Petasis/Diels–Alder/Cyclization Cascade Reactions for the Generation of Scaffolds with Multiple Stereogenic Centers and Orthogonal Handles for Library Production

A new effective strategy for the synthesis of sp³-rich small molecules for library production is presented. The key steps to generate complexity involve a Petasis three-component reaction followed by an intramolecular Diels–Alder and cyclization to generate a densely enriched tricyclic or tetracyclic scaffolds with 3–4 stereocenters and three handles for decoration. The strategy was used for the production of 143 molecules for the European Lead Factory.