Nucleophilic Substitution Sequence Research Articles

NIS-Promoted Chemodivergent and Diastereoselective Synthesis of Pyrrolinyl and Cyclopentenyl Spiropyrazolones via Regulated Cyclization of Alkylidene Pyrazolones with Enamino Esters.

An N-iodosuccinimide-promoted annulation of alkylidene pyrazolones with enamino esters has been explored to construct a spiropyrazolone moiety through a Michael addition/iodination/intramolecular nucleophilic substitution sequence. When the reaction was performed in acetonitrile at 100 °C, it furnished pyrrolinyl spiropyrazolones exclusively in an anti configuration through N-attacking cyclization. When the reaction was performed in dimethyl sulfoxide at 80 °C in the presence of K2HPO4, it afforded cyclopentenyl spiropyrazolones exclusively in the syn configuration through C-attacking cyclization. A plausible mechanism has also been proposed.

A Three‐Component Domino Reaction Enabled by Phase‐Transfer Catalysis for the Assembly of 3‐Thioquinoline‐2,5‐Diones

AbstractA three‐component phase‐transfer catalytic domino reaction involving cyclohexane‐1,3‐dione‐derived enaminones, 5‐alkenyl rhodanines, and haloalkanes has been developed. This protocol produces a wide range of 3‐thioquinoline‐2,5‐diones in yields of 52–81%. The construction of a C−S bond at the C‐3 position of the quinoline‐2,5‐dione framework expands its structural diversity. Studies into the reaction mechanism revealed that the reaction undergoes a conjugate addition, ammonolysis, elimination, and nucleophilic substitution sequence. The synthetic potential of the reaction was demonstrated by the gram‐scale syntheses of representative products. Chloroalkyl chains were installed on the sulfur atoms of most products obtained in this reaction. Diversified product derivatives were obtained by exploiting the favorable leaving nature of the chloride moiety.

Enantioselective construction of spirodihydrofuran oxindoles via one-pot organo-/iodine sequential catalysis

An efficient strategy for the enantioselective construction of spirodihydrofuran oxindoles with vicinal quaternary stereocenters was first developed via a one-pot Michael/iodization/SN2 nucleophilic substitution sequence.

Halogen-Imparted Reactivity in Lithium Carbenoid Mediated Homologations of Imine Surrogates: Direct Assembly of bis-Trifluoromethyl-β-Diketiminates and the Dual Role of LiCH2I.

The selective formal insertion (homologation) of a carbon unit bridging the two trifluoroacetamidoyl chlorides (TFAICs) units is reported. The tactic is levered on a highly chemoselective homologation-metalation-acyl nucleophilic substitution sequence which precisely enables to assemble novel trifluoromethylated β-diketiminates within a single synthetic operation. Unlike previous homologations conducted with LiCH2Cl furnishing aziridines, herein we exploit the unique capability of iodomethyllithium to act contemporaneously as a C1 source (homologating effect) and metalating agent. The mechanistic rationale grounded on experimental evidences supports the hypothesized proposal and, the structural analysis gathers key aspects of this class of valuable ligands in catalysis.

Halogen‐Imparted Reactivity in Lithium Carbenoid Mediated Homologations of Imine Surrogates: Direct Assembly of bis‐Trifluoromethyl‐β‐Diketiminates and the Dual Role of LiCH2I

AbstractThe selective formal insertion (homologation) of a carbon unit bridging the two trifluoroacetamidoyl chlorides (TFAICs) units is reported. The tactic is levered on a highly chemoselective homologation–metalation–acyl nucleophilic substitution sequence which precisely enables to assemble novel trifluoromethylated β‐diketiminates within a single synthetic operation. Unlike previous homologations conducted with LiCH2Cl furnishing aziridines, herein we exploit the unique capability of iodomethyllithium to act contemporaneously as a C1 source (homologating effect) and metalating agent. The mechanistic rationale grounded on experimental evidences supports the hypothesized proposal and, the structural analysis gathers key aspects of this class of valuable ligands in catalysis.

Intermolecular Three-Component Synthesis of Fluorene Derivatives by a Rhodium-Catalyzed Stitching Reaction/Remote Nucleophilic Substitution Sequence.

A three-component synthesis of multisubstituted fluorene derivatives has been developed by devising a rhodium-catalyzed stitching reaction/remote nucleophilic substitution sequence. A variety of nucleophiles can be installed in the second step including both heteroatom and carbon nucleophiles. An efficient synthesis of 5H-benzo[a]fluoren-5-ones has also been realized using N-(2-alkynyl)benzoylpyrrole as the reaction partner through a new reaction pathway.

Regio- and Diastereoselective Access to 4-Imidazolidinones via an Aza-Mannich Initiated Cyclization of Sulfamate-Derived Cyclic Imines with α-Halo Hydroxamates.

An efficient regio- and diastereoselective cyclization of sulfamate-derived cyclic imines with unsubstituted or monosubstituted α-halo hydroxamates is developed under mild conditions. This reaction proceeds smoothly under transition-metal-free conditions via a domino aza-Mannich addition/intramolecular nucleophilic substitution sequence, providing a convenient route to access 2-monosubstituted and 2,5-disubstituted 4-imidazolidinones. Notably, the products were obtained with single trans-isomers in moderate to excellent yields.

Rapid and Effective Synthesis of α-Acyloxy-α-alkynyltrimethylsilanes.

α-Alkynyl-α'-trimethylsilylhydrazones are readily oxidized into diazo compounds under simple experimental conditions. These stable diazo species can in turn react with a range of carboxylic acids via a protonation-nucleophilic substitution sequence, leading to valuable α-acyloxy-α-alkynyltrimethylsilanes. This procedure avoids the delicate preparation and manipulation of α-hydroxypropargyltrimethylsilanes.

Metal-free Deamidative Ugi Access to Isoindolinones

A two-step isoindolone synthesis has been achieved by using an Ugi/oxidative vicarious nucleophilic substitution sequence starting from 3-nitrobenzoic acid and aromatic aldehydes. Loss of the amido group was observed as well as a further oxidative process towards hydroxyisoindolone derivatives after prolonged stirring open to the atmosphere.

Stability of a high-voltage ionic liquid with a substituted piperidinium cation and a TFSI anion, promising for electrochemical applications

The novel ionic liquid N-methyl-N-[2-(2-methoxyethoxy)-ethyl]piperidinium bis(trifluoromethylsulfonyl)imide was synthesized from N-methylpiperidine by a sequence of nucleophilic substitution and anion exchange reactions and characterized by physico-chemical and electrochemical methods.

ChemInform Abstract: A Highly‐Efficient Palladium‐Catalyzed Aminocarbonylation/SNAr Approach to Dibenzoxazepinones.

AbstractVarious 2‐aminophenols and 2‐bromofluorobenzenes are used as substrates for the convenient one‐pot synthesis of a wide range of dibenzoxazepinones by a palladium‐catalyzed aminocarbonylation/aromatic nucleophilic substitution sequence.

A simple and convenient synthesis of 5-amino-substituted tetrazolo[1,5-a]-1,3,5-triazin-7-one salts

A simple and convenient three-step synthesis of 5-amino-substituted tetrazolo[1,5-a]-1,3,5-triazin-7-one sodium salts based on a fairly simple sequence of nucleophilic substitution of chlorine atoms in cyanuric chloride has been developed. The corresponding tetrabutylammonium salts were synthesized by cation-exchange with tetrabutylammonium chloride. The structures of the products were characterized by IR, 1H NMR and 13C NMR spectroscopy, and by elemental and X-ray analysis.

ChemInform Abstract: Synthesis of Thiazole Derivatives Bearing an Incorporated Z‐5‐Aminopent‐3‐enoic Acid Fragment.

AbstractThe title compounds (VII) are prepared from 5‐bromolevulinic esters (I) (applied as mixtures with their less reactive 3‐bromo‐regioisomers) through a sequence of nucleophilic substitution, bromination, Hantzsch‐type heterocyclization and Gabriel‐like deprotection.

Synthesis of thiazole derivatives bearing an incorporated Z-5-aminopent-3-enoic acid fragment

Novel compounds bearing a joint thiazole and a Z-5-aminopent-3-enoic acid fragments have been synthesized from readily accessible 5-bromolevulinic esters through a sequence of nucleophilic substitution, bromination, Hantzsch-type heterocyclization and Gabriel-like deprotection reactions. A majority of these reactions proceed in ionic liquid media that enhances their efficiency and selectivity in comparison to the corresponding reactions in conventional organic solvents. The compounds have a significant pharmaceutical potential.

ChemInform Abstract: Synthesis of Hexahydrobenzo[b]pyrimido[4,5‐h][1,6]naphthyridines via an Intramolecular Hetero‐Diels—Alder Reaction.

Method development was completed for a strategy to access a novel pyrimidine-fused heterocyclic scaffold. The key step for this synthetic route entails an intramolecular inverse electron demand hetero-Diels−Alder reaction of imines or iminiums formed in situ from allylaminopyrimidinealdehydes 3 and anilines. The reactions provided exclusively cis-configuration products 6. Products 6 were readily precipitated in the reaction solution in good to excellent yields. Further transformations of the phenylthio group were demonstrated by an oxidation and subsequent nucleophilic substitution sequence. The synthetic strategy provides an efficient way to access libraries of the tetracyclic pyrimidine-fused heterocycles that can be explored for potential pharmaceutical or biological activities.

Synthesis of Hexahydrobenzo[b]pyrimido[4,5-h][1,6]naphthyridines via an Intramolecular Hetero-Diels−Alder Reaction

Method development was completed for a strategy to access a novel pyrimidine-fused heterocyclic scaffold. The key step for this synthetic route entails an intramolecular inverse electron demand hetero-Diels-Alder reaction of imines or iminiums formed in situ from allylaminopyrimidinealdehydes 3 and anilines. The reactions provided exclusively cis-configuration products 6. Products 6 were readily precipitated in the reaction solution in good to excellent yields. Further transformations of the phenylthio group were demonstrated by an oxidation and subsequent nucleophilic substitution sequence. The synthetic strategy provides an efficient way to access libraries of the tetracyclic pyrimidine-fused heterocycles that can be explored for potential pharmaceutical or biological activities.

Consecutive nucleophilic substitution and aza Diels–Alder reaction—an efficient strategy to functionalized 2,2′-bipyridines

An efficient strategy for the synthesis of functionalized 2,2′-bipyridines is reported. The strategy is based on readily available 3-pyridyl-1,2,4-triazine 4-oxides and uses a reaction sequence of nucleophilic substitution of hydrogen and aza Diels–Alder reaction.

Characteristic Features of Nucleophilic Substitution in the Series of 4‐RSO2‐6‐nitro‐1‐phenyl‐1H‐indazoles and benzo[d]isoxazoles.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Characteristic features of nucleophilic substitution in the series of 4-RSO2-6-nitro-1-phenyl-1H-indazoles and benzo[d]isoxazoles

Oxidation of 3-substituted 4-R-6-nitro-1-phenyl-1H-indazoles and benzo[d]isoxazoles (R = Ph, CH2CO2Me) gave the corresponding sulfones treatment of which with PhSH—K2CO3 in N-methylpyrrolidone results in replacement of only the RSO2 group in position 4 with the 6-NO2 group remaining intact, contrary to the known sequence of nucleophilic substitution for meta-arranged nucleofuges.

Tandem reaction of α-hypervalent iodo functionalized phosphonium and arsonium ylides as umpolung reagents

α-Hypervalent iodo functionalized phosphonium and arsonium ylides 2 can be used as umpolung ylides to react with nucleophiles to give α-heteroatom substituted ylides 4 in good yields. A tandem sequence of nucleophilic substitution then Wittig reaction occurs smoothly to form ( Z)-α-halo-α,β-unsaturated esters 6 , stereoselectively, in moderate to excellent yields.