Active Ester Functionalized Azobenzenes as Versatile Building Blocks

Azobenzenes are important molecular switches that can still be difficult to functionalize selectively. A high yielding Pd-catalyzed cross-coupling method under mild conditions for the introduction of NHS esters to azobenzenes and diazocines has been established. Yields were consistently high with very few exceptions. The NHS functionalized azobenzenes react with primary amines quantitatively. These amines are ubiquitous in biological systems and in material science.

Cure kinetics and properties of high-performance epoxy thermosets cured with active ester-terminated poly (aryl ether ketone)

Benzene-1,3,5-triyl tribenzoate (TBB), both 3,5-bis(benzoyloxy)benzoate-terminated poly (aryl ether ketone) oligomers (BPAPK and TMPK), containing active ester (Ph−O−(C=O)− structure), were prepared and served as curing agents for dicyclopentadiene novoalc epoxy (DCPD). The curing kinetics and properties of three epoxy thermosets were systematically investigated. The model reaction of TBB and glycidyl phenyl ether was designed to understand the curing mechanism of oxirane ring with active ester. TMPK/DCPD displays the lowest reaction activation energy, which is the result of the combined influence of free volume and diffusion. In addition, TMPK/DCPD has the highest Tg value (218°C), which enhances 34.6% and 42.5% compared with BPAPK/DCPD and TBB/DCPD, respectively. Meanwhile, TMPK/DCPD also shows superior dielectric and water resistance properties due to no secondary alcohol generated after curing and hydrophobic tetramethyl-substituted biphenyl structure. Herein, TMPK/DCPD as high-performance epoxy thermosets has potential applications in electronic packaging fields.

Sodium N-(3,5-Bis(ethoxycarbonyl)-2,6-dimethyl-1,4-dihydropyridine-4-carbonyl)-l-methioninate

The development of the methods for amide bond formation is important for various uses in the laboratory and industrial applications. The compounds combined in their structures 1,4-dihydroisonicotinic acids and amino acids linked with an amide bond can be considered as “privileged structures” due to their broad range of biological activities. Herein, the formation of amide bond between 1,4-dihydroisonicotinic acid and l-methionine is reported. The coupling of l-methionine with pentafluorophenyl active ester of 1,4-dihydroisonicotinic acid appears to be a convenient and effective method for amide bond formation. Sodium N-(3,5-bis(ethoxycarbonyl)-2,6-dimethyl-1,4-dihydropyridine-4-carbonyl)-l-methioninate has been successfully synthesized via a procedure where the key step is amide formation from 5-diethyl 4-(perfluorophenyl) 2,6-dimethyl-1,4-dihydropyridine-3,4,5-tricarboxylate and l-methionine. Sodium salt formation was performed to improve physicochemical properties, such as solubility of the l-methionine-derived 1,4-dihydroisonicotinamide. The obtained target compound was fully characterized by UV, IR, 1H NMR, 13C NMR, MS, and microanalysis.

A Trisbenzimidazole Phosphoramidite Building Block Enables High-Yielding Syntheses of RNA-Cleaving Oligonucleotide Conjugates

The RNA cleaving catalyst tris(2-aminobenzimidazole) when attached to the 5’ terminus of oligonucleotides cuts complementary RNA strands in a highly site-specific manner. Conjugation was previously achieved by the acylation of an amino linker by an active ester of the catalyst. However, this procedure was low yielding and not reliable. Here, a phosphoramidite building block is described that can be coupled to oligonucleotides by manual solid phase synthesis in total yields around 85%. Based on this chemistry, we have now studied the impact of LNA (locked nucleic acids) nucleotides on the rates and the site-specificities of RNA cleaving conjugates. The highest reaction rates and the most precise cuts can be expected when the catalyst is attached to a strong 5’ closing base pair and when the oligonucleotide contains several LNA units that are equally distributed in the strand. However, when placed in the 5’ position, LNA building blocks tend to diminish the specificity of RNA cleavage.

Nucleophilic (Radio)Fluorination of Redox-Active Esters via Radical-Polar Crossover Enabled by Photoredox Catalysis

<p>We report a redox-neutral method for nucleophilic fluorination of N-hydroxyphthalimide esters using an Ir photocatalyst under visible light irradiation. The method provides access to a broad range of aliphatic fluorides, including primary, secondary, and tertiary benzylic fluorides as well as unactivated tertiary fluorides, that are typically inaccessible by nucleophilic fluorination due to competing elimination. In addition, we show that the decarboxylative fluorination conditions are readily adapted to radiofluorination with [¹⁸F]KF. We propose that the reactions proceed by two electron transfers between the Ir catalyst and redox-active ester substrate to afford a carbocation intermediate that undergoes subsequent trapping by fluoride. Examples of trapping with O- and C-centered nucleophiles and deoxyfluorination via N-hydroxyphthalimidoyl oxalates are also presented, suggesting that this approach may offer a general blueprint for affecting redox-neutral SN1 substitutions under mild conditions.</p>

Nucleophilic (Radio)Fluorination of Redox-Active Esters via Radical-Polar Crossover Enabled by Photoredox Catalysis

<p>We report a redox-neutral method for nucleophilic fluorination of N-hydroxyphthalimide esters using an Ir photocatalyst under visible light irradiation. The method provides access to a broad range of aliphatic fluorides, including primary, secondary, and tertiary benzylic fluorides as well as unactivated tertiary fluorides, that are typically inaccessible by nucleophilic fluorination due to competing elimination. In addition, we show that the decarboxylative fluorination conditions are readily adapted to radiofluorination with [¹⁸F]KF. We propose that the reactions proceed by two electron transfers between the Ir catalyst and redox-active ester substrate to afford a carbocation intermediate that undergoes subsequent trapping by fluoride. Examples of trapping with O- and C-centered nucleophiles and deoxyfluorination via N-hydroxyphthalimidoyl oxalates are also presented, suggesting that this approach may offer a general blueprint for affecting redox-neutral SN1 substitutions under mild conditions.</p>

IL@CQD catalyzed active ester rearrangement for the detection and removal of cyanide ions

Recognition of cyanide ion with IL@CQDs catalyzed rearranged product.

Design and Synthesis of a Cyclic Double-Grafted Polymer Using Active Ester Chemistry and Click Chemistry via A “Grafting onto” Method

Combing active ester chemistry and click chemistry, a cyclic double-grafted polymer was successfully demonstrated via a “grafting onto” method. Using active ester chemistry as post-functionalized modification approach, cyclic backbone (c-P2) was synthesized by reacting propargyl amine with cyclic precursor (poly(pentafluorophenyl 4-vinylbenzoate), c-PPF4VB6.5k). Hydroxyl-containing polymer double-chain (l-PS-PhOH) was prepared by reacting azide-functionalized polystyrene (l-PSN3) with 3,5-bis(propynyloxy)phenyl methanol, and further modified by azide group to generate azide-containing polymer double-chain (l-PS-PhN3). The cyclic backbone (c-P2) was then coupled with azide-containing polymer double-chain (l-PS-PhN3) via CuAAC reaction to construct a novel cyclic double-grafted polymer (c-P2-g-Ph-PS). This research realized diversity and complexity of side chains on cyclic-grafted polymers, and this cyclic double-grafted polymer (c-P2-g-Ph-PS) still exhibited narrow molecular weight distribution (Mw/Mn < 1.10).