Subsequent Ring Opening Research Articles

DFT study of carbene formation and olefin metathesis catalyzed by [RuCl2(PPh3)2(Py)2] complex

A DFT approach was used to clarify the structure of [RuCl2(PPh3)2(Py)2] complex, which came out to be hexacoordinate with the similar ligands trans-positioned regarding each other. We addressed different pathways analyzing the formation of [RuCl2(Py)2(=CHCOOCH2CH3)] carbene active species using [RuCl2(PPh3)2(Py)2] and ethyldiazoacetate. Our findings show that the mechanism most likely to happen presents an immediate coordination of the Cα of the EDA to the ruthenium atom, with an affordable activation energy (10.5 kcal·mol−1). Subsequent ring opening metathesis of norbornene catalyzed by the ruthenium-carbene active species is also considered. Experimental yields available in the literature present correlation with the activation energy and the favorability of the products in our mechanism.

Asymmetric Synthesis of Saturated Hydroxy Fatty Acids and Fatty Acid Esters of Hydroxy Fatty Acids

The recent discovery of a novel class of endogenous lipids, named Fatty Acid esters of Hydroxy Fatty Acids (FAHFAs), that present antidiabetic and anti‐inflammatory activities, has attracted the interest on hydroxy fatty acids (HFAs) and their derivatives. We present herein the development of a convenient and general methodology for the asymmetric synthesis of HFAs and FAHFAs. The enantioselective organocatalytic synthesis of asymmetric terminal epoxides starting from monoprotected α,ω‐diols and their subsequent ring opening by a Grignard reagent are the key‐steps for our methodology, allowing the introduction of the hydroxy group at different positions of the long chain by proper selection of the starting diol and the Grignard reagent. MacMillan's third generation imidazolidinone organocatalyst has been employed for the epoxide formation, ensuring products in high enantiomeric purity. Furthermore, an approach for the synthesis of deuterated HFAs and FAHFAs was developed, leading to deuterated derivatives, which can be useful in biological studies and in mass spectrometry studies as internal standards.

An electrocatalytic route for transformation of biomass-derived furfural into 5-hydroxy-2(5H)-furanone.

Development of efficient strategies for biomass valorization is a highly attractive topic. Herein, we conducted the first work on electrocatalytic oxidation of renewable furfural to produce the key bioactive intermediate 5-hydroxy-2(5H)-furanone (HFO). It was demonstrated that using H2O as the oxygen source and metal chalcogenides (CuS, ZnS, PbS, etc.) as electrocatalysts, the reaction could proceed efficiently, and the CuS nanosheets prepared in this work showed the best performance and provided high HFO selectivity (83.6%) and high conversion (70.2%) of furfural. In addition, the CuS electrocatalyst showed long-term stability. Mechanism investigation showed that furfural was oxidized to HFO via multistep reactions, including C-C cleavage, subsequent ring opening and oxidation, and intramolecular isomerization.

Lignin oxidation with an organic peroxide and subsequent aromatic ring opening

The oxidation of an organosolv lignin with tert-butylhydroperoxide, initiated by titanium grafted into the lignin structure, was investigated. Titanation of reactive groups on lignin is responsible for the cross-linking of the lignin structure. IR and MAS 13C NMR spectroscopy spectra confirmed the oxidation of the lignin structure and other pronounced structural changes. A study with guaiacol as a model compound helped to recognise that aromatic ring opening occurs under the given conditions and is catalysed by the grafted titanium. The structure of the oxidised lignin becomes less robust and therefore potentially more susceptible to be depolymerised and converted into monomeric units.

Single C-F Bond Activation of the CF3 Group with a Lewis Acid: CF3 -Cyclopropanes as Versatile 4,4-Difluorohomoallylating Agents.

The selective activation of one C-F bond (single activation) of the CF3 group on cyclopropanes was achieved for the first time. When (trifluoromethyl)cyclopropanes were treated with arenes, allylsilanes, silyl enol ethers, or hydrosilanes in the presence of Me2 AlCl, fluoride elimination and the subsequent ring opening proceeded to afford 4,4-difluorohomoallylated products. In the absence of external nucleophiles, an alkyl group of AlR3 was effectively introduced to provide the corresponding 1,1-difluoroalkenes.

Base-Mediated Cascade Cyclization: Stereoselective Synthesis of Benzooxazocinone.

A new strategy for the synthesis of the oxa-azabicyclo[3.3.1]nonane subunit, a component of the naucleamide E core structure, has been developed. This annulation reaction between 1-substituted 3,4-dihydroisoquinolines and coumarin derivatives conveniently affords the oxa-azabicyclo[3.3.1]nonane framework via a base-mediated cascade cyclization under aqueous conditions. The value of this work lies in the efficient formation of the oxa-azabicyclo[3.3.1]nonane skeleton via a process whereby all the C-C, C-O, and C-N bond formations occur in a single chemical operation. In addition, the subsequent ring opening of these compounds furnished pyridoisoquinoline derivatives.

UV laser-induced photolysis of matrix isolated o-guaiacol

A matrix isolation study of structure and infrared spectra of o-guaiacol (o-methoxyphenol, GU) has been performed showing that the most stable conformer of the compound is present in argon and xenon matrices. Photochemical reactions of o-guaiacol were induced using UV-laser radiation and followed by the FTIR spectroscopy. Four photolysis pathways have been considered based on the positions of new bands appearing during irradiation of the matrices. It was concluded that the cleavage of the OH bond is an initial step of the reactions and a number of photoproducts have been identified originating from the subsequent ring opening and decarbonylation processes as well as the OCH3 bond cleavage. Among the photoproducts are cyclopetadienone and long-chain ketenes with conjugated/cumulated CO and CC bonds.

Divergent Elementoboration: 1,3-Haloboration versus 1,1-Carboboration of Propargyl Esters.

This work showcases the 1,3‐haloboration reaction of alkynes in which boron and chlorine add to propargyl systems in a proposed sequential oxazoliumborate formation with subsequent ring‐opening and chloride migration. In addition, the functionalization of these propargyl esters with dimethyl groups in the propargylic position leads to stark differences in reactivity whereby a formal 1,1‐carboboration prevails to give the 2,2‐dichloro‐3,4‐dihydrodioxaborinine products as an intramolecular chelate. Density functional theory calculations are used to rationalize the distinct carboboration and haloboration pathways. Significantly, this method represents a metal‐free route to highly functionalized compounds in a single step to give structurally complex products.

Ruthenium-Catalyzed Asymmetric Reduction of Isoxazolium Salts: Access to Optically Active Δ4-Isoxazolines

A tethered MsDPEN-ruthenium catalyst reduces a series of isoxazolium salts, affording optically active Δ4-isoxazolines in moderate to good yields and enantioenrichment. The redundancy of heating or high pressures allowed for chemoselective reduction with no subsequent heterocyclic ring opening. Our results reinforce our understanding of the workings of these Noyori-class catalysts.

Stereoselective Synthesis and Biological Evaluation of ent‐Asperolide C and its Analogues

A stereoselective synthesis of ent‐asperolide C and its analogues is described. A chiral‐pool approach was used with a linear sequence of 10 steps, starting from readily available and inexpensive andrographolide. The approach features the construction of a five‐membered lactone skeleton with suitable chiral centres from andrographolide through diastereoselective epoxidation of the exocyclic double bond, and tandem oxidative cleavage of the C‐14=C‐15 double bond and subsequent epoxide ring opening. The stereochemistry of 8 was established by X‐ray crystallographic analysis. Four analogues of ent‐asperolide C were synthesized, and their biological activities were evaluated against A539 and HeLa cell lines. Compound 12 was found to show a weak to moderate antiproliferation effect against both cell lines.

Preparation of pendant group-functionalized amphiphilic diblock copolymers in the presence of a monomer activator and evaluation as temperature-responsive hydrogels

Temperature-responsive hydrogels have been widely developed for biomedical applications. In this study, 4-benzyloxy-ε-caprolactone (CL-OBn) was synthesized and the subsequent ring opening polymerization (ROP) of ε-caprolactone (CL) and CL-OBn monomers was performed by using the hydroxyl group of methoxy polyethylene glycol (MPEG) in the presence of HCl·Et2O as a monomer activator. MPEG-b-poly (ε-caprolactone) (MC) with benzyl pendant groups (MC-OBn) was successfully obtained in almost quantitative yield and the segment ratios and molecular weights were close to the theoretical values. Deprotection of the benzyl pendant groups successfully provided MC with hydroxyl pendant groups (MC-OH). Suspensions of MC-OBn and MC-OH exhibited distinct sol-to-gel phase transitions as a function of the temperature. The sol-to-gel phase transition of the MC-OBn and MC-OH diblock copolymers depended on the type (benzyl or hydroxyl) and amount of pendant groups in the diblock copolymer structure. The pendant group on the MC-OBn and MC-OH diblock copolymers either stabilized and/or destabilized hydrophobic aggregation between the MC segments. The hydrophobic aggregation was confirmed by the detection of crystallinity in the MC-OBn and MC-OH diblock copolymer suspensions. In conclusion, MC-OBn and MC-OH diblock copolymers were successfully prepared and served as temperature-responsive hydrogels.

Synthetic studies towards lagunamide C: Polyketide assembly investigations

Lagunamide C is a depsipeptide natural product with low nM cytotoxicity towards numerous cancer cell lines. Synthetically, it is disconnected to a pentapeptide backbone and polyketide unit that possesses four stereogenic centers, of which two of centers are in question (C38 & 40). Our model system highlights a high-selective aldol addition via a Crimmin’s auxiliary setting the C40 ester linkage, and a non-facially selective cyclopropanation with subsequent ring opening for the installation of the C38 methyl center.

Preparation, characterization and degradation study of polyesteramide copolymers

Poly (ester-amide) s (PEA) were synthesized via a polycondensation reaction of 1, 3-phenylene bis (2-Oxazoline) carboxylic anhydride, and diol. The polymerization proceeds through the formation of a dicarboxy ester by reaction of two anhydride molecules with one diol molecule and subsequent 2-oxazoline ring opening by attack of the dicarboxy ester. The expected structures of the polymers were confirmed by FTIR and 1 H-NMR. Thermal properties of the poly (ester amide) s were characterized by Differential scanning calorimeter (DSC), X-ray diffraction (XRD) and Thermogravimetric analysis (ATG). Hydrolytic and enzymatic degradations in solid media using Aspergilus Niger of the materials were performed. The biodegradation of polymers were also carried in liquid medium and the source of microorganisms is an inoculum based on activated sludge, by measuring the net biochemical oxygen demand (BOD) under the aerobic conditions. The biodegradation of polymers was observed by changing of BOD a long of 7 days.

Cu-Catalyzed Three-Component Carboamination of Alkenes.

Copper-catalyzed intermolecular carboamination of alkenes with α-halocarbonyls and amines is presented with 42 examples. Electron rich, electron poor, and internal styrenes, as well as α-olefins, are functionalized with α-halocarbonyls and aryl or aliphatic amines. Mechanistic investigations suggest the reaction is proceeding through addition of a carbon-centered radical across an olefin followed by oxidation to form a 5-membered oxocarbenium intermediate and subsequent nucleophilic ring opening to forge the C-N bond.

Cu(I)-Catalyzed Synthesis of β,γ-Unsaturated Amides

Readily available propargyl alcohols were found to be useful substrates for the copper(I)-catalyzed synthesis of β,γ-unsaturated amides. Nucleophilic attack by the alcohol on the in situ generated keten­imine followed by base-catalyzed elimination and subsequent ring opening yields the desired products under mild conditions.

A thiourea-appended rhodamine chemodosimeter for mercury(II) and its bioimaging application

A rhodamine-thiourea conjugate RTP with an o-phenylenediamine linker was developed as a fluorogenic chemodosimeter for Hg2+ detection. In the presence of Hg2+, a colorless solution of RTP turned pink with a maximum absorption band at 555nm and with a 62-fold fluorescence enhancement at 578nm (Φ=0.34). RTP is highly selective to Hg2+ among other metal ions with a detection limit of 1.6nM (0.3ppb). A similar rhodamine analog with a flexible ethylenediamine spacer was less selective and less sensitive than RTP. Hg2+ induced cyclic guanylation to yield a benzimidazole moiety and a subsequent ring-opening of the spirolactam unit resulted in chromogenic and fluorogenic changes. The membrane-permeable RTP probe was successfully demonstrated in monitoring of Hg2+ in cultured HeLa cells.

Influence of ligand substitution on molybdenum catalysts with tridentate Schiff base ligands for the organic solvent-free oxidation of limonene using aqueous TBHP as oxidant

The oxidation of limonene by aqueous TBHP has been analyzed in the presence of molybdenum complexes [MoO2L]2 as catalysts with five different tridentate ligands L in the absence of organic solvents (greener reaction conditions). The ligands are based on a common salicylidene amino(thio)phenolate, SA(T)P, backbone with differences in the coordination sphere (ONO for L=SAP vs. ONS for L=SATP) or in the salicyl moiety functionalization by OH groups for the ONO ligands. The process gives a regioselective endocyclic epoxidation to a kinetically controlled 1:1 mixture of the cis-LimO and trans-LimO epoxides and/or the isomeric diols ax-LimD and eq-LimD by the subsequent ring opening in the presence of water, with a product distribution that depends on the ligand, reaction time and temperature. In combination with control experiments of the cis/trans-LimO ring opening, the investigations demonstrate the catalytic action of the metal complexes in both the epoxidation and the ring opening steps, with the cis-LimO stereospecifically producing the ax-LimD product and the less reactive trans-LimO leading to a 4:3 mixture of ax-LimD and eq-LimD. The ONS system [MoO2(SATP)]2 exhibits the highest catalytic activity in both steps.

Substitution of aqua ligands from cis-platinum(II) complexes bearing 2-(phenylthiomethyl)pyridine spectator ligands

Cis-Pt(II) complexes, namely [Pt{2-(phenylthiomethyl)pyridine}(H2O)2](CF3SO3)2 Pt(pyS Ph ), [Pt{2-(4-tert-butylphenylthiomethyl)pyridine}(H2O)2](CF3SO3)2 Pt(pyS Ph( t -But) ) and [Pt{2-(4-fluorophenylthiomethyl)pyridine}(H2O)2](CF3SO3)2 Pt(pyS PhF ), were synthesised and characterised. The pK a1 and pK a2 values of the complexes were determined titrimetrically. Substitution of the aqua ligands from these complexes by thiourea nucleophiles was studied at a pH of 2 and ionic strength of 0.1 M under pseudo-first-order conditions using stopped-flow and UV–visible spectrophotometric techniques. Substitution of the aqua ligands depends on both the nature and concentration of the incoming ligand, with low enthalpy and negative entropy of activation values. Substitution of the first and second aqua ligands occurs sequentially and fits the rate laws: k obs (1/2) = k (1/2) [Nu]. The second-order rate constant, k 1, relates to the substitution trans to sulphur, while k 2 is the second-order rate constant for the subsequent substitution of the aqua ligand trans to pyridine. The rate of substitution of the first aqua ligand decreases in the order: Pt(pyS Ph( t -But) ) > Pt(pyS PhF ) > Pt(pyS Ph ), while that of the second decreases in the order: Pt(pyS Ph( t -But) ) > Pt(pyS Ph ) > Pt(pyS PhF ), reflecting the influence of the substituents on the spectator ligands. 195Pt NMR spectra of aged solutions of complexes with the thiourea nucleophile suggest a subsequent but rapid concentration-independent ring opening of the N,S-bidentate ligand to form a PtS 4 species. The crystal structure of Pt(pyS PhF )Cl 2 was elucidated by X-ray diffraction analysis.

Prehydrated One-Electron Attachment to Azido-Modified Pentofuranoses: Aminyl Radical Formation, Rapid H-Atom Transfer, and Subsequent Ring Opening.

Methyl 2-azido-2-deoxy-α-d-lyxofuranoside (1a) and methyl 2-azido-2-deoxy-β-d-ribofuranoside (2) were prepared from d-xylose or d-arabinose, respectively. Employing ESR and DFT/B3LYP/6-31G* calculations, we investigated (i) aminyl radical (RNH·) formation and (ii) reaction pathways of RNH·. Prehydrated electron attachment to 1a and 2 at 77 K produced transient azide anion radical (RN3·-) which reacts via rapid N2 loss at 77 K, forming nitrene anion radical (RN·-). Rapid protonation of RN·- at 77 K formed RNH· and -OH. 15N-labeled-1a confirmed this mechanism. Investigations employing in-house synthesized site-specifically deuterated derivatives of 1a (e.g., CH3 (1b), C4 (1c), and C5 (1d)) established that (a) a facile intramolecular H atom transfer from C5 to RNH· generated C5· and RNH2. C5· formation had a small deuterium kinetic isotope effect suggesting that this reaction does not occur via direct H atom abstraction. (b) Subsequently, C5· underwent a facile unimolecular conversion to ring-opened C4·. Identification of ring-opened C4· intermediate confirms the mechanism of C5'· mediated unaltered base release associated with DNA-strand break. However, for 2, ESR studies established thermally activated intermolecular H atom abstraction by RNH· from the methyl group at C1. Thus, sugar ring configuration strongly influences the site and pathway of RNH· mediated reactions in pentofuranoses.

Synthesis, Characterization and Thermal Properties of Poly(ethylene oxide), PEO, Polymacromonomers via Anionic and Ring Opening Metathesis Polymerization.

Branched polymers are a valuable class of polymeric materials. In the present study, anionic polymerization techniques were employed for the synthesis of low molecular weight poly(ethylene oxide) (PEO) macromonomers bearing norbornenyl end groups. The macromonomers were characterized by SEC, MALDI-TOF and NMR spectroscopy. Subsequent ring opening metathesis polymerization (ROMP) of the macromonomers using ruthenium catalysts (Grubbs catalysts of the 1st, 2nd and 3rd generations) afforded the corresponding polymacromonomers. The effects of the macromonomer molecular weight, the type of the catalyst, the nature of the solvent, the monomer concentration and the polymerization temperature on the molecular characteristics of the branched polymers were examined in detail. The crystallization behavior of the macromonomers and the corresponding polymacromonomers were studied by Differential Scanning Calorimetry (DSC). The thermal stability and the kinetics of the thermal decomposition of the samples were also studied by Thermogravimetric Analysis (TGA). The activation energies of the thermal decomposition were analyzed using the Ozawa–Flynn–Wall and Kissinger methodologies.