Generation of Carbamoyl Radicals and 3,4-Dihydroquinolin-2(1H)-ones Enabled by Iron Photoredox Catalysis

Abstract

A new protocol for accessing 3,4-dihydroquinolin-2(1H)-ones was established through a sequence of iron-catalyzed photoredox generation of carbamoyl radicals from oxamic acids, addition of the carbamoyl radicals to electron-deficient alkenes, intramolecular cyclization, and aromatization. The process is compatible with a variety of N-phenyloxamic acids and monosubstituted, 1,1-disubstituted, and trisubstituted electron-deficient alkenes. Employing cheap, readily available, and environmentally benign iron as the catalyst, the protocol provides an excellent alternative for synthesis of 3,4-dihydroquinolin-2(1H)-ones.

Key words

iron catalysis - photoredox catalysis - dihydroquinolinones - carbamoyl radicals - oxamic acids

Publication History

Received: 21 March 2024

Accepted after revision: 16 April 2024

Article published online:
16 May 2024

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• 11 3,4-Dihydroquinolin-2(1H)-ones 3a–y; General ProcedureA 10 mL reaction vial was sequentially charged with FeCl₃ (5.0 mg, 0.03 mmol, 0.1 equiv), picolinic acid (7.4 mg, 0.06 mmol, 0.2 equiv), NaBrO₃ (90.6 mg, 0.6 mmol, 2 equiv), the appropriate oxamic acid (0.3 mmol), MeCN (2.5 mL), H₂O (2.5 mL), and the appropriate alkene (0.6 mmol). The vial was sealed and the mixture was irradiated by blue LEDs (2 × Kessil 40 W, λ = 427 nm) for 16 h at r.t., and then the mixture was diluted with EtOAc (40 mL) and H₂O (5 mL), and the organic layer was recovered, washed with brine, dried (Na₂SO₄), filtered, and concentrated under reduced pressure. The residue was purified by column chromatography.Ethyl 1-Methyl-2-oxo-1,2,3,4-tetrahydroquinoline-4-carboxylate (3a)Prepared according to the general procedure from N-methyl-N-phenyloxamic acid (1a; 53.8 mg, 0.3 mmol) as a pale-yellow solid; yield: 46.8 mg (67%).¹H NMR (400 MHz, CDCl₃): δ = 7.31 (ddd, J = 8.4, 8.0, 1.6 Hz, 1 H), 7.26 (d, J = 7.6 Hz, 1 H), 7.05 (ddd, J = 8.4, 7.6, 0.8 Hz, 1 H), 7.00 (d, J = 8.4 Hz, 1 H), 4.19–4.10 (m, 2 H), 3.84 (dd, J = 6.0, 4.4 Hz, 1 H), 3.35 (s, 3 H), 3.02 (AB q, J = 16.4, 4.4 Hz, 1 H), 2.78 (dd, J = 16.0, 6.0 Hz, 1 H), 1.22 (t, J = 7.1 Hz, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 171.5, 168.1, 140.2, 128.7, 128.5, 123.0, 122.7, 115.1, 61.4, 42.1, 33.7, 29.5, 14.0.Ethyl 4-Cyano-1-methyl-2-oxo-3-phenyl-1,2,3,4-tetrahydroquinoline-4-carboxylate (3p)Prepared according to the general procedure from N-methyl-N-phenyloxamic acid (1a; 54.1 mg, 0.3 mmol) as a white solid; yield: 47.1 mg (47%).IR (film): 1744, 1684, 1469, 1362, 1235, 702 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 7.52–7.45 (m, 2 H), 7.32–7.26 (m, 2 H), 7.26–7.23 (m, 1 H), 7.21–7.13 (m, 4 H), 4.45 (s, 1 H), 4.30–4.16 (m, 2 H), 3.46 (s, 3 H), 1.20 (t, J = 7.2 Hz, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 166.0, 165.7, 139.3, 132.8, 130.9, 129.1 (2 C), 128.8, 128.8 (2 C), 128.1, 124.1, 118.3, 115.7, 63.9, 53.0, 52.4, 30.1, 13.7. FTMS (ESI⁺): m/z (%) = 335 (100) [M + H]⁺. HRMS (ESI⁺): m/z [M + H]⁺ calcd for C₂₀H₁₉N₂O₃: 335.1390; found: 335.1389.