Organic Chemistry Portal
Organic Chemistry Highlights

Monday, October 10, 2016
Douglass F. Taber
University of Delaware

Benzene Derivatives: The Li Synthesis of Ileabethoxazole

Edgars Suna of the Latvian Institute of Organic Synthesis showed (J. Org. Chem. 2016, 81, 371. DOI: 10.1021/acs.joc.5b02728) that the intermediate from iodination of 1 could be coupled with 2 in the presence of a Cu catalyst to deliver the aryl ether 3. Chad C. Eichman of Loyola University found (Eur. J. Org. Chem. 2016, 2925. DOI: 10.1002/ejoc.201600531) that the arene 4 could be directly prenylated with isoprene 5 to give 6.

Zhuangzhi Shi of Nanjing University (J. Org. Chem. 2016, 81, 14. DOI: 10.1021/acs.joc.5b02557) and Oleg V. Larionov of the University of Texas at San Antonio (J. Am. Chem. Soc. 2016, 138, 2985. DOI: 10.1021/jacs.6b01376) greatly extended the utility of a dimethyl aniline such as 7 by showing that it could be borylated to 8 or the corresponding BPin derivative. Maralinganadoddi P. Sadashiva of the University of Mysore established (Chem. Lett. 2016, 45, 268. DOI: 10.1246/cl.151087) conditions for the ozonolysis of the areneboronic acid 8 to the phenol 9.

The Ni-catalyzed coupling of anisole derivatives such as 10 developed by Wenkert had been limited to Grignard reagents lacking β-hydrogen atoms. Mamoru Tobisu and Naoto Chatani of Osaka University using Grignard reagents such as 11 (J. Am. Chem. Soc. 2016, 138, 6711. DOI: 10.1021/jacs.6b03253) and Franziska Schoenebeck and Magnus Rueping of RWTH Aachen University using trialkyl aluminum reagents (Angew. Chem. Int. Ed. 2016, 55, 6093, not illustrated. DOI: 10.1002/anie.201510497) have shown the efficient conversion of 10 to 12. This was also extended to the stereoretentive coupling with enol ethers, again pioneered by Wenkert. The classic Heck coupling is well known for generating E alkenes. Fengtian Xue of the University of Maryland School of Pharmacy and Chao Jiang of the Nanjing University of Science and Technology devised (Org. Biomol. Chem. 2016, 14, 3298. DOI: 10.1039/C6OB00164E) an alternative protocol, coupling 13 with 14 to give the Z alkene 15.

P. Beier of the Academy of Sciences of the Czech Republic established (Chem. Commun. 2016, 52, 7237. DOI: 10.1039/C6CC02235A) a procedure for the ortho amination of a nitro aromatic 16, leading to 17. Xinhao Zhang of the Peking University Shenzen Graduate School and Yu Rao of Tsinghua University observed (Chem. Sci. 2016, 7, 2229. DOI: 10.1039/C5SC03905C) that depending on the catalyst used, 18 could be selectively hydroxylated to either 19 or 20.

The classic Kolbe-Schmitt carboxylation of 21 to 23 requires high CO2 pressure. Igor Larossa of the University of Manchester established (Chem. Eur. J. 2016, 22, 6798. DOI: 10.1002/chem.201601114) a procedure, mediated by 22, that proceeded at atmospheric pressure. Dan-Dan Li of Xuchang University opened (Eur. J. Org. Chem. 2016, 3090. DOI: 10.1002/ejoc.201600335) the epoxide 25 with the intermediate from ortho metalation of the methoxime 24, leading to 26.

Meihua Xie of Anhui Normal University assembled (J. Org. Chem. 2016, 81, 3329. DOI: 10.1021/acs.joc.6b00308) the substituted benzene 29 by adding 27 to 28. Thomas R. Hoye of the University of Minnesota (J. Am. Chem. Soc. 2016, 138, 4318, DOI: 10.1021/jacs.6b01025; Nature 2016, 532, 484, DOI: 10.1038/nature17429) and Daesung Lee of the University of Illinois at Chicago (Org. Biomol. Chem. 2016, 14, 4782. DOI: 10.1039/C6OB00524A) have explored the cyclization and regioselective functionalization of tetraynes, as illustrated by the combination of 30 with 31 and 32 to give 33.

Ileabethoxazole (36) shows promising anti-tubercular activity. En route to 36, Ang Li of the Shanghai Institute of Organic Chemistry prepared (Angew. Chem. Int. Ed. 2016, 55, 2851. DOI: 10.1002/anie.201510568) the benzene core by the cyclization of 34 to 35.

D. F. Taber, Org. Chem. Highlights 2016, October 10.