ABSTRACT The site‐selective functionalization of indoloquinoxaline scaffolds remains underexplored despite their significant biological and pharmaceutical relevance. In this context, we report a practical and efficient method for the regioselective chalcocyanation of indoloquinoxaline hybrids under a mild aqueous protic solvent system. This approach utilizes the synergistic use of the inexpensive and operationally convenient reagents, namely ammonium thiocyanate/potassium selenocyanate as an effective source of chalcocyanating reagent, along with ceric ammonium nitrate (CAN) as an oxidizing agent. The formation of a wide range of thiocyanated/selenocyanated indoloquinoxaline products integrated with biologically important phenyl, benzoyl, benzoylester and phthalazinone functionalities at room temperature in a short reaction time are the notable feature of this reaction.
A new strategy is described for the first time to synthesize a heterocyclic hybrid system of 1,5-disubstituted-1H-tetrazole-bis-1,2,3-triazoles through a double one-pot sequence. The approach involves (i) a one-pot five-component process to obtain the key 1,5-DS-T-bis-propargyl compounds 11a-n, using propargylamine as an orthogonal reagent, followed by (ii) a pseudo-three-component reaction consisting of a double CuAAC process with aromatic azides to afford the target hybrids 6a-n in moderate yields. The protocol is operationally simple, proceeds under mild reaction conditions, and some products were purified by recrystallization from methanol. Notably, this is the first example of a higher-order multicomponent sequence combined with a classical pseudo-multicomponent reaction, underscoring the synthetic utility of this approach for the rapid assembly of structurally complex hybrid scaffolds relevant to medicinal chemistry. Finally, the feasibility of accessing the target hybrids in a truly one-pot manner was demonstrated starting from propargylamine, with the overall process forming six C-N bonds, one C-C bond, and one N-N bond within a single operation.
Manganese-catalyzed chelation-assisted C-H alkenylation and alkylation of heteroarenes using alkynes or alkenes has emerged as an important and efficient strategy. In contrast to commonly used second- and third-row transition metal catalysts, manganese systems exhibit broader substrate scope, accommodating both terminal and internal alkynes, and offer unique reactivity in C-H activation with advantageous atom- and step-economy. In manganese-catalyzed reactions between heteroarenes and unsaturated hydrocarbons, the formation of key manganese-containing intermediates-particularly those involving Mn-C bond formation-plays a pivotal role in determining reaction outcomes. Our systematic theoretical investigation employed 10 DFT functionals to evaluate Mn-C bond dissociation enthalpy (BDE) values across 16 model complexes, revealing that the M05 functional provides optimal accuracy (RMSE = 2.8 kcal/mol) for these calculations. Subsequent M05-based analyses of manganese-carbon complexes I and III, complemented by NBO and frontier molecular orbital studies, elucidated the substituent effects on Mn-C bond strength in these catalytic systems. Transition state characterization further uncovered a direct correlation between Mn-C bond strength and activation barriers, establishing a trend that connects thermodynamic stability with mechanistic feasibility in these manganese-catalyzed transformations.
ABSTRACT 3 H ‐Pyrrolo[2,3‐ c ]quinoline is a typical tricyclic heterocyclic scaffold with a fused 6‐6‐5 ring system. This class of compounds exhibits outstanding medicinal and biological activities and possesses excellent metal‐ion detection performance, making it a research hotspot in medicinal and materials chemistry. This review summarizes the synthetic strategies for 3 H ‐pyrrolo[2,3‐ c ]quinoline reported in the recent literature and classifies these methods according to their ring formation modes. For each category of synthetic strategy, the reaction mechanisms, key steps, typical examples, and advantages and limitations of representative methods (including the Pictet–Spengler reaction, Morgan–Walls reaction, Heck/Suzuki coupling reactions, Fischer indole synthesis, and Bartoli indole synthesis) are elaborated in detail. Furthermore, this review discusses the current research challenges in this field and the exploration status of ring formation strategies. Finally, the potential applications of novel indole synthesis reactions and artificial intelligence‐assisted drug design in the development of efficient synthetic methods for 3 H ‐pyrrolo[2,3‐c]quinoline are highlighted. This review aims to provide a comprehensive reference for the design and development of novel synthetic strategies for this important tricyclic scaffold.
A facile and efficient DIPEA-promoted 1,3-dipolar cycloaddition reaction to access novel spirocyclic hexahydropyrrolo[2,1-a]isoquinoline-tetrahydroindolizines has been developed. Acyl-stabilized dihydroisoquinolinium ylides, generated in situ from dihydroisoquinolinium bromides, serve as key 1,3-dipolar species to react with (E)-7-arylidene-6,7-dihydroindolizin-8(5H)-ones. The current reaction allows straightforward assembly of diverse complicated spiroheterocycles in moderate to high yields with complete stereoselectivity. Metal-free operation and feasibility for gram-scale amplification demonstrate the reliability and practical value of the developed synthetic method.
