Small-Molecule Diversity Using a Skeletal Transformation Strategy

We describe a short synthetic sequence resulting in >4000 skeletally diverse small molecules that have three distinct skeletal frameworks
among other unique structural features. The sequence entails skeletal transformations pioneered by Winterfeldt and co-workers. We use
epoxide ring openings and subsequent functionalizations that provide, e.g., spirocyclic oxazolidines, Lewis acid catalyzed Diels−Alder reactions
of a steroid-derived diene that afford stable and isolable ring B adducts, and subsequent retro-Diels−Alder fragmentations that yield
14-membered paracyclophanes.