Organic Chemistry Portal
Organic Chemistry Highlights

Monday, June 13, 2011
Douglass F. Taber
University of Delaware

Substituted Benzenes: The Kirsch Synthesis of Cybrodol

Stephen L. Buchwald of MIT established (J. Am. Chem. Soc. 2010, 132, 14076. DOI: 10.1021/ja107481a) a Pd-catalyzed protocol for conversion of an aryl triflate 1 to the halide 2. Jie Wu of Fudan University prepared (Tetrahedron Lett. 2010, 51, 6646. DOI: 10.1016/j.tetlet.2010.10.054) aromatic halides from the corresponding carboxylic acids.

Yong-Chua Teo of Nanyang Technological University described (Tetrahedron Lett. 2010, 51, 3910. DOI: 10.1016/j.tetlet.2010.05.098) the Mn-mediated conversion of 3 to 5, suggesting a benzyne intermediate. Takanori Shibata of Waseda University effected (Synlett 2010, 2601. DOI: 10.1055/s-0030-1258774) the direct Ru-mediated coupling of aryl halides with amines, and Paul Helquist of the University of Notre Dame prepared (J. Org. Chem. 2010, 75, 4887. DOI: 10.1021/jo101002p) anilines by coupling aryl halides with NaN3.

Chao-Jun Li of McGill University devised (Tetrahedron Lett. 2010, 51, 5486. DOI: 10.1016/j.tetlet.2010.08.040) the Pd-catalyzed decarbonylative Heck coupling of 6 with 7 to give 8. Mats Larhed of Uppsala University showed (Angew. Chem. Int. Ed. 2010, 49, 7733. DOI: 10.1002/anie.201003009) that Pd could also catalyze the decarboxylative coupling of an aromatic acid 9 with a nitrile to give the ketone 10.

Dennis G. Hall of the University of Alberta found (Tetrahedron Lett. 2010, 51, 4256. DOI: 10.1016/j.tetlet.2010.06.035) that an areneboronic acid could promote the Zr-catalyzed ortho condensation of a phenol 11 with an aldehyde, leading to 12, that could then be carried on to a range of other products. Professor Hall also showed (Angew. Chem. Int. Ed. 2010, 49, 2883. DOI: 10.1002/anie.200906710) that areneboronic acids are stable to many standard organic transformations, and that the product boronic acids can be readily purified by extraction into sorbitol/Na2CO3. Professor Buchwald reported (J. Am. Chem. Soc. 2010, 132, 14073. DOI: 10.1021/ja1073799) an optimized source of Pd for the Suzuki-Miyaura coupling, allowing the room temperature participation even of unstable boronic acids such as 13.

Wing-Yiu Yu of the Hong Kong Polytechnic University observed (J. Am. Chem. Soc. 2010, 132, 12862. DOI: 10.1021/ja106364r) that 17 was an effective donor for the Pd-catalyzed ortho C-H amination of 16. Nicholas C. O. Tomkinson of Cardiff University uncovered (Synlett 2010, 2471. DOI: 10.1055/s-0030-1258546) the facile rearrangement of 19 to 20.

Professor Buchwald described (J. Am. Chem. Soc. 2010, 132, 9990. DOI: 10.1021/ja1044874) the coupling of 21, prepared from the aryl halide, with 22 to give the benzofuran 23. Professor Yu devised (Org. Lett. 2010, 12, 3926. DOI: 10.1021/ol101618u) the Pd-catalyzed ortho C-H coupling of 24 with an aldehyde 25 to give the ketone 26.

For highly-substituted benzene derivatives, it is sometimes more effective to construct the benzene ring. In the course of a synthesis of Cybrodol (29), Stefan F. Kirsch of the Technische Universität München cyclized (Angew. Chem. Int. Ed. 2010, 49, 4661. DOI: 10.1002/anie.201001113) the alkyne 27 to 28 with N-iodosuccinimide.

D. F. Taber, Org. Chem. Highlights 2011, June 13.