Metal-Free Visible-Light-Induced C–H/C–H Cross-Dehydrogenative-Coupling of Quinoxalin-2(H)-ones with Simple Ethers

Abstract

A convenient and practical metal-free visible-light-promoted method to synthesize 3-oxyalkylated quinoxalin-2­(1H)-ones was developed at room temperature. The present transformation could be accomplished through Rose Bengal-catalyzed C–H/C–H cross-dehydrogenative-coupling of quinoxalin-2­(H)-ones with simple ethers, providing an efficient and operationally simple method to access various 3-oxyalkylated quinoxalin-2­(1H)-ones with moderate to good yields.

Recent Advances in Photocatalytic Functionalization of Quinoxalin‐2‐ones

“…In mid-2018, the research group of Wei exploited this possibility conducting the C-C bond forming reaction between quinoxalin-2-ones and simple ethers. [37] After an exhaustive optimization process, they established that Rose Bengal, [38] in combination with tert-butyl hydroperoxide (TBHP) as oxidant and DABCO, under the irradiation of Blue LEDs can promote the generation of C-centered radicals at alpha position of the ethers, that can be engaged in an alkylation reaction with quinoxalin-2-ones. This protocol led the authors to obtain a collection of twenty-seven C-3-alkylated quinoxalin-2-ones with several ethers, as well as tetrahydrothiophene (Scheme 16).…”

Copper‐Catalyzed C3−H Difluoroacetylation of Quinoxalinones with Ethyl Bromodifluoroacetate

“…According to the radical trapping experiments and previous studies,,–, a preliminary mechanism is proposed in Scheme . Initially, the electrophilic difluoroalkyl radical ( A ) is generated from bromodifluoro reagent 2 via bromine abstraction by the copper(I) complex, meanwhile, releasing copper(II) complex .…”

“…Initially, the electrophilic difluoroalkyl radical ( A ) is generated from bromodifluoro reagent 2 via bromine abstraction by the copper(I) complex, meanwhile, releasing copper(II) complex . Subsequently, the difluoroalkyl radical attacks quinoxalin‐2(1 H )‐one 1 a to produce the aminyl radical intermediate B , which undergoes 1,2‐hydrogen shift to produce carbon radical intermediate C . The intermediate C can be oxidized by copper(II) complex to generate carbocation intermediate D through a single electron transfer process,, followed by deprotonation with the assistance of base to offer the target product 3 a .…”

Metal Free Benzylation and Alkylation of Quinoxalin‐2(1H)‐ones with Alkenes Triggered by Sulfonyl Radical Generated from Sulfinic Acids

“…[3] While much development has been made with respect to arylation, [3a-j] acylation, [3k-l] amination, [3m-q] phosphonylation [3r-s] directly at the C3 position using easily available quinoxalin-2(1H)-ones, functionalization by benzyl, [4] alkyl [5] and fluoroalkyl [6] groups are less explored, despite the importance and predominance of this scaffold as pharmaceuticals that include MDR antagonist, aldose reductase inhibitor, MAO-A inhibitor, ion channel blocker, antitumor, anti-inflamatory, and anti-obesity agents ( Figure 1). [7][8][9] Very recently, C3 position of quinoxalin-2(1H)-one has been directly benzylated [4] and alkylated [10] using methylarenes and ethers, respectively (Scheme 1a). Three reports describing cyanoalkylation [11] at the C3 of quinoxalin-2(1H)-one have been very recently disclosed (Scheme 1b).…”

“…While many solvents (toluene, 1,4-dioxane, THF, ethanol and water) disfavored this reaction, to our great delight, 1,2-dichloroethane (DCE) provided 4 a in 90% yield (entries 3-8). Further attempts by using either excess TBHP (entry 9) or other oxidants such as TBPB, DCP, DTBP, K 2 S 2 O 8 (entries [10][11][12][13][14] to increase the yield were unsuccessful. Oxygen had complete detrimental effect on the yield of the reaction (entry 13).…”