Direct C–H sulfenylation of quinoxalinones with thiols under visible-light-induced photocatalyst-free conditions

Abstract

We have developed a metal-free and catalyst-free visible-light-promoted direct C–H sulfenylation of quinoxalin-2(1H)-ones with thiols for the synthesis of diverse 3-sulfenylquinoxalin-2(1H)-ones.

Recent Advances in Photocatalytic Functionalization of Quinoxalin‐2‐ones

“…Regarding the direct formation of C-S bonds, in late 2019, Pan and collaborators reported a visible-light-enabled photocatalyst-free protocol for the sulfenylation of quinoxalin-2-ones with thiols. [71] After screening some photocatalysts, they realized that the reaction could proceed without photocatalyst. Therefore, the researchers optimized the reaction conditions between quinoxalin-2-one and p-mercaptoanisole under catalyst-free conditions, and they found out that conducting the transformation in NMP at 50°C under the irradiation of Blue LEDs allows them to obtain the desired product in 76 % yield while diminishing the amount of p-mercaptoanisole dimer formation.…”

“…Surprisingly, they reported that this transformation does not proceed without photocatalyst, as opposed to the Pan work. [71] The researchers applied the optimized reaction conditions to other differently substituted quinoxalin-2-ones and distinct thiols, with forty examples including a variety of aliphatic thiols and quinoxalinones bearing electron-donating (Me) and electron-withdrawing groups (F, Cl, CO 2 Me, CF 3 , NO 2 ) (Scheme 52). The applicability of the thioetherification protocol was confirmed on a gram scale under…”

“…The final oxidant of the reaction is, again the oxygen from the air. Comparing these last two methodologies, one can realize that the catalyst-free protocol of Pan [71] worked efficiently with both aliphatic and aromatic thiols (although with moderate yields) and the Wei-Hin Me [73] approach worked very well with aliphatic thiols but was quite unsuccessful with the aromatic derivatives. Despite the similarity in the reported transformation, the catalytic system is substantially distinct, and it should be the reason for the different performance.…”

“…Regarding the direct formation of C–S bonds, in late 2019, Pan and collaborators reported a visible‐light‐enabled photocatalyst‐free protocol for the sulfenylation of quinoxalin‐2‐ones with thiols . After screening some photocatalysts, they realized that the reaction could proceed without photocatalyst.…”

The C3-H Bond Functionalization of Quinoxalin-2(1H)-Ones With Hypervalent Iodine(III) Reagents

“…Some bioactive molecules containing quinoxalin-2(1 H )-one skeleton, such as Compounds 1 - 3 , also show potential applications in medicinal chemistry fields (Meyer et al, 2006 ; Khattab et al, 2015 ; Qin et al, 2015 ) ( Figure 1A ). Because of their synthetic usefulness and potential biological importance, the introduction of functional groups into the C3-position of the quinoxalin-2(1 H )-ones has already become a research hotspot, and various protocols for the direct C3-H functionalization of quinoxalin-2(1 H )-ones have been reported (Ebersol et al, 2019 ; Gu et al, 2019 ; Hong et al, 2019 ; Li et al, 2019 ; Peng et al, 2019 ; Rostoll-Berenguer et al, 2019 ; Teng et al, 2019 ; Wang et al, 2019a , 2020 ; Xie et al, 2019b ; Zhao et al, 2019 ; Zheng and Studer, 2019 ; Tian et al, 2020 ; Yuan et al, 2020 ). In particular, the C3-H functionalization of quinoxalin-2(1 H )-ones involving hypervalent iodine reagents has drawn wide attention for the aforementioned advantages of hypervalent iodine reagents, mainly including arylation (Paul et al, 2017 ; Yin and Zhang, 2017 ), trifluoromethylation (Wang et al, 2018 ; Xue et al, 2019a ), alkylation (Wang et al, 2019b ; Xie et al, 2019a ; Xue et al, 2019b ; Shen et al, 2020 ), and alkoxylation (Xu et al, 2019 ; Yang et al, 2019 ) of quinoxalin-2(1 H )-ones, which provide convenient and environmentally friendly means for the synthesis of 3-substituted quinoxalinone derivatives.…”