7- and 2,8-enynyl-1-ol derivatives where the ene moiety is a part of a ring with a Ti(O-i-Pr)4/2 i-PrMgCl reagent proceeds smoothly with excellent stereoselectivity to afford carbo- or aza-bicyclo[4.3.0] and [4.4.0] compounds, respectively, in high yields.

An Iterative Approach tocis-Oligodiacetylenes

Phenyl-terminated cis-oligodiacetylenes such as 18, containing a π-conjugated backbone with four triple and three double bonds, were synthesized using Pd-catalysed Sonogashira coupling reactions. Compound 18 represents the longest cis-oligoenyne system to date, but it suffers from the drawback of cis/trans isomerization observed in solution. In order to avoid cis/trans isomerization in such cis-oligodicacetylenes, the ene moieties within the oligomeric backbone were locked by incorporation into ring systems. 1,2-Dibromocyclopentene was used as an olefinic building block for this purpose, permitting the iterative synthesis of the cis-oligodiacetylenes 27 and 28, possessing the same π-conjugated backbone as 18. Unlike that compound, however, 27 and 28 are stable both in solution and in the solid state. Whereas X-ray crystallography revealed a completely planar structure for 27 in the single crystal, NMR and computational investigations suggest that a preferred helical conformation is likely in solution.

Ring size effects in the C2–C6 biradical cyclisation of enyne–allenes and the relevance for neocarzinostatin

The regioselectivity of the thermal cyclisations of enyne–allenes 1 can be toggled as a function of the ring size of the cycloalkene. With a cyclopentene as the ene moiety the Myers–Saito (C2–C7) cycloaromatisation product is formed, whereas with six- and seven-membered cycloalkenes the novel C2–C6 cyclisation is observed. DFT calculations are used to rationalise these changes. The implications of these findings for alternative thermal biradical cyclisations of neocarzinostatin are discussed.