Copper-Catalyzed Three-Component Synthesis of ß-Hydroxysulfides from Styrene Oxide, Aryl Iodide, and Carbon Disulfide.

A copper-catalyzed three-component coupling reaction of styrene oxide, aryl iodide, and carbon disulfide for the construction of ß-hydroxysulfides has been developed. In this process, readily available CS2 was used as the sulfur source to construct C-S bonds for the synthesis of phenyl-ß-hydroxysulfides and (benzo[d]thiazol)-ß-hydroxysulfides. This process features mild reaction conditions, simple operation, and wide substrate scope (>50 examples).

Three-Component Synthesis of 2-Substituted Quinolines and Benzo[f]quinolines Using Tertiary Amines as the Vinyl Source.

A metal-free method for the construction of 2-substituted quinolines and benzo[f]quinolines from aromatic amines, aldehydes, and tertiary amines has been demonstrated. Cheap and readily available tertiary amines acted as the vinyl source. A new pyridine ring was selectively formed via [4 + 2] condensation that was promoted by ammonium salt under neutral conditions and an oxygen atmosphere. This strategy provided a new route for the preparation of various quinoline derivatives with different substituents at the pyridine ring, which provides the possibility of further modification.

Three-Component Tandem Amidosulfenylation of Alkenes for the Synthesis of ß-Succinimide Sulfides.

An environmentally benign multicomponent strategy for the amidosulfenylation of alkenes for the synthesis of ß-succinimide sulfides is disclosed. In this process, common disulfides smoothly act as a sulfur-based source, and N-iodosuccinimide (NIS) is used not only as a free radical initiator but also as an N-nucleophile. A broad range of functional groups are tolerated in this reaction system.

CuBr2-Catalyzed Annulation of 2-Bromo-N-Arylbenzimidamide with Se/S8 Powder for the Synthesis of Benzo[d]isoselenazole and Benzo[d]isothiazole.

A CuBr2-catalyzed annulation of 2-bromo-N-arylbenzimidamide with selenium/sulfur powder for the synthesis of benzo[d]isoselenazole and benzo[d]isothiazole in generally good yields was investigated. This synthetic strategy features good substrate scope and functional group tolerance. Furthermore, the corresponding products could be converted into N-aryl indoles via rhodiumIII-catalyzed ortho C-H activation of the N-phenyl ring, providing an efficient approach for axial aromatic molecules.

Modular Synthesis of Tetrasubstituted Pyrroles through a Four-Component Cyclization Strategy Using Ammonium Salt as the Nitrogen Source.

A four-component synthesis of tetrasubstituted pyrroles was developed under metal-free conditions. The pyrrole ring was formed in one pot through [2 + 1 + 1 + 1] condensation using ammonium salt as the nitrogen source. In this strategy, 1,4-naphthoquinones and maleimides were used as the versatile C2 fragments to provide substituted benzo[f]isoindole-4,9-diones and pyrrolo[3,4-c]pyrrole-1,3-diones, respectively. This work is highlighted by using ammonium salt as the nitrogen source, readily available starting materials and multibond formation (two C-C and two C-N bonds) in a single operation.

Metal- and Solvent-Free Synthesis of Substituted Pyrimidines via an NH4I-Promoted Three-Component Tandem Reaction.

A facile and practical approach for the preparation of substituted pyrimidines from ketones, NH4OAc, and N,N-dimethylformamide dimethyl acetal has been described. This NH4I-promoted three-component tandem reaction affords a broad range of substituted pyrimidines in acceptable yields under metal- and solvent-free conditions. The present methodology features the advantages of simple and easily available starting materials, metal- and solvent-free conditions, a broad substrate scope with good functional group tolerance, and gram-scale synthesis.

TBHP-mediated photochemical coupling/cyclization of N-arylacrylamides with thiols.

The effective photoredox-mediated oxidative thiolation and cyclization of N-arylacrylamides with thiols leads to biologically interesting 3-thionated oxindoles through C-S and C-C bond formation. This process represents a straightforward reaction that starts from non-prefunctionalized thiolating reagents. Mechanistic studies demonstrated that the TBHP serves as a key radical initiator with visible-light catalysis.

Three-component selective synthesis of phenothiazines and bis-phenothiazines under metal-free conditions.

An iodine-containing reagent promoted three-component method for the selective synthesis of phenothiazines and bis-phenothiazines has been developed. The present protocol starts from simple and easily available cyclohexanones, elemental sulfur, and inorganic ammonium salts, selectively producing phenothiazines and bis-phenothiazines in satisfactory yields under aerobic conditions. This method has the advantages of simple and readily available starting materials and metal-free conditions, affording a facile and practical approach for the preparation of phenothiazines and bis-phenothiazines.

Brønsted Acid Promoted Facile Synthesis of Benzoacridines from Aromatic Aldehydes and N-Phenyl Naphthylamines.

A facile method for the rapid synthesis of benzoacridines has been described. This protocol promoted by p-toluenesulfonic acid starts from aromatic aldehydes and N-phenyl naphthylamines, affording a variety of benzoacridines in 30-90 % yields under metal-free conditions. The present approach involves a cascade of condensation, Friedel-Crafts alkylation, annulation and dehydroaromatization in one pot.

Metal- and Solvent-Free Synthesis of Tetrahydrobenzo[c]carbazolones through NaI-Catalyzed Formal [4 + 2] Annulation.

A novel strategy for the preparation of functional carbazoles through NaI-catalyzed formal [4 + 2] annulation of 2-(indol-3-yl)cyclohexanones and alkynes/alkenes has been developed. The present approach started from easily available raw materials and provided a variety of tetrahydrobenzo[c]carbazolones in satisfactory yields under metal- and solvent-free conditions. Furthermore, the products could be further transformed into structurally valuable carbazole-based conjugated derivatives.

Photoredox Neutral Decarboxylative Hydroxyalkylations of Heteroarenes with α-Keto Acids.

Photoredox neutral decarboxylative hydroxyalkylations of heteroarenes with α-keto acids under mild conditions are described. Stable and readily available α-keto acids were employed as hydroxyalkylating reagents with only CO2 released as the byproduct. A range of aromatic and aliphatic α-keto acids were successfully converted into hydroxyalkylated products with various heteroarenes. This transformation proceeded through a decarboxylation/Minisci addition/SCS sequence, generating a variety of valuable hydroxyalkylated heteroarenes.

A Mild Two-Step Synthesis of Structurally Valuable Indole-Fused Derivatives.

A mild two-step synthetic approach for the preparation of structurally valuable indolo[3',2':4,5]pyrrolo[3,2,1-kl]phenothiazines has been developed. In this work, cyclohexanone was used as the key bridge to connect the indole and phenothiazine frameworks to construct a structurally valuable indole-fused derivative. The present protocol achieved the cascade construction of multiple C-hetero bonds, affording a convenient approach access to hexacyclic-fused system that contained both indole and phenothiazine, two privileged skeletons.

Synthesis of Indenoquinolinones and 2-Substituted Quinolines via [4 + 2] Cycloaddition Reaction.

We have reported a metal-free protocol for the synthesis of indenoquinolinones and 2-substituted quinolines via [4 + 2] cycloaddition reaction using readily available 2-aminobenzaldehydes and ketones as starting materials. Different quinoline derivatives can be selectively synthesized by changing the type of ketones. O2 and dimethyl sulfoxide (DMSO) as co-oxidants play an important role in the synthesis of indenoquinolinones. This condensation/oxidation strategy involves the formation of C-N, C-C, and C-O bonds, with the advantages of high yields and a broad substrate range.

Site-Selective Synthesis of Aryl Sulfides via Oxidative Aromatization of Cyclohexanones with Thiophenols.

We have introduced a metal-free facile access for the thiolation/aromatization of cyclohexanones with thiophenols to the corresponding aryl sulfides. The dehydroaromatic reaction of non-aromatic cyclohexanones proceeded smoothly using oxygen as a green oxidant.

Copper-catalyzed three-component N-alkylation of quinazolinones and azoles.

A Cu-catalyzed three-component N-alkylation coupling reaction of N-heteroarenes with methyl ketones and DMPA as a carbon source has been developed. Using methyl ketones as alkylation reagents and DMPA (N,N'-dimethylpropionamide) as a carbon source, the reaction proceeded smoothly under the Cu-based oxidative system and led to a series of functionalized N-heterocycles including 4-quinazolinones, triazoles and pyrazoles.

Iodine/DMSO-Promoted Selective Direct Arylthiation of Anilines with Thiols under Metal-Free Conditions.

An iodine-promoted divergent thiolation of unprotected anilines with thiols for the synthesis of sulfide anilines has been described. The combinational use of I2 and DMSO played an important role to realize this kind of transformation without the aid of a metal catalyst and strong oxidants. The reaction selectivity was well controlled to provide mono-, bis-, and trisubstituted diaryl sulfide derivatives. More importantly, iodination and sulfenylation can occur simultaneously to provide useful multifunctionalized iodoaniline products. This method afforded an efficient protocol for the construct C-S and C-I bonds from the C-H bond under mild reaction conditions.

Three-Component Synthesis of Dibenzoxazepinamines and Dibenzothiazepinamines under Transition-Metal-Free Conditions.

A convenient and efficient strategy for the synthesis of dibenzoxazepinamines and dibenzothiazepinamines has been developed. This three-component approach started from 2-nitrobenzaldehydes, 2-aminophenols, and methoxyammonium chlorides under metal-free conditions. The protocol has the advantages of readily available starting materials, simple and facile conditions, gram-scale synthesis, and broad substrate scope, providing an efficient and practical strategy for the preparation of potential drug-active dibenzoxazepinamines and dibenzothiazepinamines in one pot.

Metal-Free Synthesis and Photophysical Properties of 1,2,4-Triarylpyrroles.

A three-component reaction has been developed for the construction of multiaryl-substituted pyrrole derivatives from arylketones, amines, and nitrovinylarenes under metal-free conditions. Hence, homologous 1,2,4-triaryl-substituted pyrrole products were obtained in good to high yields. Furthermore, 2,3,5-triaryl-substituted pyrroles were selectively formed in the absence of nitrovinylarenes. The photophysical properties of some pyrrole products have been investigated to show good aggregation-induced emission (AIE) activity.

Cu-Catalyzed Oxidative Dual Arylation of Active Alkenes: Preparation of Cyanoarylated Oxindoles through Denitrogenation of 3-Aminoindazoles.

A novel and mild Cu-catalyzed oxidative dual arylation of carbon-carbon double bonds in acrylamides with 3-aminoindazoles is proposed for the synthesis of cyanoarylated oxindoles. Notably, 3-aminoindazoles are employed as efficient arylating agents via the cleavage of two C-N bonds. This oxidative dual arylation of active alkenes involves a radical process and undergoes a sequence of 3-aminoindazole oxidation, two-C-N-bond cleavage, cyanoaryl radical addition, and intramolecular cyclization.

Recent advances in the transition metal-free oxidative dehydrogenative aromatization of cyclohexanones.

Cyclohexanone is a simple and widely available raw material that can be obtained from lignin biomass, highlighting its renewable and sustainable features. Cyclohexanone, as an important synthon in organic chemistry, has been demonstrated to be viable for constructing functionalized arenes and benzoheteroarenes, with recent extensive development on transition metal-free oxidative dehydrogenative aromatization. This review focuses on recent research progress on the transition metal-free derivation of cyclohexanones via oxidative dehydrogenative aromatization.