Abstract: The copper-catalyzed cyclization of activated alkenes with cyclobutanone O-acyl oximes under redox-neutral conditions has been reported. This facile protocol provided an efficient approach to a variety of cyanoalkylated oxindoles and dihydroquinolin-2(1H)-ones with a broad substrate scope and excellent functional group tolerance. In this reaction, sequential C–C bond cleavage, radical addition, and cyclization processes were involved, wherein multiple bonds were constructed in a one-pot reaction. Mechanistic studies suggest that the reaction probably proceeded via a radical pathway.

Abstract: Catalytic activation of hydroxyl functionalities is of great interest for the production of pharmaceuticals and commodity chemicals. Here, 2-alkoxycarbonyl- and 2-phenoxycarbonyl-phenylboronic acid were identified as efficient catalysts for the direct and chemoselective activation of oxime N–OH bonds in the Beckmann rearrangement. This classical organic reaction provides a unique approach to prepare functionalized amide products that may be difficult to access using traditional amide coupling between carboxylic acids and amines. Using only 5 mol % of boronic acid catalyst and perfluoropinacol as an additive in a polar solvent mixture, the operationally simple protocol features mild conditions, a broad substrate scope, and a high functional group tolerance. A wide variety of diaryl, aryl-alkyl, heteroaryl-alkyl, and dialkyl oximes react under ambient conditions to afford high yields of amide products. Free alcohols, amides, carboxyesters, and many other functionalities are compatible with the reaction cond...

Abstract: Cu-catalyzed redox-divergent [3+3] coupling of oxime esters with β-CF3 enones and acrylates is described. This redox-neutral coupling with enones and acrylates affords trifluoromethylated pyridines and pyridones, respectively. Under reductive conditions, difluoromethylated pyridines, difluoromethlated pyridones, and trifluoromethylated dihydropyridones are obtained. The reactions occur under mild conditions with broad substrate scope and regio/redox selectivity.

Abstract: Hydrazone and oxime bond formation between α-nucleophiles (e.g. hydrazines, alkoxy-amines) and carbonyl compounds (aldehydes and ketones) is convenient and is widely applied in multiple fields of research. While the reactants are simple, a substantial drawback is the relatively slow reaction at neutral pH. Here we describe a novel molecular strategy for accelerating these reactions, using bifunctional buffer compounds that not only control pH but also catalyze the reaction. The buffers can be employed at pH 5-9 (5-50 mM) and accelerate reactions by several orders of magnitude, yielding second-order rate constants of >10 M-1 s-1. Effective bifunctional amines include 2-(aminomethyl)imidazoles and N,N-dimethylethylenediamine. Unlike previous diaminobenzene catalysts, the new buffer amines are found to have low toxicity to human cells, and can be used to promote reactions in cellular applications.

Abstract: A new series of 3‐hydroxy‐2‐pyridine aldoxime compounds have been designed, synthesised and tested in vitro, in silico, and ex vivo as reactivators of human acetylcholinesterase (hAChE) and butyrylcholinesterase (hBChE) inhibited by organophosphates (OPs), for example, VX, sarin, cyclosarin, tabun, and paraoxon. The reactivation rates of three oximes (16–18) were determined to be greater than that of 2‐PAM and comparable to that of HI‐6, two pyridinium aldoximes currently used by the armies of several countries. The interactions important for a productive orientation of the oxime group within the OP‐inhibited enzyme have been clarified by molecular‐modelling studies, and by the resolution of the crystal structure of the complex of oxime 17 with Torpedo californica AChE. Blood–brain barrier penetration was predicted for oximes 15–18 based on their physicochemical properties and an in vitro brain membrane permeation assay. Among the evaluated compounds, two morpholine‐3‐hydroxypyridine aldoxime conjugates proved to be promising reactivators of OP‐inhibited cholinesterases. Moreover, efficient ex vivo reactivation of phosphylated native cholinesterases by selected oximes enabled significant hydrolysis of VX, sarin, paraoxon, and cyclosarin in whole human blood, which indicates that the oximes have scavenging potential.

Abstract: Oxime directed cobalt-catalyzed arene sp2 C–H bond conjugation addition to maleimide was reported, the reaction showed great tolerance to different functional groups, and various succinimide derivatives were efficiently produced This protocol exhibited specific reactivity with only producing a mono-C–H bond addition product and no external base was needed, which suggested a unique reactivity of this Co-based catalytic system

Abstract: We report the divergent catalytic transformation of alkene-tethered isoxazol-5(4H)-ones by using rhodium and cobalt catalysts to afford 2H-pyrroles (with Rh catalyst) and azabicyclic cyclopropanes (with Co catalyst). The rhodium-catalyzed 2H-pyrrole formation involving hydrogen shift is supported by deuterium-labeling experiments. The control experiments in the cobalt-catalyzed reaction indicate that the bicyclic aziridines as the primary product undergo a skeletal rearrangement assisted by metal iodide salts.

Abstract: Conversion of lignin to aromatic compounds via C–C/C–O bond cleavage has been an attractive but challenging subject in recent years. We herein report the first protocol that converts lignin models and preoxidized lignin to isoxazole and aromatic nitrile. The isoxazole motif is constructed by condensation of β-hydroxyl ketone with hydroxylamine. Magnesium oxide promotes an oximation reaction and an intramolecular condensation. Aromatic nitriles and esters are obtained via Beckmann rearrangement or an acidolysis reaction depending on the selected additive. The hydroxylamine-mediated strategy works well for the preoxidized lignin conversion to aromatic isoxazole, nitrile, and ester monomers with up to 7.6% yield.

Abstract: A novel copper/amine co-catalyzed formal regioselective [3 + 2] cycloaddition reaction of an O-acyl oxime with α,β-unsaturated aldehydes is developed. This novel transformation provided an efficient protocol for the assembly of multifunctionalized pyrroles with good yields and diverse functional group tolerance.

Abstract: In this protocol, we developed a reductive strategy for 1,2-iminoacylation of alkenes. Under the catalysis of the Ni-biquinoline system, various oxime esters incorporating a pendant terminal olefinic unit were successfully reacted with acid chlorides or anhydrides as electrophilic acylating reagents in the presence of Zn as a reductant, furnishing a series of pyrrolines in moderate to excellent yields. This reaction is distinguished by safe and mild reaction conditions that avoid the use of CO gas as a carbonyl source, pregenerated organometallics and strong bases as reaction additives.

Abstract: A copper-catalyzed aerobic oxidative C-C single bond cleavage of acyclic unstrained oxime acetates is reported, providing various aryl nitriles and ketones in good yields. Mechanistic studies indicate a radical procedure is involved in this transformation, and the oxygen atom in the ketone products is originated from O2 in the air. Oxime acetates as an internal oxidant have been proved to be an initiator, which may promote the discovery of novel protocol for C-C bond cleavage and dioxygen activation.

Abstract: Six crystalline polyoxo-titanium clusters (PTCs) derived from oximes, namely, Ti4(μ4-O)(OMe)6(L1)4 (PTC-125; H2L1 = salicylaldoxime), H[Ti5(μ2-O)(μ3-O)2(OMe)3(L1)6] (PTC-126), Ti6(μ2-O)(μ3-O)2(OiPr)10(OAc)2(L2)2 (PTC-127; H3L2 = salicylhydroxamic acid; HOAc = acetic acid), Ti7(μ3-O)2(OEt)18(L2)2 (PTC-128), Ti12(μ2-O)4(μ3-O)4(OEt)20(L2)4 (PTC-129), and Ti18(μ2-O)10(μ3-O)8(μ4-O)2(OEt)30(L3)2 (PTC-130; HL3 = acetoxime) have been solvothermally synthesized and structurally characterized. Compared with the reported solid-state monomer, dimer, trimer, and tetramer titanium oximes, these compounds possess high nuclearity structures in the range Ti4, Ti5, Ti6, Ti7, Ti12, and Ti18 as a result of the presence of oxo bridges. Even though three examples of tetranuclear and hexanuclear derivatives have been documented, PTC-130 with a centrosymmetric Ti18 cluster core represents the currently highest PTC compound in the oxime system. In addition, Ti/oximate ratio by solvothermal synthesis in this work possessed a broad...

Abstract: An efficient oximation method has been developed on the basis of NO+ -initiated semipinacol rearrangement and subsequent proton elimination. The procedure enabled the rapid construction of a series of oximes and oxime ethers with spiro quaternary stereocenters from allylic silyl ethers. Additional features of this reaction include wide substrate tolerance as well as the commercial availability of the safe nitrosation reagent NOBF4 . The key N-heterotricyclic cores of three natural alkaloids, tuberostemoninol B, (+)-quebrachidine, and an insecticide, were also constructed efficiently by this method.

Abstract: To develop novel anti-inflammatory agents, a series of new pentadienone oxime ester compounds were designed and synthesized. The structures were determined by IR, 1H NMR, 13 C NMR, and HRMS. All compounds have been screened for their anti-inflammatory activity by evaluating their inhibition against LPS-induced nitric oxide (NO) release in RAW 264.7 cell. Among them, compound 5j was found to be one of the most potent compounds in inhibiting NO and IL-6 (IC50 values were 6.66 µM and 5.07 µM, respectively). Preliminary mechanism studies show that title compound 5j could significantly suppress expressions of nitric oxide synthase, COX-2, and NO, IL-6 through Toll-like receptor 4/mitogen-activated protein kinases/NF-κB signalling pathway. These data support further studies to assess rational design of more efficient pentadienone oxime ester derivatives with anti-inflammatory activity in the future.

Abstract: A copper-catalyzed iminyl radical-mediated C–C bond cleavage/cross-coupling tandem reaction of cyclobutanone oxime esters with aryl thiols in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) at room temperature was developed, and aryl cyanopropyl sulfides were smoothly synthesized in 20–88% yields. By altering the copper reagent and the molar ratio of cyclobutanone oxime ester/aryl thiol/DBU, substitutional product N-arylthio cyclobutanone imines were selectively generated in 50–91% yields. Using this protocol, C–S bond and N–S bond formations using aryl thiols as sulfur sources were realized under very mild conditions without the use of photocatalysis and electrocatalysis techniques.

Abstract: A set of eight derivatives of betulinic acid (2) and 12 derivatives of platanic acid (3) has been prepared and screened for their cytotoxic activity using SRB assays. First synthetic approaches were focused on the preparation of augustic acid (4) analogs of 2 and 3 by introducing a second hydroxyl group on the A-ring of both triterpenoic acids leading to compounds 5–14. Further structural modifications were performed at the C-20 keto group of the platanic acid backbone by its transformation into an oxime moiety and subsequent reduction to 20-amino-30-norlupan derivatives 17–24. In the SRB assays low EC50 values were observed especially for methyl (3β, 20 R)-3-acetyloxy-20-amino-30-norlupan-28-oate (21), methyl (3β, 20 S)-3-acetyloxy-20-amino-30-norlupan-28-oate (22), and (3β, 20 R)-3,28-diacetyloxy-20-amino-30-norlupane (24) all holding an amino function at C-20. Compound 21 was selected for extensive biological testing that showed this compound to cause cell death by inducing apoptosis.

Abstract: Amide bond formation reactions are the most important transformations in (bio)organic chemistry because of the widespread occurrence of amides in pharmaceuticals, natural products and biologically active compounds. The Beckmann rearrangement is a well-known method used for the preparation of secondary amides from ketoximes. But, most of the traditional protocols used for the Beckmann rearrangement create enormous amount of wastes. Thus, the atom economical synthesis of amides has got high priority among the chemists. However, under classical Beckmann conditions, aldoximes do not rearrange into the corresponding primary amides. Indeed, reactions of aldoximes lead to nitriles. In recent years, it has been demonstrated that the aldoxime rearrangements can be carried out efficiently and selectively with the help of metal catalysts. Objective: This review focuses on the recent progress in the amides synthesis via ketoxime and aldoxime rearrangements. Applications of the rearrangements in the synthesis of heterocycles and natural products are also covered in this review. In the first part of the review, relevant pathways of oxime rearrangements are discussed and it is shown that several catalytic systems have been developed for the atom-economical synthesis of N-substituted amides from ketoximes. But similar reactions with aldoximes are, however, more challenging. The advances reached in the aldoxime rearrangement are also covered in this review. It is revealed that a large variety of homogeneous and heterogeneous metal catalysts have been developed to affect aldoxime rearrangements.