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The Role of Trichloroacetimidate To Enable Iridium-Catalyzed Regio- and Enantioselective Allylic Fluorination: A Combined Experimental and Computational Study

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posted on 2019-09-09, 17:05 authored by Alexandre M. Sorlin, Jason C. Mixdorf, Madeline E. Rotella, Robert T. Martin, Osvaldo Gutierrez, Hien M. Nguyen
Asymmetric allylic fluorination has proven to be a robust and efficient methodology with potential applications for the development of pharmaceuticals and practical synthesis for 18F-radio­labeling. A combined computational (dispersion-corrected DFT) and experimental approach was taken to interrogate the mechanism of the diene-ligated, iridium-catalyzed regio- and enantio­selective allylic fluorination. Our group has shown that, in the presence of an iridium­(I) catalyst and nucleo­philic fluoride source (Et3N·3HF), allylic trichloro­acet­imidates undergo rapid fluoride substitution to generate allylic fluoride products with excellent levels of branched-to-linear ratios. Mechanistic studies reveal the crucial role of the trichloro­acet­imidate as a potent leaving group and ligand to enable conversion of racemic allylic trichloro­acet­imidates to the corresponding enantio­enriched allylic fluorides, via a dynamic kinetic asymmetric transformation (DYKAT), in the presence of the chiral bicyclo­[3.3.0]­octadiene-ligated iridium catalyst.