Benzene derivatives trisubstituted, synthesis

A recent synthesis of mellein involves a Diels-Alder reaction, which gives the expected 1,2,3-trisubstituted benzene derivative... 

Subsequently, MBH adducts were successfully utilized as novel stereodefined electrophiles in the Friedel-Crafts reaction with benzene in the presence of a Lewis acid " and sulfuric acid, leading to the stereoselective synthesis of (Z)- and ( )-functionalized trisubstituted alkenes. Notably, MBH adducts obtained from acrylonitrile provide high (Z)-stereoselectivities, while adducts derived from methyl acrylate and aromatic aldehydes give high ( )-stereo-selectivities. When the MBH adducts drived from methyl acrylate and aliphatic aldehydes were involved in the Friedel-Crafts reaction, no significant stereoselectivity was observed (Scheme 3.29). 

The syntheses of fully and partly reduced benzofuran and isobenzofuran derivatives have been the subject of numerous publications. The ring systems figure prominently in natural product chemistry and the possibility of further modification makes them versatile intermediates. A short, efficient synthesis of 4-amino-2,3-dihydrobenzofuran (96) from readily available m-anisidine has been described. The compound, which had previously only been cited in the patent literature, was obtained in 46% overall yield using the directed lithiation procedure shown. This type of reaction has received a great deal of attention recently and there are numerous examples of 1,2,3-trisubstituted benzenes formed this way. The principal utility of (96) lies in its ready conversion to other products. 

---