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 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.

Copper-Catalyzed Synthesis of 3-Aryl-9H-imidazo[1,5-a]indol-9-ones Using Oxygen as the Sole Oxidant.

A three-component strategy was developed for 3-phenyl-9H-imidazo[1,5-a]indol-9-one preparation from indole-2-carboxaldehydes, aromatic aldehydes, and ammonium acetate under copper catalysis conditions. In this process, a new five-membered ring was formed and the C3 position in the indole substrate was selectively oxidized into a ketone skeleton using oxygen as the sole oxidant and ammonium acetate as the nitrogen source. Furthermore, same products also could be achieved from indole-2-carboxaldehydes and benzyl amines under similar reaction conditions.

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 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.

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.

Pd-Catalyzed C-O Bond Formation Enabling the Synthesis of Congested N,N,O-Trisubstituted Hydroxylamines.

A Pd-catalyzed C-O cross-coupling of O-acyl hydroxylamines and tertiary or secondary alkyl electrophiles was reported without the cleavage of the rather fragile N-O bond. The described strategy provides direct access to congested N,N,O-trisubstituted hydroxylamines bearing an α-quaternary carbon center under mild conditions in high yields and features exclusively chemoselective C-O bond formation, a broad substrate scope, and excellent functional group tolerance. The synthetic potential of the cross-coupling was established via pharmaceuticals derivatizations and a series of postcatalytic modifications.

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.

A Four-Component Reaction for the Synthesis of Thienopyrrolediones under Transition Metal Free Conditions.

A three-starting-material four-component reaction strategy is described to construct thienopyrrolediones (TPDs) from the simplest raw materials, elemental sulfur, aldehydes, and ß-ketoamides, under transition metal free conditions. Compared with traditional multistep reaction sequences, this process is simple, efficient, environmentally friendly, and atom-economic and has laid the foundation for further development of an easily synthesized TPD unit.

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.

Base-controlled divergent synthesis of vinyl sulfones from (benzylsulfonyl)benzenes and paraformaldehyde.

A tuneable metal-free protocol for the selective preparation of α-substituted vinyl sulfone and (E)-vinyl sulfone derivatives has been described. In this process, stable paraformaldehyde was used as the carbon source. The base played an important role in the selectivity control of transformations. More than 50 products were synthesized with excellent chemoselectivity and broad functional group tolerance.

Copper-Catalyzed Three-Component Domino Cyclization for the Synthesis of 4-Aryl-5-(arythio)-2-(trifluoromethyl)oxazoles.

A copper-catalyzed oxidative cyclization of oxime, arylthiol, and trifluoroacetic anhydride for the construction of trisubstituted oxazoles has been developed. This transformation combines N-O bond cleavage, C-H functionalization, and intramolecular annulation, providing a practical protocol for the introduction of a trifluoromethyl (-CF3) group at oxazole rings.

A three-component approach to isoxazolines and isoxazoles under metal-free conditions.

A 1,3-dipolar cycloaddition of 2-methylquinoline, tert-butyl nitrite (TBN) and alkynes or alkenes for the synthesis of biheteroaryls containing both isoxazoline/isoxazole and quinoline motifs has been developed. In this protocol, TBN serves as a convenient N-O source to convert 2-methylquinoline into intermediate nitrile oxides in situ.

A Three-Component Strategy for Benzoselenophene Synthesis under Metal-Free Conditions Using Selenium Powder.

An efficient three-component benzoselenophenes formation has been developed from substituted indoles, acetophenones, and selenium powder under metal-free conditions. 2-Aryl indoles played an important role to promote benzoselenophene formation from acetophenone derivatives and selenium powder. One C-C and two C-Se bonds were selectively formed to provide 40 new benzoselenophenes in good yields.

Metal-Free Double Csp2-H Bond Functionalization: Strategy for Synthesizing Benzo[ a]carbazoles from 2-Arylindoles and Acetophenones/Alkynes.

A metal-free strategy for the synthesis of benzocarbazoles from 2-arylindoles and aryl ketones is developed. Various 2-aryl-3-vinyl-indoles were generated in situ through dehydrative condensation of aryl ketones and indoles. These key intermediates could be selectively converted into the corresponding benzo[ a]carbazoles via a direct cyclization process between two Csp2-H bonds. Furthermore, terminal alkynes also could be used as the versatile C2 source to afford the corresponding products in good yields.

Regioselective three-component synthesis of 1,2-diarylindoles from cyclohexanones, α-hydroxyketones and anilines under transition-metal-free conditions.

A facile method for the one-pot synthesis of 1,2-diarylindoles under transition-metal-free conditions is described. Cyclohexanones were used as the aryl sources via the dehydrogenative aromatization process. One C-C and two C-N bonds were selectively formed via a domino reaction. This protocol provides a convenient approach for the construction of valuable bioactive 1,2-diarylindoles from readily available cyclohexanones, α-hydroxyketones and anilines.

Three-Component Cascade Synthesis of Carbazoles through [1s,6s] Sigmatropic Shift under Metal-Free Conditions.

A novel method was developed for the synthesis of substituted carbazoles from commercially available starting materials under metal-free conditions. This strategy involves a [1s,6s] sigmatropic shift step and introduces an electron-withdrawing ester substituent at the C2 position of the carbazole ring. The present protocol afforded the desired carbazole derivatives with good regioselectivity and well functional group tolerance. DFT calculations were carried out to support the reaction pathway.

Iron-Promoted Three-Component 2-Substituted Benzothiazole Formation via Nitroarene ortho-C-H Sulfuration with Elemental Sulfur.

A three-component procedure for the preparation of 2-substituted benzothiazoles from nitroarenes, alcohols, and sulfur powder is described. The reaction showed a good functional group tolerance to provide the heterocyclic products in moderate to good yields. The sequential assembly involving nitro reduction, C-N condensation, and C-S bond formation has been realized in one pot.

Concise synthesis of N-thiomethyl benzoimidazoles through base-promoted sequential multicomponent assembly.

An efficient method for the synthesis of N-thiomethyl benzimidazoles from o-phenylenediamines, thiophenols, and aldehydes via C-N/C-S bond formation under metal-free conditions is described. A broad range of functional groups attached to the substrates were well tolerated in this reaction system. Stable and low-toxicity paraformaldehyde was used as the carbon source.

Three-Component Ordered Annulation of Amines, Ketones, and Nitrovinylarenes: Access to Fused Pyrroles and Substituted Indoles under Metal-Free Conditions.

An efficient synthesis of pyrroles and indoles has been developed via three-component ordered annulation of amines, ketones, and nitrovinylarenes. The reaction selectivity can be well controlled under metal-free conditions to afford the corresponding heterocyclic products in good yields.