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

ABSTRACT: The mechanism of the aryl iodide-catalyzed asymmetric migratory geminal difluorination of ?-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-? 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 ?···? stacking, C-H···O, and C-H···? 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.

SUBMITTER: Zhou B 

PROVIDER: S-EPMC6261351 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature