Highly Diastereo- and Enantioselective Synthesis of Quinuclidine Derivatives by an Iridium-Catalyzed Intramolecular Allylic Dearomatization Reaction

Abstract

Asymmetric construction of quinuclidine derivatives has been realized by an iridium-catalyzed allylic dearomatization reaction. The catalytic system, derived from [Ir(cod)Cl] 2 and the Feringa ligand, tolerates a broad range of substrates. A large array of quinuclidine derivatives can be obtained under mild conditions in good to excellent yields (68%–96%), diastereoselectivity (up to >20/1 dr), and enantioselectivity (up to >99% ee). These products feature versatile functional group diversity and can undergo diverse transformations. A model that accounts for the origin of the stereoselectivity has been proposed based on density functional theory (DFT) calculations.