Free Radical Cyclization of N-Arylacrylamides: Mild and Facile Synthesis of 3-Thiocyanato Oxindoles

Abstract

A novel and convenient oxidative radical cyclization of N-substituted N-arylacrylamides for the synthesis of 3-thiocyanated oxindoles has been developed by using AgSCN and K₂S₂O₈ as the radical source. This process allows a consistent and convenient access to SCN-containing heterocycles bearing a broad range of functional groups in good to excellent yields (up to 91%). Moreover, the use of inexpensive and readily available starting materials, operational simplicity, and excellent functional group tolerance makes this protocol practically attractive.

Key words

alkenes - oxindole - radical cyclization - silver - tandem reaction - thiocyanation

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• 22 1,3-Dimethyl-3-(thiocyanatomethyl)indolin-2-one (3a): A mixture of 1a (0.1 mmol), AgSCN (2, 0.15 mmol), K₂S₂O₈ (0.3 mmol) and Cs₂CO₃ (0.1 mmol) in CH₃CN (3.0 mL) was stirred under open air at 100 °C for 12 h. After completion of the reaction, the resulting mixture was diluted with EtOAc and H₂O and filtered through a pad of celite. Then the filtrate was extracted with EtOAc (3 ×). The combined organic layer was dried over anhyd Na₂SO₄ and concentrated under reduced pressure. The resulting crude product was purified by flash chromatography on silica gel with a mixture of petroleum ether and EtOAc as the eluent; colorless oil (21 mg, 91% yield). IR (neat): 2154, 1699, 1610, 1489, 1375, 1242, 1056, 1024, 912, 748, 694 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 7.39 (t, J = 8.0 Hz, 1 H), 7.29 (t, J = 7.2 Hz, 1 H), 7.16 (t, J = 7.6 Hz, 1 H), 6.93 (d, J = 7.6 Hz, 1 H), 3.43 (J_ab  = 16.8 Hz, 2 H), 3.25 (s, 3 H), 1.50 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 177.3, 143.3, 129.8, 129.3, 123.4, 123.1, 111.4, 108.6, 48.5, 40.7, 26.4, 22.6. HRMS: m/z [M + H]⁺ calcd for C₁₂H₁₃N₂OS: 233.0743; found: 233.0739.