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

Author(s) Sorlin, A.M.; Mixdorf, J.C.; Rotella, M.E.; Martin, R.T.; Gutierrez, O.; Nguyen, H.M.
Journal J Am Chem Soc
Date Published 2019 Sep 09
Abstract

Asymmetric allylic fluorination has proven to be a robust and efficient methodology with potential applications for the development of pharmaceuticals and practical synthesis for F-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 (EtN·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.

DOI 10.1021/jacs.9b07575
ISSN 1520-5126
Citation Sorlin AM, Mixdorf JC, Rotella ME, Martin RT, Gutierrez O, Nguyen HM. The Role of Trichloroacetimidate To Enable Iridium-Catalyzed Regio- and Enantioselective Allylic Fluorination: A Combined Experimental and Computational Study. J Am Chem Soc. 2019.