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DOI: 10.1055/a-1468-5962
Radical Cyclization of Olefinic Amides through α-C(sp3)–H Functionalization of Ketones under Catalyst-, Ligand-, and Base-Free Conditions
We thank the Fundamental Research Funds for the Provincial Universities of Zhejiang (SJLY2021004), the Zhejiang Provincial Natural Science Foundation of China (LQ19B020004), the Foundation of Zhejiang Educational Committee (Y201839490), and the Foundation of Wenzhou Basic Scientific Research Project (G20180015). Dr. Yi-Lin Fang is also grateful for Doctoral Fund of Ministry of Education of China (Western Region Postdoctoral Talent Funding Program, 2018M633616XB).
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Abstract
A new, efficient, and practical radical cyclization of olefinic amides with ketones through α-C(sp3)–H functionalization in the presence of tert-butyl peroxybenzoate (TBPB) is described for the first time. This protocol assembles a wide range of pivotal and useful benzoxazines in good to excellent yields under mild, catalyst-free, ligand-free, and base-free conditions with wide functional group tolerance. Moreover, the mechanistic study indicates that the α-carbonyl radical is involved in this transformation.
Key words
green synthesis - catalyst-free - ligand-free - base-free - radical cyclization - α-C(sp3)–H functionalizationSupporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/a-1468-5962.
- Supporting Information
Publication History
Received: 21 January 2021
Accepted after revision: 27 March 2021
Accepted Manuscript online:
27 March 2021
Article published online:
16 April 2021
© 2021. Thieme. All rights reserved
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General Procedure
To a Schlenk tube were added olefinic amides 1 (0.2 mmol), ketones 2 (1.0 mL), and TBPB (2.0 equiv). Then the tube was stirred at 120 °C sealed in air for the indicated time until complete consumption of starting material as monitored by TLC and/or GC–MS analysis. After the reaction was finished, the solution was concentrated under reduced pressure, and the mixture was purified by flash column chromatography over silica gel (hexane/ethyl acetate = 10:1) to afford the desired product 3 and was analyzed by 1H NMR and 13C NMR spectroscopy (see the Supporting Information).
Typical Data for Representative Compound 4-(4-Methyl-2-phenyl-4H-benzo[d][1,3]oxazin-4-yl)butan-2-one (3aa)
Yellow oil (0.0500 g, 85% yield). 1H NMR (500 MHz, CDCl3): δ = 8.13–8.12 (m, 2 H), 7.52–7.49 (m, 1 H), 7.46–7.43 (m, 2 H), 7.31–7.30 (m, 2 H), 7.21–7.18 (m, 1 H), 7.07 (d, J = 7.5 Hz, 1 H), 2.66–2.59 (m, 1 H), 2.48–2.42 (m, 1 H), 2.39–2.31 (m, 2 H), 2.05 (s, 3 H), 1.67 (s, 3 H). 13C NMR (125 MHz, CDCl3): δ = 207.8, 156.4, 139.1, 132.8, 131.4, 128.7 (2),128.3, 127.8, 126.8, 125.5, 122.7, 80.4, 38.4, 35.0, 30.1, 28.7.
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