Lactone Products Research Articles

Oxidation of diols using a substoichiometric quantity of an oxoammonium salt bearing the nitrate anion

The oxidation of diols to lactones, dialdehydes and diketones using a sub-stoichiometric quantity of an oxoammonium salt bearing the nitrate counterion is reported. In the case of linear aliphatic diols, when the diol substrate is shorter-chained, the lactone product predominates. When the chain is longer, the dialdehyde is the major product formed. A number of cyclic diols are also converted to their lactone, diketone or hydroxyketone congeners.

Zinc-Catalyzed Cyclization of Alkynyl Derivatives: Substrate Scope and Mechanistic Insights.

Novel alkyl zinc complexes supported by acetamidate/thioacetamidate heteroscorpionate ligands have been successfully synthesized and characterized. These complexes exhibited different coordination modes depending on the electronic and steric effects of the acetamidate/thioacetamidate moiety. Their catalytic activity has been tested toward the hydroelementation reactions of alkynyl alcohol/acid substrates, affording the corresponding enol ether/unsaturated lactone products under mild reaction conditions. Kinetic studies have been performed and confirmed that reactions are first-order in [catalyst] and zero-order in [alkynyl substrate]. DFT calculations supported a reaction mechanism through the formation of the catalytically active species, an alkoxide-zinc intermediate, by a protonolysis reaction of the Zn-alkyl bond with the alcohol group of the substrate. Based on the experimental and theoretical results, a catalytic cycle has been proposed.

Electrochemical Lactonization Enabled by Unusual Shono-Type Oxidation from Functionalized Benzoic Acids.

A novel method for electrochemical lactonization via C(sp3)-H functionalization was developed. This metal- and oxidant-free strategy enabled the efficient synthesis of various lactones. Gram-scale reaction and derivatization of the lactone product demonstrated the synthetic utility of this methodology. Mechanistic studies using control experiments and CV curves elucidated the proposed intramolecular HAT and the oxidative cyclization pathway. An unusual Shono-type oxidation was realized through this electrochemical approach, proceeding without a traditional nucleophilic addition process.

Decarboxylative - Dimerization of levulinic acid using spent Li-ion battery electrode material with lithium nickel cobalt manganese oxide as a catalyst

A low cost catalyst prepared by pyrolyzing electrode coating material from spent Li-ion battery cells was shown as an effective catalyst for the decarboxylative - dimerization of levulinic acid to a mixture of C6 and C9 fuel precursors. The highest levulinic acid conversion of 94% was observed with 10% (w/w) catalyst loading under 1.24 MPa H2 at 140 °C, 15 h. A reaction scheme was proposed to explain the novel transformation producing C9 lactone products and C6 unsaturated alcohol product through a decarboxylative pathway followed by the aldol dimerization of levulinic acid.

Access to Saturated Oxygen Heterocycles and Lactones via Electrochemical Sulfonylative Oxycyclization of Alkenes with Sulfonyl Hydrazides.

A facile electrochemical sulfonylative cycloetherification of linear unsaturated alcohols with sulfonyl hydrazides under mild conditions has been accomplished. This catalyst- and oxidant-free protocol proceeds via electro-oxidation, followed by radical addition, as well as an intramolecular oxygen nucleophilic process. This methodology is compatible with a broad substrate scope and good functional group compatibility, which provides a valuable and convenient synthetic tool for the synthesis of saturated five-, six-, seven-, and eight-membered ring oxygen heterocycles. Furthermore, sulfonylative cycloesterification of linear unsaturated acids toward the lactone products has also been established under this electrochemical system. In addition, control experiments indicated that the N-H bonds of the sulfonyl hydrazide molecule are non-essential.

Aerobic oxidative lactonization of diols at room temperature over defective titanium-based oxides in water

Lactones are applied in pharmaceutical or agriculture/forestry industry as anesthetics/sedatives, pesticide intermediates or as plant growth regulators. Selective conversion of diols into value-added lactones under mild reaction conditions is still challenging. Here, we report on an environmentally benign catalytic approach using oxygen vacancies-enriched titanium-based oxides and water as solvent at room temperature for the lactonization of various aromatic and aliphatic diols. Lactonization was found to proceed in two consecutive steps: 1) the dehydrogenation of diols to hydroxyaldehyde intermediates catalyzed by the Pt cocatalyst; 2) the subsequent oxidative lactonization of the intermediates to the lactone products over defective titanium-based oxides. Diffuse reflectance infrared Fourier transform spectroscopy analysis using pyridine as probe molecule combined with electron paramagnetic resonance results suggest that oxygen vacancies as strong Lewis acid sites are pivotal for the superior catalytic activities at room temperature, which are attributed to the enhanced reaction rate of step 2 due to stronger adsorption of the hydroxyaldehyde intermediates on the Lewis acid sites.

Asymmetric construction of phosphono dihydropyranones from α-ketophosphonates enabled by Pd/chiral isothiourea relay catalysis.

A highly enantio- and diastereoselective approach has been developed for the synthesis of chiral phosphono dihydropyranones. This approach is enabled by Pd/chiral isothiourea relay catalysis under mild reaction conditions, starting from readily available benzyl bromides, CO, and α-ketophosphonates. The cascade reaction involves the generation of a ketene intermediate from Pd-catalyzed carbonylation of benzyl bromide and subsequent chiral Lewis base catalyzed formal [4 + 2] reaction. Phosphono lactone products can also be transformed to chiral 1,5-diester products in good yield and high stereoselectivity.

N-Heterocyclic Carbene Organocatalyzed Redox-Active/Ring Expansion Reactions: Mechanistic Insights Unveiling Base Cooperativity.

N-Heterocyclic carbene (NHC) organocatalyzed transformations of redox-active chemical manifolds is a powerful strategy for interconverting and expanding the chemical space. This approach in the context of ring expansion holds promise for preparing lactones from plentiful redox active aldehydes, despite a lack of rigorous mechanistic insights into the underlying elements governing this reactivity and with-it relevance to other NHC organocatalyzed transformations. Herein, in investigating this reactivity under the lens of modern day quantum mechanical calculations, we explore the mechanism of redox-active/ring expansion reactions of aldehydes furnishing lactone products by means of NHC organocatalysis. Through this comprehensive study, the underpinning mechanism of Breslow intermediate formation and ensuing downstream processes such as intermolecular C-C bond formation providing benzoin products versus intramolecular redox pathways are outlined. Notably, this study of NHC organocatalysis reveals the diverse role of bases as cooperative agents in directing and selectively routing reactivity, as highlighted here toward ring expanded lactone products.

Tailored alkyl-imidazolium templating synthesis of extra-large-pore germanosilicate zeolite ITT as Baeyer-Villiger oxidation catalyst

Extra-large-pore germanosilicate zeolite ITT was prepared with several structure-tailored alkyl-substituted imidazolium templates. The effect of alkyl chain length and substitution number of template on zeolite topology structure was studied with the variation of synthesis Si/Ge ratio. 1-hexyl-3-methyl-imidazaolium (1H3M) exhibited superior templating effect on the formation of ITT structure within the widest range of synthesis Si/Ge molar ratio of about 2–6. 1H→13C CP/MAS NMR, TGA and molecular simulation results revealed that two 1H3M was occluded in the 18-ring channels per unit cell, presenting the lowest interaction energy with framework. With the combination of XRD, SEM, EDS, ICP, 29Si, 19F MAS NMR, FTIR, N2 physisorption results, it was found that the increase of synthesis Si/Ge ratio improved framework Si/Ge ratio within d4r unit to a certain degree, and in the meantime resulted in the decrease of zeolite crystallinity with the formation of some amorphous phase. ITT showed better Lewis-acid catalytic activity and lactone selectivity for B–V oxidation of 2-adamantanone than BEC, the best germanosilicate zeolite ever reported. The excellent catalytic performance was ascribed to the presence of 18-ring channels in ITT, which facilitated the diffusion of bulky ketone substrate and lactone product. The structure stability of ITT during the reaction was evaluated with the use of either aqueous H2O2 or non-aqueous tert-butyl hydroperoxide (TBHP) as oxidant.

Investigation of glucose electrooxidation mechanism over N-modified metal-doped graphene electrode by density functional theory approach.

In this work, various precious and non‐precious metals reported in the literature as the most effective catalysts for glucose electrooxidation reaction were investigated by the density functional theory (DFT) approach in order to reveal the mechanisms taking place over the catalysts in the fuel cell. The use of a single‐atom catalyst model was adopted by insertion of one Au, Cu, Ni, Pd, Pt, and Zn metal atom on the pyridinic N atoms doped graphene surface (NG). β form of d‐glucose in alkaline solution was used to determine the reaction mechanism and intermediates that formed during the reaction. DFT results showed that the desired glucono‐lactone was formed on the Cu‐3NG electrode in a single‐step reaction pathway whereas it was produced via different two‐step pathways on the Au and Pt‐3NG electrodes. Although the interaction of glucose with Ni, Pd, and Zn‐doped surfaces resulted in the deprotonation of the molecule, lactone product formation did not occur on these electrode surfaces. When the calculation results are evaluated in terms of energy content and product formation, it can be concluded that Cu, Pt, and especially Au doped graphene catalysts are effective for direct glucose oxidation in fuel cells reactor.

A Nonfunctional Halogenase Masquerades as an Aromatizing Dehydratase in Biosynthesis of Pyrrolic Polyketides by Type I Polyketide Synthases.

The bacterial modular type I polyketide synthases (PKSs) typically furnish nonaromatic lactone and lactam natural products. Here, by the complete in vitro enzymatic production of the polyketide antibiotic pyoluteorin, we describe the biosynthetic mechanism for the construction of an aromatic resorcylic ring by a type I PKS. We find that the pyoluteorin type I PKS does not produce an aromatic product, rather furnishing an alicyclic dihydrophloroglucinol that is later enzymatically dehydrated and aromatized. The aromatizing dehydratase is encoded in the pyoluteorin biosynthetic gene cluster (BGC), and its presence is conserved in other BGCs encoding production of pyrrolic polyketides. Sequence similarity and mutational analysis demonstrates that the overall structure and position of the active site for the aromatizing dehydratase is shared with flavin-dependent halogenases albeit with a loss in ability to perform redox catalysis. We demonstrate that the post-PKS dehydrative aromatization is critical for the antibiotic activity of pyoluteorin.

Mechanism-Dependent Selectivity: Fluorocyclization of Unsaturated Carboxylic Acids or Alcohols by Hypervalent Iodine.

To understand the unprecedented difference between 6-endo and 5-exo selectivity in hypervalent iodine (III) promoted fluorocyclization of unsaturated carboxylic acids or alcohols by difluoroiodotoluene, density functional theory (DFT) studies have been performed to systematically compare both the previous proposed “fluorination first and cyclization later” mechanism and the alternative “cyclization first and fluorination later” mechanism. Our results revealed that the selectivity is mechanism-dependent. The unsaturated alcohol prefers the fluorination first and the 6-endo-tet cyclization later pathway, leading to the experimentally observed 6-endo ether product. In contrast, the unsaturated carboxylic acid plausibly undergoes the 5-exo-trig cyclization first and the fluorination later to the experimentally observed 5-exo lactone product. The pK a property of the functional group of the substrate is found to play a key role in determining the reaction mechanism. The provided insights into the mechanism-dependent selectivity should help advance the development of fluorocyclization reactions with hypervalent iodine reagents.

Concise and Stereodivergent Approach to Chromanone Lactones through Copper-Catalyzed Asymmetric Vinylogous Addition of Siloxyfurans to 2-Ester-Substituted Chromones.

Vicinal oxygen-containing tetra- and tri-substituted stereocenters exist widely in chromanone lactone and tetrahydroxanthone natural products. Their enantioselective construction in a single step remains elusive and poses a formidable challenge for chemical synthesis. Here, we report the first copper(I)-catalyzed asymmetric vinylogous additions of siloxyfurans to 2-ester-substituted chromones, which enable concise and enantioselective assembly of chromanone lactones. Both syn and anti adducts can be accessed with excellent diastereo- and enantioselectivity by judicious choice of the chiral ligands. Our approach allowed for the efficient synthesis of (-)-blennolide B with precise stereochemical control, which provides a formal synthesis of secalonic acid A.

Concise and Stereodivergent Approach to Chromanone Lactones through Copper‐Catalyzed Asymmetric Vinylogous Addition of Siloxyfurans to 2‐Ester‐Substituted Chromones

AbstractVicinal oxygen‐containing tetra‐ and tri‐substituted stereocenters exist widely in chromanone lactone and tetrahydroxanthone natural products. Their enantioselective construction in a single step remains elusive and poses a formidable challenge for chemical synthesis. Here, we report the first copper(I)‐catalyzed asymmetric vinylogous additions of siloxyfurans to 2‐ester‐substituted chromones, which enable concise and enantioselective assembly of chromanone lactones. Both syn and anti adducts can be accessed with excellent diastereo‐ and enantioselectivity by judicious choice of the chiral ligands. Our approach allowed for the efficient synthesis of (−)‐blennolide B with precise stereochemical control, which provides a formal synthesis of secalonic acid A.

Supported Pt Enabled Proton-Driven NAD(P)+ Regeneration for Biocatalytic Oxidation.

The utilization of biocatalytic oxidations has evolved from the niche applications of the early 21st century to a widely recognized tool for general chemical synthesis. One of the major drawbacks that hinders commercialization is the dependence on expensive nicotinamide adenine dinucleotide (NAD(P)+) cofactors, and so, their regeneration is essential. Here, we report the design of carbon-supported Pt catalysts that can regenerate NAD(P)+ by proton-driven NAD(P)H oxidation with concurrent hydrogen formation. The carbon support was modified to tune the electronic nature of the Pt nanoparticles, and it was found that the best catalyst for NAD(P)+ regeneration (TOF = 581 h-1) was electron-rich Pt on carbon. Finally, the heterogeneous Pt catalyst was applied in the biocatalytic oxidation of a variety of alcohols catalyzed by different alcohol dehydrogenases. The Pt catalyst exhibited good compatibility with the biocatalytic system. Its NAD(P)+ regeneration function successfully supported biocatalytic conversion from alcohols to corresponding ketone or lactone products. This work provides a promising strategy for chemical synthesis via NAD(P)+-dependent pathways utilizing a cooperative inorganic-enzymatic catalytic system.

Electrochemical Formation and Activation of Hydrogen Peroxide from Water on Fluorinated Tin Oxide for Baeyer–Villiger Oxidation Reactions

The two-electron oxidation of water (2e-WOR) has been studied in the past as a possible method for the alternative preparation of hydrogen peroxide. Often, fluorinated tin oxide (FTO) is used as an anode and FTO itself was found also to be active for 2e-WOR. Because one use of H2O2 is as an oxygen donor for Baeyer–Villiger oxidation of ketones catalyzed by tin compounds and materials, presently we were interested in studying the use of in situ formed H2O2 for these reactions. First, the formation of H2O2 was verified in an acetonitrile/water solvent in a 2e-WOR reaction, which is more efficient than a comparable reaction in water in terms of the H2O2 concentration attained and faradaic efficiency at comparable potentials, that is, ∼3 V vs SHE. Second, initial studies on oxygenation of reactive substrates such as sulfides showed normalized reaction rates (NRRs) for two-electron oxidation reactions that were about 3 times higher than the NRR for H2O2 formation, indicating the formation of an active oxygen-donating or oxidizing species on the electrode surface prior to the formation and release of H2O2 into solution. Third, the Baeyer–Villiger oxygenation of 2-adamantanone at 2.1 V versus SHE in acetonitrile/water showed both the formation of the expected lactone product and hydroxylation at both tertiary and secondary C–H bonds. Hydroxylation is most easily explained by the presence of hydroxyl radical species as supported by the formation of a spin adduct and its identification by electron paramagnetic resonance. However, the potential used, 2.1 V versus SHE, is an underpotential for the formation of a solvated hydroxyl radical in solution, thereby leading to the conclusion that surface-bound hydroxyl species, OH*, are those that are reactive for the apparent one-electron water oxygenation reaction. Fourth, it was shown that although H2O2 can be thermally activated on FTO as a catalyst to a minor degree, electrochemical activation is by far more significant, leading to the use of FTO as an electrochemical catalyst for activation of H2O2 for the Baeyer–Villiger oxygenation and also alkene epoxidation.

Piloting an approach to scab control on Welsh sheep farms.

IntroductionSheep scab caused by Psoroptes ovis, is a disease of concern to many stakeholders in Wales due to its welfare implications. There are good diagnostic tests and treatments available to deal with the disease. Even so, it remains a problem in Welsh flocks. As such a coordinated approach is required to deal with this issue in a more sustainable manner.Pilot designSheep scab positive ‘index’ farms were initially diagnosed using a skin scrape to identify P. ovis mites. Contiguous farms were identified and antibody responses used to confirm onward infestation. All infested farms were treated by either dipping with an organophosphate (OP) dip or injecting with a licensed macrocyclic lactone (ML) product depending on farmer choice.ResultsThree positive ‘index’ farms were identified along with 12 contiguous properties. Positive serological responses were observed in seven of the 12 contiguous farms; four of which were treated by OP dip and three by an injectable ML product.DiscussionTo avoid reinfestation of treated farms, dealing with disease on contiguous properties is crucial. Through the project coordinating team, three local outbreaks of scab were dealt with in a short space of time with appropriate diagnosis and treatment being carried out. Some farmers were uncooperative and strategies such as providing additional external support and veterinary involvement might alleviate these issues in the future. This coordinated approach is recommended to veterinary surgeons in the field when dealing with scab on farm.

Enantioselective Cascade Annulation of α‐Amino‐ynones and Enals Enabled by Gold and Oxidative NHC Relay Catalysis

AbstractWe report herein an unprecedented gold and oxidative NHC relay catalysis that enables highly enantioselective cascade annulation between readily available α‐amino‐ynones with enals. This method utilizes the in situ‐generated pyrrolin‐4‐ones as a novel and versatile synthon, which engage with α,β‐unsaturated acylazolium intermediates generated from enals by oxidative NHC catalysis to produce pyrrole‐fused lactones in high yield and excellent enantioselectivity. Synthetic utility of the lactone products is also demonstrated by facile conversion to densely functionalized pyrroles and pyrrolin‐4‐ones in high yields with excellent stereopurity.

Enantioselective Cascade Annulation of α-Amino-ynones and Enals Enabled by Gold and Oxidative NHC Relay Catalysis.

We report herein an unprecedented gold and oxidative NHC relay catalysis that enables highly enantioselective cascade annulation between readily available α-amino-ynones with enals. This method utilizes the in situ-generated pyrrolin-4-ones as a novel and versatile synthon, which engage with α,β-unsaturated acylazolium intermediates generated from enals by oxidative NHC catalysis to produce pyrrole-fused lactones in high yield and excellent enantioselectivity. Synthetic utility of the lactone products is also demonstrated by facile conversion to densely functionalized pyrroles and pyrrolin-4-ones in high yields with excellent stereopurity.

Ligand-Enabled C-H Olefination and Lactonization of Benzoic Acids and Phenylacetic Acids via Palladium Catalyst.

A novel ligand propan-2-one O-(p-tolylcarbamoyl) oxime (L7) has been developed to promote C(sp2)-H olefination of benzoic acids and phenylacetic acids via a palladium catalyst. With the subsequent lactonization of the olefinated products through 1,4-addition, highly monoselective cyclic lactone products of benzofuranones and benzopyrones were obtained in moderate to excellent yields. The DFT calculation demonstrated that the novel ligand propan-2-one O-(p-tolylcarbamoyl) oxime (L7) could improve the C-H activation reaction to give cyclic lactone products elegantly.