Mechanism and Origins of Chemo- and Stereo­selectivities of Aryl Iodide-Catalyzed Asymmetric Difluorinations of β‑Substituted Styrenes

The mechanism of the aryl iodide-catalyzed asymmetric migratory geminal difluorination of β-substituted styrenes (Banik et al. Science 2016, 353, 51) has been explored with density functional theory computations. The computed mechanism consists of (a) activation of iodo­arene difluoride (ArIF2), (b) enantio­determining 1,2-fluoro­iodination, (c) bridging phenonium ion formation via SN2 reductive displacement, and (d) regio­selective fluoride addition. According to the computational model, the ArIF2 intermediate is stabilized through halogen−π interactions between the electron-deficient iodine­(III) center and the benzylic substituents at the catalyst stereogenic centers. Interactions with the catalyst ester carbonyl groups (I­(III)+···O) are not observed in the unactivated complex, but do occur upon activation of ArIF2 through hydrogen-bonding interactions with external Brønsted acid (HF). The 1,2-fluoro­iodination occurs via alkene complexation to the electro­philic, cationic I­(III) center followed by C–F bond formation anti to the forming C–I bond. The bound olefin and the C–I bond of catalyst adopt a spiro arrangement in the favored transition structures but a nearly peri­planar arrangement in the disfavored transition structures. Multiple attractive non-covalent interactions, including slipped π···π stacking, C–H···O, and C–H···π interactions, are found to underlie the high asymmetric induction. The chemo­selectivity for 1,1-difluorination versus 1,2-difluorination is controlled mainly by (1) the steric effect of the substituent on the olefinic double bond and (2) the nucleo­philicity of the carbonyl oxygen of substrate