Synthesis of Furo- and Thienoquinolines by Using an Amine Oxidase-Inspired Catalyst

Dedicated to Professor Dr. Hisashi Yamamoto on the occasion of his 80^th birthday

Abstract

We report the regioselective synthesis of furo- and thienoquinolines by using an amine oxidase-inspired catalyst (1,10-phenanthroline-5,6-dione) and an abundant Lewis acid (FeCl₃) as a co-catalyst. The aerobic amine dehydrogenation proceeds under mild conditions and produces the quinolines in high yields. Mechanistic studies helped to identify the possible reaction intermediates and the specific role of the catalyst in the multistep cascade.

Key words

biomimetic catalyst - iron catalysis - aerobic oxidation - dehydrogenation - quinolines

Publication History

Received: 30 April 2023

Accepted after revision: 31 May 2023

Accepted Manuscript online:
31 May 2023

Article published online:
19 July 2023

• References and Notes

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• 14 Quinolines 3; General Procedure A 10 mL sealed tube was charged with the appropriate aniline derivative 1 (0.1 mmol), phd (0.020 mmol, 20 mol%), FeCl₃ (0.010 mmol, 10 mol%), TsOH·H₂O (0.010 mmol, 10 mol%), and PhNO₂ (0.5 mL). Amine 2 (0.15 mmol) was added slowly, and the mixture was stirred at r.t. in the presence of O₂ (balloon; 1 atm) for about 5 min. The tube was then capped and placed in a preheated oil bath at 80 °C for 36 h. When the reaction was complete, it was quenched with H₂O (5 mL) and the mixture was extracted with EtOAc or CH₂Cl₂ (3 × 2 mL). The combined organic layer was dried (Na₂SO₄), filtered, and concentrated. The residue was purified by flash column chromatography [silica gel (100–200 or 200–400 mesh), EtOAc–hexane]. 4-(4-Methoxyphenyl)furo[2,3-c]quinoline (3aa) Colorless solid; yield: 22.0 mg (0.080 mmol, 80%); R_f = 0.4 (EtOAc–hexane, 2:98). ¹H NMR (500 MHz, CDCl₃): δ = 8.51 (d, J = 9.0 Hz, 2 H), 8.29 (d, J = 8.2 Hz, 1 H), 8.07 (d, J = 8.1 Hz, 1 H), 7.91 (d, J = 2.1 Hz, 1 H), 7.69 (t, J = 7.6 Hz, 1 H), 7.57 (t, J = 7.6 Hz, 1 H), 7.29 (d, J = 2.1 Hz, 1 H), 7.11 (d, J = 9.0 Hz, 2 H), 3.91 (s, 3 H). ¹³C NMR (126 MHz, CDCl₃): δ = 161.2, 147.4, 146.9, 144.4, 144.3, 130.8, 130.7, 129.9, 128.9, 127.7, 126.2, 123.3, 122.9, 114.2, 105.6, 55.5. HRMS (ESI⁺): m/z [M + H]⁺calcd for C₁₈H₁₄NO₂: 276.1019; found: 276.1020. 4-(4-Methoxyphenyl)-8-methylthieno[2,3-c]quinoline (3da) Colorless solid; yield: 26.0 mg (0.085 mmol, 85%); R_f = 0.4 (EtOAc–hexane, 4:96). ¹H NMR (500 MHz, CDCl₃): δ = 8.17 (d, J = 8.4 Hz, 1 H), 8.11 (d, J = 8.9 Hz, 2 H), 8.01 (s, 1 H), 7.95 (d, J = 5.3 Hz, 1 H), 7.77 (d, J = 5.5 Hz, 1 H), 7.53 (d, J = 8.5 Hz, 1 H), 7.10 (d, J = 8.9 Hz, 2 H), 3.89 (s, 3 H), 2.59 (s, 3 H). ¹³C NMR (126 MHz, CDCl₃): δ = 160.8, 152.7, 143.6, 142.5, 136.3, 132.7, 132.0, 131.3, 130.2, 130.1, 129.6, 123.4, 122.5, 121.9, 114.2, 55.5, 21.9. HRMS (ESI⁺): m/z [M + H]⁺calcd for C₁₉H₁₆NOS: 306.0947; found: 306.0956. 4-(p-Tolyl)furo[2,3-c]quinoline (3ad) Colorless solid; yield: 20.0 mg (0.077 mmol, 77%); R_f = 0.5 (EtOAc–hexane, 5:95). ¹H NMR (500 MHz, CDCl₃): δ = 8.41 (d, J = 8.2 Hz, 2 H), 8.28 (d, J = 8.4 Hz, 1 H), 8.11 (d, J = 7.9 Hz, 1 H), 7.94 (d, J = 2.0 Hz, 1 H), 7.70 (t, J = 7.7 Hz, 1 H), 7.60 (t, J = 7.6 Hz, 1 H), 7.40 (d, J = 8.2 Hz, 2 H), 7.33 (d, J = 2.1 Hz, 1 H), 2.47 (s, 3 H). ¹³C NMR (126 MHz, CDCl₃): δ = 147.6, 146.9, 144.9, 144.5, 140.0, 133.7, 130.8, 130.3, 129.5, 129.1, 127.7, 126.4, 123.3, 123.2, 105.6, 21.6. HRMS (ESI⁺): m/z [M + H]⁺calcd for C₁₈H₁₄NO: 260.1070; found: 260.1057. 4-(2-Naphthyl)furo[2,3-c]quinoline (3al) Yellowish solid; yield: 19.0 mg (0.064 mmol, 64%); R_f = 0.5 (EtOAc–hexane, 2:98). ¹H NMR (500 MHz, CDCl₃): δ = 9.06 (d, J = 2.0 Hz, 1 H), 8.67 (d, J = 8.7 Hz, 1 H), 8.36 (d, J = 7.6 Hz, 1 H), 8.14 (d, J = 8.1 Hz, 1 H), 8.10–8.04 (m, 2 H), 8.00 (d, J = 2.0 Hz, 1 H), 7.97–7.91 (m, 1 H), 7.74 (t, J = 7.6 Hz, 1 H), 7.63 (t, J = 6.9 Hz, 1 H), 7.61–7.54 (m, 2 H), 7.36 (d, J = 2.1 Hz, 1 H). ¹³C NMR (126 MHz, CDCl₃): δ = 147.7, 147.5, 144.5, 144.1, 134.3, 133.5, 133.3, 131.4, 130.0, 129.7, 129.3, 128.5, 128.1, 127.9, 127.2, 126.8, 126.5, 126.1, 123.4, 123.2, 105.8. HRMS (ESI⁺): m/z [M + H]⁺calcd for C₂₁H₁₄NO: 296.1070; found: 296.1065.
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