Organic Chemistry Portal
Organic Chemistry Highlights

Monday, June 14, 2021
Douglass F. Taber
University of Delaware

Substituted Benzenes: The Breugst/Pietruszka Synthesis of 6-Methoxymellein

Patrick L. Holland of Yale University devised conditions for the reductive coupling of toluene 1 with atmospheric nitrogen, leading to 2 (Nature 2020, 584, 221. DOI: 10.1038/s41586-020-2565-5). In the course of a next-generation synthesis of vancomycin, Dale L. Boger of Scripps/La Jolla oxidized 3 to 4 (J. Am. Chem. Soc. 2020, 142, 16039. DOI: 10.1021/jacs.0c07433).

Dong-Hui Wong of the Shanghai Institute of Organic Chemistry developed mild conditions for the conversion of the aryl bromide 5 to the phenol 6 (Org. Lett. 2020, 22, 8470. DOI: 10.1021/acs.orglett.0c03069). Shaolin Zhou of Central China Normal University assembled the aniline 9 by coupling the amine 8 with the fluoroarene 7 (Chem. Eur. J. 2020, 26, 14823. DOI: 10.1002/chem.202002315). David A. Nicewicz of the University of North Carolina reported a related study (J. Am. Chem. Soc. 2020, 142, 17187. DOI: 10.1021/jacs.0c09296).

Mukhtar Imerhasan of Xinjiang University and Jun Wang of Sun Yat-Sen University assembled the phthalide 11 from the benzamide 10 and paraformaldehyde (Eur. J. Org. Chem. 2020, 6485. DOI: 10.1002/ejoc.202001160). Gang Lu of Shandong University, David W. Lupton of Monash University and Debabrata Maiti of the Indian Institute of Technology Bombay designed a template that directed the para cyanation of 12, leading to the benzonitrile 13 (Chem. Eur. J. 2020, 26, 11558. DOI: 10.1002/chem.202001368). Lutz Ackermann of Georg-August-Universität Göttingen prepared 16 by alkylating 14 with the allene 15 (J. Am. Chem. Soc. 2020, 142, 13102. DOI: 10.1021/jacs.0c04837). Lei Liang and Hong-Ying Niu of the Henan Institute of Science and Technology used the Ritter protocol to activate 17 to the corresponding sulfonium salt, then coupled that with the alkyne 18, leading to 19 (Org. Lett. 2020, 22, 6842. DOI: 10.1021/acs.orglett.0c02364). Peng Wang, also of the Shanghai Institute of Organic Chemistry (Org. Lett. 2020, 22, 7716. DOI: 10.1021/acs.orglett.0c02913) and Felipe Garcia and Naohiko Yoshikai of Nanyang Technological University (Chem. Sci. 2020, 11, 7356. DOI: 10.1039/D0SC02737E) described related investigations.

Bill Morandi of ETH Zürich used the acid chloride 21 to effect the chlorocarbonylation of the aryl bromide 20, leading to the benzoyl chloride 22 (Angew. Chem. Int. Ed. 2020, 59, 17887. DOI: 10.1002/anie.202005891). Arenes can also be converted directly to benzoyl chlorides on exposure to oxalyl chloride/AlCl3 (J. Org. Chem. 2000, 65, 254, not illustrated. DOI: 10.1021/jo991055q). Masanori Shigeno and Yoshinori Kondo of Tohoku University used the organic superbase t-Bu-P4 to catalyze the coupling of 24 with the aryl ether 23, leading to the nitrile 25 (Org. Lett. 2020, 22, 9107. DOI: 10.1021/acs.orglett.0c03507).

Zhixiang Xie of Lanzhou University showed that the cyclohexenone 26 could be converted directly to the phenol 27 (Tetrahedron 2020, 76, 131629. DOI: 10.1016/j.tet.2020.131629). Syuzanna R. Harutyunyan of the University of Groningen effected conjugate addition to the naphthol 28, leading to the ketone 29 (Chem. Eur. J. 2020, 26, 15843. DOI: 10.1002/chem.202003392).

6-Methoxymellein (33) is a phytoalexin, induced in carrot slices by UV-C, that decreased the mRNA transcription and secretion of IL-6 and IL-8. Martin Breugst of the Universität zu Köln and Jörg Pietruszka of Heinrich-Heine-Universität Düsseldorf devised a three-step assembly of 33, based on the preparation of 32 by the conjugate addition of 31 to 30 (Angew. Chem. Int. Ed. 2020, 59, 18709. DOI: 10.1002/anie.202008365).

D. F. Taber, Org. Chem. Highlights 2021, June 14.