Ene Components Research Articles

Umpolung reactivity of strained C–C σ-bonds without transition-metal catalysis

Umpolung is an old and important concept in organic chemistry, which significantly expands the chemical space and provides unique structures. While, previous research focused on carbonyls or imine derivatives, the umpolung reactivity of polarized C–C σ-bonds still needs to explore. Herein, we report an umpolung reaction of bicyclo[1.1.0]butanes (BCBs) with electron-deficient alkenes to construct the C(sp3)-C(sp3) bond at the electrophilic position of C–C σ-bonds in BCBs without any transition-metal catalysis. Specifically, this transformation relies on the strain-release driven bridging σ-bonds in bicyclo[1.1.0]butanes (BCBs), which are emerged as ene components, providing an efficient and straightforward synthesis route of various functionalized cyclobutenes and conjugated dienes, respectively. The synthetic utilities of this protocol are performed by several transformations. Preliminary mechanistic studies including density functional theory (DFT) calculation support the concerted Alder-ene type process of C–C σ-bond cleavage with hydrogen transfer. This work extends the umpolung reaction to C–C σ-bonds and provides high-value structural motifs.

An Intramolecular Enyne Metathesis Approach for the Synthesis of Cyclic 3‐Substituted Unsaturated Sulfones

AbstractStudies into the ring‐closing enyne metathesis of a series of nine sulfone containing enynes is described. The readily accessible sulfone substrates were shown to undergo cyclisation to form 3‐subsituted 2,5‐dihydrothiophene 1,1‐dioxides (sulfolenes) and one 3,6‐dihydro‐2H‐thiopyran 1,1‐dioxide. The success of this process depended on the substrate's substitution pattern. Moderate to good yields of the products were obtained when the ene component was monosubstituted and it was found that the reactions proceeded most efficiently using the 2nd generation Grubbs catalysts, at elevated temperatures.

Thiol-ene photo-click immobilization of a chiral chromatographic ligand on silica particles

This work reports procedures for the immobilization of vinyl ligands on silica particles by UV-initiated thiol-ene radical addition reaction (photo-click immobilization). tert‑Butylcarbamoyl quinine was the functional ligand (ene component) for the synthesis of chiral stationary phases. Two distinct surface chemistries were evaluated. In one approach, the ligand was directly attached to 3-mercaptopropyl-silica triggered by radicals generated by UV irradiation from a photoinitiator. In another approach, the ligand was immobilized onto vinyl silica via poly(3-mercaptopropyl-methylsiloxane) (PMPMS) as crosslinker by a photoinitiated double click reaction in which functionalization with chiral ligand and crosslinking to vinylsilica occurred simultaneously in one synthesis step. PMPMS-bonded CSPs were prepared from suspension (slurry method) or solventless after coating of the polythiol onto the vinylsilica surface (film method). Optimization by a design of experiment approach showed that the reaction time is the prime variable to optimize the surface coverage of chiral selector which also increased with PMPMS concentration. When the film formation of the latter approach was assisted by a minute volume of toluene during photo-click immobilization, selector coverage could be significantly increased to 0.73 µmol/m2 in a 2 h synthesis compared to 0.44 µmol/m2 by the solventless film method and 0.47 µmol/m2 by the slurry method under otherwise comparable conditions. The solvent assistance improved the chromatographic efficiency of the film method and resulted equal minimal reduced plate height of 2.6 as the slurry method for a chiral probe (Fmoc-Phe). The mass transfer resistance was around factor 2 smaller with the solvent-assisted film method as compared to the film approach without toluene, presumably due to a more homogenous distribution of the thin polymer film owing to lower dynamic viscosity in presence of toluene.

Tunable and Magnetic Thiol-ene Micropillar Arrays.

Tunable and responsive surfaces offer routes to multiple functionalities ranging from superhydrophobic surfaces to controlled adhesion. Inspired by cilia structure in the respiratory pathway, magnetically responsive periodic arrays of flexible and magnetic thiol-ene micropillars are fabricated. Omnidirectional collective bending of the pillar array in magnetic field is shown. Local non-contact actuation of a single pillar is achieved using an electromagnetic needle to probe the responsiveness and the elastic properties of the pillars by comparing the effect of thiol-ene crosslinking density to pillar bending. The suitable thiol-ene components for flexible and stiff magnetic micropillars and the workable range of thiol-to-allyl ratio are identified. The wettability of the magnetic pillars can be tailored by chemical and topography modification of the pillar surface. Low-surface-energy self-assembled monolayers are grafted by UV-assisted surface activation, which is also used for surface topography modification by covalent bonding of micro- and nanoparticles to the pillar surface. The modified thiol-ene micopillars are resistant to capillarity-driven collapse and they exhibit low contact angle hysteresis, allowing water droplet motion driven by repeated bending and recovery of the magnetic pillars in an external magnetic field. Transport of polyethylene microspheres is also demonstrated.

In-situ functionalized monolithic polysiloxane-polymethacrylate composite materials from polythiol-ene double click reaction in capillary column format for enantioselective nano-high-performance liquid chromatography

This work reports on the proof-of-principle of preparation of novel one step in-situ functionalized monolithic polysiloxane-polymethacrylate composite materials in capillary columns for enantioselective nano-HPLC using a thiol-ene click reaction. Quinine carbamate as functional monomer and ethylene dimethacrylate as crosslinker were both used as ene components in a thermally initiated double click-type polymerization reaction with poly(3-mercaptopropyl)methylsiloxane as thiol component in presence of 1-propanol as porogenic solvent. Elemental analysis and on-capillary fluorescence measurement proved the successful incorporation of the functional chiral monomer into the polymer. Scanning electron microscopy images revealed a macroporous polymer morphology which is typical for a nucleation and growth mechanism of pore formation. The individual microglobules appear relatively spherical and smooth indicating a non-porous nature. Nano-HPLC experiments of the chiral monolithic capillary column provided successful enantiomer separation of N-3,5-dinitrobenzoylleucine as test compound in polar organic elution mode clearly documenting the successful implementation of the proposed concept towards new functionalized monolithic composite materials.

Silicon‐based mercaptans: High‐performance monomers for thiol‐ene photopolymerization

ABSTRACTEster‐free silane and siloxane‐based thiol monomers were successfully synthesized and evaluated for application in thiol‐ene resins. Polymerization reaction rates, conversion, network properties as well as degradation experiments of those thiol monomers in combination with triallyl‐1,3,5‐triazine‐2,4,6(1H,3H,5H)‐trione (TATT) as ene component were performed and compared with formulations containing the commercially available mercaptopropionic ester‐based thiol pentaerythritol tetra‐3‐mercaptopropionate. Kinetic analysis revealed appropriate reaction rates and conversions reaching 90% and higher. Importantly, storage stability tests of those formulations clearly indicate the superiority of the synthesized mercaptans compared with pentaerythritol tetra‐3‐mercaptopropionate/TATT resins. Moreover, photocured samples containing silane‐based mercaptans provide higher glass transition temperatures and withstand water storage without a significant loss in their network properties. This behavior together with the observed excellent degradation resistance of photocured silane‐based thiol/TATT formulations make these multifunctional mercaptans interesting candidates for high‐performance applications, such as dental restoratives and automotive resins. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016, 54, 418–424

ChemInform Abstract: Advancements in Catalytic Asymmetric Intermolecular Ene‐Type Reactions

AbstractReview: [56 refs.

Reaction of N-benzylideneaniline with 1,2-diphenylcyclopropene

In this case the reaction of [4+2]-cycloaddition occurred where the Schiff base acted not like a dienophile [4] but like a diene, and the 1,2diphenylcyclopropene was the ene component of the reaction. The formation of compound III proceeds presumably via intermediate А. The structure of compound III is proved by GC-MS and Н NMR spectra. The resonance signals of the protons of methylene group Н and Н are nonequivalent demonstrating the unsymmetrical structure of compound III.

Advancements in Catalytic Asymmetric Intermolecular Ene-Type Reactions

Correction to: Advancements in Catalytic Asymmetric Intermolecular Ene-Type ReactionsSynthesis 2014; 46(17): 2241-2257DOI: 10.1055/s-0034-1378528

Thiol-ene photopolymerizations provide a facile method to encapsulate proteins and maintain their bioactivity.

Photoinitiated polymerization remains a robust method for fabrication of hydrogels, as these reactions allow facile spatial and temporal control of gelation and high compatibility for encapsulation of cells and biologics. The chain-growth reaction of macromolecular monomers, such as acrylated PEG and hyaluronan, is commonly used to form hydrogels, but there is growing interest in step-growth photopolymerizations, such as the thiol–ene “click” reaction, as an alternative. Thiol–ene reactions are not susceptible to oxygen inhibition and rapidly form hydrogels using low initiator concentrations. In this work, we characterize the differences in recovery of bioactive proteins when exposed to similar photoinitiation conditions during thiol–ene versus acrylate polymerizations. Following exposure to chain polymerization of acrylates, lysozyme bioactivity was approximately 50%; after step-growth thiol–ene reaction, lysozyme retained nearly 100% of its prereaction activity. Bioactive protein recovery was enhanced 1000-fold in the presence of a thiol–ene reaction, relative to recovery from solutions containing identical primary radical concentrations, but without the thiol–ene components. When the cytokine TGFβ was encapsulated in PEG hydrogels formed via the thiol–ene reaction, full protein bioactivity was preserved.

Properties of methacrylate–thiol–ene formulations as dental restorative materials

Objectives The objective of this study was to evaluate ternary methacrylate–thiol–ene systems, with varying thiol–ene content and thiol:ene stoichiometry, as dental restorative resin materials. It was hypothesized that an off-stoichiometric thiol–ene component would enhance interactions between the methacrylate and thiol–ene processes to reduce shrinkage stress while maintaining equivalent mechanical properties. Methods Polymerization kinetics and functional group conversions were determined by Fourier transform infrared spectroscopy (FTIR). Cured resin mechanical properties were evaluated using a three-point flexural test, carried out with a hydraulic universal test system. Polymerization shrinkage stress was measured with a tensometer coupled with simultaneous real-time conversion monitoring. Results The incorporation of thiol–ene mixtures as reactive diluents into conventional dimethacrylate resins previously was shown to combine synergistically advantageous methacrylate mechanical properties with the improved polymerization kinetics and reduced shrinkage stress of thiol–ene systems. In these systems, due to thiol consumption resultant from both the thiol–ene reaction and chain transfer involving the methacrylate polymerization, the optimum thiol:ene stoichiometry deviates from the traditional 1:1 ratio. Increasing the thiol:ene stoichiometry up to 3:1 results in systems with equivalent flexural modulus, 6–20% reduced flexural strength, and 5–33% reduced shrinkage stress relative to 1:1 stoichiometric thiol:ene systems. Significance Due to their improved overall functional group conversion, and shrinkage stress reduction while maintaining equivalent flexural modulus, methacrylate–thiol–ene resins, particularly those with excess thiol, beyond the conventional 1:1 thiol:ene molar ratio, yield superior dental restorative materials compared with purely dimethacrylate resins.

The effect of thiol and ene structures on thiol–ene networks: Photopolymerization, physical, mechanical and optical properties

The photopolymerization of four different types of ene monomers with both primary and secondary multifunctional thiols has been evaluated. To understand the effect of ene monomer structures on polymer properties, a comprehensive investigation of the basic physical, mechanical and optical properties was conducted for the secondary and primary thiol–ene networks. The results indicate that ene structure and functionality can significantly affect the rigidity and the physical and mechanical properties of the thiol–ene networks. The heat capacity in the rubber state correlates with the network crosslink density and flexibility of the ene component. Networks formed from the secondary thiol–ene systems are basically equivalent to those made from primary thiol–enes with respect to physical, mechanical and optical properties. The secondary thiol monomer samples evaluated were found to have exceptional storage stability and relatively low odor.

Tetranuclear BINOL−Titanium Complex in Selective Direct Aldol Additions

The extremely robust and water-stable tetranuclear complex Ti(4)(micro-BINOLato)(6)(micro(3)-OH)(4) (1) catalyzes the direct aldol addition with high degrees of regioselectivity at the sterically more encumbered alpha-side of unsymmetrical ketones. The formation of quaternary stereocenters is described. Oxygen-containing ene components can also be used as starting material in these reactions. When used with aliphatic aldehydes, acetals 18 or acetals of aldol adducts 20 were observed. As few as 0.2 mol % loadings with this catalyst 1 were enough to complete the reactions. Mechanistical aspects of the reactions are discussed.

Stereoselective synthesis of 3,4-disubstituted and 3,4,5-trisubstituted piperidines by Lewis acid-catalysed ene cyclisation of 4-aza-1,7-dienes

The thermal or Lewis acid-catalysed ene cyclisation of a variety of 4-aza-1,7-dienes afforded 3,4-disubstituted or 3,4,5-trisubstituted piperidines. Activation of the enophile with a single ester facilitated a thermal ene cyclisation, although the reaction was not amenable to Lewis acid catalysis. With other activating groups on the enophile it was found that Lewis acid catalysis was facile, although there was a fine balance between the desired ene cyclisation and the competing hetero-Diels-Alder reaction, with the product distribution being influenced by the activating group on the enophile, the nature of the ene component, and the Lewis acid used. Activation of the enophile with an oxazolidinone function facilitated Lewis acid-catalysed cyclisation to afford mixtures of ene and hetero-Diels-Alder products. Activating the enophile with two ester groups gave a substrate that underwent a very facile ene cyclisation catalysed by MeAlCl(2) to give the corresponding trans 3,4-disubstituted piperidines with diastereomeric ratios of >200 : 1.

N‐Allyl‐1,3‐oxazines via a Facile Keto‐ene/Cyclization Tandem Reaction.

AbstractFor Abstract see ChemInform Abstract in Full Text.

N-Allyl-1,3-oxazines via a facile keto-ene/cyclization tandem reaction

The intramolecular keto-ene/cyclization tandem reaction of γ- N-allylamino ketones is an effective means of producing 1,3-oxazines. The reaction usually requires high temperatures and/or pressures. We discovered that N, N-diallyl amines undergo the reaction at lower temperatures than their monoallyl analogs. An extreme example, 1- N, N-diallylamino-9,10-anthraquinone, undergoes the keto-ene reaction near ambient temperature. In the case of 1- N, N′-dialkylaminoanthraquinones, electron deficient ene components can even be used, allowing the preparation of a broad spectrum of oxazines. Furthermore, the N-allyl-1,3-oxazine can be easily deallylated to produce a 1,3-oxazine that contains a secondary amine.

Theoretical Studies on the Diastereoselectivity in the Lewis Acid Catalyzed CarbonylEne Reaction: A Fundamental Role of Electrostatic Interaction

AbstractLewis acids affect reactivity, selectivity, and mechanism in the carbonyl‐ene reaction. The diastereoselectivity in the glyoxylate‐ene reaction depends on Lewis acids. While the SnCl4‐promoted reaction can be achieved with a high level of anti‐selectivity, the use of Al reagents leads to a high syn‐selectivity. The origin of the Lewis acid dependency of the diastereoselectivity in the carbonylene reaction of (E)‐but‐2‐ene with glyoxylate was theoretically studied (HF/6‐31G*) from the point of view of differences and similarities between the ene and the Diels–Alder reactions. Though it has been widely accepted that the endo‐preference would be less obvious in the ene reaction than in the Diels–Alder reaction, our ab initio molecular studies showed that the electrostatic interaction between carbonyl O‐atom lone pair and cationic allylic central C‐atom of ene component exists in the Lewis acid‐promoted carbonyl–ene reaction to affect the transition‐state conformation. It is illustrated that such an electrostatic interaction is essential to control the exo/endo‐selectivity, which provides the diastereoselectivity of the product in the transition state of the Lewis acid promoted carbonylene reaction.

Molecular Gymnastics of Alkynes Orchestrated by Ruthenium Complexes

AbstractRuthenium complexes catalyze a variety of addition or isomerization reactions that are highly atom economical. Terminal alkynes react with allyl alcohols to form β,γ‐unsaturated ketones that can be readily isomerized to α,β‐unsaturated ketones via transient vinylidene complexes. A cyclization via a transient allenylidene complex concomitant with this addition represents a novel way to build heterocycles. Ancillary studies with these catalysts revealed an internal oxidation reduction whereby allyl alcohols are isomerized to saturated ketones and propargyl alcohols are isomerized to α,β‐unsaturated carbonyl compounds. Consideration of the reaction mechanism led to a general Alder ene type reaction wherein alkynes serve as the enophile and alkenes serve as the ene component. These discoveries have led to a number of efficient total syntheses of biologically interesting targets. Mechanistic investigations into the activation of a ruthenium complex led to the discovery of a novel bis‐homo‐Diels‐Alder reaction of 1,4‐cyclooctadiene.

Intermolecular Carbonyl-Ene Approach to the Bicyclic Analogues of Enediyne Antibiotics, Neocarzinostatin, C-1027, and Kedarcidin: Highly Diastereoselective Carbonyl-Ene Reaction with an Alkyne-Cobalt Complex1

The alkoxy(methyl)aluminum chloride promoted intermolecular carbonyl-ene reaction of a conjugated ynal enophile bearing terminal ester function with an alkyne-cobalt complexed ene component is found to be highly erythro-diastereoselective, producing a multi-functionalized product which can be efficiently elaborated to the enediyne cores of neocarzinostatin, C-1027, and kedarcidin.

Reactions of Allylsilanes with Iminium Salts: Ene Reactions with Inverse Electron Demand

The N,N-dialkylmethyleneammonium hexachloroantimonates 1-SbCl6- react with allyltrimethylsilane (2a) in dichloromethane to give the alkylideneammonium ions 3 and 3‘ via ene reactions with inverse electron demand, where the allyltrimethylsilane (2a) behaves as enophile. Under the same conditions (2-methylallyl)trimethylsilane (2b) undergoes ordinary ene reactions with iminium ions, with the allylsilane 2b acting as the ene component. The different course of the ene reactions is explained by the varied steric strain in the pericyclic transition states 14−18. SE2‘ products, which are the main products under more nucleophilic reaction conditions, have only been detected in trace amounts.