Organic Chemistry Portal
Organic Chemistry Highlights

Monday, October 13, 2008
Douglass F. Taber
University of Delaware

Preparation of Benzene Derivatives

Several new methods have been put forward for the functionalization of benzene derivatives. J. S. Yadav of the Indian Institute of Chemical Technology, Hyderabad has devised (Chem. Lett. 2008, 37, 652. DOI: 10.1246/cl.2008.652) a procedure for direct thiocyanation, converting 1 into 2. Sukbok Chang of KAIST has established (Chem. Commun. 2008, 3052. DOI: 10.1039/b804637a) that both NH4Cl and aqueous NH3 could be used to directly aminate an aryl iodide such as 3. John F. Hartwig of the University of Illinois has developed (J. Am. Chem. Soc. 2008, 130, 7534. DOI: 10.1021/ja8015878) a protocol for the directed borylation of anilines such as 5 and of phenols, based on a transient silylation. Karsten Menzel of Merck West Point (Tetrahedron Lett. 2008, 49, 415. DOI: 10.1016/j.tetlet.2007.11.124) has observed selective exchange of tribromobenzene derivatives such as 7, with the direction of the selectivity being controlled by the fourth substituent on the benzene.

Gary A. Molander of the University of Pennsylvania has extensively developed the stable, readily prepared trifluoroborates, exemplified by 10 (J. Org. Chem. 2008, 73, 2052. DOI: 10.1021/jo800183q) and 14 (Org. Lett. 2008, 10, 1795. DOI: 10.1021/ol800357c) as partners for Suzuki-Miyaura coupling. The conversion of 9 to 10 is complementary to aminocarbonylation, exemplified by the conversion of 12 to 13 reported (Tetrahedron Lett. 2008, 49, 2221. DOI: 10.1016/j.tetlet.2008.02.049) by Bhalchandra M. Bhanage of the Institute of Chemical Technology, University of Mumbai. The coupling of 9 with 14 is complementary to the long-known Heck coupling of an aryl halide such as 16 with an allylic alcohol, as illustrated by the preparation of 18 described (Tetrahedron Lett. 2008, 49, 3279. DOI: 10.1016/j.tetlet.2008.03.067) by Martin E. Maier of the Universität Tübingen.

Professor Hartwig has also (Org. Lett. 2008, 10, 1545, DOI: 10.1021/ol80025781549, DOI: 10.1021/ol800258u) optimized conditions for the Pd-catalyzed arylation of ester enolates such as 19. Gang Zhou of Schering-Plough, Kenilworth, NJ has developed (Org. Lett. 2008, 10, 2517. DOI: 10.1021/ol800785g) a related transformation, the arylation of deprotonated sulfonamides. Peter Somfai of the Royal Institute of Technology, Stockholm has established (Angew. Chem. Int. Ed. 2008, 47, 1907. DOI: 10.1002/anie.200704689) a complementary procedure, base-mediated elimination of t-butoxide from 24, followed by 1,2-addition of an aryl or heteroaryl Grignard reagent.

For some substitution patterns, it is more efficient to construct the benzene ring. Professor Yadav observed (Tetrahedron Lett. 2008, 49, 3810. DOI: 10.1016/j.tetlet.2008.03.151) that 27 was aromatized to 28. Katsuyuki Ogura of Chiba University showed (J. Org. Chem. 2008, 73, 1726. DOI: 10.1021/jo701976q) that 29 cyclized to 30. Ken Tanaka of the Tokyo University of Agriculture and Technology established (Org. Lett. 2008, 10, 2537. DOI: 10.1021/ol800813g) that enol ethers or enol acetates could take the place of an alkyne partner in a trimerization reaction, as illustrated by the regioselective cycloaromatization of 31 to 33. For a related study, see Tetrahedron Lett. 2008, 49, 445, DOI: 10.1016/j.tetlet.2007.11.103. Sylvain Marque and Damien Prim of the Université de Versailles-Saint-Quentin-en-Yvelines have found (J. Org. Chem. 2008, 73, 2191. DOI: 10.1021/jo7024916) that activation of 34 by condensation with a secondary amine set the stage for Diels-Alder cycloaddition and aromatization, leading to 37. For related studies, see Org. Lett. 2008, 10, 233, DOI: 10.1021/ol702614b and Tetrahedron Lett. 2008, 49, 219, DOI: 10.1016/j.tetlet.2007.11.085.

D. F. Taber, Org. Chem. Highlights 2008, October 13.