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

Haijuan Qin; Ningning Zhou; Kun Wang; Ying Zhang; Xia Zhao; Kui Lu

doi:10.1055/a-2108-9626

Synlett, Table of Contents

Synlett 2023; 34(17): 2037-2041
DOI: 10.1055/a-2108-9626

letter

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

Haijuan Qin‡

^aResearch Centre of Modern Analytical Technology, Tianjin University of Science and Technology, Tianjin 300457, P. R. of China

,

Ningning Zhou‡

^bChina International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, P. R. of China

,

Kun Wang

^bChina International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, P. R. of China

,

Ying Zhang

^bChina International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, P. R. of China

,

Xia Zhao

^cCollege of Chemistry, Tianjin Key Laboratory of Structure and Performance for Functional Molecules, Tianjin Normal University, Tianjin 300387, P. R. of China

,

Kui Lu∗

^aResearch Centre of Modern Analytical Technology, Tianjin University of Science and Technology, Tianjin 300457, P. R. of China

^bChina International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, P. R. of China

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Abstract

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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

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References

References and Notes

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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).

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Supporting Information