Selectfluor-Mediated Tandem Cyclization of Enaminones for the Synthesis of 3-Fluorochromones

Abstract

An efficient synthesis of various 3-fluorochromones (3-fluoro-4H-chromene-4-ones) from enamino ketones by using Selectfluor is described. The key step in the synthesis involves tandem fluorination and cyclization to form 3-fluorochromones in good yields. The significant features of this method include simple operational procedures, a high purity of the product, and excellent regioselectivity.

Keywords

fluorochromones - enamino ketones - fluorination - Selectfluor

• References and Notes

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• 32 3-Fluoro-4H-chromen-4-one (3a); Typical Procedure Selectfluor (708 mg, 2 mmol) was added to a stirred solution of enaminone 2a (191 mg, 1 mmol) in DCE (5 mL) at 0 °C, and the mixture (a white suspension) was stirred at r.t. for 24 h. When the reaction was complete (TLC, 30% EtOAc–PE), the mixture was poured into ice-cold water and stirred for 10 min. The mixture was then extracted with EtOAc (3 ×) and the combined organic layers were washed with water and brine, then dried (Na₂SO₄), filtered, and concentrated. The resulting crude product was purified by flash column chromatography [silica gel (100–200 mesh), 15–20% EtOAc–PE] to give an off-white solid; yield:135 mg (82%); mp 158–162 °C. IR (KBr): 3084, 2967, 1814, 1709, 1587, 1483, 1395, 1194, 955, 753 cm^–1. ¹H NMR (500 MHz, DMSO-d ₆): δ = 8.96 (d, J = 4 Hz, 1 H), 8.16 (d, J = 8 Hz, 1 H), 7.87 (t, J = 8.5 Hz, 1 H), 7.75 (d, J = 8.5 Hz, 1 H), 7.55 (t, J = 7.5 Hz, 1 H). ¹³C NMR (125 MHz, DMSO-d ₆): δ = 169.4 (d, J = 15.5 Hz), 155.3, 149.6 (d, J = 242.2 Hz), 147.7, 145.1 (d, J = 40.6 Hz), 134.5, 125.5, 124.2, 118.7. ¹⁹F NMR (470 MHz, CDCl₃): δ = –165.7. MS (EI): m/z (%) = 165 [M + 1]⁺ (100).