Benzene Derivatives: The Qiu Synthesis of Daphenylline

Peter Beier of the Czech Academy of Sciences effected oxidative coupling of the nitroarene 1 with potassium t-butoxide, leading to the aryl ether 2 (Org. Chem. Front. 2021, 8, 77. DOI: 10.1039/D0QO01291B). Yirong Zhou of the Huazhong University of Science and Technology and Fang-Lin Zhang of the Wuhan University of Technology showed that aniline 5 was an effective catalyst for the ortho amination of the benzaldehyde derivative 3 with 4, leading to the phthalimide 6 (Org. Lett. 2021, 23, 3923. DOI: 10.1021/acs.orglett.1c01083).

Xin-Qi Hao and Mao-Ping Song of Zhengzhou University used TOSMIC 8 to para-alkylate the aniline 7, leading to the sulfone 9 (J. Org. Chem. 2021, 86, 7179. DOI: 10.1021/acs.joc.1c00500). Chao-Jun Li of McGill University and Huiying Zeng of Lanzhou University showed that under alkaline conditions, the phenol 10 could be coupled with the primary alcohol 11 to give the ortho-alkylated phenol 12 (Angew. Chem. Int. Ed. 2021, 60, 4043. DOI: 10.1002/anie.202010845). Gang Li of the Fujian Institute of Research on the Structure of Matter devised the amide 13, that under Pd catalysis could be combined with ethyl acrylate 14 to give the para-coupled product 15 (Chem. Sci. 2021, 12, 4126. DOI: 10.1039/D0SC07042D).

Many strategies have been put forward for the direct arylation of bezene derivatives. Soon Hyeok Hong of KAIST assembled the biphenyl 18 by coupling 16 with 3-bromotoluene 17 (Chem. Sci. 2021, 12, 363. DOI: 10.1039/D0SC05414C).

Patrick J. Riss of the University of Oslo established conditions for the direct Sandmeyer conversion of the aniline 19 to the fluorobenzene derivative 20 (Org. Lett. 2021, 23, 1011. DOI: 10.1021/acs.orglett.0c04209). Liqun Jin and Xinquan Hu of the Zhejiang University of Technology developed conditions for the reductive decyanation of the benzonitrile 21, leading to 22 (Chem. Commun. 2021, 57, 2273. DOI: 10.1039/D0CC07743G).

Ruben Martin of ICIQ observed high diastereoselectivity in the assembly of the cyclic ether 25 by the coupling of the activated ether 23 with 4-bromoacetophenone 24 (J. Am. Chem. Soc. 2020, 142, 20594. DOI: 10.1021/jacs.0c11172). En route to berkelic acid, Shuanglin Qu and Qianghui Zhou of Wuhan University used the modified Catellani catalyst 29 to organize the construction of 30 by the three-component coupling of the iodobenzene 26, the enone 27 and the epoxide 28 (Angew. Chem. Int. Ed. 2021, 60, 5141. DOI: 10.1002/anie.202014660).

Kelu Yan and Hua Wang of Qufu Normal University assembled the phenol 33 by coupling the ketone 31 with the diazo ester 32 (Adv. Synth. Catal. 2021, 363, 1855. DOI: 10.1002/adsc.202001456). Hidetoshi Tokuyama of Tohoku University prepared the monoester 36 by the selective saponification of the diester resulting from the combination of the acetal 34, the alkyne 35, and dimethyl acetylenedicarboxylate (Org. Biomol. Chem. 2021, 19, 765. DOI: 10.1039/D0OB02018D).

Daphenylline 40 is one of a variety of related alkaloids isolated from the genus Daphniphyllum, evergreen shrubs and trees of east and southeast Asia long used in medicinal chemistry. In the endgame of a synthesis of 40, Fayang G. Qiu of the Guangzhou Institutes of Biomedicine and Health constructed the central benzene ring by the Diels-Alder reaction of the diene 37 with the dienophile 38, leading to 39 (Angew. Chem. Int. Ed. 2021, 60, 9439. DOI: 10.1002/anie.202016212).