Photoinitiated Deaminative Alkylation of Quinoxalin‐2(1H)‐ones via Electron Catalysis

Abstract

A visible‐light initiated deaminative C3 alkylation of quinoxalin‐2(1H)‐ones with Katritzky salts is reported. This radical process provides an approach to a range of C3 alkylated quinoxalin‐2(1H)‐one derivatives in 40–96% yields under metal‐ and external photocatalyst‐free conditions. The reaction is enabled by the deprotonation of acidic aminyl radical intermediates to generate the corresponding radical anions, which act as single electron transfer reducing reagents to sustain the radical chain. The late‐stage functionalization of drug‐based amines further demonstrates the value of this approach.

Photoinduced Deaminative Alkylation of Quinoxalin‐2(1H)‐ones via an Electron Donor‐Acceptor Complex

“…Control experiments showed that the reaction did not proceed in the absence of light, demonstrating that the purple LEDs were essential (entry 9). Contrary to the known 3-alkylquinoxalin-2(1H)-one syntheses, [27] the yield of our reaction under argon was almost identical to that under air (entry 10), proving that the reaction was not sensitive to oxygen.…”

“…On the basis of the above-described experimental results and reported literature, [27] we propose that photoinduced CÀ H alkylation reactions between quinoxalin-2(1H)-ones and Katritzky salts proceed via EDA complexes by means of the mechanism illustrated in Scheme 4. First, an EDA complex is generated between the pyridinium salt and the NaOAc.…”

“…Moreover, under modified conditions (40 mL of DMSO, 22 h), the reaction could be easily carried out on a gram scale, producing 3 a in 81 % yield (1.36 g), further demonstrating the practical value of this method. Although a similar work had recently been disclosed by Qiu, Zheng and co-workers, [27] compared to known synthesis, this reaction has a wider substrate range, and most of ChemistrySelect the products have higher yields under more efficient experimental conditions.…”

“…For example, the groups of Molander [24a] and Koh [24d] accomplished Ni‐catalyzed reductive cross‐coupling reactions of aryl halides with Katritzky salts. Recently, Qiu, Zheng and co‐workers [27] reported a visible‐light initiated deaminative C3 alkylation of quinoxalin‐2(1 H )‐ones with Katritzky salts. However, oxidant‐ and metal‐free deaminative alkylation reactions of (hetero)arenes by Katritzky salts remain somewhat underexplored, perhaps because of the challenges involved in generating radicals under green, sustainable conditions.…”