Tandem Cyclization Reaction Research Articles

Highly Enantioselective Construction of Chiral Eight-Membered Cyclic Ethers through Tandem Cyclization of Ynones and Dicarbonyl Compounds.

The enantioselective synthesis of eight-membered cyclic ether has always been a challenge in organic synthesis. Herein, we reported a highly enantioselective tandem cyclization reaction of alkyne ketone and dioxypyridines mediated by chiral bifunctional catalysts. This reaction generates two adjacent stereocenters using an atomeconomic manner, providing a simple and effective method for the one-step synthesis of highly enantioselective eight-membered cyclic ethers.

Divergent Sc(OTf)3‐Catalyzed Tandem Cyclization of o‐Hydroxyphenyl Enaminones with 1,3,5‐Triazinanes: Access to C3‐Aminomethyl Chromones and Tetrahydropyrimidines

A Sc(OTf)3‐catalyzed tandem cyclization reaction of o‐hydroxyphenyl enaminones with 1,3,5‐triazinanes has been developed to generate two distinct annulated products in moderate to good yields, which is dominated by the electronic characteristics of the 1,3,5‐triazinanes. The 1,3,5‐triaryl‐1,3,5‐triazinane was treated as C–N synthon to produce C3‐aminomethyl chromone, while the 1,3,5‐trialkyl‐1,3,5‐triazinane acted as C–N–C–N synthons to deliver N,N‐dialkyl tetrahydropyrimidine with a free hydroxyl group.

Manganese-Promoted Cyclization Reaction of Enynones with Tetrasulfides: Synthesis of Multisubstituted Furanmethyl Disulfides.

A tandem cyclization reaction of enynones with tetrasulfides has been developed under manganese-promoted conditions, leading to the high-yield formation of various furanmethyl disulfides. This reaction is characterized by readily available starting materials, mild reaction conditions, and a broad substrate scope, making it attractive and practical. It provides a new strategy for the synthesis of disulfide-containing functionalized furans.

Synthesis of FSO2-Functionalized Oxindoles via a Radical Fluorosulfonylation/Intramolecular Arylation Cascade

Herein, we report the development of a FSO2 radical-initiated tandem cyclization reaction under visible light photoredox catalysis, which allows for a facile access to FSO2-functionalized oxindoles from N-aryl acrylamides. This reaction features mild reaction conditions, readily available starting materials, and SuFExable products. The introduction of sulfonyl fluoride groups into oxindoles could be of interest for the related study in the context of discovering new bioactive molecules.

Diastereoselective Synthesis of Dearomatic 2‐oxa‐7‐azaspiro[4.5]decane Derivatives through Gold and Palladium Relay Catalytic Tandem Cyclization of Enynamides with Vinyl Benzoxazinanones

We present a diastereoselective Au/Pd relay catalytic tandem cyclization reaction to produce dearomatic 2‐oxa‐7‐azaspiro[4.5]decane derivatives under mild conditions. This process involves generating furan‐derived azadiene from readily available enynamide, followed by a [2 + 4] cycloaddition with Pd‐π‐allyl dipole decarboxylated from vinyl benzoxazinanone. Our method efficiently constructs the spiro[4.5]decane skeleton, achieving yields ranging from 31‐97% and diastereoselectivities from 6:1 dr to >20:1 dr across 34 examples. This research introduces new cycloaddition sites for azadienes as 1,2‐dipoles and offers a reliable approach for constructing oxa‐azaspiro[4.5]decane frameworks.

Synthesis of Benzofuran Derivatives via a DMAP-Mediated Tandem Cyclization Reaction Involving ortho-Hydroxy α-Aminosulfones.

An efficient cascade cyclization strategy was developed to synthesize aminobenzofuran spiroindanone and spirobarbituric acid derivatives utilizing 2-bromo-1,3-indandione, 5-bromo-1,3-dimethylbarbituric acid, and ortho-hydroxy α-aminosulfones as substrates. Under the optimized reaction conditions, the corresponding products were obtained with high efficiency, exceeding 95% and 85% yields for the respective derivatives. This protocol demonstrates exceptional substrate versatility and robust scalability up to the Gram scale, establishing a stable platform for the synthesis of 3-aminobenzofuran derivative. The successful synthesis paves the way for further biological evaluations with potential implications in scientific research.

Back Cover

2‐Aminobenzothiazoles derivatives have revealed a broad spectrum of biological activities, such as anti‐HIV, anti‐inflammatory, antioxidant, anti‐microbial, anti‐tumour, anti‐infective, and anti‐convulsant activities. A great amount of 2‐aminobenzothiazole derivatives have been applied in drugs for the treatment of human diseases. A convenient approach for the construction of 2‐aminobenzothiazoles via I2‐catalyzed tandem cyclization reaction of amines and carbon disulfide has been developed. More details are discussed in the article by Deng et al. on page 846—852.image

Rapid Synthesis of 3-Methyleneisoindolin-1-ones via Metal-Free Tandem Reactions of Ester-Functionalized Aziridines.

We have disclosed a novel metal-free tandem cyclization reaction for the synthesis of 3-methyleneisoindolin-1-ones starting from ester-functionalized aziridines. This strategy can be effectively promoted by DBU and carboxylic acids. Mechanistically, it involves sequential ring opening of aziridines with carboxylic acids, lactamization, and elimination of carboxylic acids.

In Situ Activation of Azaarenes and Terminal Alkynes to Construct Bridged Polycyclic Compounds Containing Isoquinolinones.

A copper-catalyzed [4+2] cyclization reaction of isoquinolines and alkynes is developed for the one-step construction of isoquinolinone derivatives with multisubstituted bridging rings. The unique feature of this three-component tandem cyclization reaction is the functionalization of the C1, N2, C3, and C4 positions of 3-haloisoquinolines via the construction of new C-N, C═O, and C-C bonds. This dearomatization strategy for the synthesis of structurally complex isoquinolinone-bridged cyclic compounds offers good chemoselectivity, broad functional group compatibility, greenness, and high step economy.

Synthesis of 1‐(4‐hydroxybutyl)‐2‐benzoyl indoles from 2‐pyrrolidine benzaldehydes and α‐bromoacetophenones in deep eutectic solvent

AbstractA novel and highly efficient method for the synthesis of 1‐(4‐hydroxybutyl)‐2‐benzoyl indoles from 2‐pyrrolidine benzaldehyde and α‐bromoacetophenone in a choline chloride (ChCl)/ZnCl2 eutectic mixture was developed. This method, which does not require any catalyst, additive, or alkali, is useful for realizing tandem cyclization reactions. Several indoles were produced after cyclization and ring opening processes. Not all the compounds obtained are reported in the literature. This synthetic strategy proves that deep eutectic solvents can replace catalysts and organic solvents. Consequently, this is an environmentally friendly strategy that has significant potential in the development of green and sustainable chemistry.

Thioxanthone-based ionic liquid as photocatalyst for a tandem cyclization reaction to synthesize pyrroloquinolinones

Visible light catalysis provides an important platform for developing green and sustainable catalytic processes. However, traditional photosensitizers have limited their application due to their inherent limitations. Due to the structural stability and recyclability of ionic liquids (ILs), a bifunctional catalyst TXIL-Ni was designed and synthesized by introducing the photosensitizer thioxanthone (TX) and transition metal Ni(II) into ILs. TXIL-Ni exhibited remarkable photocatalytic activity for C7–H acylation of indolines to efficiently synthesize pyrroloquinolinone derivatives by a tandem cyclization reaction of decarboxylation acylation and Claisen-Schmidt condensation. The protocol provided a new strategy for the synthesis of the natural product Viridicatol and the key intermediate of farnesyltransferase inhibitors. The experimental results indicated that thioxanthone-based ionic liquid TXIL-Ni as a synergistic photocatalyst has the advantages of mild reaction conditions, recyclability, and atomic economy. This provides a new solution for the design of multifunctional and reusable catalysts.

Metal‐Free Synthesis of 2‐Aminobenzothiazoles via I2‐Catalyzed Tandem Cyclization Reaction of Amines and Carbon Disulfide

Comprehensive SummaryA convenient approach for the construction of 2‐aminobenzothiazoles via I2‐catalyzed tandem cyclization reaction of amines and carbon disulfide has been developed. The present approach starts from simple and readily available starting materials, affording a series of 2‐aminobenzothiazoles in up to 89% yields under metal‐free conditions. In this work, C—H/N—H functionalization was achieved and multiple C‐hetero bonds were successfully constructed in one pot.

Recent advances in the radical cascade reaction for constructing nitrogen heterocycles using azides as radical acceptors.

Due to the high conversion properties, azide compounds are widely utilized in organic synthesis. For instance, azide compounds readily release nitrogen to form a new N-C bond when they function as radical acceptors for the active intermediates in the reaction. Over the past decade, strategies employing azides as radical acceptors to construct nitrogen heterocycles have been extensively developed. This approach has emerged as a crucial method for synthesizing nitrogen heterocycles. Therefore, this paper provides a review of the research advancements in tandem cyclization reactions using azides as radical acceptors, summarizing the process of reaction design, exploration, reasoning of the mechanism, and prospects for further research of these reactions.

NHC catalyzed radical tandem cyclization: an efficient synthesis of α,α-difluoro-γ-lactam derivatives.

Herein, an N-heterocyclic carbene (NHC) catalyzed radical tandem cyclization reaction of N-allylbromodifluoroacetamides and aldehydes has been developed. This method is an efficient protocol for synthesizing α,α-difluoro-γ-lactam derivatives in moderate to good yields (27 examples, up to 88% yield and 10 : 1 dr). This strategy features mild and metal-free conditions, high efficiency, and a broad substrate scope.

Copper-catalyzed tandem cyclization reaction of ethynylbenzoxazinones and thiols: facile construction of 2-thiomethylene indoles.

The first successful copper-catalyzed decarboxylative cyclization reaction of ethynylbenzoxazinones and thiols has been developed. A rarely studied α-addition process to a copper-allenylidene intermediate promoted this reaction. Using this protocol, a range of 2-thiomethylene indole compounds have been obtained. This methodology offers significant advantages including mild reaction conditions, cheap catalysts, good yields and broad substrate compatibility.

Regulatable selective synthesis of benzofurans and coumarins from aryl propargyl ethers via an electrochemical tandem cyclization reaction

A divergent protocol for the selective synthesis of benzofuran-2-carboxaldehydes and 3-organoselenyl-2H-coumarins from propargylic aryl ethers in the presence of dialkyl(aryl) diselenides under electrochemical reaction conditions was established.

Palladium-catalyzed C-H bond activation and decarboxylation for the assembly of indolo[1,2-f]phenanthridine.

A direct and convenient strategy for the assembly of indolo[1,2-f]phenanthridine via a Pd-catalyzed tandem cyclization reaction is presented. The current strategy delivers a range of indolo[1,2-f]phenanthridine derivatives by utilizing readily available 1-(2-iodophenyl)-1H-indole and commercially available o-bromobenzoic acids as the starting materials. The reaction features the formation of two C-C bonds through Pd-catalyzed C-H bond activation and decarboxylation.

Silver-catalyzed cascade cyclization for the synthesis of 4-aminotetrahydrocarbazole.

A silver-catalyzed cascade cyclization strategy has been developed for the synthesis of 4-aminotetrahydrocarbazole, a common core structure found in various alkaloids. This target molecule can be synthesized through a one-step tandem cyclization reaction, thereby eliminating the need for a prior synthesis of tetrahydrocarbazole. Furthermore, the use of chiral tert-butylsulfinamide facilitates in situ chiral resolution of the resulting product.

Electrochemically Driven Tandem Cyclization Reaction of Unsaturated Sulfoximines with Diselenides

AbstractAn electrochemically enabled tandem cyclization reaction of unsaturated sulfoximines with diselenides has been well developed, affording metal‐ and external oxidant‐free access to sulfoximidoyl‐based heterocycles containing selenium in moderate to good yields. With nBu4NBr as the role of catalyst and electrolyte, this methodology shows broad substrate scope and functional group tolerance under mild conditions.

Metal‐catalyzed Cyanoalkylsulfonylation/Cyanoalkylation of N‐propenyl‐2‐Benzimidazole: Access to Cyanoalkylsulfonyl/Cyanoalkylbenzimidazole[2,1‐a] Iso‐Quinoline‐6(5H)‐Ones

AbstractThe three‐component cyanoalkylsulfonylation cyclization reaction of N‐methacryloyl‐2‐phenylbenzimidazole, DABCO ⋅ (SO2)2 and cyclobutanone oxime ester regulated by different metals (iron and nickel) and the two‐component cyanoalkylation cyclization reaction of DABCO ⋅ (SO2)2 as oxidant were described. The tandem cyclization route allows different cyanoalkylsulfonylated benzimidazole [2,1‐a] iso‐quinoline‐6(5H)‐ones/cyanoalkylated benzimidazole [2,1‐a] iso‐quinoline‐6(5H)‐ones to be obtained in moderate to good yields under mild conditions, with good functional group tolerance, readily available starting materials, and simple operation. In addition, experiments show that the tandem cyclization reaction was a free radical reaction process.