A Simple and Efficient Method for the Preparation of alpha-Halogenated Ketones Using Iron(III) Chloride and Iron(III) Bromide as Halogen Sources with Phenyliodonium Diacetate as Oxidant

摘要

alpha-Halogenated ketones are both unique structure moieties existing in biologically natural products and valuable synthetic intermediates for the preparation of functional molecules. An efficient and scalable method for the preparation of alpha-halogenated ketone using iron (III) chloride and iron (III) bromide as halogen sources with phenyliodonium diacetate as oxidant has been developed, featuring mild reaction conditions, environmentally friendly reagents, and wide substrate scope. Notably, the three-step synthesis of drug prasugrel was achieved using this developed method as a key step with 30% yield on gram-scale. Additionally, the reaction mechanism involving chloride cation was proposed based on some preliminary control experiments.