Copper-catalyzed Oxidative Cyclization Research Articles

Sequential Oxidation/Cyclization of Readily Available Imine Linkages to Access Benzoxazole-Linked Covalent Organic Frameworks.

Benzoxazole-linked covalent organic frameworks (BO-COFs), despite their exceptional chemical stability, are still in their infancy. This is primarily because the current prevalent methods require the use of special ortho-hydroxyl-substituted aromatic amines as monomers. Herein, we report an innovative strategy to access BO-COFs directly from imine-linked COFs (Im-COFs) without pre-embedded OH groups, using a two-step sequential oxidation/cyclization process. The two-step process included the oxidation of Im-COFs into amide-linked COFs, followed by a copper-catalyzed oxidative cyclization. Five representative BO-COFs were synthesized with retained crystallinity and high oxidization efficiency, offering the potential to convert a significant portion of Im-COFs into BO-COFs. The structural advantages of the newly designed BO-COFs were demonstrated through their application to photocatalytic organic transformations.

Aliphatic Acylhydrazides as Effective Alkylating Agents for the Copper-Catalyzed Oxidative Cyclization of N-Arylacrylamides

AbstractAn unprecedented use of readily accessible aliphatic acylhydrazides as alkylating agents has been demonstrated in the copper-catalyzed tandem alkylation/cyclization of N-arylacrylamides. A range of aliphatic acylhydrazides smoothly participated in the oxidative 5-exo-trig cyclization of N-arylacrylamides with CuCO3 as the catalyst and DTBP as the oxidant, delivering structurally diverse 3,3-dialkyloxindoles in moderate to good yields. This study paves the way for the synthetic applications of aliphatic acylhydrazides as alkyl radical precursors.

Construction of Spirolactams by Unexpected Oxidative Cyclization of Alkenyl Diynes via Copper Catalysis.

A copper-catalyzed oxidative cyclization of alkenyl N-propargyl ynamides is described. This protocol enables the practical synthesis of diverse spirocyclic γ-lactams bearing an exocyclic double bond with generally high Z/E selectivity in moderate to good yields. Importantly, this copper-catalyzed oxidative cyclization demonstrates a distinctive selectivity in comparison with the related gold catalysis.

Facile access to 2-hydroxy-2-substituted indole-3-ones via a copper-catalyzed oxidative cyclization of 2-arylethynylanilines.

This paper reports a practical and versatile oxidative cyclization of 2-arylethynylanilines towards 2-hydroxy-2-substituted indol-3-ones via a copper-catalyzed radical approach in the presence of O2. The transformation of 2-hydroxy-2-arylindol-3-ones to 3-hydroxy-3-arylindol-2-ones proceeds well with good yields and highlights the practicability and utility of this catalytic system. Mechanistic investigations showed that the acetyl substituent on 2-arylaethynylanilines played an important role in the formation of the cyclic products and the reaction proceeded via an N-center radical-based 5-endo-dig aza-cyclization pathway.

Rapid Access to Functionalized γ-Lactams through Copper-Catalyzed Oxidative Cyclization of Diynes

AbstractAn efficient copper-catalyzed oxidative cyclization of diynes is described. A range of functionalized γ-lactams can be readily constructed by using this protocol. This copper-catalyzed oxidative process proceeds through an alkyne oxidation, carbene/alkyne metathesis, and donor–donor carbene oxidation sequence. The use of readily available substrates, high flexibility, a simple procedure, and mild reaction conditions render the procedure a viable alternative for the preparation of functionalized γ-lactams.

Copper-Catalyzed Oxidative Cascade Cyclization of Activated Alkenes with Azobis Compounds: Access to Cyano-Substituted Benzimidazo[2,1-a]isoquinolin-6(5H)-ones

Copper-Catalyzed Oxidative Cascade Cyclization of Activated Alkenes with Azobis Compounds: Access to Cyano-Substituted Benzimidazo[2,1-a]isoquinolin-6(5H)-ones

Copper-Catalyzed Cyclization/Dimerization of Tryptamines with O2/Air as the Sole Oxidant: Direct Access to Complex Bispyrrolidino[2,3-b]indoline.

The first transition metal catalytic one-step synthesis of the 3a, 3a'-bispyrrolidino [2,3-b] indoline scaffold via tandem cyclization/dimerization of tryptamines has been realized with the environmentally friendly O2/air as the sole oxidant. Different from the traditional direct oxidation of indole "N-H" group by excess amount of metal salts, a copper-catalyzed oxidative cyclization reaction is developed for the formation of the radical pyrrolidinoindoline intermediate in the current strategy. The robustness and practicality of this methodology is demonstrated by the step-economic, divergent total synthesis of natural products (±)-folicanthine and meso-folicanthine.

Aerobic Copper-Catalyzed Intramolecular Cascade Oxidative Isomerization/[4+4] Cyclization of 2,2'-Disubstituted Stilbenes.

An aerobic copper-catalyzed cascade oxidative isomerization/[4+4] cyclization of 2,2'-disubstituted stilbenes is described. Under the mild CuCl/DBED/air catalytic system, various 5,10-heteroatom-containing tetrahydroindeno[2,1-a]indenes were efficiently prepared through the difunctionalizations of alkenes in a highly atom economic manner. Mechanistic investigations suggested the bicyclic product was likely formed through a sequence of rapid single-electron oxidation/[4+4] cyclization from 2,2'-disubstituted stilbene. The antarafacial manner of the thermally allowed [4+4] cyclization was further proven by series of control experiments and density functional theory calculations. Our findings provide an important addition to the aerobic copper-catalyzed oxidative cyclization.

Copper-Catalyzed Aerobic Oxidative Cyclization of 2-Alkynylanilines with Nitrosoarenes: Synthesis of Organic Solid Mechanoluminescence Compounds of 4-Oxo-4H-cinnolin-2-ium-1-ide

An efficient Cu(I)/DMAP/air system for the one-pot synthesis of 4-oxo-4H-cinnolin-2-ium-1-ides, which are often difficult to prepare by traditional routes from substituted 2-alkynylanilines and nitrosoarenes, was developed. These 4-oxo-4H-cinnolin-2-ium-1-ides have practical applications as mechanoluminescent materials. Preliminary mechanistic experiments were performed, and a plausible mechanism for this tandem process is proposed. The use of an inexpensive copper catalyst and molecular oxygen as the oxygen source and the oxidant make this an attractive green protocol with potential synthetic applications.

Copper-catalyzed aerobic oxidative domino cyclization of methyl azaarenes with 6-amino-pyrimidine-2,4-diones and pyrazol-5-amines: access to dipyrimidine/dipyrazolo-fused pyridines

An aerobic copper-catalyzed oxidative domino cyclization of methyl azaarenes with 6-amino-pyrimidine-2,4-diones and pyrazol-5-amines for the synthesis of dipyrimidine/dipyrazolo-fused pyridines was reported.

Visible-light-induced and copper-catalyzed oxidative cyclization of substituted o-aminophenylacetylene for the synthesis of quinoline and indole derivatives

A visible-light-induced and copper-catalyzed oxidative cyclization of substituted o-aminophenylacetylene for the synthesis of quinoline and indole derivatives was developed.

Mild and efficient copper-catalyzed oxidative cyclization of oximes with 2-aminobenzyl alcohols at room temperature: synthesis of polysubstituted quinolines.

A simple and efficient ligand-free Cu-catalyzed protocol for the synthesis of polysubstituted quinolines via oxidative cyclization of oxime acetates with 2-aminobenzyl alcohols at room temperature has been developed. The presented approach provides a new synthetic pathway leading to polysubstituted quinolines with good functional group tolerance under mild conditions. Moreover, this transformation can be applied for the preparation of quinolines on a gram scale. Oxime acetates serve as the internal oxidants in the reactions, thus making this method very attractive.

Copper-catalyzed oxidative cyclization of glycine derivatives toward 2-substituted benzoxazoles.

A novel and straightforward intramolecular cyclization of glycine derivatives to 2-substituted benzoxazoles through copper-catalyzed oxidative C-H/O-H cross-coupling was described. A variety of glycine derivatives involving short peptides underwent cross-dehydrogenative-coupling readily to afford diverse 2-substituted benzoxazoles. The synthetic method has the advantages of simple operation, broad substrate scope and mild reaction conditions, thus providing an alternative effective approach for benzoxazole construction.

Synthesis of 2,1-Benzoisoxazole-Containing 1,2,3-Triazoles through Copper-Catalyzed Three-Component Domino Reactions of o-Bromoacetophenones, Aldehydes, and Sodium Azide

We herein describe an efficient copper-catalyzed three-component domino protocol used to prepare 2,1-benzoisoxazole-containing 1,2,3-triazoles from commercially available o-bromoacetophenones, aldehydes, and sodium azide. This domino process involves Aldol condensation, copper-catalyzed azide-chalcone oxidative cyclization, 1,2,3-triazole-assisted azidation, and denitrogenative cyclization sequences. The formed compounds could be considered as benzo[c]isoxazole-functionalized combretastatin A-4 triazole analogues, which might be potential applications in the discovery of a new anticarcinogen.

Copper-Catalyzed Amination of C(sp3)-H bonds: From Anilides to Indolines.

Copper-catalyzed oxidative intramolecular cyclization of o-alkylated anilines via cleavage of C(sp3)-H and N-H bonds for the production of indolines is described. This approach provides a straightforward strategy for the synthesis of nitrogen-containing heterocyclic compounds through the functionalization of unactivated C(sp3)-H bonds with high site selectivity. The present catalytic system shows high preference for functionalization of unactivated C(sp3)-H bonds over C(sp2)-H bonds, leading to C-N bond formation.

Copper-catalyzed aerobic oxidative cyclization protocol for the synthesis of quinazolines via amination of C(sp3)-H bonds of methylazaarenes

A new aerobic copper-catalyzed three-component synthesis of azaaryl-substituted quinazolines has been developed, which featured inexpensive methylazaarenes as C1 sources, easily available copper salts as the catalysts and O2 as a sole oxidant. The transformation had very good substrate applicability towards methylazaarenes, and various azaaryl-substituted quinazolines were obtained in moderate to good yields.

Copper-Catalyzed Oxidative Cyclization of Benzylamines with 1,3-Dicarbonyl Compounds

Copper-Catalyzed Oxidative Cyclization of Benzylamines with 1,3-Dicarbonyl Compounds

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 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.

Divergent synthesis of N-heterocycles via controllable cyclization of azido-diynes catalyzed by copper and gold

Gold-catalyzed intermolecular alkyne oxidation by an N–O bond oxidant has proven to be a powerful method in organic synthesis during the past decade, because this approach would enable readily available alkynes as precursors in generating α-oxo gold carbenes. Among those, gold-catalyzed oxidative cyclization of dialkynes has received particular attention as this chemistry offers great potential to build structurally complex cyclic molecules. However, these alkyne oxidations have been mostly limited to noble metal catalysts, and, to our knowledge, non-noble metal-catalyzed reactions such as diyne oxidations have not been reported. Herein, we disclose a copper-catalyzed oxidative diyne cyclization, allowing the facile synthesis of a wide range of valuable pyrrolo[3,4-c]quinolin-1-ones. Interestingly, by employing the same starting materials, the gold-catalyzed cascade cyclization leads to the divergent formation of synthetically useful pyrrolo[2,3-b]indoles. Furthermore, the proposed mechanistic rationale for these cascade reactions is strongly supported by both control experiments and theoretical calculations.