Asymmetric Allylic C-H Amination Cross-Coupling by Palladium-Catalyzed 1,3 Migratory Carboamination of 1,4-Unconjugated Dienes

Chiral allylic amines are prominent structural motifs in natural products, pharmaceuticals and agrochemicals. Moreover, they serve as synthetically valuable intermediates for the construction of complex organic molecules. However, amines, especially aliphatic and aromatic amines with free N-H bonds, tend to coordinate with transition metals and deactivate the catalyst, posing a tremendous challenge to applying Lewis basic amines in the amination of olefins. Herein, we present the first example of synthesizing chiral allylamine via the Pd-catalyzed asymmetric 1,3-carboamination of acyclic 1,4-unconjugated dienes through the chain-walking process. The combination of a palladium catalyst, newly synthesized TY-Phos ligand enables the efficient reaction of aryl bromides, 1,4-unconjugated dienes, and aryl primary amines, affording chiral allylamines with excellent chemo-, regio-, and enantioselectivity (up to 94% ee). Remarkably, the 1,3-carboamination cyclization between 2-iodoaniline and acyclic 1,4-unconjugated dienes to synthesize chiral tetrahydroquinoline derivatives was also realized (up to 92% ee) via Pd/Ming-Phos catalytic system. The synthetic utility of this method is exemplified in the enantioselective synthesis of the alkaloids (-)-Cuspareine and (-)-Galipinine. Mechanistic investigations reveal that the reaction via a chain-walking process.