Best Synthetic Methods Functionalization of Aromatic and

Best Synthetic Methods Functionalization of Aromatic and Heteroaromatic Rings 

Aromatic and heteroaromatic rings are the heart of pharmaceutical design. It is often less expensive to purchase a ring than to build it, so efficient methods for the selective functionalization of preformed aromatic rings are important. 

In general, aromatic halogenation proceeds to give the para product. Jallal M. Gnaim of the The Triangle Regional R D Center, Kfai-Qari, Israel, has developed (Tetrahedron Lett. 2004,45, 8471) a procedure that selectively converts phenols such as 1 into the ortho chlorinated product 2. Meta substitution is even more elusive. William R. Roush, now at Scripps Florida, prepared (J. Org. Chem. 2004, 69, 4906) the valuable meta brominated phenol 4 by petbromination followed by selective reduction. 

A common application of aryl halides is Pd-mediated coupling to form C-C bonds. Graham Meek of Chirotech Technology Ltd., Cambridge, UK has found (Tetrahedron Lett. 2004, 45, 9277) that the enamide 6 participates efficiently in Heck coupling. The product 7 is an excellent substrate for enantioselective hydrogenation, to give 8. 

For some applications, it is useful to put a substrate on a solid support. Linkers that can be converted directly to desired functionality ( traceless ) are particularly valuable. Andrew M. Cammidge of the University of East Anglia and A. Ganesan of the University of Southampton independently (Chem. Commun. 2004, 19I4, I916) developed the polymeric sulfonyl chloride 9. The derived phenyl sulfonates are useful partnere for transition-metal mediated cross coupling. 

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