二氢喹唑啉酮衍生物参与的自由基反应研究进展

doi:10.6023/cjoc202501014

摘要/Abstract

作为二氢喹唑啉酮衍生物的前体, 酮是一类商品化的大宗化学品, 同时也是在自然界中广泛存在的活性骨架. 近年来, 由“酮”作为原料而合成出来的二氢喹唑啉酮化合物被证实是一类非常好的有机官能化试剂, 相关研究被陆续报道. 该类试剂经单电子转移与C—C键断裂可以产生活性自由基中间体, 继而发生多样化的化学转化构筑重要的有机分子. 综述了近年来由酮演变而来的二氢喹唑啉酮化合物参与的自由基反应研究进展, 涵盖反应设计、反应机理和研究展望等内容.

关键词: 二氢喹唑啉酮, 自由基反应, 酮

Ketones, as precursors to dihydroquinazolinone derivatives, are a class of commercially available bulk chemicals and serve as an active scaffold that is widely present in nature. In recent years, dihydroquinazolinone compounds synthesized from ketones as starting materials have proven to be excellent reagents for organic functionalization, with related studies being reported consecutively. These reagents can generate reactive radical intermediates via single-electron transfer (SET) and C—C bond cleavage, subsequently undergoing various chemical transformations to build important organic molecules. This article provides an overview of the recent advancements in free radical reactions involving dihydroquinazolinone compounds derived from ketones, discussing topics such as reaction design, mechanisms, and future research prospects. This article provides an overview of the recent advancements in free radical reactions involving dihydroquinazolinone compounds derived from ketones, discussing topics such as reaction design, mechanisms, and future research prospects.

Key words: dihydroquinazolinone, radical reactions, ketones

引用此文

李子杰, 郝铮, 杨升院, 杨文超, 金涛. 二氢喹唑啉酮衍生物参与的自由基反应研究进展[J]. 有机化学, 2025, 45(10): 3644-3654.

Zijie Li, Zheng Hao, Shengyuan Yang, Wenchao Yang, Tao Jin. Recent Advances in the Radical Reactions of Dihydroquinazolinone Derivatives[J]. Chinese Journal of Organic Chemistry, 2025, 45(10): 3644-3654.

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图/表 16

图式1. 二氢喹唑啉酮衍生物参与的有机转化

Scheme 1. Organic transformations involving dihydroquinazolinone derivatives

图式2. 烯烃的氢烷基化反应

Scheme 2. Hydrogenation alkylation reaction of olefins

图式3. 烯烃的烷基芳基化反应

Scheme 3. Alkylation-arylation reaction of olefins

图式4. 烯烃的串联环化反应

Scheme 4. Cascade reaction of alkenes

图式5. 烯烃的氢氟烷基化反应

Scheme 5. Hydrofluoroalkylation reaction of olefins

图式6. 三氟甲基取代烯烃的脱氟烷基化反应

Scheme 6. Defluoralkylation reaction of trifluoromethyl-sub- stituted alkenes

图式7. 镍催化二氢喹唑啉酮与溴代物的偶联反应

Scheme 7. Nickel-catalyzed coupling reaction of dihydroquinazolinone with brominated compounds

图式8. 二氢喹唑啉酮与三氟甲基试剂的偶联反应

Scheme 8. Coupling reaction of dihydroquinazolinone with trifluoromethyl reagents

图式9. 光催化二氢喹唑啉酮与炔基溴的反应

Scheme 9. Photocatalytic reaction of dihydroquinazolinone with alkynyl bromide

图式 10. 光催化二氢喹啉酮与砜衍生物的反应

Scheme 10. Photocatalytic reaction of dihydroquinazolinone with organic sulfone

图式11. 光催化二氢喹唑啉酮的酰基化反应

Scheme 11. Photocatalytic acylation reaction of dihydroquinazolinone

图式12. 光催化二氢喹唑啉酮与酯的反应

Scheme 12. Photocatalytic reaction of dihydroquinazolinone with esters

图式13. 光催化螺环二氢喹唑啉酮的开环偶联反应

Scheme 13. Photocatalytic ring-opening cross-coupling reaction of spirodihydroquinazolinone

图式14. 光催化螺环二氢喹唑啉酮的开环卤代反应

Scheme 14. Photocatalytic ring-opening and halogenation reaction of spirodihydroquinazolinone

图式15. 光催化螺环二氢喹唑啉酮的开环脱氟反应

Scheme 15. Photocatalytic ring-opening defluorination reaction of spirodihydroquinazolinone

图式16. 光催化螺环二氢喹唑啉酮的开环胺化反应

Scheme 16. Photocatalytic ring-opening and amination reaction of spirodihydroquinazolinone

参考文献 26

[1]	Gunaga, P.; Lloyd, J.; Mummadi, S.; Banerjee, A.; Dhondi, N. K.; Hennan, J.; Subray, V.; Jayaram, R.; Rajugowda, N.; Umamaheshwar Reddy, K.; Kumaraguru, D.; Mandal, U.; Beldona, D.; Adisechen, A. K.; Yadav, N.; Warrier, J.; Johnson, J. A.; Sale, H.; Putlur, S. P.; Saxena, A.; Chimalakonda, A.; Mandlekar, S.; Conder, M.; Xing, D.; Gupta, A. K.; Gupta, A.; Rampulla, R.; Mathur, A.; Levesque, P.; Wexler, R. R.; Finlay, H. J. J. Med. Chem. 2017, 60, 3795.
[2]	(a) Noel, R.; Gupta, N.; Pons, V.; Goudet, A.; Garcia-Castillo, M. D.; Michau, A.; Martinez, J.; Buisson, D.-A.; Johannes, L.; Gillet, D.; Barbier, J.; Cintrat, J.-C. J. Med. Chem. 2013, 56, 3404.
	(b) Wang, J.; Ansari, M. F.; Zhou, C. H. J. Med. Chem. 2021, 64, 7630.
[3]	(a) Zhong, L.-J.; Chen, H.; Shang, X.; Fan, J.-H.; Tang, K.-W.; Liu, Y.; Li, J.-H. J. Org. Chem. 2024, 89, 8721.
	(b) He, H.; Pan, C.-M.; Hou, Z.-W.; Sun, M.; Wang, L. J. Org. Chem. 2024, 89, 7531.
	(c) Zhang, M.-M.; Sun, Y.; Wang, W.-W.; Chen, K.-K.; Yang, W.-C.; Wang, L. Org. Biomol. Chem. 2021, 19, 3844.
	(d) Liu, Y.; Zhu, K.; Li, X. Tetrahedron Chem, 2024, 11, 100083.
[4]	(a) Shang, T.; Lu, L.; Cao, Z.; Liu, Y.; He, W.; Yu, B. Chem. Commun. 2019, 55, 5408.
	(b) Lv, Y.; Cui, H.; Meng, N.; Yue, H.; Wei, W. Chin. Chem. Lett. 2022, 33, 97.
	(c) Wang, X.-C.; Wu, S.-H.; Yang, R.-X.; Song, H.-J.; Liu, Y.-X.; Wang, Q.-M. Chem Sci. 2023, 14, 13367.
	(d) He, H.; Wan, Q.; Hou, Z.-W.; Zhou, Q.; Wang, L. Org. Lett. 2023, 25, 7014.
	(e) Lanb, M.; Steiniger, K.; Trigoura, L.; Wu, J.; Kundu, G.; Huang, H.; Lambert, T. Chem. Rev. 2024, 124, 12264.
	(f) Zhu, Y.-X.; Xiao, T.; Xia, D.; Yang, W-C. Chin. J. Org. Chem, 2022, 42, 4067 (in Chinese).
	(朱玉溪, 肖婷, 夏冬, 杨文超, 有机化学, 2022, 42, 4067.) doi: 10.6023/cjoc202208017
	(g) Klöpfer, V.; Chinchole, A.; Reiser, O. Tetrahedron Chem. 2024, 10, 100073.
	(h) Wang, F.-D.; Jiang, J.; Xu, T.; Yang, W.-C.; Zhang, S.-P.; Wang, M.; Li, P. Tetrahedron Chem. 2025, 13, 100119.
[5]	Smith, M. B.; March, J. March's Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, 8th ed.; John Wiley and Sons, Hoboken, NJ, 2020,pp. 1335-1438.
[6]	(a) Holmberg-Douglas, N.; Nicewicz, D. A. Chem. Rev. 2022, 122, 1925.
	(b) Gao, F.; Zhang, S.; Lv, Q.; Yu, B. Chin. Chem. Lett. 2022, 33, 2354.
	(c) Zhang, S.-P.; Guo, D.-W.; Yang, M.-L.; Xia, Y.-T.; Yang, W.-C. J. Org. Chem. 2024, 89, 10614.
	(d) Ji, Y.; Li, Z.; Yang, Y.; Yang, X.; Yang, W.-C. Chem. Eur. J. 2024,30, e202402891.
	(d) Yang, W.-C.; Sun, Y.; Bao, X.-B.; Zhang, S.-P.; Shen, L.-Y. Green Chem. 2023, 25, 3111.
	(e) Yang, W.-C.; Feng, J.-G.; Wu, L.; Zhang, Y.-Q. Adv. Synth. Catal. 2019, 361, 1700.
	(f) Huang, X.; Ji, H.; Li, X.; Luo, Q.; Li, T.; Ou, L.; He, W.-M. J. Org. Chem. 2024, 89, 10654.
	(g) Yang, W. C.; Sun, Y.; Shen, L. Y.; Xie, X.; Yu, B. Mol. Catal. 2023, 535, 112819.
[7]	(a) Zhang, Y.; Sun, K.; Lv, Q.; Chen, X.; Qu, L.; Yu, B. Chin. Chem. Lett. 2019, 30, 1361.
	(b) Zhang, S.-P.; Lan, J.-X.; Yang, M.-L.; Cao, J.-Y.; Zhang, Y.; Yang, W.-C. Org. Lett. 2024, 26, 9990.
	(c) Singh, P. P.; Sinha, S.; Gahtori, P.; Tivari, S.; Srivastava, V. Org. Biomol. Chem. 2024, 22, 2523.
	(d) Ghosh, S.; Pyne, P.; Ghosh, A.; Choudhury, S.; Hajra, A. Org. Biomol. Chem. 2023, 21, 1591.
[8]	Li, L.; Fang, L.; Wu, W.; Zhu, J. Org. Lett. 2020, 22, 5401.
[9]	Mondal, P. P.; Das, S.; Venugopalan, S.; Krishnan, M.; Sahoo, B. Org. Lett. 2023, 25, 1441.
[10]	Bag, S.; Ojha, S.; Venugopalan, S.; Sahoo, B. J. Org. Chem. 2023, 88, 12121.
[11]	(a) Chen, X.; Ouyang, W.; Li, X.; He, W.-M. Chin. J. Org. Chem. 2023, 43, 4213 (in Chinese).
	(陈祥, 欧阳文韬, 李潇, 何卫民, 有机化学, 2023, 43, 4213.) doi: 10.6023/cjoc202307026
	(b) Chen, X.; Jiang, J.; Huang, X.; He, W.-M. Org. Chem. Front. 2023, 10, 3898.
	(c) Ji, H.; Song, H.; Hou, J.; Xu, Y.; Zeng, L.; He, W.-M. J. Org. Chem. 2024, 89, 9543.
	(d) Yang, Y.; Yang, Z.; Cheng, C.; Qing, F. Chin. J. Chem. 2013, 31, 805.
	(e) Zhao, S.; Zhu, P.; Xu, B.; Ling, S.; Zhang, L.; Sun, F.-G. J. Org. Chem. 2023, 88, 9283.
	(f) Xiao, F.; Lin, J.-H.; Hao, F.; Zheng, X.; Guo, Y.; Xiao, J.-C. Org. Chem. Front. 2022, 9, 1982.
	(g) Wang, Z.; Sun, Y.; Shen, L.-Y.; Yang, W.; Meng, F.; Li, P. Org. Chem. Front. 2022, 9, 853.
[12]	Yedase, G. S.; Arif, M.; Kuniyil, R.; Yatham, V. R. Org. Lett. 2023, 25, 6200.
[13]	Yan, L.; Zhang, T.; Lv, Z.; Fu, M.-C. Org. Chem. Front. 2023, 10, 6205.
[14]	Kumar, S., Jyoti, J., Gupta, D., Singh, G., Kumar, A. SynOpen 2023, 7, 580.
[15]	(a) Lee, S.-C.; Li, L.-Y.; Tsai, Z.-N.; Lee, Y.-H.; Tsao, Y.-T.; Huang, P.-G.; Cheng, C.-K.; Lin, H.-B.; Chen, T.-W.; Yang, C.-H.; Chiu, C.-C.; Liao, H.-H. Org. Lett. 2022, 24, 85.
	(b) Lv, X.; Abrams, R.; Martin, R. Nat. Commun. 2022, 13, 2394.
[16]	Cong, F.; Mega, R. S.; Chen, J.; Day, C. S.; Martin, R. Angew. Chem., Int. Ed. 2023,62, e202214633.
[17]	Wu, H.; Chen, S.; Xiao, D.; Li, F.; Zhou, K.; Yin, X.; Liu, C.; He, X.; Shang, Y. Org. Lett. 2023, 25, 1166.
[18]	Wu, H.; Chen, S.; Liu, C.; Zhao, Q.; Wang, Z.; Jin, Q.; Sun, S.; Guo, J.; He, X.; Walsh, P. J.; Shang, Y. Angew. Chem., Int. Ed. 2024,63, e202314790.
[19]	(a) Wu, Z.; Liu, J.; Zhou, R.; Deng, M.; Li, X.; ji, H.; He, W.-M. J. Org. Chem. 2024, 89, 12693.
	(b) Ji, W.; Tan, H.; Wang, M.; Li, P.; Wang, L. Chem. Commun. 2016, 52, 1462.
	(c) Banerjee, A.; Lei, Z.; Ngai, M.-Y. Synthesis 2019, 51, 303.
	(d) Yang, W.-C.; Dai, P.; Luo, K.; Ji, Y.-G.; Wu, L. Adv. Synth. Catal. 2017, 359, 2390.
	(e) Yuan, X.; Zheng, J.; Ma, X.; Huang, X.; Lv, Q.; Sun, K.; Chen, X.; Qu, L.; Yu, B. Org. Chem. Front. 2025, 12, 849.
[20]	(a) Li, Q.-Z.; He, M.-H.; Zeng, R.; Lei, Y.-Y.; Yu, Z.-Y.; Jiang, M.; Zhang, X.; Li, J.-L. J. Am. Chem. Soc. 2024, 146, 22829.
	(b) Wang, T.; Zhang, Y.; Gao, F.; Yan, X. Org. Lett. 2024, 26, 6915.
[21]	He, K.; Jin, N.; Chen, C.; Zheng, Y.; Pan, F. Org. Lett. 2024, 26, 9503.
[22]	(a) Yang, W.-C.; Zhang, M.-M.; Feng, J.-G. Adv. Synth. Catal. 2020, 362, 4446.
	(b) Sun, Y.; Zhang, S.-P.; Yang, W.-C. J. Org. Chem. 2023, 88, 13279.
	(c) Zhang, M.; Shen, L.; Dong, S.; Li, B.; Meng, F.; Si, W.-J.; Yang, W.-C. Eur. J. Org. Chem. 2021, 4465.
	(d) Yang, W.-C.; Zhang, M. M.; Sun, Y.; Chen, C. Y.; Wang, L. Org. Lett. 2021, 23, 6691.
	(e) Li, J.-N.; Li, Z.-J.; Shen, L.-Y.; Li, P.; Zhang, Y.; Yang, W.-C. Org. Biomol. Chem. 2022, 20, 6659.
[23]	Miao, H.-J.; Zhang, J.-H.; Li, W.; Yang, W.; Xin, H.; Gao, P.; Duan, X.-H.; Guo, L.-N. Chem. Sci. 2024, 15, 8993.
[24]	(a) Yang, W.-P.; Miao, H.-J.; Liu, L.; Duan, X.-H.; Guo, L.-N. Org. Lett. 2024, 26, 7442.
	(b) Yang, W.; Miao, H.; Wang, G.; Yang, X.; Wang, X.; Liu, L.; Duan, X.-H.; Guo, L.-N. J. Org. Chem. 2024, 89, 18713.
[25]	Zhang, J.-H.; Miao, H.-J.; Li, J.-Y.; Li, W.; Ma, P.; Duan, X.-H.; Guo, L.-N. Chem. Commun. 2024, 60, 8095.
[26]	Li, W.; Miao, H.-J.; Zhang, J.-H.; Duan, X.-H.; Guo, L.-N. Chem. Eur. J. 2024,30, e202402602.