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

摘要

The mechanism of the aryl iodide-catalyzed asymmetric migratory geminal difluorination of beta-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) enantio-determining 1,2-fluoroiodination, (c) bridging phenonium ion formation via S(N)2 reductive displacement, and (d) regioselective fluoride addition. According to the computational model, the ArIF2 intermediate is stabilized through halogen-pi 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)(+)center dot center dot center dot O) are not observed in the unactivated complex, but do occur upon activation of ArIF2 through hydrogen bonding interactions with external Bronsted 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 pi center dot center dot center dot pi stacking, C-H center dot center dot center dot O, and C-H center dot center dot center dot pi 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.