In this report, we have accomplished the total synthesis of two bioactive hexahydropyrroloindole (HPI) alkaloids bearing a C3a tetrasubstituted stereocenters substituted by isopentenyl. This route was based on Cu-catalyzed cascade arylation-alkylation sequence in one-pot as a key step, providing Flustramine B and Debromoflustramine B with 9 steps in 37.6 % and 31.1 % overall yields, respectively.