Late-Stage Alkylation of N-Containing Heteroarenes Enabled by Homolysis of Alkyl-1,4-dihydropyridines under Blue LED Irradiation

Xiaoping Chen; Xiaosheng Luo; Kaiqian Wang; Feng Liang; Ping Wang

doi:10.1055/a-1294-0158

Synlett, Inhaltsverzeichnis

Synlett 2021; 32(07): 733-737
DOI: 10.1055/a-1294-0158

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Late-Stage Alkylation of N-Containing Heteroarenes Enabled by Homolysis of Alkyl-1,4-dihydropyridines under Blue LED Irradiation

Xiaoping Chen

^aKey Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province and College of Physics and Optoelectronic Engineering Shenzhen University, Shenzhen 518060, P. R. of China

,

Xiaosheng Luo

^bShanghai Key Laboratory for Molecular Engineering of Chiral Drugs, School of Chemistry and Chemical Engineering Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, P. R. of China

,

Kaiqian Wang

^cCollege of Chemistry & Chemical Engineering, Wuhan University of Science and Technology, Wuhan 430081, P. R. of China

,

Feng Liang

^cCollege of Chemistry & Chemical Engineering, Wuhan University of Science and Technology, Wuhan 430081, P. R. of China

,

Ping Wang ∗

^bShanghai Key Laboratory for Molecular Engineering of Chiral Drugs, School of Chemistry and Chemical Engineering Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, P. R. of China

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Abstract

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Abstract

Alkylated heteroarenes are widely found in bioactive molecules and pharmaceuticals. Therefore, there is great interest in developing a chemoselective alkylation of heteroarenes under mild conditions, particularly during a late-stage functionalization step for the purpose of rapid derivatization. Herein, we introduce an efficient visible-light-promoted C–H alkylation of nitrogen-containing heteroarenes by using C4-alkyl 1,4-dihydropyridines (DHPs) as radical precursors at ambient temperatures. A broad scope of heteroarenes, such as 4-hydroxyquinazoline and its derivatives, including those bearing electron-donating or electron-withdrawing groups, can be successfully alkylated in good yields by using various C4-alkyl DHPs.

Key words

alkylation - hetarenes - dihydropyridines - photochemistry - C–H functionalization

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Referenzen

References and Notes
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31 Cyclohexylation of Quinine; Typical Procedure A solution of quinine (1j; 0.2 mmol, 1.0 equiv) and DHP 2c (0.3 mmol, 1.5 equiv) in degassed TFE (2.0 mL) was bubbled with Ar for 15 min. TFA (22 μL, 0.30 mmol, 1.5 equiv) was added from a microsyringe, and the tube was sealed and irradiated by four 10 W blue LEDs at rt for 4 h. The cap then was removed and the mixture was stirred for another 4 h. After completion, the reaction was quenched by addition of Et₃N (69 μL, 0.50 mmol, 10 equiv) and concentrated. The crude mixture was purified by column chromatography (silica gel) to give 4u as a white solid; yield: 61.8 mg (76%). ¹H NMR (500 MHz, CDCl₃): δ = 12.44 (s, 1 H), 8.17 (d, J = 9.3 Hz, 1 H), 7.89 (s, 1 H), 7.36 (dd, J = 9.3, 2.3 Hz, 1 H), 7.17 (d, J = 2.5 Hz, 1 H), 6.24 (s, 1 H), 5.57 (ddd, J = 17.1, 10.5, 6.7 Hz, 1 H), 5.09–5.00 (m, 2 H), 4.17 (d, J = 11.8 Hz, 1 H), 3.84 (s, 3 H), 3.56–3.46 (m, 1 H), 3.34–3.22 (m, 2 H), 3.12 (dq, J = 16.0, 5.2 Hz, 1 H), 3.08–3.00 (m, 1 H), 2.71 (s, 1 H), 2.17 (d, J = 11.9 Hz, 1 H), 2.12–2.03 (m, 3 H), 1.98 (d, J = 11.2 Hz, 1 H), 1.85 (dt, J = 30.7, 14.1 Hz, 5 H), 1.63 (qd, J = 12.4, 3.3 Hz, 1 H), 1.58–1.41 (m, 3 H), 1.31 (ddd, J = 13.1, 8.6, 3.2 Hz, 2 H). ¹³C NMR (125 MHz, CDCl₃): δ = 160.9, 160.1, 154.1, 137.1, 134.4, 126.7, 125.2, 124.3, 117.7, 117.7, 100.3, 66.6, 60.6, 59.9, 56.7, 54.8, 43.9, 43.0, 37.1, 32.8, 32.0, 26.9, 25.9, 25.9, 24.2, 21.2.

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