Petasis/Diels-Alder/cyclization cascade reactions for the generation of scaffolds with multiple stereogenic centers and orthogonal handles for library production

Abstract

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.