Copper-catalyzed Cascade Research Articles

Cu-Catalysed synthesis of benzo[f]indole-2,4,9(3H)-triones by the reaction of 2-amino-1,4-napthoquinones with α-bromocarboxylates.

A copper-catalysed cascade ester amidation/radical cyclization of 2-amino-1,4-naphthoquinones with α-bromocarboxylates to afford benzo[f]indole-2,4,9(3H)-triones is described, and the reaction has a broad substrate scope and the desired products are obtained in mostly moderate to good yields. Mechanism-probing experiments indicate that the otherwise challenging radical coupling reaction of α-bromocarboxylates with 2-amino-1,4-naphthoquinones is facilitated by a 5-endo radical cyclization.

Copper-catalyzed cascade cyclization reaction of 3-aminocyclobutenones with electron-deficient internal alkynes: synthesis of fully substituted indoles.

A novel copper-catalyzed cascade cyclization reaction of 3-aminocyclobutenones with electron-deficient internal alkynes has been developed for the first time. This reaction provides a new and highly efficient method for the synthesis of fully substituted indoles by formation of four new bonds and two rings from readily available starting materials in a single step.

Copper-catalyzed cascade three-component azide–alkyne cycloaddition/condensation/transesterification: easy access to 3-triazolylcoumarins

A novel and efficient strategy has been developed for the synthesis of 3-triazolylcoumarins in a one-pot, copper-catalyzed multicomponent reaction involving a cascade reaction of salicylaldehydes, ethyl 2-azidoacetate, and arylacetylenes.

Copper(I)-Catalyzed Synthesis of Functionalized Indolizinones from Substituted Pyridine Homologated Ynones.

An efficient two-component copper-catalyzed cyclization cascade approach toward highly functionalized indolizinone heterocycles has been developed from reactions of pyridine-, isoquinoline-, and quinoline ynones, via 5-exo-dig cyclization. The catalysis involves the activation by diorgano diselenide and diorgano disulfide and also their incorporation into the indolizinone core. In addition, the obtained substituted indolizinones were readily transformed into 1-(organochalcogenyl)indolizin-2-ols, which are important building blocks in organic synthesis.

Copper-Catalyzed Three-Component Radical Cascade Generating Congested Dihydropyrrolones

Copper-Catalyzed Three-Component Radical Cascade Generating Congested Dihydropyrrolones

Copper-Catalyzed Cascade Cyclization Reaction of Enamines and Electron-Deficient Terminal Alkynes: Synthesis of Polysubstituted Pyrido[1,2-a]indoles.

A novel copper-catalyzed cascade cyclization reaction between enamines and electron-deficient terminal alkynes has been developed. The reaction provides a new and efficient strategy for the construction of polysubstituted pyrido[1,2-a]indoles by the formation of two rings, three C-C bonds, and one C-N bond in a single step from readily available acyclic starting materials.

Copper-Catalyzed Cascade Cyclization Reactions of Diazo Compounds with tert-Butyl Nitrite and Alkynes: One-Pot Synthesis of Isoxazoles.

A novel copper-catalyzed [3 + 2] cycloaddition reaction of alkynes with nitrile oxides generated in situ from the coupling reaction of copper carbene and nitroso radical has been developed. The three-component reaction provides a simple and efficient method for the construction of isoxazoles in a highly regioselective manner in a single step. On the basis of the experimental results and density functional theory calculations, a catalytic cycle (CuI-CuII-Cu0-CuI) for this cascade cyclization reaction is proposed.

Copper-Catalyzed Cascade Cyclization of Arylsulfonylhydrazones Derived from ortho-Alkynyl Arylketones: Regioselective Synthesis of Functionalized Cinnolines.

A novel copper-catalyzed cascade reaction of arylsulfonylhydrazones derived from ortho-alkynyl arylketones was accomplished. This reaction provides concise access to diversified cinnolines in good yields. The mechanistic investigations have disclosed involvement of the key alkynyl amination, 1,4-aryl migration, desulfonylation, and diazo radical cyclization cascade in the transformation.

Copper-Catalyzed Alkynylation/Cyclization/Isomerization Cascade for Synthesis of 1,2-Dihydrobenzofuro[3,2-b]pyridines and Benzofuro[3,2-b]pyridines.

An efficient copper-catalyzed cascade alkynylation/cyclization/isomerization reaction of aurone-derived azadienes with terminal alkynes has been developed, giving a series of 1,2-dihydrobenzofuro[3,2-b]pyridines with excellent yields. The obtained 1,2-dihydrobenzofuro[3,2-b]pyridines can be conveniently transformed into the corresponding benzofuro[3,2-b]pyridines under basic conditions. Additionally, benzofuro[3,2-b]pyridines can also be prepared from azadienes and terminal alkynes in a one-pot reaction. The synthetic utility was demonstrated by the synthesis of three bioactive molecules with potent topoisomerase inhibition in high yields. This strategy provides a facile approach to 1,2-dihydrobenzofuro[3,2-b]pyridines and benzofuro[3,2-b]pyridines.

Copper-Catalyzed Cascade Denitrogenative Transannulation/Hydrolyzation of 3-Aminoindazoles toward 2,2-Disubstituted Indanones.

A copper-catalyzed cascade denitrogenative transannulation/hydrolyzation of 3-aminoindazoles with N-(2-methylallyl)anilines was developed, affording a variety of 2-(aminomethyl)-2-methyl-indanones in moderate to good yields. 2-Cyanophenyl radical, which generated from oxidative denitrogenation of 3-aminoindazole, was proved as the reaction intermediate. This reaction features, along with the ready availability of starting materials, a cascade cleavage of two C-N bonds and construction of two C-C bonds in one pot.

Copper-Catalyzed Three-Component Cascade Michael Addition/Heck-Type Alkylation/Annulation: Accessing Fully Substituted 1,3-Dihydro-2H-pyrrol-2-ones.

We report a highly efficient copper-catalyzed three-component reaction of alkylamines, acetylenedicarboxylates, and α-bromocarbonyls for the assembly of fully substituted 1,3-dihydro-2H-pyrrol-2-ones. A variety of alkylamines and ammonium salt are functionalized with acetylenedicarboxylates and α-bromocarbonyls. N-aryl enaminoesters are also successfully alkylated with α-bromocarbonyls. This protocol is understood to proceed through radical Heck-type coupling of in-situ-generated bulky trisubstituted alkenes with bulky tertiary alkyl bromides, which is realized for the first time.

Generation of Donor/Donor Copper Carbenes through Copper-Catalyzed Diyne Cyclization: Enantioselective and Divergent Synthesis of Chiral Polycyclic Pyrroles.

The generation of metal carbenes from readily available alkynes represents a significant advance in metal carbene chemistry. However, most of these transformations are based on the use of noble-metal catalysts and successful examples of such an asymmetric version are still very scarce. Here a copper-catalyzed enantioselective cascade cyclization of N-propargyl ynamides is reported, enabling the practical and atom-economical construction of diverse chiral polycyclic pyrroles in generally good to excellent yields with wide substrate scope and excellent enantioselectivities (up to 97:3 e.r.). Importantly, this protocol represents the first copper-catalyzed asymmetric diyne cyclization. Moreover, mechanistic studies revealed that the generation of donor/donor copper carbenes is presumably involved in this 1,5-diyne cyclization, which is distinctively different from the related gold catalysis, and thus it constitutes a novel way for the generation of donor/donor metal carbenes.

Direct Access to Trifluoromethyl-Substituted Carbamates from Carbon Dioxide via Copper-Catalyzed Cascade Cyclization of Enynes.

A copper-catalyzed cascade cyclization of enynes with Togni's reagent, carbon dioxide, and amines has been successfully developed. The reaction provides a direct and efficient route to a range of trifluoromethyl-substituted carbamates, which are difficult to access using existing methods. Mild reaction conditions, good functional tolerance, and wide substrate scope are the feactures of the protocol.

Recent Progress in the Copper-Catalyzed Cascade Cyclization Involving Intramolecular Hydroamination of Terminal Alkynes

Transition-metal-catalyzed cascade cyclization initiated by intramolecular alkyne hydroamination has received considerable attention over the past decade and has been widely used in the rapid construction of a diverse array of valuable complex N-heterocycles. Recent progress in this area is reviewed with an emphasis on the cheap and environmentally benign copper-catalyzed cascade cyclization of terminal alkynes.

Copper-catalyzed radical cascade reaction of isocyanate and ethers

A novel copper-catalyzed amination of ethers using isocyanates and DTBP is developed. The reaction provides a unique approach to the synthesis of Boc-protected α-aminals through three-component radical cascade reactions. It provides an alternative method for the construction of this type of valuable motifs in high yield. Meanwhile, the method exhibits high tolerance of various functional groups, such as ether, halide, ester and acyl functionalities.

Copper-Catalyzed Cascade Cyclization of Indolyl Homopropargyl Amides: Stereospecific Construction of Bridged Aza-[n.2.1] Skeletons.

Catalytic cycloisomerization-initiated cascade cyclizations of terminal alkynes have received tremendous interest, and been widely used in the facile synthesis of a diverse array of valuable complex heterocycles. However, these tandem reactions have been mostly limited to noble-metal catalysis, and are initiated by an exo-cyclization pathway. Reported herein is an unprecedented copper-catalyzed endo-cyclization-initiated tandem reaction of indolyl homopropargyl amides, where copper catalyzes both the hydroamination and Friedel-Crafts alkylation process. This method allows the practical and atom-economical synthesis of valuable bridged aza-[n.2.1] skeletons (n=3-6) with wide substrate scope, and excellent diastereoselectivity and enantioselectivity by a chirality-transfer strategy. Moreover, the mechanistic rationale for this novel cascade cyclization is also strongly supported by control experiments, and is distinctively different from the related gold catalysis.

A Highly Efficient Heterogeneous Copper-Catalyzed Oxidative Cyclization of Benzylamines and 1,3-Dicarbonyl Compounds To Give Trisubstituted Oxazoles

The heterogeneous copper-catalyzed cascade oxidative cyclization between benzylamines and 1,3-dicarbonyl compounds was achieved by using the 3-(2-aminoethylamino)propyl-functionalized MCM-41-immobilized copper(II) complex [MCM-41-2N-Cu(OAc)2] as catalyst and t-BuOOH (TBHP) as oxidant, with iodine as additive, under mild conditions, yielding a wide variety of 2,4,5-trisubstituted oxazoles in mostly good to excellent yields. This heterogeneous copper catalyst can be facilely prepared via a simple two-step procedure from readily available and inexpensive reagents and exhibits a slightly higher activity than Cu(OAc)2. MCM-41-2N-Cu(OAc)2 is also easy to recover and can be recycled up to eight times with almost consistent activity. The reaction is the first example of heterogeneous copper-catalyzed intermolecular cyclization for the construction of polysubstituted oxazoles.

Copper-catalyzed cascade click/nucleophilic substitution reaction to access fully substituted triazolyl-organosulfurs.

A novel cascade click/nucleophilic substitution reaction is developed to access 4-heterofunctionalized fully substituted triazolyl-organosulfurs using thiocyanates as both leaving groups and organosulfur precursors. This method features high regioselectivities and board substrate scope. 33 examples are shown to demonstrate the structural diversity through the synthesis of fully substituted triazolyl-organosulfurs including triazolyl-thiocyanates, triazolyl-sulfinylcyanides, triazolyl-thioethers, triazolyl-thiols and triazolyl-disulfides from internal thiocyanatoalkynes.

Direct Synthesis of Benzo[ f]indazoles from Sulfonyl Hydrazines and 1,3-Enynes by Copper-Catalyzed Annulation.

A novel and efficient strategy for the direct synthesis of benzo[ f]indazoles via copper-catalyzed cascade reaction of sulfonyl hydrazides with 1,3-enynes under mild conditions has been developed. This method achieves the formation of two C-N bonds and one C-C bond in one pot, providing a series of benzo[ f]indazoles in moderate to good yields with good functional group tolerance and remarkable regioselectivity.

Efficient and selective microwave-assisted copper-catalyzed synthesis of quinazolinone derivatives in aqueous

Microwave-assisted copper-catalyzed cascade reactions between 2-halobenzoic acids and amidines to synthesize quinazolinone derivatives in water are reported. A variety of target products were obtained in good to excellent yields up to 94%. Its application was performed by the synthesis of 4-(1H-benzo[d]imidazol-2-ylthio)-6-methoxypteridine, which displayed significant anti-proliferation effect.