Furoic acid and derivatives as atypical dienes in Diels-Alder reactions

The furan Diels-Alder (DA) cycloaddition reaction has become an important tool in green chemistry, being central to the sustainable synthesis of many chemical building blocks. The restriction to electron-rich furans is a significant limitation of the scope of suitable dienes, in particular hampering the use of the furans most readily obtained from biomass, furfurals and their oxidized variants, furoic acids. Herein, it is shown that despite their electron-withdrawing substituents, 2-furoic acids and derivatives (esters, amides) are in fact reactive dienes in Diels-Alder couplings with maleimide dienophiles. The reactions benefit from a substantial rate-enhancement when water is used as solvent, and from activation of the 2-furoic acids by conversion to the corresponding carboxylate salts. This approach enables Diels-Alder reactions to be performed under very mild conditions, even with highly unreactive dienes such as 2,5-furandicarboxylic acid. The obtained DA adducts of furoic acids are shown to be versatile synthons in the conversion to various saturated and aromatic carbocyclic products.

Automated summary

The furan Diels-Alder (DA) cycloaddition reaction is an important tool in green chemistry, and the use of 2-furoic acids and their derivatives has been shown to be reactive in Diels-Alder couplings with maleimide dienophiles, benefiting from rate enhancement when water is used as solvent and activation through conversion to carboxylate salts. This approach allows for mild conditions to perform Diels-Alder reactions, even with unreactive dienes, and the obtained DA adducts of furoic acids are versatile in the conversion to various saturated and aromatic carbocyclic products.