A Synthetic Strategy for 2-Alkylchromanones: Fe(III)-Catalyzed ­Reductive Cross-Coupling of Unactivated Alkenes with Chromones

Abstract

A new synthetic approach for 2-alkylchromanones utilizing Fe (III)-catalyzed reductive cross-coupling of olefins with chromones has been developed. The reaction conditions are mild, and various substituted alkenes are applicable to the process. Moreover, control experiments were conducted, and a plausible mechanism is proposed.

Key words

olefin reductive cross-coupling - unactivated olefins - radical conjugate addition - 2-alkylchromanones

• References and Notes

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• 13 Experimental Procedure and Characterization Data for Compound 3af To a solution of chromone 1a (0.3 mmol, 1 equiv) and Fe(acac)₃ (31.8 mg, 0.09 mmol, 30 mol%) in EtOH (1.5 mL, 0.2 M) were added olefin 2f (0.9 mmol, 3 equiv) and PhSiH₃ (74 μL, 0.9 mmol, 3 equiv). The resulting mixture was heated in an oil bath preheated to 40 °C with stirring for 5 h. The reaction mixture was then cooled to room temperature, diluted with brine, and extracted with EtOAc (3 × 5 mL). The combined organic layers were washed with brine, dried with Na₂SO₄, filtered, and concentrated under reduced pressure. The resulting crude product was then purified by column chromatography on silica gel (petroleum ether/EtOAc = 5:1) to afford the desired product 3af as a colorless oil (58.3 mg, 83% yield). ¹H NMR (300 MHz, CDCl₃): δ = 7.83 (dt, J = 7.5, 0.5 Hz, 1 H), 7.46–7.41 (m, 1 H), 7.0–6.94 (m, 2 H), 4.14 (dd, J = 12.9, 3.6 Hz, 1 H), 3.80–3.75 (m, 2 H), 2.77–2.61 (m, 2 H), 1.94 (s, 1 H), 1.80–1.77 (m, 1 H), 1.71–1.23 (m, 1 H), 1.06 (d, J = 4.8 Hz, 6 H) ppm. ¹³C NMR (75 Hz, CDCl₃): δ = 193.33, 161.80, 135.91, 126.84, 121.18, 120.72, 117.73, 84.23, 59.06, 40.95, 38.05, 36.11, 23.38, 23.12 ppm. HRMS (ESI): m/z [M + H]⁺ calcd for C₁₄H₁₉O₃ ⁺: 235.1328; found: 235.1327.
• 14 Experimental Procedure for Compound 3if on Gram Scale To a solution of substrate 1i (1.36 g, 8 mmol, 1 equiv) and Fe(acac)₃ (0.84 g, 2.4 mmol, 30 mol%) in EtOH (40 mL, 0.2 M) were added olefin 2f (24 mmol, 3 equiv) and PhSiH₃ (2 mL, 24 mmol, 3 equiv). The resulting mixture was heated in an oil bath preheated to 40 °C with stirring for 5 h. The reaction mixture was then cooled to room temperature, diluted with brine, and extracted with EtOAc (3 × 20 mL). The combined organic layers were washed with brine, dried with Na₂SO₄, filtered, and concentrated under reduced pressure. The resulting crude product was then purified by column chromatography on silica gel (petroleum ether/EtOAc = 3:1) to afford the desired product 3if as a slightly yellow solid (1.51 g, 73% yield).