Copper‐Catalyzed Direct C‐3 Benzylation of Quinoxalin‐2(1H)‐ones with Methylarenes under Microwave Irradiation

Abstract

A novel and efficient approach to the C(sp2)–H/C(sp3)–H oxidative coupling of quinoxalin‐2(1H)‐ones with methylarenes by using CuI as catalyst is reported. Various substrates were well tolerated in this methodology and the desired products were given in moderate‐to‐good yields. This reaction features good functional group compatibility and broad substrate scope.

Copper‐Catalyzed Direct Carbamoylation of Quinoxalin‐2(1H)‐ones with Hydrazinecarboxamides Under Mild Conditions

“…On the basis of the control experiments and literature reports,, , we proposed a plausible reaction mechanism (Scheme ). The benzoyl radical is generated via homolysis or copper‐catalyzed decomposition of dibenzoyl peroxide.…”

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

“…While much development has been made with respect to arylation,– acylation,– amination,– phosphonylation– directly at the C3 position using easily available quinoxalin‐2(1 H )‐ones, functionalization by benzyl, alkyl and fluoroalkyl 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 antiobesity agents (Figure ) . Very recently, C3 position of quinoxalin‐2(1 H )‐one has been directly benzylated and alkylated using methylarenes and ethers, respectively (Scheme a). Three reports describing cyanoalkylation at the C3 of quinoxalin‐2(1 H )‐one have been very recently disclosed (Scheme b).…”

“…Our interest [13] in CÀ H functionalization reaction prompted us to hypothesize that introducing additional functionality to the existing C3 substituted quinoxalin-2(1H)-one would further enrich the pharmaceutical value of this novel scaffold. Strategically, unlike the report described by Qu et al for the generation of benzyl radical directly using methylarene as the precursor, [4] we considered to generate functionalized benzylic/alkyl radical using alkene as the precursor. Strategically, unlike the report described by Qu et al for the generation of benzyl radical directly using methylarene as the precursor, [4] we considered to generate functionalized benzylic/alkyl radical using alkene as the precursor.…”

“…Given the importance of sulfones in pharmaceuticals and agrochemicals, [14] in this pursuit, we planned for the development of metal free C3 benzylation and alkylation with the concomitant functionalization by sulfonyl group (Scheme 1). Strategically, unlike the report described by Qu et al for the generation of benzyl radical directly using methylarene as the precursor, [4] we considered to generate functionalized benzylic/alkyl radical using alkene as the precursor. We envisioned that sulfonyl radical (I) generated from suitable precursor could convert styrene to the corresponding sulfonylated benzylic radical intermediate (II) that could subsequently react at the C3 position of quinoxalin-2(1H)ones to furnish the radical intermediate III, which upon oxidation provide the novel C3 benzylated scaffold.…”

Visible‐Light‐Induced Trifluoromethylation of Quinoxalin‐2(1H)‐Ones under Photocatalyst‐Free Conditions

“…[1] Common synthetic route based on the acylation of benzene-1,2-diamines with arylglyoxylic acid, followed by subsequent cyclization, [2] suffered from several drawbacks such as prefunctionalization and multi-step procedure. Over the past years, direct CÀ H bond functionalization of quinoxalin-2(1H)-ones has emerged as an attractive approach to 3substituted quinoxalin-2(1H)-ones in modern organic synthesis, such as CÀ H arylation, [3] alkylation, [4] acylation, [5] amidation, [6] amination, [7] benzylation [8] and phosphonation [9] (Scheme 1, a).…”