Oxime Esters Research Articles

Visible-light-induced copper-catalyzed regiodivergent C(sp3)-sulfonylation of oxime esters with sodium sulfinates

A visible-light-induced copper-catalyzed regiodivergent sulfonylation of oxime esters with sodium sulfinates under mild conditions is reported, yielding a range of useful β-ketosulfones and sulfonated pyrrolines with convertible functional groups.

Thiourea as a precatalyst for the electron donor–acceptor complex photoactivation platform of oxime esters

A novel electron donor–acceptor (EDA) complex catalysis strategy has been developed using thiourea as a precatalyst under blue LED irradiation. Using 2–5 mol% of thiourea, various nitrogen-containing compounds were successfully synthesized.

Photoinduced EnT-mediated sulfonamidylimination of alkenes and (hetero)arenes with iminophenylacetic acid oxime esters.

A photoinduced EnT-mediated generation of sulfonamidyl radicals has been accomplished using rationally designed iminophenylacetic acid oxime ester reagents under metal-free conditions. This approach offers a mild, regio- and diastereoselective synthesis of N-sulfonyl diamines via diamination of alkenes and (hetero)arenes.

Photoredox-catalyzed intramolecular oxy- and aminoacylation of alkenes with acyl oxime esters: facile synthesis of acylated saturated heterocycles

A general photoredox-catalyzed intramolecular oxy- and aminoacylation of internal alkenes with acyl oxime esters to access various acyl heterocycles is developed.

Semisynthesis and Cytotoxic Activities of Novel Oxime Ester Derivatives of the Diterpene Stemodin

Stemodin (1) is a diterpene produced by Stemodia maritima L. (Scrophulariaceae) and shows antiviral and tumor cell proliferation inhibitory activities. Chemical modifications of 1 were performed to produce the known stemodinone (2), two new stemodinone oximes, Z (3) and E (4), and seven new oxime esters derivatives (5, 6, 7, 8, 9, 10, and 11). All derivatives were evaluated for their cytotoxic activity in HL60 (promyelocytic leukemia), SNB-19 (astrocytoma), HCT-116 (colon carcinoma), and PC3 (prostate) human cancer cell lines, and L929 (healthy murine cells). Oximes 3 and 4 showed lower cytotoxic values than 1 against all cancer cell lines tested. However, esters 9 and 10 exhibited cell growth inhibition percentages higher than 1 against PC3, SNB-19, and HCT-116 cancer cell lines, ranging from 62.96 to 94.27%. Many of these values exceed that presented by doxorubicin (66.05-86.87%). All compounds showed no cytotoxic effect on healthy cells at the tested concentration of 25 µg mL-1.

Visible-light-driven EDA complex-promoted cascade cyclization to construct 4-cyanoalkyl isoquinoline-1,3-diones.

Visible-light-induced EDA complex-promoted ring-opening of cycloketone oxime esters to synthesise various cyanoalkylated products with N-methacryloyl benzamides was developed. Various radical receptors were compatible with the current reaction system to furnish diverse heterocyclic compounds. Mechanistic analysis shows that the formation of an EDA complex was crucial to the photocatalytic strategy. Importantly, 4-cyanoalkyl isoquinoline-1,3-diones were obtained in high yields by using a catalytic amount of 1,4-diazabicyclo[2.2.2]octane (DABCO) through prolonging the reaction time, which provided a practical approach to give a variety of isoquinoline-1,3-dione derivatives.

Visible-light-induced C-H alkylation of 2-amino-1,4-naphthoquinones.

Simple and practical strategies for visible-light-induced C-H alkylation of 2-amino-1,4-naphthoquinones with cyclobutanone oxime esters and hydroxamic acid derivatives have been developed under mild and redox-neutral conditions. These two reactions can be carried out at room temperature and obtain a variety of 2-amino-1,4-naphthoquinone derivatives with cyano and amide groups. Moreover, the cyanoalkylation reaction of 2-amino-1,4-naphthoquinones can proceed smoothly in the absence of photocatalysts.

EnT mediated alkoxy radical generation: the construction of 1,6-amino alcohols using bifunctional oxime esters.

The generation of long-chain alkoxy radicals via visible light-induced energy transfer (EnT) has been accomplished through the design of a new class of bifunctional oxime esters derived from iminophenylacetic acid. The 1,5-hydrogen atom abstraction (HAT) of the alkoxy radicals, followed by alkylamination of alkenes, enables the construction of a 1,6-linkage across a double bond to obtain the valuable 1,6-amino alcohols.

Copper-catalyzed thiocyanation of cyclobutanone oxime esters using ammonium thiocyanate.

A copper-catalyzed thiocyanation of cycloketone oxime esters with ammonium thiocyanate has been developed for the first time. This innovative approach allows access to cyano and thiocyano bifunctionally substituted alkanes, which can be further transformed into their respective trifluoromethylthiol-substituted or difluoromethylthiol-substituted alkylnitriles, alkynyl sulfides, and phosphorothioate esters. The readily available nature of ammonium thiocyanate and the cost-effectiveness of the copper catalyst make this method a promising strategy for the synthesis of sulfur-containing alkylnitriles.

Difunctionalization of gem-difluoroalkenes for amination and heteroarylation via metal-free photocatalysis.

gem-Difluoroalkenes are widely used building blocks in fluorine chemistry. Herein, a metal-free photocatalytic amination and heteroarylation method of gem-difluoroalkenes with heteroaryl carboxylic acid oxime esters as substrates is reported. This environmentally benign reaction proceeds via radical-radical cross-coupling in energy-transfer-mediated photocatalysis and can be used in the rapid construction of heteroaryl difluoroethylamine scaffolds and late-stage modification of complex pharmaceutical structures.

Zwitterions as catalytic electron donor species for visible light-induced photoactivation of oxime esters and direct C3-alkylation of quinoxalin-2(1H)-ones

A novel ternary EDA complex catalysis strategy has been developed for the photoactivation of oxime esters. By augmenting the electron-donating properties of zwitterions with a base, a ternary EDA complex...

Preparation of Intermediates for Organic Synthsis

Several synthetic methods are described for the preparation of compounds such as derivatives of natural amino acids, unnatural amino acids, amino esters, oxime esters and amino amides that may serve as intermediates in the synthesis of active pharmaceutical ingredients (APIs) or drugs. The compounds described herein are produced in high yield and purity and the synthetic procedures are detailed along with the NMR spectra of the compounds and useful chemical data relating to these compounds.

Synthesis, Herbicidal Activity against Barnyard Grass, and Photolytic Behavior of Aryl 2,6-Dipyrimidinoxybenzoates.

In this study, we investigated the characteristics and herbicidal potential of bispyribac phenolic esters, which belong to the 2-(pyrimidin-2-yloxy)benzoic acid (PYB) class of acetohydroxyacid synthase (AHAS-)-inhibiting herbicides. These herbicides are primarily used for controlling Poaceae and broadleaf weeds. Among them, bispyribac-sodium stands out as a representative in this class. Surprisingly, other bispyribac esters, including alkanol and phenol esters exhibit considerably reduced herbicidal activity compared to bispyribac-sodium. In contrast, oxime esters (e.g., pyribenzoxim) demonstrate high activity. To further understand and develop novel PYB herbicides, we synthesized and screened a series of bispyribac phenolic esters while investigating their photochemical behaviors. Several compounds displayed excellent herbicidal activity, with compounds Ia-19 and Ic showing impressive 90% effective dosages for fresh weight inhibition of barnyard grass, measuring 0.55 and 0.60 g a.i./hm2, respectively. These values were approximately half of bispyribac-sodium or pyribenzoxim. The results indicate that the herbicidal activity of phenolic esters is influenced by both their binding ability to the AHAS enzyme and their decomposition into bispyribac acid. For instance, bispyribac phenol ester exhibited considerably reduced receptor affinity compared to bispyribac-sodium, and faced challenges in transforming into bispyribac acid, explaining its diminished herbicidal activity. However, introducing a photosensitive nitro group led to a complete transformation. This modification improved its affinity with AHAS and accelerated its decomposition into bispyribac acid, further accelerated by photocatalysis. Consequently, nitro-containing compounds displayed heightened herbicidal activity. The findings from this study open possibilities for structural optimization of phenolic esters through quantitative structure-activity relationship analysis, potentially regulating their activity-releasing period. Furthermore, the high activity of aromatic heterocyclic esters offers new insights into developing novel PYB herbicides.

Phenothiazine-based oxime ester as a photobase generator for thiol-acrylate reactions

In this work, a previously designed and synthesized phenothiazine-based oxime ester was investigated as a photobase generator for the formation of thiol-acrylate networks through the polymerization of thiol-acrylate reactions and more appealingly the base-catalyzed thiol-acrylate Michael addition reactions. This system accomplished a complete disappearance and a full conversion of the characteristic acrylate peak within 10 min of irradiation with a light-emitting diode (λ = 405 nm) or within 1 or 2 min of the same irradiation source and 24 h of heat exposure (T = 60 °C). Photobase generation was evidenced using phenol red as a pH-indicator, enabling to confirm the production of methyl amine (CH3NH2) as initiating species. Photoinitiation mechanism through which base reactive species are produced and the reactions by which the thiol-acrylate polymerization proceeds were investigated according to the base detection experiments, the obtained real-time Fourier transform infrared spectroscopy results, and according to the general photochemical base-generation reactions of oxime-esters. Finally, differential scanning calorimetry scans and Shore A and Shore D hardness experiments have been performed on the polymers obtained to examine their thermal properties and surface hardness features.

Rapid Assembly of Unsymmetrically Linked Bis-heterocycles via Palladium Domino Catalysis.

A palladium-catalyzed domino reaction of alkene-tethered oxime esters is reported. This transformation uses an air-stable palladium precatalyst that initiates a Narasaka-Heck reaction, that is interrupted with a Pd(II)-promoted cyclization. Through this methodology, a novel class of unsymmetrical alkyl-linked bis-heterocycles were synthesized in yields up to 99%. The reaction is scalable up to 1.0 mmol, with simplified purification steps. This transformation expands the scope of accessible bis-heterocycles available through Narasaka-Heck reactions beyond C-H activation and direct anionic capture termination steps.

Photocatalyzed Amination of Alkyl Halides to Access Primary Amines.

We demonstrate that oxime ester derivatives can be used as both a halogen atom transfer (XAT) agent and an imine source under photocatalytic conditions, allowing the radical amination of alkyl halides, resulting in the formation of a broad scope of imines. Hydrolysis of the latter gives direct access to the corresponding primary amines. Mechanistically, the reaction is believed to proceed through the formation of aryl radical intermediates, which are responsible for the activation of alkyl halides via XAT.

Study on the photoinitiation mechanism of carbazole-based oxime esters (OXEs) as novel photoinitiators for free radical photopolymerization under near UV/visible-light irradiation exposure and the application of 3D printing

In this work, twenty-two oxime esters bearing different functional groups and based on carbazole as the chromophore were designed and synthesized as Type I photoinitiators. Interestingly, all structures mentioned in this work have never been reported before (even for their synthesis). These oxime esters were found to have good light absorption properties in the UV–visible range, and especially at 405 nm which is a reference wavelength in photopolymerization. Noticeably, several structures showed better photoinitiation abilities than the benchmark photoinitiator i.e. diphenyl(2,4,6-trimethylbenzoyl)phosphine oxide (TPO), evidencing the interest of these structures. In order to investigate the photoinitiation mechanism of the two series of oxime esters differing by the position of the photocleavable groups, electronic absorption spectra were determined by molecular modeling and density functional theory calculations. Photopolymerization abilities of the different oxime esters and release of CO2 during the polymerization experiments were determined by Real-Time Fourier Transformed Infrared (RT-FTIR). Active free radicals were characterized by mean of Electron Spin Resonance Spin Trapping (ESR-ST) experiments. On the basis of these different complementary experiments, chemical mechanisms occurring during photopolymerization could be proposed. Experimental results showed that the decarboxylation reaction occurring subsequent to the photocleavage of oxime esters had a beneficial effect on the photoinitiation ability. Finally, 3D printed objects were successfully obtained by using oxime esters exhibiting the best photoinitiating abilities.

Imino‐Fluoroalkanesulfonylation of γ,δ‐Unsaturated Oxime Esters Enabled by Photoredox/Cu Dual Catalysis

AbstractSulfonyl‐tethered N‐containing heterocycles are valuable building blocks in synthetic and pharmaceutical chemistry. Recently, the installation of fluoroalkanesulfonyl groups into heterocycles via the difunctionalization of alkenes still remains challenging. Herein in this work, an imino‐fluoroalkanesulfonylation of γ,δ‐unsaturated oxime esters has been achieved via photoredox/Cu dual catalysis. A variety of fluoroalkanesulfonyl‐tethered pyrroline derivatives have been readily synthesized in moderate to good yields under mild conditions.

Natural terpene-based derivatives to control postharvest sclerotinia rot and the involved potential mechanism

In an effort to develop novel postharvest preservatives of satisfactory environmental compatibility from natural monoterpene, a series of terpene-based derivatives containing oxime ester were designed and prepared. In this research, the inhibitory effect of target compounds against S. sclerotiorum were evaluated though in vitro and in vivo tests. It was investigated that most compounds exhibited promising antifungal activity, especially compound 4k with EC50 value of 3.02 μg/mL, which was significantly superior to commercial fungicide trifloxystrobin. Notably, compound 4k improved the physicochemical quality of carrot including weight loss, contents of titratable acidity, ascorbic acid, carotenoid, malondialdehyde, and enzymes activities, ensuring post-harvest preservation. Simultaneously, the mycelial morphology, ultrastructure, cell wall permeability, and defense/respiration-related enzymes of S. sclerotiorum were destructed. The preliminary toxicity evaluation of target compounds indicated that the prepared target compounds possessed safety and low toxicity. Additionally, the essential chemical features for activity and interaction mode between molecule and cytochrome bc1 complex were inquired by computer-aid technology. The study provided meaningful insight into formulation of natural terpene-based fresh-keeping agent to resist postharvest decay infected by S. sclerotiorum.

Regioselective Synthesis of Phenanthridines via Pd(II)-Catalyzed Annulative C(sp2)-H Activation.

A robust synthesis of phenanthridines has been described via Pd(II)-catalyzed domino C(sp2)-H activation/N-arylation using oxime esters with aryl acyl peroxides in a highly regioselective manner. This protocol is compatible with acetophenone as well as benzophenone-derived oxime esters and allows modular construction of functionalized phenanthridines with wide tolerance of electronic functionality. Further transformations were conducted to synthesize key building blocks, and control experiments were performed to understand the plausible reaction mechanism.