Organic Chemistry Portal
Organic Chemistry Highlights

Monday, October 11, 2010
Douglass F. Taber
University of Delaware

Substituted Benzenes: The Saikawa/Nakata Synthesis of Kendomycin

Jianbo Wang of Peking University described (Angew. Chem. Int. Ed. 2010, 49, 2028. DOI: 10.1002/anie.200906699) the Au-promoted bromination of a benzene derivative such as 1 with N-bromosuccinimide. In a one-pot procedure, addition of a Cu catalyst followed by microwave heating delivered the aminated product 2. Jian-Ping Zou of Suzhou University and Wei Zhang of the University of Massachusetts, Boston, observed (Tetrahedron Lett. 2010, 51, 2639. DOI: 10.1016/j.tetlet.2010.03.029) that the phosphonylation of an arene 3 proceeded with substantial ortho selectivity.

Yonghong Gu of the University of Science and Technology, Hefei showed (Tetrahedron Lett. 2010, 51, 192. DOI: 10.1016/j.tetlet.2009.10.112) that an arylpropanoic acid 6 could be ortho hydroxylated with PIFA, to give 7. Louis Fensterbank, Max Malacria and Emmanuel Lacôte of UMPC Paris found (Angew. Chem. Int. Ed. 2010, 49, 2178. DOI: 10.1002/anie.200907237) that a benzoic acid could be ortho aminated by way of the cyano amide 8.

Daniel J. Weix of the University of Rochester developed (J. Am. Chem. Soc. 2010, 132, 920. DOI: 10.1021/ja9093956) a protocol for coupling an aryl iodide 10 with an alkyl iodide 11 to give 12. Professor Wang devised (Angew. Chem. Int. Ed. 2010, 49, 1139. DOI: 10.1002/anie.200906349) a mechanistically-intriguing alkyl carbonylation of an iodobenzene 10. This is presumably proceeding by way of the intermediate diazo alkane.

Usually, benzonitriles are prepared by cyanation of the halo aromatic. Hideo Togo of Chiba University established (Synlett 2010, 1067. DOI: 10.1055/s-0029-1219575) a protocol for the direct electrophilic cyanation of an electron-rich aromatic 15. Thomas E. Cole of San Diego State University observed (Tetrahedron Lett. 2010, 51, 3033. DOI: 10.1016/j.tetlet.2010.03.096) that an alkyl dimethyl borane, readily prepared by hydroboration of the alkene with BCl3 and Et3SiH, reacted with benzoquinone (17) to give 18. Presumably this transformation could also be applied to substituted benzoquinones.

When a highly substituted benzene derivative is needed, it is sometimes more economical to construct the aromatic ring. Joseph P. A. Harrity of the University of Sheffield and Gerhard Hilt of Philipps-Universität Marburg showed (J. Org. Chem. 2010, 75, 3893. DOI: 10.1021/jo1004907) that the Co-catalyzed Diels-Alder cyloaddition of alkynyl borinate 21 with a diene 20 proceeded with high regiocontrol, to give, after oxidation, the aryl borinate 22. Wayne F. K. Schnatter of Long Island University found (Tetrahedron Lett. 2010, 51, 921. DOI: 10.1016/j.tetlet.2009.12.029) that the addition of the readily-prepared Fe complex 23 to 24 also proceeded with high regioselectivity, to give the pentasubstituted benzene 25.

Yoko Saikawa and Masaya Nakata of Keio University took advantage (Org. Lett. 2010, 12, 1700. DOI: 10.1021/ol100229f) of arene construction in their synthesis of Kendomycin (28). Intramolecular Dötz cyclization of the Fischer carbene 26 gave 27, poised for the Claisen rearrangement that would establish the last C-C bond on the aromatic ring of the natural product.

We salute Professors Heck, Negishi and Suzuki for the 2010 Nobel Prize in Chemistry, for the development of Pd-catalyzed bond construction.

D. F. Taber, Org. Chem. Highlights 2010, October 11.