Recent advances in transition metal-catalyzed reactions of chloroquinoxalines: Applications in bioorganic chemistry

An overview on various transition metal-catalyzed reactions of chloroquinoxalines and in vitro, in silico biological studies including SAR of the products along with the current state-of-the-art as well as future directions are presented. [Display omitted] •Chloroquinoxalines participated in a range of transition metal-catalyzed reactions.•Generally, Sonogashira coupling predominated over other coupling reactions.•This allowed easy access to quinoxaline derivatives of biological and other interest.•In vitro, in silico studies including SAR of quinoxaline derivatives are presented.•Quinoxaline-based NCEs, hits or leads identified so far are mostly covered. The importance of the quinoxaline framework is exemplified by its presence in the well-known drugs such as varenicline, brimonidine, quinacillin, etc. In the past few years, preparation of a variety of organic compounds containing the quinoxaline framework has been reported by several research groups. The chloroquinoxalines were successfully used as substrates in many of these synthetic approaches due to their easy availability along with the reactivity especially towards a diverse range of metal and transition metal-catalyzed transformations including Sonogashira, Suzuki, Heck type of cross-coupling reactions. The transition metals e.g., Pd, Cu, Fe and Nb catalysts played a key role in these transformations for the construction of various CX (e.g., CC, CN, CO, CS, CP, CSe, etc) bonds. These approaches can be classified based on the catalyst employed, type of the reaction performed and nature of CX bond formation during the reaction. Several of these resultant quinoxaline derivatives have shown diverse biological activities which include apoptosis inducing activities, SIRT1 inhibition, inhibition of luciferace enzyme, antibacterial and antifungal activities, cytotoxicity towards cancer cells, inhibition of PDE4 (phosphodiesterase 4), potential uses against COVID-19, etc. Notably, a review article covering the literature based on transition metal-catalyzed reactions of chloroquinoxalines at the same time summarizing the relevant biological activities of resultant products is rather uncommon. Therefore, an attempt is made in the current review article to summarize (i) the recent advances noted in the transition metal-catalyzed reactions of chloroquinoxalines (ii) with the relevant mechanistic discussions (iii) along with the in vitro, and in silico biological studies (wherever reported) (iv) including Struc