Oxime Acetates Research Articles

Substituent-Oriented Synthesis of Substituted Pyridines/Pyrido[3,2-C]coumarins via Sequential Reactions of α-H and Me/Aryl Substituted Oxime Acetates and 3-Formylchromones.

A facile one pot sequential and highly chemoselective synthesis of substituted pyridines/pyrido[3,2-c]coumarins has been developed from oxime acetates and 3-formylchromones in the presence of FeCl2. This reaction was oriented by different substituents on the α-position (H, methyl/aryl) of oxime acetates. Mechanistic investigations suggested that substituted pyridines were formed via intramolecular aza-Michael addition followed by ring opening, while pyrido[3,2-c]coumarins were formed via intermolecular Michael addition. Besides, anti-TB activity was screened for some of the synthesized pyridines. Among the tested compounds, 3ga, 3ha, 3ja, 3ma, 3ac, 4pa, 4pb and 4sb were found to have good activity with an MIC of 12.5 μg/mL.

Synthesis of furoquinolinones/pyranones/coumarins via a copper-catalyzed heteroannulation of oxime acetates and 1,3-cyclic dicarbonyls

A divergent copper-mediated cyclization between oxime acetates and distinct 1,3-cyclic dicarbonyl compounds such as 4-hydroxyquinolinones/pyranones/coumarins was developed. Using the same reaction conditions, an array of furan-fused heterocycles such as furoquinolinones/pyranones/coumarins were prepared in good to high yields. The products possess a less common substitution pattern than those in previous syntheses. The mildness of the protocol enables a broad scope without affecting sensitive functionalities such as azido, alcohol, terminal alkyne, alkyl ester, and alkyl halide groups. Mechanistic investigations infer a purely organometallic pathway, excluding the participation of radical intermediates. Ultimately, the heteroannulation was exploited as the key step in a short and high-yielding synthesis of the phytoestrogen coumestrol.

3-Thioxo-3H-indolizinium-1-olates and Related Pseudo-Cross-Conjugated Heterocyclic Mesomeric Betaines: Synthesis and Spectral Features.

The first example of the synthesis of 3-thioxo-3H-indolizinium-1-olates, which further expands a limited class of pseudocross-conjugated heterocyclic mesomeric betaines isoconjugate to odd nonalternant hydrocarbon anion, is reported. These unique, moderately colored heterocyclic products result from a developed three-component reaction of cyclopropenones, pyridines, and sulfur. The protocol is distinguished by simple and mild reaction conditions that avoid expensive reagents or exotic catalysts, exhibiting high functional group tolerance. The broad scope of the reaction is particularly remarkable in light of the dramatic influence of pyridines' substituents on the reactivity of corresponding indolizin-1-ols, the key intermediates that proved to be highly thiophilic. In addition, an oxidative coupling of indolizin-1-ol in situ with p-tropoquinone oxime acetate is discovered. The reaction involves the C3 and C5 positions of the indolizin-1-ol and results in unusual indolizine-aminotropolone combinations. For the 3H-indolizinium-1-olate type of PCC HMBs, some general considerations concerning light absorption and NMR regularities were formulated.

TBAI/TBHP Catalyzed Synthesis of 2,4,6‐Trisubstituted Pyridines from Oxime Acetates Using Benzylamine as an Effective ArCO Surrogate under Transition Metal‐Free Conditions

AbstractAn efficient TBHP/TBAI mediated strategy has been developed for the synthesis of 2,4,6‐trisubstitued pyridines from ketoxime acetates and benzylamines under metal‐free conditions for the first time. In this protocol benzylamine acts as an effective ArCO surrogate. This methodology features use of inexpensive catalysts, avert of additional ligands and additives and high functional group tolerance. Moreover, 5‐Lipoxygenase enzyme inhibitory activities were performed for all synthesised compounds. Among all 2,4,6‐trisubstituted pyridines 3fg, 3fa and 3eg showed good activity.

Synthesis of 2H-imidazoles via copper-catalyzed homo/cross-coupling of oxime acetates.

A facile and practical protocol to construct 2H-imidazoles by applying an oxime acetate block as the sole component via oxidative homo/cross-coupling catalyzed by Cu(I) was developed. This strategy provides a straightforward method to produce a series of substituted 2H-imidazoles in moderate to excellent yields. The transformation process is straightforward to operate and is considered as a readily available catalytic system exhibiting good substrate compatibility, eliminating the necessity for pre-functionalization of azides or the use of additives.

Copper-mediated [3 + 2] oxidative cyclization of oxime acetate and its utility in the formal synthesis of fentiazac.

A new protocol for the direct synthesis of 2-aminothiazole has been developed from oxime acetate and readily available sodium thiocyanate using a copper catalyst. The present transformation has good functional group tolerance. Various thiazoles were smoothly synthesized in good to excellent yields. The applicability of the present method has been extended to the formal synthesis of the non-steroidal and anti-inflammatory drug, fentiazac via the Sandmeyer reaction and Suzuki coupling.

Swapping Copper-Catalytic Process: Selective Access to Pyrazoles and Conjugated Ketimines from Oxime Acetates and Cyclic Sulfamidate Imines.

A powerful CuCl-catalyzed sequential one-pot reaction of aryl methyl ketoxime acetates with cyclic N-sulfonyl imines followed by elimination in the presence of base is reported. This hydrazine-free method conveniently makes C-C and N-N bonds via a radical cleavage of the N-O bond, delivering a special class of C3-hydroxyarylated pyrazoles in good yields. Surprisingly, while employing CuI as a catalyst instead of CuCl, the reaction proceeds through a non-radical pathway which embodies a new tactic for the high-yielding access to value-added conjugated N-unsubstituted ketimines. Moreover, additive-free approach to sulfamidate-fused-pyrazoles was achieved by successfully catalyzing addition and oxidative N-N bond-making reactions by CuI and CuCl, respectively. Significantly, our novel technique could convert the prepared ketimines into the pharmacologically recognized 6H-benzo[c]chromene frameworks.

Iron-Catalysed [3+3] Annulation of Oxime Acetates and Enaminones towards the Synthesis of Multi-Substituted Pyridines.

A direct access to unsymmetrical and symmetrical multi-substituted pyridines has been accomplished via iron-catalysed [3+3] annulation of oxime acetates with enaminones. This protocol is featured by easily available starting materials, no requirement of expensive additives and ligands, operational simplicity, and good tolerance with diverse functional groups.

Copper-Catalyzed Oxidative [3 + 2]-Annulation of Quinoxalin-2(1H)-one with Oxime Esters toward Functionalized Pyrazolo[1,5-a]quinoxalin-4(5H)-ones as Opioid Receptor Modulators.

Pyrazolo[1,5-a]quinoxalin-4(5H)-one derivatives as novel opioid receptor modulators have been synthesized via copper-catalyzed oxidative [3 + 2]-annulation of quinoxalin-2(1H)-one and oxime-O-acetates. This hydrazine-free C-C and N-N bond formation strategy starts with the generation of C2N1 synthon using oxime acetate, which reacts in a [3 + 2] manner with quinoxalin-2(1H)-one, followed by oxidative aromatization. The synthesized compounds were tested against opioid receptors, of which eight compounds exhibited an antagonistic effect with EC50 < 5 μM at various opioid receptors. Molecular docking studies were performed to identify the binding of active pyrazolo[1,5-a]quinoxalin-4(5H)-one ligands with hKOR protein. Docking results indicated that compounds 3d and 3g participate in hydrogen bonding with the hydroxyl group of T111 of the active site pocket residue.

Copper-catalyzed [3+3] annulation of ketones with oxime acetates for the synthesis of pyridines.

A novel and efficient copper-catalyzed strategy for the synthesis of diverse pyridines through the [3+3] annulation of ketones with oxime acetates has been reported. It is very convenient to obtain various unsymmetrical 2,6-diarylpyridines by changing different substrates. The rare copper-catalyzed direct difunctionalization of saturated ketones for the synthesis of nitrogen heterocycles is developed. This protocol has excellent functional group tolerance, readily available raw materials, high chemoselectivity and broad substrate scope.

Cu-Catalyzed Dimerization of Indole Derived Oxime Acetate for Synthesis of Biimidazo[1,2-a]indoles.

A copper-mediated cyclization and dimerization of indole derived oxime acetate was developed to generate a series of biimidazo[1,2-a]indole scaffolds with two contiguous stereogenic quaternary carbons in one step.

Copper-catalyzed efficient access to 2,4,6-triphenyl pyridinesviaoxidative decarboxylative coupling of aryl acetic acids with oxime acetates

A simple and efficient strategy for the synthesis of 2,4,6- triphenyl pyridines has been developed through copper-catalysed oxidative decarboxylative coupling of C(sp3) aryl acetic acids with oxime acetates using oxygen as a sole terminal oxidant.

Mild and efficient copper-catalyzed oxidative cyclization of oximes with 2-aminobenzyl alcohols at room temperature: synthesis of polysubstituted quinolines.

A simple and efficient ligand-free Cu-catalyzed protocol for the synthesis of polysubstituted quinolines via oxidative cyclization of oxime acetates with 2-aminobenzyl alcohols at room temperature has been developed. The presented approach provides a new synthetic pathway leading to polysubstituted quinolines with good functional group tolerance under mild conditions. Moreover, this transformation can be applied for the preparation of quinolines on a gram scale. Oxime acetates serve as the internal oxidants in the reactions, thus making this method very attractive.

Chemoselective [3 + 2] annulation of oxime acetate with 2-aryl-3-ethoxycarbonyl-pyrroline-4,5-dione: an entry to pyrrolo[2,3-b]pyrrole derivatives.

A novel chemoselective [3 + 2] annulation reaction of easily accessible ketoxime acetate with 2-aryl-3-ethoxycarbonyl pyrroline-4,5-dione has been developed for the synthesis of unknown pyrrolo[2,3-b]pyrrole frameworks. This method involves copper-mediated N-O bond cleavage followed by the formation of carbon-carbon and carbon-nitrogen bonds. This operationally simple protocol provides broader functional group compatibility and good yields.

Copper-Catalyzed Annulation of Oxime Acetates with α-Amino Acid Ester Derivatives: Synthesis of 3-Sulfonamido/Imino 4-Pyrrolin-2-ones.

A copper-catalyzed annulation of oxime acetates and α-amino acid ester derivatives for the easy preparation of 4-pyrrolin-2-ones bearing a 3-amino group has been developed. This process features the oxidation of amines with oxime esters as the internal oxidant to produce the active 1,3-dinucleophilic and 1,2-dielectrophilic species concurrently. The subsequent nucleophilic cyclization realizes the efficient construction of 4-pyrrolin-2-one derivatives.

2‐Benzoyl Thienothiazoles from Annulation of C−H Bonds in Acetophenone Oximes

AbstractWe report a method for coupling of acetophenone oxime acetates, C−H bonds α to ketones, and elemental sulfur. The reactions proceeded in the presence of Li2CO3 (base) and DMSO (solvent) to afford 2‐benzoyl benzothienothiazoles. Functionalities including halogen, protected alcohol, and heterocycle groups were compatible with reaction conditions. Use of methylene C−H bonds in β‐keto esters is also viable. This marks a rare example for mild synthesis of S‐heterocycles from ketoxime acetates.

4-HO-TEMPO-Catalyzed Redox Annulation of Cyclopropanols with Oxime Acetates toward Pyridine Derivatives

A 4-HO-TEMPO-catalyzed redox strategy for the synthesis of pyridines through the annulation of cyclopropanols and oxime acetates has been developed. This protocol features good functional group tol...

CuI@Al2O3 catalyzed synthesis of 2-aminonicotinonitrile derivatives under solvent free condition

A Green approach for the synthesis of 2-aminonicotinonitriles from oxime acetate as enamine precursor, aldehyde and malononitrile under neat condition without the use of additive in presence of CuI@Al2O3 nanocatalyst is reported. Wide substrate scope, high yield in shorter reaction time, avoid the usage of bases/additives with better green chemistry matrices like low E factor and PMI, high values of atom economy, carbon efficiency and reaction mass efficiency as compared with literature methods. CuI@Al2O3 nanocatalyst was recovered and recycled five times without significant decrease in its catalytical activity.

Synthesis of Pentafluoroethylated Pyridines via Cu-Catalyzed[3+3] Cycloaddition Reaction of Oxime Acetates

Synthesis of Pentafluoroethylated Pyridines via Cu-Catalyzed[3+3] Cycloaddition Reaction of Oxime Acetates

Copper-Catalyzed Unstrained C-C Single Bond Cleavage of Acyclic Oxime Acetates Using Air: An Internal Oxidant-Triggered Strategy toward Nitriles and Ketones.

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.