Quinoxalinones are a class of heterocyclic compounds which attract extensive attention owing to their potential in the field of organic synthesis and medicinal chemistry. During the past few decades, many new synthetic strategies toward the functionalization of quinoxalinone based scaffolds have been witnessed. Regrettably, there are only a few reports on the pharmacological activities of quinoxalinone scaffolds from a medicinal chemistry perspective. Therefore, herein we intend to outline the applications of multifunctional quinoxalinones as privileged structures possessing various biological activities, including anticancer, neuroprotective, antibacterial, antiviral, antiparasitic, anti-inflammatory, antiallergic, anti-cardiovascular, anti-diabetes, antioxidation, etc. We hope that this review will facilitate the development of quinoxalinone derivatives in medicinal chemistry. 

Functionalized quinoxalinones as privileged structures with broad-ranging pharmacological activities.

Metal-free visible-light-initiated direct C3 alkylation of quinoxalin-2(1<i>H</i>)-ones and coumarins with unactivated alkyl iodides

Transition metal-free C-3 functionalization of quinoxalin-2(1H)-ones has recently emerged as a modern sustainable protocol, as C-3 functionalized quinoxalin-2(1H)-ones offer robust applications in the medicinal, pharmaceutical and agriculture industry. In recent times, various sustainable protocols for the construction of C–C, C–N, C–P, C–S, and C–O bonds via the C–H functionalization of quinoxalin-2(1H)-ones were developed. A gradual shift from metal-catalyzed to metal-free methodologies has been observed in last few years, as the latter provide an environmentally benign synthetic route in organic chemistry. The present review offers an extensive discussion on recent advances in transition metal-free C–H functionalization of quinoxalin-2(1H)-ones. The review has been decoratively categorized based on C–C, C–O/C–S and C–N/C–P bond formation using metal-free, visible light and electrochemically catalyzed strategies. In addition, mechanistic features of chemical transformation of quinoxalin-2(1H)-ones have been highlighted.

Transition metal-free C-3 functionalization of quinoxalin-2(1H)-ones: recent advances and sanguine future

An efficient visible-light promoted Riboflavin-catalyzed direct benzylation of substituted quinoxalin-2(1H)-ones for the synthesis of various C3-benzylated quinoxalin-2(1H)-one derivatives has been developed under mild conditions. The present method uses readily available...

C-H Benzylation of Quinoxalin-2(1H)-ones via Visible-Light Riboflavin Photocatalysis

We have unveiled an efficient synthesis of cyanoalkylated quinoxalin-2(1H)-ones via a three-component radical cascade reaction of quinoxalin-2(1H)-ones with vinylarenes and azobis(alkylcarbonitrile)s. K2S2O8 takes part in the reaction as a sole oxidant under base, additive, and metal-free conditions, producing the three-component products in moderate to good yields. The protocol also works with phenylacetylene in the absence of vinyl arenes and provides the respective product. Furthermore, different control experiments with radical scavengers like 2,2,6,6-tetramethylpiperidine-1-oxyl and diphenyl ethylene prove the generation of radicals during the reaction.

Metal-free three-component cyanoalkylation of quinoxalin-2(1H)-ones with vinylarenes and azobis(alkylcarbonitrile)s.

DTBP-promoted decarbonylative alkylation of quinoxaline-2(1H)-ones with aldehydes

A Mn(ii)-catalyzed efficient C-H alkylation of imidazoheterocycles with methyl ketones has been developed via dehydrogenative C(sp3)-C(sp2) coupling which can serve as a novel approach toward hydrocarboxylated imidazolopyridines. The merit of this strategy is illustrated by excellent functional group tolerance and the use of cheap and readily available starting materials.

Manganese-catalyzed dehydrogenative Csp3-Csp2 coupling of imidazo[1,2-a]pyridines with methyl ketones.

A hydrogen peroxide (H2O2)-mediated quinoxaline-2(1H)-ones hydrocarbylation reaction has been reported. The reaction is achieved through the difunctionalization of styrene. In this transformation, methyl radical resulting from dimethyl sulfoxide firstly attacks styrenes to provide alkyl radicals which then undergo alkylation at the C3 position of quinoxalin-2(1H)-one. A green, convenient, and simple protocol for the synthesis of 3-alkylquinoxalin-2(1H)-ones was provided.

Bingqing Wang

Papers

DTBP-promoted decarbonylative alkylation of quinoxaline-2(1H)-ones with aldehydes

Manganese-catalyzed dehydrogenative Csp3-Csp2 coupling of imidazo[1,2-a]pyridines with methyl ketones.

H2O2-Promoted Alkylation of Quinoxalin-2(1H)-ones with Styrenes and Dimethyl Sulfoxide