Alkynes in Multicomponent Synthesis of Heterocycles

Modular Access to Tetrasubstituted Imidazolium Salts through Acid‐Catalyzed Addition of Isocyanides to Propargylamines

“…[11c] Next, the reaction of propargylamine 4a and isocyanide 5a was investigated (Scheme 2). Several Lewis acids such as CuBr, InCl 3 , AuCl 3 , AgOTf, Sc(OTf) 3 , I 2 and ICl allowed the detection of the corresponding salt 6a in low yields. However, the combination of AgOTf/AcOH was more productive and afforded the imidazolinium salt 6a in 33 % yield.…”

“…[1] In this context, following our interest in isocyanide MCR chemistry, [2] we decided to tackle the interaction of these substrates with alkynes. [3] So far, this interaction mostly involves metal-catalyzed processes and conjugated additions to electron-deficient alkynes. [4] Although remarkable processes have been described by the Van der Eycken group, where the alkyne is a manifold substituent in some inputs of the Ugi MCR; [5] the direct transformation remains largely unexplored.…”

“…We envisaged a new reaction profile where the isocyanide would undergo addition to an acid activated triple bond, [6] and the nitrilium ion so generated would be captured by a nucleophilic amine (Scheme 1, pathway a) to yield iminopyrrolines A or tautomeric species. Alternatively, the process may proceed by isocyanide insertion [7] into the N-H bond of the secondary amine, to trigger an intramolecular amidine addition upon the alkyne [8] through a 5-exo-dig route [9] (Scheme 1, pathway b) and [1,3]-H shift, leading to the imidazolium salts B. The recent report of Zhu and co-workers, describing an analogous process using tions for aliphatic amines, whereas it is quite general regarding the aldehyde, alkyne and isocyanide inputs.…”

Synergy Effects in the Chemical Synthesis and Extensions of Multicomponent Reactions (MCRs)—The Low Energy Way to Ultra-Short Syntheses of Tailor-Made Molecules

“…[31] gave access to a versatile and broad range of prospective syntheses. MCR chemistry has seen a very fast upswing (over 500 reviews) since the turn of the millennium, while the number of new MCRs and their application is increasing steadily, demonstrated in some reviews [32][33][34][35][36][37][38][39][40][41].…”

Synthesis of Isoxazolopyridines and Spirooxindoles under Ultrasonic Irradiation and Evaluation of Their Antioxidant Activity

“…These reactions have enormous effectiveness, particularly for the construction of heterocyclic compounds which exhibit a wide range of biological activities [2][3][4][5]. Multicomponent reactions proceed in accordance with green chemistry principles in terms of a high degree of atom economy, easier progress of reactions, decreased reaction times, lack of waste products, and low power consumption [6,7].…”