Organic Chemistry Portal
Organic Chemistry Highlights

Monday, October 12, 2015
Douglass F. Taber
University of Delaware

Preparation of Substituted Benzenes: The Beaudry Synthesis of Arundamine

Stephen G. DiMagno of the University of Nebraska developed (Chem. Eur. J. 2015, 21, 6394. DOI: 10.1002/chem.201500151) a protocol for the clean monoiodination of 1 to 2. The bromomethylation (or chloromethylation, with HCl) of a benzene derivative is straightforward with formaldehyde and HBr. Naofumi Tsukada of Shizuoka University designed (Organometallics 2015, 34, 1191. DOI: 10.1021/om501139f) a Cu catalyst that mediated the coupling of an alkyne with the benzyl bromide so produced, effecting net propargylation of 3 to 5.

Triazenes such as 7, versatile intermediates for organic synthesis, are usually prepared by diazotization of the corresponding aniline. Kay Severin of the Ecole Polytechnique Fédérale de Lausanne established (Angew. Chem. Int. Ed. 2015, 54, 302. DOI: 10.1002/anie.201408597) an alternative route from the aryl Grignard reagent 6. Ping Lu and Yanguang Wang of Zhejiang University showed (Chem. Commun. 2015, 51, 2840. DOI: 10.1039/C4CC08579E) that dimethylformamide could serve as the carbon source for the conversion of 8 to the nitrile 9.

Junha Jeon of the University of Texas at Arlington effected (J. Org. Chem. 2015, 80, 4661, DOI: 10.1021/acs.joc.5b00564; Chem. Commun. 2015, 51, 3778, DOI: 10.1039/C4CC09850A) the reductive ortho silylation of 10 to give 11. Vladimir Gevorgyan of the University of Illinois at Chicago found (Angew. Chem. Int. Ed. 2015, 54, 2255. DOI: 10.1002/anie.201410375) that the phenol derivative 12 could be ortho carboxylated, leading to 13. Lutz Ackermann of the Georg-August-Universität Göttingen, starting (Chem. Eur. J. 2015, 21, 8812. DOI: 10.1002/chem.201501134) with the designed amide 14, effected ortho metalation followed by coupling, to give the methylated product 15. Tetsuya Satoh and Masahiro Miura of Osaka University used (Org. Lett. 2015, 17, 704. DOI: 10.1021/ol503722r) the dithiane of 16 to direct ortho metalation. Coupling with acrylate followed by reductive desulfurization led to the ester 17.

Jin-Quan Yu of Scripps/La Jolla designed (Angew. Chem. Int. Ed. 2015, 54, 888. DOI: 10.1002/anie.201409860) the phenylacetamide 18 to direct selective meta metalation, leading to the unsaturated aldehyde 19. In an extension of the Catellani protocol, Guangbin Dong of the University of Texas prepared (J. Am. Chem. Soc. 2015, 137, 5887. DOI: 10.1021/jacs.5b02809) the biphenyl 21 by net meta metalation of the benzylamine 20.

Several methods for the de novo assembly of benzene derivatives have recently been put forward. Rajeev S. Menon of the Indian Institute of Chemical Technology condensed (Org. Lett. 2015, 17, 1449. DOI: 10.1021/acs.orglett.5b00318) the unsaturated aldehyde 22 with the sulfonyl ester 23 to give 24. Joseph P. A. Harrity of the University of Sheffield observed (Chem. Eur. J. 2015, 21, 2701. DOI: 10.1002/chem.201405863) substantial regioselectivity in the addition of the cyclobutenone 26 to the alkyne 25, leading to 27.

Arundamine 30 is representative of a family of alkaloids isolated from the roots of the Asian grass Arundo donax. Christopher M. Beaudry of Oregon State University assembled (Angew. Chem. Int. Ed. 2014, 53, 11931. DOI: 10.1002/anie.201407336) 30 by the intramolecular Diels-Alder addition of the yneamine of 28 to the furan, followed by opening to 29.

D. F. Taber, Org. Chem. Highlights 2015, October 12.