Electro-catalytic multicomponent reaction toward asymmetrical biaryls through heteroarylation of in situ generated fused polycyclic heteroaromatics

Abstract

Biaryls have a wide range of applications in medicines, natural products, materials and ligands for metal catalysts. However, it is a huge challenge for the selective cross-coupling between two different...

Electrosynthesis of Highly Functionalized Polycyclic N-Heteroaromatics through Cascade Radical Cyclization and Alkoxylation in Batch and Continuous-Flow

“…In contrast, electrosynthesis using microflow cells features a small electrode distance and large ratio of electrode surface-to-reactor volume, which contributes to excellent mass transfer, heat removal, and temperature control. − And, steady production might be achieved under supporting electrolyte-free conditions or only using a small amount of electrolytes. In this context, we have developed some continuous-flow electrochemical synthesis methodologies, ,,− although it remains rare to develop new reactions using this enabling technology. With our continued interest in continuous-flow electrosynthesis, a flow electrolysis cell was designed and produced, as shown in Figure a.…”

“…Organic electrochemistry, employing “electrons” as traceless “reagents” to promote redox reactions, has been recognized as a more green and practical synthetic technology, which avoids the use of exogenous oxidants and reductants. − Moreover, the electrolysis process uses a controlled potential and can be switched-off anytime easily. − In this regard, electro-oxidative radical cascade cyclization to a series of highly functionalized PNAs in the absence of exogenous oxidants or reductants has attracted wide interest and research. − In particular, Xu and co-workers reported some straightforward preparation of PNAs through intramolecular cascade cyclization from an N-centered radical which was generated from anodic oxidation. − Besides, some electrochemical intermolecular radical addition onto alkynes or alkenes and cyclization to PNAs were developed. − Furthermore, the highly functionalized PNAs could also be generated from electrochemical oxidative π-extension of unfunctionalized heterobiaryl compounds via the radical cyclization processes. − We had also reported the electrosynthesis of PNAs from N, , C, − S, , or halogen radical intermediates.…”

Photoredox-Cobaloxime Catalysis for Selective Oxidative Dehydrogenative [4+2] Annulation of Imidazo-Fused Heterocycles with Alkenes

“…Thus, considerable research efforts have been devoted to developing efficient and practical methodologies for synthesizing such compounds over the past decades . Typical methods to access these structures generally use alkynes as π-extending reagents through the [3+2]/[4+2] annulation reactions with imidazopyridines. ,, The problem is that expensive Cp*Rh­(III) catalysts are required to achieve selective [4+2] cyclization reactions, whereas electrochemical processes involving radical intermediates mainly yield [3+2] cyclization products, and only electron-deficient alkynes could convert to [4+2] cyclization products. On the other hand, alkenes are used as synthetic units in cyclization reactions − or alkylation reactions , as well; however, the main challenge is that alkenes may be converted to cycloadducts under reaction conditions involving radical intermediates, which need to undergo electron/H transfer processes to accomplish aromatization or π-extension facilitated by external suitable oxidants .…”

“…Notably, the oxidative [4+2] annulation reactions were greatly inhibited by replacing the cobaloxime catalyst with some traditional oxidants such as O 2 , K 2 S 2 O 8 and H 2 O 2 , due to the overoxidation of 4-methoxystyrene (Table S1, entries 16–18). Additionally, electrochemical oxidation conditions from prior reports were applied to the reaction of 2-phenylimidazo­[1,2-a]­pyridine with 4-methoxystyrene. However, no desired [4+2] annulation product 3aa was detected (for details, see the SI, Figure S5).…”