Radical Denitrogenative Ring Opening of N-Benzyl-benzotriazoles for the Synthesis of 6-Substituted Phenanthridines under Visible Light Conditions

doi:10.6023/cjoc202403008

Chinese Journal of Organic Chemistry ›› 2025, Vol. 45 ›› Issue (5): 1770-1777.DOI: 10.6023/cjoc202403008 Previous Articles Next Articles

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可见光条件下N-苄基苯并三氮唑自由基脱氮气开环合成6-取代菲啶

李慧^a, 阿布力米提•阿布都卡德尔^a^,^*(), 周磊^a^,^b^,^*()

^a 新疆大学化学学院省部共建碳基能源资源化学与利用国家重点实验室乌鲁木齐 830046
^b 中山大学化学学院绿色化学与分子工程研究院广州 510275

收稿日期:2024-03-05 修回日期:2024-03-20 发布日期:2024-04-24
基金资助:
国家自然科学基金(22271318); 国家自然科学基金(22061040)

Radical Denitrogenative Ring Opening of N-Benzyl-benzotriazoles for the Synthesis of 6-Substituted Phenanthridines under Visible Light Conditions

Hui Li^a, Ablimit Abdukader^a^,^*(), Lei Zhou^a^,^b^,^*()

^a State Key Laboratory of Chemistry and Utilization of Carbon Based Energy Resources, College of Chemistry, Xinjiang University, Urumqi 830046
^b Institute of Green Chemistry and Molecular Engineering, School of Chemistry, Sun Yat-Sen University, Guangzhou 510275

Received:2024-03-05 Revised:2024-03-20 Published:2024-04-24
Contact: * E-mail: ablimit1970@126.com; zhoul39@mail.sysu.edu.cn
Supported by:
National Natural Science Foundation of China(22271318); National Natural Science Foundation of China(22061040)

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Abstract

Phenanthridines are the essential core structural units in a variety of natural alkaloids and biologically active compounds. With organic fluorescein 4CzIPN as the visible light photocatalyst, radical denitrogenative ring opening of N-benzyl-benzotriazoles was achieved under mild conditions. The resultant aryl radicals bearing an ortho-imine unit undergo intramolecular cyclization with arenes, providing a series of 6-substituted phenanthridines efficiently. The generation of biaryl ketone side-products via the extrusion of benzotriazole can be significantly suppressed by using 10% (volume fraction) oxygen as the oxidant.

Key words: benzotriazole, denitrogenative, aryl radical, phenanthridine, visible light photoredox catalysis

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Hui Li, Ablimit Abdukader, Lei Zhou. Radical Denitrogenative Ring Opening of N-Benzyl-benzotriazoles for the Synthesis of 6-Substituted Phenanthridines under Visible Light Conditions[J]. Chinese Journal of Organic Chemistry, 2025, 45(5): 1770-1777.

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Fig. & Tab. 5

Scheme 1. Strategies for the synthesis of phenanthridines and radical denitrogenative ring-opening of benzotriazoles

Entry	Photocatalyst	Base	Oxidant	Yield^b/%
Entry	Photocatalyst	Base	Oxidant	2a	3
1	Ru(bpy)₃Cl₂	Cs₂CO₃	Air	45	52
2	Ru(phen)₃Cl₂	Cs₂CO₃	Air	22	73
3	Eosin B	Cs₂CO₃	Air	35	55
4	Riboflavin	Cs₂CO₃	Air	0	0
5	FeFc	Cs₂CO₃	Air	0	63
6	Rose Bengal	Cs₂CO₃	Air	Trace	0
7	Methylene blue	Cs₂CO₃	Air	15	83
8	Acr^＋ $ClO 4 －$	Cs₂CO₃	Air	34	43
9	4CzIPN	Cs₂CO₃	Air	64	22
10	4CzIPN	^tBuOK	Air	15	42
11	4CzIPN	K₂CO₃	Air	0	0
12	4CzIPN	NaHCO₃	Air	0	0
13	4CzIPN	DABCO	Air	17	0
14	4CzIPN	Cs₂CO₃	O₂	34	56
15^c	4CzIPN	Cs₂CO₃	O₂ (10%)	87	11
16^d	4CzIPN	Cs₂CO₃	O₂ (5%)	78	19
17^e	4CzIPN	Cs₂CO₃	O₂ (10%)	0	0
18	4CzIPN	None	O₂ (10%)	0	0
19	None	Cs₂CO₃	O₂ (10%)	Trace	0

Entry	Photocatalyst	Base	Oxidant	Yield^b/%
Entry	Photocatalyst	Base	Oxidant	2a	3
1	Ru(bpy)₃Cl₂	Cs₂CO₃	Air	45	52
2	Ru(phen)₃Cl₂	Cs₂CO₃	Air	22	73
3	Eosin B	Cs₂CO₃	Air	35	55
4	Riboflavin	Cs₂CO₃	Air	0	0
5	FeFc	Cs₂CO₃	Air	0	63
6	Rose Bengal	Cs₂CO₃	Air	Trace	0
7	Methylene blue	Cs₂CO₃	Air	15	83
8	Acr^＋ $ClO 4 －$	Cs₂CO₃	Air	34	43
9	4CzIPN	Cs₂CO₃	Air	64	22
10	4CzIPN	^tBuOK	Air	15	42
11	4CzIPN	K₂CO₃	Air	0	0
12	4CzIPN	NaHCO₃	Air	0	0
13	4CzIPN	DABCO	Air	17	0
14	4CzIPN	Cs₂CO₃	O₂	34	56
15^c	4CzIPN	Cs₂CO₃	O₂ (10%)	87	11
16^d	4CzIPN	Cs₂CO₃	O₂ (5%)	78	19
17^e	4CzIPN	Cs₂CO₃	O₂ (10%)	0	0
18	4CzIPN	None	O₂ (10%)	0	0
19	None	Cs₂CO₃	O₂ (10%)	Trace	0

Table 1. Optimization of reaction conditions

Scheme 2. Substrate scope for the reaction

Scheme 3. Cyclization of 1a under oxygen-free conditions

Scheme 4. Plausible mechanism for the reaction

References 22

[1]	(a) Dostál J.; Slavík J. Stud. Nat. Prod. Chem. 2002, 27, 155.
	(b) Denny W. A. Curr. Med. Chem. 2002, 9, 1655.
[2]	Berkov S.; Martinez-Frances V.; Bastida J.; Codina C.; Rios S. Phytochemistry 2014, 99. 95.
[3]	Stevens N.; O’Connor N.; Vishwasrao H.; Smaroo D.; Kandel E. R.; Akins D. L.; Drain C. M.; Turro N. J. J. Am. Chem. Soc. 2008, 130, 7182. doi: 10.1021/ja8008924 pmid: 18489094
[4]	(a) Lynch M. A.; Duval O.; Sukhanova A.; Devy J.; MacKay S. P.; Waigh R. D.; Nabiev I. Bioorg. Med. Chem. Lett. 2001, 11, 2643. pmid: 11551768
	(b) Phillips S. D.; Castle R. N. J. Heterocycl. Chem. 1981, 18, 223. pmid: 11551768
	(c) Suffness M.; Cordell G. A. In The Alkaloids, Vol. 25, Ed. Brossi, A., Academic Press, New York, 1985, p. 178. pmid: 11551768
[5]	(a) Kshirsagar N.; Sonawane R.; Pathan S.; Kamble G.; Singh G. P. Lett. Org. Chem. 2022, 19, 434.
	(b) Talukdar V.; Vijayan A.; Katari N. K.; Radhakrishnan K. V.; Das P. Adv. Synth. Catal. 2021, 363, 1202.
	(c) Del Tito A.; Abdulla H. O.; Ravelli D.; Protti S.; Fagnoni M. Beilstein J. Org. Chem. 2020, 16, 1476.
[6]	(a) Dey A.; Kumar V.; Chatterjee R.; Behera A.; Maurya R. K.; Burra A. G.; Kumar S.; Khatravath M.; Dandella R. Asian J. Org. Chem. 2023, 12, e202300369.
	(b) Ye H.-B.; Zhou X.-Y.; Li L.; He X.-K.; Xuan J. Org. Lett. 2022, 24, 6018.
	(c) He X.-K.; Lu J.; Ye H.-B.; Li L.; Xuan J. Molecules 2021, 26, 6843.
[7]	(a) Natarajan P.; Kumar N.; Sharma M. Org. Chem. Front. 2016, 3, 1265.
	(b) Wu Y.; Wong S. M.; Mao F.; Chan T. L.; Kwong F. Y. Org. Lett. 2012, 14, 5306.
[8]	(a) Katritzky A. R.; Lan X.; Yang J. Z.; Denisko O. V. Chem. Rev. 1998, 98, 409. pmid: 19799386
	(b) Katritzky A. R.; Rachwal S. Chem. Rev. 2010, 110, 1564. doi: 10.1021/cr900204u pmid: 19799386
	(c) Li W.; Zhang J. Chem. Eur. J. 2020, 26, 11931. pmid: 19799386
	(d) Akter M.; Rupa K.; Anbarasan P. Chem. Rev. 2022, 122, 13108. pmid: 19799386
[9]	(a) Wentrup C.; Freiermuth B.; Aylward N. J. Anal. Appl. Pyrol. 2017, 128, 187.
	(b) Lener G.; Carbonio R. E.; Moyano E. L. ACS Catal. 2013, 3, 1020.
	(c) Chattopadhyay B.; Gevorgyan V. Angew. Chem., Int. Ed. 2012, 51, 862.
[10]	(a) Teders M.; Gómez-Suárez A.; Pitzer L.; Hopkinson M. N.; Glorius F. Angew. Chem., Int. Ed. 2017, 56, 902.
	(b) Teders M.; Pitzer L.; Buss S.; Glorius F. ACS Catal. 2017, 7, 4053.
	(c) Jian Y.; Chen M.; Huang B.; Jia W.; Yang C.; Xia W. Org. Lett. 2018, 20, 5370.
[11]	(a) Su Y.; Petersen J. L.; Gregg T. L.; Shi X. Org. Lett. 2015, 17, 1208.
	(b) Kim T.; Kim K. Tetrahedron Lett. 2010, 51, 868.
[12]	Li J.; Wang S.; Zhao J.; Li P. Org. Lett. 2022, 24, 5977.
[13]	(a) Katritzky A. R.; Yang B. J. Heterocycl. Chem. 1996, 33, 607.
	(b) Katritzky A. R.; Yang B. J. Org. Chem. 1998, 63, 1467.
	(c) Katritzky A. R.; Du W.; Matskawa Y.; Ghiviriga I.; Denisenko S. N. J. Heterocycl. Chem. 1999, 36, 927.
[14]	Maerky M.; Schmid H.; Hansen H. J. Helv. Chim. Acta 1979, 62, 2129.
[15]	Rezaei Z.; Khabnadideh S.; Zomorodian K.; Pakshir K.; Kashi G.; Sanagoei N.; Gholami S. Arch. Pharm. 2011, 344, 658. doi: 10.1002/ardp.201000357 pmid: 21984016
[16]	Dong X.; Xu Y.; Liu J. J.; Hu Y.; Xiao T.; Zhou L. Chem. Eur. J. 2013, 19, 16928.
[17]	(a) Flynn A. R.; McDaniel K. A.; Hughes M. E.; Vogt D. B.; Jui N. T. J. Am. Chem. Soc. 2013, 142, 9163. pmid: 32433521
	(b) McAtee R. C.; Noten E. A.; Stephenson C. R. J. Nat. Commun. 2020, 11, 2528. doi: 10.1038/s41467-020-16369-4 pmid: 32433521
[18]	Dong Y.; Yang P.; Zhao S.; Li Y. Nat. Commun. 2020, 11, 4096.
[19]	Maiti D.; Halder A.; De, Sarkar. S. Adv. Synth. Catal. 2019, 361, 4941.
[20]	Xiao T.; Li L.; Lin G.; Wang Q.; Zhang P.; Mao Z.-W.; Zhou L. Green Chem. 2014, 16, 2418.
[21]	Tobisu M.; Koh K.; Furukawa T.; Chatani N. Angew. Chem., Int. Ed. 2012, 51, 11363.
[22]	Gerfaud T.; Neuville L.; Zhu J. Angew. Chem., Int. Ed. 2009, 48, 572.

可见光条件下N-苄基苯并三氮唑自由基脱氮气开环合成6-取代菲啶

Radical Denitrogenative Ring Opening of N-Benzyl-benzotriazoles for the Synthesis of 6-Substituted Phenanthridines under Visible Light Conditions

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