Applications of N-Halo Reagents in Multicomponent Reactions: A Still Underrated Approach for the Construction of Heterocyclic Scaffolds

Abstract

Abstract:Heterocyclic scaffolds are important from both academic and industrial points of view. Due to their biological and pharmacological activities, they are useful intermediates in organic synthesis and have great interest in medicinal and natural products chemistry. N-halo compounds bearing an electron-withdrawing group on nitrogen (e.g., carbonyl, sulfonyl) present the unique chemical properties of the N-X bond that give them broad synthetic utility for diverse organic transformation. In the past years, significant progress has been achieved in the synthesis of heterocyclic compounds with the intermediacy of N-halo compounds. Numerous strategies (e.g., electrophilic cyclizations, asymmetric halocyclizations, oxidative cyclizations, radical processes) were implemented featuring high atom- and step-economy, and more efficient procedures are continually being developed. An interesting approach consists of using Nhalo compounds to promote multicomponent reactions (MCRs), which rapidly became an emerging field in heterocyclic construction. MCRs are recognized for their mild conditions, high convergence, and efficiency. Thus, the present review will focus attention on the main topics and utilization of N-halo compounds (N-halosuccinimides, trihaloisocyanuric acids, N-halosulfonamides, etc.) as green and convenient reagents in heterocyclic construction via MCRs. Examples of the preparation of azoles, pyridines, 1,4-dihydropyridines, chromenes, and xanthenes, among other scaffolds are presented and discussed.