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

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.