Furan and Benzofuran Synthesis

The Feist-Benary and Paal-Knorr syntheses are commonly employed in the preparation of furan ring systems. In special cases where furan derivatives are difficult to prepare by other methods, Diels-Alder and retro-Diels-Alder reactions have become important methods for their synthesis. Finally, transition metal-catalyzed cyclization and cycloisomerization reactions have recently gained significant attention for their utility in the synthesis of highly functionalized furans. Key examples of these syntheses are highlighted in the sections below. 

The Feist-Benary furan synthesis, first described in 1902, is especially useful for the synthesis of substituted furan rings. This reaction occurs 

The Feist-Benary synthesis proceeds via an aldol reaction followed by intramolecular O-alkylation and dehydration to yield the fiiran product as 

The Feist-Benary furan synthesis is most commonly used for the preparation of 2-substituted 3-furoates, including ethyl 2-methyl-3-furoate, the original compound prepared by Benary. The resulting ester is generally converted into a carboxylic acid for use in a variety of transformations, including decarboxylation to produce the corresponding 2-substituted furan. For example, reaction of ethyl 7-methyl-3-oxooct-6-enoate with 

The Feist-Benary reaction has also been used to prepare trisubstituted furanoates as well. At present, only one 2,4-disubstituted 3-furoate has been prepared using the Feist-Benary reaction. Reaction of chloroacetone with ethyl acetoacetate in cold hydrochloric acid followed by exposure to cold triethylamine provided ethyl 2,4-dimethyl-3-furoate in 54-57% yield over multiple trials.  

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