Catalyst-free activation of methylene chloride and alkynes by amines in a three-component coupling reaction to synthesize propargylamines

Abstract

Propargylamines are synthesized via metal-free activation of the C-halogen bond of dihalomethanes and the C-H bond of terminal alkynes in a three-component coupling without catalyst or additional base and under mild reaction conditions. The dihalomethanes are used both as solvents as well as precursors for the methylene fragment (C1) in the final product. The scope of the reaction and the influence of various reaction variables has been investigated. A plausible reaction mechanism is proposed and the involvement of various intermediates that can be generated in situ in the process is discussed. The metal-free conditions also make this protocol environmentally benign and atom economical.

Beyond the Simple Copper(II) Coordination Chemistry with Quinaldinate and Secondary Amines

“…Its recrystallization from dichloromethane inadvertently resulted in (pyroH)[Cu(quin) 2 Cl] (3), a product, which confirms that pyrrolidine, initially present as a ligand in the copper(II) complex, reacted with the solvent. With dichloromethane, commonly employed as a solvent in synthesis and extraction processes, undesired reactions with primary and secondary aliphatic amines were observed previously, in particular when the solutions were left to stand for extended periods [43][44][45]. Later studies have confirmed that pyrrolidine rapidly reacts with dichloromethane at room temperature with the major products being 1,1 -methylenebis(pyrrolidine), known as aminal, and pyrrolidinium hydrochloride.…”

N‐Heterocyclic Carbene‐Protected Ag Nanoparticles Immobilized on Polyacrylonitrile Fiber as Efficient Catalysts for a Three‐Component Coupling Reaction

“…As sustainability is a significant concern in the chemical industry, the neat reaction is preferable, as it allows the assembly of complex compounds without the requirement for solvents. Furthermore, the reported AgNP‐catalyzed reaction was carried out smoothly at 25 °C, and proceeded at lower temperatures compared with previously reported AHA reactions …”

“…Furthermore, the reported AgNP-catalyzed reaction was carried out smoothly at 25 8C, and proceeded at lower temperatures compared with previously reported AHA reactions. [45,46,48] With the optimized conditions in hand, the substrate scope of the AHA coupling reactionw as investigated ( Table 1). Dichloromethane, dibromomethane, diiodomethane, and dibromomethylbenzenea ll produced good results( Table S3 in the Supporting Information, entries 11 and 12, and Ta ble 1, 4b), and excellent yields were achieved when using cyclic,h eterocyclic, anda cyclica liphatic amines as the substrates (Table 1, 4a, 4l,a nd 4d).…”

Recyclable Cu/C3N4 composite catalyzed AHA/A3 coupling reactions for the synthesis of propargylamines

“…On the other hand, a metal-free AHA reaction was also developed, but only moderate yields were obtained. 16 Moreover, as a special secondary amine, tetrahydroisoquinolines (THIQs) are found widely existed in natural products and have many biological activities. 17 Thus, many novel and valid methods were developed to synthesize THIQ derivatives, and most of them focused on the activation of THIQ's C1 atom.…”