Unravelling the Synthesis and Chemistry of Stable, Acyclic, and Double‐Deficient 1,3‐Butadienes: An endo‐Selective Diels–Alder Route to Hedgehog Pathway Inhibitors

The first synthetic access to stable and acyclic 1,3‐butadienes with two electron‐withdrawing carbonyl groups and their potential to deliver new molecular scaffolds through intriguing endo‐selective Diels–Alder cycloadditions are presented. The bicyclic scaffolds produced through the cycloaddition chemistry of electron‐deficient dienes afforded potent Hedgehog signaling pathway inhibitors. Uniquely deficient! A facile synthetic access to stable, electron‐deficient and acyclic 1,3‐butadienes bearing two orthogonal electron‐withdrawing groups is presented. This method opens the door to many molecular frameworks, including new Hedgehog pathway inhibitors.