A calix[n]arene-catalysed three-component Povarov reaction: Microwave-assisted synthesis of julolidines and mechanistic insights

A new one-pot cascade reaction-based application of Povarov reactions (MCPRs) with a p-sulfonic acid calix[4]arene (CX4SO3H) catalyst for the synthesis of a series of 34 julolidines derivatives with substituents at C8 or C9 in good to excellent yields is reported. These microwave-assisted reactions proceed efficiently, had short reaction times, were metal-free, were low cost, and used an inexpensive, easily available and nontoxic catalyst. These advantages, along with a simple work-up procedure, make this protocol a very efficient and green alternative to the traditional methods for constructing these types of N-heterocyclic skeletons. In addition, this protocol allows the formation of julolidine structures, which requires the construction of four new C−C bonds and two C−N bonds. A mechanism for the Povarov reaction involving a stepwise sequence via ionic intermediates was proposed and validated.