Asymmetric Synthesis of 10-Demethoxyvincorine Enabled by Dual Ni/Ti-Catalyzed Reductive Cyclization

Herein, we report the asymmetric synthesis of 10-demethoxyvincorine in 12 steps. The synthesis is highlighted by several key transformations: (1) a Pd-catalyzed Catellani-type reaction for the preparation of C2-alkylated tryptamine, (2) a chiral phosphoric acid (CPA)-catalyzed asymmetric bromocyclization to construct enantioenriched 3a-bromo-hexahydropyrroloindoline, (3) a dual Ni/Ti-catalyzed reductive cyclization to establish the bridged ring system, and (4) a SmI2-promoted reductive cyclization to forge the strained E-ring.