Three-component tandem knoevenagel/hetero Diels-Alder reactions - Total synthesis of (±)-preethulia coumarin

Starting from 4-hydroxy-5-methylcoumarin (7), (±)-preethulia coumarin (3) was synthesized in six steps and in 4% over-all yield. The key synthetic procedure was a new type of Lewis acid catalysed, three-component Knoevenagel/hetero Diels-Alder reaction, which employs α-dicarbonyl compounds to generate chromandiones, and vinyl ethers to trap them. Some unexpected rearrangements were observed during the manipulation of various acetalic Diels-Alder adducts, resulting in the serendipitous assembly of bridgehead and fused tetracyclic coumarin assemblies.