Enol-Ugi Reaction for the Synthesis of Amino Acid Derived Coumarins

Multicomponent reactions are highly convergent processes that are advantageously used for the synthesis of complex and diverse molecular libraries. We have recently demonstrated that enols react with amines, carbonyl compounds and isocyanides to give stable enamines, in a reaction similar to the classical Ugi condensation. In particular, heterocyclic enols can conveniently afford diversely functionalized heterocycles in an experimentally simple manner. Coumarins constitute a large family of plant metabolites possessing significant biological activities. In particular, 3- and 4-aminocoumarins constitute the structural core of numerous compounds with distinct therapeutic activities as, for example, antiproliferative and anti-HIV agents.

Here we wish to report the enol-Ugi reaction of 3- and 4-hydroxycoumarins, containing electron-withdrawing groups at positions 4 and 3 respectively, to give 3- and 4-aminocoumarins in a highly atom-economic and convergent process.