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Metal-, Photocatalyst-, and Light-Free Minisci C-H Acetylation of N-Heteroarenes with Vinyl Ethers

Jianyang Dong, Jianhua Liu, Hongjian Song, Yuxiu Liu and Qingmin Wang*

*Research Institute of Elemento-Organic Chemistry, College of Chemistry, Nankai University, Tianjin 300071, People’s Republic of China, Email:

J. Dong, J. Liu, H. Song, Y. Liu, Q. Wang, Org. Lett., 2021, 23, 4374-4378.

DOI: 10.1021/acs.orglett.1c01310

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The use of vinyl ethers as robust, inexpensive acetyl sources enables a mild, operationally simple Minisci C-H acetylation of N-heteroarenes. The reaction does not require a catalyst or high temperature and is therefore significantly more sustainable than previously reported methods in terms of cost, reagent toxicity, and waste generation.

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proposed mechanism

General Procedure for the alkylation of N-heteroarenes:

To a 15 mL glass vial was added heteroarene (0.2 mmol, 1.0 equiv), n-butyl vinyl ether (78 μL, 0.6 mmol, 3.0 equiv), Na2S2O8 (142.8 mg, 0.6 mmol, 3.0 equiv), TFA (30 μL, 0.4 mmol, 2.0 equiv) and 6 mL of DMSO. The reaction mixture was degassed by bubbling with argon for 30 s with an outlet needle and the vial was sealed with PTFE cap. The mixture was then stirred rapidly at 60°C for 24 h. The mixture was diluted with 20 mL of aqueous 1 M NaHCO3 solution, and extracted with DCM (3 × 20 mL). The combined organic extracts were washed with brine (40 mL), dried over Na2SO4, and concentrated in vacuo. Purification of the crude product by flash chromatography on silica gel using petroleum ether / EtOAc (20:1 - 3:1) afforded the desired product.

Key Words

isoquinolines, quinazolines, quinolines, sodium peroxydisulfate

ID: J54-Y2021