Palladium-Catalyzed Autotandem Hydrogenolysis/Hydrogenation for the Synthesis of Hexahydro-β-carbolines Containing Three Contiguous Stereocenters

Autotandem catalysis is an efficient and step-economical reaction involving two or more mechanistically distinct reaction processes under the action of only a single catalyst. Herein, an unprecedented asymmetric autotandem catalysis reaction merging hydrogenolysis and hydrogenation of hydroxylactam-fused indoles through a dynamic kinetic resolution process with palladium hydride as the same active species was developed, affording hexahydro-β-carbolines containing three contiguous stereocenters with excellent enantio- and diastereoselectivity. Versatile synthetic transformations of the chiral heterocyclic products were carried out without loss of enantiomeric purity, even affording octahydroindole derivatives containing up to five contiguous stereocenters. Mechanistic studies including deuterium-labeling experiments and control experiments supported that the dynamic kinetic resolution process is crucial for excellent diastereoselectivity performance.