Asymmetric Mannich/Radical Debromination Cascade of alpha-Bromoketones by Dipeptide-Phosphonium Salt Catalysis: Enantioselective Synthesis of beta-Amino Ketone-Pyrazolinones

We herein demonstrated an organocatalytic asymmetric Mannich/radical debromination cascade of alpha-brominated ketones. With this protocol, a diversity of chiral beta-amino ketone-pyrazolinone scaffolds, which have important versatilities in medicine and chemical synthesis, were constructed in high yields (up to 94%) with excellent enantioselectivities (up to 99% ee). This methodology features mild reaction conditions, broad substrate scope, and high functional group tolerance. Moreover, mechanistic investigations revealed that this cascade reaction proceeds through a bifunctional phosphonium salt-catalyzed Mannich reaction of alpha-brominated ketones with pyrazolinone ketimines, which is followed by an oxygen-induced radical debromination. This protocol represents a novel activation mode for alpha-brominated ketones and opens new avenues for catalytic enantioselective radical reactions under ion-pair system.