(3 + 2) Cycloadditions by Nucleophilic Organocatalysis

Five-membered carbo- and heterocycles are ubiquitous in a variety of pharmacological agents and natural products. The recent decades have witnessed the exuberant development of cornucopias of (3 + 2) cycloaddition reactions, in particular via the means of nucleophilic organocatalysis, in a highly asymmetric fashion, to construct chiral five-membered rings showcasing novel substrate activation modes. With global concerted efforts, dedicated libraries of nucleophilic organocatalysts, based on phosphines, primary/secondary/tertiary amines, and N-heterocyclic carbenes, of either mono- or multifunctionality, derived from various chiral backbone scaffolds, have been rationally designed, meticulously optimized, and strategically applied for the preparation of such crucial molecular frameworks. In the following sections, enantioselective and diastereoselective (3 + 2) cycloaddition reactions catalyzed by chiral phosphines (P-nucleophiles), chiral amines (N-nucleophiles), and chiral N-heterocyclic carbenes (C-nucleophiles) reported over the past few decades are summarized and discussed in sequence. © 2024 Elsevier Ltd. All rights reserved.