Direct Alkylation of Quinoxalinones with Boracene-Based Alkylborate under Visible Light Irradiation

Abstract

An efficient synthesis of a variety of 3-alkyl quinoxalinones via C–H direct alkylation by photoredox catalysis between quinoxalinones and alkylborates is reported. A range of quinoxalinones was tolerated well. This visible-light photocatalysis reaction allows access to structurally diverse 3-alkyl quinoxalinones in good to excellent yields. The practicality of this protocol was demonstrated by the concise synthesis of a potential bioactive nonpeptide angiotensin II receptor antagonist.

Visible-Light-Promoted Deoxygenative Alkylation of Quinoxalin-2(1H)-ones with Activated Alcohols

“…Yellow solid (30.7 mg, 71%); mp 81–82 °C (lit . 80.0–80.7 °C); R f = 0.2 (1:5:25 EA:DCM:PE); 1 H NMR (400 MHz, CDCl 3 ) δ 7.83 (dd, J H–H = 8.0 Hz, J H–H = 1.4 Hz, 1H), 7.54–7.50 (m, 1H), 7.35–7.26 (m, 2H), 3.70 (s, 3H), 2.95 (t, J H–H = 7.7 Hz, 2H), 1.81–1.73 (m, 2H), 1.52–1.43 (m, 2H), 0.97 (t, J H–H = 7.4 Hz, 3H); 13 C­{ 1 H} NMR (100 MHz, CDCl 3 ) δ 161.4 (CO), 154.9, 133.1, 132.7, 129.6, 129.4, 123.5, 113.5, 34.1, 29.0, 28.9, 22.7, 13.9; HR MS (ESI) m / z calcd for C 13 H 17 N 2 O [M + H] + 217.1335, found 217.1335.…”

“…In recent years, photoredox-catalyzed radical alkylation of quinoxalin-2­(1 H )-ones has emerged as a preeminent handle for the versatile, functional group-tolerant synthesis of 3-alkylated quinoxalin-2­(1 H )-one derivatives . A series of alkyl radical precursors, such as hydrocarbons, halohydrocarbons, aldehydes, carboxylic acids, redox-active esters, alkylborates, etc., have been elegantly employed to introduce structurally diverse alkyl units into quinoxalin-2­(1 H )-ones under mild conditions (Scheme a). Despite these advances, there appear to be no reports of deoxygenative alkylation of quinoxalin-2­(1 H )-ones under visible-light irradiation using naturally abundant and widely occurring alcohols as alkyl radical precursors upon C–O bond cleavage.…”

Photo‐Induced C−H Methylation Reactions

“…In 2023, Li et al utilized alkylborates as the alkylating source for the CÀ H modification of quinoxaline-2(1H)-ones (15 b) (Scheme 16). [45] In one example, a methylated quinoxaline-2(1H)-one product (16 b) was obtained with a yield of 69 %. Mechanistic studies support the hypothesis that this reaction proceeds through a sequence involving methyl radical formation.…”

Photoinduced radical tandem annulation of 1,7-diynes: an approach for divergent assembly of functionalized quinolin-2(1H)-ones

“…Aza -heterocyclic compounds are found in a wide variety of natural drugs and biologically active molecules, many of which are pharmacologically important ( Pozharskii et al, 1997 ; Wen et al, 2022 ; Zhao et al, 2023 ; Liu et al, 2023a ; Liu et al, 2023b ). Among these, quinolin-2(1H)-one and its analogs are an important class of nitrogen-containing heterocycle scaffolds and are widely encountered in a myriad of pharmaceutical molecules and synthetic compounds ( Sliskovic et al, 1991 ; Suzuki et al, 2001 ; Bach et al, 2002 ; Kuethe et al, 2005 ) which display versatile biological and pharmacological activities ( McQuaid et al, 1992 ; Michael, 1995 ; Peifer et al, 2008 ), such as P2X7 receptor antagonist, rebamipide, and MAP kinase inhibitor ( Figure 1 ) ( Maignan et al, 2016 ; Tan et al, 2016 ; Miliutina et al, 2017 ; Wu et al, 2020 ).…”