Enantioselective Pd-catalyzed tandem allylic alkylation reaction using monodentate phosphoramidite ligands for the formal total synthesis of huperzine A

Abstract

A small library of fine-tunable monodentate phosphoramidite (MPN) ligands was found useful in selecting a highly efficient chiral ligand for the enantioselective Pd-catalyzed tandem allylic alkylation reaction. The reaction gave a critical tricyclic key intermediate with high enantiopurity for the formal total synthesis of (−)-huperzine A, a Lycopodium alkaloid derived from the club moss Huperzia serrata that possesses potent inhibitory activity against acetylcholine esterase (ACHe).