ABSTRACT 3‐(2‐formylcycloalkenyl)‐acrylic ester (FCAE) acts as an important building block in synthetic organic chemistry. Co‐existence of α, β‐unsaturated ester and α, β‐unsaturated aldehyde makes it a useful scaffold for the synthesis of diverse carbocyclic and heterocyclic compounds through Michael addition, condensation reaction, coupling reaction, multicomponent reaction, cascade cyclization, functional group conversion, and asymmetric synthesis. The literature covers the area since last couple of decades. In this review, we outline the various pathways for bicyclic, tricyclic, tetracyclic, pentacyclic, and polycyclic heterocyclic scaffolds with their mechanistic details.

Site-selective reactions are important tools in the synthesis of useful multisubstituted compounds, including pharmaceuticals and functional molecules. Such reactions convert functional groups in a selective manner, thereby enabling the synthesis of various compounds with different substitution patterns from a single starting compound. Although a number of transition metal-catalyzed site-selective reactions have been developed, site-selectivity is usually controlled by the substrate, limiting the scope of the reaction. In contrast, catalyst-controlled site-selective reactions of single substrates have been reported, wherein ligand-controlled reactions are of particular interest. Previously, our group developed hydroxyterphenylphosphine ligands to achieve the palladium-catalyzed ortho-selective cross-coupling reactions of dihalogenated phenols/anilines. In this system, the hydroxy groups of the ligand bind to the substrate via the metal, and the proximity of palladium to the halogen at the ortho-position accelerates the reaction at this less reactive position. These reactions have been employed to synthesize multisubstituted benzofurans and indoles from dichlorophenols/anilines using a one-pot ortho-selective Sonogashira coupling/cyclization/Suzuki-Miyaura coupling protocol. The developed catalyst also has enabled the direct C3-selective arylation of N-nonsubstituted indoles, and both tricyclic pyrroloindolines and pyridoindolines have been obtained from tryptamine derivatives via a C3-dearomative arylation/cyclization strategy. Furthermore, the site-selective arylation of N-nonsubstituted 1H-pyrroles has been achieved by changing the ligand, and the reaction proceeded selectively at the C2 or C3 position, yielding 2,2,5-trisubstituted 2H-pyrroles and other compounds whose preparation is challenging via conventional approaches. Finally, the regioselective synthesis of polycyclic aromatic compounds using appropriate palladium catalysts has been performed using the site-selective approach.

A novel and highly efficient heterogeneous bioorganic nanocatalyst for the green synthesis of diverse heterocyclic compounds

Performance comparison of magnetically recoverable Fe3O4-chitosan nanocatalysts in the sustainable synthesis of heterocyclic compounds

Aliphatic azo compounds as programmable nitrogen donors in alkyne-mediated heterocycle synthesis: Implications for medicinal chemistry.

Sustainable sonochemistry in medicinal heterocycle design: Advances and anticancer implications.

Magnetic carbon nanotubes in multicomponent reactions: A path to sustainable heterocyclic synthesis

Redox-Active Cobalt Substituted Manganese Spinel Ferrite as Recyclable Catalyst for Multicomponent Heterocyclic Synthesis

Morden organic synthesis prizes efficiency, robustness, and generality─hallmarks of click chemistry. Here, we introduce a metal-free catalytic method for synthesizing diverse tetrazole heterocycles from simple, shelf-stable precursors. Central to this powerful strategy is leveraging cyclopropenium ions as phase-transfer catalysts, providing a practical and efficient approach to tetrazoles from nitriles and azides. The scope, mechanism, and synthetic utility of this methodology are detailed, highlighting its potential to expand the click chemistry tool box for heterocycle synthesis.

Utilization of Magnetic Covalent Organic Framework (COF) as an Efficient Catalyst in the Synthesis of Nitrogen-Containing Heterocyclic Compounds: Relevance in Sports Recovery of Athletes and Regenerative Biochemistry

The review discusses the utility of C-H functionalization approaches involving alkynes, which act as multifaceted coupling partners due to their unsaturation property, small size, and potential to participate in multiple reaction pathways, such as annulations, alkylation, alkenylation, and alkynylation. The review emphasises the investigation of palladium catalysis for these transformations. It highlights the developments in Pd-catalysed C-H functionalization-based synthesis of simple and complex carbo- and heterocyclic compounds, as well as biologically active and alkynyl-functionalized molecules.

Abstract:: A novel electrochemical iodocyclization of N-alkylated alkenyl ureas has been developed, offering a direct and sustainable route to iodinated imidazolidin-2-ones. The method utilizes in situ electrooxidation of potassium iodide (KI) to generate active iodine species, eliminating the need for catalysts or external oxidants. Reactions proceed under mild conditions (room temperature, methanol) and exhibit broad substrate scope, tolerating various aryl substituents. Moderate to good yields (up to 72%) have been achieved. Mechanistic studies, including radical trapping and cyclic voltammetry, suggest a cationic pathway initiated by anodic iodide oxidation. Compared to traditional harsh methods, this electrochemical approach provides a greener, operationally simple synthesis of these privileged heterocycles.

A highly efficient enantioselective hydrogenation of polynitrogen heterocycle-substituted phenylacrylonitriles catalyzed by the Rh-f-spiroPhos complex has been developed. A series of chiral α- and β-polynitrogen heterocycle-substituted nitriles were obtained in high yields (up to 99%) with excellent enantioselectivities (up to 99.9% ee). This method provides an efficient straightforward approach for synthesis of chiral polynitrogen heterocycles, which is one of the most important and prevalent structures in pharmaceuticals and natural products.

Nitro-functionalized compounds and their derivatives have attracted considerable attention because of their synthetic value/special biological activities. Direct cascade cyclization reactions of unsaturated hydrocarbons with nitro-reagents are of particular interest to the chemical community because these strategies provide opportunities for the introduction of important nitro groups onto target frameworks with high step and atom economy. In recent years, tert-butyl nitrite (TBN) has shown considerable promise in cascade cyclization reactions due to its distinctive chemical properties, offering a novel platform for the efficient and diverse synthesis of heterocyclic compounds. This review highlights recent advances in this field, categorizing the discussion by reaction substrates and featuring representative examples and mechanisms. It also addresses the current challenges and future research directions.

Copper- and silver-catalyzed reactions of active methylene isocyanides provide powerful and versatile strategies for the construction of heterocyclic architectures relevant to pharmaceutical and materials science. Owing to their unique ambiphilic reactivity, active methylene isocyanides serve as key building blocks for the synthesis of fused, bicyclic, polycyclic, and spirocyclic heterocycles under mild catalytic conditions. This review summarizes recent advances in the copper- and silver-catalyzed transformation of functionalized isocyanides toward multi-substituted five- and six-membered heterocyclic frameworks. Particular emphasis is placed on [3+n] cycloaddition reactions, as well as tandem processes involving cycloaddition, annulation, alkylation, and insertion pathways. In addition, emerging strategies that exploit nonfunctionalized isocyanides, strained alkene surrogates, and multi-isocyanide reaction manifolds are discussed, highlighting new opportunities for complexity generation and asymmetric heterocycle synthesis.

Cycloalkynes are highly reactive coupling partners in a variety of cycloaddition manifolds, but the synthetic utility of cycloalkynes with fewer than 8 atoms is limited by their fleeting stability. To expand access to heterocycles derived from formal cycloadditions to cycloalkynes, we have developed a methodology in which alkenylthianthrenium salts are used as synthetic equivalents of cycloalkynes in reactions with azides. This methodology enables expedient access to a variety of 1,2,3-triazoles from alkene building blocks in two steps, including triazoles fused with 5-, 6-, 7-, and 8-membered carbocycles. Rather than serving as precursors to in situ-generated alkynes, we discovered that many alkenylsulfonium salts react with azides as dipolarophiles, generating 1,2,3-triazoles via a distinct cycloaddition-elimination mechanism. We show that this methodology is viable for both acyclic and cyclic alkenylsulfonium salts and demonstrate its applications as a tool for the synthesis of new small molecule heterocycles and functional polymeric materials.

Nitrenes serve as key reactive intermediates in ring-closing C-H amination reactions for the synthesis of heterocyclic compounds. In this study, we established an efficient method for preparing disubstituted oxindoles using iminophosphoranes as effective nitrene precursors. Our findings demonstrate that iminophosphoranes, upon activation by m-CPBA, can generate nitrene intermediates that enable ring-closure C-H amidation reactions. Detailed mechanistic insights were obtained through density functional theory (DFT) calculations and supporting control experiments. This protocol demonstrates excellent scalability to gram quantities and has been successfully applied in the total synthesis of the natural product coixspirolactam A and the bioactive CRTH2 receptor antagonist, underscoring its practical synthetic utility.

Hydroisoquinoline and benzosultam motifs represent privileged heterocyclic frameworks with broad pharmacological relevance. We report a divergent photoredox strategy that enables selective access to both scaffolds from a simple precursor. The transformation proceeds via radical addition to an unactivated olefin followed by a domino cyclization. While conventional reactivity strongly favors hydroisoquinoline formation, we discovered that chain-length modulation imposes ring strain on the arene pathway, thereby suppressing the competing cyclization and promoting the challenging sulfonyl-arene closure. This strain-guided approach offers a unified entry to hydroisoquinolines and benzosultams under mild conditions, expanding the toolkit for heterocycle synthesis.

This study investigates the green methods of making heterocyclic compounds with safe catalysts. Results are analyzed using data-driven techniques to assess their efficiency, spectral authenticity and activity towards living organisms. For this study, a set of 1000 heterocycles was made using experimental values from the literature for reaction yield, melting point, NMR, IR, UV-V is spectra and both antioxidant and antimicrobial properties. The investigation of interactions between synthetic and functional properties was made possible by the application of descriptive analytics, Pearson correlation, Principal Component Analysis (PCA), KMeans clustering and hypothesis testing. Most of the developed compounds showed a high yield (85–95%) and could withstand heat (melting point 200–250°C), in addition to showing effective antioxidant (80–95%) and antibacterial (20–25 mm inhibition zone) qualities. The study's calculations matched the spectra expected for actual compounds containing aromatic and conjugated groups. Significantly, using statistics revealed no conflict between drug effectiveness and drug production which means pharmaceutical goals can be met with green chemistry. The study shows a repeatable method that can be used outside a lab, where cheminformatics, spectral modeling and statistical learning are incorporated to support green synthesis and preserve bioactivity. It allows the use of a flexible system to test, group and improve the use of heterocycles for sustainable pharmaceutical chemistry.

This review examines eco-friendly strategies for the synthesis of heterocyclic compounds through the application of green chemistry principles. Traditional synthetic routes often rely on hazardous reagents, toxic solvents, and energy-intensive processes, leading to environmental and safety concerns. In contrast, green approaches emphasize mild reaction conditions, non-toxic catalysts, renewable feedstocks, and energy-efficient techniques to reduce waste and enhance sustainability. Key methods discussed include catalysis, solvent-free and green solvent systems, biocatalysis, and the use of biomass-derived starting materials. The review also highlights applications of green heterocyclic synthesis in pharmaceuticals, materials science, and environmental remediation. By integrating these sustainable strategies, heterocyclic chemistry can advance toward safer, more efficient, and environmentally responsible production, providing a roadmap for future research and industrial practice.