Synthetic Strategies of N‐Heterocyclic Olefin (NHOs) and Their Recent Application of Organocatalytic Reactions and Beyond

Abstract

N‐heterocyclic olefin (NHO) derivatives have an electron‐rich as well as highly polarized carabon‐carbon (C=C) double bond because of the electron‐donating nature of nitrogen and sulphur atoms. While NHOs have been developing as novel organocatalysts and ligands for transition‐metal complexes in various organic compound syntheses, different research groups are currently interested in preparing imidazole and triazolium‐based chiral NHO catalysts. Some of them have been used for enantioselective organic transformations, but were still elusive. N‐heterocyclic olefins, the alkylidene derivatives of N‐heterocyclic carbenes (NHC), have shown promising results as effective promoters for numerous organic syntheses such as asymmetric catalysis, hydroborylation, hydrosilylation, reduction, CO2 sequestration, alkylation, cycloaddition, polymerization and the ring‐opening reaction of aziridine and epoxides, esterification, C−F bond functionalization, amine coupling, trifluoromethyl thiolation, amination etc. NHOs catalysts with suitable structures can serve as a novel class of Lewis/Bronsted bases with strong basicity and high nucleophilicity properties.These facts strongly suggest their enormous chemical potential as sustainable catalysts for a wide variety of reactions in synthetic chemistry. The synthesis of NHOs and their properties are briefly reviewed in this article, along with a summary of the imidazole and triazole core of NHOs′ most recent catalytic uses.

Triazoles in Medicinal Chemistry: Physicochemical Properties, Bioisosterism, and Application

“…Further mechanism confirms the possibility of developing a novel treatment for cisplatin resistance with the combination of iron homeostasis intervention and reveals the roles of RNA modification in mechanisms of preventing DNA damage repair. This downregulates the cellular free iron and the subsequent appearance of the decrease of RNA demethylases followed by enhancing the PNA m 6 A levels. 145 The prodrug design strategy of combining DFX and cisplatin provides a fanciful foresight to solve resistance problems of other chemotherapeutic agents through iron homeostasis intervention.…”

“…Triazoles serve as versatile ligands for transition metal complexes and nonmetallic organic catalysts for C–C bond formation, frequently used as precursors for carbenes. , By deprotonating the corresponding N-heterocyclic carbene (NHC) precursors using appropriate bases, they can be converted into active NHCs . Thus, determining the acidity of triazoles is crucial for heterocyclic dehydrogenation metalation reactions.…”

“…4,5 Furthermore, due to their unique pK a characteristics, both 1,2,3-triazole and 1,2,4-triazole are versatile ligands for transition metal complexes and nonmetal organic catalysts for forming C−C bonds and are commonly used as precursors for carbonyl compounds. 6,7 The unique structural features of triazole allow diverse noncovalent interactions with various biological targets, showcasing its capacity to act as both a hydrogen bond donor (HBD) and a hydrogen bond acceptor (HBA). 8,9 The physicochemical properties inherent in triazole and its fused homologues make it indispensable in the design of bioactive heterocycles.…”

“…These properties make it an appealing heterocycle for drug design, serving as a less lipophilic alternative to the phenyl ring, or substituting heterocycles such as homologous azines. Moreover, it can mimic various functional groups such as amides and esters. − Particularly noteworthy is the synthesis of 1,2,3-triazole through “click” chemistry, which serves as a versatile linker connecting two pharmacophore fragments. , Furthermore, due to their unique p K a characteristics, both 1,2,3-triazole and 1,2,4-triazole are versatile ligands for transition metal complexes and nonmetal organic catalysts for forming C–C bonds and are commonly used as precursors for carbonyl compounds. , The unique structural features of triazole allow diverse noncovalent interactions with various biological targets, showcasing its capacity to act as both a hydrogen bond donor (HBD) and a hydrogen bond acceptor (HBA). , The physicochemical properties inherent in triazole and its fused homologues make it indispensable in the design of bioactive heterocycles.…”