Substituted Benzenes: The Alvarez-Manzaneda Synthesis of (-)-Taiwaniquinone G

Continuing efforts toward the direct functionalization of aromatic C-H bonds, Nobutaka Fujii and Hiroaki Ohno of Kyoto University described (Chem. Commun. 2009, 3413. DOI: 10.1039/b905586j) a Pd-mediated protocol for the ortho hydroxylation of aryl tetrahydropyrimidines such as 1. To use a boronic acid as an activating/directing group, Michinori Suginome, also of Kyoto University, devised (J. Am. Chem. Soc. 2009, 131, 7502. DOI: 10.1021/ja902314v) the pyrazolylpyridyl derivative 3. The product 4 could be returned to the boronic acid or carried on to the borate ester, in each case with recovery of the directing group. Eiichi Nakamura of the University of Tokyo established (Angew. Chem. Int. Ed. 2009, 49, 2925. DOI: 10.1002/anie.200900454) that ortho arylation of 5 could be accomplished even in the presence of a reactive aryl halide. In a complementary approach, Matthew J. Gaunt of the University of Cambridge developed (Science 2009, 323, 1593. DOI: 10.1126/science.1169975) a procedure for C-H arylation of anilides such as 7 that showed good meta selectivity.

Mamoru Tobisu and Naoto Chatani of Osaka University have found (Chem. Lett. 2009, 38, 710. DOI: 10.1246/cl.2009.710) for the conversion of aryl ethers such as 9 to the tertiary amine. Masahito Ochiai of the University of Tokushima observed (J. Am. Chem. Soc. 2009, 131, 8392. DOI: 10.1021/ja903544d) the remarkable inversion of an arene sulfonamide such as 11 to the protected aniline 12. Matthias Beller of the Universität Rostock established (Angew. Chem. Int. Ed. 2009, 49, 918. DOI: 10.1002/anie.200804898) a Pd-mediated procedure for the conversion of even a congested aryl halide 13 to the phenol 14.

The first C-C bond formations with phenols used very reactive, but expensive, leaving groups such as triflates. With improving ligand design, conditions have been found that work well even with inexpensive mesylates. Now, Zhang-Jie Shi of Peking University (J. Am. Chem. Soc. 2008, 130, 14468. DOI: 10.1021/ja8056503) and Neil K. Garg of UCLA (J. Am. Chem. Soc. 2008, 130, 14422. DOI: 10.1021/ja806244b) , working independently, developed similar procedures for the Ni-mediated arylation of esters such as 15. Both groups found that pivalates worked particularly well.

For some highly-substituted benzene derivatives, construction of the aromatic ring can be an economical approach. Atul Goel of the Central Drug Research Institute, Lucknow, found (Tetrahedron Lett. 2009, 50, 2086. DOI: 10.1016/j.tetlet.2009.02.117) that the direct coupling of a pyrone such as 17 with an aldehyde 18 delivered the aryl ester 19. Gerhard Hilt of Philipps-Universität Marburg developed (Org. Lett. 2009, 11, 773. DOI: 10.1021/ol802837m) Co catalysts for the Diels-Alder cyclization of 20 with 21, with subsequent oxidation to the arene 22. With the proper choice of catalyst, either regioisomer of the Diels-Alder adduct could be made to dominate. Kazuhiro Yoshida and Akira Yanagisawa of Chiba University found (J. Org. Chem. 2009, 74, 3632. DOI: 10.1021/jo900456g) a similar flexibility in a Ru-mediated arene construction. Cyclization of 23 followed by dehydration gave 24, while oxidation followed by cyclization delivered the phenol 25. Enrique Alvarez-Manzaneda of the Universidad de Granada, in the course (Chem. Commun. 2009, 592. DOI: 10.1039/b816812a) of a synthesis of (-)-Taiwaniaquinone G (29), built the aromatic ring by cyclization of 26 to 27, followed by oxidation to 28.