BF3-Promoted, Carbene-like, C-H Insertion Reactions of Benzynes.

Boron trifluoride is observed to promote a variety of C-H insertion reactions of benzynes bearing pendant alkyl groups. Computations and various mechanistic studies indicate that BF3 engages the strained π-bond to confer carbene-like character on the adjacent, noncoordinated benzyne carbon. This represents an unprecedented catalytic role for a non-transition metal such as BF3.

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

The mechanism of the aryl iodide-catalyzed asymmetric migratory geminal difluorination of ß-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.

Mechanism of the reactions of alcohols with o-benzynes.

We have studied reactions of secondary and primary alcohols with benzynes generated by the hexadehydro-Diels-Alder (HDDA) reaction. These alcohols undergo competitive addition vs dihydrogen transfer to produce aryl ethers vs reduced benzenoid products, respectively. During the latter process, an equivalent amount of oxidized ketone (or aldehyde) is formed. Using deuterium labeling studies, we determined that (i) it is the carbinol C-H and adjacent O-H hydrogen atoms that are transferred during this process and (ii) the mechanism is consistent with a hydride-like transfer of the C-H. Substrates bearing an internal trap attached to the reactive, HDDA-derived benzyne intermediate were used to probe the kinetic order of the alcohol trapping agent in the H2-transfer as well as in the alcohol addition process. The H2-transfer reaction is first order in alcohol. Our results are suggestive of a concerted H2-transfer process, which is further supported by density functional theory (DFT) computational studies and results of a kinetic isotope effect experiment. In contrast, alcohol addition to the benzyne is second order in alcohol, a previously unrecognized phenomenon. Additional DFT studies were used to further probe the mechanistic aspects of the alcohol addition process.

Catalytic, Enantioselective 1,2-Difluorination of Cinnamamides.

The enantio- and diastereoselective synthesis of 1,2-difluorides via chiral aryl iodide-catalyzed difluorination of cinnamamides is reported. The method uses HF-pyridine as a fluoride source and mCPBA as a stoichiometric oxidant to turn over catalyst, and affords compounds containing vicinal, fluoride-bearing stereocenters. Selectivity for 1,2-difluorination versus a rearrangement pathway resulting in 1,1-difluorination is enforced through anchimeric assistance from a N- tert-butyl amide substituent.