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Comprehensive Summary: Herein, we report rhodium catalyzed N‐arylation via addition of arylboronic acids to electron‐deficient α‐iminoesters which can be prepared in high efficiency by using easily accessible β‐carbonyl esters. The reaction is highly regiospecific to achieve the N‐aryl addition efficiently with up to 99% yield under mild conditions. The corresponding product can be further efficiently converted into indoles and a series of other important building blocks. [ABSTRACT FROM AUTHOR]

ABSTRACT Protected lysine esters (Boc‐L‐Lys(Boc)‐OSu) an intermediate of high repute in the peptide synthesis and diverse chemical synthetic applications, was the subject of synthetic process development studies, unveiling process‐related impurities. These impurities were synthesized, characterized, and identified by different analytical tools, with their retention times verified by HPLC co‐injection with commercial products. Detailed discussions ensued on the potential formation pathways and synthetic strategies of these process‐related impurities. [ABSTRACT FROM AUTHOR]

A general and highly enantioselective method for the preparation of tetra‐substituted 3‐hydroxyphthalide esters via isothiourea‐catalysed acylative dynamic kinetic resolution (DKR) is reported. Using (2S,3R)‐HyperBTM (5 mol %) as the catalyst, the scope and limitations of this methodology have been extensively probed, with high enantioselectivity and good to excellent yields observed (>40 examples, up to 99 %, 99 : 1 er). Substitution of the aromatic core within the 3‐hydroxyphthalide skeleton, as well as aliphatic and aromatic substitution at C(3), is readily tolerated. A diverse range of anhydrides, including those from bioactive and pharmaceutically relevant acids, can also be used. The high enantioselectivity observed in this DKR process has been probed computationally, with a key substrate heteroatom donor O⋅⋅⋅acyl‐isothiouronium interaction identified through DFT analysis as necessary for enantiodiscrimination. [ABSTRACT FROM AUTHOR]

The development of methods to allow the selective acylative dynamic kinetic resolution (DKR) of tetra‐substituted lactols is a recognised synthetic challenge. In this manuscript, a highly enantioselective isothiourea‐catalysed acylative DKR of tetra‐substituted morpholinone and benzoxazinone‐derived lactols is reported. The scope and limitations of this methodology have been developed, with high enantioselectivity and good to excellent yields (up to 89 %, 99 : 1 er) observed across a broad range of substrate derivatives incorporating substitution at N(4) and C(2), di‐ and spirocyclic substitution at C(5) and C(6), as well as benzannulation (>35 examples in total). The DKR process is amenable to scale‐up on a 1 g laboratory scale. The factors leading to high selectivity in this DKR process have been probed through computation, with an N−C=O⋅⋅⋅isothiouronium interaction identified as key to producing ester products in highly enantioenriched form. [ABSTRACT FROM AUTHOR]

Elemental sulfur has shown to be a promising alternative feedstock for development of novel polymeric materials with high sulfur content. However, the utilization of inverse vulcanized polymers is restricted by the limitation of functional comonomers suitable for an inverse vulcanization. Control over properties and structure of inverse vulcanized polymers still poses a challenge to current research due to the dynamic nature of sulfur‐sulfur bonds and high temperature of inverse vulcanization reactions. In here, we report for the first time the inverse vulcanization of norbornenyl pentafluorophenyl ester (NB‐PFPE), allowing for post‐modification of inverse vulcanized polymers via amidation of reactive PFP esters to yield high sulfur content polymers under mild conditions. Amidation of the precursor material with three functional primary amines (α‐amino‐ω‐methoxy polyethylene glycol, aminopropyl trimethoxy silane, allylamine) was investigated. The resulting materials were applicable as sulfur containing poly(ethylene glycol) nanoparticles in aqueous environment. Cross‐linked mercury adsorbents, sulfur surface coatings, and high‐sulfur content networks with predictable thermal properties were achievable using aminopropyl trimethoxy silane and allylamine for post‐polymerization modification, respectively. With the broad range of different amines available and applicable for post‐polymerization modification, the versatility of poly(sulfur‐random‐NB‐PFPE) as a platform precursor polymer for novel specialized sulfur containing materials was showcased. [ABSTRACT FROM AUTHOR]

Considerable synthetic effort has been devoted to acid‐ or base‐catalysed transesterification of alkyl salicylate with alcohol in order to synthesize salicylate esters efficiently. In this study, the transesterification of methyl salicylate with 12 different alcohols was carried out by the use of Zn dust as a catalyst. Depending on the alcohol used in the transesterification reaction, the completion of the reaction was within a range of 8–15 h at a temperature between 100 and 170°C. The use of Zn dust provided reusability and almost complete recovery with moderate to excellent yields (42%–97%). The structural elucidation of the products was performed using IR, 1H NMR, 13C NMR and GC–MS data obtained from the Wiley GC/MS Library and the in‐house "Parkim Fragrance House GC/MS Library." [ABSTRACT FROM AUTHOR]

Our newly developed menthyl esters of valine and isoleucine exhibit anti‐inflammatory properties beyond those of the well‐known menthol in macrophages stimulated by lipopolysaccharide (LPS) and in a mouse model of colitis induced by sodium dextran sulfate. Unlike menthol, which acts primarily through the cold‐sensitive TRPM8 channel, these menthyl esters displayed unique mechanisms that operate independently of this receptor. They readily penetrated target cells and efficiently suppressed LPS‐stimulated tumour necrosis factor‐alpha (Tnf) expression mediated by liver X receptor (LXR), a key nuclear receptor that regulates intracellular cholesterol and lipid balance. The menthyl esters showed affinity for LXR and enhanced the transcriptional activity through their non‐competitive and potentially synergistic agonistic effect. This effect can be attributed to the crucial involvement of SCD1, an enzyme regulated by LXR, which is central to lipid metabolism and plays a key role in the anti‐inflammatory response. In addition, we discovered that the menthyl esters showed remarkable efficacy in suppressing adipogenesis in 3T3‐L1 adipocytes at the mitotic clonal expansion stage in an LXR‐independent manner as well as in mice subjected to diet‐induced obesity. These multiple capabilities of our compounds establish them as formidable allies in the fight against inflammation and obesity, paving the way for a range of potential therapeutic applications. [ABSTRACT FROM AUTHOR]

We report a photochemical method for the semipinacol rearrangement of unactivated allylic alcohols. Aliphatic as well as aromatic groups participate as migrating groups, yielding a variety of α,α‐disubstituted ketones. The reaction proceeds under mild conditions and is compatible with ethers, esters, halides, nitriles, carbamates, and substituted arenes. The operationally simple and fully catalytic conditions prescribe 1 mol % benzothiazinoquinoxaline as organophotocatalyst, 0.5 mol % Co‐salen, and 10 mol % lutidinium triflate and, importantly, display reactivity complementary to procedures employing Brønsted acid. We showcase the utility of the protocol in late‐stage drug diversifications. [ABSTRACT FROM AUTHOR]

In this work, six benzothioxanthene‐based oxime esters were employed as photoinitiators for photopolymerization under visible light (LED) and sunlight. Their abilities to behave as Type I photoinitiators by mean of a photocleavage mechanism of oxime esters but also in multicomponent photoinitiating systems with an iodonium salt (through an electron transfer mechanism) were both explored with the different structures. Due to their broad absorption spectra tailing up 600 nm, photoinitiating properties of the benzothioxanthene‐based oxime esters were systematically tested under excitation with low‐intensity LED light at wavelengths of 405 nm and 450 nm. Additionally, parallel to the polymerization tests done under artificial light, the different benzothioxanthene‐based oxime esters were also investigated as solar photoinitiators and displayed a high reactivity in France (Western Europe) even in winter conditions. For the best candidates i.e. the most reactive structures, direct laser write experiments were carried out, evidencing the interest of these structures. [ABSTRACT FROM AUTHOR]

Diels‐Alder between nitroalkenes derived from a sugar scaffold and cyclopentadiene were examined. Depending on chemical structure of nitroalkene and polarity of solvent used, the reaction proceeded via the formation of a nitronate intermediate. Cyclic nitronates highly functionalized were obtained as chemically stable and stereochemically pure compounds. [3,3] sigmatropic shift of these ones afforded the Diels Alder cycloadducts in quantitative yield. Mechanistic aspects of reaction between nitroalkenes and cyclopentadiene has been studied using DFT computational methods. Nitronate derivatives are attractive intermediates and open the way for the construction of valuable compounds with potential applications. [ABSTRACT FROM AUTHOR]

We report herein a blue‐light‐promoted iron‐catalyzed reduction of carboxamides and carboxylic esters. Conducting the reaction under hydrosilylation conditions and blue light (2×24 W, 450–460 nm) in the presence of an iron(0) based pre‐catalyst, Fe(CO)4(IMes), amines and alcohols were obtained, respectively, notably at ambient conditions, whereas using white light, higher reaction temperatures up to 100 °C were required. Preliminary mechanism studies highlighted the crucial role of blue light not only to generate the catalytic active species, but also in some steps of the catalytic cycle. [ABSTRACT FROM AUTHOR]

A silver‐catalyzed regioselective one‐pot cyclization reaction of diazo reagents with fluoronitroalkenes was developed. This transformation presents a method for accessing a series of 4‐aryl‐3‐fluoropyrazoles that are substituted with various groups such as trifluoromethyl, carboxylic ester, nitrile, and phosphonate ester. Further synthetic transformations offered the corresponding fluorinated and trifluoromethylated analogues of two fungicide compounds. [ABSTRACT FROM AUTHOR]

In this manuscript a general photocatalytic approach for the synthesis of alkyl‐substituted gem‐difluoroalkenes using readily available oxime esters and 1‐bromo‐1,1‐difluoroprop‐2‐ene (BDFP) has been established. This strategy involving a radical bromo elimination provides access to a large variety of value‐added fluorinated molecules. The mild reaction conditions are compatible with many functional groups including complex natural products or drug molecules. Experimental and theoretical mechanistic investigations indicate that the efficiency of the process relies on the crucial role of imine radical, which is formed after photoexcitation via energy transfert (EnT) and decarboxylation of the oxime ester. Indeed, the imine radical would either behave as a bromine radical scavenger or an XAT promoter in this reaction. [ABSTRACT FROM AUTHOR]

The facile generation of the α‐acyloxy carboxamide radical is hereby reported for the first time, utilizing a photoredox catalyzed reaction of Passerini adducts synthesized using a 4‐formyl‐1,4‐dihydropyridine as the carbonyl component. This radical effectively engages in a Giese reaction with a range of olefins, ultimately leading to the synthesis of novel Passerini‐derived products not previously amenable to direct aldehyde‐based transformations. Consequently, the resulting strategy, developed both in batch and in flow, offers a promising opportunity to expand the chemical space accessible through the Passerini reaction, virtually incorporating “impossible” aldehydes. [ABSTRACT FROM AUTHOR]

Coumalic acid methyl ester (methyl coumalate), a biomass‐derived building block, was converted into (E)‐enaminoesters by an original uncatalyzed stereoselective 1,6‐addition/fragmentation cascade involving secondary amines. The transformation occurred under useful experimental conditions as a simple heating of a stoichiometric mixture of the starting compounds led to the desired products. The reaction could be extended to a range of alkyl coumalates and a variety of secondary amines. Given the original character of the transformation, the reaction mechanism was discussed. Therefore, the cascade is supposed to involve a 1,6‐conjugate addition followed by a fragmentation sequence leading ultimately to the decarboxylative elimination of (E)‐enaminoesters. Using this procedure, renewable coumalic acid proved to be a valuable alternative to fossil fuel‐based propiolates for the preparation of enaminoesters. [ABSTRACT FROM AUTHOR]

A one‐pot tandem process was developed aiming at the concise and expeditious enantioselective synthesis of dihydrobenzofuran, dihydrobenzosulfone, and dihydroindole scaffolds under mild, and open‐flask conditions. This process combines the in situ generation of aryldiazonium salt directly from the anilines in methanol telescoped to an intramolecular Heck‐Matsuda reaction linked to a redox relay process to provide the final products as the dimethyl acetals. These Heck products were smoothly converted into the corresponding primary alcohols or esters. The robustness and the efficiency of the protocol are demonstrated by the synthesis of 24 enantioenriched dihydrobenzofurans, dihydrobenzosulfones, and dihydroindoles in overall yields up to 78 % in enantiomeric ratios up to 99 : 1 by a sequential 5‐step protocol. [ABSTRACT FROM AUTHOR]

A photocatalytic decarboxylative functionalization of cyclopropenes is reported. Starting from a broad range of redox‐active ester‐substituted cyclopropenes, cyclopropenylphthalimides can be synthesized in the absence of a nucleophile. Alternatively, different carbon and heteroatom nucleophiles can be introduced. The transformation proceeds most probably through the formation of an aromatic cyclopropenium cation, followed by trapping with the nucleophiles. [ABSTRACT FROM AUTHOR]

The copper‐catalyzed coupling of thiols with alcohols was achieved under air atmosphere. The reaction proceeded smoothly in the presence of a base such as Cs2CO3 or Rb2CO3 affording sulfinic esters in good yields. Furthermore, disulfides were also available in the procedure. Both sulfide‐groups on disulfide were efficiently consumed. [ABSTRACT FROM AUTHOR]

Traditional textile dyeing processes usually require large quantities of water and energy and generate wastewater that can be harmful to the environment. Dyeing in supercritical carbon dioxide (sc‐CO2) media is promising in textile coloration due especially to it providing a waterless process and eliminating the need for an energy intensive drying step. The natural anthraquinone emodin showed promising results for dyeing different fibres through sc‐CO2 process. However, emodin is mutagenic. The aim of this study was to develop non‐mutagenic derivatives of emodin that can be applied to textiles using sc‐CO2. Emodin structure was modified incorporating acryloyl groups, which are considered suitable for decreasing potential for DNA intercalation, and thus mutagenicity. The presence of acryloyl groups would also enable atmospheric plasma induced bonding with fibres. Molecular modelling studies showed that emodin derivatives became less planar with increasing number of attached acryloyl groups, making intercalation unlikely. The derivatives produced were tested to assess mutagenicity in vitro (Salmonella/microsome assay, TA1537, 10% S9) and in vivo (micronucleus test in hemocytes of aquatic crustacean). We found that emodin can be derivatised using acryloyl chlorides to give mono‐ and di‐acrylate esters suitable for dyeing polyester fibres in sc‐CO2. However, the new dyes presented mutagenicity for both in vitro and in vivo. Although the derivatives provided greenish‐yellow alternatives to emodin for dyeing synthetic fibres, they do not appear to be viable alternatives from the point of view of preserving human and environmental health. Plasma bonding studies are underway. [ABSTRACT FROM AUTHOR]

Carboxylesterases comprise a major class of α/β‐fold hydrolases responsible for the cleavage and formation of ester bonds. Found ubiquitously in nature, these enzymes are crucial for the metabolism of both endogenous and exogenous carboxyl esters in animals, plants and microorganisms. Beyond their essential physiological roles, carboxylesterases stand out as one of the important classes of biocatalysts for biotechnology. BlEst2, an enzyme previously classified as Bacillus licheniformis esterase, remains largely uncharacterized. In the present study, we elucidate the structural biology, molecular dynamics and biochemical features of BlEst2. Our findings reveal a canonical α/β‐hydrolase fold similar to the ESTHER block L of lipases, further augmented by two additional accessory C‐terminal domains. Notably, the catalytic domain demonstrates two insertions, which occupy conserved locations in α/β‐hydrolase proteins and commonly form the lid domain in lipase structures. Intriguingly, our in vitro cleavage of C‐terminal domains revealed the structure of the active form of BlEst2. Upon activation, BlEst2 showed a markedly elevated hydrolytic activity. This observation implies that the intramolecular C‐terminal domain serves as a regulatory intramolecular inhibitor. Interestingly, despite exhibiting esterase‐like activity, BlEst2 structural characteristics align more closely with lipases. This suggests that BlEst2 could potentially represent a previously unrecognized subgroup within the realm of carboxyl ester hydrolases. [ABSTRACT FROM AUTHOR]

BACKGROUND RESULTS CONCLUSION The preparation of malic acid starch ester (MSE) is mostly carried out using a high temperature method, but there are problems such as high energy consumption, long preparation time, and uneven heating. Microwave technology can be used to overcome these limitations. The semi‐crystalline structure of starch granules hinders the modifier's access to the matrix, thus limiting the esterification reaction. Physical techniques can act on the interior of the starch to create a number of active sites, thereby facilitating the reaction of the starch with esterification reagents. Therefore, this study investigated the effect of starch pretreatment by microwave, heat‐moisture, and ultrasonic techniques on the degree of substitution (DS), structure, and physicochemical properties of MSE synthesized by the microwave method.The DS of MSE was increased after pretreatments. The modified starch obtained by different pretreatment methods did not show new characteristic peaks, while the MSE synthesized showed new absorption peaks near 1735 cm−1. The granular structure and morphology of the modified starch obtained by microwave and heat‐moisture pretreatment were gelatinized and aggregated, while some of the starch particles of the modified starch obtained by ultrasonic pretreatment appeared pore‐sized. The relative crystallinity and gelatinization enthalpy of the MSE were reduced, but the crystallization pattern remained as A‐type.Overall, the results suggest that various pretreatment methods can enhance the DS of MSE by disrupting the structure of starch. The findings of this study provide theoretical support for improving the DS of esterified starch. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Transition metal‐catalyzed synthesis of propargylic esters has been widely investigated, offering distinctive opportunities to build 1,3‐diene skeletons. Access to 1,2,3,4‐tetrasubstituted 1,3‐dienes has been a longstanding challenge in organic synthesis due to a great diversity of stereoisomers from four substituents and unpredictable regioselectivity. Given the synthetic challenges and the importance, inventing methods for the generation of this valuable architecture has gathered much more attention. Recently, several intriguing works concerning this topic have been achieved towards the high regio‐ and stereoselective elaborate 1,2,3,4‐tetrasubstituted 1,3‐dienes. Herein, this concept summarizes recent advances in transition metal‐catalyzed construction of 1,2,3,4‐tetrasubstituted 1,3‐dienes from propargylic esters and discusses the mechanism as well as their applications. [ABSTRACT FROM AUTHOR]

An improved, scalable, industrially feasible telescopic process for multigram synthesis of highly commercialized antidepressant drug, moclobemide has been developed. Unlike the conventional approaches, this process enjoys the privilege of being an economical, operationally simple, effectively scalable, and quantitative method for the synthesis of amide‐containing drug moclobemide, showcasing easy isolation and purification without the aid of column chromatography. An environmentally benign reagent combination of TBN and NHS very effectively converts the acyl source, 4‐chlorobenzaldehyde into its N‐hydroxysuccinimide ester intermediate, which simply affords the drug molecule after nucleophilic substitution with the amine source. The synthetic process has successfully been scaled‐up upto ~145 g scale with 75 % overall yield and >95 % first crop HPLC purity. [ABSTRACT FROM AUTHOR]

The glycosylphosphatidylinositol (GPI)‐anchored protein cluster of differentiation 109 (CD109) is expressed on many human cell types and modulates the transforming growth factor β (TGF‐β) signaling network. CD109 belongs to the alpha‐macroglobulin family of proteins, known for their protease‐triggered conformational changes. However, the effect of proteolysis on CD109 and its conformation are unknown. Here, we investigated the interactions of CD109 with proteases. We found that a diverse selection of proteases cleaved peptide bonds within the predicted bait region of CD109, inducing a conformational change that activated the thiol ester of CD109. We show CD109 was able to conjugate proteases with this thiol ester and decrease their activity toward protein substrates, demonstrating that CD109 is a protease inhibitor. We additionally found that CD109 has a unique mechanism whereby its GPI‐anchored macroglobulin 8 (MG8) domain dissociates during its conformational change, allowing proteases to release CD109 from the cell surface by a precise mechanism and not unspecific shedding. We conclude that proteolysis of the CD109 bait region affects both its structure and location, and that interactions between CD109 and proteases may be important to understanding its functions, for example, as a TGF‐β co‐receptor. [ABSTRACT FROM AUTHOR]

Comprehensive SummaryThe EDA complex‐mediated reactions involving oxime esters have been few studied. Herein, an EDA complex formed by thiophenolate anion and oxime ester is reported for photoinduced divergent synthesis of thioethers, depending on different types of oxime esters. Operational simplicity, mild reaction conditions, and flexible options of leaving group demonstrate the generality and synthetic utility of this approach. Such an approach can also enable an interesting thiol‐catalysis for the synthesis of phenanthridines. [ABSTRACT FROM AUTHOR]

A new strategy for the synthesis of 3‐substituted phthalides has been developed via a Lewis acid‐catalyzed intramolecular ring opening of aziridines with esters. Broad substrate scope, good yields and mild conditions made the cyclization reaction very suitable for the rapid construction of libraries of 3‐substituted phthalide compounds. [ABSTRACT FROM AUTHOR]

A tandem Cu‐catalyzed oxidation‐intramolecular Cannizzaro reaction leading to bioactive α‐hydroxyesters from α‐hydroxyketones is reported. The process uses oxygen as a sole oxidant to achieve the formation of glyoxals, which are efficiently converted in situ to important α‐hydroxyesters. The mechanistic insights are provided by isotopic labeling and supported by DFT calculations. The transformation proved a robust synthetic tool to achieve the synthesis of human metabolites and hydroxyl esters of various biologically active steroid derivatives. [ABSTRACT FROM AUTHOR]

Epoxy-cyanate ester blends have attracted significant attention due to their unique synergistic properties and versatility in high-performance applications. However, achieving precise control over the phase-separated structures in these blends remains a challenge. In this work, we present a strategy for the preparation of epoxy-cyanate ester blends with high-performance through staged curing-induced phase separation. By incorporating a thermally latent catalyst, 4-ethyl-2-methylimidazole tetraphenylborate, into the epoxyanhydride-cyanate system, the reactivity differences of multiple curing reactions within the blend were precisely controlled, thereby inducing the formation of well-defined nanophase-separated structures. The polymer systems prepared exhibit high mechanical properties and heat resistance, primarily due to the interpenetrating networks created by the epoxy-anhydride-cyanate ester and the formation of nanodomains induced by the staged curing process. Furthermore, epoxy-cyanate ester blends demonstrate outstanding hygrothermal resistance due to the low polarity of the crosslinked network structure. This work provides new insights into regulating the microstructure of the thermosetting blends and expands the potential applications of these materials in fields requiring long-term durability and reliability. [ABSTRACT FROM AUTHOR]

Sulfonate esters are a class of organic impurities that includes highly potent mutagenic substances that typically need to be controlled down to a low ppm level in pharmaceutical development. In this work, two genotoxic impurities of sulfonate esters in Posaconazole, for example, ((3S,5R)‐5‐((1H‐1,2,4‐triazol‐1‐yl)methyl)‐5‐(2,4‐difluorophenyl)tetrahydrofuran‐3‐yl)methyl‐4‐methylbenzenesulfonate and (2S,3S)‐3‐ (4‐(4‐(4‐(4‐(((3R,5R)‐5‐((1H‐1,2,4‐triazol‐1‐yl)methyl)‐5‐(2,4‐difluorophenyl)tetrahydrofuran‐3‐yl)methoxy)phenyl)piperazin‐1‐yl)phenyl)‐5‐oxo‐4,5‐dihydro‐1H‐1,2,4‐triazol‐1‐yl)pentan‐2‐yl‐4‐methylbenzenesulfonate, were synthesized and characterized. The genotoxicity which was evaluated by two (quantitative) structure‐activity relationships prediction methodologies showed positive. Furthermore, a novel high‐performance liquid chromatography‐tandem mass spectrometry limit test method for detecting these two impurities in Posaconazole has been established and validated. The chromatographic separation of analytes was conducted on an ACQUITY BEH C18 column, and performed with 0.05% methanoic acid‐water and 0.05% methanoic acid‐acetonitrile as mobile phases A and B, respectively. Six batches of commercial‐scale Posaconazole samples were detected by the validated method and the results were in accordance with the Food and Drug Administration acceptance criteria for the genotoxic impurities in drug substances. Finally, a tentative mechanism for these two impurities was proposed, they are generally accepted to undergo an SN2‐type reaction, resulting in 7‐methylguanine as the predominant adduct in double‐stranded DNA. [ABSTRACT FROM AUTHOR]

A formal atom transfer radical [3+2] annulation (ATRAn) reaction between different homoallyl radical precursors and 1,1‐diborylethene was developed. It provides a rapid access to polysubstituted cyclopentanes containing a gem‐diboronic ester moiety. The synthetic utility of theses uniquely functionalized 5‐membered rings is highlighted by their easy conversion to attractive borylated building blocks such as 1‐borylated bicyclo[3.1.0]hexanes. The ATRAn reaction was extended to homopropagylic radicals giving access to unique allylic gem‐diboronic esters that could be used in allylboration of aldehydes. Furthermore, this work highlights that 1,1‐diborylethene represents a synthetic equivalent to ketene, a so far elusive radical trap due to its daunting reactivity. [ABSTRACT FROM AUTHOR]

Geminal and vicinal bis(trifluoromethanesulfonate) esters are highly reactive alkylene synthons used as potent electrophiles in the macrocyclization of imidazoles and the transformation of bypyridines to diquat derivatives via nucleophilic substitution reactions. Herein we report the crystal structures of methylene (C3H2F6O6S2) and ethylene bis(trifluoromethanesulfonate) (C4H4F6O6S2), the first examples of a geminal and vicinal bis(trifluoromethanesulfonate) ester characterized by single‐crystal X‐ray diffraction (SC‐XRD). With melting points slightly below ambient temperature, both reported bis(trifluoromethanesulfonate)s are air‐ and moisture‐sensitive oils and were crystallized at 277 K to afford two‐component non‐merohedrally twinned crystals. The dominant interactions present in both compounds are non‐classical C—H...O hydrogen bonds and intermolecular C—F...F—C interactions between trifluoromethyl groups. Molecular electrostatic potential (MEP) calculations by DFT‐D3 helped to quantify the polarity between O...H and F...F contacts to rationalize the self‐sorting of both bis(trifluoromethanesulfonate) esters in polar (non‐fluorous) and non‐polar (fluorous) domains within the crystal structure. [ABSTRACT FROM AUTHOR]

N‐Alkyl‐2‐nitroanilines deoxygenated with tributylphosphine form intermediate 2‐(alkylamino)aryliminophosphoranes, which were subjected, without isolation, to various cyclocondensation reactions with CS2, CO2, alkyl isocyanates, acyl chlorides, anhydrides, or esters. A simple, convenient, one‐pot procedure provided derivatives of unsymmetrically substituted 1‐alkylbenzimidazoles functionalized at C2 in good to excellent yields. The method does not require the use of metals, sensitive catalysts, or pressure. [ABSTRACT FROM AUTHOR]

Palladium‐catalyzed carbonylation of aryl sulfonium salts with CO2 as a CO surrogate has been successfully developed via a one‐pot two‐step procedure. Thus, by merging thianthrenation and the carbonylation, site‐selective aromatic C−H carbonylation of a plethora of readily available arenes can be realized with CO2, providing access to a variety of structurally diverse and useful benzamides, esters and carboxylic acids. Simple operation, broad substrate scope, good functional group tolerance and mild reaction conditions are the attractive features of the method. Late‐stage functionalization of complex bioactive molecules as well as the precise synthesis of pharmaceuticals 1‐BCP and butoxycaine demonstrated the potential application of the established protocol. [ABSTRACT FROM AUTHOR]

A novel alkenylation reaction between N‐hydroxyphthalimide (NHPI) esters and alkenyl sulfones is reported. It undergoes the formation of electron donor‐acceptor (EDA) complex and a series of alkenes are obtained in good to excellent yields. It has the advantages of simple operation, mild reaction conditions, and metal‐free. [ABSTRACT FROM AUTHOR]

In this investigation, a strongly acidic exchange resin was used for the transesterification of methyl acetate with n‐propanol, n‐butanol, and iso‐butanol. Kinetic and equilibrium experiments for the three systems were conducted using a temperature‐controlled batch reactor setup. The effects of the following operating parameters on the transesterification were explored: reaction temperature, catalyst loading, and methyl acetate‐to‐alcohol molar ratio. The conversion of the limiting reactant in the reaction mixture increased with increasing reaction temperature, catalyst loading, and varying reactant proportions from 1:1 to other ratios. It was found that excess methyl acetate would result in higher limiting reactant conversion than using excess alcohol with the same initial molar proportionality between the excess and the limiting reactants. It was found that an increase in the chain length of the alcohol and/or branching suppressed the conversion of the reactants owing to steric hindrance. To mathematically correlate the data, several kinetic models were tested, and the Eley–Rideal model was selected. Accordingly, a reaction mechanism was proposed. [ABSTRACT FROM AUTHOR]

Using benzene‐1,3,5‐tricarboxylic acid, trimellitic anhydride, 2‐propylheptanol and 2‐ethylhexanol as raw materials, four kinds of environmental plasticizers were prepared, which were used as additives for polyvinyl chloride (PVC) products. Compared with commercially available di (2‐ethylhexyl) phthalate (DOP), di (2‐ethylhexyl) terephthalate (DOTP), and tributyl citrate (TBC), the application performance and plasticizing performance were compared. The structure of the target product was analyzed by fourier transform infrared spectroscopy and nuclear magnetic resonance spectroscopy to verify the fingerprint region of the molecular structure of the product. The properties of plasticized PVC films were tested by thermal weight loss analysis, oven thermal aging test, migration and volatility resistance test, DMA analysis, and scanning electron microscopy. The plasticizing mechanism was confirmed through quantum chemical calculations, and the results of the calculations were in line with the migration outcomes. The results showed that compared with commercially available plasticizers, benzene polyacid ester plasticizers had better thermal stability, and better cold resistance in the polar environments, suitable for high‐temperature and water‐based environments. Highlights: The four plasticizers prepared in this study were compared with reference plasticizers, and the plasticizing mechanism was validated through quantum chemical calculations.The PVC film plasticized with benzene polyacid ester prepared in this study demonstrates outstanding thermal stability, surpassing certain plasticizers reported in current literature.Benzene polyacid esters plasticized PVC film has migration stability under various conditions, it has great potential in packaging and other applications. [ABSTRACT FROM AUTHOR]

A key aspect for the applicability of 89Zr‐radioimmunoconjugates is inert modification and radiolabeling. The two commercially available bifunctional variants of the siderophore desferrioxamine (DFO), Fe‐DFO‐N‐suc‐TFP‐ester and p‐NCS‐Bz‐DFO, are most often used for clinical 89Zr‐immuno‐PET. The use of Fe‐DFO‐N‐suc‐TFP‐ester is advantageous with regard to higher radiolysis stability and more facile assessment of radiochemical purity as well as chelator‐to‐mAb ratio. However, not all mAbs withstand the Fe‐removal step at relatively low pH (4–4.5) using EDTA, which is needed after conjugation to allow 89Zr labeling. In this study, it was investigated whether hydroxybenzyl ethylenediamine (HBED) or the clinically approved deferiprone (DFP) can serve as an alternative for EDTA to establish a pH‐independent mild method for Fe‐removal and thereby broaden the applicability of Fe‐DFO‐N‐suc‐TFP‐ester. Carrier‐added [59Fe]Fe‐DFO‐N‐suc‐TFP‐ester was used for mAb modification to enable direct tracking of the Fe‐removal efficiency under various conditions. Whereas incomplete Fe‐removal with HBED was observed at pH 5 or higher, Fe‐removal with DFP was possible at a broad pH range (4–9). This provides a mild, pH‐independent method for Fe‐removal, improving the applicability and attractiveness of Fe‐DFO‐N‐suc‐TFP‐ester for 89Zr‐mAb preparation. [ABSTRACT FROM AUTHOR]

Carbon‐14 labeling synthesis of RORγt inhibitor JNJ‐61803534 (1) was accomplished in four steps with the C14 label located at the thiazole‐2‐carboxamide carbon. The synthesis featured a highly efficient conversion of nitrile [14C]‐12 to ester [14C]‐17 under mild conditions via an imidate intermediate, overcoming the unsuccessful direct hydrolysis of nitrile 12 under either acidic or basic conditions. Since carbon‐14 labeling via [14C]‐nitrile installation and subsequent conversion to [14C]‐carboxylic acid derivatives is a common labeling strategy, an efficient conversion of a nitrile to an ester under mild conditions could be of use for the future C14 labeling syntheses. [ABSTRACT FROM AUTHOR]

A novel strategy has been developed for the synthesis of 2,3‐diarylindanones and 2‐arylindenes through the formation of trisubstituted α,β‐unsaturated esters by the ring opening of 2,3‐diarylcyclopropenones in the presence of a catalytic amount of TPP under mild reaction conditions. Initially, PPh3 activates the diarycyclopropenone to generate the phosphonium adduct, which simultaneously reacts with 4‐hydroxycoumarins to afford α,β‐unsaturated esters instead of Wittig olefination. Subsequently, these α,β‐unsaturated esters undergo a smooth Friedel–Crafts‐type cyclization with arenes in the presence of AlCl3 to give a new series of 2,3‐diarylindanones in good to excellent yields. Additionally, the reduction of α,β‐unsaturated esters with NaBH4 followed by acid‐catalyzed cyclization of the resulting allylic alcohols afforded 2‐arylindenes in good yields. This is the first report on the use of α,β‐unsaturated esters as precursors for the synthesis of diarylindanones and arylindenes. [ABSTRACT FROM AUTHOR]

Carbamoyl azide is a pivotal compound used in the transformation into urea and amines, as well as in nitrene insertion reactions. In this study, we present a pioneering method for synthesizing carbamoyl azide directly from acid redox active esters without the use of metals or oxidants. This approach demonstrates tolerance for various functional groups, enhancing its applicability. Furthermore, this technique facilitates late‐stage modifications of natural products and pharmaceuticals, thereby accelerating the development and identification of novel drug candidates. [ABSTRACT FROM AUTHOR]

An iron‐catalyzed protocol for the synthesis of 3‐amino‐3‐aminomethyl‐2‐oxindole heterocyclic structures is disclosed employing isatins and non‐nucleophilic N‐methoxybenzamides. This reaction class is associated with broad scope and tolerates numerous functionalities, such as fluoro, chloro, bromo, iodo, trifluoromethyl, nitrile, ester, ether, and alkenyl, including heteroaryl – thiophene, benzothiophene, carbazolyl, indolyl, eugenol, and polycyclic cholesterol moieties. Detailed mechanistic investigations reveal that the reaction proceeds via iron‐catalyzed N−O bond cleavage in N‐methoxybenzamides, generating formaldehyde and benzamide, and through the intermediacy of isatin‐ketimines and N‐(hydroxymethyl)benzamides. Overall, this amidation reaction involves one C−C and two C−N bond‐forming tandem processes, providing a range of β‐amino‐aminomethyl‐oxindoles (45 examples) in up to 88% yields. [ABSTRACT FROM AUTHOR]

Herein we describe an efficient methodology for metal‐free hydroborative cleavage of lactones and esters with HBPin (Pin=pinacol) to the corresponding alcohol derivatives using ammonia borane as a pre‐catalyst. The reactions proceed under mild conditions, can be performed in a solvent‐free manner, and do not require an inert atmosphere. Combined experimental and computational mechanistic studies suggest a novel mechanism that involves μ‐aminodiboranes as catalytically active species. [ABSTRACT FROM AUTHOR]

The Pd‐catalysed decarboxylative asymmetric allylic alkylation (DAAA) of sterically hindered α‐aryl,β‐amido allyl ester lactams has been developed. The key step in the synthesis of a range of α‐aryl lactam substrates for catalysis was a Pb‐mediated α‐arylation of a β‐amido allyl ester affording 14 novel examples of α‐aryl‐β‐amido allyl ester lactams in good yields (up to 80 %). The Pd‐catalysed DAAA was optimised with the 2,4,6‐trimethoxyphenyl‐containing substrate. Using (S,S)‐DACH‐phenyl Trost as the optimal chiral ligand, enantioselectivities of up to 82 % ee were obtained. A substrate scope of 11 examples of α‐aryl‐β‐amido allyl ester lactams showed that products containing the di‐ortho‐methoxy‐substituted phenyls and naphthyl groups gave rise to the highest ees, whereas products not bearing this substitution pattern showed lower enantioselectivities (<60 % ee). Transition states to rationalise the observed stereochemical outcome are proposed. [ABSTRACT FROM AUTHOR]

Here we report an aerobic photoredox catalysis approach to oxamate ester synthesis using bromodifluoroacetate esters and amines under open‐air conditions. Oxamate ester is an important skeleton found in bioactive molecules and used as a synthetic building block. However, previous synthetic methods require the use of moisture‐ and air‐sensitive precursors and/or harsh conditions, limiting accessible oxamate esters. The present method uses bench‐stable bromodifluoroacetate esters and amines under mild photoredox catalytic conditions to furnish a wide variety of oxamate esters. Combining photoredox catalysis with aerobic oxygenation enables the use of bromodifluoroacetate ester as a precursor for the synthesis of oxamate esters via fluoroglyoxylate esters. [ABSTRACT FROM AUTHOR]

The catalytic asymmetric reaction of 5‐aminopyrazoles with naphthoquinone esters has been established. A wide range of unprecedented axially chiral naphthylpyrazole derivatives (29 examples) have been synthesized in moderate to excellent yields (up to 99 % yield) with excellent enantioselectivities (up to 99 % ee) by utilizing chiral phosphoric acid as a catalyst. This protocol features mild reaction conditions, a broad substrate scope, good scalability and facile derivatization. Moreover, preliminary mechanistic investigation was conducted to elucidate the mechanism. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: A general and convenient photoredox‐catalyzed acylation and alkylcyanation of MBH acetates has been established, enabling the assembly of the C(sp2)–C(sp3) bond by a nitrogen‐centered radical strategy for the synthesis of trisubstituted alkenes in moderate to excellent chemical yields (48 examples in total). The reaction of MBH acetates with acyl (indanone) oxime esters afforded trisubstituted alkenes containing 1,4‐dicarbonyl groups. Interestingly, the use of Eosin Y as a photocatalyst in the catalytic system resulted in the formation of distal cyano group‐anchored trisubstituted alkenes via deconstructive functionalization of cycloketone oxime esters. Notably, these resulting 1,4‐dicarbonyl compounds could be applied to late‐stage transformations, providing important methods for the synthesis of dihydropyridazin‐3(2H)‐one. [ABSTRACT FROM AUTHOR]

SUMMARY: Genome‐wide association studies (GWAS) are an effective approach to identify new specialized metabolites and the genes involved in their biosynthesis and regulation. In this study, GWAS of Arabidopsis thaliana soluble leaf and stem metabolites identified alleles of an uncharacterized BAHD‐family acyltransferase (AT5G57840) associated with natural variation in three structurally related metabolites. These metabolites were esters of glucuronosylglycerol, with one metabolite containing phenylacetic acid as the acyl component of the ester. Knockout and overexpression of AT5G57840 in Arabidopsis and heterologous overexpression in Nicotiana benthamiana and Escherichia coli demonstrated that it is capable of utilizing phenylacetyl‐CoA as an acyl donor and glucuronosylglycerol as an acyl acceptor. We, thus, named the protein Glucuronosylglycerol Ester Synthase (GGES). Additionally, phenylacetyl glucuronosylglycerol increased in Arabidopsis CYP79A2 mutants that overproduce phenylacetic acid and was lost in knockout mutants of UDP‐sulfoquinovosyl: diacylglycerol sulfoquinovosyl transferase, an enzyme required for glucuronosylglycerol biosynthesis and associated with glycerolipid metabolism under phosphate‐starvation stress. GGES is a member of a well‐supported clade of BAHD family acyltransferases that arose by duplication and neofunctionalized during the evolution of the Brassicales within a larger clade that includes HCT as well as enzymes that synthesize other plant‐specialized metabolites. Together, this work extends our understanding of the catalytic diversity of BAHD acyltransferases and uncovers a pathway that involves contributions from both phenylalanine and lipid metabolism. Significance Statement: Combining untargeted metabolomics with genome‐wide association can lead to the discovery of new aspects of plant metabolism. Here, this approach uncovered a new BAHD acyltransferase that assembles phenylacetyl acyl glucuronosylglycerol esters. Acyl glucuronosylglycerol esters are widespread in plants, but their biosynthesis has not previously been characterized. We show that the glucuronosylglycerol component is made through a transferase associated with lipid remodeling under P‐starvation. This work expands our knowledge of BAHD acyltransferase function and identifies a new link between glycerolipid and phenylpropanoid metabolism. [ABSTRACT FROM AUTHOR]

Hydrocarboxylation of methyl 2‐octynoate, a chemical commercially available at a low cost, with N‐protected amino acids was developed with a gold‐zinc cooperative catalyst constructed with a 5‐[(2,2′‐bipyridin)‐5‐yl]imidazo[1,5‐a]pyridin‐3‐ylidene to prepare α‐methoxycarbonyl enol esters as acylating reagents. The α‐methoxycarbonyl enol esters were isolable through silica‐gel column chromatography and storable without precautions regarding moisture. Acylation of free amines with the α‐methoxycarbonyl enol esters proceeded without epimerization of the stereogenic center derived from the enol esters, affording analytically pure dipeptide compounds through filtration and hexane‐washing. [ABSTRACT FROM AUTHOR]

An organocatalyzed three‐component protocol using diazoacetonitrile to access a wide range of cyanopyrazole derivatives is reported here. This strategy, which proceeds through a piperidine‐catalyzed Knoevenagel condensation/formal [3+2] cycloaddition/dehydrocyanation sequence, provides an efficient route to construct dicyanopyrazoles from aldehydes, malononitrile, and diazoacetonitrile regioselectively. Interestingly, by engaging cyanoacetate and cyanoacetamide in this protocol, we could achieve cyanopyrazole esters and carboxamides. [ABSTRACT FROM AUTHOR]

Peptidols were prepared through the reductive cleavage of benzotriazole intermediates obtained from the on‐bead activation of 3,4‐diaminobenzoyl linkers. Remarkably, this method used commercially available amino acid residues and resins without further modification. Pure peptidols were collected with only filtration in 49%–87% yield. Only the derivatives with aspartic acid as the first C‐terminal residue required sophisticated chromatography purification. Esters and carboxylic acids were identified as side products and were suppressed by additional reduction or reduction in DMF. Remarkably, the reduction of peptides with the first aspartic acid residue at the C‐terminal afforded a C‐terminal lactone, which could be reduced by deprotection at 0 °C. For the synthesis of branched peptidols, the bulky wedge structures of the branched peptides resulted in low total yields, which were improved to 23%–28% by using peripheral Boc groups and SPPS on the Tental gel resin. In addition, this method gave two peptaibols, SPF‐5506‐A4 and Ac‐Gramicidin A, in 11% and 46% yields, respectively. [ABSTRACT FROM AUTHOR]