Bromonitroalkenes as efficient intermediates in organic synthesis.

Bromonitroalkenes are useful molecules in synthetic organic chemistry. They are mainly prepared from nitroalkenes via bromination reactions. In this review, the application of bromonitroalkenes as partners in the reaction with a diversity of mono- and bi-functional molecules, including aldehydes and ketones, active methylene compounds, 1,2-dicarbonyls, enamines, enols, electron-rich arenes, amidines, azomethine ylides, azirines, diazo compounds, and many others, is reviewed. By using these substrates, various biologically active scaffolds, such as heterocycles, carbocycles, spirocycles, polycyclic systems, natural products, and other useful acyclic compounds, were prepared. In addition, due to their dielectrophilic character, electrophilic and nucleophilic character, and ability to participate in cycloaddition reactions, bromonitroalkenes were efficiently applied in asymmetric cascade/domino/tandem reactions catalyzed by chiral catalysts. In this manuscript, around 55 papers are summarized and discussed during the years 2000-2023.

Catalyst/Metal/Solvent-Free Markovnikov Hydrothiolation of Unactivated Alkenes with Dithiocarbamic Acids.

Catalyst-free Markovnikov-selective hydrothiolation of unactivated alkenes still remains a great challenge. Herein, we develop a catalyst/metal/solvent-free methodology for the Markovnikov hydrothiolation of unactivated alkenes with in situ prepared dithiocarbamic acids, providing a wide array of alkyl dithiocarbamates. A variety of terminal, internal, cyclic, and acyclic unactivated alkenes were applied successfully in this protocol. This three-component thiol-ene reaction can be considered as a new family of click reactions.

The chemistry of 2-hydroxy-ß-nitrostyrenes: versatile intermediates in synthetic organic chemistry.

The applications of 2-hydroxy-ß-nitrostyrenes as efficient bifunctional intermediates in organic synthesis are investigated in this review. For this purpose, reactions of 2-hydroxy-ß-nitrostyrenes with diverse molecules, including carbonyl compounds, 1,3-dicarbonyl compounds, α,ß-unsaturated carbonyl compounds, hemiacetals, nitroalkenes, γ-butenolides, tetronic acid, azalactones, pyrazolones, enamines, malononitrile, methyleneindolinones, ylides, etc., were investigated to construct interesting biologically active scaffolds such as chromans, chromenes, coumarins, benzofurans and their fused and spiro rings, natural products, and other useful cyclic and acyclic compounds. The main focus is on the asymmetric synthesis of these compounds via cascade/domino/tandem reactions catalyzed by chiral organocatalysts. In this review, around 60 papers reported between the years 2000 and 2022 are presented.

Catalyst free one pot three components synthesis of 2-iminothiazoles from nitroepoxides and thiourea.

Nitroepoxides were introduced as efficient substrates for the one-pot three-component synthesis of 2-iminothiazoles under catalyst-free conditions. Reaction of amines, isothiocyanates, and nitroepoxides in THF at 10-15 °C afforded corresponding 2-iminothiazoles in high to excellent yields. The reaction proceeds via the in situ formation of thiourea from an amine and an isothiocyanate, followed by nitroepoxide ring opening with the sulfur of thiourea, cyclization reaction, and dehydration cascade. The structures of products were confirmed by IR, NMR, HRMS analyses and X-ray crystallography.

Multicomponent synthesis of fully substituted thiazoles using glycine-based dithiocarbamates, acetic anhydride and nitroalkenes.

Reaction of glycine-based dithiocarbamates with nitroalkenes in the presence of acetic anhydride was utilized for the synthesis of fully substituted 2-(alkylsulfanyl)-4-(nitroalkyl)-5-acyloxy-1,3-thiazoles. The reaction proceeds via the in situ formation of thiazol-5(4H)-one from glycine-based dithiocarbamates, followed by the Michael addition of this intermediate to nitroalkenes, aromatization, and esterification reaction cascade. This new one-pot three-component reaction afforded a diverse library of fully substituted thiazoles in high to excellent yields under solvent-free conditions.

Nitroepoxide ring opening with thionucleophiles in water: synthesis of α-xanthyl ketones, ß-keto sulfones and ß-keto sulfonic acids.

Nitroepoxide ring opening with thionucleophiles such as potassium xanthates, sodium aryl sulfinates and sodium bisulfite in water is investigated. It provides a direct and green route for the synthesis of α-xanthyl-α-aryl-2-propanones (P2P-xanthate derivatives), ß-keto sulfones and ß-keto sulfonic acids. High to excellent yields, performing the reaction in water under catalyst-free conditions, and easy work-up are the main advantages of this protocol.

Synthesis of a novel category of pseudo-peptides using an Ugi three-component reaction of levulinic acid as bifunctional substrate, amines, and amino acid-based isocyanides.

The synthesis of a novel category of pseudo-peptides via intramolecular Ugi reaction of levulinic acid (4-oxopentanoic acid), aromatic and aliphatic amines, and amino acid-based isocyanides is reported. Levulinic acid was applied as a bifunctional substrate containing both carbonyl and acid moieties suitable for the Ugi reaction. This article provides a facile and convenient one-pot procedure for the synthesis of peptide-like heterocyclic molecules containing 2-pyrrolidone (γ-lactam), amide and ester functional groups with good to excellent yields.

Regioselective Opening of Nitroepoxides with Unsymmetrical Diamines.

Nitroepoxides are easily transformed into benzodiazepines, tetrahydrobenzodiazepines, imidazopyridines, and N-alkyl tetrahydroquinoxalines by treatment with 2-aminobenzylamines, 2-aminopyridines, and N-alkyl 1,2-diaminobenzenes, respectively. Regioselectivity is controlled through attack of the most nucleophilic nitrogen of the unsymmetrical diamine to the ß position of the epoxide. These reactions represent an efficient way to prepare privileged bioactive structures.

Synthesis of N,S-Heterocycles and Dithiocarbamates by the Reaction of Dithiocarbamic Acids and S-Alkyl Dithiocarbamates with Nitroepoxides.

A facile and efficient procedure for the synthesis of substituted thiazole-2(3H)-thiones and thiazolidine-2-thiones by the reaction of primary amines, carbon disulfide, and nitroepoxides is described. By using secondary amines in this protocol, the corresponding dithiocarbamate-substituted phenyl-2-propanones were prepared in excellent yields. In addition, substituted thiazoles and 1-(alkylthio)-1-phenylpropan-2-ones were prepared in reactions of S-alkyl dithiocarbamates and nitroepoxides.

Four-Component Reaction for the Synthesis of Dithiocarbamates Starting from Cyclic Imines.

An efficient one-pot, four-component reaction for the synthesis of dithiocarbamates using carbon disulfide, cyclic imines, acid chlorides, and commercially available primary or secondary amines has been developed by performing an acid chloride addition to a heterocyclic imine followed by subsequent nucleophilic substitution of in situ generated dithiocarbamic acid. With the aid of the newly developed and powerful multicomponent reaction, a direct route for the synthesis of 24 unknown dithiocarbamates in moderate to good yield under mild conditions is enabled.

Tandem Esterification/1,4-Addition-Type Friedel-Crafts Alkylation Reactions of Phenols/Naphthols with Olefinic Thioazlactones: Access to Functionalized 1,2-Dihydrobenzo[f]chromen-3-ones and 3,4-Dihydrochromen-2-ones.

An efficient approach for the synthesis of novel alkyl 2,3-dihydro-3-oxo-1-aryl-1H-benzo[f]chromen-2-ylcarbamodithioates and alkyl 3,4-dihydro-2-oxo-4-aryl-2H-chromen-3-ylcarbamodithioates from 2-(alkylthio)thioazlactones (thioazlactones) and phenols or naphthols catalyzed by PTSA was developed. The reaction proceeds via a domino esterification/intramolecular 1,4-addition-type Friedel-Crafts alkylation reaction to afford interesting complex molecules by a simple procedure with high yields and diastereoselectivity. An X-ray analysis was carried out to firmly establish the stereochemistry of the products.

Investigation of the reaction of dithiocarbamic acid salts with aromatic aldehydes.

A reaction of dithiocarbamic acid salts with carbonyl compounds was investigated for the first time in the presence of BF(3)·OEt(2). The reaction is temperature dependent and gives gem-bis(dithiocarbamates) at 35-45 °C as a molecule with high equivalents of dithiocarbamate groups. At lower temperatures (15-20 °C), the 2-iminium-1,3-dithietane is obtained as the only product. The structure of a 2-iminium-1,3-dithietane was accomplished by X-ray crystallographic analysis.