Visible-Light Palladium Catalysis for Alkylated and Difluoroalkylated Pyrazolones

Abstract

We report a photoinduced palladium-catalyzed protocol for the synthesis of biologically relevant alkylated and difluoroalkylated pyrazolones via a radical cascade between N'-arylidene-N-acryloylphenylhydrazides and unactivated alkyl and difluoroalkyl halides. Mechanistic studies support a Pd-mediated radical generation and capture pathway, accommodating both electrophilic and nucleophilic carbon-centered radicals. The protocol exhibits broad substrate scope, good functional group tolerance, and applicability to complex drug and natural product-derived fragments, providing a practical platform for late-stage molecular diversification.