Mechanistic Study of the Formal [6＋2−1] Cycloaddition of Benzoquinones and Alkynes to Tropones

doi:10.6023/cjoc202605026

Chinese Journal of Organic Chemistry ›› 2026, Vol. 46 ›› Issue (9): 3624-3629.DOI: 10.6023/cjoc202605026 Previous Articles Next Articles

ARTICLE

苯并醌与炔烃的形式[6＋2−1]环加成反应的机理研究

张谦玮^a, 孔令荃^a, 陈自立^b, 余志祥^a^,^*()

^a 北京大学化学与分子工程学院生物有机与分子工程教育部重点实验室北京 100871
^b 中国人民大学化学系北京 100872

收稿日期:2026-05-25 修回日期:2026-07-27 发布日期:2026-08-03
通讯作者: 余志祥
基金资助:
国家自然科学基金(22361142835); 北京大学高性能计算校级公共平台资助项目.

Mechanistic Study of the Formal [6＋2−1] Cycloaddition of Benzoquinones and Alkynes to Tropones

Qianwei Zhang^a, Ling-Quan Kong^a, Zili Chen^b, Zhi-Xiang Yu^a^,^*()

^a Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, College of Chemistry, Peking University, Beijing 100871
^b Department of Chemistry, Renmin University of China, Beijing, 100872

Received:2026-05-25 Revised:2026-07-27 Published:2026-08-03
Contact: Zhi-Xiang Yu
About author:
Dedicated to the 100th anniversary of the birth of Professor Xikui Jiang.
Supported by:
National Natural Science Foundation of China(22361142835); High-Performance Computing Platform of Peking University.

1. .pdf(891KB)

Abstract

A formal [6＋2−1] reaction between benzoquinones and alkynes mediated by BF₃, giving tropones and liberating carbon monoxide, was discovered by Chen previously. A mechanistic investigation of this [6＋2−1] reaction through density functional theory (DFT) calculations was reported. Our study reveals that the originally proposed mechanism involving energetically demanding dearomative Diels-Alder (D-A) reaction between benzoquinones and alkynes, followed by a skeleton rearrangement, is difficult. Instead, the [6＋2−1] reaction starts from a nucleophilic attack of alkynes to the carbonyl of benzoquinones coordinated to BF₃, followed by Friedel-Crafts type addition, giving intermediates with a [3.2.1] skeleton, which then release carbon monoxide and the final tropones. The substituent effects on the regioselectivity of this [6＋2−1] reaction have also been studied when 1-alkyl-2-aryl acetylenes as the 2-π components were used.

Key words: [6＋2−1] cycloaddition, mechanistic study, benzoquinones, tropones

Cite this article

Qianwei Zhang, Ling-Quan Kong, Zili Chen, Zhi-Xiang Yu. Mechanistic Study of the Formal [6＋2−1] Cycloaddition of Benzoquinones and Alkynes to Tropones[J]. Chinese Journal of Organic Chemistry, 2026, 46(9): 3624-3629.

Export EndNote|Reference Manager|ProCite|BibTeX|RefWorks

share this article

Fig. & Tab. 6

Scheme 1. Selected cycloaddition reactions for the synthesis of tropones

Scheme 2. Originally and newly proposed mechanisms of [6＋2−1] reaction of benzoquinones and alkynes mediated by BF3

Figure 1. (a) Gibbs free energy profile of the non-catalyzed D-A reaction pathway; (b) Gibbs free energy profile of the BF3-catalyzed D-A reaction pathway

Figure 2. (a) Gibbs free energy profile of new pathway; (b) Structures of key intermediate and transition states

Figure 3. Explanation for the regioselectivity reported by Chen group (Gibbs free energies are given in reference to the sum of dibenzoquinone 1e, alkyne 2e and BF3•Et2O)

Figure 4. Calculations of other possible pathways for the [6＋2－1] reaction

References 21

[1]	Dastan, A.; Kilic, H.; Saracoglu, N. Beilstein J. Org. Chem. 2018, 14, 1120. doi: 10.3762/bjoc.14.98 pmid: 29977384
[2]	Shan, Z.; Nisar, M. F.; Li, M.; Zhang, C.; Wan, C.(Craig). Oxid. Med. Cell. Longev. 2021, e6256618.
[3]	Kelly-Hunt, A. E.; Mehan, A.; Brooks, S. D.; Leanca, M. A.; Jack; Mahamed, N.; Lambert, D. J.; Dempster, N. M.; Allen, R. J.; Evans, A. R.; Sarker, S. D.; Nahar, L.; Sharples, G. P.; Drew, M. G. B.; Fielding, A. J.; Ismail, F. M. D. J. Chem. Educ. 2021, 99, 983. doi: 10.1021/acs.jchemed.1c00699
[4]	Selected examples of the synthesis of benzocycloheptane compounds: (a) , Takada, T.; Arisawa, M.; Gyoten, M.; Hamada, R.; Tohma, H.; Kita, Y. J. Org. Chem. 1998, 63, 7698. doi: 10.1021/jo980704f
	(b) Leblanc, M.; Fagnou, K. Org. Lett. 2005, 7, 2849. doi: 10.1021/ol0505959
[5]	(a) Thiele, J.; Schneider, J. Liebigs Ann. Chem. 1909, 369, 287. doi: 10.1002/jlac.v369:3 pmid: 10810706
	(b) Thiele, J.; Weitz, E. Liebigs Ann. Chem. 1910, 377, 1. doi: 10.1002/jlac.v377:1 pmid: 10810706
	(c) Cook, M. J.; Forbes, E. J. Tetrahedron 1968, 24, 4501. doi: 10.1016/S0040-4020(01)96287-8 pmid: 10810706
	(d) Ewing, G. D.; Paquette, L. A. J. Org. Chem. 1975, 40, 2965. doi: 10.1021/jo00908a028 pmid: 10810706
	(e) Mort, M.; Inouye, Y.; Kakisawa, H. Chem. Lett. 1989, 1021. pmid: 10810706
	(f) Haro, G.; Mori, M.; Ishitsuka, M. O.; Kusumi, T. Bull. Chem. Soc. Jpn. 1991, 64, 3422. doi: 10.1246/bcsj.64.3422 pmid: 10810706
	(g) Takahashi, T.; Sun, W.-H.; Duan, Z.; Shen, B. Org. Lett. 2000, 2, 1197. pmid: 10810706
	(h) Albert, U.; Van Nguyen, T. H.; Langer, P. J. Org. Chem. 2004, 69, 3417. doi: 10.1021/jo049736v pmid: 10810706
	(i) Keshipour, S.; Shojaei, S.; Shaabani, A. Cellulose 2013, 20, 973. doi: 10.1007/s10570-012-9852-8 pmid: 10810706
[6]	Ranken, P. F.; Harty, B. J.; Kapicak, L.; Battiste, M. A. Synth. Commun. 1973, 3, 311. doi: 10.1080/00397917308065924
[7]	Nair, V.; D.Sethumadhavan, ; Nair, S. M.; Rath, N. P.; Eigendorf, G. K. J. Org. Chem. 2002, 67, 7533. doi: 10.1021/jo016098x
[8]	Li, F.; Liu, X.; Chen, Z. Synthesis 2023, 55, 1187. doi: 10.1055/a-2011-6969
[9]	Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Scalmani, G.; Barone, V.; Mennucci, B.; Petersson, G. A.; Nakatsuji, H.; Caricato, M.; Li, X.; Hratchian, H. P.; Izmaylov, A. F.; Bloino, J.; Zheng, G.; Sonnenberg, J. L.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; S 87 Vreven,, T.; Montgomery, J. A.; Peralta, Jr., J., E.; Ogliaro, F.; Bearpark, M.; Heyd, J. J.; Brothers, E.; Kudin, K. N.; Staroverov, V. N.; Keith, T.; Kobayashi, R.; Normand, J.; Raghavachari, K.; Rendell, A.; Burant, J. C.; Iyengar, S. S.; Tomasi, J.; Cossi, M.; Rega, N.; Millam, J. M.; Klene, M.; Knox, J. E.; Cross, J. B.; Bakken, V.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Martin, R. L.; Morokuma, K.; Zakrzewski, V. G.; Voth, G. A.; Salvador,, P.; Dannenberg, J. J.; Dapprich, S.; Daniels, A. D.; Farkas, Ö.; Foresman, J. B.; Ortiz, J. V.; Cioslowski, J.; Fox, D. J. Gaussian 09, Revision E.01, Gaussian, Inc., Wallingford, CT, 2013.
[10]	(a) Becke, A. D. J. Chem. Phys. 1993, 98, 5648. doi: 10.1063/1.464913 pmid: 9944570
	(b) Lee, C.; Yang, W.; Parr, R. G. Phys. Rev. B 1988, 37, 785. doi: 10.1103/physrevb.37.785 pmid: 9944570
[11]	(a) Grimme, S.; Antony, J.; Ehrlich, S.; Krieg, H. A. J. Chem. Phys. 2010, 132, 154104. doi: 10.1063/1.3382344
	(b) Grimme, S.; Ehrlich, S.; Goerigk, L. J. Comput. Chem. 2011, 32, 1456. doi: 10.1002/jcc.v32.7
[12]	(a) Hehre, W. J.; Ditchfield, R.; Pople, J. A. J. Chem. Phys. 1972, 56, 2257. doi: 10.1063/1.1677527
	(b) Francl, M. M.; Pietro, W. J.; Hehre, W. J.; Binkley, J. S.; Gordon, M. S.; DeFrees, D. J.; Pople, J. A. J. Chem. Phys. 1982, 77, 3654. doi: 10.1063/1.444267
[13]	Tomasi, J.; Mennucci, B.; Cammi, R. Chem. Rev. 2005, 105, 2999. doi: 10.1021/cr9904009
[14]	Zhao, Y.; Truhlar, D. G. Chem. Acc. 2008, 120, 215. doi: 10.1007/s00214-007-0310-x
[15]	(a) Krishnan, R.; Binkley, J. S.; Seeger, R.; Pople, J. A. J. Chem. Phys. 1980, 72, 650.
	(b) McLean, A. D.; Chandler, G. S. J. Chem. Phys. 1980, 72, 5639. doi: 10.1063/1.438980
[16]	Marenich, A. V.; Cramer, C. J.; Truhlar, D. G. J. Phys. Chem. B 2009, 113, 6378. doi: 10.1021/jp810292n
[17]	Mammen, M.; Shakhnovich, E. I.; Deutch, J. M.; Whitesides, G. M. J. Org. Chem. 1998, 63, 3821. doi: 10.1021/jo970944f
[18]	(a) Riplinger, C.; Sandhoefer, B.; Hansen, A.; Neese, F. J. Chem. Phys. 2013, 139, 134101. doi: 10.1063/1.4821834
	(b) Riplinger, C.; Pinski,, P.; Becker, U.; Valeev, E. F.; Neese, F. J. Chem. Phys. 2016, 144, 024109. doi: 10.1063/1.4939030
	(c) Riplinger, C.; Neese, F. J. Chem. Phys. 2013, 138, 034106. doi: 10.1063/1.4773581
	(d) Neese, F.; Wennmohs, F.; Hansen, A. J. Chem. Phys. 2009, 130, 114108. doi: 10.1063/1.3086717
	(e) Neese, F.; Hansen, A.; Liakos, D. G. J. Chem. Phys. 2009, 131, 064103. doi: 10.1063/1.3173827
	(f) Guo, Y.; Riplinger, C.; Becker, U.; Liakos, D. G.; Minenkov, Y.; Cavallo, L.; Neese, F. J. Chem. Phys. 2018, 148, 5.
	(g) Bistoni, G.; Riplinger, C.; Minenkov, Y.; Cavallo, L.; Auer, A. A.; Neese, F. J. Theor. Comput. Chem. 2017, 13, 3220. doi: 10.1021/acs.jctc.7b00352
[19]	(a) Weigend, F.; Ahlrichs, R. Phys. Chem. Chem. Phys. 2005, 7, 3297. doi: 10.1039/b508541a
	(b) Hellweg, A.; Hattig, C.; Hofener, S.; Klopper, W. Theor. Chem. Acc. 2007, 117, 587. doi: 10.1007/s00214-007-0250-5
[20]	Legault, C. Y. CYLview20, Université de Sherbrooke, 2020; http://www.cylview.org (accessed August 19, 2026).
[21]	Zaitseva, E. R.; Smirnov, A. Y.; Timashev, V. I.; Malyshev, V. I.; Zhigileva, E. A.; Mikhaylov, A. A.; Medvedev, M. G.; Baleeva, N. S.; Baranov, M. S. Eur. J. Org. Chem. 2022, e202200547.

苯并醌与炔烃的形式[6＋2−1]环加成反应的机理研究

Mechanistic Study of the Formal [6＋2−1] Cycloaddition of Benzoquinones and Alkynes to Tropones

RichHTML

PDF

Supporting Info.

Knowledge

Abstract

Cite this article

share this article

Fig. & Tab. 6

References 21

Related Articles 4

Recommended Articles

Metrics

Comments

[1]	Yi-Yu Liu, Yudong Hu, Qing-Wei Zhang. Advances in Mechanistic Studies of Metal-Catalyzed Hydrophosphinylation of Non-Activated Alkynes [J]. Chinese Journal of Organic Chemistry, 2024, 44(12): 3678-3685.
[2]	Xu Dongdong, Shan Chunhui, Bai Ruopeng, Lan Yu. Mechanism of Alkaline Earth Metal Catalyzed Hydroboration of Carbodiimides: A Theoretical Study [J]. Chin. J. Org. Chem., 2017, 37(5): 1231-1236.
[3]	Du Lijuan, Wu Caihong, Gu Honghong, Li Juan. A Density Functional Theory Study of the Mechanism of Cu(II)-Catalyzed Synthesis of Pyrido[1,2-a]benzimidazoles [J]. Chin. J. Org. Chem., 2015, 35(8): 1726-1732.
[4]	Yang Yang, Chen Jiejun, Zhang Dayong, Dong Xiaofang, Zhao Changqi. Chemical Constituent and Biological Activities of the Genus Iris [J]. Chin. J. Org. Chem., 2013, 33(06): 1244-1253.