Synthesis of Functionalized β-Lactams and Pyrrolidine-2,5-diones through a Metal-Free Sequential Ugi-4CR/Cyclization Reaction

Abstract

An efficient approach for the synthesis of functionalized β-lactams and pyrrolidine-2,5-diones was achieved through a sequential Ugi-4CR/cyclization reaction. Diversity-oriented synthesis, good to high yields, easy workup, and short reaction times are advantages of this procedure.

Diversity‐Oriented Synthesis of β‐Lactams and γ‐Lactams by Post‐Ugi Nucleophilic Cyclization: Lewis Acids as Regioselective Switch

“…Initially, the Ugi four-component reaction (4-CR) [16] of imidazo[1,2-a]pyridine-2-carbaldehyde (1a), p-methoxybenzylamine (2a), propiolic acid (3a), and cyclohexyl isocyanide (4a) in methanol at room temperature generated adduct 5a in 84 % yield, which was selected to optimize the reaction conditions of the next step. In continuation of our previous success with gold and silver catalysis for the activation of alkynes, [14] we began our studies by screening these catalysts in 1,2-dichloroethane (DCE) at 120°C for 12 h (Table 1, entries 1-3). However, none of the catalysts was able to complete the reaction.…”

“…[5] As a result, several new synthetic approaches have been developed, [6] with particular emphasis on the generation of α-methylene β-lactams, [7] which are versatile compounds delivering building blocks for the construction of various β-lactam antibiotics [7c] (Scheme 1). Recently, bromoacetic acid [13] and phenylpropiolic acid [14] have been used to synthesize functionalized β-lactams involving a sequential base-catalyzed tandem Ugi reaction and intramolecular cyclization. Over the last few decades, multicomponent reactions (MCR) [8] and transition-metal-catalyzed [9] post-MCR transformations have enabled easy access to complex heterocyclic scaffolds in a few steps.…”

“…[10] Strategies for generating β-lactams by employing β-amino acids [11] or β-keto acids [12] as functionalized substrates in the Ugi reaction have also been developed. Recently, bromoacetic acid [13] and phenylpropiolic acid [14] have been used to synthesize functionalized β-lactams involving a sequential base-catalyzed tandem Ugi reaction and intramolecular cyclization. Nonetheless, newer methodologies in terms of increased substrate scope as well as starting material availability are always welcome.…”

New tricks of well-known aminoazoles in isocyanide-based multicomponent reactions and antibacterial activity of the compounds synthesized

“…In addition, the application of polyfunctional reagents in Ugi-4CR opens ways to different post-cyclization reactions, thereby broadening the scope. Thus the Ugi-4CR involving substituted propiolic acids, can be followed by electrophilic ipso-iodocyclization [62] or transition-metal-initiated [63–68] and metal-free cyclizations [69–70]. …”

An environmentally friendly approach for the synthesis of quinazolinone sulfonamide

“…In continuation of our research work [54][55][56][57][58][59][60][61][62][63][64], we report herein the synthesis of quinazolinone sulfonamides through the four-component reaction of isatoic anhydride, hydrazine hydrate, benzaldehyde derivatives, and saccharin under solvent-free conditions using propylsulfonic acid …”