A Novel Route to 2-Arylquinolines: Reductive Cleavage of 2′-Nitroaryl-∆²-isoxazolines

The article is dedicated to Prof. Dr. Michael Schmittel on the occasion of his 60^th birthday.

Abstract

A novel synthetic route for the synthesis of quinolines starting from Δ²-isoxazolines under reductive conditions is reported. The ­reductive cyclization to quinolines is achieved under both metal and metal-free conditions. The reaction proceeds via an intramolecular N–H···O hydrogen bond intermediate, accelerating the reductive cleavage 1000-fold (DFT calculations) in comparison with non-hydrogen bonded system.

Key words

heterocycles - cyclization - reduction - isoxazoline - quinolines

• References and Notes

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• 32 2-Arylquinoline Derivatives 3; General Procedure 2 To a solution of 2′-nitroaryl-Δ²-isoxazoline 1 (1.00 mmol, 1.0 equiv) in DMSO (7.0 mL) was added sodium dithionite (6.00 mmol, 6.0 equiv) at r.t. The suspension was warmed to 100 °C and stirred for 3–5 h. The reaction was monitored by TLC and LC-MS and, after complete conversion, the reaction mixture was cooled to 25 °C. The reaction mixture was poured into an icecold solution of sodium hydroxide and stirred for 10 min. The aqueous phase was extracted with diethyl ether (3 × 10.0 mL) and the combined organic layers were washed with water (10.0 mL) followed by brine (10.0 mL), dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated under reduced pressure to give the crude product which was purified by flash chromatography. 2-(2,4,6-Trifluorophenyl)quinoline (3l) White solid; yield: 137 mg (53%); mp 97–98 °C. ¹H NMR (CDCl₃, 400 MHz): δ = 8.26 (d, J = 8.2 Hz, 1 H), 8.19 (d, J = 8.2 Hz, 1 H), 7.88 (d, J = 8.3 Hz, 1 H), 7.77 (ddd, J = 8.5, 7.0, 1.4 Hz, 1 H), 7.60 (t, J = 7.5 Hz, 1 H), 7.54 (d, J = 8.5 Hz, 1 H), 6.83 (t, J = 8.0 Hz, 2 H). ¹³C NMR (CDCl₃, 101 MHz): δ = 164.1–159.5 (m, 3 C), 149.1, 148.2, 136.5, 130.0, 129.7, 127.6, 127.3, 127.1, 123.2, 101.0–100.4 (m, 2 C). HRMS (ESI-TOF): m/z [M + H]⁺ calcd for C₁₅H₈F₃N: 259.0608; found: 259.0608.