Computational and Experimental Studies of Regioselective S_NAr Halide Exchange (Halex) Reactions of Pentachloropyridine

The Halex reaction of pentachloropyridine with fluoride ion was studied experimentally and computationally with a modified ab initio G3MP2B3 method. The G3 procedure was altered, as the anionic transition state optimizations failed due to the lack of diffuse functions in the small 6-31G* basis set. Experimental Halex regioselectivities were consistent with kinetic control at the 4-position. The reverse Halex reaction of fluoropyridines with chloride sources was demonstrated using precipitation of LiF in DMSO as a driving force. Reverse Halex regioselectivity at the 4-position was predicted by computations and was consistent with kinetic control. Scrambling of halide ions between chlorofluoropyridines was catalyzed by <i>n</i>-Bu₄PCl, and the products of these reactions were shown to result from a combination of kinetic and thermodynamic control. Comparison of the C–F and C–Cl homolytic bond dissociation energies suggests that an important thermodynamic factor which controls regioselectivity in this system is the weak C2–Cl bond. The differences between Δ<i>H</i>° values of chlorofluoropyridines can be explained by a combination of three factors: (1) the number of fluorine atoms in the molecule, (2) the number of fluorine atoms at the C2 and C6 positions, and (3) the number of pairs of fluorine atoms which are ortho to one another

Nucleophilic Deoxyfluorination of Phenols via Aryl Fluorosulfonate Intermediates

This report describes a method for the deoxyfluorination of phenols with sulfuryl fluoride (SO₂F₂) and tetramethylammonium fluoride (NMe₄F) via aryl fluorosulfonate (ArOFs) intermediates. We first demonstrate that the reaction of ArOFs with NMe₄F proceeds under mild conditions (often at room temperature) to afford a broad range of electronically diverse and functional group-rich aryl fluoride products. This transformation was then translated to a one-pot conversion of phenols to aryl fluorides using the combination of SO₂F₂ and NMe₄F. Ab initio calculations suggest that carbon–fluorine bond formation proceeds via a concerted transition state rather than a discrete Meisenheimer intermediate