BODIPY-4H-Pyran Hybrids Synthesis

Developing new methodologies to efficiently and rapidly prepare structurally complex compounds remains a key objective in synthetic chemistry. One of the most effective approaches to quickly achieve molecular complexity is through multicomponent reactions (MCRs). As defined by Ugi et al., “Multicomponent reactions (MCRs) are one-pot processes involving more than two starting materials—typically three, four, up to seven—where most of the atoms from the reactants are incorporated into the final product.”

In recent years, MCRs have found increasing application in the synthesis of complex molecules incorporating fluorophores. To explore the scope and limitations of this approach, we applied it to the preparation of 4H-pyranes, a family of heterocyclic compounds of significant biological and pharmaceutical relevance. Numerous synthetic strategies for 4H-pyranes have been reported, with one of the most common involving a base-catalyzed MCR of an aryl aldehyde, malononitrile, and ethyl acetoacetate.

In this work, several formylaryl-containing BODIPY derivatives were prepared via the Liebeskind–Srogl cross-coupling reaction. The formyl-functionalized fluorescent scaffolds were subsequently reacted with malononitrile and ethyl acetoacetate to afford a series of emissive 4H-pyranes. We report a novel strategy for the synthesis of 4H-pyran–BODIPY derivatives via an MCR performed in an EtOH/water mixture. Nine products were obtained under conventional stirring with good yields (25–72%), and six additional derivatives were synthesized under ultrasound-assisted conditions.