N-Difluoromethylation of N-pyridyl-substituted anilines with ethyl bromodifluoroacetate

Abstract

A general protocol for N-difluoromethylation of aniline derivatives is developed. Commercially available ethyl bromodifluoroacetate serves as a difluorocarbene source in the presence of a base. This carbene surrogate is attractive owing to its favorable stability, environmental friendliness and inexpensiveness. This reaction system features notable operational simplicity (bench top-grade solvents can be used without any pre-drying and do not require inert atmosphere protection). A wide range of functional groups in aniline derivatives are well-tolerated, and good-to-excellent product yields are generally obtained.