Copper-catalyzed Three-component Reaction Research Articles

Copper-catalyzed three-component reaction for the synthesis of fluoroalkoxyl imidates

A Cu-catalyzed three-component reaction of aromatic terminal alkynes with aryl sulfonyl azides and primary fluoroalkyl alcohols for the synthesis of fluoroalkoxyl imidates was developed. This simple method enabled the efficient synthesis of trifluoroethoxyl, pentafluoropropoxyl, and heptafluorobutoxyl imidates in good to excellent yields under mild reaction conditions with excellent functional group tolerance.

3 + 2] Cycloaddition of Nitrile Ylides with Diazonium Salts: Copper-Catalyzed One-Pot Synthesis of Fully Substituted 1,2,4-Triazoles.

A novel [3 + 2] cycloaddition between nitrile ylides and diazonium salts was well-established. This copper-catalyzed three-component reaction was distinguished by mild conditions, ready availability, and operational simplicity, thus opening access to 1,2,4-triazoles with a diverse set of substitution patterns.

Consecutive Multicomponent Reactions: Synthesis of 3-Acyl-4-alkynyl-Substituted 1,3-Thiazolidines

This work describes the synthesis of compounds containing thiazolidine and propargylamidic motifs. Their preparation follows a synthetic route containing two multicomponent reactions. First, the Asinger four-component reaction is used to prepare 3-thiazolines and 3-oxazolines. Secondly, these heterocyclic imines are converted into propargylamides by a copper-catalyzed three-component reaction using acyl chlorides and terminal alkynes. The synthetic route is characterized by mild conditions and many functional groups are tolerated. The formation of an unexpected α-alkynoxyamide is also presented.

Copper-catalyzed aerobic cyclizations of tetrahydroisoquinolines with bromoketones and alkenes for the synthesis of 5,6-dihydropyrrolo[2,1-a]isoquinolines

A new copper-catalyzed oxidative cyclization protocol was developed for the synthesis of 5,6-dihydropyrrolo[2,1-a]isoquinolines via a three-component reaction of tetrahydroisoquinolines with bromoketones and electron-deficient alkenes with air as a terminal oxidant. A variety of functional groups survived under the reaction conditions and the target products were obtained in good yields. This reaction features such advantages as eco-friendly reaction conditions, a simplified operation process and a broad substrate scope.

Copper-catalyzed diarylation of Se with aryl iodides and heterocycles

The site-selective copper-catalyzed three-component coupling reaction of electron-deficient heterocycles, Se powder and aryl iodides is disclosed, providing an efficient and practical pathway to access 2-arylselenated heterocycles.

Synthesis of benzimidazoles by CuI-catalyzed three-component reaction of 2-haloaniline, ammonia and aldehyde in water.

An efficient copper-catalyzed three-component reaction of 2-haloaniline, ammonia and aldehyde for the synthesis of benzimidazoles with 1,10-phenanthroline as the ligand has been developed. A variety of substituted benzimidazole derivatives can be obtained in yields up to 95%.

A copper-catalyzed sulfonylative C–H bond functionalization from sulfur dioxide and aryldiazonium tetrafluoroborates

Sulfonylative C–H bond functionalization through a copper-catalyzed three-component reaction of 8-aminoquinoline amides, DABCO·(SO2)2 and aryldiazonium tetrafluoroborates is developed. Excellent selectivity in the para-position is observed.

Copper-catalyzed three-component reaction of imidazo[1,2-a]pyridine with elemental sulfur and arylboronic acid to produce sulfenylimidazo[1,2-a]pyridines

In this work, an efficient copper-catalyzed three-component reaction for the synthesis of sulfenylimidazo[1,2-a]pyridines using elemental sulfur as the sulfenylating agents has been developed. The reaction could proceed smoothly with a high degree of functional group tolerance and provide the desired products in moderate to good yield.

Copper-Catalyzed Oxidative Cross-Dehydrogenative Coupling/Oxidative Cycloaddition: Synthesis of 4-Acyl-1,2,3-Triazoles.

A copper-catalyzed three-component reaction of methyl ketones, organic azides, and various one-carbon (C1) donors was developed that provides 4-acyl-1,2,3-triazoles in moderate to good yields. While DMF, DMA, TMEDA, or DMSO can serve as the C1 donor, best yields were obtained using DMF. The transformation is proposed to proceed via an oxidative C-H/C-H cross-dehydrogenative coupling followed by an oxidative 1,3-dipolar cycloaddition.

Copper-Catalyzed Three-Component Carboazidation of Alkenes with Acetonitrile and Sodium Azide.

A copper-catalyzed three-component reaction of alkenes, acetonitrile, and sodium azide afforded γ-azido alkyl nitriles by formation of one C(sp3 )-C(sp3 ) bond and one C(sp3 )-N bond. The transformation allows concomitant introduction of two highly versatile groups (CN and N3 ) across the double bond. A sequence involving the copper-mediated generation of a cyanomethyl radical and its subsequent addition to an alkene, and a C(sp3 )-N bond formation accounted for the reaction outcome. The resulting γ-azido alkyl nitrile can be easily converted into 1,4-diamines, γ-amino nitriles, γ-azido esters, and γ-lactams of significant synthetic value.

Tunable Diastereoselective Desymmetrization of Cyclohexadienones Triggered by Copper-Catalyzed Three-Component Coupling Reaction.

Catalytic tandem diastereoselective desymmetrization of cyclohexadienone-containing 1,6-enynes has been achieved through copper-catalyzed [3 + 2]-cycloaddition followed by ketenimine formation and subsequent intramolecular conjugate addition. The cascade reaction provides cis-hydrobenzofurans in good yields with excellent diastereoselectivity. The exo- or endo-selectivity of bicyclic scaffolds depends on the selection of the base in the reaction. In addition, N-tethered bicyclic products further transformed into tricyclic compounds via intramolecular Michael addition.

Copper-Catalyzed Three-Component Coupling Reaction of Azoles, Se Powder, and Aryl Iodides.

A copper-catalyzed three-component coupling reaction of azoles, Se powder, and aryl iodide is described for the first time. This transformation provides a straightforward and facile pathway to synthesis 2-arylselanyl-azoles via a copper-catalyzed double C-Se bonds formation process. This reaction is attractive and practical since the cheap copper catalyst is employed and it does not require ligands, proceeds in generally good yields, and has a broad range of functional groups tolerance.

Enantioselective Copper-Catalyzed Three-Component Reaction

Key words copper catalysis - imines - allenes - diboranes - multicomponent reaction

ChemInform Abstract: Copper‐Catalyzed Formal [2 + 2 + 1] Heteroannulation of Alkenes, Alkylnitriles, and Water: Method Development and Application to a Total Synthesis of (.+‐.)‐Sacidumlignan D.

AbstractThe utility of this method is demonstrated in the synthesis of rac‐sacidumlignan D (XIX).

ChemInform Abstract: Synthesis of 2‐Arylbenzothiazoles by Copper‐Catalyzed One‐Pot Three‐Component Reactions in Water.

Copper-catalyzed three-component reactions of 2-iodoanilines, benzylamines, and sulfur powder are reported to afford benzothiazoles in a simple one-pot procedure by using water as solvent. A variety of 2-arylbenzothiazoles were obtained in moderate to good yields up to 88%.

Copper-Catalyzed Three-Component Tandem Cyclization for One-Pot Synthesis of 1,4-Benzothiazines.

A copper-catalyzed three-component tandem reaction has been developed for the convenient and practical synthesis of 1,4-benzothiazines. A variety of terminal alkynes and 2-iodo/bromophenyl isothiocyanates underwent this one-pot cyclization with aqueous ammonia to afford 1,4-benzothiazines in moderate to good yields.

Cu-Catalyzed Three-Component Coupling of Aryne, Alkyne, and Benzenesulfonothioate: Modular Synthesis of o-Alkynyl Arylsulfides.

A copper-catalyzed three-component coupling reaction of in situ formed arynes, terminal alkynes, and benzenesulfonothioates is described. This reaction provides an efficient modular synthesis of o-alkynyl arylsulfides from easily available starting materials. This process involves one C-S bond and one C-C bond formation in one pot.

Solvent-free copper-catalyzed three-component synthesis of 2-substituted quinazolin-4(3H)-ones

A novel and efficient approach for the synthesis of quinazoline-4(3H)-ones through a one-pot copper-catalyzed three-component reaction of isatoic anhydrides, aryl nitriles, and ammonium acetate under solvent-free conditions in good yields is described.

Copper-Catalyzed Formal [2+2+1] Heteroannulation of Alkenes, Alkylnitriles, and Water: Method Development and Application to a Total Synthesis of (±)-Sacidumlignan D.

A copper-catalyzed three-component reaction of alkenes, alkylnitriles, and water affords γ-butyrolactones in good yields. The domino process involves an unprecedented hydroxy-cyanoalkylation of alkenes and subsequent lactonization with the creation of three chemical bonds and a quaternary carbon center. The synthetic potential of this novel [2+2+1] heteroannulation reaction was illustrated by a concise total synthesis of (±)-sacidumlignan D.

Copper-catalyzed three-component synthesis of aminonaphthoquinone–sulfonylamidine conjugates and in vitro evaluation of their antiproliferative activity

A series of aminonaphthoquinone–sulfonylamidine conjugates were synthesized via a copper-catalyzed three-component reaction of N-propargyl aminonaphthoquinone, sulfonyl azides and various amines. Majority of the compounds exhibited promising antiproliferative potential when evaluated against a panel of four cancer cell lines. Docking experiments of representative compounds indicated that the conjugates can occupy the ATP-binding pocket of topoisomerase-II enzyme.