Synlett 2021; 32(09): 905-912
DOI: 10.1055/a-1468-5962
letter

Radical Cyclization of Olefinic Amides through α-C(sp3)–H Functionalization of Ketones under Catalyst-, Ligand-, and Base-Free Conditions

Fu-Hua Qin
a  Key Laboratory of Advanced Mass Spectrometry and Molecular Analysis of Zhejiang Province, School of Materials Science and Chemical Engineering, Ningbo University, Ningbo, Zhejiang, 315211, P. R. of China
,
Qing-Qing Kang
a  Key Laboratory of Advanced Mass Spectrometry and Molecular Analysis of Zhejiang Province, School of Materials Science and Chemical Engineering, Ningbo University, Ningbo, Zhejiang, 315211, P. R. of China
,
Jun-Yao Zhang
a  Key Laboratory of Advanced Mass Spectrometry and Molecular Analysis of Zhejiang Province, School of Materials Science and Chemical Engineering, Ningbo University, Ningbo, Zhejiang, 315211, P. R. of China
,
Sen-Jie Hu
a  Key Laboratory of Advanced Mass Spectrometry and Molecular Analysis of Zhejiang Province, School of Materials Science and Chemical Engineering, Ningbo University, Ningbo, Zhejiang, 315211, P. R. of China
,
Yi Liu
a  Key Laboratory of Advanced Mass Spectrometry and Molecular Analysis of Zhejiang Province, School of Materials Science and Chemical Engineering, Ningbo University, Ningbo, Zhejiang, 315211, P. R. of China
,
Yiping Ruan
a  Key Laboratory of Advanced Mass Spectrometry and Molecular Analysis of Zhejiang Province, School of Materials Science and Chemical Engineering, Ningbo University, Ningbo, Zhejiang, 315211, P. R. of China
,
Hongxing Zheng
b  Institution of Functional Organic Molecules and Materials, School of Chemistry and Chemical Engineering, Liaocheng University, Liaocheng, 252059, P. R. of China
c  State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, Collaborative Innovation Center for Guangxi Ethnic Medicine, School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin, 541199, P. R. of China
,
Yi-Lin Fang
c  State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, Collaborative Innovation Center for Guangxi Ethnic Medicine, School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin, 541199, P. R. of China
,
Hongxin Liu
d  College of Chemistry and Materials Engineering, Institute of New Materials & Industrial Technology, Wenzhou University, Wenzhou, 325035, P. R. of China
,
Wen-Ting Wei
a  Key Laboratory of Advanced Mass Spectrometry and Molecular Analysis of Zhejiang Province, School of Materials Science and Chemical Engineering, Ningbo University, Ningbo, Zhejiang, 315211, P. R. of China
› Author Affiliations
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).


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.

Supporting Information



Publication History

Received: 21 January 2021

Accepted after revision: 27 March 2021

Publication Date:
27 March 2021 (online)

© 2021. Thieme. All rights reserved

Georg Thieme Verlag KG
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  • 11 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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