Catalytic Annulation Reactions: Preface to the Special Issue

1. Introduction

Catalytic annulation reactions have emerged as a cornerstone in modern synthetic chemistry, enabling the efficient construction of complex cyclic and heterocyclic frameworks with high atom economy and precision. These reactions are pivotal in pharmaceutical, materials, and environmental sciences, offering sustainable pathways for the development of bioactive molecules, functional materials, and green chemical processes. Since their inception over a century ago, numerous annulation reactions, such as the Robinson annulation reaction, Nazarov annulation reaction, and Pschorr annulation reaction, have been discovered. Recent advances have further expanded this field, underscoring the need for the continued exploration of novel annulation methodologies.

This Special Issue highlights cutting-edge developments in catalytic annulation, focusing on innovative catalyst design, mechanistic insights, and diverse applications. The articles included in this Special Issue address transition-metal catalysis, organocatalysis, and metal-free approaches, showcasing the versatility and transformative potential of these strategies. Below, we present the selected contributions and discuss their significance.

2. Contributions

Contribution 1 explores the hydrochloric acid-mediated [4+2] annulation of N-benzyl cyanamides with 2-amino aryl ketones, yielding 2-aminoquinazoline derivatives with broad substrate tolerance and high efficiency. Mechanistic studies suggest that an acid-promoted reaction pathway is involved. While this method is practical, the use of corrosive HCl may limit its applicability. Future directions include greener mediators, computational optimization, and the expanded scope of substrates for medicinal and material applications. Future developments could focus on finding greener and more efficient mediators. Computational chemistry could be used to predict and optimize reaction pathways, and efforts should be made to expand the reaction scope to include more complex substrates, enabling the synthesis of more diverse quinazoline-based compounds for medicinal and material applications.

Contribution 2 addresses the use of a recyclable Ni-containing coordination polymer (Ni-CIA) as a catalyst for the synthesis of oxindole and quinoline derivatives via the borrowing hydrogen strategy. The protocol could effectively catalyze the reactions under optimized conditions, with the catalyst’s unique structure promoting ion diffusion and mass transfer. Mechanistic studies reveal the roles of the catalyst and intermediates in the reaction. The method’s utility is demonstrated by the successful synthesis of various derivatives with good to excellent yields. In addition, the catalyst can be reused at least five times, showing good stability. Future work could broaden the scope of the substrates and employ computational methods to refine the design of catalysts, leading to the discovery of novel synthetic routes for a wider range of valuable heterocyclic compounds.

Contribution 3 presents the development of gold self-relay catalysis, which enables the intramolecular annulation and intermolecular Michael addition of 3-yne-1,2-diols with aurone-derived azadienes or para-quinone methides in order to synthesize unsymmetrical furanized triarylmethanes. The protocol features a good substrate scope, a high tolerance to functional groups, and mild conditions, with the reaction proceeding without inert atmosphere protection. However, the cost of gold catalysts may hinder scalability. Research into cost-effective alternatives is therefore warranted.

Contribution 4 studies the transition metal-free synthesis of 3-acylquinolines via the formal [4+2] annulation of anthranils and enaminones. The protocol features easy operation, high yields, a broad substrate scope and excellent efficiency, with methanesulfonic acid (MSA) and NaI playing important roles. Mechanistic studies suggest that no radical step is involved, and the method’s utility is demonstrated in the synthesis of a wide range of 3-acylquinolines, which could be employed in various fields due to the valuable properties of quinoline derivatives. The metal-free approach is operationally simple, but the prolonged reaction time could be optimized for industrial applications.

Contribution 5 presents the one-pot synthesis of benzoxazole/benzothiazole-substituted esters via Michael addition, selectively constructing C–N/C–S bonds. The protocol features high selectivity, high atomic economy, mild conditions, and good functional tolerance, with yields ranging from good to excellent. The mechanistic details are not fully explored, but the method’s utility is demonstrated in the preparation of various substituted esters, which could be employed in the synthesis of biologically and pharmaceutically active compounds. This work provides an efficient means of selectively constructing C–N/C–S bonds with mild conditions and good yields. While the method exhibits high atom economy, the mechanistic details remain unexplored. Future studies could employ computational tools to elucidate the pathway and expand the substrate diversity.

Furthermore, Contribution 6 reports a four-component synthesis of 2-phenyl-9H- pyrimido [4,5-b]indoles using indole-3-carboxaldehydes, aromatic aldehyde, and ammonium iodide as raw materials under transition-metal-free conditions. The protocol produced a pyrimidine ring in one pot through [4+2] the annulation reaction and four C–N bonds were formed, promoted by iodine and iodide additives. Mechanistic studies suggest a pathway involving nucleophilic addition and oxidative dehydrogenation. The method shows good functional group tolerance and a wide substrate scope, and its utility is demonstrated by the synthesis of various substituted pyrimido [4,5-b]indoles. Despite its simplicity, the harsh conditions (150 °C, 16 h) require the method to be optimized to ensure its broader utility.

Contribution 7 presents a comprehensive review that covers the transition-metal-catalyzed chalcogenative heteroannulation of alkenes and alkynes. It showcases a variety of reactions and mechanisms, highlighting the significance of these methods in heterocycle synthesis. However, some limitations exist. The use of noble metals in some reactions raises concerns regarding its cost and sustainability. In addition, the reaction conditions for many protocols remain harsh, and the substrate scope could be broadened. Future developments could focus on exploring more earth-abundant and low-cost metal catalysts. Additionally, researchers should endeavor to optimize the reaction conditions to make them milder and more environmentally friendly, while expanding the range of applicable substrates to enhance the synthetic utility.

Finally, Contribution 8 presents a review regarding the synthesis of dihydroquinolin-2(1H)-ones (DHQOs) via the catalytic annulation of α,β-unsaturated N-arylamides, offering a comprehensive summary of various methods. The protocols include electrophilic cyclization, radical-initiated cyclization, and photochemical cyclization reactions. These methods can be conducted under relatively mild conditions, with diverse substrates and reaction mechanisms. The utility of these methods is demonstrated in the preparation of various DHQOs, which could be utilized as bioactive compounds in the fields of medicine and drug discovery. Regarding the protocols presented in this review, there are areas for improvement. Some reaction conditions are harsh due to the use of strong acids or high temperatures, and the application of toxic or expensive reagents limits large-scale applications. Additionally, the regioselectivity and enantioselectivity of some reactions could be enhanced. Future work should address the harsh conditions, and selectivity and sustainability of reagents in such reactions.

3. Outlook and Acknowledgments

Catalytic annulation reactions continue to revolutionize organic synthesis, yet challenges persist regarding their selectivity, substrate scope, and the sustainability of the catalyst. Future advancements may integrate computational screening, flow chemistry, and novel solvent systems to address these limitations.

We extend our gratitude to the authors, reviewers, and editorial team for their invaluable efforts in establishing this Special Issue.