Copper-catalyzed Tandem Reaction Research Articles

Enantioselective formal total synthesis of dihydrospirotryprostatin B

Spirotryprostatins are representative members of medicinally interesting bioactive molecules of the spirooxindole natural products. In this communication, we present a novel enantioselective total synthesis of the spirooxindole alkaloid dihydrospirotryprostatin B. The synthesis takes advantage of copper-catalyzed tandem reaction of o-iodoanilide chiral sulfinamide derivatives with alkynone to rapidly construct the key quaternary carbon stereocenter of the natural product dihydrospirotryprostatin B.

Synthesis of 2-iminothiazolidin-4-ones via copper-catalyzed [2 + 1 + 2] tandem annulation.

In this paper, an efficient synthesis of 2-iminothiazolidin-4-ones through a copper-catalyzed tandem annulation reaction of alkyl amines, isothiocyanates and diazo acetates is presented. Notable advantages of this [2 + 1 + 2] cyclization methodology include readily accessible starting materials, simple operation, mild reaction conditions, high yields, step-economy and diverse functional group tolerance. In addition, the reaction is applicable to the gram scale synthesis and the preparation of bioactive molecules.

Merging Ullmann-type cyclization and ring-expansion: a facile assembly of pyrimidine-fused quinazolinones by copper catalysis

A copper-catalyzed tandem cyclization reaction of readily available 4-bromoisatins and amidine hydrochlorides has been developed for the first time, enabling the efficient synthesis of pyrimidoquinazolinones in useful yields.

Directed Copper-Catalyzed Tandem Radical Cyclization Reaction of Alkyl Bromides and Unactivated Olefins.

The free radical cyclization reaction is a promising strategy for ring framework formation. Herein, we report a copper-catalyzed tandem radical cyclization strategy for preparing substituted lactam derivatives. This reaction proceeds through a radical coupling approach, which not only allows a wide range of alkenes but also is quite compatible with the primary, secondary, and tertiary radicals. In addition, density functional theory calculations were performed to gain insights into the reaction mechanism.

Synthesis of acridines via copper-catalyzed amination/annulation cascades between arylboronic acids and anthranils.

Copper-catalyzed tandem cyclization reactions between arylboronic acids and anthranils have been established, providing new approaches for one-pot assembly of azacycle acridines. This one-pot protocol features simple operation, precious-metal-free conditions and good functional group compatibility, thus providing an efficient approach for the synthesis of a variety of acridines in moderate to good yields.

Copper-catalyzed tandem reaction of cyclic esterification/selenoxide for 11-oxo-11H-5-oxa-11-selena-benzo[a] fluoren-6-ones synthesis

Copper-catalyzed tandem reaction of cyclic esterification/selenoxide for 11-oxo-11H-5-oxa-11-selena-benzo[a] fluoren-6-ones synthesis

Copper-Catalyzed Tandem Cross-Coupling/Thermally Promoted [2 + 2] Cycloaddition of 1,6-Enynes and Diazo Compounds To Assemble Methylenecyclobutane-Fused Ring System.

An unprecedented copper-catalyzed tandem reaction of 1,6-enynes with diazo compounds via a cross-coupling/[2 + 2] cycloaddition sequence was reported. A library of methylenecyclobutane-fused ring systems including cyclobuta[b]indolines, cyclobuta[b]benzofuran, benzo[b]cyclobuta[d]thiophene, and bicyclo[3.2.0] structures were obtained in moderate to excellent yields under very mild reaction conditions. The reaction exhibited high proximal-regioselectivity and diastereoselectivity. Moreover, 1,6-allenene has proven to be the key intermediate and proceeds via a thermally promoted [2 + 2] cycloaddition in the absence of copper catalyst.

Synthesis of 1,2,3-Triazole-Fused Indole Derivatives via Copper-Catalyzed Cascade Reaction

AbstractA copper-catalyzed tandem reaction has been developed for the synthesis of 1,2,3-triazole-fused indole derivatives. This protocol allowed us to access a wide range of 1,2,3-triazole-fused indole derivatives in moderate to excellent yields. The 1,2,3-triazole-fused indole derivatives emit blue and greenish light when excited at 365 nm. The products were further explored for their quantum efficiency and photophysical properties.

Copper(I)-catalyzed tandem synthesis of 2-acylquinolines from 2-ethynylanilines and glyoxals.

An efficient one-step synthesis of 2-acylquinolines using a copper-catalyzed tandem reaction of 2-ethynylanilines with glyoxals in the presence of piperidine has been developed. This new protocol successfully avoids multi-step operation and the use of highly toxic cyanides required in traditional methods, and provides a practical tool for synthetic and pharmaceutical chemists. Various 2-acylquinolines are obtained with perfect regioselectivity in moderate to good yields (up to 86%). The potential synthetic utility of this method is exemplified by a large-scale experiment and synthetic transformation of the products.

Copper-Catalyzed Tandem Reactions of 2-Amine-[1,3,5]triazines with Nitriles.

Copper-catalyzed intermolecular annulation of 2-amine-[1,3,5]triazines and aryl nitriles for the synthesis of [1,2,4]triazolo[1,5- a][1,3,5]triazines via N-C bond formation and oxidative N-N coupling [oxidative 3 + 2 cyclization] is presented. A wide range of aryl nitriles, including electron-rich benzonitriles, electron-poor benzonitriles, 2-cyanothiophene, and 4-cyanopyridine, were all functionalized with 2-amine-[1,3,5]triazines. Furthermore, amidation of 2-amine-[1,3,5]triazines via Cu-catalyzed C-CN bond cleavage of phenylacetonitriles is also demonstrated. The reaction occurred in moderate to satisfactory yields and tolerated alkyl- or aryl-substituted 2-amine-[1,3,5]triazines. Aniline, aminopyridine, and aminopyrimidine also afforded the desired products.

One-Pot Synthesis of 4-Sulfonyliminotetrahydropyrimidin-2-one Derivatives through a Copper-Catalyzed Tandem Reaction

A novel and efficient synthesis of 4-iminotetrahydropyrimidin-2-one derivatives was developed through a Cu(I)-catalyzed three-component tandem reaction employing propargylamines, isocyanates, and sulfonyl azides as starting materials. A wide range of polysubstituted 4-sulfonyliminotetrahydropyrimidin-2-ones, which might be useful in biological chemistry and medicinal science, were conveniently and efficiently assembled in one pot.

One-pot synthesis of [1,2,4]Triazolo[1,5-a]pyridines from azines and benzylidenemalononitriles via copper-catalyzed tandem cyclization

A simple and efficient copper-catalyzed tandem radical cyclization reaction has been discovered for the synthesis of triaryl [1,2,4]triazolo[1,5-a]pyridines from easily accessible azines and benzylidenmalononitriles. The new transformation involves multiple CH/CC bonds cleavage and CC/CN bonds formation, with extrusion of gaseous hydrogen and methane. A wide variety of substrates with different functional groups could be converted into the corresponding products in good yields. The fused heterocycles have strong blue fluorescence with large Strokes shifts and high quantum yields.

Copper-catalyzed tandem reaction of 2-alkynylanilines with benzoquinones: efficient access to 3-indolylquinones.

A simple, mild, catalytic and efficient method for the straightforward synthesis of an interesting class of 2-aryl/alkyl-substituted-3-indolyl quinones in good to high yields is reported for the first time. This atom-efficient method proceeds via copper-catalyzed one-pot sequential intramolecular hydroamination (C–N bond formation) of 2-alkynylanilines followed by oxidative C–C coupling with benzoquinones.

Synthesis of 2-Pyridinemethyl Ester Derivatives from Aldehydes and 2-Alkylheterocycle N-Oxides via Copper-Catalyzed Tandem Oxidative Coupling-Rearrangement.

Successful benzylic C(sp3)-H acyloxylation of 2-alkylpyridine, 2-alkylpyrazine, and 2-alkylthiazole compounds was achieved using simple aldehydes. This was carried out via a copper-catalyzed tandem reaction, involving oxidative esterification followed by O-atom transfer of the resultant high yield formed Boekelheide intermediate. The method enables the preparation of functional heterocycles and the desymmetrization of 2,6-dialkylpyridines for efficient synthesis of dissymmetric pincer ligands, thus offering a new life for more practical Boekelheide rearrangement.

A Copper-Catalyzed Tandem Cyclization Reaction of Aminoalkynes with Alkynes for the Construction of Tetrahydropyrrolo[1,2-a]quinolines Scaffold

A synthetic method for diversely substituted tetrahydropyrrolo[1,2-a]quinolines was developed via CuCl-catalyzed cascade transformation of internal aminoalkynes with alkynes under microwave- irradiation.

Copper-catalyzed tandem reaction directed toward synthesis of 2,2-disubstituted quinazolinones from vinyl halides and 2-aminobenzamides

A copper-catalyzed tandem reaction with vinyl halides and 2-aminobenzamides has been developed. In this synthetic route, cross-coupling reaction of the amide moiety with vinyl halides initially progresses, followed by hydroamination, to provide 2,2-disubstituted quinazolinone derivatives. Moreover, the tandem reaction is used in a one-pot synthesis beginning with alkyne hydroiodination by PPh3, I2, and H2O.

Diversified Synthesis of 2-(4-Oxo[1,2,3]triazolo[1,5-a]quinoxalin-5(4H)-yl)acetamide Derivatives through Ugi-4-CR and Copper-Catalyzed Tandem Reactions

A diversified synthesis of 2-(4-oxo[1,2,3]triazolo-[1,5-a]quin­oxalin-5(4H)-yl)acetamide derivatives is demonstrated. The protocol employs a Ugi four-component reaction for the assembling of N-(2-haloaryl)propynamide intermediates and followed by a copper-catalyzed tandem reaction of the synthetic N-(2-haloaryl)propynamides with sodium azide. Such a method provides rapid access to structurally varied and complex fused tricyclic scaffolds through readily available starting materials.

Copper-Catalyzed Tandem Reaction of Terminal Alkynes and Sulfonyl Azides for the Assembly of Substituted Aminotriazoles.

A simple combination of CuI/LiOtBu/DMF enables the tandem Huisgen [3 + 2] cycloaddition/amidation reaction of terminal alkynes and sulfonyl azides to 5-sulfamide-1-(N-sulfonyl)-1,2,3-triazoles I, which can undergo an alkylation/desulfonation sequence to deliver highly substituted aminotriazoles II by one-pot or one-pot, two-step procedures.

Copper-catalyzed tandem reaction of 2-haloanilines with thiocarbamoyl chloride: Synthesis of 2-aminobenzothiazoles

ABSTRACTA simple and efficient protocol for the synthesis of 2-aminobenzothiazoles by a ligand-free copper-catalyzed tandem reaction has been developed. In the presence of CuBr and t-BuOK, a variety of 2-haloanilines (halogen = Br, I) underwent the reaction with thiocarbamoyl chloride efficiently to afford the corresponding 2-aminobenzothiazoles in good yields (83–94%). The features of this method include good yield, cheap catalyst, mild reaction conditions, and broad substrate scope, which make the protocol practical and attractive in the preparation of some potential pharmaceutically active compounds.

Copper-catalyzed tandem aryl-halogen hydroxylation and CH2Cl2-based N,O-acetalization toward the synthesis of 2,3-dihydrobenzoxazinones.

The concise synthesis of 2,3-dihydro-4H-benzo[e][1,3]oxazin-4-ones has been accomplished by copper-catalyzed tandem reactions of o-halobenzamides, LiOH and dichloromethane. The aryl-halogen bond hydroxylation and subsequent N,O-acetalization on CH2Cl2 are enabled under catalytic conditions which allows the generation of C(sp2)-O, C(sp3)-O and C(sp3)-N bonds to give the target products.