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

Abstract

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.

Keywords: 1,3-butadienes; Diels-Alder reaction; allenes; dienes; phosphine catalysis.