Stereoselective Synthesis of Benzo[a]quinolizidines via Aerobic DDQ-Catalyzed Allylation and Reductive Cyclization.

Abstract

Stereoselective synthesis of C4-substituted benzo[a]quinolizidines via redox-controlled catalytic C–C-bond-forming reactions was carried out. Aerobic DDQ-catalyzed allylation of N-Cbz tetrahydroisoquinolines efficiently provided α-allylated products 5, which were transformed to enones 6 via cross-metathesis reactions using the second-generation Hoveyda–Grubbs catalyst. Palladium-catalyzed hydrogenation of 6 prompted alkene reduction, protecting group removal, and intramolecular reductive amination in one step to afford the desired benzo[a]quinolizidines 7 as single diastereomers.