Application of Conjugated Carbonyls in the Synthesis of Heterocycles via Oxidative Cycloaddition and Cyclization Reactions

Abstract

Synthesis of pharmaceutically active heterocycles is always appealing as the majority of the widely used drugs contain heterocyclic moieties as their core structure. So, the straightforward construction of heterocycles from readily available/accessible reagents is one of the prime targets of the synthetic chemists. In this context, CÀ H functionalization has emerged as an effective tool for the designing and synthesis of various heterocyclic moieties as it offers a straightforward and step-economic pathway. On the other hand, the readily available/accessible conjugated carbonyls are well-known reagents for the construction of carbocycles and heterocycles over the years. However, the employment of CÀ H functionalization of the two CÀ H bonds of the conjugated alkene in carbocycle/heterocycle synthesis was not so explored. In the last decade, much focus has been paid on the synthesis of various pharmaceutically active heterocycles through CÀ H bond functionalization of α,β-unsaturated aldehydes/ketones. These protocols have been developed through either oxida-tive coupling of conjugated carbonyls with suitable coupling partners or intramolecular CÀ H bond functionalization of conjugated carbonyls. In this review, we will discuss all the methodologies developed for the synthesis of heterocycles employing intermolecular CÀ H bond functionalization of conjugated carbonyls. The mechanistic pathways and usefulness of the methodologies will be also highlighted.

Recent advances in the transition metal-free synthesis of heterocycles from α,β-unsaturated ketones

“…In 2019 Zhou et al devised an asymmetric synthesis of tetrahydrobenzofuro[2,3-b]quinolines and tetrahydrobenzo [4,5] thieno [3,2-b]quinolines 119 via an organocatalyzed dearomative aza-Michael/Michael addition of 2-nitrobenzofuran/ 2-nitrobenzothiophene 116 with 2-aminochalcones 117 (Scheme 42). This protocol successfully affords the chiral quinoline derivatives 119 containing multiple stereocenters with good enantioselectivity.…”

“…1). 4–6 Molecules of this class possess multiple reaction sites, including both nucleophilic and electrophilic centers (Fig. 2).…”

Hydroxy(tosyloxy)iodobenzene (HTIB): A Convenient Oxidizing Agent for the Synthesis of Heterocycles

“…These transformations afford the morphed scaffolds possess structural rigidity and biological activities. This methodology is broadly employed to synthesize natural products [76] and several heterocyclic systems [77–84] . HTIB mediated synthesis of valuable heterocyclic compounds via oxidative cyclization methodology is outlined as.…”

Synthetic strategy toward furyl- and benzofuryl-containing building blocks for organic materials

“…In the present work, we propose a way for the utilization of the Butin reaction products as building blocks for construction hetaryl-substituted furans [28] and benzofurans [29] as potential functional molecules. The synthetic design relies on the possibility for the oxidation of the alkanone side chain followed by chemical engagement of the formed α,β-unsaturated ketone fragment into chemical transformations to obtain novel heterocyclic systems [30,31,32] (Scheme 1).…”