Visible-Light-Induced C-3 Difluoroalkylation of Quinoxalin-2(1H)-ones with Difluoroiodane(III) Reagents under Catalyst-Free Conditions

Abstract

A visible-light-induced radical difluoroalkylation of quinoxalin-2(1H)-ones by hypervalent-iodine-based reagents was developed. To facilitate the final oxidative step, [bis(trifluoroacetoxy)iodo]benzene (PIFA) was employed as an oxidant. Moreover, a one-pot protocol for this transformation was realized by generating the difluoroalkylation reagent in situ. The readily accessible reagents and the mild reaction conditions make this reaction an alternative and practical strategy for the synthesis of C(3)-difluoroalkylated quinoxalin-2(1H)-ones.

Key words

difluoroalkylation - quinoxalinones - hypervalent iodine reagents - photocatalysis - catalyst-free reaction

Publication History

Received: 28 March 2023

Accepted after revision: 12 June 2023

Accepted Manuscript online:
12 June 2023

Article published online:
18 August 2023

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• 17 Difluoroalkylated Quinoxalin-2(1H)-ones 3a–aa; General Procedure A flame-dried 10 mL Schlenk tube equipped with a magnetic stirring bar was charged with the appropriate quinoxalin-2(1H)-one 1 (0.30 mmol), iodane 2 (0.60 mmol, 2.0 equiv), and PIFA (258 mg, 0.45 mmol). Anhyd 1,4-dioxane (1.5 mL) was added from a syringe under argon, and the mixture was stirred and irradiated by 24 W blue LEDs at 40 °C for 12 h. The mixture was then diluted with H₂O (10 mL) and extracted with EtOAc (3 × 10 mL). The combined organic phase was dried (Na₂SO₄) and concentrated, and the residue was purified by chromatography (silica gel, PE–EtOAc). Ethyl Difluoro(4-methyl-3-oxo-3,4-dihydroquinoxalin-2-yl)acetate (3a) Yellow solid; yield: 81 mg (96%). ¹H NMR (400 MHz, CDCl₃): δ = 8.02 (dd, J = 8.1, 1.5 Hz, 1 H), 7.71 (ddd, J = 8.7, 7.3, 1.5 Hz, 1 H), 7.50–7.39 (m, 2 H), 4.42 (q, J = 7.1 Hz, 2 H), 3.72 (s, 3 H), 1.37 (t, J = 7.2 Hz, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 162.3 (t, J = 31.0 Hz, 1 C), 152.72, 147.8 (t, J = 24.0 Hz, 1 C), 134.1, 132.8, 131.6, 131.5, 124.5, 114.0, 109.6 (t, J = 251.0 Hz, 1 C), 61.0, 29.3, 14.1. ¹⁹F NMR (376 MHz, CDCl₃): δ = –110.60 (s, 2 F).