Coupling Reaction of Aryl Halides with Orthoformate Ester

Abstract

Herein, we report that orthoformate ester and N,N-dimethylformamide di-tert-butyl acetal can be a source of alkoxy radicals. We have developed a coupling reaction with aryl halides as a way of utilizing them. This has led to the synthesis of aromatic ethers with tertiary alkoxy groups, which are generally considered difficult to synthesize.

Key word

C–O bond formation - hydrogen atom transfer - tertiary alkoxy group - photoredox reaction

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• 22 General Procedure for 3a In the glovebox, a 5 mL glass vial, equipped with a Teflon stir bar, was charged with NiBr₂·glyme (15.5 mg, 50.0 μmol, 0.100 equiv), dtbbpy (20.2 mg, 75.0 μmol, 0.150 equiv), and trimethyl orthoformate (5.00 mL). The nickel catalyst solution was stirred for 20 min, forming a green suspension. To a separate 5 mL glass vial, equipped with a Teflon stir bar, was added 4CzIPN (11.8 mg, 15.0 μmol, 0.0300 equiv) and trimethyl orthoformate (3.00 mL). The photoredox catalyst solution was stirred for 10 min. Meanwhile, a 12 mL borosilicate reaction tube with a Teflon stir bar was charged with methyl 4-bromobenzoate (215 mg, 0.500 mmol), K₃PO₄ (212 mg, 1.00 mmol, 2.00 equiv), quinuclidine (5.50 mg, 50.0 μmol, 0.100 equiv), and trimethyl orthoformate (2.00 mL). The photocatalyst solution and nickel catalyst solutions were then added sequentially (total solvent volume: 10.0 mL, 50.0 μM). The reaction tube was capped with a Teflon septum cap, sealed with electrical tape, and removed from the glovebox. The reaction was stirred for 20 h while illuminating with 427 nm Kessil LED lump placed horizontally at 2 cm distances on either side of the reaction tube (Scheme S1 and S2). Upon completion, the reaction mixture was filtered through Celite and washed with dichloromethane. The residue was purified by column chromatography (20 cm × 300 cm, SiO₂ 60g, hexane/ethyl acetate = 10/1). Compound 3a: yield 77%, colorless solid. ¹H NMR (400 MHz, CDCl₃): δ 7.99–8.01 (d, J = 8.93 Hz, 2 H), 6.91–6.93 (d, J = 8.93 Hz, 2 H) 3.89 (s, 3 H), 3.86 (s, 3 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 167.0, 163.4, 131.7, 122.7, 113.7, 55.5, 52.0 ppm. HRMS (ESI): m/z [M + H]⁺ calcd for C₉H₁₁O₃: 167.0708; found: 167.0692.