Domino Synthesis of Coumarins via Phosphine-Mediated Formal Oxa -[4 + 2] Cycloaddition: Discovering a Missing Recyclization of Maleimides with Salicylaldehydes

High Resolution Image Download MS PowerPoint Slide A one-pot procedure for direct access to a hybrid of coumarin-acetamide through a tributylphosphine-mediated reaction between maleimides and salicylaldehydes under microwave irradiation is presented. The process involves the in situ ylide formation, followed by a Wittig reaction, itaconimide isomerization, and intramolecular cyclization, and represents a recyclization of maleimides via formal oxa -[4 + 2] cycloaddition. A broad scope of 24 derivatives was selectively formed in up to a 68% overall yield, after crystallization. This protocol was also transposed to continuous flow (up to 65% yield), allowing for the reaction scale-up to a 3 mmol scale. Control reactions and computational calculations revealed that the tributylphosphine plays a dual role, acting not only as a substrate for the phosphonium ylide formation but also as a catalyst for itaconimide isomerization. The synthesized coumarins exhibited fluorescence properties, with large Stokes shift values and fluorescence quantum yields (up to 84%), significantly influenced by substituents.