A General Iridium-Catalyzed Reductive Dienamine Synthesis Allows a Five-Step Synthesis of Catharanthine via the Elusive Dehydrosecodine

Abstract

A new reductive strategy for the stereo- and regioselective synthesis of functionalized isoquinuclidines has been developed. Pivoting on the chemoselective iridium(I)-catalyzed reductive activation of β,γ-unsaturated δ-lactams, the efficiently produced reactive dienamine intermediates readily undergo [4 + 2] cycloaddition reactions with a wide range of dienophiles, resulting in the formation of bridged bicyclic amine products. This new synthetic approach was extended to aliphatic starting materials, resulting in the efficient formation of cyclohexenamine products, and readily applied as the key step in the shortest (five-step) total synthesis of vinca alkaloid catharanthine to date, proceeding via its elusive biosynthetic precursor, dehydrosecodine.