Catalytic, asymmetric difluorination of alkenes to generate difluoromethylated stereocenters

2016/07/01 by Steven M. Banik, Jonathan William Medley, Eric N. Jacobsen · 26 citations
Pharmacology, Toxicology and Pharmaceutics · Chemistry · #Fluorine in Organic Chemistry #Asymmetric Synthesis and Catalysis #Radical Photochemical Reactions

paper · doi:10.1126/science.aaf8078

Abstract

Difluoromethyl groups possess specific steric and electronic properties that invite their use as chemically inert surrogates of alcohols, thiols, and other polar functional groups important in a wide assortment of molecular recognition processes. We report here a method for the catalytic, asymmetric, migratory geminal difluorination of β-substituted styrenes to access a variety of products bearing difluoromethylated tertiary or quaternary stereocenters. The reaction uses commercially available reagents (m-chloroperbenzoic acid and hydrogen fluoride pyridine) and a simple chiral aryl iodide catalyst and is carried out readily on a gram scale. Substituent effects and temperature-dependent variations in enantioselectivity suggest that cation-π interactions play an important role in stereodifferentiation by the catalyst.

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