Three-component tandem Knoevenagel/hetero Diels-Alder reactions total synthesis of (+/-)-preethulia coumarin

Starting from 4-hydroxy-5-methylcoumarin (3), (+/-)-preethulia coumarin (S) was synthesized in six steps and in 4% overall yield. The key synthetic pr ocedure was a new type of Lewis acid catalysed, three-component Knoevenagel /hetero Diels-Alder reaction, which employs alpha -dicarbonyl compounds to generate chromandiones, and vinyl ethers to trap them. Some unexpected rear rangements were observed during the manipulation of various acetalic Diels- Alder adducts, resulting in the serendipitous assembly of bridgehead and fu sed tetracyclic coumarin assemblies.